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:C0151814 (coronary occlusion)
3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ro 40-5967 is a new calcium channel antagonist that binds at the same membrane sites as verapamil, yet has minimal negative inotropic effects. The effects of Ro 40-5967 on the susceptibility to ventricular fibrillation were investigated and compared to diltiazem. Ventricular fibrillation (VF) was induced in 40 mongrel dogs with healed myocardial infarctions by a 2-min coronary occlusion during exercise. Twenty-four animals were found to be susceptible to VF and were given the treatments described below. Pretreatment with Ro 40-5967 (n = 17, 1000 micrograms/kg i.v.) significantly (P < 0.001) reduced the incidence of VF (13 of 17 protected) during the exercise plus ischemia test. Diltiazem (n = 8, 1000 micrograms/kg) completely suppressed VF. Lower doses of diltiazem and Ro 40-5967 did not prevent VF. The hemodynamic effects of Ro 40-5967 were also compared to diltiazem and verapamil. Diltiazem and verapamil, but not Ro 40-5967, increased P-R interval in a dose-dependent manner. Even when reflex tachycardia was controlled by beta-adrenoceptor blockade, Ro 40-5967 still exerted only minimal effects on P-R interval. Verapamil, but neither Ro 40-5967 nor diltiazem, provoked a dose-dependent negative inotropic response. All three drugs elicited large increases in coronary blood flow. These data support the hypothesis that calcium entry may play a critical role in the development of malignant arrhythmias during ischemia. Further, Ro 40-5967 can protect against ventricular fibrillation without significant negative inotropic or dromotropic effects.
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PMID:Ro 40-5967, a novel calcium channel antagonist, protects against ventricular fibrillation. 149 May 22

Data concerning the time of onset of myocardial infarction were obtained for 540 of the 544 patients with creatinine kinase (CK)-MB-confirmed non-Q wave myocardial infarction enrolled in the multicenter Diltiazem Reinfarction Study. Data were also collected for 627 patients who were screened but excluded. Among the 1,167 patients, no diurnal pattern of onset could be found at either 2- or 6-hour intervals. Among the 540 patients enrolled in the trial, no pattern could be found at these intervals either, although at 8-hour intervals, 27% of infarctions occurred between midnight and 8:00 AM, compared with 37% between 8:00 AM and 4:00 PM and 36% between 4:00 PM and 12:00 AM (p = 0.02). In contrast to the patterns previously noted for Q wave myocardial infarction, there was no preponderance of non-Q wave infarction in the late morning. Circadian rhythm was also absent among patients not treated with beta-blockers as well as among patients presenting with ST segment elevation on their enrollment electrocardiograms. Diabetics, women, and patients with first infarction were more likely to present during the afternoon hours. We conclude that the late morning preponderance seen for Q-wave myocardial infarction is not discernable in patients with non-Q wave myocardial infarction. This observation suggests that the pathogenesis of these two infarct subtypes is different or that the process of thrombotic coronary occlusion in Q wave infarction (sustained) differs from that in non-Q wave infarction (nonsustained).
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PMID:Lack of diurnal variation in the onset of non-Q wave infarction. 196 58

Diltiazem and nifedipine improve coronary blood flow and reduce peripheral determinants of myocardial oxygen demand through activation of similar but distinct cellular mechanisms. To identify differences during myocardial ischemia, systemic and coronary hemodynamics were measured continuously before and during brief periods of left anterior descending coronary balloon occlusion in 23 patients undergoing single-vessel angioplasty. Data were compared for two matched ischemic periods, one control and one "drug" period. In 13 patients, diltiazem, 10 mg (intravenous bolus with continuous 500 mg/min infusion), was given; in 10 patients, nifedipine, 10 mg sublingual, was given and after 15 minutes, ischemia was reinduced. Both drugs significantly reduced systolic and mean arterial pressure (for diltiazem, 108 +/- 15 to 93 +/- 10 mm Hg; and for nifedipine, 117 +/- 20 to 96 +/- 8 mm Hg, both p less than 0.01). Diltiazem significantly reduced heart rate-pressure product (with heart rate unchanged), while both drugs maintained the resting great vein blood flow (for diltiazem, 97 +/- 25 to 91 +/- 34 ml/min; for nifedipine, 115 +/- 49 to 98 +/- 58 ml/min, p = ns) with reduced arterial pressure. Coronary flow during occlusion was unchanged (for control versus diltiazem, 63 +/- 21 versus 59 +/- 14 ml/min; for nifedipine, 66 +/- 33 versus 73 +/- 38 ml/min, both p = ns). Neither drug improved collateral hemodynamics or resistance index during ischemia. Both diltiazem and nifedipine prolonged the time to ischemic ST segment alteration (for diltiazem, 27 +/- 10 to 40 +/- 16 seconds, p less than 0.05; for nifedipine, 24 +/- 14 to 38 +/- 14 seconds, p = ns) during transient coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of diltiazem and nifedipine on systemic and coronary hemodynamics and ischemic responses during transient coronary artery occlusion in patients. 229 73

Quantification of intramyocardial hemorrhage was performed in 69 pigs submitted to various protocols of coronary artery occlusion and reperfusion. The study groups include 1) permanent occlusion; 2) reperfusion after periods of coronary occlusion of 30, 45, 60, 90, and 120 minutes; 3) reperfusion with diltiazem and with 4) methoxamine after a 60-minute occlusion period; and 5) permanent reocclusion after a 30-minute period of reperfusion. Red blood cell counts were directly assessed by visual examination of histologic slices of myocardium and in a subgroup of animals by counts of red blood cells labeled with 99m-technetium pertechnetate. Hemorrhage occurs in infarcts reperfused after a duration of 45 minutes or more of coronary occlusion and after a period of reperfusion maintained for at least 30 minutes. Red blood cell counts were maximal in the mid portions of transmural sections of the infarcts, with decreasing values toward epicardium and endocardium. Diltiazem decreased total red blood cell counts, whereas methoxamine increased it and also caused subendocardial hemorrhage. The most powerful predictors of the severity of hemorrhage after sustained reperfusion were infarct size and higher blood pressure.
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PMID:Determinants of hemorrhagic infarcts. Histologic observations from experiments involving coronary occlusion, coronary reperfusion, and reocclusion. 238 98

The calcium entry-blocking drugs produce effects on the coronary vasculature that might be expected to exert anti-ischemia activity. Although these agents cause little vasodilation of the epicardial coronary arteries during basal conditions, they block vasoconstriction that can increase stenosis severity during isometric exercise and interrupt coronary artery spasm in patients with variant angina. Administration of the calcium blockers causes transient vasodilation of the coronary resistance vessels, followed by decreased responsiveness to a brief ischemic stimulus. This results in decreased coronary reactive hyperemia after transient coronary occlusion. By preventing excessive ischemic vasodilation of the resistance vessels, these agents can enhance perfusion of the subendocardium distal to a flow-limiting coronary stenosis. The calcium entry blockers have relatively little effect on the immature coronary collateral vessels that exist at the time of acute coronary occlusion. Diltiazem, however, has been demonstrated to increase collateral blood flow in animals in which chronic coronary occlusion has resulted in growth of moderately well-developed collateral vessels.
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PMID:Effects of calcium entry blockade on myocardial blood flow. 255 78

The effects of diltiazem during transient myocardial ischemia were studied in 17 patients (age 58 +/- 11 years, 12 men, 5 women) undergoing 1-vessel left anterior descending percutaneous transluminal coronary angioplasty (PTCA). After hemodynamic, echocardiographic and electrocardiographic data were obtained during the control ischemic periods, diltiazem (10 mg intravenous bolus with 500 micrograms/min infusion) was given and 15 minutes later ischemia reinduced. Diltiazem reduced mean arterial pressure (113 +/- 16 to 95 +/- 15 mm Hg, p less than 0.05) and heart rate-pressure product (p less than 0.05) with no change in heart rate, pulmonary pressures or coronary (sinus, thermodilution technique) blood flow at rest. After diltiazem, times to ischemia-induced 1.0 mm ST-segment elevation (28 +/- 10 to 42 +/- 17 seconds, p less than 0.05) and new left ventricular wall motion abnormalities (by 2-dimensional echocardiography, 24 +/- 8 to 36 +/- 12 seconds, p less than 0.001) were prolonged without significant augmentation of great cardiac vein flow during coronary occlusion. Left ventricular (LV) ejection fraction decreased from 51 +/- 7 to 41 +/- 12% (p less than 0.05) during control ischemia, but declined less after diltiazem (54 +/- 12 to 47 +/- 14%, difference not significant; 47 +/- 14 vs 41 +/- 12%, p less than 0.01). Diltiazem can attenuate, but not abolish, some of the effects of myocardial ischemia on LV function during transient coronary artery occlusion. These data support the use of diltiazem as a beneficial adjunct that may be used acutely and safely during routine PTCA.
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PMID:Hemodynamic and echocardiographic assessment of the effects of diltiazem during transient occlusion of the left anterior descending coronary artery during percutaneous transluminal coronary angioplasty. 267 30

The ability of diltiazem to prevent early ischemia and reperfusion-induced arrhythmias was investigated in conscious rats with coronary artery occlusion. During a 30-min period of occlusion of the left coronary artery, 100% of placebo-treated animals exhibited ventricular tachycardia, 65% exhibited ventricular fibrillation and the mean total number of premature ventricular complexes was 1076 +/- 254. Diltiazem (0.5 or 2.0 mg/kg body weight, given intravenously 10 mins prior to coronary occlusion), reduced the incidence of ventricular tachycardia to 62% (P less than 0.01) and 54% (P less than 0.001), respectively and the incidence of ventricular fibrillation to 31% (P = NS) and 15% (P less than 0.01), respectively. The total number of premature ventricular complexes was also reduced to 248 +/- 78 (P = NS) and 156 +/- 55 (P less than 0.02). The development of ST segment elevation, induced by coronary artery occlusion, was delayed in both drug-treated groups. Similarly, diltiazem, at the same doses, reduced the incidence of ventricular fibrillation induced by reperfusion after 5 mins of coronary artery occlusion from 100% to 50% (P less than 0.01) and 25% (P less than 0.001) and mortality from 87% to 42% (P less than 0.02) and 25% (P less than 0.01), respectively. The anti-arrhythmic effects of diltiazem were not related to changes in heart rate and all groups showed similar occluded zone sizes, as measured by a fluorescent microsphere technique. Thus, diltiazem affords substantial protection against both early ischemia-induced ventricular arrhythmias and reperfusion-induced arrhythmias and this action may be associated with the beneficial effects on ischemia-induced ST segment elevation.
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PMID:'Early' ischemia and reperfusion-induced arrhythmias: antiarrhythmic effects of diltiazem in the conscious rat. 335 53

This study was designed to examine whether diltiazem, a calcium channel-blocker, inhibits the cardiac ultrastructural alterations induced by coronary occlusion with or without reperfusion, in dogs anesthetized with pentobarbital. The left anterior descending coronary artery (LAD) was completely occluded for 60 min with or without reperfusion (induced by release of occlusion) for 20 min. Coronary occlusion increased ST segment in the ischemic area, and also produced typical ultrastructural alterations including decreased glycogen granules, destruction of mitochondria, and margination of the nuclear chromatin, especially in the subendocardium. Reperfusion of the ischemic area resulted in more severe alterations of the myocardial ultrastructure, including many myofibrillar contraction bands. Diltiazem was injected intravenously at the dose of 200 micrograms/kg (bolus injection) 20 min before LAD occlusion, and was then infused intravenously at the rate of 80 micrograms/kg/min for 10 min starting at the beginning of LAD occlusion, the total dose being 1 mg/kg. Diltiazem decreased heart rate and diastolic blood pressure, inhibited the increase in ST segment, and also inhibited the ultrastructural alterations induced by coronary occlusion, regardless of reperfusion. A bolus injection of diltiazem alone (200 micrograms/kg), however, did not inhibit markedly the ultrastructural alterations induced by coronary occlusion, regardless of reperfusion. It is concluded that the large dose of diltiazem (1 mg/kg) protects the myocardium from ischemic injury.
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PMID:Protective effect of diltiazem on ultrastructural alterations induced by coronary occlusion and reperfusion in dog hearts. 371 50

The effects of diltiazem on ventricular arrhythmias and ventricular vulnerability for fibrillation, both in the very beginning of myocardial ischemia and in the early stage of myocardial necrosis, were evaluated in 13 mongrel dogs. In part I of the study, repeated coronary occlusions were performed. Time course and extent of ventricular ectopy were continuously recorded, and changes in ventricular fibrillation threshold were assessed, both after coronary artery occlusion and release. In part II, a permanent coronary artery occlusion was performed, and the changes in frequency of ventricular arrhythmias were assessed. Diltiazem displayed strong antiarrhythmic and antifibrillatory effects on early ventricular occlusion arrhythmias. The drop in ventricular fibrillation threshold 5 min after coronary occlusion was significantly attenuated. Following the release of coronary artery obstruction, diltiazem failed to reduce the frequency of ventricular fibrillation immediately after the onset of reperfusion. However, during the early postreperfusion period, the drug was able to accelerate significantly the increase in the ventricular fibrillation threshold. Late phase ventricular arrhythmias were not influenced by the drug even when high doses were applied. The different antiarrhythmic actions of diltiazem on early and late phase ventricular arrhythmias can be assumed to be due to differences in the arrhythmogenesis at the very onset of myocardial ischemia compared to the stage of myocardial necrosis.
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PMID:Antiarrhythmic and antifibrillatory action of diltiazem on early and late phase ventricular arrhythmias following coronary artery occlusion and on reperfusion ventricular arrhythmias. 373 71

The effective refractory period (ERP) during the period of the alternation of the ST-T complex (STTA) in the ischemic myocardium was determined using a synchronized system of electrical stimulators and a bipolar epicardial electrode during acute coronary occlusion in anesthetized dogs. Epicardial unipolar electrograms (UP), epicardial bipolar electrograms (BP) and monophasic action potentials (MAP) were also recorded from ischemic areas. ERP in ischemic areas was prolonged, as ischemia progressed, and during the period of STTA ERP also alternately changed. A lower or negative deflection of the ST-T complex was accompanied by a longer ERP, and a higher or monophasic ST-T complex was accompanied by a shorter ERP. A good correlation was observed between the degrees of alternation in ERP and of STTA. MAP also showed an alternation in its duration and its amplitude. The alternation in duration preceded the alternation in amplitude. A lower or negative deflection of the ST-T complex corresponded to a MAP with a longer duration and a larger amplitude. During the period of STTA, a long conduction delay followed the negative deflection of the ST-T complex. A marked conduction delay appeared only during a period of STTA. Diltiazem and nifedipine inhibited STTA and an alternation in ERP. In conclusion, STTA is associated with an alternation in ERP and in conduction delay, and calcium antagonists attenuate both STTA and an alternation in ERP.
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PMID:Alternation in refractoriness and in conduction delay in the ischemic myocardium associated with the alternation in the ST-T complex during acute coronary occlusion in anesthetized dogs. 380 58


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