Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute hemodynamic and hormonal effects of incremental doses of a specific ovine renin inhibitor (RI: EMD 52 297) and captopril were compared in an ovine model of heart failure. Both RI and captopril inhibited the renin-angiotensin II (ANG II) system, although the decrease in plasma aldosterone (ALDO) was significant only during captopril infusion. Both agents exhibited strong vasodilator properties with similar decreases in mean arterial pressure (MAP, maximum decrease: RI = -20.5 +/- 2.2 mm Hg, p less than 0.001; captopril = -19.8 +/- 1.7 mm Hg, p less than 0.001) and left atrial pressure (LAP, maximum, decrease: RI = -6.8 +/- 1.5 mm Hg, p less than 0.01; captopril = -6.9 +/- 0.4 mm Hg, p less than 0.01) along with a slight increase in cardiac output (CO, maximum increase: RI = 0.54 +/- 0.11 L/min; captopril = 0.79 +/- 0.26 L/min). The slope of the response between MAP and LAP was similar in all animals, indicating that the agents have a similar effect on cardiac preload and afterload. The similar hemodynamic actions of RI and captopril in this model of congestive heart failure suggest that beneficial effects are due to inhibition of ANG II. Thus, orally active renin inhibitors may offer a useful therapeutic alternative when side effects preclude use of angiotensin-converting enzyme (ACE) inhibitors.
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PMID:Comparison of the effect of renin inhibition and angiotensin-converting enzyme inhibition in ovine heart failure. 137 84

Peak III phosphodiesterase (PDE) inhibitors have combined positive inotropic and vasodilator effects. We studied 10 patients with chronic heart failure during and after infusion of intravenous (i.v.) ICI 153,110, an investigational peak III PDE inhibitor. Maximum hemodynamic response for the group occurred after cessation of infusion at a lower plasma drug concentration. At maximum hemodynamic response, cardiac index (CI) increased (2.4 +/- 0.5 vs. 3.2 +/- 0.37 L/min/m2, p less than 0.05) with a decrease in mean arterial pressure (MAP 91 +/- 5 vs. 80 +/- 3 mm Hg, p less than 0.05), pulmonary capillary wedge pressure (PCWP 25 +/- 2 vs. 17 +/- 3.1 mm Hg, p less than 0.01), systemic vascular resistance (SVR 1,422 +/- 106 vs. 983 +/- 97 dynes.s.cm-5, p less than 0.05) and pulmonary vascular resistance (PVR 227 +/- 39 vs. 16 +/- 31 dynes.s.cm-5, p less than 0.05). During the infusion, plasma renin activity (PRA) decreased from 6.34 +/- 2.53 to 3.6 +/- 3 ng/ml/h (NS). The five patients with high baseline PRA had a significant decrease (11.2 +/- 2.5 vs. 5.4 +/- 1.67 ng/ml/h, p less than 0.01) that preceded changes in CI and SVR by 1-2 h. These data suggest that reduction in PRA may have contributed to the hemodynamic effects of this peak III PDE inhibitor.
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PMID:Acute neurohormonal and hemodynamic response to a new peak III phosphodiesterase inhibitor (ICI 153,110) in patients with chronic heart failure. 170 Feb 5

The hemodynamics of 18 patients (subgroup A) with severe heart failure (baseline Cl less than or equal to 1.55 l.min-1.m-2), including three patients with cardiogenic shock, and another 22 patients (subgroup B) with moderate heart failure (baseline Cl from 1.55 to 2.5 l.min-1.m-2) were investigated during a 24 h milrinone infusion, combined with investigation of the response of the sympathetic tone (plasma catecholamine levels) and the renin-angiotensin-aldosterone system to the hemodynamic improvement in both subgroups. Cl increased (p less than or equal to 0.001) to 162.7% after 5 min and further to 206.4% of baseline after 30 min of milrinone therapy in subgroup A, and in B to 139.3% and further to 146.4% after 15 min. PCWP decreased (p less than or equal to 0.001) to 83.8% and further to 65.5% of baseline after 30 min in subgroup A, and to 58.4% in subgroup B. Heart rate decreased (p less than or equal to 0.05) from 99.4 to 94.7 bpm in A and showed a decreasing tendency in B. MAP rose in A from 75.5 to 79.4 after 1 h and further to 83.3 mm Hg (p less than or equal to 0.01) after 24 h; in subgroup B, MAP did not change. Plasma noradrenaline level decreased (p less than or equal to 0.001) in A from 1419.5 (B: 782.9) to 838.2 (B: 529.6) after 1 h and further to 655.1 (B: 467.9) pg/ml after 24 h. Plasma renin decreased (p less than or equal to 0.01) in A from 1047.6 (B: 460.2) to 597.4 (B: 222.5) and further to 392.6 (B: 191.7) microU/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of hemodynamic changes in 24-hour milrinone infusion on sympathetic activity and the renin-angiotensin-aldosterone system in patients with severe heart failure]. 186 68

It was demonstrated recently that a local renin-angiotensin system (RAS) exists in the heart and coronary vessels, and the angiotensin converting enzyme inhibitors can protect the heart from ischemia. Eight patients with NYHA class II-IV subjected to valve replacement were studied in protecting the heart from global ischemia with captopril during open heart surgery. After the ascending aorta was clamped, 500-1000 ml 4 degrees C modified St. Thomas No 1 cardioplegic solution containing 0.058-0.23 mmol/L captopril was perfused into coronary arteries under pressure until the electrocardiogram showed disappearance of myocardial electroactivity. The cardioplegic perfusion was repeated every 30 minutes thereafter during cardiopulmonary bypass (CPB). All the hearts rebeat after reperfusion either spontaneously or from defibrillation without any trouble. Three patients developed an A-V dissociation which returned to sinus rhythm or atrial fibrillation after a tiny dose of dopamine or isoprenaline intravenously. All the patients weaned from the CPB easily with a stable heart rate and a reasonable MAP. None of them needed inotropic support, even those with severe heart failure before operation did not either, and all recovered uneventfully.
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PMID:Captopril as a component of cardioplegia in protecting the myocardium from global ischemia during open heart surgery. A preliminary clinical report. 187 3

Because of the growing interest in the use of coronary artery ligation (CAL) in rats as a model for studies on heart failure, we have investigated the acute hemodynamic changes following CAL in conscious rats. Animals were equipped for measurement of cardiac output (CO), arterial pressure (MAP), and central venous pressure (CVP). These parameters were measured before CAL, immediately after, and 24 h after. Furthermore, peak CO, obtained by rapid infusion of 12 ml Ringer's solution (in 1 min) was measured 2 days before and 1 day after CAL. CAL resulted in immediate reduction of CO, because of reduced stroke volume (SV). CO as well as SV were inversely correlated with infarct size as determined 24 h after CAL. Heart rate (HR) and MAP did not change. Twenty-four hours later, CO was still reduced. MAP was now reduced, possibly as a result from resetting of nervous reflex mechanisms. Before CAL, peak CO and SV were similar in CAL and sham animals. At 24 h after CAL, these parameters were greatly reduced in CAL rats. Peak values were strongly correlated to infarct size. Results indicate that CAL in rats leads to hemodynamic changes similar to the ones observed following myocardial infarction in man. Cardiac function is related to infarct size and is altered both at rest and during maximal stimulation.
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PMID:Acute hemodynamic effects of coronary artery ligation in conscious rats. 232 51

In conscious dogs, we examined the hypothesis that the effects of atrial natriuretic peptide (ANP) are mediated by cyclic GMP and tested whether stimulation of the intracellular pathway beyond the ANP receptor level still exerts ANP-like effects during tolerance to ANP in heart failure. We studied the hemodynamic, renal, and hormonal effects of the cyclic GMP analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP) in conscious dogs before and after induction of congestive heart failure by right ventricular pacing. In healthy dogs, 8-Br-cyclic GMP (1-100 micrograms/kg/min) dose-dependently decreased mean arterial pressure (MAP -19% by 100 micrograms/kg/min) and total peripheral resistance (TPR -22%) with no change in cardiac output (CO) and right atrial pressure, increased urine flow (UF 52%), and sodium excretion (UNaV 135%). Plasma renin (62%) and norepinephrine (NE 24%) were increased. In dogs with heart failure, 8-Br-cyclic GMP induced a similar arteriolar dilation (MAP -16%, TPR -23%) with no change in CO and preload. However, the effects on renal excretory function were abolished or markedly attenuated (UF -4%, UNaV 7%). Plasma renin (163%) and aldosterone (40%) were increased. Our findings support the hypothesis that the renal effects of ANP are mediated by cyclic GMP in vivo. The attenuation of renal effects of 8-Br-cyclic GMP in heart failure does not prove but is in agreement with the hypothesis that an intracellular defect beyond cyclic GMP production might be involved in the tolerance to ANP in heart failure.
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PMID:Hemodynamic, renal, and hormonal effects of 8-Br-cyclic GMP in conscious dogs with and without congestive heart failure. 247 97

The new phosphodiesterase-III inhibitor (PDI) enoximone is a non-catecholamine, non-glycoside cardiotonic agent with concomitant vasodilating properties. It has proved beneficial in patients with severe chronic heart failure. The influence of enoximone i.v. on hemodynamics was investigated during cardiac surgery under various conditions. METHODS. A randomized series of 60 patients undergoing elective aorto-coronary bypass grafting were studied. The hemodynamic effects of 0.5 mg/kg enoximone given i.v. as a bolus (30 s) were investigated before anesthesia (n = 10), during anesthesia (n = 10), and during extracorporeal circulation (ECC, n = 10) and compared with those observed in corresponding control groups (n = 10 in each control) of patients who had received saline solution as placebo. Anesthesia was maintained with weight-dependent dosages of fentanyl, midazolam and pancuronium bromide. All patients were invasively monitored by means of a pulmonary artery catheter. Additionally, left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP) and dp/dtmax were measured before the initiation of ECC. During ECC direct vascular effects were investigated with measurement of perfusion pressure and the volume of the oxygenator. RESULTS. Before the induction of anesthesia no significant change in MAP and HR could be observed, whereas CI increased (+20%) and TSR decreased (-24%) significantly. During anesthesia, the injection of enoximone was followed by a significant decrease in MAP only in the 1st min (-17%); baseline level was reached again after 6 min; and HR was slightly increased (+8%). TSR (-31%) and LVEDP (-38%) decreased, whereas CI (+17%) and dp/dtmax (+45%) were increased significantly. During ECC perfusion pressure (-37%) and the volume of the oxygenator (-17%) were significantly decreased, demonstrating direct vasodilating effects on both the arteries and the vein. CONCLUSION. Arterial and venous vasodilation with an increase in myocardial performance (dp/dtmax) resulting in an increase in CI were the predominant hemodynamic effects of enoximone i.v. No arrhythmogenic effects or interactions with the anesthetics used were observed in this study.
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PMID:[Hemodynamic effects of the new phosphodiesterase inhibitor enoximone in heart surgery patients]. 252 51

The present study was designed to evaluate the regional vascular profile of milrinone in the setting of experimental heart failure. Utilizing the rat model of myocardial infarction and failure (average infarct size 28%), we measured cardiac output (CO), arterial pressure (MAP), LVEDP, heart rate and systemic vascular resistance, as well as regional blood flow (radioactive microspheres 15 +/- 5 microns) before and after milrinone i.v. (20 microns/kg bolus, 3 micrograms/kg/min infusion) in the conscious state (LVEDP 22 mm Hg versus 10 mm Hg in the sham-operated group, p less than 0.01). Similarly, central hemodynamics and regional blood flow were determined before and after dobutamine or captopril, administering equipotent doses. Milrinone reduced LVEDP more than dobutamine, both more than captopril; MAP was decreased by captopril only. Although all three drugs reduced SVR to a similar extent and increased CO, a quite different blood flow distribution occurred. Improvement in flow to skeletal muscle and splanchnic circulatory bed was exerted by milrinone only. Thus, milrinone attenuated the vasoconstriction in those circulations known to be impaired in heart failure. In contrast to captopril, the effects of milrinone on renal perfusion were modest. These results demonstrate the potent vasodilator activity of milrinone, which is independent of its direct-positive inotropic effects, being most prominent in the splanchnic, coronary and skeletal muscle circulation. The latter might have clinical relevance since improved muscular flow during exercise is likely to improve exercise capacity in heart failure after long-term treatment.
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PMID:[Central and regional vascular hemodynamics of milrinone in experimental heart failure: comparison with captopril and dobutamine]. 331 15

Heart rate (HR), cardiac output (CO), coronary sinus blood flow (CSF), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), mean arterial (MAP), and coronary arteriovenous difference for oxygen (AVDcO2) were measured in patients with stable angina pectoris without cardiac failure before and 40 to 60 minutes after administration of 2 or 3 mg of molsidomine. In 20 patients these measurements were made in basal state during spontaneous rhythm. In eight of these patients (including three receiving beta blockers) the measurements were made during atrial pacing. In eight other patients, all receiving long-term beta-blocker therapy, the measurements were made during cold pressor test. At the basal state in spontaneous rhythm, a gradual reduction in the LVSP to 70% or less of its initial value was observed in four patients receiving 3 mg of molsidomine (two of whom received beta-blocker treatment). The LVSP was immediately restored by vascular filling. In the 16 other patients molsidomine decreased LVSP, LVEDP, MAP, CO, and double product (DP = LVSP X HR). The AVDcO2 was unchanged. CSF and myocardial oxygen uptake index (MVO2 = CSF X AVDcO2) were decreased. During atrial pacing, hemodynamic and coronary effects were similar to those seen in the basal state. During the cold pressor test, the increases in LVSP, MAP, and LVEDP were significantly reduced by molsidomine. The variations in CSF and coronary resistance (MAP/CSF) were also significantly different after administration of molsidomine, with better metabolic regulation of the coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic and coronary effects of molsidomine at basal state, during atrial pacing, and during cold pressor test in patients with stable angina pectoris. 383 4

The hemodynamic and cardiometabolic effects of dopamine were evaluated in propoxyphene-induced circulatory shock in eight pentobarbital anesthetized pigs. Circulatory shock was induced by an infusion of propoxyphene chloride 15 mg . min-1 i.v. At shock, i.e. CI less than or equal to 2.0 l . min-1 . m-2 and/or MAP less than or equal to 60 mmHg, dopamine was infused at 10, 20, 40, 80 and 160 micrograms . kg-1 . min-1 with an interval between increments of 8 min. After 30 min at 160 micrograms . kg-1 . min-1, the infusion rate was reversibly decreased. The propoxyphene infusion of 15 mg . min-1 was continued throughout the study. Dopamine improved the circulation in seven animals; one animal died in refractory shock during dopamine infusion. Dopamine infusion at shock level resulted in an increase of the following variables (% of baseline value): MAP (69%), HR (109%), CI (138%) and SVI (129%). Normalisation was seen in MRAP (120%) and in MPAOP (100%). A profound decrease in systemic vascular resistance was unchanged. Increases were seen in left and right ventricular stroke work index, to 88% and 176% of baseline, respectively. Left ventricular dP/dt increased (170%). In the coronary circulation myocardial blood flow increased (133%) as did myocardial oxygen consumption (65%) concomitant with a decrease in myocardial oxygen uptake (41%), but coronary vascular resistance progressively decreased (38%). The myocardial propoxyphene extraction changed from +54% to -86% during peak dopamine infusion. In conclusion, dopamine reversed cardiac failure in propoxyphene overdose by a marked positive inotropic stimulation restoring contractility. A marked positive chronotropic stimulation maintained a sufficient cardiac index and a normal blood pressure in spite of a profound vasodilatation which was unresponsive to dopamine.
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PMID:The effects of dopamine on central hemodynamics and myocardial metabolism in experimental propoxyphene-induced shock. 406 Oct 11


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