Adenosine and lidocaine (AL) combination dilates intimally damaged rat thoracic aortic rings and guinea pig mesenteric arteries: possible significance to cardiac surgery

Arsyad, Aryadi, Sokoya, Elke, and Dobson, Geoffrey P. (2018) Adenosine and lidocaine (AL) combination dilates intimally damaged rat thoracic aortic rings and guinea pig mesenteric arteries: possible significance to cardiac surgery. American Journal of Translational Research, 10 (6). pp. 1841-1851.

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Abstract

New pharmacotherapies are required to improve vessel graft protection and prevent vasoconstriction and spasm in CABG surgery. Previously we have studied adenosine (A) and lidocaine (L) relaxation in rat aortic rings, and reported a possible crosstalk between L relaxation and adenosine A(2a) receptor inhibition. The aim of the present study was to examine the effect of AL combination compared to A and L alone on relaxation in intact and denuded rat aortic rings and in guinea-pig pressurized mesenteric arterial segments. Aortic rings were harvested from Sprague-Dawley rats and equilibrated in an organ bath containing modified Krebs-Henseleit (KH) solution, pH 7.4, 37 degrees C. Rings were pre-contracted sub-maximally with 0.3 mu M norepinephrine, and the effects of increasing AL, A or L (up to 1.0 mM) were examined in intact and denuded rings. Mesenteric artery segments were isolated from guinea-pigs and mounted in an arteriograph containing KH solution and pressurised to 60 mmHg. Arteries were preconstricted with 10(-8) M vasopressin and AL, A, or L was administered luminally or abluminally. Diameters were measured using video-microscopy. We report in intact rat aortic rings, AL increased relaxation from 21 to 100% (0.1-1.0 mM) and relaxation was endothelium-independent. Adenosine alone was also a potent relaxant of aortic rings but, unlike AL relaxation, it was partially endothelium-dependent. In intact mesenteric artery segments, increasing luminal AL produced a potent endothelium-independent dilation (up to 90%). Adenosine dilation was endothelium-independent but not lidocaine, which produced 33% dilation only after endothelial removal. Extra-luminal AL and A led to 76% and 80% dilationin intact segments respectively, whereas L resulted in constriction (10-17%). In conclusion, we show that AL can dilate aortic rings and mesenteric artery segments by up to 90% regardless of whether the endothelium is intact. We discuss the potential translational significance of AL to improve conduit protection in cardiac surgery, and other major surgeries.

Item ID: 54753
Item Type: Article (Research - C1)
ISSN: 1943-8141
Keywords: rat aorta, mesenteric, artery, adenosine, lidocaine, relaxation, vasodilation, CABG, vasospasm
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Copyright Information: [Published] under the “Creative Commons Attribution Noncommercial License”, enabling the unrestricted non-commercial use, distribution, and reproduction of the published article in any medium, provided that the original work is properly cited.
Funders: James Cook University (JCU), Flinders Medical Centre Seeding Grant
Date Deposited: 25 Jul 2018 07:55
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110299 Cardiovascular Medicine and Haematology not elsewhere classified @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 50%
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