Peptide BPC-157 Resolves Ischemia-Reperfusion Damage from Pringle Maneuver in Rats

The Pringle maneuver, a temporary clamping of the portal triad (hepatic artery, portal vein, bile duct), is used in liver surgery to control bleeding but causes significant ischemia-reperfusion injury. This leads to a cascade of damage, including portal hypertension, organ damage (liver, lungs, intestine), heart strain, and thrombosis. Current solutions to mitigate this damage are limited. The stable gastric pentadecapeptide BPC-157 is being investigated due to its previously documented cytoprotective and beneficial effects in other ischemia/reperfusion models, where it has been shown to resolve vessel occlusions by rapidly recruiting collateral vessels.

Deeply anesthetized rats underwent a 30-minute portal triad obstruction (Pringle maneuver). They were then allowed to reperfuse for either 15 minutes or 24 hours. The peptide BPC-157 was administered as a single challenge at doses of 10 µg/kg or 10 ng/kg. The timing of administration varied: either during the ischemic period (intraperitoneally at 5 minutes before clamping, or as a bath at 5 or 30 minutes into clamping) or during reperfusion (as a bath at 1 or 15 minutes post-clamping, or intraperitoneally at 24 hours post-clamping). Researchers assessed outcomes via gross and microscopic pathology, malondialdehyde levels, serum enzymes, electrocardiogram, portal/caval/aortal pressure, thrombosis, and venography.

BPC-157 counteracted the severe organ and systemic damage caused by the Pringle maneuver. During both ischemia and reperfusion, it attenuated or completely abrogated portal hypertension, severe aortal hypotension, and ascites formation. It also counteracted thrombosis in the portal vein tributaries, inferior caval vein, and hepatic artery. The therapy resolved electrocardiogram disturbances, including increased P wave amplitude and the S1Q3T3 QRS pattern. Critically, BPC-157 rapidly established a vascular shunting pathway to bypass the obstruction.

This collateral pathway, involving the portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein, provided an adequate shunt that immediately affected the disturbed hemodynamics. The protective effects extended to multiple organs, counteracting lung capillary congestion, liver vein dilation, intestinal edema and villous damage, splenomegaly, and right heart strain.

Written by TitrateLab, separately from the study summarized above.