engleski

Complications of portal triad obstruction and reperfusion in rats. Pentadecapeptide BPC 157 counteracts venous and arterial thrombosis and arrhythmias

Aim. Pentadecapeptide BPC 157 therapy in temporary portal triad obstruction (PTO) (hepatic artery (HA), portal vein (PV), bile duct occlusion for 30 min in rats), and in reperfusion period thereafter, in post-PTO-period. The counteraction of the Pringle maneuver complications (rapid cloth formation in the PV, superior mesenteric vein (SMV), lienal vein (LV), inferior caval vein (ICV) HA, peaked P wave and tachycardia). Previously, in rats with PTO BPC 157 beneficially increases vessels branching in intestinal serosa and counteracts intestinal lesions, counteracts free radicals formation and most importantly, counteracts portal hypertension and caval hypotension (Gastroenterology 2017, Vol. 152, Issue 5, S909–S910 ; 2015, Vol. 148, Issue 4, S- 650 ; 2015, Vol. 148, Issue 4, S-548). Likewise, due to its particular effect on endothelial maintenance, BPC 157 prevents and reverses venous (Vascul Pharmacol 2018 Jul ; 106:54-66) and arterial thrombosis (J Physiol Pharmacol 2009 Dec ; 60 Suppl 7:161- 5). Methods: Medication (BPC 157 (10 μg/kg, 10 ng/kg), or saline (5 ml/kg) (controls)) was applied as a bath at the clamped area immediately after portal triad clamping in rats with PTO or at the area that used to be clamped at 1 min or at 24 h reperfusion time. Results: A period of 30 min of PTO regularly produced considerable thrombosis in the ICV, PV, SMV, LV and HA. Contrarily, in BPC 157 treated rats, the weights of the formed clots were considerably smaller in the ICV, PV, SMV, LV and HA. PTO rats immediately exhibited peaked P wave values and significant tachycardia, an effect persisting throughout the whole ischemic period. The peaked P waves and tachycardia were completely absent in all BPC 157-treated rats. In particular, QRS complexes like right bundle branch block (RBBB) pattern appear in all control rats, but were completely absent in all BPC 157 treated rats (Fisher exact probability test P≤0.05 at least vs. control) (Fig.1, BPC 157 10 μg/kg (light gray bars), 10 ng/kg (dark gray bars), *P≤0.05, at least vs. control (white bars))). Also after PTO, rats in post-PTO-period, during reperfusion constantly exhibited peaked P wave values and significant tachycardia, an effect persisting throughout the whole reperfusion period. All applications of BPC 157 (given at 1 min or at 24 h reperfusion time) quickly resulted in the absence of the peaked P waves. Tachycardia was also affected ; sinus rhythm appeared in a normal range of heart frequency (Fig.1, *P≤0.05, at least vs. control). Conclusion. Confronted with Pringle maneuver and its consequences, BPC 157 therapy distinctively mitigates the whole syndrome, having therapy effect applied in ischemia (PTO-period) much like therapy effect given in reperfusion (post- PTO-period), involving the counteraction of the course of the thrombosis in both veins and arteries, and ECG acute right ventricular overload.

BPC 157 ; portal triad

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