ELECTROPHYSIOLOGIC CHANGES IN ISCHEMIC VENTRICULAR MYOCARDIUM .1. INFLUENCE OF IONIC, METABOLIC, AND ENERGETIC CHANGES

Myocardial ischemia leads to significant changes in the intracellular and extracellular ionic milieu, high-energy phosphate compounds, and a ccumulation of metabolic by-products, Changes are measured in extracel lular pH and K+, and intracellular pH, Ca2+, Na+, Mg2+, ATP, ADP, and inorganic phosphate, Alterations of membrane currents occur as a conse quence of these ionic changes, adrenergic receptor stimulation, and ac cumulation of lactate, amphipathic compounds, and adenosine, Changes i n the volume of the extracellular and intracellular spaces contribute further to the ultimate perturbations of active and passive membrane p roperties that underlie alterations in excitability, abnormal automati city, refractoriness, and conduction, These characteristic changes of electrophysiologic properties culminate in loss of excitability and fa ilure of impulse propagation and form the substrate for ventricular ar rhythmias mediated through abnormal impulse formation and reentry, The ability to detail the changes in ions, metabolites, and high-energy p hosphate compounds in both the extracellular and intracellular spaces and to correlate them directly with the simultaneously occurring elect rophysiologic changes have greatly enhanced our understanding of the e lectrical events that characterize the ischemic process and hold promi se for permitting studies aimed at developing interventions that may l essen the lethal consequences of ischemia.