Preservation of Neonatal Myocardial Function Following Ischemic Arrest

The protection of the ischemic neonatal myocardium was studied utilizing both cardioplegic and noncardioplegic solutions. Six groups of seven-day-old isolated working rabbit hearts, exposed to 120 minutes of hypothermic (3()oC) arrest, were treated with either an oxygenated or nonoxygenated cardioplegic or physiologic saline solution. The results indicated that postischemic aortic flow, stroke volume and cardiac output were significantly depressed in all oxygenated groups, but not in the nonoxygenated cardioplegic groups. Recovery of cardiac output remained near baseline in hearts treated with either single dose (94.4.±.2.5% mean±.SEM) or m ultidose (94.3±,2.3%) nonoxygenated cardioplegia, but was significantly depressed in multidose oxygenated cardioplegia (76.2,±6.2%), multidose oxygenated physiological saline (74.8±3.0% ), and single dose physiological saline (74.8.±,3.0% ), all at p<OS. Coronary sinus creatine kinase was significantly elevated during ischemia in all physiological saline groups as well as the multidose oxygenated cardioplegia group, and remained elevated following reperfusion. In the nonoxygenated cardioplegic groups, creatine kinase was not elevated. This study has demonstrated that the addition of oxygen to either cardioplegic or noncardioplegic physiological saline solutions failed to protect the neonatal myocardium from ischemic or reperfusion related injury. INTRODJJCTIQN The underlying goal of myocardial protection is the preservation of cellular and mechanical function following ischemia. Due to the normally aerobic nature of the myocardium, various methods of cardioplegic arrest have included the addition of oxygen to hemoglobin in sanguineous solutionsl,2 to perflurocarbon emulsions3.4 or in the dissolved state in crystalloid solutions.5 However, oxygen may not be totally innocuous and has been implicated in the etiology of Direct communications to: Alfred H. Stammers, BS,CCP, Division of Thoracic Surgery, University of Michigan Hospital, 1500 E. Medical Center Drive, Taubman Health Care Center, 2110 Box 0344, Ann Arbor, MI 48109 myocardial injury. 6,7 It has been shown that certain toxic intermediates, free oxygen radicals, are generated during reperfusion/reoxygenation and participate in cellular and subcellular injury. s The generation of these metabolites during reperfusion of ischemic muscle can exacerbate tissue damage altering compromised areas from reversible to irreversible injury. Recently several investigators have been able to identify the injury created during ischemia from that occurring during the reperfusion period.8•9•10 The majority of work evaluating the efficacy of oxygenated cardioplegia has thus far been completed utilizing the mature myocardium as a model, with few studies examining immature hearts. Known ontogenic differences, however, do exist which include cardiac ultrastructure,l1.12 metabolic activity13 and calcium homeostasis,2.1o all of which may influence differential response to ischemic arrest. In this study, we have examined the neonatal rabbit myocardium in an isolated working heart preparation to evaluate myocardial protection established with either: 1) oxygenated and nonoxygenated physiologic saline solutions, or 2) oxygenated and nonoxygenated St. Thomas' cardioplegic solutions. MATERIALS AND METHODS An isolated working heart preparation was utilized in all experiments and has been previously described)4,15 All animals received care according to the "Principles of Laboratory Animal Care of the National Society of Medical Research" and the "Guide for the Care and Use of Laboratory Animals" prepared by the National Academy of Sciences (NIH Publication No. 80-23, revised 1978). Neonatal (6 to 8 days old) New Zealand white rabbits of either sex were utilized in all experiments. Following anesthesia with Ketamine• (100 mg/kg) and Xylazineb (Smg/kg) all animals were intubated and ventilated with a small animal respirator<'. The chest was opened via a median sternotomy and the pericardium incised. The thymus was removed exposing the great vessels and the heart was rapidly excised and placed in 4°C a Ketamine, Parke-Davis, Morris Plains, NJ b Xylazine, Mobay Co., Shawnee, KA c Harvard Apparatus Co. Inc., Millis, MA