Intravenous Infusion Of Dopamine Research Articles

Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs

BackgroundIntrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses.MethodsAt 119–120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPSDA, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTLDA, n = 7). Post-mortem brain tissue was collected 3–4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit.ResultsLPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte “end feet” vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS.ConclusionLPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury.

The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced following intrauterine inflammation and dopamine infusion

BackgroundNeurovascular coupling leads to an increase in local cerebral blood flow and oxygenation in response to increased neural activity. Reduced cerebral functional responses may predispose to tissue hypoxia when neural activity is increased. Intrauterine inflammation, identified clinically as chorioamnionitis, is a major contributor to the neuropathology arising after preterm birth. The impact of chorioamnionitis on the preterm cerebral functional haemodynamic response is unknown. Previously, we have reported that somatosensory stimulation produces predominantly positive cerebral haemodynamic responses (i.e., increased cerebral oxygenation) in preterm lambs, which are reduced with dopamine treatment. As preterm infants born after chorioamnionitis often suffer from hypotension and are treated with dopamine, we aimed to investigate how chorioamnionitis with and without dopamine treatment affect the cerebral haemodynamic response in preterm lambs. MethodsAt 119 days of gestation, intrauterine inflammation was induced by intra-amniotic injection of lipopolysaccharide (LPS) in pregnant ewes. At 126–7 days of gestation (term is ~147 days), these LPS-exposed lambs were delivered and mechanically ventilated. The cerebral functional response was assessed by near infrared spectroscopy as changes in cerebral oxy- and deoxyhaemoglobin (ΔoxyHb, ΔdeoxyHb), following left median nerve stimulation of 1.8, 4.8 and 7.8 s durations without dopamine; and 4.8 and 7.8 s stimulations with intravenous dopamine infusion. ResultsStimulation for 1.8, 4.8 and 7.8 s durations led to negative functional responses (decreased ΔoxyHb) in 5 (62.5%), 5 (62.5%) and 4 (50%) of 8 preterm lambs respectively, while other lambs showed positive responses (increased ∆oxyHb). Dopamine infusion increased baseline tissue oxygenation index (TOI), oxyHb and total Hb. In lambs with a positive functional response, dopamine decreased the evoked ΔoxyHb response, increasing the overall incidence of negative cerebral haemodynamic responses. ConclusionsSomatosensory stimulation produced mostly negative responses with decreased cerebral oxygenation in preterm lambs exposed to intrauterine inflammation, contrasting with our previous findings of predominantly positive responses in non-inflamed, control, preterm lambs. Dopamine increased baseline cerebral oxygenation, but further increased the incidence of negative functional responses. Impaired neurovascular coupling leading to intermittent localised tissue hypoxia may therefore contribute to the neuropathy in infants with chorioamnionitis, with the risk of injury exacerbated with dopamine treatment.

Dopamine Reverses Lung Function Deterioration After Cardiopulmonary Bypass Without Affecting Gas Exchange

To investigate the effects of dopamine on the adverse pulmonary changes after cardiopulmonary bypass. A prospective, nonrandomized clinical investigation. A university hospital. One hundred fifty-seven patients who underwent elective cardiac surgery that required cardiopulmonary bypass. Fifty-two patients were administered intravenous infusion of dopamine (3 µg/kg/min) for five minutes after weaning from cardiopulmonary bypass; no intervention was applied in the other 105 patients. Measurements were performed under general anesthesia and mechanical ventilation before cardiopulmonary bypass, after cardiopulmonary bypass, and after the intervention. In each protocol stage, forced oscillatory lung impedance was measured to assess airway and tissue mechanical changes. Mainstream capnography was performed to assess ventilation- and/or perfusion-matching by calculating the normalized phase-3 slopes of the time and volumetric capnograms and the physiologic deadspace. Arterial and central venous blood samples were analyzed to characterize lung oxygenation and intrapulmonary shunt. After cardiopulmonary bypass, dopamineinduced marked improvements in airway resistance and tissue damping, with relatively small decreases in lung tissue elastance. These changes were associated with decreases in the normalized phase-3 slopes of the time and volumetric capnograms. The inotrope had no effect on physiologic deadspace, intrapulmonary shunt, or lung oxygenation. Dopamine reversed the complex detrimental lung mechanical changes induced by cardiopulmonary bypass and alleviated ventilation heterogeneities without affecting the physiologic deadspace or intrapulmonary shunt. Therefore, dopamine has a potential benefit on the gas exchange abnormalities after weaning from cardiopulmonary bypass.

Evaluation of Extreme Bradyarrhythmias in Symptomatic Adults.

Scenario: This 12-lead electrocardiogram (ECG) was obtained by paramedics on an 81-year-old man with chief complaints of dizziness, weakness, nausea, and vomiting for 2 days. The patient reported that he had experienced 2 similar near-syncopal episodes the preceding week. The patient denied chest pain or shortness of breath. He had a complex medical history that included coronary artery disease, arrhythmias, and renal failure. During the prehospital evaluation, the patient was lethargic, had a weak pulse at 28 beats per minute, and his blood pressure was undetectable.Atrial flutter with complete heart block and 4 ventricular escape beats of multifocal origin. Although the fourth beat looks narrow, it is unlikely to be of supraventricular origin given the lack of distinctive waveform morphology in leads V4 through V6.The 4 QRS complexes (ie, heartbeats) seen in this rhythm (arrows) are mostly of ventricular origin, as indicated by the characteristic bizarrely shaped QRS complexes that are wide, not related to a P wave, and have a discordant T wave (opposite direction to the QRS deflection). All of the escape beats have different QRS morphologies, suggesting that they are multifocal in origin; that explains the lack of a detectable heart rate, which is why the term beats is used rather than escape rhythm. An escape rhythm typically sustains some cardiac output and therefore is usually lifesaving and is common when atrial activity is not propagated through the normal conduction pathway. Complete heart block can be caused by acute myocardial infarction, structural heart disease, electrolyte imbalance, or atrioventricularnodal blocking medications (eg, calcium channel blockers). The absence of a sustainable escape rhythm despite supraventricular activation is usually referred to as ventricular standstill and should be treated as an asystole equivalent. The rapid atrial flutter combined with the infrequent random escape beats explains the patient’s slow, weak pulse. In addition, these escape beats were not sufficient to maintain a detectable blood pressure, which explains the patient’s syncopal symptoms.Remarkably, he was able to survive this extreme bradycardia event. Because this rhythm was an asystole equivalent, the patient was given a bolus of intravenous epinephrine and multifunction pads were applied to the torso in case transcutaneous pacing was needed. On arrival at the emergency department, the patient was oriented, with a heart rate of ~50/min. Initial cardiac workup was negative for acute myocardial infarction, and serum electrolyte levels were normal. However, a repeat 12-lead ECG showed atrial flutter with left bundle branch block, a potentially life-threatening combination usually seen in patients with progressive conduction system disease due to structural cardiac remodeling (eg, necrosis due to atherosclerotic disease as in this scenario). The patient was admitted to the intensive care unit for intravenous dopamine infusion, later received a permanent biventricular implantable cardiac defibrillator, and was eventually discharged home.

Impact of hypoxia-ischemia and dopamine treatment on dopamine receptor binding density in the preterm fetal sheep brain.

Dopamine is often used to treat hypotension in preterm infants who are at risk of hypoxic-ischemic (HI) brain injury due to cerebral hypoperfusion and impaired autoregulation. There is evidence that systemically administered dopamine crosses the preterm blood-brain barrier. However, the effects of exogenous dopamine and cerebral HI on dopaminergic signaling in the immature brain are unknown. We determined the effect of HI and dopamine on D1 and D2 receptor binding and expressions of dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the striatum of the preterm fetal sheep. Fetal sheep (99 days of gestation, term = 147days) were unoperated controls (n = 6) or exposed to severe HI using umbilical cord occlusion and saline infusion (UCO + saline, n = 8) or to HI with dopamine infusion (UCO + dopamine, 10 µg/kg/min, n = 7) for 74 h. D1 and D2 receptor densities were measured by autoradiography in vitro. DAT, TH, and cell death were measured using immunohistochemistry. HI resulted in cell death in the caudate nucleus and putamen, and dopamine infusion started before HI did not exacerbate or ameliorate these effects. HI led to reduced D1 and D2 receptor densities in the caudate nucleus and reduction in DAT protein expression in the caudate and putamen. Fetal brains exposed to dopamine in addition to HI were not different from those exposed to HI alone in these changes in dopaminergic parameters. We conclude that dopamine infusion does not alter the striatal cell death or the reductions in D1 and D2 receptor densities and DAT protein expression induced by HI in the preterm brain.NEW & NOTEWORTHY This is the first study on the effects of hypoxia-ischemia and dopamine treatment on the dopaminergic pathway in the preterm brain. In the striatum of fetal sheep (equivalent to ∼26-28 wk of human gestation), we demonstrate that hypoxia-ischemia leads to cell death, reduces D1 and D2 receptors, and reduces dopamine transporter. Intravenous dopamine infusion at clinical dosage used in preterm human infants does not alter the striatal cell death, D1 and D2 receptor density levels, and DAT protein expressions after hypoxia-ischemia in the preterm brain.

Peripheral Chemoreceptors Hemodynamic Responses During Simulated Hemorrhage Under Hypoxia Conditions

BackgroundMaintaining baroreflex sensitivity is integral to ensuring blood pressure maintenance and end‐organ perfusion during hemorrhage. This is especially true under conditions of hypoxemia, where decreased tolerance to central hypovolemia is commonly observed. Hypoxia activates peripheral chemoreceptors and reduces baroreceptor‐vascular resistance reflex sensitivity. However, a direct role for the peripheral chemoreceptors in the hemodynamic response to hemorrhage in hypoxia remains unclear.ObjectiveWe tested the hypothesis that attenuation of peripheral chemoreceptor activity (low‐dose dopamine; 1–2 μg/kg/min) during acute hypoxia would promote maintenance of mean arterial pressure, pulse pressure, and other hemodynamic markers [heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR)] during simulated hemorrhage.MethodsTen healthy men (35±3 years, BMI 25±1 kg/m2) participated in a randomized, double‐blind, placebo controlled study. Participants completed two experimental visits (saline and low‐dose dopamine) at which lower body negative pressure (LBNP) was conducted during hypoxia (SpO2 ~85%; PaO2 ~52 mmHg) delivered via a non‐rebreather mask. Ventilation [V̇ (turbine transducer)], arterial blood pressure (brachial artery catheter), HR (ECG), and central venous pressure (peripherally inserted central catheter) were measured continuously and SV, CO, and TPR were calculated. Following a 5‐min rest, participants underwent LBNP for 5‐min at 3 intervals (−15, −30, and −45 mmHg). Outcome values were analyzed and compared using a mixed linear model (SAS PROC MIXED) with a direct product AR(1) covariance structure using indicator variables for saline vs. dopamine. Data from the mixed linear model are reported as an estimated change per 15 mmHg of LBNP.ResultsDopamine had no effect on hypoxia PaO2, PaCO2, V̇ or respiratory rate (all P>0.05) and this relationship persisted throughout all LBNP stages. The mixed linear model showed no effect of dopamine vs. saline on changes in: central venous pressure (−1.1±0.4 vs −1.3±0.3 mmHg, P=0.15), mean arterial pressure (−4.7±2.3 vs −5.3±1.4 mmHg, P=0.25), pulse pressure (−6.7±1.5 vs −8.3±1.4 mmHg, P=0.50), HR (7.8±1.5 vs 6.1±1.5 bpm, P=0.41), SV (−10.9±1.9 vs −11.6±3.3 mL, P=0.41), CO (−0.3±0.2 vs −0.4±0.4 L · min−1, P=0.31) or TPR (0.2±0.4 vs 0.7±0.6 mmHg · L · min−1P=0.27).DiscussionIntravenous infusion of low‐dose dopamine designed to attenuate peripheral chemoreflex activity during acute hypoxia did not alter the integrated hemodynamic response to simulated hemorrhage. Our data suggests that peripheral chemoreceptors have a limited role during hypoxic central hypovolemia. More research is needed to understand the sensitivity and cross‐talk between chemoreceptors and baroreceptors during hemorrhage.Support or Funding InformationFunding: W81XWH‐13‐2‐0038 (DOD), DK90541 (NIH), UL1 TR000135 (NIH).

N-octanoyl dopamine is superior to dopamine in protecting graft contractile function when administered to the heart transplant recipients from brain-dead donors

The major source of heart transplantation comes from brain-dead (BD) donors. However, brain death and myocardial ischemia/reperfusion injury during transplantation may lead to cardiac dysfunction and hemodynamic instability. A previous work demonstrated that pre-treatment of BD donors with dopamine improved the graft survival of heart allograft in recipient after transplantation. However, low-dose dopamine treatment might result in tachycardia and hypertension. Our previous experimental study showed that pre-treatment of BD donor rats with the dopamine derivate N-octanoyl dopamine (NOD), devoid of any hemodynamic effects, improved graft function after transplantation. Herein, we hypothesized that NOD confers superior myocardial protection than dopamine, in terms of graft function. Male Lewis donor rats were either subjected to sham-operation or brain death via a subdurally placed balloon followed by 5.5 h monitoring. Then, the hearts were explanted and heterotopically transplanted into Lewis recipient rats. Shortly before the onset of reperfusion, continuous intravenous infusion of either NOD (14.7 μg/kg/min, BD + NOD group, n = 9), dopamine (10 μg/kg/min, BD + Dopamine group, n = 8) or physiological saline vehicle (sham, n = 9 and BD group, n = 9) were administered to the recipient rats. In vivo left-ventricular (LV) graft function was evaluated after 1.5 h reperfusion. Additionally, immunohistochemical detection of 4-hydroxy-2-nonenal (HNE, an indicator of oxidative stress) and nitrotyrosine (a nitro-oxidative stress marker), was performed. After heart transplantation, systolic and diastolic functions were significantly decreased in the BD group compared to sham. Treatment with NOD but not dopamine, resulted in better LV graft systolic functional recovery (LV systolic pressure BD + NOD 90 ± 8 vs BD + Dopamine 66 ± 5 vs BD 65 ± 4 mmHg; maximum rate of rise of LV pressure dP/dtmax BD + NOD 2686 ± 225 vs BD + Dopamine 2243 ± 70 vs BD 1999 ± 147 mmHg/s, at an intraventricular volume of 140 μl, p < 0.05) and myocardial work compared to BD group. The re-beating time (time to restoration of heartbeat) was significantly shorter in BD + NOD group than that of BD hearts (32 ± 4 s vs. 48 ± 6 s, p < 0.05), Dopamine treatment had no impact on all of these parameters. Furthermore, NOD as well as dopamine decreased HNE and nitrotyrosine immunoreactivity to the same level. NOD is superior to dopamine in terms of protecting LV graft contractile function when administered to the heart transplant recipients from BD donors.

Haemodynamic or metabolic stimulation tests to reveal the renal functional response: requiem or revival?

ABSTRACTRenal stimulation tests document the dynamic response of the glomerular filtration rate (GFR) after a single or a combination of stimuli, such as an intravenous infusion of dopamine or amino acids or an oral protein meal. The increment of the GFR above the unstimulated state has formerly been called the renal functional reserve (RFR). Although the concept of a renal reserve capacity has not withstood scientific scrutiny, the literature documenting renal stimulation merits renewed interest. An absent or a blunted response of the GFR after a stimulus indicates lost or diseased nephrons. This information is valuable in preventing, diagnosing and prognosticating acute kidney injury and pregnancy-related renal events as well as chronic kidney disease. However, before renal function testing is universally practiced, some shortcomings must be addressed. First, a common nomenclature should be decided upon. The expression of RFR should be replaced by renal functional response. Second, a simple protocol must be developed and propagated. Third, we suggest designing prospective studies linking a defective stimulatory response to emergence of renal injury biomarkers, to histological or morphological renal abnormalities and to adverse renal outcomes in different renal syndromes.

Carotid chemoreceptor control of muscle sympathetic nerve activity in hypobaric hypoxia.

What is the central question of this study? High-altitude hypoxia increases muscle sympathetic nerve activity (MSNA), but whether intravenous infusion of dopamine, to blunt the responsiveness of the carotid chemoreceptors, reduces MSNA at high altitude is not known. What is the main finding and its importance? Muscle sympathetic nerve activity was elevated after 15-17days of high-altitude hypoxia (3454m) compared with values at 'sea level' (432m). However, intravenous dopamine infusion to blunt the responsiveness of the carotid chemoreceptors did not significantly decrease MSNA either at sea level or at high altitude, suggesting that high-altitude sympathoexcitation arises via a different mechanism. High-altitude hypoxia causes pronounced sympathoexcitation, but the underlying mechanisms remain unclear. We tested the hypothesis that i.v. infusion of dopamine to attenuate carotid chemoreceptor responsiveness would reduce muscle sympathetic nerve activity (MSNA) at high altitude. Nine healthy individuals [mean (SD); 26 (4) years of age] were studied at 'sea level' (SL; Zurich) and at high altitude (ALT; 3454m; 15-17days after arrival), both while breathing the ambient air and during an acute incremental hypoxia test (eight 3min stages; partial pressure of end-tidal O2 90-45mmHg). Intravenous infusions of dopamine (3μgkg-1 min-1 ) and placebo (saline) were administered on both study days, according to a single-blind randomized cross-over design. Sojourn to high altitude decreased the partial pressure of end-tidal O2 (to ∼60mmHg) and increased minute ventilation [V̇E; mean±SEM, SL versus ALT: saline, 8.6±0.5 versus 11.3±0.6lmin-1 ; dopamine, 8.2±0.5 versus 10.6±0.8lmin-1 ; P<0.05] and MSNA burst frequency by ∼80% [SL versus ALT: saline, 16±3 versus 28±4burstsmin-1 ; dopamine, 16±4 versus 31±4burstsmin-1 ; P<0.05) when breathing the ambient air, but were not different with dopamine. Increases in MSNA burst frequency and V̇E during the acute incremental hypoxia test were greater at ALT than SL (P<0.05). Dopamine did not affect the magnitude of the MSNA burst frequency response to acute incremental hypoxia at either SL or ALT. However, V̇E was lower with dopamine than saline administration throughout the acute incremental hypoxia test at ALT. These data indicate that i.v. infusion of low-dose dopamine to blunt the responsiveness of the carotid chemoreceptors does not significantly decrease MSNA at high altitude.

Deciphering an Unexpected Serum Creatinine Result in a Critically Ill Patient.

A 74-year-old man with acute congestive cardiac failure complicated by cardiogenic shock came for emergency care. He required admission to the coronary care unit because of circulatory collapse and was given inotropic support with simultaneous intravenous infusions of dopamine and dobutamine. These medications were administered via a central line. An unexpected change in the patient's serial serum creatinine (SCr) resulted in a >60% change within 24 h (71 μmol/L/0.8 mg/dL from the earlier 186 μmol/L/2.1 mg/dL; reference interval 59–104 μmol/L/0.67–1.17 mg/dL). However, other surrogate markers of renal function (urea and potassium) did not show the same magnitude of variability in their measurements (Fig. 1). Fig. 1. Patient serum creatinine (SCr), urea (Ur), and potassium (K) results over the period of hospitalization in the intensive care unit. All SCr measurements were performed with same enzymatic-based method. Reference intervals for SCr, 59–104 μmol/L/0.67–1.17 mg/dL; Ur, <11.9 mmol/L/<71 mg/dL; and K, 3.5–5.1 mmol/L. The isolated change affecting 1 analyte did not suggest a dilutional effect by sample contamination. Preanalytical errors related to sample misidentification were excluded, and serum indices did not indicate the possibility of hemolysis, icterus, or lipemia interference. Another urgent blood sample was requested, and this was reanalyzed with the same methods used previously for urea, SCr, and potassium. The repeat results yielded values for SCr of 66 μmol/L/0.75 mg/dL, urea of 31 mmol/L/87 mg/dL urea nitrogen (reference interval <11.9 mmol/L/<71 mg/dL), and potassium …

Effects of intravenous low-dose dopamine infusion on glucose regulation during prolonged aerobic exercise.

The carotid body chemoreceptors are activated during hypoglycemia and contribute to glucoregulation during prolonged exercise in dogs. Low-dose intravenous infusions of dopamine have been shown to blunt the activation of the carotid body chemoreceptors during hypoxia. Therefore, we tested the hypotheses that dopamine would blunt glucoregulatory responses and attenuate plasma glucose during prolonged aerobic exercise in healthy participants. Twelve healthy participants completed two randomized exercise sessions at 65% peak oxygen consumption for up to 120 min. Saline was infused during one exercise session, and dopamine (2 μg·kg-1·min-1) was infused during the other session. Arterial plasma glucose, growth hormone, glucagon, cortisol, norepinephrine, and epinephrine were measured every 10 min. Exercise duration during dopamine infusion was 107 ± 6 and 119 ± 0.8 min during saline infusion. Glucose area under the curve during exercise was lower during dopamine (9,821 ± 686 vs. 11,194 ± 395 arbitrary units; P = 0.016). The ratio of circulating growth hormone to glucose and the ratio of glucagon to glucose were greater during dopamine ( P = 0.045 and 0.037, respectively). These results indicate that the infusion of dopamine during aerobic exercise impairs glucoregulation. This suggests that the carotid body chemoreceptors contribute to glucoregulation during prolonged exercise in healthy exercise-trained humans.

Life-Threatening Upper Airway Obstruction as a Complication of Corrective Spinal Surgery in a Patient with Parkinson ’s Disease: A Case Report

A 74-year-old female with a 10-year history of Parkinson’s disease visited our hospital complaining of severe kyphoscoliosis deformity. Corrective spinal surgery was performed through a posterior approach. Oral anti-Parkinson medication was continued until the day of surgery, when continuous intravenous dopamine infusion was initiated; dopamine was discontinued and oral medication restarted on the day after surgery. Four weeks after surgery, the patient developed dyspnea. Laryngeal examination revealed rigidity of the neck muscles causing upper airway obstruction. Emergency tracheotomy was performed and the patient’s respiratory condition improved immediately. Because of difficulty of swallowing, gastrostomy was performed 2 weeks after tracheotomy. After tracheotomy and gastrostomy, the patient’s respiratory condition improved. Life-threatening upper airway obstruction can occur after corrective spine surgery in patients with Parkinson’s disease. It is important to ensure the oral administration of anti- Parkinson medication after surgery.

Myocardial Infarction with Ventricular Septal Rupture and Cardiogenic Shock

A 72-year-old woman with a history of systemic arterial hypertension presented to the emergency department with chest pain, and an electrocardiogram showed acute anterior myocardial infarction with striking ST-segment elevation, upright T waves, and large Q waves in leads V1 to V4 (Figure). Furthermore, the ST-segment elevation > 0.25 mV in lead V1, the ST depression ≥ 0.1 mV in lead III, and the ST elevation ≥ 0.1 mV in lead aVL indicated that the left anterior descending coronary artery was occluded proximal to both the first major septal perforating branch and the first diagonal branch (1–4). Figure. Electrocardiogram recorded on the patient's arrival in the emergency department. See text for explication. Also, note that there was sinus rhythm at a rate of 106 beats/min with the next to last QRS complex being a fusion of a premature ventricular complex ... Anterior infarcts from such proximal left anterior descending occlusions tend to be quite large and are often associated with cardiogenic shock (2, 4, 5), which this woman manifested soon after her arrival in the emergency department. An echocardiogram showed a left ventricular ejection fraction of approximately 40% with akinesis of the apex and distal two-thirds of the ventricular septum. The right ventricle was considerably dilated. Through a defect in the distal ventricular septum, blood shunted from left to right during systole with reversal of flow during diastole, suggesting an elevated right ventricular diastolic pressure. Laboratory studies of the patient's blood confirmed myocardial damage and indicated chronic kidney disease and acute metabolic acidosis (Table). Table. Laboratory results from blood drawn on admission The patient had a run of ventricular tachycardia while in the emergency department. Once stable, she was transported to the cardiac catheterization laboratory; an intra-aortic balloon was placed via the left femoral artery, and 1:1 counterpulsation was begun. Coronary arteriography, performed via the right femoral artery, showed proximal total occlusion of the left anterior descending coronary artery, diffuse disease of the left circumflex coronary artery with a totally occluded first obtuse marginal branch and 90% narrowing of the third obtuse marginal branch, and diffuse disease of the right coronary artery with a long 80% to 90% narrowing in its mid segment. Despite repeated inflations of first a 2.5 × 20 mm balloon and then a 2.0 × 25 mm balloon in the proximal and distal portions of the left anterior descending artery, there was no flow. Hypotension, bradycardia, and acidosis (arterial blood pH = 6.9; reference = 7.4) were temporarily combated with atropine, epinephrine, and sodium bicarbonate, and the patient was sent to the intensive care unit with an intravenous dopamine infusion and 1:1 intra-aortic balloon counterpulsation. She died several hours later. Ventricular septal rupture formerly occurred in 1% to 3% of patients with acute myocardial infarction and did so within the first week in more than 75% of them (6). Subsequently, among patients treated with fibrinolysis, the incidence of ventricular septal rupture was only 0.2%, and the median time from the onset of the infarct was 1 day (7). Approximately one-half of ventricular septal ruptures are in the setting of an anterior infarct, and one-half occur in patients with inferior infarcts (8, 9). At least two-thirds of patients with myocardial infarction and ventricular septal rupture die, and many of these, like our patient, are older and have cardiogenic shock; early operation by superb surgeons seems to improve the chances of survival (10). The large upright fused ST segments and T waves seen in the figure have been referred to as “tombstoning,” probably because of the appearance of tombstones and because they are signs of more extensive myocardial damage and of a poor prognosis (11). Sclarovsky believes that this pattern of deep anterior Q waves with persistently elevated ST segments and tall T waves indicates lack of reperfusion of the myocardium due to a severely damaged microcirculation (12).

Preventing or attenuating amphotericin B nephrotoxicity with dopamine receptor agonists: a literature review

Nephrotoxicity is generally considered as the most clinically significant and dose-limiting adverse reaction of amphotericin B. Currently, only the clinical effectiveness of salt loading and administering lipid formulations of amphotericin B have been clearly demonstrated to prevent its nephrotoxicity. In this review, we collected the published data related to dopamine receptor agonists in preventing amphotericin B nephrotoxicity. A literature search was conducted by the relevant keywords like ‘‘amphotericin B”, “nephrotoxicity’’, and ‘‘dopamine’’ in databases such as Scopus, Medline, Embase and ISI Web of Knowledge. Four relevant articles were considered. Results of all the 3 experimental studies demonstrated that co-administration of dopamine (0.5-10 μg/kg/min) as continuous intravenous infusion, SK&F R-105058 (10 mg/kg twice daily), a prodrug of fenoldopam, orally, or fenoldopam, a relatively selective dopamine receptor type 1 agonist, (0.5 or 1 μg/kg/min) as continuous intravenous infusion can at least significantly mitigate the decrease in creatinine clearance caused by amphotericin B. Furthermore, fenoldopam and SK&F R-105058 can also protect against or delay amphotericin B-induced tubular damages. In contrast, the only clinical trial published until now found that simultaneous continuous intravenous infusion of low dose dopamine (3 μg/kg/min) had no beneficial effects on the incidence, severity, as well as time onset of developing amphotericin B-induced nephrotoxicity in autologous bone marrow transplant and leukemia patients. Considering the lack of beneficial effects in different settings such as acute kidney injury of any cause, negative results of the only clinical trial, and risk of significant adverse reactions, continuous intravenous infusion of low dose dopamine (1-3 μg/kg/min) or selective dopamine receptor type 1 agonists (e.g., fenoldopam) currently appears to have no real clinical role in preventing or attenuating amphotericin B nephrotoxicity.

Bilateral symmetrical digital gangrene of upper and lower limbs due to purpura fulminans caused by Streptococcus pyogenes: A rare entity.

Sir, We report an unusual case of 72-year-old female with acute gastroenteritis due to Streptococcus pyogenes, leading to low cardiac output state and acute kidney injury, who developed bilateral symmetrical peripheral gangrene (SPG) of upper and lower limbs [Figures ​[Figures11 and ​and2].2]. All peripheral pulses were palpable and color Doppler of upper and lower limb vessels indicated normal flow. Investigations revealed hemoglobin 10.9 g/dL, platelet count 44,000 cells/mm3, PT INR 1.72, low antithrombin-lll levels and deranged liver function. Plasma was positive for fibrin degradation products and D-dimers. She was shifted to Intensive Care Unit suspecting septic shock and resuscitated with intravenous (IV) fluids and dopamine infusion. In view of persisting hypotension and desaturation, she was intubated and mechanically ventilated. Unfractionated heparin was started to treat digital gangrene, attributing it to the pro-thrombotic state of sepsis. She developed bleeding per vaginally and orally in course of 2 days while her PT-INR rose to 2.8, platelet count decreased to 11,000 cells/mm3 and fibrinogen levels were 65 mg/dL, indicative of consumptive coagulopathy. This was treated with transfusion of six units FFP, four units each of cryoprecipitate and platelet, and bleeding was controlled within 2 days. Figure 1 Digital gangrene of both lower limbs, involving forefoot on the right side Figure 2 Digital gangrene of both upper limbs After 72 h, blood culture was positive for S. pyogenes, sensitive to ceftriaxone, amoxicillin/ampicillin and tetracycline/doxycycline, which was started immediately. The diagnosis of pupura fulminans (PF) due to S. pyogenes leading to SPG was made. Her general condition improved within 72 h with no further progression of gangrenous areas, which were well delineated in a week. She was discharged against medical advice on day 11 due to the economic constraint. Pupura fulminans is an acute life-threatening complication of disseminated intravascular coagulation (DIC) manifested by rapidly progressive cutaneous hemorrhage and necrosis leading to SPG.[1] Clinical features include tissue necrosis, intact peripheral pulse, elevated serum lactate, association with vasospastic disorders and multi-organ failure. This is attributed to the pro-thrombotic state of DIC, which leads to widespread microvascular thrombosis.[2] Common pathogens responsible for PF include Meningococci, Pneumococci, Staphylococci, Klebsiella and Enterococci.[3] S. pyogenes the causative organism in our case has not been reported till now in the literature. Awareness of this clinical condition will help in the prompt recognition, early administration of treatment to prevent the spread of gangrenous areas and avoidance of expensive investigations like angiography or unwanted surgical procedure in the critically ill patient. Aggressive resuscitation using IV fluids, vasopressor infusions, correction of acid-base and electrolyte imbalance and mechanical ventilation can stop the spread of gangrenous area along with rapid recovery. Mortality associated with SPG can be reduced by early recognition and administration of culture sensitive antibiotics. Although heparinization is associated with thrombotic (peripheral gangrene) as well as bleeding tendencies (consumptive coagulopathy), posing therapeutic dilemma, it remains the mainstay of treatment to control thrombosis.[4] Amputation of gangrenous areas is deferred till the general condition of the patient improves, and the gangrenous area is well-demarcated.[3] Protection of gangrenous extremities with antiseptic dressing, halting the spread and demarcation by topical nitroglycerine paste, phentolamine, epoprostenol or sympathetic blockade can be tried.[2] Novel modalities of treatment include plasmapheresis, papaverine, streptokinase, hyperbaric oxygen therapy, dextran-40, epsilon aminocaproic acid, ketanserin, and hirudin.[1,3,5,6,7]

How Can a Large Left Atrial Myxoma Cause a Selective Mid-Diastolic Right-to-Left Atrial Shunt?

A 76-YEAR-OLD MAN was admitted to the authors’ institution for evaluation of syncope. The patient suffered a witnessed, brief (15 to 20 seconds) loss of consciousness after standing up from a seated position in his home. The patient’s wife called emergency medical services. The patient had no neurologic deficits or other injuries related to the fall, but persistent hypotension was observed in the emergency department that was unresponsive to volume administration. An intravenous infusion of dopamine was required to increase his arterial blood pressure to the normal range. The patient anecdotally reported gradually worsening dyspnea on exertion, lower extremity swelling, and modest weight gain. The past medical history was notable for atrial fibrillation, which was first recognized 1 week before the current admission; treatment with digoxin and furosemide was begun at that time. Transthoracic echocardiography was performed as part of the diagnostic evaluation and revealed a 7.6×4.0 cm smooth, highly mobile mass with a broad-based pedicle attachment to the atrial septum that prolapsed through the mitral valve into the left ventricle during diastole. Computed tomography verified these findings. The imaging studies suggested that the mass was most likely a left atrial myxoma. The patient suffered another episode of near-syncope in the hospital during which, his wife reported, he “turned blue.” He spontaneously recovered after assuming a recumbent position. The patient subsequently was transported to the operating room for resection of the presumed myxoma. After anesthetic induction and endotracheal intubation, transesophageal echocardiography (TEE) confirmed the preoperative diagnosis (Fig 1, Fig 2, Fig 3). The left ventricle was relatively underfilled and the right ventricle was markedly dilated (Fig 4). A pulmonary artery catheter was inserted. Central venous and mean pulmonary arterial pressures were elevated (average values of 28 and 36 mmHg, respectively) despite administration of an intravenous infusion of milrinone. An atrial right-to-left shunt tracking along the mass’s anterior-superior surface was observed during mid-diastole (Fig 5). The shunt was absent throughout the remainder of the cardiac cycle. Two additional images were obtained (Fig 6, Fig 7). What is the diagnosis? Fig 2Midesophageal four-chamber transesophageal echocardiography view obtained during systole showing large left atrial mass occupying the majority of the left atrium. View Large Image Figure Viewer Download Hi-res image Fig 3Midesophageal four-chamber transesophageal echocardiography view obtained during mid-diastole showing large left atrial mass prolapsing through the mitral valve into the left ventricle. View Large Image Figure Viewer Download Hi-res image Fig 4Midesophageal transgastric short-axis transesophageal echocardiography view obtained at end-diastole showing marked right ventricular dilatation. View Large Image Figure Viewer Download Hi-res image Fig 5Modified midesophageal aortic valve short-axis color Doppler transesophageal echocardiography view obtained during mid-diastole showing a right-to-left atrial shunt (red) tracking along the anterior-superior border of the left atrial mass. View Large Image Figure Viewer Download Hi-res image Fig 6Modified midesophageal aortic valve short-axis transesophageal echocardiography view obtained during early diastole showing deformation of the anterior atrial septum (white arrow) by the movement of the left atrial mass. View Large Image Figure Viewer Download Hi-res image Fig 7Modified midesophageal aortic valve short-axis transesophageal echocardiography view obtained during mid-diastole showing transient opening in the anterior atrial septum (white arrow) as a result of deformation by movement of the left atrial mass. View Large Image Figure Viewer Download Hi-res image

Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial.

IntroductionIntravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics.MethodsSubjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge.ResultsA total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m2P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04).ConclusionsIn the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months.Trial registrationClinicalTrials.gov NCT01441245. Registered 23 September 2011.

Use of dopamine infusion improved oxygenation in a patient of Ebstein′s anomaly with atrial septal defect

We present the successful perioperative management of an adult patient with Ebstein's anomaly for abdominal rectopexy surgery. The patient developed mild hypotension and a fall in peripheral oxygen saturation (SpO 2 ) after administration of a graded epidural block. Correction of the fall in the blood pressure; however, did not improve the SpO 2 . The patient was administered an intravenous infusion of dopamine to improve the cardiac output and this led to improvement in the SpO 2 .

Effect of Cerebral Perfusion Pressure on Cerebral Cortical Microvascular Shunting at High Intracranial Pressure in Rats

Recently, we showed that decreasing cerebral perfusion pressure (CPP) from 70 mm Hg to 50 mm Hg and 30 mm Hg by increasing intracranial pressure (ICP) with a fluid reservoir induces a transition from capillary (CAP) to microvascular shunt (MVS) flow in the uninjured rat brain. This transition was associated with tissue hypoxia, increased blood-brain barrier (BBB) permeability, and brain edema. Our aim was to determine whether an increase in CPP would attenuate the transition to MVS flow at high ICP. Rats were subjected to progressive, step-wise increases in ICP of up to 60 mm Hg by an artificial cerebrospinal fluid reservoir connected to the cisterna magna. CPP was maintained at 50, 60, 70, or 80 mm Hg by intravenous dopamine infusion. Microvascular red blood cell flow velocity, BBB integrity (fluorescein dye extravasation), and tissue oxygenation (nicotinamide adenine dinucleotide) were measured by in vivo 2-photon laser scanning microscopy. Doppler cortical flux, rectal and cranial temperatures, ICP, arterial blood pressure, and gases were monitored. The CAP/MVS ratio increased (P<0.05) at higher ICP as CPP was increased from 50 to 80 mm Hg. At an ICP of 30 mm Hg and CPP of 50 mm Hg, the CAP/MVS ratio was 0.6±0.1. At CPP of 60, 70, and 80 mm Hg, the ratio increased to 0.9±0.1, 1.4±0.1, and 1.9±0.1, respectively (mean±SEM; P<0.05). BBB opening and increase of reduced form of nicotinamide adenine dinucleotide occurred at higher ICP as CPP was increased. Increasing CPP at high ICP attenuates the transition from CAP to MVS flow, development of tissue hypoxia, and increased BBB permeability.

Effect of intravenous dopamine infusion on pituitary and thyroid function and on nephroprotection

INTRODUCTION; Catecholamines, including dopamine, are used in cardiac intensive care. The aim of the study was to assess the effect of intravenous dopamine infusion on the function of pituitary gland in patients with acute cardiac failure. We analyzed changes in the serum levels of thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH), as well as potential nephroprotection. The study involved 29 patients with chronic decompensated heart failure (New York Heart Association class III/IV; mean age 77.4 ± 13.3 years). Dopamine was administered intravenously in doses varying from 1 to 5 μg/kg/min. Measurements of TSH, free triiodothyronine (FT3), free thyroxine (FT4), and ACTH were taken directly before dopamine infusion, after 12 hours of continuous infusion, and 12 hours after the 72-hour infusion was completed. Serum FT3 levels were significantly higher before dopamine infusion than at 12 hours post infusion (5.12 ± 1.16 vs. 4.27 ± 0.89 pmol/l, P < 0.005). Serum FT4 levels before the infusion were significantly higher than after 12 hours of continuous infusion as well as after 12 hours post infusion (18.79 ± 5.33 vs. 17.06 ± 4.61 pmol/l, P < 0.05; 18.79 ± 5.33 vs. 16.26 ± 4.53 pmol/l, P < 0.05, respectively). There were no statistically significant differences between serum TSH and ACTH levels or in creatinine clearance before, during, and 12 hours post infusion. Intravenous infusion of dopamine may downregulate endocrine thyroid function; however, it has no significant effect on the pituitary gland-derived TSH and ACTH. There was no significant nephroprotective effect of low-dose dopamine infusion in patients with chronic decompensated chronic heart failure.