A novel survival model of cardioplegic arrest and cardiopulmonary bypass in rats: a methodology paper

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Background
Although considerable progress has been made in surgical techniques and other perioperative management to allow for the majority of patients to undergo cardiac surgery without significant mortality, more than 25% of this surgical population may still experience substantial morbidity related to adverse cardiovascular events. These include prolonged contractile dysfunction (stunning), myocardial infarction, low-output syndromes, and overt ventricular failure, all resulting in prolonged intensive care unit stay and reduced functional capacity at discharge, and ultimately contribute to overall mortality 12. Mortality after perioperative myocardial infarction is 40-50% 3. The etiology of myocardial dysfunction following cardiac surgery is multifactorial but frequently involves perioperative myocardial ischemia reperfusion injury 4.
Since the advent of cardiopulmonary bypass (CPB), cardioplegic arrest has been an essential component of cardiac surgery but remains associated with ischemia-reperfusion injury to the myocardium 567. As the population ages and percutaneous coronary interventions have become a standard therapy, patients referred for cardiac surgery generally present with a higher risk for perioperative cardiovascular complications 89. These complications are primarily due to increased comorbidities and more complex surgical interventions resulting in the need for more prolonged aortic crossclamp and CPB times, all making optimized myocardial protection strategies an essential component of cardiac surgery procedures. Experimental efforts to better understand the underlying mechanism associated with postoperative myocardial reperfusion injury and to improve established myocardial protection protocols have been limited to either costly large animal models or ex vivo heart preparations 101112. The use of normothermic cardioplegia solutions has shown beneficial results, but research is limited and principally relies on isolated heart models 131415. However, these models do not facilitate research on long-term effects of myocardial reperfusion injury or novel therapeutic interventions. To advance the field, additional research in a suitable rodent model with good survivability appears to be warranted. Such a model would not only allow to further elucidate mechanisms of adverse myocardial outcomes following cardioplegic arrest but also permits the characterization of genetic, proteomic, and histologic changes as well as long-term functional outcomes in response to injury and therapy. It might also facilitate further research aiming to optimize current cardioprotective strategies in vivo and facilitate myocardial gene delivery studies 1617.

Based on an existing beating-heart model of CPB in the rat 18, we developed a novel in vivo survival model that allows administration of antegrade cardioplegia and endoaortic crossclamping. To rule out any gross neurological damage due to cannulation of the right carotid artery, a functional assessment and histological evaluation of the brains was performed.

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