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)

Data from the first 103 human heart transplantations performed on 100 recipients (aged 14-62 years) at a single center from November 1983 to January 1990 were analyzed in order to detect morbidity-causing risk factors. Cumulative one- and five-year graft survival was 82% and 68%. Multivariate analysis revealed three independent risk factors for early rejection, viz. HLA-DR and HLA-B mismatches and no prior cardiac surgery. Graft ischemic time exceeding 71 min was an independent risk factor for rejection, especially for moderate or severe events, and for infection. HLA-DR mismatch was an independent risk factor for moderate and severe rejection events and for infections. Finally, patients operated on because of end-stage ischemic heart disease were at significantly higher risk of rejection than those with other cardiac disorders. The study has several implications: Prospective tissue typing for cardiac transplantation and selection of donors may have an impact on graft function: Damage to the graft by prolonged ischemia may be reduced by improved organ preservation.
Scand J Thorac Cardiovasc Surg 1992
PMID:Morbidity risk factors in human cardiac transplantation. Histoincompatibility and protracted graft ischemia entail high risk of rejection and infection. 133 24

Bucindolol is a new beta blocker with marked vasodilatory properties and intrinsic sympathomimetic activity. We tested its potential effect against ventricular fibrillation (VF), in a pig model of acute myocardial ischemia. Bucindolol 6 mg/kg IV was administered in two equally divided doses, the first 30 minutes prior to, and the second 10 minutes after, ligation of the anterior descending coronary artery (CAL) in anesthetized open-chest pigs. Bucindolol decreased the incidence of VF to 1/11 versus 14/16 in the control group (p less than 0.005). Bucindolol also decreased the duration of ventricular tachycardia, 15 +/- 8 seconds versus 104 +/- 32 seconds in the control group (p less than 0.01). Bucindolol maintained LVmaxdP/dt at predrug and pre-CAL values, whereas LVmaxdP/dt was decreased by CAL in the control group. Bucindolol decreased arterial pressure and heart rate. Bucindolol increased blood flow in the peripheral ischemic zone (24.6 +/- 1.8% versus 16.2 +/- 1.7% (percent of pre-CAL value) in controls, p less than 0.002), as well as in the nonischemic zones (periischemic zone: 126.4 +/- 6.1% versus 96.7 +/- 4.8% in the control group, p less than 0.0005; remote nonischemic zone: 126.6 +/- 7.1% versus 87.1 +/- 4.3% of pre-CAL value in the control group, p less than 0.0001). Bucindolol had marked antiarrhythmic effects that were associated with beneficial effects on the mechanical function of the left ventricle and on blood flow to the ischemic myocardium.
Cardiovasc Drugs Ther 1992 Jun
PMID:Bucindolol, a beta blocker, decreased ventricular fibrillation and maintained mechanical function in a pig model of acute myocardial ischemia. 135 66

Recent investigations of SMI occurring during daily life have advanced our understanding of the pathophysiology of myocardial ischemia. These contributions have directed our attention away from "chest pain" alone and physical exertion as the central provoking factor toward transient myocardial ischemia and its broader triggers and consequences. Transient myocardial ischemic episodes, the majority of which are silent, are found in a subset of patients with any clinical manifestations of CAD (eg, stable angina, unstable angina, myocardial infarction, and sudden death), as well as in those patients with CAD who are and have been totally asymptomatic. These episodes are an independent predictor of increased risk for future cardiac events. Most medical therapy and revascularization therapies have the potential to prevent or relieve these silent episodes; however, we do not yet know which method is superior in reducing SMI episodes or preventing future cardiac events. Furthermore, the benefit of reducing SMI versus the cost and potential morbidity of these chosen therapies is not known. At least three trials are now underway to examine some of these concerns (Table 2). Focus on pain relief alone does not appear to be an adequate approach to alter outcome in patients with CAD and may prove insufficient to control SMI. Until these issues are resolved, we believe a conservative approach to the management of patients with CAD is warranted. Documentation of ischemia (painful or painless) is essential. Three general principles should be kept in mind. First, the presence of detectable ischemia is of central importance. This information should be used in the overall risk assessment of the patient. Second, the level of concern or aggressiveness of treatment should be based on the risk associated with the ischemic abnormalities documented (Table 3). The exercise stress test is the most useful to begin this process. The detection of ischemic-type ST-segment depression, either silent or painful, at a low workload (eg, less than or equal to 120 beats per minute or less than or equal to 6.5 metabolic equivalents [METS]) implies high risk for adverse outcome. Likewise, these ST-segment changes occurring in leads that reflect multiple coronary artery distribution, of greater than 2 mm in magnitude and persisting for greater than 6 minutes, are all markers for high risk. Thallium redistribution defects occurring at low work loads, in multiple areas, associated with increased lung uptake and enlargement of the cardiac pool all imply high risk.(ABSTRACT TRUNCATED AT 400 WORDS)
Prog Cardiovasc Dis
PMID:Treatment strategies for daily life silent myocardial ischemia: a correlation with potential pathogenic mechanisms. 135 7

A number of studies have addressed the response to calcium antagonists, used alone or combined with other therapy, in patients with silent myocardial ischemia (SMI). Nifedipine, the first calcium antagonist to be studied, was shown to be superior to pindolol in patients with effort angina. Although both nifedipine and diltiazem significantly reduced episodes of ST depression, compared with placebo, in patients with stable effort angina, the addition of nifedipine to diltiazem removed the beneficial effect of diltiazem in another study. Studies have shown a reduced incidence of ischemic episodes during nicardipine treatment in patients with ambulatory ischemia, predominantly SMI, and rest angina due to coronary artery spasm. Other workers similarly reported that verapamil was superior to both placebo and propranolol in reducing painful and painless ischemia in patients with angina at rest. It has been demonstrated that, compared with placebo, nifedipine reduced ischemic episodes by 50% and also markedly reduced total ischemic time in totally asymptomatic men with coronary artery disease and SMI. It was suggested that the well-documented increase in SMI occurring between 0600 and 1200 h was reduced, but not eliminated, by nifedipine. Diltiazem may also attenuate the circadian variation in SMI. Nifedipine has been shown to be particularly effective in SMI when combined with a beta-blocker. This has been substantiated in a large group of patients; both drugs reduced the number of episodes of SMI when used as monotherapy, and the combination decreased the incidence by 95%. These findings collectively indicate that calcium antagonists are effective in reducing or preventing SMI.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1990
PMID:Clinical effects of calcium antagonists in silent ischemia. 136 8

Myocardial ischemia followed by reperfusion was produced in artificially respirated, open-chest rats. Coronary artery ligation for 6 min rarely evoked arrhythmias; however, reperfusion after this period rapidly produced severe dysrhythmias in all control animals. Reperfusion after 12 min of ischemia produced less frequent dysrhythmias than after coronary occlusion for 6 min. Feeding of a linoleic acid-rich diet, applying 12% sunflower seed oil in rat food pellet for 4 weeks, decreased the incidence of reperfusion-induced ventricular fibrillation both after 6 min (2/15 vs. 7/11) and 12 min (0/11 vs. 2/8) of myocardial ischemia and the incidence of other arrhythmias was also decreased. The number of animals developing no arrhythmias during reperfusion was increased (8/15 after 6 min of ischemia, 4/11 after 12 min of ischemia vs. 0/11 and 0/8 in controls, respectively). Our results indicate that increased dietary consumption of linoleic acid decreased the occurrence of life-threatening arrhythmias both during the acute phase of myocardial ischemia and during reperfusion in anesthetized rats.
J Cardiovasc Pharmacol 1992 Jan
PMID:Effect of dietary sunflower seed oil on the severity of reperfusion-induced arrhythmias in anesthetized rats. 137 86

Class III antiarrhythmic agents such as E-4031 have demonstrated efficacy in preventing and/or terminating malignant ventricular arrhythmias in experimental models. It has recently been suggested that Class III agents might possess additional antiischemic properties that may translate into a reduction in the frequency or severity of arrhythmia. The potential for the Class III antiarrhythmic agent E-4031 to limit the extent of developing myocardial infarction was assessed in a barbiturate-anesthetized canine model of ischemic-reperfusion injury. Untreated control (n = 13) and E-4031-treated animals (n = 8, 300 micrograms/kg, i.v., immediately preceding myocardial ischemia) were subjected to a 90-min period of left circumflex coronary artery occlusion followed by a 5-h period of reperfusion. The predominant hemodynamic effect displayed by E-4031 was a reduction in heart rate throughout the period of coronary artery occlusion and early reperfusion. Areas at risk of infarction, expressed as percentages of left ventricle, were equivalent in the control and E-4031 treatment groups (38.5 +/- 1.0 and 34.6 +/- 1.9%, respectively). Posterolateral myocardial infarct sizes, expressed either as percentages of risk area or of total left ventricle, were reduced slightly but not significantly in the E-4031 treatment group compared to the control group (35.2 +/- 5.6 and 45.4 +/- 3.0% of risk area, respectively; 12.7 +/- 2.4 and 17.6 +/- 1.4% of left ventricle, respectively). Regional myocardial blood flows in nonischemic and central ischemic zones of myocardium did not differ significantly between the control and E-4031 treatment groups before and during the period of coronary artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1992 Jun
PMID:Effect of E-4031, a class III antiarrhythmic agent, on experimental infarct size in a canine model of myocardial ischemia-reperfusion injury. 137 9

The in vivo protective effects of diltiazem, nifedipine, and verapamil on large and small coronary artery constriction induced by intracoronary injection of acetylcholine were compared by coronary arteriography in pigs. The percent narrowing of the epicardial major right coronary artery was used as an indicator of large coronary artery constriction, and the time required for contrast medium to reach the posterior descending coronary artery from the ostium of the right coronary artery was used as an indicator of small coronary artery constriction. Doses of 12.5, 25, 50, 100, and 200 micrograms of acetylcholine were administered into the right coronary artery under left ventricular pacing to keep the systemic hemodynamics constant. Marked prolongation of the flow time of contrast medium to greater than or equal to 8.1 s (control of less than or equal to 1.8 s) with mild narrowing of the epicardial major right coronary artery (less than or equal to 35%) was observed at doses of 12.5-50 micrograms of acetylcholine and was accompanied by myocardial ischemia. Over 50% narrowing of the epicardial major coronary artery plus markedly slow flow of contrast medium were induced in 12 of the 15 pigs by 100-200 micrograms of acetylcholine. Narrowing of the epicardial major coronary artery and the delay time of contrast medium flow induced by acetylcholine were both significantly reduced to 12-33% (control: 36-81%) and to 4.3-16.8 s (control: 16.2-37.7 s) after intracoronary injection of 100 micrograms of diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1992 Jun
PMID:Comparative effects of diltiazem, nifedipine, and verapamil on large and small coronary artery constriction induced by intracoronary acetylcholine in pigs. 137 13

The purpose of this study was to determine whether the selective type IV cAMP-phosphodiesterase inhibitor rolipram could reduce the reperfusion injury that occurs during myocardial infarction in the anesthetized dog. This question was tested in pentobarbital-anesthetized dogs subject to 90 min of regional myocardial ischemia and 5 h of reperfusion. Dogs were treated with 1 mg/kg of rolipram (i.v., 15 min before reperfusion) followed by a 1 mg/kg/h infusion over the duration of the 5 h of reperfusion. Rolipram was tested in vitro for efficacy in inhibition of isolated human neutrophil superoxide generation. Rolipram produced significant inhibition of superoxide production over the concentration range of 0.1-100 microM rolipram when neutrophils were stimulated with a 10(-7) M concentration of the chemotactic peptide f-Met-Leu-Phe. Rolipram significantly inhibited superoxide generation from human and canine granulocytes in whole blood stimulated by zymosan. Therapeutic concentrations of rolipram in the blood of dogs were achieved during the course of the experiments with a plasma concentration of 0.761 +/- 0.095 micrograms/ml (2.76 +/- 0.34 microM) at the time of reperfusion, and 0.574 +/- 0.098 micrograms/ml (2.08 +/- 0.36 microM) at the end of the reperfusion period. The relative severity of myocardial ischemia between the two treatment groups was similar as assessed with radiolabeled microsphere measurement of myocardial blood flow. Transmural myocardial blood flows were not significantly different between the two groups after coronary occlusion (control, 0.05 +/- 0.01 ml/min/g, n = 6, vs. rolipram, 0.18 +/- 0.07 ml/min/g, n = 6; p = 0.48).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1992 Jun
PMID:Inhibition of granulocyte cAMP-phosphodiesterase by rolipram in vivo is not sufficient to protect the canine myocardium from reperfusion injury. 137 23

Calcium is a ubiquitous cation involved in a wide variety of physiological processes. Normally, cytosolic calcium is maintained within narrow limits but under certain conditions the levels rise--either because of excess calcium entry, internal release, or failure of the extrusion mechanisms. Such conditions include hypertension and myocardial ischemia. Calcium ions are also involved in the formation of atherosclerotic lesions. Hypertension, ischemic heart disease, and atherosclerosis are all amenable to calcium antagonist therapy. The efficacy of this class of drugs in the management of such a wide spectrum of disorders is in accord with the central role played by calcium in the etiology of these disorders. To some extent, however, the disorders are interrelated, with hypertension being a major risk factors for ischemic heart disease and atherosclerosis.
J Cardiovasc Pharmacol 1992
PMID:Calcium, calcium antagonism, atherosclerosis, and ischemia. 137 99

Previous results on the effects of angiotensin-converting enzyme (ACE) inhibition in myocardial ischemia are conflicting. To determine whether acute ACE inhibition may influence myocardial perfusion deficit during ischemia and reduce ischemia-reperfusion injury, anesthetized open-chest dogs underwent 2-h left anterior descending coronary artery (LAD) occlusion followed by 6-h reperfusion. After 1-h coronary occlusion, each dog was randomized to receive either captopril [5 mg/kg intravenous (i.v.) bolus and 0.25/kg/h infusion for 7 h] or saline. Whereas arterial pressure was reduced (p = 0.001), captopril did not influence myocardial perfusion deficit: Blood flow in the central ischemic zone represented 17.1 +/- 2.8% of the flow in the nonischemic zone versus 20.5 +/- 3.8% before treatment (NS). The values of the control group were 17.8 +/- 2.5 and 16.7 +/- 2.4%, respectively. In addition, there was no difference in infarct size: 35.9 +/- 3.3% of the area at risk in captopril-treated dogs versus 40.0 +/- 3.6% in controls. Analysis of subgroups based on the level of the collateral flow indicated, however, that ACE inhibition had an adverse effect on infarct size in dogs with high collateral flow: 31.9 +/- 4.6% in captopril dogs versus 17.6 +/- 4.7 (p = 0.048). This effect was related to a decrease in collateral flow because animals exhibiting the highest increase in perfusion deficit presented the greatest increase in infarct size (r = -0.92, p = 0.003). Although in dogs with low collateral flow, ACE inhibition appeared to exert a slight beneficial effect on infarct size, we conclude that at least in this dog model, acute ACE inhibition could exacerbate myocardial injury.
J Cardiovasc Pharmacol 1992 Mar
PMID:Importance of the flow perfusion deficit in the response to captopril in experimental myocardial infarction. 137 9


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