Prevention of Ventricular Fibrillation, Acute Myocardial Infarction (Myocardial Necrosis), Heart Failure, and Mortality by Bretylium

Abstract

It is widely, but mistakenly, believed that ischemic heart disease (IsHD) and its complications are the sole and direct result of reduced coronary blood flow by obstructive coronary artery disease (CAD). However, cardiac angina, acute myocardial infarction (AMI), and sudden cardiac death (SCD) occur in 15%-20% of patients with anatomically unobstructed and grossly normal coronaries. Moreover, severe obstructive coronary disease often occurs without associated pathologic myocardiopathy or prior symptoms, ie, unexpected sudden death, silent myocardial infarction, or the insidious appearance of congestive heart failure (CHF). The fact that catecholamines explosively augment oxidative metabolism much more than cardiac work is generally underappreciated. Thus, adrenergic actions alone are likely to be more prone to cause cardiac ischemia than reduced coronary blood flow per se. The autonomic etiology of IsHD raises contradictions to the traditional concept of anatomically obstructive CAD as the lone cause of cardiac ischemia and AMI. Actually, all the signs and symptoms of IsHD reflect autonomic nervous system imbalance, particularly adrenergic hyperactivity, which may by itself cause ischemia as in rest angina. Adrenergic activity causing ischemia signals cardiac pain to pain centers via sympathetic efferent pathways and tend to induce arrhythmogenic and necrotizing ischemic actions on the cardiovascular system. This may result in ischemia induced metabolic myocardiopathy not unlike that caused by anatomic or spasmogenic coronary obstruction. The clinical study and review presented herein suggest that adrenergic hyperactivity alone without CAD can be a primary cause of IsHD. Thus, adrenergic heart disease (AdHD), or actually adrenergic cardiovascular heart disease (ACVHD), appears to be a distinct entity, most commonly but not necessarily occurring in parallel with CAD. CAD certainly contributes to vulnerability as well as the progression of IsHD. This vicious cycle, which explains the frequent parallel occurrence of arteriosclerosis and IHD, an association that appears to be linked by the same cause, comprises a common vulnerability to deleterious adrenergic actions on the myocardium, lipid metabolism, and vascular system alike, rather than viewing CAD and IsHD as having a putative cause and effect relationship as commonly thought. Adrenergic actions can also cause the abnormal lipid metabolism that is associated with CAD and IsHD by catecholamine-induced metabolic actions on lipid mobilization by activation of phospholipases. This may also be part of toxic catecholamine hypermetabolic actions by enhancing deleterious cholesterol and lipid actions in damaging coronary vessels by plaque formation as well as inducing obstructive coronary spasm and platelet aggregation. This may also cause direct toxic necrosis on the myocardium as well as atherosclerosis in blood vessels. In fact, drugs that inhibit adrenergic actions like propranolol, reserpine, and guanethidine all inhibit arteriosclerosis induced by hypercholestero...

Plasma Catestatin in Patients with Acute Coronary Syndrome

“…We speculated that catestatin may play an important role through an imbalance between catestatin and catecholamine. The sympathetic nervous system is involved in the process of atherosclerosis and the development of CAD [22]. During myocardial ischemia, the sympathetic system is activated, and there is an increase in catecholamine release [23].…”

Factors Related to Silent Myocardial Damage in Hemodialysis Patients

“…[25] It was previously speculated that there was a link between cardiac ischemia and systemic hypertension, although the exact mechanisms were not known. [26] One of the postulated mechanisms is the impairment of coronary endothelial dysfunction by hypertension. Presence of inflammation [27] and oxidative stress [28] may play a role for the endothelial dysfunction.…”

Plasma Catecholamines and Ischemic Heart Disease

“…8 Moreover, catecholamines accelerate progression of myocardial cell damage and are capable of producing necrosis even in the nonischemic heart. 2,9 Also, a positive correlation between enhanced sympathetic activity, elevated cardiac norepinephrine concentrations and the incidence of arrhythmias have been reported 10 in contrast to observations, in which no causal relation existed. 11 On the other hand, the protective effects of β-blockade in myocardial infarction have been repeatedly shown.…”

“…Activation of the sympathoadrenal system expressed as increased levels of circulating catecholamines, epinephrine and norepinephrine may accelerate the development of ischemic heart disease (IHD) and acute myocardial infarction (AMI) may lead to activation of the sympathoadrenal system. 1,2 Increased levels of circulating catecholamines occur early in AMI. 3,4 In addition, high amounts of norepinephrine are released from the sympathetic nerve terminals of the heart 3,4 and massive accumulation of norepinephrine occurs in the extracellular space of the ischemic area.…”