Catecholamine cardiotoxicity

Abstract

The morphologic-functional correlative studies that we have carried out in the past 25 years with the various catecholamines have served as an example for analyzing myocardial reaction patterns and the reactions of the cardiac muscle cells to insult. These studies disclosed the unique nature of isoproterenol in producing 'infarct-like' myocardial necrosis. It appears that the pathogenesis of the catecholamine-induced myocardial necrosis is multifactorial. Our early studies suggested the role of relative hypoxia. Later studies by using extracellular fine structural protein tracers demonstrated the importance of microcirculatory effects as well as, in the norepinephrine model, that of early sarcolemmal membrane permeability alteration. The Ca2+ overload theory is supported not only by the experimental observations but also by its successful application in clinical cardiology. A new contribution is the recognition of catecholamine oxidation products in producing myocardial injury. Experimental data indicate that catecholamines play an important role in reperfusion and ischemic myocardial injuries. The sequence of events demonstrated by our studies with catecholamines might represent a common pathway in the evolution of myocardial changes in humans who develop myocardial lesions without narrowing or obstruction of coronary arteries. Investigation in the field of molecular and cellular cardiology has led to a better understanding of current clinical problems and helped to devise procedures for the prevention and management of human myocardial disorders. The isoproterenol-induced myocardial necrosis served as model to Professor A. Fleckenstein to formulate the Ca2+ overload theory of myocardial injury and develop a series of now widely used Ca2+ antagonistic drugs for the management and the prevention of human myocardial diseases.

Effect of Isoproterenol on Tissue Defense Enzymes, Hemodynamic and Left Ventricular Contractile Function in Rats

“…In low concentrations they exert positive inotropic action on the myocardium and, are beneficial in regulating cardiac function [1]. On the other hand, their higher concentrations produce deleterious effects on cardiac function and metabolism [1,2]. Nevertheless, excessive release of catecholamines is responsible for the development of various cardiac dysfunctions, e.g.…”

“…Nevertheless, excessive release of catecholamines is responsible for the development of various cardiac dysfunctions, e.g. in cardiac remodeling following acute myocardial infarction, myocyte death in heart failure and myocardial lesions or infarction [1][2][3][4][5].…”

“…The biochemical and histopathological changes occurring after administration of isoproterenol in rats have been well documented and demonstrated to be a deleterious outcome of isoproterenolinduced imbalance of oxidant and antioxidants in hearts [2][3][4][5][6][7]. Isoproterenol inflicted complex biochemical and structural changes leading to cell damage and necrosis show similarity with human myocardial infarction [1,2]. However, few studies available to demonstrate the effect of isoproterenol-induced deteriorated biochemical defense on cardiac function [4][5][6].…”

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

“…Chronically, however, elevated catecholamines are deleterious, with pro‐arrhythmogenic effects [with the attendant decrease in coronary blood flow and increased myocardial O 2 demand (Rona, 1985)] and direct cardiotoxic effects via cAMP‐mediated calcium overload, particularly influx through the verapamil‐sensitive calcium channel, which is pro‐apoptotic (Mann et al ., 1992). These effects are ameliorated by β‐Adrenoceptors antagonists, a heterogeneous group of pharmacotherapeutic agents.…”

Mekanik Ventilatördeki Tavşanlarda Propofol İnfüzyonu İle Oluşan Metabolik ve Biokimyasal Değişikliklerde L-Karnitin Tedavisinin Etkileri

“…Propofol infüzyon sendromu; ciddi metabolik asidoz, rabdomiyoliz, böbrek yetmezliği ve kardiyak yetersizlik ile karakterize nadir fakat ölümcül olabilen ve tedavisi tam olarak bilinmeyen bir sendromdur (1)(2)(3)(4). İlk olarak 48 saatten uzun süreli ve 4 mg/kg/saat'ten yüksek dozda propofol tedavisi uygulanan kritik olarak hasta çocuklarda tanımlan-masına rağmen propofolün geniş çapta kullanıma girmesi ile erişkinlerde de ortaya çıkabileceği gösterilmiştir (1)(2)(3).…”