A collective work on "experimental studies of coronary artery bypass grafts, function of coronary circulation and related clinical studies in cardiac surgery"

Cardiovascular diseases are the major killers and cardiac operations are frequently performed. My research interests in the last decade in the following fields in cardiovascular and surgical research are under one major theme - to understand the mechanism of cardiac surgery related vascular systems and to improve the results of cardiac surgery. These fields are: 1) analyses of operative results in coronary artery bypass grafting (CABG) and heart valve operations; 2) experimental studies on the endothelial function related to nitric oxide (NO) and endothelium-dependent hyperpolarization; 3) experimental studies on the grafts for CABG, particularly on arterial grafts; 4) experimental studies on function of the coronary circulation directly related to open heart surgery and heart transplantation. The vascular endothelial function is composed of complex substances and NO is the major mediator. When the NO production is inhibited, another mechanism - endothelium-dependent hyperpolarization plays an important role in the endothelium-smooth muscle function. We for the first time directly measured the NO release by electrochemical methods and the hyperpolarization by electrophysiological methods in the human vessels used as arterial and venous grafts. In CABG, venous grafts have high occlusion rates and successful use of various arteries is achieved. However, arterial grafts have different tendency to develop spasm and the long-term patency of the grafts may be different. A unanimous opinion on the choice of the grafts has not been formed. We have performed a serious of experiments to investigate I) the smooth muscle contraction and the endothelial function; 2) the possible spasmogens (vasoconstrictors); 3) receptor function; 4) morphometric characteristics; and 5) segmental differences regarding the reactivity. Based on these studies, we have proposed, for the first time, a functional classification to understand the difference among arterial grafts. Further, we have carried out extensive pharmacologic studies to examine the effect of a wide range of vasodilators to form a scientific basis for clinical antispastic therapy in the arterial grafts. This has resulted in successful clinical protocols. Further, the coronary endothelial function is related to the postoperative heart function. Previous studies were focused on the nitric oxide (NO) release in the coronary circulation. We have demonstrated that NO release is tolerant to the cardioplcgic exposure if the ischemic effect is excluded. However, the endothelium-derived hyperpolarizing factor (EDHF)mediated function (electrical hyperpolarization and mechanical relaxation) in both large and micro coronary arteries is altered after the hyperkalemic cardioplcgic arrest or donor heart preservation with hyperkalemic solutions. We have, for the first time, demonstrated this and proposed a mechanism that this is related to the prolonged partial depolarization of the cellular membrane of the smooth muscle and inhibition of potassium (K⁺) channels. Further, for the first time again, our work has demonstrated that hyperpolarizing cardioplegia using K⁺ channel openers (such as aprikalim or KRN4884) is superior to the depolarizing (hyperkalemic) cardioplegia with regard to the protection of the EDHF-related endothelial function. We anticipate that the findings from my studies will be useful in the further improvement of the results of cardiac surgery.