Catecholamines and cardiomyopathy: The pathogenesis and potential importance of myofibrillar degeneration
TL;DR: Since repcated episodes potentially may produce myocadial fibrosis, this lesion is worthy of more serious consideration in the evaluation of human heart disease manifest by impaired cardiac function and interstitial fibrosis.
About: This article is published in Human Pathology.The article was published on 1970-03-01. It has received 282 citations till now. The article focuses on the topics: Cardiomyopathy & Lesion.
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TL;DR: In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose- related reductions in mortality and hospitalization rate and was generally well tolerated.
Abstract: Background We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a “third-generation” β-blocking agent with vasodilator properties, in chronic heart failure. Methods and Results Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive treatment with placebo, 6.25 mg BID carvedilol (low-dose group), 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction [EF] units in the low-, medium-, ...
1,280 citations
TL;DR: These results constitute the initial demonstration at the cellular level that adrenergic stimulation leads to cyclic AMP-mediated calcium overload of the cell, with a resultant decrease in synthetic activity and/or viability.
Abstract: BACKGROUNDTo delineate the mechanism(s) of catecholamine-mediated cardiac toxicity, we exposed cultures of adult cardiac muscle cells, or cardiocytes, to a broad range of norepinephrine concentrations.METHODS AND RESULTSNorepinephrine stimulation resulted in a concentration-dependent decrease in cardiocyte viability, as demonstrated by a significant decrease in viable rod-shaped cells and a significant release of creatine kinase from cells in norepinephrine-treated cultures. Norepinephrine-mediated cell toxicity was attenuated significantly by beta-adrenoceptor blockade and mimicked by selective stimulation of the beta-adrenoceptor, whereas the effects mediated by the alpha-adrenoceptor were relatively less apparent. When norepinephrine stimulation was examined in terms of cardiocyte anabolic activity, there was a concentration-dependent decrease in the incorporation of [3H]phenylalanine and [3H]uridine into cytoplasmic protein and nuclear RNA, respectively. The decrease in cytoplasmic labeling was largel...
858 citations
TL;DR: Cocaine is the most commonly used illicit drug among subjects seeking care in hospital emergency departments or drug-treatment centers, and it is also the most frequent drug-related visits to emergency departments.
Abstract: Cardiovascular complications are among the most common and dangerous complications of cocaine abuse, ranging from episodic arrhythmias to myocardial infarction, strokes, cardiomyopathy, and sudden death. The central nervous system-mediated action of cocaine triggers an increase in circulating catecholamines, resulting in arterial vasoconstriction, increase in myocardial oxygen demand, myocardial ischemia, tachycardia, and other arrhythmias. The peripheral cardiovascular action of cocaine involves the inhibition of reuptake of catecholamines at adrenergic nerve terminals, with local release of epinephrine, direct stimulation and vasospasm of the coronary arteries, coronary intimai hyperplasia, inhibition of baroreceptors, interference with the electrical conduction through the myocardium, and direct myocardial toxicity. The cardiovascular complications of cocaine include cardiac dysrhythmias and hypertension, acute myocardial infarction, myocarditis, infectious endocarditis, ventricular dysfunction, dilated cardiomyopathy, hypotensive shock, and cerebral strokes. Cocaine-related vascular changes in the pregnant woman and fetus have been related to an increased incidence of abortion, abruptio placentae, and congenital anomalies of the fetus.
723 citations
TL;DR: It is shown that cardiogenic shock is associated with extensive loss of left ventricular myocardium due to new and frequently old infarcts as well, and a sharp reduction in coronary perfusion pressure could explain this combination of findings.
Abstract: The amount of left ventricular myocardium destroyed by recent and old infarcts in patients with acute myocardial infarction with and without cardiogenic shock was compared in hearts obtained at autopsy. All 20 patients with, and only one of 14 without, shock had lost 40 per cent or more of the left ventricle. The remainder lost 35 per cent or less. These results indicate that cardiogenic shock is associated with extensive loss of left ventricular myocardium due to new and frequently old infarcts as well. In five cases the new infarct was small as compared to the total amount of myocardial destruction. Patients with cardiogenic shock consistently showed marginal extension of the recent infarct (unlike those not in shock) and focal areas of necrosis throughout both left and right ventricles. Similar focal lesions were encountered in a third series of 20 patients with shock from other causes. A sharp reduction in coronary perfusion pressure could explain this combination of findings, which indicate ...
656 citations
TL;DR: Analysis of clinical and pathological findings in seven people in whom nonintravenous "recreational" use of cocaine was temporally related to acute myocardial infarction, ventricular tachycardia and fibrillation, myocarditis, sudden death, or a combination of these events suggests cocaine has medical consequences that are equal in importance to its well-documented psychosocial consequences.
Abstract: The increasingly widespread use of cocaine in the United States has been accompanied and perhaps exacerbated by the misconception that the drug is not associated with serious medical complications. In particular, the potential for cocaine to precipitate life-threatening cardiac events needs to be reemphasized. We report the clinical and pathological findings in seven people in whom nonintravenous "recreational" use of cocaine was temporally related to acute myocardial infarction, ventricular tachycardia and fibrillation, myocarditis, sudden death, or a combination of these events. We also review data on 19 previously reported cases of cocaine-related cardiovascular disorders. Analysis of all 26 patients indicated the following findings: the cardiac consequences of cocaine abuse are not unique to parenteral use of the drug, since nearly all the patients took the drug intranasally; underlying heart disease is not a prerequisite for cocaine-related cardiac disorders; seizure activity, a well-documented noncardiac complication of cocaine abuse, is neither a prerequisite for, nor an accompanying feature of, cardiac toxicity of cocaine; and the cardiac consequences of cocaine are not limited to massive doses of the drug. Although the pathogenesis of cardiac toxicity of cocaine remains incompletely defined, available circumstantial evidence suggests that cocaine has medical consequences that are equal in importance to its well-documented psychosocial consequences.
567 citations
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TL;DR: The clinical material, the experimental results, and some comments on the pathology of the electrographic abnormalities of this heart lesion are presented.
Abstract: LECTROCARDIOGRAPHIC (ECG) abnormalities associated with central nervous system disorders are weU known, having been reported with such diverse conditions as status epilepticus, 2~ subarachnoid hemorrhage, meningitis, cerebral infarction, and intracranial mass lesions. 1,~,m7 A variety of ECG alterations have been reported, seen most consistently with subarachnoid and intracerebral hemorrhages. The most common abnormalities are depression or elevation of ST segments, prolongation of Q-T intervals, and inversion of T waves. No pathological changes in the heart were described until 1964 when Koskelo, et al., ~~ reported three cases of subarachnoid hemorrhage with ECG changes, and mentioned several small subendocardial petechial hemorrhages seen at postmortem. No other cardiac abnormalities were noted, and the pathogenesis of the electrographic abnormalities has remained unclear. We have seen a variety of structural changes in hearts of patients dying with subarachnoid hemorrhage, several of whom had abnormal ECG's, and we have produced similar changes experimentally in cats. In this communication we will present our clinical material, the experimental results, and some comments on the pathology of this heart lesion.
289 citations
TL;DR: The posterior papillary muscle is an area of maximum ischemia in the large posterolateral infarct resulting from high occlusion of the circumflex branch of the left coronary artery in the dog heart, and is used as a source of nonischemic control tissue.
Abstract: The sudden onset of ischemia in myocardium is followed within a few seconds by a series of striking functional changes: The area becomes cyanotic; cooler; hydrogen accumulates; electrocardiographic changes appear; and, within 30 to 60 seconds, contraction ceases in the affected myocardium. These changes within the ischemic focus are directly related to the development of local anoxia, which causes the affected cells to shift from an aerobic to an anaerobic form of metabolism, resulting in a substantial decrease in energy production. Although injured and nonfunctional, these severely ischemic, markedly anoxic cells are viable and survive for a period of time. Early restoration of the coronary blood flow to an ischemic focus is followed by almost instantaneous restoration of aerobic metabolism and contractile function. However, if the period of ischemia is more prolonged, restoration of the blood supply is not followed by restoration of function, since the affected cells are either dying or dead. The severely ischemic viable cells are reversibly injured, whereas the severely ischemic dead cells are irreversibly injured. Our chief interest has been in determining what event or series of events within the cells dictates the onset of irreversible injury.' Our studies are predicated on the assumption that intracellular events discoverable by direct analysis of the tissue lead to the development of the irreversible state. Tissue known to be severely ischemic and fairly uniformly injured is required for analysis in direct studies of early changes in structure and/or function during ischemic injury. One must be able to identify and sample the affected tissue even though it appears normal upon gross examination. We have found that the posterior papillary muscle is an area of maximum ischemia in the large posterolateral infarct resulting from high occlusion of the circumflex branch of the left coronary artery in the dog heart.2 The posterior papillary muscle is easily identified, and the upper two-thirds of the muscle are uniformly injured in those dogs in which the cyanosis extends to the apex of the heart posteriorly. The muscle is ultimately almost completely replaced by scar tissue. The anterior superior portion of the septum of the left ventricle is not involved in this infarct; therefore it is used as a source of nonischemic control tissue.
210 citations