Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The accumulation of intermediates subsequent to impaired beta-oxidation of free fatty acid (FFA) has been suggested as a cause of cellular damage in ischemic myocardium. We investigated the effects of propranolol and diltiazem on carnitine metabolism in ischemic myocardium. Propranolol (0.2 mg/kg/min, i.v.) and diltiazem (0.1 mg/kg/min, i.v.) were administered for 5 min, the administration started 10 min before coronary occlusion. ECGs were continuously recorded throughout the experiment. Myocardial samples were prepared from both the non-ischemic and ischemic areas 40 min after coronary ligation. Adenosine triphosphate (ATP), free carnitine, long chain acyl carnitine and long chain acyl CoA were assayed. Propranolol reduced the decrease of ATP and the accumulation of long chain acyl CoA, induced by myocardial ischemia. Diltiazem reduced the decrease of ATP and free carnitine, and the accumulation of long chain acyl carnitine in the ischemic area. Propranolol and diltiazem significantly reduced the grade of ventricular arrhythmia. These results suggest that the protective mechanisms of propranolol and diltiazem on myocardium are based, at least in part, on their beneficial effects upon myocardial carnitine metabolism.
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PMID:Effects of propranolol and diltiazem on carnitine derivatives and acyl CoA in ischemic myocardium. 409 37

The slow channel calcium blocking drugs have been shown to be efficacious in patients with chronic stable angina. They provide effective first alternative therapy to beta-blockers in preventing recurrent episodes of myocardial ischemia in patients who do not tolerate treatment with beta-blocking drugs because of, for example, pulmonary bronchospasm or hypoglycemia. The calcium blocking drugs often provide an additive effect in reducing anginal episodes when combined with beta-blocking agents and sometimes provide effective relief of chronic stable angina when beta-blocking drugs are unsuccessful. Diltiazem, nifedipine and verapamil are important additions to our therapeutic armentarium for the treatment of exercise-induced angina pectoris.
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PMID:Calcium channel blocking drugs for chronic, stable angina. 612 20

Calcium channel blockade appears to be at least as effective as beta-blockade in the treatment of anginal syndromes, but whether a similar protective effect is afforded against sudden death is unknown. In order to compare experimental antifibrillatory effects of calcium channel blockade (diltiazem), beta-adrenoceptor blockade (timolol), and nitroglycerin, we measured ventricular fibrillation (VF) thresholds in anesthetized, open-chest dogs before and after 3 min of coronary ischemia before and after i.v. administration of each of these drugs or saline. In control studies, VF occurred after delivery of 11.8 +/- 5.3 mA (X +/- SD) in the nonischemic state and 9.4 +/- 4.6 mA during ischemia (n = 25). During saline administration, no significant change in VF threshold occurred during ischemia, and a minimal increase over time occurred in the nonischemic state. Diltiazem (0.04-0.08 mg/kg/min; n = 10) increased VF thresholds under both ischemic (by 7.7 mA, p less than .01) and nonischemic (by 5.5-5.8 mA, p less than .05) conditions. Timolol (0.03 mg/kg; n = 8) caused substantially greater increases in VFT during nonischemia and ischemia: 11.2 +/- 2.8 mA to 51.6 +/- 38.5 mA (nonischemia) and 8.4 +/- 3.8 mA to 28.7 +/- 16.4 mA (ischemia), both p less than 0.02. VF thresholds were not changed after nitroglycerin (n = 8). Differing experimental effects of these drugs emphasize the need for clinical studies to establish the relative potential of calcium channel blockade and nitroglycerin to reduce mortality in ischemic heart disease.
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PMID:Experimental antifibrillatory effects of calcium channel blockade with diltiazem: comparison with beta-blockade and nitroglycerin. 620 80

The pharmacokinetics, clinical efficacy, and adverse effects of three calcium-channel blocking agents--verapamil, nifedipine, and diltiazem--are reviewed. Verapamil, nifedipine, and diltiazem are absorbed well after oral dosing, but absolute bioavailability of each is reduced substantially by a first-pass effect. Each drug is metabolized extensively (verapamil and diltiazem to moderately active metabolites) by the liver. A substantial percentage of each drug is bound to plasma proteins, but the binding is of clinical importance only for nifedipine (92--98% protein bound). Intravenous verapamil has become the agent of first choice for treatment of acute paroxysmal supraventricular tachycardia (PSVT); use of chronic oral verapamil therapy for prophylaxis remains controversial. Verapamil and diltiazem have been evaluated with mixed results for atrial flutter and fibrillation. For treatment of myocardial ischemia, calcium-channel blockers may be of some value (possibly in combination with nitrates of B blockers). All three agents have been studied in patients with exertional angina with good results. Calcium-channel blockers appear to be equal with nitrates for treatment of variant angina. Patients with hypertropic cardiomyopathy have been treated with verapamil and nifedipine with promising results. Nifedipine has been effective for treatment of essential hypertension. Adverse effects of calcium-channel blockers have been relatively minor or infrequent. Diltiazem overall has the best side-effect profile, with adverse effects causing discontinuation of therapy in about 2--10% of patients; verapamil in intermediate (8--10%) and nifedipine the worst (17%) in this respect. The most common side effects generally are fatigue, headache, dizziness, skin rash, and peripheral edema. While they generally should be reserved for patients in whom more conventional therapy has failed (except those with PSVT), calcium-channel blockers appear to have a valid role as reserve agents for exertional and variant angina, cardiomyopathy, and hypertension.
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PMID:Update on calcium-channel blocking agents. 635 66

Resting coronary and left ventricular hemodynamic effects of diltiazem and nitroglycerin, given intravenously in combination, were studied in 12 patients with coronary heart disease. Results observed with this combination were compared with those in seven patients given diltiazem initially (group I) and five patients given nitroglycerin initially (group II). The diltiazem-nitroglycerin combination reduced systolic blood pressure 27 percent (p less than or equal to 0.05) with no significant change in heart rate to affect a 22 percent (p less than or equal to 0.05) decrease in the rate-pressure product. Left ventricular end-diastolic pressure (-36 percent) and dp/dt (-6.4 percent) both declined (p less than or equal to 0.05). Coronary flow and cardiac output were both maintained. Diltiazem alone and nitroglycerin alone also reduced systolic pressure and the rate-pressure product but to a lesser degree than the combination. Diltiazem did not significantly affect left ventricular end-diastolic pressure and dp/dt. Nitroglycerin reduced left ventricular end-diastolic pressure to an extent similar to the reduction produced by the combination but increased heart rate whereas this determinant of myocardial oxygen demand did not increase significantly with the combination. These findings suggest that the combination of diltiazem and nitroglycerin produces a greater reduction in myocardial oxygen demand than either drug alone. In addition, the combination maintains coronary blood flow without increases in determinants of myocardial oxygen demand. This potentially beneficial drug combination warrants further trial in patients with myocardial ischemia.
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PMID:Hemodynamic effects of nitroglycerin combined with diltiazem in patients with coronary artery disease. 643 77

The antidysrhythmic and antifibrillatory actions of the calcium entry blocker diltiazem were examined in three experimental canine models: 1) ventricular fibrillation thresholds in the anesthetized dog; 2) programmed electrical stimulation in the conscious dog during the subacute phase of myocardial infarction; and 3) a conscious canine model of sudden coronary death wherein ventricular fibrillation was produced by acute myocardial ischemia in the presence of previous anterior myocardial infarction. Diltiazem administration failed to alter ventricular fibrillation thresholds determined under normal physiologic conditions and during acute occlusion of the distal left anterior descending coronary artery. Diltiazem did not prevent ventricular tachyarrhythmias produced by programmed electrical stimulation in the subacute phase of myocardial infarction. The coupling intervals of premature beats producing ventricular tachycardia and the cycle length of the ventricular tachycardias were unchanged by diltiazem administration. In a conscious canine model of sudden coronary death, left circumflex coronary artery thrombosis was produced in the presence of previous anterior myocardial infarction. Acute myocardial ischemia as evidenced by ST-segment changes in saline-treated animals (145 +/- 26 min) was followed by the development of premature ventricular beats (150 +/- 27 min) and ventricular tachycardia (154 +/- 26 min). Ventricular fibrillation occurred in 9 of 10 animals at 156 +/- 28 min. Diltiazem administration did not affect the time to development of ST-segment changes (196 +/- 38 min), premature ventricular beats (202 +/- 37 min) or ventricular tachycardia (209 +/- 37 min). Although the development of ventricular fibrillation was not prevented by diltiazem (9 of 10 animals developed ventricular fibrillation), the time to onset of the fatal arrhythmia was delayed significantly (P less than .01). These data fail to suggest a protective action for the calcium entry blocker diltiazem.
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PMID:Effects of diltiazem upon experimental ventricular dysrhythmias. 683 74

The calcium channel blocker, diltiazem, has been studied in the same model used for evaluation of cold blood-potassium cardioplegia. Six dogs (Group 1) had one hour of myocardial ischemia with topical ice (myocardial temperature, 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing diltiazem, 400 micrograms per kilogram of body weight. Seven dogs (Group 2) had two hours of ischemia after perfusion with 200 ml of cold blood containing 200 micrograms/kg and reperfusion every 30 minutes with 100 ml of cold blood and diltiazem, 100 micrograms/kg. Baseline studies were repeated after rewarming and 40 minutes of reperfusion. No inotropic agents or calcium were used. Heart rate, peak systolic pressure, velocity of the contractile element, peak + rate of rise of left ventricular pressure (dP/dt), peak - dP/dt, dP/dt over common peak isovolumic pressure, left ventricular compliance and stiffness, and heart water were unchanged in Group 1. In Group 2, heart rate slowed (p less than 0.025) and compliance decreased (p less than 0.02). In both groups, coronary vascular resistance declined (p less than 0.001) and recovery of adenosine triphosphate (p less than 0.001), adenosine diphosphate (p less than 0.025), and the adenosine pool (p less than 0.001) was impaired. Ultrastructure was well preserved, but myofibrillar lesions were noted in Group 2. Diltiazem cardioplegia was associated with good functional recovery, but there was impairment of high-energy phosphate metabolism.
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PMID:Cold blood-diltiazem cardioplegia. 706 65

Diltiazem is a calcium slow-channel blocking drug that may be effective in the treatment of chronic stable angina pectoris. To evaluate the therapeutic efficacy 3 hours after a single oral dose of 120 mg, 12 men with chronic stable angina pectoris performed a maximal exercise test on a bicycle ergometer after ingesting either placebo or diltiazem administered in a double-blind fashion. During submaximal exercise at a fixed work load, diltiazem decreased the average heart rate response from 119 +/- 17 to 107 +/- 14 beats/min (p less than 0.01), systolic blood pressure from 182 +/- 15 to 175 +/- 15 mm Hg (p less than 0.05) and the rate-pressure product from 21.8 +/- 4.2 to 18.8 +/- 3.2 x 10(-3) units (p less than 0.01). The average submaximal work load at which significant ST-segment depression (0.1 mV) first appeared was increased from 355 +/- 142 to 525 +/- 143 seconds (p less than 0.01) after diltiazem. At peak exercise after diltiazem, the average depth of ST-segment depression in any one lead and the extent of myocardial ischemia observed in all 12 ECG leads were decreased (p less than 0.01), even though the average work load was increased by 29% (p less than 0.01). Peak heart rate, systolic blood pressure and rate-pressure product were similar with placebo and diltiazem. The plasma diltiazem concentration was 13.9 +/- 29 ng/ml 3 hours after ingestion and was significantly (p less than 0.05) related to the increased time to the onset of important ST-segment depression (r = 0.65) and to the decrease in the extent of myocardial ischemia observed in all 12 ECG leads (r = -0.61) compared with placebo. Thus, diltiazem is effective in treating chronic stable angina pectoris. It decreases myocardial oxygen requirements during upright exercise and appears to increase myocardial oxygen delivery.
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PMID:Increased exercise tolerance and reduced electrocardiographic ischemia with diltiazem in patients with stable angina pectoris. 708 12

The protective effects of diltiazem, a calcium channel blocker, were studied in isolated, blood-perfused cat hearts subjected to 60 or 90 min of global ischemia, followed by reperfusion of 60 or 120 min, respectively. Ischemia-induced alterations of left ventricular (LV) developed pressure (DP) and compliance, measured with an intraventricular fluid-filled latex balloon, were correlated with respiratory activity in vitro of mitochondria isolated from ischemic-reperfused LV myocardium. Nontreated isolated hearts sustained severe declines of LVDP as a result of 60 (-50 +/- 8%) and 90 min (-83 +/- 7%) of ischemia, whereas diltiazem-treated hearts demonstrated only minor losses of LVDP (-17 +/- 8 and -26 +/- 2%). Diltiazem prevented losses of compliance caused by 60 or 90 min of ischemia, which were severe in nontreated hearts after the latter period of ischemia. The progressive deterioration of mechanical function observed in nontreated hearts was paralleled by depressed mitochondrial oxygen consumption and respiratory control. The respiratory activity of mitochondria isolated from cat heart mitochondria. Diltiazem also prevented significant elevations of tissue and mitochondria Ca++ content, reflecting inhibition of Ca++ influx during ischemia and reperfusion. Also, recovery of ATP levels was greater after 60 min each of ischemia and reperfusion in diltiazem-treated hearts. Thus, diltiazem exerts direct, cardioprotective effects during myocardial ischemia, presumably by inhibiting transmembrane Ca++ fluxes.
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PMID:Protective effects of diltiazem during myocardial ischemia in isolated cat hearts. 726 49

Diltiazem, a calcium antagonist, was found to lessen the effect of ischemia resulting from coronary occlusion in dogs. For example, this agent preserves the high energy phosphate reservoir and decreases the inhibition of glycolytic flux at the phosphofructokinase level caused by myocardial ischemia. Diltiazem produced a marked reduction in ischemia-induced damage to the contractile elements. Increased tissue levels of lactate and free fatty acids attributable to ischemia were lowered by diltiazem. Although diltiazem increased contractility of isolated ischemia heart muscle fibers, it did not lessen the effect of ischemia on mitochondrial respiration or mitochondrial calcium binding. On the other hand, diltiazem was found to counteract the effects of ischemia followed by reperfusion on mitochondrial oxygen consumption and calcium binding.
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PMID:Action of anti-anginal drugs on cardiac metabolism. 742 59


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