Impaired Coronary Contraction to Phenylephrine After Cardioplegic Arrest in Diabetic Patients

Overview

Journal J Surg Res

Specialty General Surgery

Date 2018 Aug 14

PMID 30100044

Citations 4

Authors

Nicholas Sellke

Caroline Gordon

Isabella Lawandy

Anastassia Y Gorvitovskaia

Laura A Scrimgeour

James G Fingleton

Frank W Sellke

Jun Feng

Affiliations

Soon will be listed here.

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 to 10 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.

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References

Fischer G, Levin M . Vasoplegia during cardiac surgery: current concepts and management. Semin Thorac Cardiovasc Surg. 2010; 22(2):140-4. DOI: 10.1053/j.semtcvs.2010.09.007. View

Ruel M, Khan T, Voisine P, Bianchi C, Sellke F . Vasomotor dysfunction after cardiac surgery. Eur J Cardiothorac Surg. 2004; 26(5):1002-14. DOI: 10.1016/j.ejcts.2004.07.040. View

Feng J, Chu L, Robich M, Clements R, Khabbaz K, Hagberg R . Effects of cardiopulmonary bypass on endothelin-1-induced contraction and signaling in human skeletal muscle microcirculation. Circulation. 2010; 122(11 Suppl):S150-5. PMC: 2943858. DOI: 10.1161/CIRCULATIONAHA.109.928226. View

Rossen J, Winniford M . Effect of increases in heart rate and arterial pressure on coronary flow reserve in humans. J Am Coll Cardiol. 1993; 21(2):343-8. DOI: 10.1016/0735-1097(93)90673-o. View

Feng J, Liu Y, Chu L, Singh A, Dobrilovic N, Fingleton J . Changes in microvascular reactivity after cardiopulmonary bypass in patients with poorly controlled versus controlled diabetes. Circulation. 2012; 126(11 Suppl 1):S73-80. PMC: 3448935. DOI: 10.1161/CIRCULATIONAHA.111.084590. View

Haffner S, Lehto S, Ronnemaa T, Pyorala K, Laakso M . Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998; 339(4):229-34. DOI: 10.1056/NEJM199807233390404. View

McAlister F, Man J, Bistritz L, Amad H, Tandon P . Diabetes and coronary artery bypass surgery: an examination of perioperative glycemic control and outcomes. Diabetes Care. 2003; 26(5):1518-24. DOI: 10.2337/diacare.26.5.1518. View

Licker M, Neidhart P, Lustenberger S, Valloton M, Kalonji T, Fathi M . Long-term angiotensin-converting enzyme inhibitor treatment attenuates adrenergic responsiveness without altering hemodynamic control in patients undergoing cardiac surgery. Anesthesiology. 1996; 84(4):789-800. DOI: 10.1097/00000542-199604000-00005. View

Feng J, Liu Y, Singh A, Ehsan A, Sellke N, Liang J . Effects of diabetes and cardiopulmonary bypass on expression of adherens junction proteins in human peripheral tissue. Surgery. 2016; 161(3):823-829. PMC: 5305435. DOI: 10.1016/j.surg.2016.08.057. View

10.

Feng J, Liu Y, Clements R, Sodha N, Khabbaz K, Senthilnathan V . Calcium-activated potassium channels contribute to human coronary microvascular dysfunction after cardioplegic arrest. Circulation. 2008; 118(14 Suppl):S46-51. PMC: 2646506. DOI: 10.1161/CIRCULATIONAHA.107.755827. View

11.

Wang S, Stamler A, Tofukuji M, Deuson T, Sellke F . Effects of blood and crystalloid cardioplegia on adrenergic and myogenic vascular mechanisms. Ann Thorac Surg. 1997; 63(1):41-9. DOI: 10.1016/s0003-4975(96)00644-3. View

12.

Lim A . Diabetic nephropathy - complications and treatment. Int J Nephrol Renovasc Dis. 2014; 7:361-81. PMC: 4206379. DOI: 10.2147/IJNRD.S40172. View

13.

Feng J, Anderson K, Singh A, Ehsan A, Mitchell H, Liu Y . Diabetes Upregulation of Cyclooxygenase 2 Contributes to Altered Coronary Reactivity After Cardiac Surgery. Ann Thorac Surg. 2017; 104(2):568-576. PMC: 5891657. DOI: 10.1016/j.athoracsur.2016.11.025. View

14.

Sellke F, Quillen J . Altered effects of vasopressin on the coronary circulation after ischemia. J Thorac Cardiovasc Surg. 1992; 104(2):357-63. View

15.

Argenziano M, Chen J, Choudhri A, Cullinane S, Garfein E, Weinberg A . Management of vasodilatory shock after cardiac surgery: identification of predisposing factors and use of a novel pressor agent. J Thorac Cardiovasc Surg. 1998; 116(6):973-80. DOI: 10.1016/S0022-5223(98)70049-2. View

16.

Crescenzi G, Bove T, Pappalardo F, Scandroglio A, Landoni G, Aletti G . Clinical significance of a new Q wave after cardiac surgery. Eur J Cardiothorac Surg. 2004; 25(6):1001-5. DOI: 10.1016/j.ejcts.2004.02.030. View

17.

Feng J, Chu L, Dobrilovic N, Liu Y, Singh A, Sellke F . Decreased coronary microvascular reactivity after cardioplegic arrest in patients with uncontrolled diabetes mellitus. Surgery. 2012; 152(2):262-9. PMC: 3407967. DOI: 10.1016/j.surg.2012.04.009. View

18.

Feng J, Bianchi C, Sandmeyer J, Li J, Sellke F . Molecular indices of apoptosis after intermittent blood and crystalloid cardioplegia. Circulation. 2005; 112(9 Suppl):I184-9. DOI: 10.1161/CIRCULATIONAHA.104.526160. View

19.

Sodha N, Feng J, Clements R, Bianchi C, Boodhwani M, Ramlawi B . Protein kinase C alpha modulates microvascular reactivity in the human coronary and skeletal microcirculation. Surgery. 2007; 142(2):243-52. DOI: 10.1016/j.surg.2007.03.010. View

20.

Thourani V, Weintraub W, Stein B, Gebhart S, Craver J, Jones E . Influence of diabetes mellitus on early and late outcome after coronary artery bypass grafting. Ann Thorac Surg. 1999; 67(4):1045-52. DOI: 10.1016/s0003-4975(99)00143-5. View