Effect and mechanism of cardioplegic arrest on the coronary endothelium-smooth muscle interaction.
1. During cardiac surgery, the heart is arrested and protected by hyperkalaemic cardioplegia. The coronary endothelium may be damaged by ischaemia-reperfusion and cardioplegia. Subsequently, this may affect cardiac function immediately after cardiac surgery and cause mortality and morbidity. 2. We investigated coronary endothelium-smooth muscle interaction after exposure to depolarizing (hyperkalaemic; K+ 20 or 50 mmol/L) and hyperpolarizing (the K+ channel opener aprikalim) cardioplegia and organ preservation solution (University of Wisconsin (UW) solution). Endothelium-dependent relaxation and hyperpolarization of the coronary smooth muscle were studied in the porcine and human large conductance and micro-coronary arteries. Intracellular free calcium concentration in endothelial cells was also measured. 3. The endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation to A23187, bradykinin, and substance P in arteries contracted by either U46619 (10 nmol/L) or K+ (25 mmol/L) was reduced after exposure to either high K+ or UW solution, but was maximally preserved after exposure to aprikalim. The hyperpolarization of the membrane potential in response to the above endothelium-derived relaxing factor stimuli was also reduced by exposure to depolarizing cardioplegia. Studies in microcoronary arteries are in accordance with findings in large arteries. The intracellular free calcium concentration remained unchanged after exposure to hyperkalaemia. 4. We concluded that: (i) during cardiac surgery, the function of coronary circulation may be changed due to exposure to depolarizing cardioplegia or preservation solutions; (ii) the functional change in the coronary circulation is related to the altered interaction between the endothelium and smooth muscle; (iii) depolarizing (hyperkalaemia) cardioplegia or hyperkalaemic organ preservation solutions affect endothelium-smooth muscle interaction through the EDHF pathway; (iv) EDHF relaxes the porcine large and microcoronary arteries through multiple K+ channels; and (v) that hyperpolarizing vasodilators (K+ channel openers) may protect EDHF-mediated endothelial function when used as cardioplegia.
He
G W
GW
Division of Cardiothoracic Surgery, Grantham Hospital, Hong Kong. gwhe@hkucc.hku.hk
D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D002118:Calcium / Q000032:analysis; D006348:Cardiac Surgical Procedures; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D008564:Membrane Potentials; D008833:Microcirculation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D013552:Swine; D014664:Vasodilation
D001685:Biological Factors; D002314:Cardioplegic Solutions; C067410:endothelium-dependent hyperpolarization factor; D002118:Calcium