UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study examined the regional vascular effects (radioactive microspheres) of converting-enzyme inhibition (captopril, 1 mg/kg) and calcium-antagonism (diltiazem, 1 mg/kg) in a rat model of cardiac failure due to large myocardial infarction (n = 18, infarct size 40% of the left ventricle) both at rest and during submaximal treadmill exercise. Diltiazem increased renal, gastrointestinal, coronary and cutaneous blood flow at rest by 29%, 28%, 26% and 37% (p less than 0.05 each) and enhanced skeletal muscle blood flow during exercise by 16% (p less than 0.05). Captopril improved primarily renal and coronary blood flow at rest (by 59% and 23%, respectively, p less than 0.05) and reduced vascular resistance in the gastrointestinal bed by 25% (p less than 0.05) without significant effects in other circulatory beds. We conclude that the regional vascular effects elicited by converting-enzyme inhibition and calcium antagonism differ considerably in this animal model of congestive heart failure and may be clinically important. The favourable regional vascular profile of diltiazem deserves further clinical investigation.
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PMID:[Modification of organ perfusion by calcium blocker and converting enzyme inhibitor in the conscious rat with heart failure]. 388 15

To determine whether verapamil, diltiazem, or nifedipine affect digitoxin kinetics, glycoside plasma concentrations and renal excretion were measured before and during steady-state dosing in 30 patients with cardiac insufficiency. The mean (+/- SD) digitoxin plasma concentration was 14.27 +/- 3.66 ng/ml before and 18.15 +/- 5.33 ng/ml during verapamil dosing in 10 patients over a period of 4 to 6 weeks. Renal digitoxin clearance was not influenced by verapamil, but total body clearance and extrarenal clearance of digitoxin were reduced by 27% and 29%, respectively. Diltiazem resulted in a 6% to 31% (mean = 21%) increase in plasma digitoxin concentrations in five of 10 patients because of reduced extrarenal clearance of digitoxin. In contrast to verapamil, the concomitant dosing of nifedipine over 4 to 6 weeks did not alter digitoxin plasma levels or daily renal excretion. Based on these observations, the risk of digitalis intoxication after combined dosing with verapamil and digitoxin is much less pronounced than that after digoxin, and thus this glycoside is a valuable alternative.
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PMID:Effects of verapamil, diltiazem, and nifedipine on plasma levels and renal excretion of digitoxin. 390 67

To examine the relative potencies of verapamil, nifedipine and diltiazem on left ventricular (LV) function under ischemic conditions, 20 conscious closed-chest dogs that had partial occlusion of their circumflex coronary arteries were studied. Myocardial blood flow was measured by microspheres, LV function by radionuclide angiography. Drug effects were compared at doses causing equal decreases in mean arterial pressure (MAP) and in coronary vascular resistance of the nonischemic zone. Global ejection fraction (EF) and EF of the ischemic region were significantly decreased by verapamil (p less than 0.002) and increased by nifedipine (p less than 0.001); diltiazem caused no significant changes. Verapamil significantly increased peak diastolic filling rate (p less than 0.001); nifedipine also increased diastolic filling rate but only at doses that markedly decreased MAP and coronary vascular resistance. Diltiazem was not significantly different from placebo. For doses causing an equal decrease in MAP, verapamil decreased heart rate (p less than 0.001), and diltiazem and nifedipine increased heart rate (p less than 0.05). Myocardial ischemic zone flow remained unchanged during placebo, verapamil, diltiazem or nifedipine infusion. To study the influence of heart failure on the hemodynamic effects of the calcium-channel blocking agents, 6 foxhounds underwent total occlusions of the left anterior descending coronary artery, resulting in myocardial infarction, volume loading to increase left atrial pressure and partial occlusion of the circumflex coronary artery. Verapamil depressed global left ventricular ejection fraction and increased left atrial pressure to as high as 40 to 45 mm Hg. In contrast, nifedipine decreased left atrial pressure and increased global EF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of calcium-channel blocking agents on left ventricular function during acute ischemia in dogs with and without congestive heart failure. 396 56

Although it has been suggested that calcium channel blocking agents may be utilized as vasodilators in patients with congestive heart failure, these agents also have the potential to cause a deterioration in cardiac function because of their negative inotropic actions. There is considerable variation among the available agents with regard to their relative effects on the vasculature, myocardial inotropy, and myocardial chronotropy. Thus, at clinically relevant dosages, nifedipine is a potent systemic and coronary vasodilator, but it has little or no direct effect on inotropy and chronotropy. In contrast, verapamil exerts significant negative inotropic and chronotropic effects at vasodilatory dosages, whereas diltiazem is a potent vasodilator with a negative chronotropic action at dosages that do not affect inotropy. In patients with heart failure, the largest experience so far has been with nifedipine. Data derived from over 100 patients with moderate to severe congestive heart failure indicate a generally beneficial net hemodynamic response to nifedipine, with substantial improvements in cardiac index (+24 percent) and left ventricular filling pressure (-15 percent). The major effect seems to be on arteriolar resistance vessels, resulting in a reduction in afterload, with relatively little effect on venous pressures. Limited data suggest that the initial effect is sustained during long-term therapy. The clinical experience with verapamil and diltiazem in patients with heart failure is at present limited. In patients with normal or mildly impaired left ventricular function, verapamil's vasodilator and negative inotropic effects are counterbalanced. With severe left ventricular dysfunction, however, treatment with verapamil can result in abrupt decompensation and development of overt pulmonary edema and hypotension. Diltiazem's relative lack of negative inotropic effects may allow it to be used safely in patients with congestive heart failure, particularly when control of supraventricular tachyarrhythmia is required.
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PMID:Calcium channel blockers in congestive heart failure: theoretic considerations and clinical experience. 397 95

The acute hemodynamic effects of intravenous diltiazem were studied in 8 patients with coronary artery disease, left ventricular (LV) failure (New York Heart Association functional class III), a rest ejection fraction (EF) less than 40% or a cardiac index less than 2.4 liters/min/m2. Hemodynamic measurements and LV angiograms were performed at rest before and after the administration of diltiazem, 0.5 mg/kg, administered at a speed of 5 mg/min. Diltiazem treatment induced a decrease in heart rate from 68 +/- 12 to 55 +/- 9 beats/min (p less than 0.001). Mean aortic pressure decreased from 94 +/- 14 to 81 +/- 15 mmHg (p less than 0.05). Thus, the pressure-rate product significantly decreased under the influence of the drug, from 8,791 +/- 2,465 to 6,342 +/- 1,808 beats mm Hg/min, (p less than 0.001). Diltiazem induced no significant change of LV end-diastolic pressure, pulmonary wedge pressure, cardiac index and LV stroke work index. Systemic vascular resistance decreased (p less than 0.01), whereas pulmonary vascular resistance showed no change. End-systolic volume diminished (p less than 0.02), which accounts for the increase of stroke volume and ejection fraction (p less than 0.001). Disorders of regional contractility were not aggravated by diltiazem, and even improved in individual cases. Thus, intravenous diltiazem may be used safely in patients with heart failure. However, in view of the marked bradycardic effects seen in some cases, heart rate should be carefully monitored.
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PMID:Hemodynamic effects of intravenous diltiazem with impaired left ventricular function. 648 22

We tested the effectiveness and safety of i.v. diltiazem in the management of paroxysmal supraventricular tachyarrhythmias in 39 patients, 21 with organic heart disease and seven in heart failure. Fifteen patients presented with supraventricular tachycardia, 12 with atrial fibrillation and 12 with atrial flutter. End points were conversion to sinus rhythm or slowing of the ventricular rate to 100 beats/min or less. Diltiazem was given as an i.v. bolus of either 150 or 300 micrograms/kg over 2 minutes. A second injection was administered to patients who received the lower dose and failed to reach either end point within 30 minutes. The overall success rate was 82% (32 of 39 patients). Time to end point was 5 minutes or less in 20 patients. Conversion to sinus rhythm occurred in 13 of 15 patients (87%) with supraventricular tachycardia and in two of 12 patients with atrial fibrillation. Treatment side effects included a slow ventricular rate in one patient who had a sick sinus syndrome and hypotension in two patients that rapidly responded to fluid administration. We conclude that i.v. diltiazem is effective and well tolerated and advocate its use in the management of paroxysmal supraventricular tachyarrhythmias.
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PMID:Beneficial effect of intravenous diltiazem in the acute management of paroxysmal supraventricular tachyarrhythmias. 684 9

1. Calcium channel blockers increase cardiovascular morbidity and mortality in patients with left ventricular dysfunction. These adverse effects are probably related to the negative inotropic effect of calcium channel blockers and/or a neurohormonal activation. 2. The present study was designed to examine, in conscious dogs, the acute haemodynamic and sympathetic effects of diltiazem and Ro 40-5967 (a novel calcium channel blocker) in the control state and in heart failure. 3. Thirteen dogs were instrumented with a micromanometer and an aortic catheter. After completion of experiments in the control state, heart failure was induced by right ventricular pacing (250 beats min-1, 3 weeks). Diltiazem and Ro 40-5967 were given intravenously (0.8 mg kg-1 and 1.0 mg kg-1 respectively). Cardiac output was measured by a thermodilution technique. 4. In the control state, both agents decreased similarly mean aortic pressure with significant increases in heart rate, cardiac output (both +1.0 l min-1 and P < 0.001) and plasma noradrenaline (both +55%) without changes in left ventricular dP/dtmax. In heart failure, for matched decreases in mean aortic pressure, neither diltiazem nor Ro 40-5967 changed heart rate significantly; diltiazem decreased cardiac output (-0.3 l min-1, P < 0.02) and dP/dtmax (-14%, P < 0.001) while Ro 40-5967 still increased cardiac output (+0.3 l min-1, P < 0.02) although the increased amount was smaller than in the control state. Plasma noradrenaline level was increased more during diltiazem infusion (+120%) than during Ro 40-5967 infusion (+38%, P < 0.001). 5. Diltiazem and Ro 40-5967 have similar haemodynamic and sympathetic effects in the control state.Heart failure alters haemodynamic and sympathetic responses to both calcium channel blockers but the magnitude of the alteration appears to be different. Diltiazem exerts a depressant effect on cardiac function which cannot be overcome by its vasodilator effect and sympathetic stimulation, while Ro 40-5967 has little effect on cardiac function. These data suggest that novel calcium channel blockers with less depressant effect may not be detrimental in heart failure.
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PMID:Effects of the calcium channel blockers, diltiazem and Ro 40-5967, on systemic haemodynamics and plasma noradrenaline levels in conscious dogs with pacing-induced heart failure. 783 90

Because controversies surround the increased negative inotropic effects of calcium antagonists in heart failure, other mechanisms may explain their lack of efficacy in this condition. We hypothesized that altered coronary sensitivity through endothelial dysfunctions may be involved. Our goal was to evaluate the effects of heart failure on coronary and cardiac sensitivity to the calcium antagonist diltiazem. Left ventricular developed pressure (LVP) and coronary flow (CF) were assessed in isovolumetrically beating, perfused, failing hearts from cardiomyopathic hamsters (UM-X7.1) and hearts from normal hamsters. Diltiazem concentration-response curves for both coronary dilation and its negative inotropic effects were charted under control conditions and in the presence of the specific nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 30 microM), and the cyclooxygenase inhibitor, indomethacin (10 microM). Diltiazem concentration-response curves for its negative inotropic action were similar in normal and failing hearts (IC50 1.2 and 2.3 microM, respectively). In contrast, the coronary dilator effects of diltiazem were impaired in failing hearts (EC50 for diltiazem-induced coronary dilation increased from 90 nM in normal hearts to 1.1 microM in failing hearts, p < 0.01). The involvement of endothelial dysfunctions in the observed coronary "desensitization" to diltiazem in heart failure was evaluated through the NO-synthase and cyclooxygenase pathways. Diltiazem concentration-response curves from failing hearts were not modified in the presence of L-NAME, whereas indomethacin normalized the coronary response to diltiazem in heart failure. These findings suggest that coronary "desensitization" to diltiazem occurs through parallel production and/or release of a vasoconstricting factor or factors originating from the cyclooxygenase pathway. Heart failure was not associated with increased cardiac sensitivity to diltiazem but rather with altered coronary sensitivity. These findings suggest that coronary desensitization may play a role in the lack of efficacy of diltiazem in heart failure and provide a better understanding of factors modulating the effects of calcium antagonists in heart failure.
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PMID:Impaired coronary sensitivity to diltiazem in experimental heart failure: involvement of the cyclooxygenase but not the nitric oxide-synthase pathway. 885 78

Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospective, and have various drawbacks. Specifically, the metaanalysis of Furberg et al is fraught with mistakes, of borderline significance, and based on old data pertaining to short-acting nifedipine only (which should not be given in patients who have suffered an acute heart attack). The case control study of Psaty et al suggested that hypertensive patients who were treated with short-acting verapamil, diltiazem, and nifedipine had an excessive rate of myocardial infarction when compared with patients who were treated with diuretics. Two out of the three calcium antagonists that were used in this study were not approved for the treatment of hypertension by the US Food and Drug Administration. Some patients were taking these drugs only once a day whereas, because of their short duration of action, at least a three or four times daily regimen would be required to achieve an acceptable blood pressure control throughout a 24-h period. The cohort study of Pahor et al suggested distinct differences among various calcium antagonists with regard to survival. Blood pressure was controlled in < 40% of all patients, and in some patients blood pressure was never even measured. Recent studies, such as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), the third Vasodilator-Heart Failure Trial (VHeFT-III), the second Doppler Flow and Echocardiography in Functional Cardiac Insufficiency Assessment of Nisoldipine Therapy (DEFIANT II), the Angina Prognosis Study in Stockholm (APSIS), and the Shanghai Trial of Nifedipine in the Elderly (STONE), attest to the safety and efficacy of the newer long-acting calcium antagonists in patients with a wide spectrum of heart disease. Several ongoing trials including the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with amlodipine, the International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) with nifedipine, the Hypertension Optimal Treatment study (HOT) with felodipine, the Systolic Hypertension in the Elderly in Europe Trial (SYST-EUR) with nicardipine, the Second Swedish Trial in Old Patients with Hypertension (STOP II) with felodipine, and Nordic Diltiazem Study (NORDIL) with diltiazem, will give us morbidity and mortality data in patients with high blood pressure within the next few years. Until these results are available, we can be confident that the lowering of blood pressure and providing relief of patients with symptomatic angina can be achieved safely and efficiently with the presently available long-acting calcium antagonists.
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PMID:What, if anything, is controversial about calcium antagonists? 896 30

Recently, there has been some controversy concerning calcium antagonists, suggesting the need for further debate on this heterogeneous class of drugs. Three chemical families, dihydropyridines (DHP), phenylalkylamines (verapamil) and benzothiazepines (diltiazem) bind to the type L receptors of the calcium channels with different binding, modulation and tissue selectivity characteristics. DHP are selective for type L receptors and block the extracellular portion of the channel leading to vigorous vasodilatation and little or no cardiodepressive effect. Diltiazem and verapamil also interfere with type T channel receptors. These drugs have a cardiodepressive and a bradycardia effect. Verapamil blocks the intracellular portion of the calcium channel at the site where part of the catecholamine effect occurs, leading to less reflex sympathetic activation than with other calcium antagonists (namely DHP). Deleterious sympathetic stimulation is proportional to the intensity and degree of rapid onset of arterial vasodilatation and is attenuated with slow-release formulations. Calcium antagonists in general have an anti-angina effect but high-dose short-acting DHP can cause excessive vasodilatator leading to subsequent ischemia. In chronic stable angina, slow-release verapamil has been shown to have a preventive clinical effect comparable to that of beta blockers. Slow-release nifedipine is effective and safe but must be associated with betablockers. In unstable angina, only those calcium antagonists with a bradycardia effect appear to have an effect similar to beta blockers. Beta blockers are nevertheless to be preferred in these patients (excepting Prinzmetal angina) until results of convincing clinical studies are available. After the initial phase of myocardial infarction, again only calcium antagonists with a bradycardia effect have been shown to have a beneficial effect, in patients without cardiac failure: diltiazem in infarction without Q-wave and verapamil in all infarctions, in case of residual ischemia to reduce the risk of recurrence.
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PMID:[Calcium antagonists in ischemic heart disease]. 941 Oct 6

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