Reduction In End-diastolic Pressure Research Articles

Effect of anti-heart failure therapy on diastolic function in children with single-ventricle circulations.

Children with functionally univentricular circulations have chronic volume loading of the systemic ventricle, potentially affecting ventricular function. Medications including angiotensin-converting enzyme inhibitors and β-blockers are used to treat ventricular dysfunction, despite limited evidence of their efficacy in this population. To determine the effects of angiotensin-converting enzyme inhibitors on elevated filling pressures in children with single ventricle physiology. We performed a single-centre, retrospective review of patients with single ventricle physiology who underwent multiple cardiac catheterisations between 1991 and 2013. Study population comprised of patients who commenced or had optimised dosing of angiotensin-converting enzyme inhibitors between assessments in response to high ventricular filling pressures. Patients undergoing interventions influencing loading conditions between assessments were excluded. A total of 17 patients were identified, with dominant morphologic right ventricle in eight patients (47.1%). Among them, 11 (64.7%) were pre-Fontan and six (35.3%) were post-Fontan completion. Median inter-assessment interval was 9.4 months (range 7.3-19.1). There was a reduction in end-diastolic pressure from 13 to 10 mmHg (p=0.002), mean pulmonary artery pressure from 16 to 13 mmHg (p=0.049), and mean atrial pressure from 12 to 9 mmHg (p=0.001). There was one cardiac transplant, and there were no patient deaths at median follow-up after 31 months. We observed a reduction in ventricular end-diastolic pressure, pulmonary artery pressure, and mean atrial pressure following treatment with angiotensin-converting enzyme inhibitors in patients with single ventricle physiology. Our study provides insights into the potential impact of anti-heart failure therapy in single ventricle circulations and calls for larger, controlled studies to assess for a therapeutic response.

Intra-aortic balloon pump for high-risk percutaneous coronary intervention.

The intra-aortic balloon pump (IABP) was first introduced into clinical practice in 1968.1 Early experimental and clinical trials suggested that intra-aortic balloon counterpulsation could provide circulatory assistance to a failing left ventricle.2,3 Counterpulsation—balloon inflation during diastole and deflation in systole—augments the intrinsic Windkessel effect, whereby potential energy stored in the aortic root during systole is converted to kinetic energy with the elastic recoil of the aortic root. Counterpulsation leads to a decline in afterload, a reduction in cardiac work, and therefore myocardial oxygen requirements of the ventricle. Augmentation of diastolic pressure when the balloon is fully inflated together with reduction in left ventricular (LV) filling pressures contribute to improved coronary perfusion (Figures 1 and 2).4 This proposed improvement in myocardial energetics has been further supported by a significant reduction in systemic lactate.5 These physiological enhancements are thought to be of particular benefit after acute myocardial infarction (AMI), supported by animal studies, which have shown a reduction in infarct size when counterpulsation is used.6,7 Figure 1. Coronary perfusion. Coronary flow is predominantly diastolic and further enhanced by counterpulsation, which augments diastolic blood flow and thus coronary perfusion. In addition, aortic recoil during diastole further improves efficiency of the left ventricle. Figure 2. Systemic arterial pressure waveform on introduction of intra-aortic balloon pump–assisted diastolic augmentation. The intra-aortic balloon pump inflates at the dicrotic notch, leading to peak-augmented diastolic pressure. As the balloon deflates, assisted end diastolic pressure is seen to be lower than unassisted end diastolic pressure and assisted systolic pressure is lower than unassisted systolic pressure. Peak diastolic augmentation should be greater than the unassisted systolic pressure and both assisted pressures should be less than the unassisted pressures. Intra-aortic balloon counterpulsation was initially used as a means of supporting patients undergoing surgical revascularization. Percutaneous delivery …

Intramyocardial transplantation of fibroblasts expressing vascular endothelial growth factor attenuates cardiac dysfunction

In this study, we analyzed whether transplantation of cardiac fibroblasts (CFs) expressing vascular endothelial growth factor (VEGF) mitigates cardiac dysfunction after myocardial infarction (MI) in rats. First, we observed that the transgene expression lasts longer (45 vs 7 days) when fibroblasts are used as vectors compared with myoblasts. In a preventive protocol, induction of cardiac neovascularization accompanied by reduction in myocardial scar area was observed when cell transplantation was performed 1 week before ischemia/reperfusion and the animals analyzed 3 weeks later. Finally, the therapeutic efficacy of this approach was tested injecting cells in a fibrin biopolymer, to increase cardiac retention, 24 h post-MI. After 4 weeks, an increase in neovascularization and a decrease in myocardial collagen were observed only in rats that received cells expressing VEGF. Basal indirect or direct hemodynamic measurements showed no differences among the groups whereas under pharmacological stress, only the group that received cells expressing VEGF showed a significant reduction in end-diastolic pressure and improvement in stroke volume and cardiac work. These results indicate that transplantation of CFs expressing VEGF using fibrin biopolymer induces neovascularization and attenuates left ventricle fibrosis and cardiac dysfunction in ischemic heart.

Does prostaglandin E1 infusion affect the left ventricular filling pattern of end-stage dilated cardiomyopathy? A combined hemodynamic-echo Doppler study.

Prostaglandin E1 improves hemodynamics in patients with severe dilated cardiomyopathy and pulmonary hypertension through it's reducing action on pulmonary resistances. However, few data are available to indicate whether these beneficial effects on right heart hemodynamics translate into any improvement of the altered left ventricular filling pattern that characterizes this condition. We studied 12 patients with dilated cardiomyopathy during preoperative evaluation for cardiac transplantation before and after prostaglandin E1, 30-50 ng/kg/min i.v. Patients underwent catheterization of the right heart and left ventricle by Swan-Ganz catheter, giving simultaneous assessment of pressure by micromanometer and of volume derived from two-dimensional echo-guided Doppler mitral flow velocity, where volume equals mitral velocity integral x valvular area. Prostaglandin E1 induced a significant reduction in mean pulmonary (from 38 to 30 mm Hg; p = 0.0001) and aortic (from 79 to 75 mm Hg, p = 0.05) pressures but no change in heart rate or tau. Peak A wave increased from 28 to 33 cm/s (p = 0.02), along with a reduction in end-diastolic pressure from 29 to 26 mm Hg (p < 0.04), whereas peak E wave did not change. E/A ratio decreased slightly (from 2.5 to 2.1; p < 0.0007) but did not reverse. Systolic volumes decreased (from 231 to 212 ml; p < 0.05), and cardiac index increased from 2.1 to 2.6 L/min/m2 (p = 0.0002) because of a reduction in pulmonary and systemic vascular resistances. The diastolic pressure-volume relation shifted downward along the same curve. Prostaglandin E1 infusion in patients with severe dilated cardiomyopathy and pulmonary hypertension reduces pulmonary and systemic resistances without affecting heart rate, relaxation, or passive diastolic left ventricular properties. Systolic right and left ventricular unloading increases cardiac index, facilitating ventricular emptying. E/A ratio does not reverse, although it decreases slightly, with mechanisms, however, that appear independent of any direct effect of the drug on the ventricular diastolic properties.

The effect of alpha 2-adrenoceptor antagonists in isolated globally ischemic rat hearts.

The alpha 2-adrenoceptor antagonist, yohimbine, has been reported to protect hypoxic myocardium. Yohimbine has several other activities, including 5-HT receptor antagonism, at the concentrations at which protection was found. Therefore we designed a study to determine if yohimbine was protecting ischemic myocardium via antagonism of alpha 2-adrenoceptors. In isolated globally ischemic rat hearts, the effects of two structurally distinct classes of alpha 2-adrenoceptor antagonists, the indole alkaloids (yohimbine and rauwolscine) and the imidazolines (idozoxan and tolazoline) were investigated. Pretreatment with yohimbine (1-10 microM) caused a concentration-dependent increase in reperfusion left ventricular developed pressure and a reduction in end diastolic pressure and lactate dehydrogenase release. The structurally similar compound rauwolscine (10 microM) also protected the ischemic myocardium. In contrast, idozoxan (0.3-10 microM) or tolazoline (10 microM) had no protective effects. The cardioprotective effects of yohimbine were partially reversed by 30 microM 5-HT. These results indicate that the mechanism for the cardioprotective activity of yohimbine may involve 5-HT receptor antagonistic activity.

Stimulation of myocardial lactate extraction by oxfenicine (L-hydroxyphenylglycine).

In animal experiments oxfenicine (L-hydroxyphenylglycine) (LHPG) has been shown to increase myocardial carbohydrate utilization and decrease fat consumption. Seven patients, six of whom proved to have coronary artery disease, were studied during diagnostic cardiac catheterization. Myocardial substrate extraction, coronary sinus flow, cardiac output and left ventricular pressure were measured at basal heart rale and three pacing rates before and after 800 mg oxfenicine (LHPG). A small decrease in systolic pressure at low heart rates and reduction of end-diastolic pressure at the highest pacing rate were the only haemodynamic changes observed after the drug. Coronary sinus flow and myocardial oxygen uptake did not change, although there was a small fall in arterio-venous oxygen difference at basal heart rate. After the drug lactale extraction ratio increased in all patients at each heart rate. Pyruvate extraction ratio increased after oxfenicine (LHPG) significantly at basal heart rate and the lowest pacing rate. Arterial free fatty acid concentration rose and extraction ratio fell. It is concluded that oxfenicine (LHPG) has a potent effect upon lactate metabolism and is without major haemodynamic effects.

Haemodynamic effect of dobutamine in cardiac failure (author's transl)

Dobutamine, a new catecholamine with a positive inotropic action, was given by infusion to 9 patients with cardiac failure in a dosage of 5 and 7.5 mug/kg-min over a period of 15 minutes. An improvement of left ventricular function was proven by an increase of cardiac output by 33%, a reduction of end-diastolic pressure from 21 to 14 mm Hg, an improvement of left ventricular ejection fraction from 29 to 39% and of the mean circumferential fibre contraction velocity from 0.4 to 0.8 circ/s. The systolic aortic pressure increased by a mean of 14% (5 mug/kg-min) and 23% (7.5 mug/kg-min). However, the resistance of the systemic circulation decreased from 1858 to 1439 and 1444 dyn-s-cm-5. Cardiac frequency remained unchanged with a dosage of 5 mug/kg-min and increased by a mere 7 beats/min with a dosage of 7.5 mug/kg-min. There was no increased tendency for arrhythmia. Dobutamine thus appears to act relatively selectively on myocardial beta-1 receptors. Results so far indicate therapeutic success in patients with severe cardiac failure, particularly in the low-output syndrome.

Effect of digitalis on contractility of the failing right and left ventricles during exercise (authors transl)

Intra-venticular pressures were measured at rest and during simulated exercise before and after intravenous administration of 0.6 mg beta-methyldigoxin in 16 patients (right ventricular measurements in 11, left ones in five), measurements in the right ventricle being taken before and 30-45 min after, in the left ventricle before and 20 min after injection of the drug. There was an increase in stroke volume and maximal cardiac work, while end-diastolic pressure fell. Cardiac glycosides can, therefore, favourably influence congestive cardiac failure on physical exertion. Digitalization indicated in those patients who, on exercise, have an increased end-diastolic pressure and reduced contractility. The positive digitalis effect consists of improved contractility and sustained reduction in end-diastolic pressure. On maintenance digitalization it is to be expected that the heart will profit from both mechanisms, both at rest and during exercise. The increased contractility caused by the glycosides is, however, so small that it does not cause any significant change in oxygen consumption.

Ischemic heart failure: Sustained inotropic response to small doses of L-epinephrine without toxicity

As a prelude to a study of severe ischemic heart failure, the therapeutic response of the ischemic ventricle to epinephrine and acetylstrophanthidin in nontoxic doses was determined in 24 intact anesthetized dogs undergoing a first episode of acute regional ischemia. A thrombotic obstruction was produced in the left anterior descending coronary artery, effecting moderate left ventricular dysfunction. The elevation of end-diastolic pressure and reduced stroke volume in control dogs were not significantly altered by administration of strophanthidin. Epinephrine (0.05 μg/kg per min) elicited a significant reduction in end-diastolic pressure and increase in stroke volume. The latter was not attended by an increased incidence of ventricular fibrillation, whereas fibrillation occurred in half of the group given strophanthidin. Thus, the catecholamine was selected to study pump failure. Severe ischemic heart failure was assessed in two groups with scar from previous infarction for up to 4 hours. By 60 minutes of ischemia, the increase in end-diastolic pressure and volume and decrease in stroke volume and ejection fraction were comparable in both groups. Thereafter, alternate animals received small doses of epinephrine (0.05 to 0.15 μg/kg per min) with graded increments at 60 minute intervals to counter tachyphylaxis and findings were compared with those in control dogs. Over the subsequent 3 hours, there was progressive deterioration of left ventricular function in the untreated group with an increase in end-diastolic pressure from 10 ± 1 to 33 ± 2.4 mm Hg. End-diastolic volume increased by 63 percent; stroke volume and ejection fraction decreased by 48 and 66 percent, respectively. The infusion of epinephrine was attended by a significantly lower end-diastolic pressure of 20 ± 2.5 mm Hg, whereas end-diastolic volume, stroke volume and ejection fraction were restored to control levels after 4 hours of ischemia. Mortality in the untreated group was 62 percent by 4 hours; all seven animals in the treated group survived.