Abstract
BACKGROUND: We have previously found that hyperkalemic cardioplegic arrest in the setting of cardiopulmonary bypass (CP/CPB) is associated with impairment of the coronary arteriolar response to phenylephrine in nondiabetic (ND) patients. We hypothesized that diabetes may alter coronary arteriolar response to alpha-1 adrenergic agonist in the setting of CP/CPB. In this study, we further investigated the effects of diabetes on the altered coronary arteriolar response to phenylephrine in patients undergoing cardiac surgery. METHODS: Coronary arterioles (90-150 μm in diameter) were harvested pre- and post-CP/CPB from the ND and diabetic mellitus (DM) patients (n = 8/group) undergoing cardiac surgery. In-vitro microvascular reactivity was examined in response to phenylephrine. The protein expression/localization of the alpha-1 adrenergic receptors in the atrial myocardium was measured by Western blotting and immunohistochemistry. RESULTS: Phenylephrine (10(-9) to 10(-4) M) induced a dose-dependent contractile response in both ND and DM vessels pre- and post-CP/CPB. There was no significant difference in the pre-CP/CPB contractile responses to phenylephrine between ND and DM groups. The post-CP/CPB contractile response was significantly diminished in both ND and DM groups compared with the respective pre-CP/CPB response (P < 0.05 versus pre-CP/CPB). This diminished contractile response was more pronounced in vessels from DM patients compared with vessels from ND patients (P < 0.05 versus ND). There were no significant differences in the protein expression of alpha-1A and alpha-1B receptors in the atrial myocardium between the ND and DM groups or tissue harvested pre- or post-CP/CPB. CONCLUSIONS: Diabetes is associated with a decreased contractile response of coronary arterioles to phenylephrine in the setting of CP/CPB versus that observed in ND patients. This alteration may contribute to the vasomotor dysfunction of coronary microcirculation seen early after CP/CPB in patients with diabetes.