01.02 Decreased Coronary Arteriolar Response to KCa channel Opener after CP/CPB in Diabetic Patients

Y. Liu1, V. Cole1, F. W. Sellke1, J. Feng1  1Rhode Island Hospital,Cardiothoracic/Surgery,Providence, RI, USA

Introduction: We have found recently that diabetes is associated with inactivation of endothelial KCa channels, which may contribute to endothelial dysfunction in diabetic patients at baseline.  In the current study, we further investigated the effects of cardioplegic ischemia and reperfusion (CP) and CPB (cardiopulmonary bypass) on coronary arteriolar responses to the calcium-activated potassium channel (KCa) opener NS309 in diabetic and non-diabetic patients undergoing coronary artery bypass grafting (CABG).

Methods: The protein expression/localization of KCa channels in the harvested  atrial tissue were assayed by Western blotting and immunohistochemistry. Coronary arterioles from the harvested right atrial tissues were dissected pre- and post-CP/CPB from diabetic and non-diabetic patients (n = 5-6/group) undergoing CABG surgery. In-vitro relaxation response of pre-contracted arterioles was examined in the presence of the selective small (SKCa) and intermediate (IKCa) conductance KCa opener NS309 (10-9-10-5 M) and other vasodilatory agents.

Results: There were no significant differences in the total protein levels of IKCa, and SKCa between diabetic and non-diabetic groups or between pre- and post-CP/CPB (P>0.05). The relaxation response to NS309 post-CP/CPB was significantly decreased in diabetic and non-diabetic groups compared to their pre-CP/CPB responses, respectively (P<0.05). Furthermore, this decrease was greater in the diabetic group than that of non-diabetic group (P<0.05).

Conclusion: Our data suggest that diabetes further inactivates KCa channels of coronary microvasculature early after CP/CPB and CABG surgery. This alteration may contribute to post-operative endothelial dysfunction in diabetic patients after cardiac surgery.