Calcium entry blockers: potential applications in shock.
Failure of the myocardium and vascular smooth muscle to maintain intracellular calcium homeostasis results in intracellular calcium overload leading in turn to cell death and tissue necrosis. This phenomenon can occur in myocardium in response to such diverse etiologies as catecholamine-induced necrosis, prolonged periods of hypoxia, low-flow states, and reperfusion of a previously ischemic vascular bed. Such conditions exist in the shock syndrome with its various etiologies. Cardiogenic shock is associated with primary myocardial failure and a low-flow state. The later stages of septic and endotoxin shock are associated with increasing peripheral vascular resistance and decreasing cardiac output. Experimental and clinical hemorrhagic shock are both associated with prolonged periods of low flow, and then with subsequent transfusion, reperfusion of previously ischemic vascular beds occurs. Therefore, in the shock syndrome, at least the potential for intracellular calcium overload exists. It is the purpose of this communication to discuss the pathophysiologic sequence of the shock syndrome, to illustrate the potential role of intracellular calcium overload in the progression of shock, to present a data base of the use of slow calcium channel blockers in the study of shock, and to suggest a future study of calcium entry blockers as potential therapeutic agents in the shock syndrome.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D012769:Shock / Q000188:drug therapy* / Q000503:physiopathology; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013577:Syndrome; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine