Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to evaluate the potential role of a perioperative calcium-channel blocker (Diltiazem) infusion in improving myocardial preservation. Forty consecutive CAD patients were randomly assigned to a control (C; n = 20) and a treated (D; n = 20) group. In patients in the latter group diltiazem was continuously infused at 0.5 to 2.0 mcg/kg/min i.v. from anesthesia induction until the aortic cross-clamping, and from myocardial reperfusion till the 48th postoperative hour. During the preCPB phase hypertension occurred less frequently in group D (3 vs 12 cases, p = 0.0033). In the immediate postischemic period, depression of contractility and the need for inotropic support were observed in 3 cases in group D and in 9 in group C (p = 0.0384). Postoperatively, group D patients had a lower incidence rate of hyperkinetic arrhythmias or conduction disturbances (p = 0.0218), as well as of ECG signs of ischemia (p = 0.0016). Significant CK enzyme level increase was noted in 13 patients in group C versus 4 in group D (p = 0.0040). Two perioperative myocardial infarctions were diagnosed, both in group C. These clinical data show that continuous perioperative infusion of diltiazem can effectively increase myocardial preservation during ischemic arrest, without unfavorable effects on the hemodynamics, electrical activity or mechanical performance of the heart.
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PMID:Myocardial protection by perioperative diltiazem drip: a clinical evaluation. 242 30

This study was performed to determine if diltiazem can reduce the severity of pacing-induced ischemia independently of its peripheral hemodynamic effects and of increases in ischemic region blood flow. Twelve anesthetized dogs were subjected to atrial pacing and had their left anterior descending coronary arteries (LAD) occluded gradually until ischemia ensued (greater than 10 mV epicardial ST-segment elevation). Cessation of pacing resulted in abolition of ST-segment elevation. ST-segment elevation, as well as peripheral and coronary hemodynamics, was measured during 5-min periods of pacing + LAD stenosis before and 0, 30, and 60 min after treatment with intracoronary (just distal to the stenosis) saline or 1.8 micrograms/kg diltiazem. Myocardial blood flow was measured using radioactive microspheres during pacing, pacing + stenosis, and pacing + stenosis + drug treatment at 60 min. Diltiazem significantly reduced ST-segment elevation approximately 50% at 0, 30, and 60 min compared with elevations seen in animals treated with saline as well as predrug values. No changes in blood pressure, heart rate, or LAD flow occurred with diltiazem. Overall ischemic tissue flow and its transmural distribution were not different with diltiazem compared with saline treatment. Thus, diltiazem can decrease the severity of pacing-induced ischemia independently of its peripheral effects and of increased ischemic region blood flow.
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PMID:Effect of intracoronary diltiazem on ST-segment elevation and myocardial blood flow during pacing-induced ischemia. 244 4

Effect of intracoronary infusion of diltiazem (1 microgram/min) on regional myocardial blood flow (RMBF) was studied using 15-microns radioactive microspheres in 11 excised cross-circulated canine left ventricles. With total coronary blood flow (CBF) and heart rate (HR) held constant, regional ischemia was induced by ligating the left anterior descending coronary artery (LAD). Diltiazem at the dose used had no effects on ventricular Emax before and after LAD ligation. RMBF expressed by the counts divided by the counts averaged in all segments in each layer significantly (p less than 0.05) increased under diltiazem only in the low-flow region that had less than 50% RMBF before diltiazem; from 21% (+/- 12%) to 35% (+/- 18%) in the epicardial, from 22% (+/- 12%) to 32% (+/- 18%) in the midwall, and from 24% (+/- 10%) to 31% (+/- 12%) in the endocardial layers. We conclude that the beneficial effect of diltiazem on the ischemic heart involves a direct action on the coronary vascular system and does not necessarily depend on the concomitant changes in hemodynamics.
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PMID:Effect of diltiazem on coronary blood flow distribution in dog heart under ischemia. 247 1

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 prognosis for patients with non-Q-wave myocardial infarction (MI) remains controversial, although a number of studies have shown a less favorable outlook after hospital discharge for patients with non-Q-wave than for those with Q-wave infarction. Numerous management strategies are available to the clinician, many of which involve an interventional strategy (myocardial revascularization with coronary bypass surgery or angioplasty) or a more conservative approach which emphasizes secondary prevention with medical therapy. This review summarizes the role of identifying risk variables in patients with non-Q-wave MI and their importance to clinical decision making. Based on data obtained from the Diltiazem Reinfarction Study (DRS), it has been shown that 20% of patients experience one or more episodes of spontaneous postinfarction angina which is associated with a significant increased (33%) 2-week mortality and an appreciable fivefold increased incidence of early reinfarction compared to patients without early recurrent ischemia. Similar findings have been observed in this same cohort of patients who were followed for one year, in that there was twofold higher incidence of death and late reinfarction at one year of follow-up. Other risk factors also appear to be important determinants of adverse long-term outcome after non-Q-wave MI and include persistent ST segment depression on serial electrocardiograms, congestive heart failure, and left ventricular hypertrophy. Medical therapy employed for secondary prophylaxis after non-Q-wave MI has failed to show a convincing therapeutic rationale for beta blocker administration. In contrast, diltiazem has been shown to influence the early and late outcome following non-Q-wave MI favorably.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Strategies for managing the patient with acute non-Q-wave myocardial infarction. 257 20

Diltiazem may provide a protective effect to ischemic and reperfused myocardium through preservation of high-energy phosphate metabolism. To test this hypothesis, rabbits had a 1.3 cm solenoidal coil placed over the myocardium to be rendered ischemic. Data were acquired with a 22 cm bore nuclear magnetic resonance spectrometer at 2.0 T. Animals were treated with diltiazem (200 micrograms/kg intravenous bolus of drug followed by a 15 micrograms/kg/min continuous intravenous infusion, n = 10) or by an equal volume of saline (n = 6). The left circumflex artery was occluded and reperfused using a reversible snare while electrocardiogram-gated spectra were accumulated. Levels of phosphocreatine were decreased during occlusion in both groups; however, this decrease was attenuated in the diltiazem treated animals compared to control (in relative percent area: 7.8 +/- 1.0 to 2.5 +/- 0.5, p less than 0.01). Levels of phosphocreatine promptly returned to baseline following reperfusion and there was no difference between the two groups. The inorganic phosphate metabolites of high-energy phosphate consumption increased with occlusion, though more so in the control group compared with the diltiazem-treated rabbits (in relative percent area: 72.5 +/- 0.9 to 55.4 +/- 1.3, p less than 0.01). With reperfusion, levels of inorganic phosphates returned toward baseline in both groups; however, the diltiazem group had a more complete recovery relative to control (in relative percent area: 38.8 +/- 2.1 to 47.6 +/- 2.7, p less than 0.05). Levels of adenosine triphosphate decreased in both groups relative to baseline; however, the amount of decrease was similar in the two groups. With reperfusion there was a definite though incomplete recovery of levels of adenosine triphosphate in the diltiazem-treated group (in relative percent area: 10.7 +/- 1.0 at occlusion, 12.3 +/- 0.4 during reperfusion, p less than 0.05), but in the control group levels of adenosine triphosphate remained depressed (in relative percent area: 9.8 +/- 0.6 at occlusion, 9.8 +/- 0.8 during reperfusion, p = NS). During ischemia there was a trend toward attenuation of intracellular acidosis in the diltiazem group; however, this trend did not reach statistical significance. These data indicate that diltiazem provides a protective effect on myocardial high-energy phosphate metabolism during regional ischemia and reperfusion in the intact animal.
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PMID:Effects of diltiazem on phosphate metabolism in ischemic and reperfused myocardium using phosphorus31 nuclear magnetic resonance spectroscopy in vivo. 258 62

Although Q wave and non-Q wave MI are often referred to as "transmural" and "nontransmural," there is no anatomic evidence to justify this distinction. Nevertheless, a distinction is important, because the two entities have a different prognosis. At the present time, between 25% and 35% of MIs are non-Q wave. They are frequently observed in patients with previous coronary events. They occur in a relatively older population and involve a slightly higher proportion of women than do Q wave MIs. The degree of cardiac damage is less, reflected by a smaller rise in enzyme level and less impairment of left ventricular ejection fraction; early reperfusion may occur, after spontaneous thrombolysis or resolution of coronary spasm. The immediate mortality rate is half that of Q wave MI but identical in the long term. Reinfarction and angina are more frequent because of a peri-infarction zone of ischemia maintained by a high-grade coronary stenosis and inadequate collateral circulation. Early characterization of those MIs likely to progress is important. Diltiazem seems effective in this context if given between 24 and 72 hours of the onset of the event. Other therapeutic approaches need further assessment.
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PMID:"Non-Q wave," alias "nontransmural," myocardial infarction: a specific entity. 264 80

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 calcium-channel inhibiting agent, diltiazem, has been shown to enhance salvage of reperfused myocardium independent of effects on coronary blood flow or myocardial work. Because lipid peroxidation may be a mediator of reperfusion injury and modifiable by calcium-sensitive pathways, we evaluated the effects of diltiazem on the formation of malondialdehyde (MDA), a product of lipid peroxidation, in isolated rabbit hearts perfused with buffer under control conditions or after 60 minutes of ischemia with or without 3 minutes of reperfusion. Diltiazem (5 x 10(-7)M) reduced tissue MDA content in seven reperfused hearts compared with levels measured in 14 hearts reperfused without drug (1.54 +/- 1.09 [SD] compared with 3.57 +/- 1.88 nmol/g, p less than 0.05). Superoxide dismutase and catalase were ineffective in reducing tissue MDA content in reperfused hearts (n = 8; MDA concentration, 3.88 +/- 2.82 nmol/g) although they were effective in preventing lipid peroxidation in separate studies in which oxygen-centered free radicals were generated directly by an infusion of xanthine oxidase and hypoxanthine. These results suggest that the salutary effects of diltiazem in the setting of reperfusion may be mediated by reduction of lipid peroxidation at a locus not accessible to scavengers of oxygen-centered free radicals or by a mechanism not mediated by free radical pathways.
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PMID:Reduction of lipid peroxidation in reperfused isolated rabbit hearts by diltiazem. 276 94

The safety and efficiency of the administration of diltiazem was evaluated in 10 patients with class II-III chronic stable angina. All the patients had ischemic heart disease documented by coronary angiography and/or an abnormal exercise test. A dose related improvement in both frequency of angina and exercise capacity were obtained by diltiazem administered in increased doses using a single blind protocol. The weekly frequency of angina was reduced from 7.5 +/- 9.8 with placebo to 3.8 +/- 5.5, 1.1 +/- (p less than 0.05) and 0.7 +/- 0.9 (p less than 0.01) with doses of 120, 240 and 360 mg/day respectively. The exercise duration on treadmill was significantly increased from 8.5 +/- 3.6 to 10.6 +/- 3.7 min (p less than 0.05) with the 360 mg/day dose. The mean exercise time required to develop 1 mm ST depression was 6.1 +/- 3 min on placebo and was significantly delayed to 9.0 +/- 3.8 min (p less than 0.05) with the 240 mg/day dose and to 10.7 +/- 4.0 min with 360 mg (p less than 0.01). In a double blind randomized crossover phase, the time to the onset of ischemia during exercise was increased from 8.5 +/- 3.8 min with placebo to 11.05 +/- 2.8 min with 360 mg/day of diltiazem (p less than 0.01). Diltiazem in doses ranging from 120 to 360 mg/day is an effective antianginal agent with no significant adverse effects.
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PMID:[Diltiazem in chronic stable angina]. 294 27


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