Recipient of 1987 Fellowship Award in Cardiovascular Perfusion Age Related Differences in Oxygen Free Radical Injury during Myocardial Ischemia

_____________________________ __ (J. Extra-Corpor. Techno/. 19[3] p. 245-257 Fall 1987, 42 ref.) Myocardial protection with an oxygenated cardioplegic solution was studied in mature and immature animals. Isolated adult and neonatal rabbit hearts were exposed to 90 minutes of hypothermic 30°C ischemia, and one of the following treatments: multidose oxygenated (p02>650 torr) cardioplegia, multidose nonoxygenated (p02<200 torr) cardioplegia, and a noncardioplegic Krebs-Henseleit solution. Upon reperfusion, adult hearts that had not received either cardioplegia treatment failed to recover postischemic hemodynamic function. However, neonates given the same treatment were able to recover 74.0 ± 2.4% (Mean± SEM) of preischemic cardiac output and 69.2±5.7% recovery of stroke work. Oxygenated cardioplegia administered to adult and neonatal hearts resulted in postischemic cardiac output recovery of 90.8 ± 2.4% and 86.5 ± 8.6%, respectively. Cardiac output recovery in nonoxygenated cardioplegia groups was 105.3 ± 3.9% in the adults, and 95.2 ± 6.6% in the neonates. Coronary sinus creatine kinase was substantially elevated in all adult groups, but not in the cardioplegia treated neonates. Membrane lipid peroxidation was assessed by measuring malondialdehyde in myocardial tissue homogenates. Malondialdehyde remained at control levels across all neonatal groups, but in the mature hearts the nonoxygenated cardioplegia group had significantly lower peroxidative products than the oxySupported in part by American Society of Extra-Corporeal Technology Research Grant #0186, 1986-87. Direct communications to: Alfred H. Stammers, Department of Surgery, SUNY Health Science Center, Syracuse, NY 13210 genated hearts. The results of this study indicate an increased susceptibility of the mature myocardium to both the damaging effects of ischemia and free oxygen radicals. Administration of an oxygenated cardioplegic solution failed to provide adequate protection during moderate hypothermic arrest, and resulted in increased membrane peroxidative activity. Introduction __________________________ _ The formulation of cardioplegic solutions has long intrigued both the clinician and the basic scientist. The underlying premise of cardioplegia is to protect the ischemic myocardium by either enhancing metabolic function, or promoting an environment that minimizes the perturbations produced during interrupted flow. Many researchers have shown that the maintenance of aerobic metabolism during ischemia has the desired effect of generating high energy phosphate compounds, which help maintain cellular homeostasis. · ·'·" Sanguineous cardioplegic solutions have increased oxygen carrying capacity, but may not provide optimum oxygen delivery. Increases in viscosity with decreasing temperature combined with alterations in oxyhemoglobin dissociation characteristics'i may represent limitations in the use of blood cardioplegia. Improved myocardial protection by the hyperoxygenation of crystalloid cardioplegic solutions has been shown. n.7 Several of the physical laws governing oxygen concentrations in crystalloid solutions include: increased oxygen solubility as temperature decreases, increased availability and utilization of oxygen, and substantially lower temperature related alterations in solution viscosity. 6 Recently a group of highly toxic and reactive substances derived from molecular oxygen, free oxygen