Myocardial high energy phosphate metabolism during ventricular fibrillation with total circulatory arrest

Abstract

The study of high energy phosphates in myocardial energy metabolism has provided important insights into the factors that affect cellular injury during ischemia and metabolic and mechanical recovery with reperfusion. The term high energy phosphates (HEP) in the context of this paper includes adenine nucleotides (ATP and ADP) and creatine phosphate (CP). ATP directly provides the energy for mechanical, homeostatic, and synthetic myocardial functions. CP is postulated to function as an energy reservoir, transferring high energy bonds in the cytosol for the regeneration ATP from ADP. During severe or complete ischemia, myocytes become oxygen deficient and oxidative phosphorylation in the mitochondria ceases. As a result energy utilization exceeds production and myocardial HEP are depleted. Although no causal relationship has been demonstrated, under physiologic conditions there is a strong association between the depletion of myocardial HEP during ischemia, and the onset of myocardial injury. During reperfusion, the regeneration of HEP may also provide an indication of cell viability and adequacy of reperfusion. The focus of this paper is on myocardial HEP metabolism during cardiac arrest due to ventricular fibrillation (VF), which will be referred to as ventricular fibrillation with total circulatory arrest (VF-TCA). This is to be distinguished from cardiopulmonary bypass studies in which circulation to extra-cardiac organs can be maintained during VF. Since few studies to date have investigated HEP metabolism during in vivo VF-TCA, most of the information presented here is derived from other models of ischemia. Considerable variation exists among these experimental models of myocardial ischemia and the methods used to quantify myocardial HEP. These factors make comparison of studies difficult. For the most part, however, HEP depletion and associated myocardial injury during ischemia