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 cardioselective beta-adrenoceptor blocking agent practolol was used in the management of ventricular and supraventricular dysrhythmias associated with acute myocardial infarction in 134 patients, and in the management of these dysrhythmias in 19 atients with acute myocardial ischemia. Practolol was frequently effective in controlling ventricular dysrhythmias which occurred within the first 24 hours after the onset of symptoms of acute myocardial infarction. It was also effective in controlling the ventricular dysrhythmias which occurred after resuscitation from ventricular fibrillation. It was of particular value when therapeutic doses of lidocaine had been ineffective. Practolol was much less effective in controlling ventricular dysrhythmias which occurred more than 24 hours after acute infarction. Atrial fibrillation and atrial flutter were infrequently abolished by practolol in undigitalized patients after acute myocardial infarction. There was no correlation between the effectiveness of practolol and the blood concentration of the drug. One adverse effect of practolol was the occurence of sinus bradycardia with or without an increase in the frequency of ventricular ectopic beats. Bradycardia was sometimes accompanied by hypotension. Severe hypotension occasionally occurred in the absence of bradycardia.
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PMID:The effects of practolol on the dysrhythmias complicating acute ischemic heart disease. 111 67

An in situ working swine heart preparation is described in which total coronary perfusion was controlled. At normal rates of coronary flow, oxygen, glucose, and fatty acid utilization were stable for at least a 60-min perfusion period. With a 50% reduction in coronary flow, oxygen and glucose consumption were reduced during 30 min of perfusion and fatty acid extraction was lower at the end of 30 min. Glycogen utilization was increased, but tissue levels of creatine phosphate, ATP, and lactate were similar to those in hearts receiving normal flow. With a 60% reduction in coronary flow, uptake of oxygen, glucose, and fatty acids were further decreased. Tissue levels of high-energy phosphates and glycogen were decreased and ADP, AMP, and lactate increased. Mechanical performance progressively deteriorated in these hearts, and ventricular fibrillation developed after about 20 min (19.8 plus or minus 3.0 min). The data indicate that this preparation is suitable for the study of myocardial metabolism during mild and severe ischemia and may be useful for the evaluation of pharmacological interventions designed for the treatment of myocardial ischemia.
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PMID:Metabolic responses to varying restrictions of coronary blood flow in swine. 111 86

Most deaths from ischaemic heart disease are sudden, occur outside hospital, and result from ventricular fibrillation. But defibrillators have only limited availability because of their size and weight. A miniature defibrillator has been developed. A singe low-energy shock succeeded in removing ventricular fibrillation in 73 out of 82 episodes, and a further shock was successful in seven more episodes. Primary ventricular fibrillation probably always responds to low-energy electrical shocks, which challenges the conventional view that correction of ventricular fibrillation requires high-energy direct-current shock. Thus even smaller and lighter defibrillators are possible. Furthermore low-energy shocks cause less myocardial damage.
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PMID:Electrical requirements for ventricular defibrillation. 113 22

The effects of various combinations of streptokinase-induced hyperfibrinolysis, electric shock, myocardial ischemia, and ventricular fibrillation on cat pericardial and epcardial fibrinolytic activity were studied. Streptokinase alone or electric shock alone slightly increased the periepicardial fibrinolytic activity but epicardial rebleeding did not occur. However, streptokinase infusions followed by electric shock and/or myocardial ischemia and/or ventricular fibrillation significantly incrased the periepicardial fibrinolytic activity and rebleeding of the epicardium occurred. Topical application of the fibrinolytic inhibitor epsilonaminocaproic acid (EACA) prevented the epicardial rebleeding.
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PMID:Periepicardial fibrinolytic activity: relation to cardiac bleeding. 115 66

To determine whether transmural metabolite gradients develop in the contracting, ischemic left ventricle due to factors other than a nonuniform distribution of myocardial blood flow, right and left coronary artery inflow was completely stopped with vessel occluders in open-chest dogs for 15 or 30 seconds before a transmural myocardial tissue sample was obtained for regional analysis of creatine phosphate, adenosine triphosphate (ATP), and lactate. Heart rate was controlled, and the decline in left ventricular systolic pressure during the period in which coronary blood flow was stopped was attenuated by aortic constriction. Studies were also performed in dogs that were (1) pretreated with propranolol, (2) subjected to ventricular fibrillation, and (3) volume loaded. Control studies revealed no transmural metabolite gradients in the normally perfused ventricle, but creatine phosphate was slightly lower in the inner region than it was in the outer and middle ventricular wall regions. With coronary blood flow stopped for 30 seconds, a significant lactate gradient, increasing from the outer to the inner region, was present. Propranolol-treated dogs with their coronary blood flow stopped for 30 seconds also exhibited a lactate gradient, but dogs with ventricular fibrillation and their coronary blood flow stopped for 30 seconds did not. Volume-loaded dogs with their coronary blood flow stopped for only 15 seconds had a significant lactate gradient. Reciprocal gradients occurred in creatine phosphate but not in ATP. The findings suggest that the contracting ventricle uses energy unevenly and that in myocardial ischemia one of the factors causing greater subendocardial vulnerability is a greater energy need in this region.
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PMID:Transmural gradients in ventricular tissue metabolites produced by stopping coronary blood flow in the dog. 118 35

The adrenergic neurohumors, when present locally in the myocardium in high concentrations, can produce a variety of cardiac arrhythmias which may develop into ventricular fibrillation (VF). Of particular importance are the arrhythmias observed immediately after experimentally induced acute myocardial infarction (AMI). Fatal VF, often seen to occur after acute coronary occlusion in the canine heart, may be related to the release of endogenous catecholamines, and a similar phenomenon might be responsible for sudden coronary death (SCD) in man. If adrenergic amines play a vital role in the development of arrhythmias and VF in response to acute myocardial ischemia, then it is conceivable that pharmacological means may be undertaken in an attempt to prevent the release of the adrenergic neurotransmitter or to prevent its arrhythmogenic actions by specific blockade of cardiac beta-adrenergic receptors. Drugs that have a central site of action and are capable of producing a decrease in sympathetic outflow might also play a valuable role in the prevention of arrhythmias and SCD. While the activity of the autonomic nervous system can modify the type and severity of arrhythmias resulting from AMI, existing pharmacological agents have little to offer in preventing the potential adverse effects of adrenergic stimulation without compromising the level of consciousness or cardiovascular function through the removal of adrenergic support to the heart. It would seem more beneficial to direct drug therapy at the electrophysiological defect in the myocardium in an effort to prevent arrhythmias and fatal VF. While currently available antiarrhythmic agents fail to achieve the desired effect, the recent evidence dealing with the quaternary ammonium derivatives of propranolol, lidocaine, and bretylium provides some hope for the future development of drugs with antiarrhythmic as well as antifibrillatory properties which may provide a therapeutic approach to the prevention of SCD.
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PMID:Pharmacological modification of arrhythmias after experimentally induced acute myocardial infarction. Drugs acting on the nervous system. 118 77

This review summarizes previously unpublished and recently published autopsy findings of prehospital sudden coronary death (SCD) in four different counties (Olmsted, Minnesota; Albany, New York; Dade, Florida; and San Francisco Bay Area, California), totaling 868 patients. The prevalence of cardiomegaly and significant coronary atherosclerosis, and the relative infrequency of acute coronary thrombosis in prehospital SCD, well documented in the past, have been reaffirmed in current studies. Differences in the patient populations and laboratory techniques notwithstanding, these independent autopsy studies showed that 62% to 74% of cases of SCD had either acute or old myocardial infarction (MI); the incidence of acute MI ranged from 12% to 47%, and that of old MI from 22% to 53%. The prospective autopsy study of 120 Olmsted County SCD cases showed that among those with established acute MI, subendocardial lesions outnumbered transmural lesions by the ratio of 2:1, and the infarcts ranged in histological age from less than 24 hours to 4 weeks. Evidence of acute myocardial ischemia, as determined by the histological criteria of myofibrillar degeneration, sinuous fibers, and positive HBFP staining, was present in 52% to 81% of patients. Such high incidence of myocardial ischemia is compatible with the proposed mechanism of the terminal event in SCD, namely ventricular fibrillation or asystole, and underscores the importance of presymptomatic diagnosis of coronary heart disease. The lack of specific or acute anatomical lesions in the conduction system in SCD, however, does not preclude the possibility of bradyarrhythmias occurring shortly before death.
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PMID:Pathology of the myocardium and the conduction system in sudden coronary death. 118 81

A special high viscosity preparation of water soluble radiopaque contrast media was explored in animals for its suitability in selective coronary angiography. The high viscosity required power injection to accomplish adequate filling during selective coronary arteriography. The anticipated angiographic advantages, such as prolonged visualization and coating of the vascular walls, were marginal. Comparison with conventional preparations of the same contrast agent suggests that the high viscosity itself exerts some protective effect with regard to the immediate side effects on the electrocardiogram and mechanical function of the myocardium. However, the high viscosity preparation induced electrocardiographic signs compatible with myocardial ischemia not usually seen to follow the injection of conventional contrast agents. These were followed by mechanical heart failure or ventricular fibrillation resulting in death of 6 of the 10 experimental animals. It was concluded that high viscosity contrast media preparations are unsuitable for use in clinical selective coronary arteriography as presently practiced.
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PMID:Evaluation of high viscosity contrast media in canine selective coronary arteriography. 122 26

Therapy with antiarrhythmic drugs may offer the best immediate hope for reducing the large number of deaths due to arrhythmias among patients with ischemic heart disease (IHD). For the prevention of sudden death from ventricular fibrillation, chronic use of these drugs is reasonable in high-risk ambulatory IHD patients, in any patient in whom acute myocardial infarction (MI) is suspected, and in some patients hospitalized for acute MI. However, the effectiveness and possible risks of administering antiarrhythmic drugs in these settings remain essentially unknown. The selection of IHD patients who will benefit most from prophylactic antiarrhythmic drug therapy, the best times for starting and stopping this therapy, and the choice of drug cannot yet be guided by controlled clinical experience. Carefully controlled prospective studies of the beneficial and untoward effects of different drugs in IHD patients are urgently required to provide better guidelines for the clinical use of these potentially life-saving drugs.
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PMID:Antiarrhythmic drugs for ischemic heart disease. 126 12

Dofetilide is a potent and selective class III antiarrhythmic agent that is under development for the treatment of re-entrant tachyarrhythmias (ventricular tachycardia/ventricular fibrillation, atrial fibrillation/atrial flutter, and paraoxysmal supraventricular tachycardia). In animal studies, dofetilide selectively inhibits the rapid component of the time-dependent outward potassium current (IKr) and therefore increases the effective refractory period and action potential duration without affecting the fast inward sodium current. Studies in dogs have shown that dofetilide (a) prolongs the effective refractory period in a dose-dependent manner, (b) elevates ventricular fibrillation threshold, (c) facilitates conversion of electrically induced ventricular fibrillation or fibrilloflutter to sinus rhythm, (d) does not influence conduction within the His-Purkinje system or within the myocardium, (e) does not impair cardiac contractility, and (f) reduces dispersion of ventricular repolarization. Dofetilide has been administered to healthy volunteers as well as to patients with ischemic heart disease or with supraventricular arrhythmias; the compound has generally been well tolerated. Side effects have occasionally been reported, but have generally been transient and mild and occur in placebo-treated subjects as well. No clinically significant changes in laboratory safety tests have been detected. The pharmacokinetic profile of dofetilide both in healthy volunteers and patients includes a linear dose-plasma concentration relationship and also a linear plasma concentration-QTc relationship. The terminal plasma elimination half-life is approximately 9-10 h and systemic bioavailability in the region of 100%. The elimination pattern is balanced, with 50% being excreted unchanged via the kidney, the remaining 50% being metabolized in the liver to inactive metabolites, with greater than 90% of circulating drug-related material being unchanged dofetilide. After intravenous administration of the compound, a slight hysteresis in the plasma drug level-QTc relationship has been detected. Pharmacodynamic data demonstrate dose- and concentration-dependent effects on myocardial repolarization as evidenced by prolongations of the QTc interval. This is reflected in significant prolongations in the effective and functional refractory periods and monophasic action potential duration throughout the myocardium. No effects on sinus node function, conduction parameters, or cardiac contractility have been detected in any of the clinical studies, supporting the contention that dofetilide is a highly selective class III antiarrhythmic agent.
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PMID:Dofetilide, a novel class III antiarrhythmic agent. 127 16


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