Endothelium-dependent and -independent hepatic artery vasodilatation is not impaired in a canine model of liver ischemia-reperfusion injury

Abstract

We investigated whether hepatic artery endothelium may be the earliest site of injury consequent to liver ischemia and reperfusion. Twenty-four heartworm-free mongrel dogs of either sex exposed to liver ischemia/reperfusion in vivo were randomized into four experimental groups (N = 6): a) control, sham-operated dogs, b) dogs subjected to 60 min of ischemia, c) dogs subjected to 30 min of ischemia and 60 min of reperfusion, and d) animals subjected to 45 min of ischemia and 120 min of reperfusion. The nitric oxide endothelium-dependent relaxation of hepatic artery rings contracted with prostaglandin F 2α and exposed to increasing concentrations of acetylcholine, calcium ionophore A23187, sodium fluoride, phospholipase-C, poly-L-arginine, isoproterenol, and sodium nitroprusside was evaluated in organ-chamber experiments. Lipid peroxidation was estimated by malondialdehyde activity in liver tissue samples and by blood lactic dehydrogenase (LDH), serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) activities. No changes were observed in hepatic artery relaxation for any agonist tested. The group subjected to 45 min of ischemia and 120 min of reperfusion presented marked increases of serum aminotransferases (ALT = 2989 ± 1056 U/L and AST = 1268 ± 371 U/L; P < 0.01), LDH = 2887 ± 1213 IU/L; P < 0.01) and malondialdehyde in liver samples (0.360 ± 0.020 nmol/mgPT; P < 0.05). Under the experimental conditions utilized, no abnormal changes in hepatic arterial vasoreactivity were observed: endothelium-dependent and independent hepatic artery vasodilation were not impaired in this canine model of ischemia/reperfusion injury. In contrast to other vital organs and in the ischemia/reperfusion injury environment, dysfunction of the main artery endothelium is not the first site of reperfusion injury.

Vascular relaxation of canine visceral arteries after ischemia by means of supraceliac aortic cross-clamping followed by reperfusion

“…A clinical study revealed that the visceral ischemic time during supraceliac, above the superior mesenteric artery or suprarenal clamping, and not clamp location, is the only independent predictor of operative mortality and that visceral ischemia time longer than 32 minutes is the strongest predictor of early death [19]. On the other hand, an experimental study with dogs showed that liver ischemic time equal or less than 60 minutes does not induce vascular dysfunction in hepatic artery [20]. Not only the ischemic time, but also the reperfusion time is an important feature in the development of vascular dysfunction.…”

Effects of pharmacological intervention on coagulopathy and organ function in xenoperfused kidneys

“…Despite the fact that prostacycline and nitroprusside are known to have vasodilatatory, platelet modulating and endothelial‐cell protective effects [16–21], both drugs failed to abrogate XAC (Figs 3 and 5). The reason for the failure could be that these drugs affect activation of coagulation only indirectly by modulating platelet response, improving microcirculation and reducing endothelial cell activation, which is in contrast to APC, that has a direct inhibitory effect on plasmatic coagulation.…”

“…Nitroprusside is an NO donor that has vasodilatatory effects, improves microcirculation, and it can provide endothelial cell protection and can alter platelet response [16][17][18][19]. In several animal models, nitroprusside reduced reperfusion injury [16,17]. Prostacycline is known to have effects on inhibition of platelet aggregation, vasodilatation, and endothelial cell protection [19][20][21].…”

“…APC was used to study the role of the generation of APC by the thrombin/thrombomodulin interaction in preventing XAC. Nitroprusside is an NO donor that has vasodilatatory effects, improves microcirculation, and it can provide endothelial cell protection and can alter platelet response [16–19]. In several animal models, nitroprusside reduced reperfusion injury [16,17].…”

Short-Term Effects of N-Acetylcysteine and Ischemic Preconditioning in a Canine Model of Hepatic Ischemia-Reperfusion Injury

“…Fifteen purpose-bred dogs ( ϳ 20 kg body weight) from Juhasz Limited (Pécs, Hungary) were housed in the Unit for Laboratory Animal quarters for at least 1 week before surgery. Canines were used for the study due to established liver I-R protocols by several groups [19,20] . Canines have an advantage because they are gentle and easy to handle and monogastric like humans.…”