J. Li1, D. D. Harris1, S. Sabe1, D. Banerjee1, E. Pearson1, J. Nho1, A. Ehsan1, N. Sodha1, J. Feng1, F. W. Sellke1 1Brown University School Of Medicine, Cardiothoracic Surgery, Providence, RI, USA
Introduction: We have previously found that cardioplegic arrest and cardiopulmonary bypass (CP/CPB) is associated with altered coronary arteriolar response to serotonin (5-HT) in patients undergoing cardiac surgery. In this study, we investigated the effects of hypertension on coronary microvascular vasomotor tone in response to 5-HT and myocardial protein expression of 5-HT receptors in the setting of CP/CPB.
Methods: Coronary arterioles (90-150 µm in diameter) were dissected from harvested pre- and post-CP/CPB right atrial tissue samples of patients undergoing cardiac surgery with normotension (control), controlled hypertension, and uncontrolled hypertension. The vasomotor tone was assessed by video-myography, and the protein expression of 5-HT receptors (1A, 1B, 2A, and 2B) in the right atrial tissue samples (n=4-6/group) were measured using immunoblotting methods.
Results: At baseline (pre-CP/CPB), 5-HT induced moderate relaxation responses of coronary arterioles in normotensive and controlled hypertension patients, whereas 5-HT caused moderate contractile responses in patients with uncontrolled hypertension. Post-CP/CPB caused contractile responses of coronary arterioles in all three groups, respectively. The post-CP/CPB contractile responses to 5-HT were significantly profound in the uncontrolled hypertensive groups compared to that of normotensive or controlled hypertensive groups (p<0.05). At baseline (pre-CP/CPB), expression of the 5-HT1A receptor was significantly lower in the uncontrolled hypertension group compared to the normotensive (control) group (p<0.05). However, post-CP/CPB, there was no significant difference in 5-HT1A expression among the three patient groups. In addition, the controlled hypertension group saw a significant increase in 5-HT1A expression post-CP/CPB compared to baseline (p<0.05). There were no significant differences in 5-HT1B receptor expression at baseline (pre-CP/CPB) among the three groups. The post-CP/CPB 5-HT1B expression in the uncontrolled hypertensive group tended to increase compared to baseline. Importantly, the levels of 5-HT1B expression were higher in the uncontrolled hypertension group compared to the normotensive or controlled hypertension groups (p<0.05). Finally, there were no significant changes in expression of 5-HT 2A and 2B receptors among the three groups either pre- or post-CP/CPB.
Conclusion: Uncontrolled hypertension and/or CP/CPB are associated with increased coronary contractile response of coronary microvessels to 5-HT and altered 5-HT1B protein expression. This alteration may contribute to postoperative coronary spasm and worsened recovery of coronary perfusion in patients with or without hypertension following CP/CPB and cardiac surgery.
