Decreased coronary microvascular reactivity after cardioplegic arrest in patients with uncontrolled diabetes mellitus

Background. We investigated the effects of cardioplegic arrest and reperfusion on coronary arteriolar responses to endothelium-dependent and -independent vasodilators and associated Signaling pathways in uncontrolled diabetic, well controlled diabetic, and case-matched nondiabetic patients undergoing coronary artery bypass graft surgery. Methods. Coronary arterioles from harvested right atrial tissues were dissected pre- and post-cardioplegic arrest and reperfusion from uncontrolled diabetic (n = 10; hemoglobin A1c = 9.3 +/- 0.3), well controlled diabetic (n = 10; hemoglobin A1c = 6.2 +/- 0.2), and nondiabetic patients (n = 10; hemoglobin A1c = 5.1 +/- 0.1) undergoing coronary artery bypass graft surgery. Results. The baseline microvascular response to adenosine 5'-diphosphate, substance P, and sodium nitroprusside of arterioles from uncontrolled diabetic patients were decreased compared to the respective response from nondiabetic or well controlled diabetic patients (P < .05). The vasodilatory responses to adenosine 5'-diphosphate and substance P after cardioplegic arrest and reperfusion were significantly decreased in all 3 groups compared to pre-cardioplegic arrest and reperfusion responses (P < .05). However, these decreases were more pronounced in the uncontrolled diabetic group (P < .05). The expression of protein kinase C-alpha, Protein kinase C-beta, and protein oxidation in atrial tissues was significantly increased in the uncontrolled diabetic group compared to the nondiabetic or controlled diabetes groups. Conclusion, Uncontrolled diabetes is associated with endothelium-dependent and -independent vascular dysfunction of coronary arterioles. In addition, uncontrolled diabetes worsens the recovery of coronary arteriolar function after cardioplegic arrest and reperfusion. These alterations are associated with an increased expression/activation of protein kinase C-alpha and protein kinase C-beta and enhanced oxidative stress. (Surgery 2012;152:262-9.)