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 Class III agent E-4031 was evaluated for its antiarrhythmic and antifibrillatory actions in conscious dogs 3-5 days after anterior myocardial infarction that were responsive to the induction of tachyarrhythmia by programmed electrical stimulation. The administration of E-4031 as an intravenous loading dose (100 micrograms/kg) followed by an infusion for 90 min (10 micrograms/kg/min) suppressed the induction of ventricular tachycardia by programmed electrical stimulation in 6 of 12 dogs and prolonged the cycle length of the induced arrhythmia in 5 of the 6 remaining animals. Continued administration of E-4031 in a dose regimen of 1,000 microgram/kg every 2 h provided significant protection (8 of 10 dogs) against the development of ventricular fibrillation (sudden coronary death) within the first hour after the onset of myocardial ischemia in a region of the ventricle remote from the infarct-related vessel. The incidence of sudden coronary death was 80% in a comparable control group of electrically inducible postinfarcted dogs. Increases in ventricular myocardial refractoriness in the paced QT and QTc intervals suggest that Class III electrophysiologic actions contribute to the antiarrhythmic and antifibrillatory actions of E-4031. The findings suggest that E-4031 may be of clinical utility in the prevention of life-threatening arrhythmias in the setting of myocardial ischemia in the postinfarcted heart.
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PMID:Electrophysiology and antiarrhythmic actions of E-4031 in the experimental animal model of sudden coronary death. 170 34

It was found, that adaptation of rats to cold and physical exercise prevented ventricular fibrillation, caused by the occlusion of the left anterior coronary artery. An adaptation to cold only or to physical exercise do not prevent ventricular arrhythmias. An significant increase of prostacyclin/thromboxane index in plasma and heats was estimated in rats adapted to cold and physical exercise in relation to control non-adapted group in condition of functional rest or acute myocardial ischemia. It was assumed that an increase of prostacyclin/thromboxane ratio has a significant role in antiarrhythmic action of adaptation.
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PMID:[Participation of the prostacyclin-thromboxane system in the mechanisms of prevention of arrhythmia caused by occlusion of the coronary artery in adapted rats]. 171 83

The endothelium-derived peptide, endothelin, has been shown to exert powerful constrictor activity in both isolated and in situ coronary arteries. Recent in vitro data on isolated cardiac myocytes suggest that the substance might also possess electrophysiologic properties. We investigated the possibility that endothelin (ET-1) may exert proarrhythmic effects when infused selectively in the coronary circulation of open-chest-anesthetized dogs. Animals were instrumented for the measurement of left anterior descending (LAD) or left circumflex (LCX) coronary artery blood flow, left systolic ventricular pressure (LSVP), dP/dtmax, mean arterial pressure (MAP), and epicardial electrocardiogram (ECG; three leads). Data were recorded during infusion (2 min) of saline (n = 5) or increasing doses of endothelin (5-80 pmol/kg) given selectively in either the LCX (n = 10) or the LAD (n = 10). When infused into the LCX, endothelin produced a dose-dependent decrease in flow (40 +/- 23% at 80 pmol/kg, mean +/- SD, p less than 0.01) with a concomitant increase in coronary resistance and a decrease in dP/dtmax and MAP. ECG changes typical of myocardial ischemia paralleled the decrease in flow and culminated in ventricular fibrillation at the highest dose (80% of dogs). Endothelin caused similar hemodynamic effects when infused in the LAD, but fatal arrhythmias occurred for lower doses and for little or no change in coronary blood flow. Thirty percent of the animals died at 10 and 60% died at 20 pmol/kg, doses that induced only a moderate decrease (8 +/- 7 and 21 +/- 12%, respectively) in LAD total blood flow. Ventricular tachycardia always preceded ventricular fibrillation and death.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proarrhythmic activity of intracoronary endothelin in dogs: relation to the site of administration and to changes in regional flow. 171 4

The prognostic significance of arrhythmogenic response to an antiarrhythmic drug was studied. In 782 patients with ischemic heart disease (IHD) and frequent and/or complex ventricular premature beats (VPBs), 1,041 drug tests guided by 24-hour Holter monitoring were conducted. The following drugs were assessed: beta blockers, disopyramide, mexiletine, amiodarone. Proarrhythmia was defined as: (1) greater than 4-fold increase in VPBs, (2) greater than 10-fold increase in repetitive forms, or (3) new occurrence of ventricular tachycardia or ventricular fibrillation (VT/VF). During a follow-up of 1-49 months (mean 22) patients were treated with antiarrhythmic drugs found to be safe in control Holter monitoring. Proarrhythmic effects were observed in 8.4% of patients. No drug was completely free of this type of reaction. In long-term observation, cardiac death and sudden death occurred in 53 and 32 patients, respectively. With actuarial analysis (Kaplan-Meier method, log-rank test) there was a significant difference in cardiac death (P less than 0.01) and sudden death rate (P less than 0.05) of proarrhythmia (+) compared with proarrhythmia (-) patients at 1 year (11% vs 4%, 7% vs 3%) and 3 years (24% vs 11%, 16% vs 7%). Proarrhythmic response was an independent risk factor apart from myocardial infarction, VT/VF, ejection fraction less than 40% and QTc greater than 440 msec. Arrhythmogenic response to antiarrhythmic drugs seems to be an additional predictor of sudden death in IHD.
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PMID:Proarrhythmic response to antiarrhythmic drug as a risk factor for sudden cardiac death in patients with ischemic heart disease. 172 Dec 4

Calcium-channel antagonists are widely used in the treatment of supraventricular tachyarrhythmias. The potential benefits of these agents in the management of ventricular arrhythmias, however, are not widely appreciated. Ventricular arrhythmias result from abnormalities of impulse generation and/or impulse conduction. The calcium ion has been implicated in both mechanisms. Myocardial cytosolic calcium increases during ischemia and sympathetic nervous system activation. Elevations in cytosolic calcium provoke oscillatory depolarizations of the cardiac membrane, triggering sustained action potential generation and extrasystoles. Myocardial ischemia also results in a dispersion of refractory period, producing random re-entrant circuits and ventricular fibrillation. Alterations in action potential duration that produce this dispersion of refractory period are associated with spatial and temporal nonuniformities of intracellular calcium transients. Calcium-channel antagonists have been shown to prevent afterdepolarizations and to reduce the endocardial to epicardial dispersion of the refractory period during myocardial ischemia, and therefore could prevent malignant arrhythmias. A slow inward calcium current may, in fact, be required for the initiation and maintenance of ventricular fibrillation. Calcium antagonists reduce, whereas calcium agonists enhance, the susceptibility to ventricular fibrillation induced by the combination of exercise and acute myocardial ischemia. The cardioprotection occurs independently of actions on vascular smooth muscle. Thus, calcium antagonists that exert direct myocardial actions may prove to be particularly effective in the prevention of sudden cardiac death in patients. The challenge remains to develop calcium antagonists that selectively modulate myocardial calcium entry without compromising cardiac mechanical function.
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PMID:The antiarrhythmic and antifibrillatory effects of calcium antagonists. 172 98

The initiating cause of the first ectopic beat and its precipitation of sustained lethal arrhythmia in acute myocardial ischemia is not clear. Comparable uncertainties surround sudden death in myocardial failure. Progress in control of ventricular fibrillation has been slow, perhaps because diagnosis and treatment have been based on the premise that ischemic biochemical changes solely cause the alterations in electrophysiological behavior. Alternative approaches need exploration. Evidence that mechanical changes can initiate electrophysiological changes by a process sometimes referred to as "mechanoelectric feedback" is accumulating. It operates when any primary mechanical change in ventricular muscle, e.g., contraction produces a change in its electrical properties. Mechanical changes are prevalent in ischemia and cardiac failure. If mechanoelectric feedback operates here, it is not surprising that arrhythmias in some of these pathologies parallel the degree of mechanical myocardial dysfunction rather than electrophysiological changes, independent of etiology. This mechanoelectric feedback system may exist as an intrinsic property of normal myocardium, providing a feedback control of activation processes at both the cellular and gross levels. Its disruption during pathological events produces instability in the system and thus ventricular arrhythmia. This concept provides a new potential avenue for arrhythmia therapy.
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PMID:Myocardial mechanics and arrhythmia. 172 49

Extensive atherosclerotic coronary artery disease is by far the most common pathological finding in patients with sudden cardiac death, and acute myocardial ischemia is often a contributing factor. Clinical trials using beta-blockers in postinfarction patients and bypass coronary artery surgery in patients with stable coronary artery disease have demonstrated a reduction in both sudden and total cardiac mortality after intervention. Information concerning the presence and extent of coronary artery disease, global and regional ventricular function, the presence or absence of ventricular aneurysms, and whether or not ischemia is inducible influences therapeutic management. Myocardial revascularization should be considered a primary therapy in patients with critical coronary artery stenosis, significant regions of myocardium at risk, and no inducible ventricular arrhythmias at electrophysiological testing. In patients with inducible polymorphic ventricular tachycardia or ventricular fibrillation, postoperative testing is essential, since only 50% will be suppressed by coronary artery surgery alone. In patients with inducible sustained monomorphic ventricular tachycardia and scars due to prior myocardial infarction, surgical revascularization alone will usually not be sufficient to prevent postoperative induction of the same arrhythmia. There are no data to support percutaneous transluminal coronary angioplasty as the sole therapy for post-sudden death patients who have inducible ventricular tachycardia or ventricular fibrillation on electrophysiological testing.
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PMID:Role of myocardial revascularization in sudden cardiac death. 172 93

Ventricular tachyarrhythmias are the most common arrhythmias documented at the time of sudden cardiac death. Since pharmacological therapy often does not completely suppress these arrhythmias, surgical procedures have been developed to provide an alternative mode of therapy. Coronary artery revascularization in patients with ischemic heart disease is associated with decreased sudden death mortality in patients with left ventricular dysfunction who have no history of prior cardiac arrest or ventricular tachycardia. In sudden death survivors, coronary revascularization appears effective chiefly for patients without inducible ventricular tachycardia or with inducible ventricular fibrillation. Cardiac arrest survivors with sustained monomorphic ventricular tachycardia at electrophysiological study require an ablative procedure that is usually guided by electrophysiological mapping. Current technique should permit elective operations to be carried out with a less than 10% mortality and a greater than 85% rate for suppressing ventricular tachycardia. Nonsurgical catheter ablation techniques have already shown promise in patients with slower, well-tolerated tachycardias that allow extensive catheter mapping. Application of these techniques in patients with the rapid tachycardias associated with sudden death has, to date, been very limited, but as catheter mapping and energy delivery techniques continue to evolve, they may be feasible even in these patients.
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PMID:Management of sudden cardiac death survivors. Role of surgical and catheter ablation. 172 95

Study of the detailed pathology of the myocardium and coronary arteries in ambulatory subjects dying suddenly of coronary heart disease shows that they can be divided into two groups. In one group, there is atherosclerosis with a new vascular event involving coronary thrombosis, which initiates acute myocardial ischemia. In the other group, there is chronic high-grade stenosis due to atherosclerosis, but there is no recent vascular change; the myocardium in this group shows scarring from a previously healed infarction acting as a substrate for reentrant ventricular arrhythmias. A study of 168 consecutive cases of sudden coronary death in London showed 73.3% to have had a recent coronary thrombotic lesion, giving a ratio of 2.7:1 for patients with versus patients without new acute myocardial ischemia. The widely differing ratios reported in the literature probably reflect the patterns of case selection. Prodromal pain immediately before the onset of ventricular fibrillation in a patient without previous known coronary disease selects for a thrombotic cause and acute myocardial ischemia. Absence of pain in a patient known to have had a previous infarction selects for a primary arrhythmia on the basis of preexisting myocardial hypertrophy and/or scarring.
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PMID:Anatomic features in victims of sudden coronary death. Coronary artery pathology. 172

The analysis of the autonomic control of the heart, by means of indirect markers, may represent a new approach for identifying patients at higher risk for sudden cardiac death after a myocardial infarction. This possibility is based on the evidence that autonomic responses during acute myocardial ischemia are a major determinant of the outcome (i.e., occurrence of ventricular fibrillation or survival). Specifically, sympathetic activation can trigger malignant arrhythmias, whereas vagal activity may exert a protective effect. Several experimental observations have provided new insights on the relation between sympatho-vagal interactions and the likelihood for the occurrence of ventricular fibrillation. In an established experimental model for sudden death involving conscious dogs with a healed myocardial infarction, either depressed reflex chronotropic responses during a blood pressure rise or reduced variability of heart rate (respectively, markers of reflex and tonic cardiac vagal activity) identify dogs at greater risk to develop malignant arrhythmias during a new ischemic episode. In anesthetized cats, direct neural recording of vagal activity to the heart confirmed that vigorous reflex vagal activation during acute myocardial ischemia is associated with protection from ventricular fibrillation. Furthermore, in these experiments the reflex neural response to acute myocardial ischemia was predicted by the analysis of baroreflex sensitivity. The antifibrillatory effect of vagal activation is confirmed by the prevention of ventricular fibrillation during acute ischemia in dogs susceptible to sudden cardiac death by direct electrical stimulation of the right vagus. The clinical counterpart of these experimental data lies in three separate prospective studies showing a higher cardiac mortality in patients who after a myocardial infarction have a depressed baroreflex sensitivity or a decreased heart rate variability. A definitive answer on the role that the analysis of markers of cardiac vagal activity may play in risk stratification of patients with coronary artery disease should be provided by Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI), an ongoing prospective study. In ATRAMI, baroreflex sensitivity and heart rate variability will be assessed within 20 days after a myocardial infarction in 1,200 patients enrolled in Europe, U.S.A., and Japan with a minimum follow up of one year.
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PMID:Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. 172 9


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