The use of cardioplegia and hypothermia for myocardial preservation is an essential component of modern cardiac surgery. While preservation of myocardial function and perfusion is usually adequate, it is frequently not optimal. Episodic coronary ischemia and spasm may present during or following cardiac surgery in which cardiopulmonary bypass and the administration of cardioplegia has been performed. Preliminary studies from our laboratory have found significant alterations of both endothelium- dependent and direct smooth muscle responses following cardiopulmonary bypass and cold cardioplegia. The proposed research will examine if 1) ischemia followed with reperfusion alters endothelium-dependent and independent vascular responses in the porcine coronary microcirculation, if 2) hyperkalemic, hypothermic cardioplegia alters or preserves coronary microvascular function, if 3) these alterations are influenced by the type of cardioplegia used, if 4) the infusion pressure or route of administration of cardioplegia, or the reperfusion pressure following ischemic cardioplegia have an effect on microvascular reactivity, and if 5) vascular damage can be reduced with the use of additives to the cardioplegic solution. Since arteries less than 200 mum in diameter provide a majority of control over myocardial perfusion, these vascular segments will be examined. In a porcine model of acute myocardial ischemia, pigs will be anesthetized and the circumflex coronary artery will be occluded for 1 hour. The ischemic myocardium will then be reperfused for 1 hour. Using a porcine model of cardiopulmonary bypass, either blood or crystalloid hyperkalemic [25 mEq K+/1] cardioplegic solution or hyper- magnesemic cardioplegic solution will be infused into the aortic root at either 60 or 150 mmHg, or into the coronary sinus at 40 mmHg. Following 1 hour of ischemic cardioplegia, the heart will be reperfused for 1 hour while the pig will be separated from cardiopulmonary bypass. Following both experiments, the diameter of pressurized coronary microvessels (100- 200 mum in diameter) will be examined in a no-flow state using a unique in vitro microvessel imaging apparatus, to eliminate autoregulatory and metabolic influences. Both epicardial and endocardial coronary microvessels will be studied. Following precontraction with acetylcholine, various endothelium-dependent and independent vasoactive substances will be applied. The morphology of the vascular smooth muscle and endothelium will be assessed with electron microscopy. This study has significant clinical implications in cardiac surgery and will better define the adverse effects of ischemia and cardioplegia on coronary microvascular reactivity. The alteration of vascular response may not only offer clues to the mechanism of failure of myocardial preservation, but may also provide another method of evaluating the efficacy of different methods of myocardial protection, and of newer additives such as free radical scavengers and metabolic enhancers.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Beth Israel Deaconess Medical Center
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Feng, Jun; Liu, Yuhong; Sabe, Ashraf A et al. (2016) Differential impairment of adherens-junction expression/phosphorylation after cardioplegia in diabetic versus non-diabetic patients. Eur J Cardiothorac Surg 49:937-43
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