Altered coronary microvascular serotonin receptor expression after coronary artery bypass grafting with cardiopulmonary bypass

Robich, Michael P.; Araujo, Eugenio G.; Feng, Jun; Osipov, Robert M.; Clements, Richard T.; Bianchi, Cesario; Sellke, Frank W.

doi:10.1016/j.jtcvs.2009.05.032

« Previous Next »The Journal of Thoracic and Cardiovascular Surgery
Volume 139, Issue 4 , Pages 1033-1040, April 2010

Altered coronary microvascular serotonin receptor expression after coronary artery bypass grafting with cardiopulmonary bypass

Michael P. Robich, MD
- Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
Eugenio G. Araujo, DVM, PhD
- School of Veterinary Medicine, Federal University of Goias, Goiania, Brazil
Jun Feng, MD, PhD
- Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
Robert M. Osipov, MD
- Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
Richard T. Clements, PhD
- Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
Cesario Bianchi, MD, PhD
- Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
Frank W. Sellke, MD
- Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
- Department of Surgery, Division of Cardiothoracic Surgery, Warren Alpert School of Medicine, Brown University, Providence, RI
- Address for reprints: Frank W. Sellke, MD, Beth Israel Deaconess Medical Center, 330 Brookline Ave. DANA 801, Boston, MA 02215.

Received 20 February 2009; received in revised form 16 May 2009; accepted 31 May 2009. published online 27 July 2009.

Objective

We evaluated roles of serotonin 1B and 2A receptors, thromboxane synthase and receptor, and phospholipases A₂ and C in response to cardiopulmonary bypass.

Methods

Patients' atrial tissues were harvested before and after cardiopulmonary bypass with cardioplegia (n = 13). Coronary microvessels were assessed for vasoactive response to serotonin with and without inhibitors of serotonin 1B and 2A receptors and phospholipases A₂ and C. Expressions of serotonin receptor messenger RNA were determined with reverse transcriptase polymerase chain reaction. Expressions of serotonin receptors and thromboxane A₂ receptor and synthase proteins were determined with immunoblotting and immunohistochemistry.

Results

Microvessel exposure to serotonin elicited 7.3% ± 2% relaxation before bypass, changing to contraction of −19.2% ± 2% after bypass (P <.001). Additions of specific serotonin 1B receptor antagonist and inhibitor of phospholipase A₂ resulted in significantly decreased contraction, −8.6% ± 1% (P < .001) and 2.8% ± 3% (P = .001), respectively. Serotonin 1B receptor messenger RNA expression increased 1.82 ± 0.34-fold after bypass (p = .044); serotonin 2A receptor messenger RNA expression did not change. Serotonin 1B but not 2A receptor protein expression increased after bypass by 1.35 ± 0.7-fold (P = .0413). Thromboxane synthase and receptor expressions were unchanged after bypass. Serotonin 1B receptor increased mainly in arterial smooth muscle. There were no appreciable differences in arterial expressions of thromboxane synthase or receptor.

Conclusions

Serotonin-induced vascular dysfunction after cardiopulmonary bypass with cardioplegic arrest may be mediated by increased expression of serotonin 1B receptor and subsequent phospholipase A₂ activation in myocardial coronary smooth muscle.

CTSNet classification: 17, 23, 27

Abbreviations and Acronyms: 5-HT1B, serotonin (5-hydroxytryptamine) receptor type 1B, 5-HT2A, serotonin (5-hydroxytryptamine) receptor type 2A, CP-CPB, cardioplegic cardiopulmonary bypass, mRNA, messenger RNA, PLA₂, phospholipase A₂, TR, thromboxane receptor, TS, thromboxane synthase, TXA₂, thromboxane A₂