Dobutamine Administration Research Articles

1068

Introduction: To examine the independent predictive value of reaching a central venous oxygen saturation (ScvO2) of 70% or greater among emergency department (ED) patients with severe sepsis or septic shock treated with early goal-directed therapy (EGDT). Methods: Retrospective analysis of a prospective database of 2894 patients with severe sepsis or septic shock treated with EGDT in 21 EDs between March 2010 and September 2012. Patients were included if they qualified for ScvO2-guided therapies as defined by two consecutive ScvO2 measurements less than 70% at least 15 minutes apart with a concomitant CVP of at least 8 mmHg and a MAP of at least 65 mmHg. Variables abstracted during the first six hours of EGDT included age, gender, initial ScvO2, final ScvO2, highest CVP, initial serum lactate, percent serum lactate clearance, mechanical ventilation, shock index, vasopressor or dobutamine administration, red blood cell (RBC) transfusion, lowest hemoglobin, 6-hour Sequential Organ Failure Assessment (SOFA) score and a modified electronic Simplified Acute Physiology Score III (eSAPS 3). Multivariable logistic regression was used to assess the predictive value of each variable on the outcome of in-hospital mortality. Results: 580 (20%) patients were included. In-hospital mortality was 21%. Patients with in-hospital mortality were older(p-0.001), more likely to require mechanical ventilation (p<0.001) or vasopressors (p=0.02), had higher initial serum lactates (p<0.001), 6-hour SOFA (P<0.001) and eSAPS 3 scores (p<0.001), and had lower percentage serum lactate clearances (p=0.002). On logistic regression analysis (c statistic = 0.75), variables associated with the outcome were 6-hour SOFA (OR = 1.14 [1.03-1.26], p=0.014), eSAPS 3 (OR = 1.06 [1.02-1.10], p=0.007), initial lactate (OR = 1.15 [1.03-1.27], p=0.005) and lactate clearance less than 50% (OR = 1.90 [1.03-3.51], p=0.04). Dobutamine administration, RBC transfusion, initial ScvO2 or final ScvO2 were not statistically associated with the outcome before or after adjustment for covariates. Conclusions: When CVP and MAP goals were reached, successful resuscitation to an ScvO2 of 70% or greater was not an independent predictor of in-hospital mortality in this adjusted retrospective analysis. These findings suggest that lactate clearance may be an alternate resuscitation endpoint in this cohort.

Cerebral Arterial Pulsation Drives Paravascular CSF–Interstitial Fluid Exchange in the Murine Brain

CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloid β, in a pathway that we have termed the "glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ~50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ~60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloid β, in the aging brain.

Assessment of ventricular relaxation and stiffness using early diastolic mitral annular and inflow velocities in pediatric patients with heart disease

This study was undertaken to test the hypothesis that noninvasive echocardiographic indexes obtained using early diastolic mitral annular and inflow velocities reflect diastolic function in children. We included in this study 61 consecutive pediatric patients (age 0.4–13 years) who underwent cardiac catheterization for various heart diseases with biventricular circulation. Left ventricular (LV) pressure was measured using a high-fidelity manometer to obtain the time constant of relaxation (τ) and LV chamber stiffness (K). Echocardiography was simultaneously performed during catheterization. Data acquisition was repeated after the administration of dobutamine. The peak early mitral annular velocity (e′) and τ showed a significant inverse correlation (r = −0.42). Receiver-operating characteristic (ROC) analysis to determine the 90th percentile of τ yielded an area under the curve (AUC) of 0.86 for a septal e′ < 6.2 cm/s, with sensitivity and specificity of 0.83. The dobutamine-induced changes in e′ closely correlated with those in τ (r = −0.69). The deceleration time (DT) showed a significant but weak negative correlation with K (r = −0.35), and ROC analysis to determine the 90th percentile of Κ yielded an AUC of 0.82 for a DT <100 ms, with sensitivity of 0.80 and specificity of 0.77. The ratio of peak early mitral inflow velocity (E) to e′ (E/e′) significantly correlated with LV end-diastolic pressure (EDP; r = 0.48, P < 0.0005), and ROC analysis to determine the 90th percentile of EDP (>12.96 mmHg) yielded an AUC of 0.81 for an E/e′ > 16.4, with sensitivity of 0.71 and specificity of 0.93. The e′, DT, and E/e′ values in our study reflect the diastolic function in our pediatric population. However, the weak correlations between these indexes and invasive measures of diastolic function suggest that these indexes are useful in detecting diastolic dysfunction but not in determining the absolute values of diastolic dysfunction. Therefore, a future study is warranted to develop an efficient algorithm for systematic noninvasive evaluation of LV diastolic function in children.

Predictors of Dobutamine and Red Blood Cell Administration Among Patients Treated With Early Goal-Directed Therapy in the Emergency Department

Predictors of Dobutamine and Red Blood Cell Administration Among Patients Treated With Early Goal-Directed Therapy in the Emergency Department

β-1 Adrenergic Agonist Mitigates Unloading-Induced Bone Loss by Maintaining Formation

Recent data indicate a direct relationship between the sympathetic nervous system and bone metabolism. The purpose of this study was to evaluate the effects of a beta-1 adrenergic (Adrb1) agonist, dobutamine (DOB), on disuse-induced changes in bone integrity during 28 d of hindlimb unloading (HU). Male Sprague-Dawley rats, age 6 months, were assigned to either a normal cage activity (CC) or HU (n = 24/group). Animals were given one daily bolus dose (4 mg·kg body weight a day) of DOB (n = 12) or an equal volume of saline (VEH, n = 12). In vivo peripheral quantitative computed tomography scans revealed a 9% loss in proximal tibia metaphysis (PTM) volumetric bone mineral density (vBMD) over 28 d of disuse. DOB administration during HU significantly attenuated reductions in PTM vBMD and inhibited reductions in mid-diaphysis tibia cross-sectional moment of inertia. A significant decline in PTM bone formation rate in the HU-VEH group (-56% vs CC-VEH) was completely abolished in the HU-DOB group. Significant reductions in strength of the femoral shaft and neck in the HU-VEH group (14% and 15%, respectively) were prevented with DOB treatment. In conclusion, DOB administration during HU effectively attenuates significant declines in total vBMD at PTM by mitigating associated decrements in bone formation rate. Positive effects of DOB were observed only in unloaded animals, with no effects observed in normal weight-bearing rats. These data provide evidence for the importance of Adrb1 signaling in maintaining osteoblast function during periods of mechanical unloading.

Abstract 399: Whole-Body Deletion of PPAR? in Mice Increases Sympathetic Nerve Activity

PPARγ and sympathetic nerve activity (SNA) antagonistically regulate energy metabolism and cardiovascular function with the former promoting anabolism and vasorelaxation and the later favoring catabolism and vasoconstriction. However, the precise relationship between these two factors is not known. The present study examined the influence of PPARγ deletion on SNA. Systemic inactivation of PPARγ was generated constitutively by using Mox2-Cre mice (MoxCre/flox) or inducibly by using the tamoxifen system (EsrCre/flox/TM). Radiotelemetry demonstrates consistent increases in resting daytime heart rate (HR) in both strains of null mice; this was associated a more than 10-fold increase in urinary epinephrine and norepinephrine levels. Subsequently, more detailed analysis of SNA was performed in Esr/flox/TM mice. In response to a bolus ip injection of the gangalion blocker pentolinium at 7.5 mg/kg, the decreases in HR and MAP were greater in the null mice than in the flox controls (delta HR:-254.2 vs. 92.3 beat/min; delta MAP: -67.8 vs. 33.4 mmHg). The HR decrease in response to the beta-blocker metaprolol (12 mg/kg, ip) was greater in the null mice than in the flox controls so was the MAP decease in response to the alpha1-blocker prazosin (1 mg/kg, ip). Baroreflex sensitivity (BRS) was assessed by the measurement of the HR responses to bolus injections of sodium nitroprusside (NP-BRS) or phenylephrine (PE-BRS). EsrCre/flox/TM mice displayed normal PE-BRS but blunted NP-BRS. Echocardiography under anesthesia demonstrated that the ejection fraction (EF) was 11% lower after administration of metaprolol contrasting to a drop of only 1.5% for the flox controls, in parallel with a greater reduction of HR in the KO mice. In contrast, the increase in HR following administration of the beta1 agonist dobutamine (0.8 mg/kg, ip) was less in the KO mice than in the flox controls. Together, we conclude: 1) PPARγ deletion causes the activation of SNA, 2) the parasympathetic nervous system may be unaffected, 3) the blunted response to dobutamine suggest suppressed beta1 receptor activity possibly as a result of compensatory response to sympathoactivation.

Cerebral oximetry to adjust cerebral and systemic circulation after cardiac arrest

Dear Editor, We report the case of a comatose survivor from cardiac arrest (CA) in whom cerebral oximetry helped insure adequate brain perfusion. A 64-year old man was admitted to our Department of Intensive Care after out-of-hospital CA secondary to ventricular fibrillation. Urgent coronary angiography did not reveal any significant lesion. Cardiac output (CO) (PiCCO, PULSION Medical Systems AG, Munich, Germany) was 3.9 L/min, stroke volume variation (SVV) 10 %, superior vena cava oxygen saturation (SvcO2) 69 % and lactate 4.2 mEq/L (Table 1). Bilateral transcranial doppler (TCD, Philips S4-2 probe, USA) of the middle cerebral arteries (MCA) and cerebral oxygen saturation (StO2) by frontal oximetry (Fore-sight, Casmed, Branford, CT—normal values [65 %) were within normal ranges (Table 1). The patient was cooled with blankets to achieve therapeutic hypothermia (TH). Blood temperature progressively decreased to 33 C within 70 min at which time CO was 2.2 L/min, SVV 9 % and SvcO2 68 %. Transesophageal echocardiography (TEE) showed global biventricular hypokinesia and a left ventricular ejection fraction of 25 %; however, arterial lactate level had decreased to 2.4 mEq/L and urine output exceeded 1 ml/kg/h. Although PaCO2 was constant between 34 and 36 mmHg, TCD showed a slight reduction in mean MCA velocities (MCAV) and increase in pulsatility index (PI) (Table 1) from baseline values; StO2 was only 55 and 57 % on the left and right sides, respectively. Increasing mean arterial pressure (MAP) to 80 mmHg with norepinephrine had no impact on brain oxygenation. Initiation of a dobutamine infusion (5 lg/kg/min) resulted in an increase in CO to 3.7 L/min and SvcO2 to 76 %, without significant changes in MAP; PI, mean MCA velocities, and StO2 values increased (Table 1, Fig. 1). Dobutamine was maintained for 48 h, until the patient recovered consciousness. He was discharged after 16 days with only moderate amnesia. Brain damage remains the most important cause of disability and death among CA survivors. Despite restoration of an adequate systemic blood pressure, complex pathological phenomena lead to reduced cerebral blood flow (CBF) and inadequate oxygen supply, which contribute to secondary brain injury [1]. During TH, a reduction in global metabolism and blood flow is expected, however systemic hemodynamic variables cannot predict cerebral oxygen delivery and cerebral hypoperfusion may persist; moreover, hypocapnia is frequent during TH, and can induce cerebral vasoconstriction and further decrease cerebral perfusion [2]. In this setting, monitoring of CBF and oxygenation is of paramount importance. The TCD provides information on CBF autoregulation during dynamic interventions, even after CA [3]; we found that dobutamine administration raised MCAV while reducing PI, which suggested an increase in blood flow. However, TCD is not useful for estimating brain oxygenation. The adequacy of cerebral hemispheric oxygenation can be estimated by the venous hemoglobin saturation measured in the internal jugular vein, but this requires

Prediction of improvement in cardiac function by high dose dobutamine stress echocardiography in patients with recent onset idiopathic dilated cardiomyopathy

The prognosis of patients with recent onset idiopathic dilated cardiomyopathy (DCM) is grave and highly variable [1]. Dobutamine stress echocardiography (DSE) has been used to assess contractile reserve in patients with ischemic and idiopathic DCM. Several studies have suggested that contractile reserve assessed by DSE can be of prognostic value inpatientswith idiopathic DCM [2–5]. In this study,we investigated whether contractile reserve on DSE could predict late improvement of cardiac function and had incremental prognostic value for future cardiac events in recent onset idiopathic DCM. Between December 2004 and May 2011, forty-one patients were enrolled in this study. The study population consisted of patients with idiopathic DCMwho had symptom durations of less than 6 months. All study subjects underwent coronary angiography to exclude ischemic heart disease, and endomyocardial biopsies were performed in 35 patients (85%) to exclude reversible causes, such as myocarditis. Patients with chronic kidney disease (estimated glomerular filtration rate b60 ml/min/1.73 m) were also excluded. All patients had a complete echocardiographic study and follow-up echocardiogram was performed after 6 month and 12 month, then when any clinical events occurred. The interval between the time of DSE and last follow-up echocardiogramwas 16±15 months. Dobutamine was infused in 5-min dose increments, starting from 5 μg/kg/min and increasing to 10, 20, 30, and finally, to the maximal dose of 40 μg/kg/min. The infusion was discontinued before the maximal dose was reached if 85% of the maximal predicted heart rate for the age group was achieved, or if symptomatic complex ventricular arrhythmias, defined as the presence of multiform or repetitive ventricular extrasystoles, were observed. Beta-blockers were stopped 48 h before dobutamine testing in all patients taking these agents. The institutional committee of Kyungpook National University Hospital approved the study protocol. Informed consent was obtained in all patients. Cardiac death and hospitalization were combined end-point. The mean age of the patients was 50±14.8 years, and 24 patients (59%)weremale. During themean follow-up period of 30±24 months, 14 patients (34%) experienced cardiac events, and 5 (12%) of them died. Three (7%) of themwere sudden cardiac death, and two (4%) were low cardiac output death. Of the remaining patients, 9 (21%) were rehospitalized due to aggravation of heart failure. During dobutamine infusion, no significant complications occurred. Tenpatientsdidnot reachapeakdoseof dobutamine. Sixpatients reached maximal heart rates before thepeakdose of dobutamine, and in 4patients the test was stopped before the peak dose due to frequent premature complex. The mean value of the maximal dobutamine dose given was 35.6±8.7 μg/kg/min. We investigated the correlation between follow-up LVEFand clinical and echocardiographic parameters (Table 1). The followup LVEF correlated with baseline LVEDV (r=−0.519, p=0.001), LVESV (r=−0.499, p=0.001), LVEDV at peak dose (r=−0.509, p=0.001), LVEFat peakdose (r=0.692, pb0.001), and the changeof LVEF (r=0.515, p=0.001) from baseline to peak dose of dobutamine. Among them, LVEF at the peak dose of dobutamine was the most significant predictor of follow-up LVEF. Follow-up LVEFwas predicted by LVEF at the peak dose of DSE (y=1.033×−0.979, r=0.465, p=0.001). Receiver-operating characteristic analysis was used to determine the optimal cutoff value for predicting cardiac events with respect to the change of LVEF. The optimal change in LVEFwas 9.8%, The Kaplan–Meier survival estimates were stratified according to the results of baseline to peak LVEF variation during dobutamine administration (Fig. 1). The presence of inotropic response after dobutamine infusion, identified in this study as a change of LVEF≥9.8%, showed a significantly better outcome than little inotropic response (pb0.001). In the Cox-proportional hazard model, the change of LVEF from peak to baseline (hazard ratio [HR] 0.834, 95% confidence interval [CI] 0.713–0.976, p=0.024), in addition to age (HR 0.921, 95% CI 0.863– 0.984, p=0.015), log NT-ProBNP (HR 0.261, 95% CI 0.091–0.749, p=0.013), deceleration time (HR 0.964, 95% CI 0.932–0.998, p=0.039) and E/E′ ratio (HR 1.177, 95% CI 1.046–1.325, p=0.007) was also a significant independent predictor of cardiac event (Table 2). Moreover, the LVEF change in DSE had incremental prognostic value to

Ageing is the main determinant of haemodynamics and autonomic cardiac changes observed in post-menopausal female rats

The aim of this study was to evaluate and compare the effects of early and physiological menopause on cardiac autonomic parameters in aged female rats. To this end, female Wistar rats (22 and 82 weeks old, N=96) were divided into 4 groups: Young Sham-operated Rats, Aged Sham-operated Rats, Young Ovariectomised (OVX) Rats, and Aged OVX Rats. Young Sham-operated and OVX rats were used as controls. The cardiac autonomic parameters were investigated using different approaches: 1) pharmacological evaluation of the autonomic tonus with methylatropine and propranolol; 2) isolated cardiac contractility with β-adrenergic agonists; and 3) quantification of the mRNA and protein level expression of cardiac β-adrenergic receptors. Among the groups of aged female rats, both the Sham-operated and OVX rats showed higher basal mean arterial pressure and heart rate (HR) values compared to their respective young counterparts. The aged groups also showed a predominance of the sympathetic autonomic component in the determination of HR, whereas the young rats showed a vagal predominance. An assessment of cardiac contractility showed that aged Sham-operated and OVX rats had lower contractile responses following the administration of dobutamine compared to their respective young counterparts. In addition, the aged groups showed higher mRNA and protein expression levels of the β1-adrenergic receptors. In conclusion, our results show that haemodynamic alterations and impairment of the autonomic parameters were similar between the groups of rats subjected to early and physiological menopause. Moreover, these results seem to be due to the ageing process and not ovarian hormone deprivation.

685 Dobutamine Improves Microcirculation in a Model of Controlled Cardiac Output

BackgroundCardiopulmonary bypass is associated with microcirculatory disturbances which are reversible at the bypass weaning. Catecholamines have cardiac and peripheral vascular effects, which are difficult to separate. Previous studies have suggested that Dobutamine may have a direct peripheral vascular effect in septic shock patients. The aim of the present study is to investigate the effect of dobutamine in a model of impaired microcirculation and a fixed cardiac output.MethodsThe sublingual microcirculation in 40 patients undergoing elective cardiac surgery on normothermic cardiopulmonary bypass was measured using side-stream dark-field imaging. 20 patients received dobutamine for 30 minutes before having their microcirculation measured followed by 30 minutes saline. the other half of the group had or saline was Each patient was it's own control. Only vessels below 25 μm in diameter were studied and flow was categorized using a semi-quantitative approach. The total vessel length per microscope field was measured.ResultsAnesthesia induction was associated with an improvement of microcirculation with a decrease in intermittent and sluggishly perfused vessels. Cardio-pulmonary bypass is associated with a microcirculatory shut down with a 40% decrease in continuously perfused vessels. Dobutamine was associated with slight (NS) improvement of in the continuously perfused vessels but this still remain below pre-induction functional capillary density as shown in Table 1.Tabled 1ConclusionThis investigation showed that anesthesia induction improves micro-circulation, cardio-pulmonary bypass impairs micro-circulation and dobutamine administration partially improves this micro-circulatory shut down independently of a cardiac effect. The mechanism, effect on post-operative outcome and it's effect of other situations where microcirculation is impaired requires further studies. BackgroundCardiopulmonary bypass is associated with microcirculatory disturbances which are reversible at the bypass weaning. Catecholamines have cardiac and peripheral vascular effects, which are difficult to separate. Previous studies have suggested that Dobutamine may have a direct peripheral vascular effect in septic shock patients. The aim of the present study is to investigate the effect of dobutamine in a model of impaired microcirculation and a fixed cardiac output. Cardiopulmonary bypass is associated with microcirculatory disturbances which are reversible at the bypass weaning. Catecholamines have cardiac and peripheral vascular effects, which are difficult to separate. Previous studies have suggested that Dobutamine may have a direct peripheral vascular effect in septic shock patients. The aim of the present study is to investigate the effect of dobutamine in a model of impaired microcirculation and a fixed cardiac output. MethodsThe sublingual microcirculation in 40 patients undergoing elective cardiac surgery on normothermic cardiopulmonary bypass was measured using side-stream dark-field imaging. 20 patients received dobutamine for 30 minutes before having their microcirculation measured followed by 30 minutes saline. the other half of the group had or saline was Each patient was it's own control. Only vessels below 25 μm in diameter were studied and flow was categorized using a semi-quantitative approach. The total vessel length per microscope field was measured. The sublingual microcirculation in 40 patients undergoing elective cardiac surgery on normothermic cardiopulmonary bypass was measured using side-stream dark-field imaging. 20 patients received dobutamine for 30 minutes before having their microcirculation measured followed by 30 minutes saline. the other half of the group had or saline was Each patient was it's own control. Only vessels below 25 μm in diameter were studied and flow was categorized using a semi-quantitative approach. The total vessel length per microscope field was measured. ResultsAnesthesia induction was associated with an improvement of microcirculation with a decrease in intermittent and sluggishly perfused vessels. Cardio-pulmonary bypass is associated with a microcirculatory shut down with a 40% decrease in continuously perfused vessels. Dobutamine was associated with slight (NS) improvement of in the continuously perfused vessels but this still remain below pre-induction functional capillary density as shown in Table 1.Tabled 1 Anesthesia induction was associated with an improvement of microcirculation with a decrease in intermittent and sluggishly perfused vessels. Cardio-pulmonary bypass is associated with a microcirculatory shut down with a 40% decrease in continuously perfused vessels. Dobutamine was associated with slight (NS) improvement of in the continuously perfused vessels but this still remain below pre-induction functional capillary density as shown in Table 1. ConclusionThis investigation showed that anesthesia induction improves micro-circulation, cardio-pulmonary bypass impairs micro-circulation and dobutamine administration partially improves this micro-circulatory shut down independently of a cardiac effect. The mechanism, effect on post-operative outcome and it's effect of other situations where microcirculation is impaired requires further studies. This investigation showed that anesthesia induction improves micro-circulation, cardio-pulmonary bypass impairs micro-circulation and dobutamine administration partially improves this micro-circulatory shut down independently of a cardiac effect. The mechanism, effect on post-operative outcome and it's effect of other situations where microcirculation is impaired requires further studies.

CO2-Dependent Vasomotor Reactivity of Cerebral Arteries in Patients with Severe Traumatic Brain Injury: Time Course and Effect of Augmentation of Cardiac Output with Dobutamine

Failing cerebral blood flow (CBF) autoregulation may contribute to cerebral damage after traumatic brain injury (TBI). The purpose of this study was to describe the time course of CO(2)-dependent vasoreactivity, measured as CBF velocity in response to hyperventilation (vasomotor reactivity [VMR] index). We included 13 patients who had had severe TBI, 8 of whom received norepinephrine (NE) based on clinical indication. In these patients, measurements were also performed after dobutamine administration, with a goal of increasing cardiac output by 30%. Blood flow velocity was measured with transcranial Doppler ultrasound in both hemispheres. All patients except one had an abnormal VMR index in at least one hemisphere within the first 24 h after TBI. In those patients who did not receive catecholamines, mean VMR index recovered within the first 48 to 72 h. In contrast, in patients who received NE within the first 48 h period, VMR index did not recover on the second day. Cardiac output and mean CBF velocity increased significantly during dobutamine administration, but VMR index did not change significantly. In conclusion, CO(2) vasomotor reactivity was abnormal in the first 24 h after TBI in most of the patients, but recovered within 48 h in those patients who did not receive NE, in contrast to those eventually receiving the drug. Addition of dobutamine to NE had variable but overall insignificant effects on CO(2) vasomotor reactivity.

Intermittent dobutamine administration mimicked exercise‐induced cardiac phenotype and protected against left ventricular acute pressure overload

The aim of the present study was to address if the submission to a stimuli that mimicked the intermittent cardiac overload imposed by exercise training, would result in a comparable cardioprotective phenotype. Male Wistar rats were submitted to treadmill running (Ex,n=20), dobutamine (Dob; 2mg/kg,s.c.,n=20) or placebo administration (Cont,n=20) for 5 days/week during 8 weeks. After that, half were sacrificed for histological and biochemical analysis and half were submitted to hemodynamic evaluation at baseline and during 2 hours of left ventricular acute pressure (LVP) overload (35% increase in LVPmax). Both Ex and Dob showed cardiac hypertrophy with normal MHC isoforms, fibrosis, osteopontin‐1 and calcineurin protein levels. Moreover, they presented increased SERCA2a and phospho Akt/mTOR protein levels. Both Ex and Dob protected from cardiac dysfunction induced by acute LVP overload. These data suggest that chronic submission to intermittent cardiac overload induced by dobutamine provides a cardioprotective phenotype resembling exercise training.

Acute effect of sildenafil on central hemodynamics in mechanically ventilated patients with WHO group III pulmonary hypertension and right ventricular failure necessitating administration of dobutamine

Background/ObjectivesSildenafil decreases pulmonary vascular resistance index (PVRI), in patients with pulmonary hypertension (PH). We investigated sildenafils' effects on central hemodynamics of mechanically ventilated patients with WHO group-III PH and RV failure necessitating dobutamine administration. MethodsProspective non-controlled study involving 12 (9 males, 59±4years old), patients with the above characteristics. All patients in phase-1 (days 1–2) received dobutamine (5μg/kg/min IV). During phase-2 (days 3–6), sildenafil was started via nasogastric tube (80mg/day) and dobutamine discontinuation was attempted. Patients were designated responders or non-responders based on whether dobutamine could be stopped or not. Phase-3 lasted from day 7 to day of weaning from mechanical ventilation; or if weaning failed, until day 20 following admission (end-of-study). Invasive and echocardiographic parameters were repeatedly recorded throughout the study. ResultsSignificantly changed parameters (P<0.025) from baseline to phase-1, -2 and -3 (%change of mean ratios), in responders (n=7) included among others PVRI (−40%, −51%, −42%), RV stroke work index (RVSWI: 43%, 79%, 41%) and cardiac index (49%, 54%, 48%), which also differed significantly from non-responders (N=5). In phases-1 and -3 non-responders had not significant changes, in phase-2 PVRI (27%) and RVSWI (−22%) changed significantly. In contrast to non-responders, all responders were weaned from mechanical ventilation until the end-of-study (P<0.025). ConclusionsSildenafil may improve central hemodynamics and RV function indices in ventilated patients with WHO group-III PH and RV failure requiring dobutamine infusion, when they respond favorably to the latter. Accordingly, an adequate RV systolic reserve may be mandatory for sildenafil to exert its actions.

Effects of ivabradine on heart rate and left ventricular function in healthy cats and cats with hypertrophic cardiomyopathy

To evaluate the effects of the pacemaker funny current (I(f)) inhibitor ivabradine on heart rate (HR), left ventricular (LV) systolic and diastolic function, and left atrial performance in healthy cats and cats with hypertrophic cardiomyopathy (HCM). 6 healthy cats and 6 cats with subclinical HCM. Anesthetized cats underwent cardiac catheterization and were studied over a range of hemodynamic states induced by treatment with esmolol (200 to 400 μg/kg/min, IV), esmolol and dobutamine (5 μg/kg/min, IV), ivabradine (0.3 mg/kg, IV), and ivabradine and dobutamine. Left ventricular systolic and diastolic function, cardiac output, and left atrial function were studied via catheter-based methods and echocardiography. Treatment with ivabradine resulted in a significant reduction of HR, rate-pressure product, and LV contractile function and a significant increase in LV end-diastolic pressure, LV end-diastolic wall stress, and LV relaxation time constant (tau) in cats with HCM. Concurrent administration of ivabradine and dobutamine resulted in a significant increase of LV contractility and lusitropy, with blunted chronotropic effects of the catecholamine. Left atrial performance was not significantly altered by ivabradine in cats with HCM. Regression analysis revealed an association between maximum rate of LV pressure rise and tau in cats with HCM. Ivabradine had significant effects on several cardiovascular variables in anesthetized cats with HCM. Studies in awake cats with HCM are needed to clinically validate these findings.

Echocardiographic changes during acute pulmonary edema subsequent to scorpion sting

Acute pulmonary edema (APE) occurring after scorpion sting is the leading cause of death of the victims of scorpion envenomation. The APE origin is still questioned by physicians treating these patients. Based on echocardiographic study of 20 patients with severe envenomation treated in Ouargla Hospital resuscitation ward during the last four years, the APE etiology seems more likely cardiogenic, referring to cardiac symptoms confirmed by echocardiography although other mechanisms may also be involved. This hypothesis is further confirmed by the positive response of patients to the administration of dobutamine.

Effects of a constant rate infusion of detomidine on cardiovascular function, isoflurane requirements and recovery quality in horses

ObjectiveTo examine the influence of a detomidine constant rate infusion (CRI) on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing elective surgery. Study designProspective, randomized, blinded, clinical trial. AnimalsTwenty adult healthy horses. MethodsAfter sedation (detomidine, 10 μg kg−1 intravenously [IV]) and induction of anaesthesia (midazolam 0.06 mg kg−1, ketamine 2.2 mg kg−1 IV), anaesthesia was maintained with isoflurane in oxygen/air (inspiratory oxygen fraction 55%). When indicated, the lungs were mechanically ventilated. Dobutamine was administered when MAP < 70 mmHg. The horses were randomly allocated to one of two groups and throughout anaesthesia, received either a detomidine (5 μg kg−1 hour−1) (D) or saline (S) CRI, with the anaesthetist unaware of the treatment. Monitoring included end-tidal isoflurane concentration, arterial pH, PaCO2, PaO2, dobutamine administration rate, heart rate (HR), arterial pressure, cardiac index (CI), systemic vascular resistance (SVR), stroke index and oxygen delivery index ( D˙O2I). For recovery from anaesthesia, all horses received 2.5 μg kg−1 detomidine IV. Recovery quality and duration were recorded in each horse. For statistical analysis, anova, Pearson chi-square and Wilcoxon rank sum tests were used as relevant. ResultsHeart rate (p = 0.0176) and D˙O2I (p = 0.0084) were lower and SVR higher (p = 0.0126) in group D, compared to group S. Heart rate (p = 0.0011) and pH (p = 0.0187) increased over time. Significant differences in isoflurane requirements were not detected. Recovery quality and duration were comparable between treatments. Conclusions and clinical relevanceA detomidine CRI produced cardiovascular effects typical for a2-agonists, without affecting isoflurane requirements, recovery duration or recovery quality.

The Off-Pump Implantation of an Apicoaortic Valved Graft is Safe and Has No Negative Impact on Coronary Flow and Hemodynamics

: To determine the hemodynamic effect of an off-pump apicoaortic valved graft (AAVG) implantation, we performed a quantitative coronary flow analysis in a swine model of severe aortic stenosis. : In 10 swine, cardiac output, coronary flow, right common carotid artery flow, and internal mammary artery flow were measured along with left and right ventricular pressures and aortic and pulmonary artery pressures. A novel AAVG was implanted off-pump on the left ventricular (LV) apex using a specially designed implantation tool and anastomosed to the descending thoracic aorta. Aortic flow was measured proximally and distally of the AAVG-to-descending thoracic aorta anastomosis. After AAVG implantation, epicardial echo confirmed occlusion of the LV outflow tract by a valvuloplasty balloon. Baseline simultaneous measurements of all parameters were repeated after AAVG implantation and intravenous Dobutamine administration. : The AAVG was implanted without any blood loss. After AAVG implantation and LV outflow tract occlusion, the aortic flow proximal to the AAVG-to-descending thoracic aorta anastomosis changed from antegrade (1508 ± 435 mL/min) to retrograde (-529 ± 241 mL/min, P < 0.001). All other measured parameters remained unchanged compared with baseline. After intravenous Dobutamine administration, LV pressure increased from 88 ± 20 to 184 ± 36 mm Hg (+209%, P < 0.0001) and coronary flow increased from 75 ± 34 to 193 ± 90 mL/min (+257%, P = 0.001). : The off-pump implantation of an AAVG is bloodless, safe, reproducible and has no negative impact on coronary flow and hemodynamics. In addition, to the best of our knowledge, this is the first study where blood flow in all coronary arteries was measured simultaneously during an AAVG implantation.

Drug detection in breath: effects of pulmonary blood flow and cardiac output on propofol exhalation

Breath analysis could offer a non-invasive means of intravenous drug monitoring if robust correlations between drug concentrations in breath and blood can be established. In this study, propofol blood and breath concentrations were determined in an animal model under varying physiological conditions. Propofol concentrations in breath were determined by means of two independently calibrated analytical methods: continuous, real-time proton transfer reaction mass spectrometry (PTR-MS) and discontinuous solid-phase micro-extraction coupled with gas chromatography mass spectrometry (SPME-GC-MS). Blood concentrations were determined by means of SPME-GC-MS. Effects of changes in pulmonary blood flow resulting in a decreased cardiac output (CO) and effects of dobutamine administration resulting in an increased CO on propofol breath concentrations and on the correlation between propofol blood and breath concentrations were investigated in seven acutely instrumented pigs. Discontinuous propofol determination in breath by means of alveolar sampling and SPME-GC-MS showed good agreement (R(2)=0.959) with continuous alveolar real-time measurement by means of PTR-MS. In all investigated animals, increasing cardiac output led to a deterioration of the relationship between breath and blood propofol concentrations (R(2)=0.783 for gas chromatography-mass spectrometry and R(2)=0.795 for PTR-MS). Decreasing pulmonary blood flow and cardiac output through banding of the pulmonary artery did not significantly affect the relationship between propofol breath and blood concentrations (R(2)>0.90). Estimation of propofol blood concentrations from exhaled alveolar concentrations seems possible by means of different analytical methods even when cardiac output is decreased. Increases in cardiac output preclude prediction of blood propofol concentration from exhaled concentrations.

Reverse Remodeling With Left Ventricular Assist Devices

Over the last 2 decades, numerous advancements in medical therapies have improved patient outcomes in heart failure (HF). However, a significant number of patients still progress to end-stage HF, in which treatment options are largely limited to cardiac transplantation. As patient demands for transplant continue to exceed the supply of available organs, mechanical assist devices—specifically, the left ventricular assist device (LVAD)—were initially introduced as a bridge to cardiac transplantation. LVADs have 2 important beneficial effects. First, LVADs are placed in parallel to the native left ventricle (LV), causing pressure and volume unloading of the LV. Second, LVADs restore cardiac output and subsequent perfusion to the organs. As a result of these 2 effects, it became evident that some patients had actual improvement in LV function after LVAD placement. The term reverse remodeling was used to describe the improvement in myocardial function that was observed in patients with a seemingly end-stage disease. With reverse remodeling, a new hope for the treatment of HF was born—using LVADs as a bridge to recovery; however, to date, this promise has largely been unrealized. This probably is reflective of the fact that the sequela of mechanical ventricular unloading are quite complex and appear to involve the engagement of competing biological pathways including regression of cardiomyocyte hypertrophy as well as progressive cell atrophy. Although the promise of ventricular recovery still persists, its actualization will await a more comprehensive dissection of these competing biological processes. This review will discuss the beneficial clinical effects of LVAD support as well as review what is known about the cellular and molecular response to mechanical unloading and mechanisms of reverse remodeling. Key research findings have been summarized in the Table. View this table: Table. Summary of Research of LVAD Support on Clinical Effects and the Cellular and Molecular Changes That May Contribute to Reverse …

Impaired Left Ventricular Stroke Volume Reserve During Clinical Dobutamine Stress Predicts Future Episodes of Pulmonary Edema

The purpose of this study was to determine whether dobutamine-induced abnormal stress changes in left ventricular stroke volume (LVSV) and aortic stiffness predict future pulmonary edema. Increased aortic stiffness that decreases LVSV during adrenergic stress may serve as a marker for future pulmonary edema (PE). We measured LVSV, ventriculovascular stiffness (pulse pressure/LVSV(index)), and aortic distensibility at rest and during intravenous dobutamine administration using cardiovascular magnetic resonance. Personnel blinded to dobutamine cardiovascular magnetic resonance followed participants longitudinally over time to identify those admitted to the hospital with PE. Data for 44 participants who had a hospital admission for PE were compared with data for 72 participants of similar age, sex, and resting left ventricular ejection fraction who remained PE free. Expressed as median and interquartile range, participants with and without PE exhibited a decreased stress/rest LVSV ratio (0.9 [range 0.7 to 1.1] vs. 1.0 [range 0.9 to 1.2], respectively; p = 0.002), an increased ventriculovascular stiffness stress/rest ratio (1.4 [range 1.0 to 1.6] vs. 1.0 [range 0.8 to 1.3], respectively; p ≤ 0.001); and a decreased stress-induced measure of aortic distensibility (0.8 mm Hg(-3) [range 0.3 to 1.3 mm Hg(-3)] vs. 1.6 mm Hg(-3) [range 1.2 to 3.2 mm Hg(-3)], respectively; p = 0.002). After accounting for age, sex, left ventricular ejection fraction, risk factors for PE, and the presence of dobutamine-induced ischemia, LVSV reserve and the stress/rest ventriculovascular stiffness ratio still differed (p < 0.008 for both) in those with and without PE. In patients without inducible ischemia during dobutamine stress testing in whom one might otherwise assume a favorable prognosis, the failure to increase LVSV or an increase in ventriculovascular stiffness indicates patients at risk of subsequent PE.