Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Milrinone (Win 47203) is a dipyridine related to amrinone, which is about 20-50 times as effective as amrinone when assayed on cardiac contractility. In dog heart-lung preparations, milrinone in a concentration of 0.25-0.5 microM produced a near maximal positive inotropic effect on a variety of acute heart failures. This dosage produced a minimal increase in heart rate and reduced the PR interval. Large doses of milrinone did not produce cardiac irregularities and in Nifedipine heart failure with ventricular irregularities, it eliminated these irregularities. Papaverine-induced heart failure was resistant to ouabain, epinephrine and milrinone therapy. In the presence of positive inotropic amounts of papaverine or theophylline, a pentobarbital heart failure was superimposed. This heart failure responded poorly to milrinone, although it responded to both the addition of epinephrine and ouabain. It is thus possible that milrinone, papaverine and theophylline have closely related sites of action.
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PMID:The search for a digitalis substitute II milrinone (Win 47203). Its action on the heart-lung preparation of the dog. 664 77

This report summarizes five years of laboratory investigations and the initial six-month clinical experience with a calcium antagonist, nifedipine, added to a cold hyperkalemic cardioplegic solution for enhancement of myocardial protection. Regional ischemia was created in 112 dogs and global ischemia in 98 dogs, under normothermic and two hyperthermic states. Control solutions, two clinical cardioplegic solutions, and nifedipine solutions were compared. Infusion of nifedipine during regional ischemia and reperfusion intervals resulted in a two-to-threefold reduction in injury volume and maintenance of normal left ventricular function in contrast infusion of nitroprusside. Nifedipine solutions (0.2 microgram/ml) provided superior preservation of left ventricular function in comparison to the two cardioplegic solutions after one hour of global ischemia at 37 degrees C and two hours at 18 C. In a clinical trial of nifedipine in cold potassium cardioplegia, 38 high risk patients with poor ventricular function have been treated; 22 of which were intensively studied serially with radionuclide ventriculography and pyrophosphate scans, myocardial isoenzyme determinations, 24 hour EKG recordings and intra- and postoperative hemodynamic studies. Of the 35 patients admitted to the intensive care unit (ICU), 33 have survived. Stroke work and cardiac indices return promptly to near normal levels after operation. The time-isoenzyme activity curves are low and radionuclide determined ejection fractions show no change for the study group. Death from acute postischemic cardiac failure did not occur in treated patients and the usage of intra-aortic balloon pump (IABP) has decreased threefold in comparison with 40 similar high risk patients treated concurrently with cardioplegic solution alone. It is concluded that nifedipine is a potent adjunct to cold hyperkalemic cardioplegic solution in high risk patients.
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PMID:Laboratory and initial clinical studies of nifedipine, a calcium antagonist for improved myocardial preservation. 701 25

Nifedipine, the Ca++ antagonistic coronary vasodilator, was administered by oral, sublingual and enema routes. 1) In 6 severe hypertensive patients (systolic pressure greater than or equal to 200 mmHg, diastolic greater than or equal to 120 mmHg), nifedipine, administered orally, induced prompt and reliable fall of arterial pressure (systolic pressure: -28% of control level, diastolic: -27%). 2) In 10 patients with hypertensive emergencies, including malignant hypertension, intracranial bleeding, hypertensive encephalopathy and acute hypertensive heart failure, sublingual and enema administration of nifedipine were performed with excellent hypotensive efficacy. 3) Pressure began to fall within 5--15 min, 30 min and 30--60 min after sublingual (or dissolved), enema and oral (capsule), respectively, and reached its lowest levels in the next 10--20 min. The fall of pressure lasts for 2--4 hours. 4) In the combination of nifedipine with alpha-methyldopa, antihypertensive response in short-term was increased about +11% over nifedipine alone and lasted for 8 hours. In combination with beta-blocker (propranolol), hypotensive efficacy increased +39% over nifedipine alone, but the effective duration of this combination was the same as nifedipine alone. 5) Side effects, including dryness of the mouth and burning sensation in face and legs, were observed in few patients.
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PMID:Treatment of severe hypertension and hypertensive emergency with nifedipine, a calcium antagonistic agent. 726 56

The acute haemodynamic effects of nifedipine (10 mg sublingually) and isosorbide dinitrate (5 mg sublingually) were compared in 13 patients with heart failure due to acute myocardial infarction. Nifedipine induced a significant reduction in systolic (from 122 +/- 5 to 107 +/- 3 mm Hg: mean +/- SEM; P less than 0.002) and diastolic blood pressure (from 85 +/- 3 to 75 +/- 2 mm Hg; P less than 0.01). Heart rate did not change significantly, nor did mean right atrial pressure. The mean pulmonary arterial pressure was lowered from 31 +/- 2 to 27 +/- 2 mm Hg (P less than 0.005). The left ventricular filling pressure decreased from 24 +/- 1 to 19 +/- 1 mm Hg (P less than 0.0001). A significant increase in cardiac index (from 2.33 +/- 0.13 to 2.69 +/- 0.15 l/min per m2; P less than 0.001) and in stroke volume index (from 24 +/- 2 to 28 +/- 2 ml/beats per m2; P less than 0.005) was registered. Systemic vascular resistance fell from 1742 +/- 145 to 1308 +/- 85 dynes/sec per cm-5 (P less than 0.00005). After isosorbide dinitrate was administered a significant reduction in mean right atrial pressure (from 9.5 +/- 1.6 to 5.1 +/- 1.2 mm Hg; P less than 0.0001), in mean pulmonary arterial pressure (from 32 +/- 1 to 23 +/- 1 mm Hg; P less than 0.00001) and in left ventricular filling pressure (from 23 +/- 1 to 16 +/- 1 mm Hg; P less than 0.0001) was seen. No significant change in systolic and diastolic blood pressure, heart rate, cardiac index, stroke volume index and systemic vascular resistance was registered. No side-effects were seen after nifedipine and isosorbide dinitrate were administered.
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PMID:Comparison of acute haemodynamic effects of nifedipine and isosorbide dinitrate in patients with heart failure following acute myocardial infarction. 733 18

The results of the medical treatment of primary pulmonary hypertension are usually very poor. A case of severe primary pulmonary hypertension in chronic heart failure was treated with the calcium antagonist nifedipine, a powerful vasodilator which acts directly on vascular smooth muscle. Nifedipine, administered in a dose of 20 mg sublingually, caused a pronounced fall in pulmonary and systemic vascular resistances (54 and 49%, respectively) and a rise in cardiac output (90.3%). Improvement was maintained over a three-month period. These data suggest that nifedipine can be used in the treatment of this condition.
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PMID:Primary pulmonary hypertension: effects of nifedipine. 742 94

Experimental evidence for antiatheromatous of effects of calcium antagonists has been impressive. Clinical experience has, in contrast, been more difficult to obtain. Primary prevention with calcium antagonists has not been studied due to obvious difficulties. Secondary prevention, however, has been investigated: Several studies have addressed influence of calcium antagonists upon atheromatous arterial wall changes as demonstrated by quantitative coronary angiocardiography. A review of these studies reveals considerable methodological problems. For nifedipine it could be demonstrated, however, that the occurrence of "new lesions" can be retarded to a certain extent (3-6). Nicardipine has been studied, but the preventive effect reported cannot be considered valid, because distribution of risk factors to the study groups was not statistically homogeneous. Another approach has been the application of calcium antagonists to patients with acute myocardial infarction. Here, vascular and myocardial effects come into play. In non-Q-wave, i.e. not transmural infarction, the calcium antagonist diltiazem definitely has preventive effects as regards re-infarction (2). The large multicenter post-myocardial infarction trial MDPIT showed an improvement of cardiac envent rate and re-infarction. This effect was seen only if pulmonary congestion was not present. Calcium antagonists have negative effects if cardiac failure is present. Verapamil was shown to have beneficial effects in acute myocardial infarction in the large DAVIT trials. Here again, the effect was only seen if heart failure was not present. Otherwise negative results were recorded. Nifedipine demonstrated only borderline myocardial protective effects in acute myocardial infarction (7). We conclude that calcium antagonists have vascular and myocardial protective effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of calcium antagonists in progression of arteriosclerosis. Evidence from animal experiments and clinical experience. Part II. Clinical experience with preventive effects of calcium channel blockers in atheromatous coronary artery disease. 794 72

The effects of nifedipine (10(-8) and 10(-7) M) on alpha-adrenergic responses of the dorsal pedal artery and saphenous vein were examined from dogs with pacing-induced heart failure. Two groups of dogs had their right ventricles paced at 250 beats/min: group (1) 1 week of pacing (mild heart failure) and group (2) paced for a mean period of 25.8 days (peak heart failure). Nifedipine non-competitively antagonised 6-allyl-2-amino-5,6,7,8-tetrahydro-4H- thiazolo[4,5-d]azepin dihydrochloride (BHT 920)-induced contractions to the same extent (i.e. at control, mild heart failure and peak heart failure) and IC50 values were as follows: for dorsal pedal artery 3.9 (1.8-6.1) nM, 4.4 (1.2-8.4) nM and 8.5 (2.9-38.9) nM, respectively; for saphenous vein 13.0 (4.6-26.0) nM, 13.0 (7.3-18.6) nM and 19.0 (9.3-32.8) nM, respectively). Before the onset of pacing, nifedipine did not affect concentration-effect curves generated to noradrenaline or phenylephrine in either the artery or the vein. After 1 week of pacing, nifedipine (10(-7) M) inhibited contractions to noradrenaline in the artery and the vein (70 +/- 5% for the artery and 51 +/- 4% for the vein). Nifedipine had no effect on phenylephrine-induced contractions. At peak heart failure, nifedipine inhibited both noradrenaline and phenylephrine contractions. These results indicate that nifedipine is useful in differentiating contractile activity of vascular smooth muscle with respect to alpha-adrenoceptor agonism.
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PMID:Nifedipine inhibits responses to alpha-adrenoceptor stimulation in canine blood vessels: impact of heart failure. 825 8

This study examines the hypothesis that nifedipine may increase splanchnic vascular capacitance and thus change the distribution of blood between the splanchnic and pulmonary circulation in heart failure patients. Relative regional blood volumes were determined by equilibrium blood pool scintigraphy during a 10 min baseline period and for 30 min after nifedipine 20 mg sublingually, with simultaneous recordings of systemic and pulmonary arterial pressures, hepatic venous wedge pressure, and cardiac output. Eight patients with ischaemic heart failure received nifedipine. Four patients served as controls. Nifedipine reduced mean arterial pressure and systemic vascular resistance in every patient. There were no significant changes in the relative blood volumes of the intestinal, hepatic, or splenic regions or in hepatic venous wedge pressure (reflecting portal venous pressure), suggesting unchanged splanchnic vascular pressure-volume relationship. Nifedipine caused a 6.3 +/- 1.0% increase in relative pulmonary blood volume and a slight increase in pulmonary vascular distending pressure from 16.1 +/- 2.9 mmHg to 17.5 +/- 2.8 mmHg (P < 0.05), suggesting that the increase in pulmonary blood volume was passively mediated. In conclusion, nifedipine did not change splanchnic vascular capacitance, but caused a small increase in pulmonary blood volume, which probably was a passive response to increased distending pressure.
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PMID:Effect of nifedipine on splanchnic and pulmonary vascular capacitance. 851 60

Controversy surrounds the safety of digoxin use in patients recovering from acute myocardial infarction. Previous observations yielded contradictory conclusions. To determine whether digoxin therapy is associated with increased mortality in patients recovering from acute myocardial infarction, we analyzed data from 1731 survivors of acute myocardial infarction enrolled in the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT), from which patients with severe heart failure were excluded. At the time of hospital discharge, 175 patients (10%) were taking digoxin. Mortality over 1 year after infarction was significantly higher in patients treated with digoxin than in patients who were not receiving digoxin [27 of 175 (15%) vs. 60 of 1556 (4%); p < 0.0001]. Digoxin administration was associated with increased mortality in several subsets of patients. Since patients treated with digoxin had baseline characteristics predictive of mortality more frequently than their counterparts, we adjusted for these differences. Multivariate analysis performed by the Cox proportional hazards model identified treatment with digoxin as an independent determinant associated with increased death during the first year after myocardial infarction [relative risk (RR) 2.8; 90% confidence interval (CI) 1.8-4.2]. Subgroup multivariate analysis indicated digoxin as an independent predictor of first year death in 464 patients who developed heart failure during their hospital stay (RR 2.3; 90% CI 1.3-4.0), as well as among 1267 patients who did not (RR 3.4; 90% CI 1.7-6.9). The present study suggests a significant excess mortality associated with digoxin therapy after myocardial infarction. The increased mortality risk may be related to unidentified variables associated with the severity of disease in patients treated with digoxin. However, our findings raise concern that the administration of digoxin may contribute to increased mortality in survivors of acute myocardial infarction.
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PMID:Digoxin and mortality in survivors of acute myocardial infarction: observations in patients at low and intermediate risk. The SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial. 854 12

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


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