Dobutamine Infusion Research Articles

The relationship between intestinal and oral mucosa microcirculation in anaesthetized horses

ObjectiveTo compare alteration in intestinal blood flow in anaesthetized horses with changes in oral mucosa blood flow. Study designProspective, randomized clinical study. AnimalsEight warmblood horses. MethodsAfter induction with guaifenesin and ketamine, anaesthesia was maintained with isoflurane at 1.5 vol% in oxygen. The tissue blood flow was measured using laser Doppler flowmetry at the jejunum, colon, rectal mucosa, oesophageal mucosa and the oral mucosa. After three baseline measurements, blood flow was first increased by dobutamine infusion and thereafter decreased by increasing isoflurane concentration and all measurements repeated twice. anova was used for comparing the measured parameters to baseline and correlation between the different measurement localizations was examined using Pearson correlation (p < 0.05). ResultsMicroperfusion at all measurement sites increased significantly during dobutamine infusion and decreased significantly during high isoflurane concentration. There was a significant correlation between flow at the oral mucosa and flow at the jejunum (r2 = 0.77, p = 0.002), colon (r2 = 0.76, p < 0.001), rectal mucosa (r2 = 0.88, p < 0.001) and oesophageal mucosa (r2 = 0.83, p <0.001). Conclusions and clinical relevanceOral mucosa blood flow can be used in isoflurane anaesthetized horses to reflect changes of intestinal microcirculation.

Early Development of Right Ventricular Ischemic Lesions in a Novel Large Animal Model of Acute Right Heart Failure in Chronic Thromboembolic Pulmonary Hypertension

BackgroundOur aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration. Methods and ResultsWe used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation. The median duration of ARHF before sacrifice was 162 (135–189) minutes. Although ventriculoarterial coupling (measured with multibeat pressure-volume loops) and stroke volume decreased after iterative pulmonary embolism and improved with dobutamine, relative pulmonary to systemic pressure increased by 2-fold and remained similarly increased with dobutamine. Circulating high-sensitivity troponin I increased after hemodynamic restoration. We found an increase in right ventricular subendocardial and subepicardial focal ischemic lesions and in expression of autophagy-related protein LC3-II (Western blot) in the ARHF-cPH group compared with the cPH (n = 5) and control (n = 5) groups. ConclusionsWe developed and phenotyped a novel large animal model of ARHF on cPH in which right ventricular ischemic lesions were observed early after hemodynamic restoration.

Dobutamine aggravates haemodynamic deterioration induced by pleural effusion: A randomised controlled porcine study.

Pleural effusion is a common finding in critically ill patients and may contribute to circulatory instability and the need for inotropic support. We hypothesised that dobutamine would affect the physiological determinants preload, afterload, contractility and changes of inferior vena cava characteristics during experimental pleural effusion. A randomised, controlled laboratory study. Animal laboratory, conducted from March 2013 to May 2013. Twenty-four Landrace and Yorkshire female piglets (21.3 ± 1.7 kg). Twenty piglets were included in the analyses. After inducing bilateral pleural effusion (30 ml kg), the piglets were block randomised to either incremental dobutamine infusion (n = 10) or control (n = 10). Ultrasonographic measures of left ventricular end-diastolic area, left ventricular afterload, left ventricular fractional area change and inferior vena cava diameter and distensibility were used to assess the basic physiological effect of incremental dobutamine administration during experimental pleural effusion. In the dobutamine group, preload, measured as left ventricular end-diastolic area, decreased from 11.3 ± 2.0 cm after creation of the pleural effusion to 8.1 ± 1.5 cm at a dobutamine infusion rate of 20 μg kg min (P < 0.001). In the same period, central venous pressure and the expiratory diameter of the inferior vena cava decreased from 9 ± 3 to 7 ± 4 mmHg (P < 0.001) and from 1.1 ± 0.2 to 0.9 ± 0.1 cm (P = 0.008), respectively. In a porcine model of pleural effusion, dobutamine affected basic haemodynamic determinants substantially by decreasing left ventricular preload. Changes in central venous pressure and inferior vena cava characteristics were minimal, discouraging their use as indices of preload. This study underlines the significance of evaluating basic haemodynamic determinants to avoid inappropriate, potentially harmful treatment.

β-Adrenergic Responsiveness in the Type 2 Diabetic Heart: Effects on Cardiac Reserve.

This study aimed to determine the chronotopic and inotropic response of the type 2 diabetic heart to β-adrenergic stimulation. Eight people with uncomplicated T2D and seven matched controls performed a dual-energy x-ray absorptiometry scan and V˙O2peak test. Plasma catecholamines were determined at rest and during peak exercise. On a second visit, HR and left ventricular contractility were assessed using echocardiography during supine rest, parasympathetic blockade (atropine), and during incremental β-adrenergic stimulation (dobutamine). V˙O2peak and HR reserve were lower in T2D (P < 0.05) as expected. Both groups increased norepinephrine comparably (P = 0.23) during peak exercise; however, epinephrine increased less in the T2D group (P < 0.05). The dobutamine dose required to achieve 85% of age-predicted maximal HR was 36% higher in CON (P < 0.05). Resting HR was higher (P < 0.01) and stroke volume indexed to fat free mass was smaller (P < 0.05) in T2D. During dobutamine infusion the response (% change) in HR, end-diastolic volumeFFM, stroke volume, ejection fraction, and cardiac output were not different between the groups. However, HR was higher (P < 0.01) and end-diastolic volume indexed to fat free mass (P < 0.01), stroke volumeFFM (P < 0.01), ejection fraction (P < 0.05), and stroke work (P < 0.01) were lower in T2D. Although the type 2 diabetic heart worked at smaller volumes, the HR and contractile response to β-adrenergic stimulation were unaffected by diabetes. The reduced cardiac reserve observed in uncomplicated T2D was not explained by impaired myocardial sympathetic responsiveness but may reflect changes in the loading conditions or function of the diabetic left ventricle.

Myocardial contractile reserve predicts left ventricular reverse remodeling and cardiac events in dilated cardiomyopathy

BackgroundCatecholamine sensitivity estimated using a dobutamine stress test (DST) is recognized as a measure of the beta-adrenergic myocardial contractile reserve, which is involved with left ventricular reverse remodeling (LV-RR). We investigated whether the prognostic ability of the DST for LV-RR could predict cardiac events. MethodsThere was a total of 192 enrolled patients with dilated cardiomyopathy (DCM). DCM was defined as a LV ejection fraction (LV-EF) ≤45% and LV end-diastolic dimension (LVDd) ≥55mm. One hundred patients were subjected to micromanometer-based measurement of the maximal first derivative of LV pressure (LVdP/dtmax), an index of LV contractility, at baseline and following the infusion of dobutamine (10μg/kg/min) via a pigtail catheter. Percentage changes in LVdP/dtmax from the baseline to peak values under dobutamine stress (ΔLVdP/dtmax) were also calculated. After excluding 17 patients who received cardiac resynchronization therapy within 3 months of undergoing DST (n=15) and who did not receive follow-up echocardiography (n=2), 83 patients were enrolled (52.5±12.3 years). ResultsDuring the follow-up period (4.7±2.6 years), LV-RR was recognized in 49 of 83 patients (59.0%). A multivariate logistic regression analysis revealed that ΔLVdP/dtmax (hazard ratio: 1.024, p=0.007) and the symptom duration (hazard ratio: 0.977, p=0.003) were independent predictors of LV-RR. A receiver operating characteristic curve analysis revealed a ΔLVdP/dtmax cut-off value of 75.1% for LV-RR and a significantly lower cardiac event rate in the ΔLVdP/dtmax≥75.1% group (p=0.045). ConclusionsΔLVdP/dtmax estimated using DST was a useful predictor of LV-RR and cardiac events in patients with DCM.

The importance of myocardial contractile reserve in predicting response to cardiac resynchronization therapy.

To perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure. We searched MEDLINE/PubMed and Cochrane for all papers published up to 26 April 2016, supplemented by manual searches of reference lists from retrieved articles. The search strategy yielded nine observational studies that met our eligibility criteria with a total of 767 patients of which 757 provided data for this analysis. Contractile reserve after dobutamine infusion was present in 496 patients (66%). During follow-up 474 patients (63%) qualified as CRT responders. The presence of contractile reserve was associated with a higher chance of CRT response (odds ratio 4.42, 95% confidence interval 2.15-9.07, P < 0.001) using a random-effects model. There was evidence of publication bias. Imputation of missing studies attenuated the association to some extent, but the positive association between contractile reserve and CRT response remained with an odds ratio of 2.42 (95% confidence interval 1.17-5.05, P = 0.018). The presence of global contractile reserve at baseline, as assessed by dobutamine stress echocardiography, is associated with a higher chance of CRT response in patients with heart failure.

Anomalous Coronary Arteries and Myocardial Bridges: Risk Stratification in Children Using Novel Cardiac Catheterization Techniques.

The evaluation of the vast majority of children with anomalous aortic origin of a coronary artery (AAOCA) and/or myocardial bridges is performed with non-invasive testing. However, a subset of these patients may benefit from invasive testing for risk stratification. All patients included in the Coronary Anomalies Program (CAP) at Texas Children's Hospital who underwent cardiac catheterization were included. Techniques included selective coronary angiograms (SCA), intravascular ultrasound (IVUS), and fractional flow reserve (FFR) measurements with provocative testing using adenosine and/or dobutamine infusions. Out of the 131 patients followed by the CAP between 12/12-4/16, 8 (6%) patients underwent 9 cath investigations at median age 13.1 (2.6-18.7) years and median weight 49.5 (11.4-142.7) kg. Six patients presented with cardiac signs/symptoms. Four patients had myocardial bridges of the left anterior descending (LAD) coronary artery, 2 patients had isolated AAOCA, and 2 patients had an anomalous left coronary artery (LCA) with an intramyocardial course of the LAD. SCA was performed in all patients. FFR was positive in 4/6 patients: IVUS showed >70% intraluminal narrowing in 3/5 patients. One patient had hemodynamic instability that reversed with catheter removal from the coronary ostium. Based on the catheterization data obtained, findings were reassuring in three patients, surgery was performed in three patients, and two patients are being medically managed/restricted from competitive sports. In our small cohort of patients, we demonstrated that IVUS and FFR can safely be performed in children and may help to risk stratify some patients with AAOCA and myocardial bridges.

Takostubo Cardiomyopathy Induced by Dobutamine Infusion

Dobutamine stress echocardiography (DSE) is a widely used and very safe cardiac imaging modality. One of the rare complications of DSE is Takostubo cardiomyopathy. It is characterized by transient left ventricular systolic dysfunction, most commonly involving the apical segments with compensatory hyperkinesis in basal segments leading to “apical ballooning”. The exact mechanism of this pathology is not completely understood. Takostubo cardiomyopathy has an increased prevalence in post-menopausal females, and is commonly precipitated by emotional or physiologic stress. We present a rare case of a 55-year-old woman who developed Takostubo cardiomyopathy associated with DSE. The patient developed severe apical hypokinesis at peak dobutamine infusion. Subsequent cardiac catheterization did not show evidence of obstructive coronary artery disease (CAD). Partial recovery of her left ventricular systolic dysfunction was noted after 48 hours with complete recovery present on follow up imaging three months after the initial encounter.

Clinical usefulness of intravenous constant rate infusion of fentanyl and medetomidine under sevoflurane anesthesia in Thoroughbred racehorses undergoing internal fixation surgery

ABSTRACTA total of 20 racehorses with longitudinal fractures underwent internal fixation surgery under sevoflurane anesthesia combined with infusion of medetomidine (3 µg/kg/hr) alone (10 horses, group M) or medetomidine and fentanyl (7 µg/kg/hr) (10 horses, group FM). In group FM, the end-tidal sevoflurane concentration during surgery was maintained significantly lower than in group M (2.8–2.9% for group M vs. 2.2–2.6% for group FM, P<0.01). The mean arterial blood pressure was maintained over 70 mmHg using dobutamine infusion (group M, 0.36–0.54 µg/kg/min; group FM, 0.27–0.65 µg/kg/min), and the recovery qualities were clinically acceptable in both groups. In conclusion, co-administration of fentanyl and medetomidine by constant rate infusion may be a clinically useful intraoperative anesthetic adjunct for horses to reduce the requirement of sevoflurane when they undergo orthopedic surgery.

Inotropic support against early brain injury improves cerebral hypoperfusion and outcomes in a murine model of subarachnoid hemorrhage.

Early brain injury/ischemia is a recent therapeutic target that contributes to triggering delayed cerebral ischemia (DCI) in the setting of subarachnoid hemorrhage (SAH). This study aimed to determine the role of dobutamine for inotropic cardiac support in improving cerebral blood flow (CBF) and outcomes after experimental SAH, mediated by hypoxia-inducible factor (HIF). Thirty-one mice were subjected to SAH by endovascular perforation, and assigned to either 2% isoflurane postconditioning performed between 1 and 2.5h after SAH induction or concomitant intravenous dobutamine infusion (15μg/kg/min) with or without HIF inhibitor 2-methoxyestradiol (2ME2) (10mg/kg) administered intraperitoneally. Neurobehavioral function was assessed daily by neurological scores and open field testing. DCI was defined 3days later by detecting a new infarction on MRI. Global CBF depression was notable early after SAH, but dobutamine showed significant improvement in CBF, lower incidence of DCI, and better recovery of neuroscores and open field test variables compared with isoflurane postconditioning (P<0.05). CBF over the entire brain on day 1 predicted DCI with a cut-off of 36.5ml/100g/min (80% specificity and 67% sensitivity), with a better area under the curve (0.83 versus 0.75) than the hemispheric CBF measured on the perforated side. The dobutamine-mediated outcomes were attenuated (P<0.05) by 2ME2 pretreatment. The data suggest that cardiac support with dobutamine improves global CBF depression induced by early brain injury, leading to reduced prevalence of DCI and better functional outcomes after experimental SAH, in which HIF may be acting as a critical mediator.

Pressure–volume loop-derived cardiac indices during dobutamine stress: a step towards understanding limitations in cardiac output in children with hypoplastic left heart syndrome

BackgroundChildren with a single systemic right ventricle, such as in hypoplastic left heart syndrome (HLHS), frequently experience reduced exercise capacity. Elucidating the causes could help with optimising treatment strategies. MethodsProspective data from 10 consecutive symptomatic patients with HLHS undergoing clinical cardiac magnetic resonance with catheterisation (XMR) were analysed. Mean age 8.6years (range 3.5–11.6years), mean time since Fontan completion 5.5years. MR-compatible catheters were placed in the systemic right ventricle and branch pulmonary arteries to record pressures at rest, with dobutamine infusion at 10mcg/kg/min and at 20mcg/kg/min. Cine short-axis stacks of the ventricle were performed at each condition and used to construct pressure–volume loops. ResultsCompared to rest, cardiac index increased with low-dose dobutamine (p<0.01) with no further rise at peak stress despite a further, albeit, blunted rise in heart rate (p=0.002). A fall in stroke volume occurred (p=0.014) despite good contractility (74% increase, p=0.045) and a well-coupled ventriculo-arterial ratio. End-diastolic pressure and early active relaxation, markers of diastolic function, were normal at rest. However, preload fell at peak stress (p<0.008) while pulmonary vascular resistance (PVR) was low throughout. This group of HLHS patients demonstrated a fall in SV at peak stress, coinciding with a fall in preload. ConclusionsMarkers of systolic and diastolic function remained normal. Failure to adequately fill the ventricle implies a ceiling of maximal flow through the Fontan circuit despite low PVR.

Effects of dobutamine hydrochloride on cardiovascular function in horses anesthetized with isoflurane with or without acepromazine maleate premedication.

OBJECTIVE To determine the effects of acepromazine maleate premedication on cardiovascular function before and after infusion of dobutamine hydrochloride for 30 minutes in isoflurane-anesthetized horses. ANIMALS 6 healthy adult horses. PROCEDURES Each horse was anesthetized once following premedication with acepromazine (0.02 mg/kg, IV) administered 30 minutes prior to anesthetic induction (ACP+ treatment) and once without premedication (ACP- treatment). Anesthesia was induced with IV administration of xylazine hydrochloride (0.8 mg/kg), ketamine hydrochloride (2.2 mg/kg), and diazepam (0.08 mg/kg). Horses were positioned in right lateral recumbency, and anesthesia was maintained via inhalation of isoflurane delivered in oxygen. End-tidal isoflurane concentration was adjusted to achieve a target mean arterial blood pressure of 60 mm Hg (interquartile range [25th to 75th percentile], 57 to 63 mm Hg) for at least 15 minutes. Cardiac index, oxygen delivery index, and femoral arterial blood flow indices were determined 60 minutes after anesthetic induction (baseline). Dobutamine was then infused to achieve a target mean arterial blood pressure of 80 mm Hg (interquartile range, 76 to 80 mm Hg). Data collection was repeated 30 minutes after the start of dobutamine infusion for comparison with baseline values. RESULTS Complete data sets were available from 5 of the 6 horses. Dobutamine administration resulted in significant increases in oxygen delivery and femoral arterial blood flow indices but no significant change in cardiac index for each treatment. However, at baseline or 30 minutes after the start of dobutamine infusion, findings for the ACP+ and ACP- treatments did not differ. CONCLUSIONS AND CLINICAL RELEVANCE In isoflurane-anesthetized horses, dobutamine administration increased oxygen delivery and femoral arterial blood flow indices, but these changes were unaffected by premedication with acepromazine.

Hemodynamic and metabolic effects of a new pediatric dobutamine formulation in hypoxic newborn pigs.

The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans. Newborn pigs (n = 18) were exposed to 2-h hypoxia (10-15% oxygen) followed by reoxygenation (21-30% oxygen 4 h). After 1-h reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10-15 or 15-20 µg/kg/min. Dobutamine groups received two dobutamine doses during 30 min with a 60 min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals, an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF. Hypoxia significantly decreased CI, systemic vascular resistance and mean arterial blood pressure (MABP). Dobutamine doses significantly increased heart-rate, CI, and oxygen-delivery without changes in stroke-volume and MABP. Only 10-15 µg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared spectroscopy. A positive correlation was observed between SVCF and CI. The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials.

Magnetic resonance imaging assessment of cardiac function in a swine model of hibernating myocardium 3 months following bypass surgery

ObjectiveClinical studies demonstrate delayed recovery of hibernating myocardium (HM) following coronary artery bypass graft (CABG) surgery. Cardiac magnetic resonance (CMR) imaging is effective in identifying HM in clinical settings. Our animal model of HM shows partial but incomplete functional recovery 1 month following CABG using echocardiography. This study uses CMR imaging to determine completeness of recovery 3 months post-CABG. MethodsSwine (N = 12) underwent left anterior descending artery (LAD) 1.5-cm constrictor placement creating a territory of HM over 12 weeks. CMR at 12 weeks confirmed hibernation without infarction (N = 12). Off-pump left internal thoracic artery (LITA) to the LAD was performed in 9 animals. Three animals were killed as HM controls. CMR imaging was repeated in revascularized animals before death at 1 (n = 4) or 3 months (n = 5). CMR imaging was performed at baseline and with dobutamine infusion (5 μg/kg/min). ResultsTwelve weeks after constrictor placement, CMR imaging confirmed viability in LAD region and LAD stenosis in all animals. In HM, wall thickening is reduced at baseline but with contractile reserve present during dobutamine infusion. Following revascularization, CMR imaging confirmed patent LITA graft (n = 9). Analysis of baseline regional function shows incomplete recovery of HM following CABG, with reduced contractile reserve at both 1 and 3 months post-CABG. ConclusionsCMR imaging provides accurate spatial resolution of regional contractile function and confirms the presence of HM at 12 weeks following instrumentation of the LAD. Three months following CABG, partial recovery of HM with contractile reserve is present in the single LAD territory.

Discussion of the best time to use dobutamine after myocardium ischemia/reperfusion

Objective Using isolated rat heart ischemia/reperfusion injury(I/RI) model to compare the effects of dobutamine giving at different time points after reperfusion on cardiac function and myocardial injury and to explore the best time to use dobutamine after myocardium ischemia/reperfusion(I/R). Methods Thirty-six male SD rats, establishing isolated heart I/RI model in Langendorff perfusion apparatus with 15 min equilibrium, 30 min global ischemia and followed by 60 min reperfusion, were randomly divided into four groups(n=9). Different treatment was taken in reperfusion period. Group I/R: reperfused with Kreb's-Henseleit(K-H) solution, dobutamine group one(group D1): received dobutamine for 30 min after 5 min of reperfusion, other time perfused with K-H solution. Dobutamine group two (group D2): given dobutamine for 30 min after 15 min of reperfusion, other time perfused with K-H solution. Dobutamine group three(group D3): administrated dobutamine for 30 min after 25 min of reperfusion, other time perfused with K-H solution. Dobutamine infusion dose was 10 μg·kg-1·min-1. Heart function indexes of each group at the end of balance reperfusion(T0) and 10 min (T1), 20 min(T2), 30 min(T3), 60 min(T4) of reperfusion: HR, left ventricular end diastolic pressure(LVEDP), left ventricular developed pressure(LVDP), the maximum rate of left ventricular pressure change(±dp/dtmax) and coronary flow(CF) were recorded. The coronary flow at T0-T4 time points was used to measure the activity of lactate dehydrogenase (LDH) and creatine kinase(CK) according to the test methods attached to LDH and CK test kit. Myocardial infarct size(MIS) were measured with 2,3,5-triphenyl tetrazolium chloride (TTC) staining method. Sarcoendoplasmic reticulum Ca2+-ATPase (SERCA2a) and ryanodine receptors(RyR2) expression were determined by Western bloting. Results After giving dobutamine, HR, LVEDP, LDH and CK activity and MIS of group D1 were higher than those in group I/R(P 0.05). SERCA2a expression between the above groups was no significant difference. While RyR2 expression was higher in groups with dobutamin compared to group I/R. There was no significant difference in above data between group D2 and D3 after using dobutamine. Conclusions Giving dobutamine after 15 min of myocardial I/R in rats is superior to the other time points. Using dobutamine at this time point can timely and effectively improve HR, increase CF, improve myocardial contractile function, and does not aggravate myocardial injury. Key words: Myocardial; Ischemia/reperfusion injury; Dobutamine

Abstract 11383: Reversal of Post-stroke Cerebral Microvascular Dysfunction by Neuroprotective and Hyperdynamic Therapy for Experimental Subarachnoid Hemorrhage

Introduction: Early brain injury characterized by microvascular dysfunction in cerebral vessels may play an important role in the development of delayed cerebral ischemia (DCI) or vasospasm after subarachnoid hemorrhage (SAH). However, little is known as to the microcirculatory mechanism(s) to treat post-SAH DCI. Hypothesis: To clarify the utility of neuroprotective and hyperdynamic therapy in relieving cerebral microcirculatory dysfunction affected by vasospasm after experimental SAH. Methods: Male C57BL/6 mice were subjected to SAH by endovascular perforation and minocycline for antibiotic and anti-inflammatory use was started. Closed cranial bone window was then made over the left somatosensory cortex. In vivo real-time imaging was performed using 2-photon laser-scanning microscopy at postoperative day 3 to record alterations on the level of cerebral microvessels and the effects of dobutamine hyperdynamic therapy at clinical dose were evaluated. Comparison was made with a group without minocycline administration. Results: According to the 3-dimentional observation, &gt;50% of pial and penetrating arteries constricted moderately (25-50%) from day 2 to 3 after SAH, which was greater in number in a group without minocycline pretreatment (p&gt;0.05). In areas close to the microvasospasm, blood cell flow as measured by line scan increased by 24% (range, from 7 to 39%) following dobutamine infusion. Reversal of flow stagnation by dobutamine was more prominently observed in animals with minocycline pretreatment in pial and penetrating arteries (1.2 ± 0.5 vs. 1.8 ± 1.0 mm/s, p&lt;0.05). Diameters of the microvessels or location of microthrombi in precapillary arterioles were not affected in any of the groups (p&gt;0.05). Conclusions: The data suggest that early neuroprotection followed by inotropic hemodynamic therapy can improve microcirculation in specific areas affected by microvasospasm, which may in part, explain novel therapeutic targets for the early treatment of DCI after SAH.

Case 1: Absent Lower Limb Pulses in a Neonate

A 3-kg term male infant is born to a 26-year-old primigravida woman after 5 years of primary infertility secondary to polycystic ovary syndrome. Vacuum extraction is performed for fetal distress, and the infant is resuscitated with positive pressure ventilation and chest compressions for 60 seconds. In the NICU, mechanical ventilation is initiated. The first blood gas measurement 10 minutes after birth reveals a pH of 6.6, partial pressure of carbon dioxide of 64 mm Hg (8.5 kPa), partial pressure of oxygen of 100.8 mm Hg (13.4 kPa), and bicarbonate of 5.4 mEq/L (5.4 mmol/L). Systemic hypothermia is initiated for perinatal asphyxia with moderate encephalopathy. He develops features of poor perfusion 6 hours after birth and is resuscitated with 2 normal saline boluses. A dobutamine infusion is started, followed by epinephrine infusion for refractory shock. Packed red blood cells are transfused, because the hematocrit is only 35% (0.35) and the infant has a subgaleal hemorrhage. He is given phenobarbitone, phenytoin, and levetiracetam, and later midazolam infusion for refractory seizures. In view of the refractory shock, systemic hypothermia is discontinued and the infant is rewarmed over a period of 8 hours. As his perfusion improves, it is noted that the femoral pulses are weaker than the brachial pulses, with systolic blood pressures 20 mm Hg higher in the upper limbs. The infant is suspected to have critical coarctation of the aorta and a prostaglandin infusion is started. However, an echocardiography at the bedside shows a normal thoracic aorta and aortic arch. A computed …

Ventricular-vascular dynamics in pediatric patients with heart failure and preserved ejection fraction

ObjectiveThe details of the ventricular-vascular dynamics of heart failure with preserved ejection fraction (HFpEF) in children remain poorly understood. We tested the hypothesis that pediatric HFpEF patients have ventricular systolic, diastolic, and arterial stiffening at rest as well as impaired reserve function associated with coronary supply/demand imbalance. MethodsWe studied the ventricular pressure-area relationship in 22 pediatric HFpEF patients and 22 control subjects before and after dobutamine infusion and during abdominal compression. Coronary supply/demand balance was assessed by subendocardial viability ratio (SEVR) calculated from the aortic pressure waveform. ResultsCompared with controls, the HFpEF patients had significantly higher end-systolic (Ees) and arterial (Ea) elastance. Increased ventricular diastolic stiffness also occurred in the HFpEF patients, resulting in modest elevation of end-diastolic pressure (EDP) at rest (13.6±4.3 vs. 7.3±2.3mmHg, P<0.0001). The difference in EDP became more evident with a preload increase through abdominal compression, indicating a limited diastolic reserve in HFpEF patients (EDP changes; 11.3±6.2 for HFpEF vs. 3.4±0.6mmHg for controls, P=0.016). The HFpEF patients exhibited impaired beta-adrenergic reserve in ventricular contractility and ventricular-arterial coupling in response to dobutamine infusion. SEVR was significantly lower in the HFpEF (0.64±0.11) than in the control (0.79±0.07, P<0.0001) and was significantly correlated with LV diastolic stiffness and dobutamine-induced changes in ventricular contractility. ConclusionsHFpEF in children involves higher ventricular-arterial stiffness at rest as well as impaired systolic and diastolic reserve, which closely correlate with impaired coronary supply/demand balance.

Noninvasive assessment of myocardial bridging by coronary flow velocity reserve with transthoracic Doppler echocardiography: vasodilator vs. inotropic stimulation

BackgroundTo consider hemodynamic assessment of myocardial bridging (MB) adequate, it is believed that inotropic stimulation with dobutamine should be estimated because its dynamic nature depends on the degree of extravascular coronary compression. This study evaluated comparative assessment of hemodynamic relevance of MB using coronary flow velocity reserve (CFVR) measurements by transthoracic Doppler echocardiography (TTDE) with vasodilatative and inotropic challenges. MethodsThis prospective study included forty-four patients with angiographic evidence of isolated MB of the left anterior descending coronary artery (LAD) and systolic compression of ≥50% diameter stenosis. All patients were evaluated by exercise stress-echocardiography (ExSE) test for signs of myocardial ischemia, and CFVR of the distal segment of LAD during iv.infusion of adenosine (ADO:140μg/kg/min) and iv.infusion of dobutamine (DOB:10-40μg/kg/min), separately. ResultsExercise-SE was positive for myocardial ischemia in 8/44 (18%) of patients. CFVR during ADO was significantly higher than CFVR during peak DOB (2.85±0.68 vs. 2.44±0.48, p=0.002). CFVR during peak DOB was significantly lower in SE-positive group in comparison to SE-negative group (2.01±0.16 vs. 2.54±0.47, p<0.001), but not for ADO (2.47±0.51 vs. 2.89±0.70, p=0.168), respectively. Multivariable logistic analysis showed that CFVR peak DOB was the most significant predictor of functional significant MB (OR 0.011, 95%CI: 0.001–0.507, p=0.021). Receiver-operating characteristic curves have shown that TTDE-CFVR obtained by high-dose of dobutamine infusion is better than those by adenosine regarding to functional status of MB (AUC 0.861, p=0.004; AUC 0.674, p=0.179, respectively). ConclusionsNon-invasive CFVR measurement by TTDE during inotropic stimulation, in comparison to vasodilation, provides more reliable functional evaluation of MB.

MPS 18-04 FASUDIL PREVENTS CORONARY MICROVASCULAR ENDOTHELIAL DYSFUNCTION AND CARDIAC CONTRACTILE DYSFUNCTION IN A RAT MODEL OF HYPERTENSIVE DIABETES MORE THAN LOSARTAN

Objective: Diabetes, hypertension and obesity are risk factors for the development of heart failure. Rho kinase (ROCK) appears to drive the coronary and contractile dysfunction in early diabetes and in hypertension. We hypothesised that ROCK activation plays a critical role in diabetic heart failure. Design and Method: Using synchrotron radiation microangiography and in vivo small-angle X-ray scattering (SAXS) approaches, we investigated the effect of combined hypertension and insulin resistance on coronary microvessel and cardiac function in lean male rats. Young adult Goto-Kakizaki (GK) rats (n = 9 /group) were maintained on a high salt (6%NaCl) diet for 8 weeks with normal drinking water or water containing fasudil (30 mg/kg/d) or losartan (10 mg/kg/d) before imaging at the SPring-8 synchrotron. Results: Chronic fasudil treatment resulted in a significant improvement in nitric oxide mediated vasodilation ability compared to the untreated control group as acetylcholine administration after inhibition of dilation with indomethacin + charybdotoxin + apamin only evoked consistent dilation of the in situ small arteries and arterioles (30–100 μm diameter) in fasudil treated rats. Losartan did not prevent coronary endothelial dysfunction. Fasudil treatment improved positive inotropy in all layers of the in situ myocardium (assessed as localized cross-bridge cycling with SAXS) during dobutamine infusion. However, losartan treatment was less consistent as some rats showed subendocardial diastolic dysfunction at the cross-bridge level. Conclusions: Fasudil treatment improved coronary flow and contractile reserves more than treatment with an ARB. In particular, fasudil increased nitric oxide bioavailability in the coronary circulation. Furthermore, fasudil was more effective than losartan in normalizing cross-bridge dysfunction that was most pronounced in subepicardial and subendocardial myocardium in untreated rats.