Search

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability., Methods: Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry., Results: There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance., Conclusions: There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability., (Copyright © 2015 Elsevier Inc. All rights reserved.)