Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats.

Marijan Tepeš ,Ivica Kocman,Sven Seiwerth,Mariam Samara,Ivica Sjekavica,Lovorka Batelja,Antonio Kokot,Toni Kolak,Goran Šantak ,Zrinko Madžar ,Karol Šimonji ,Anita Škrtić ,Helena Žižek ,Martina Knežević ,Sanja Štrbe ,Slaven Gojković ,Alenka Boban Blagaić ,Eva Lovrić ,Hrvoje Vraneš ,Marija Milavić ,Sunčana Sikirić ,Ivan Barišić ,Ivan Krezić ,Predrag Sikirić

doi:10.3389/fphar.2021.718147

Abstract

Recently, the stable gastric pentadecapeptide BPC 157 was shown to counteract major vessel occlusion syndromes, i.e., peripheral and/or central occlusion, while activating particular collateral pathways. We induced abdominal compartment syndrome (intra-abdominal pressure in thiopental-anesthetized rats at 25 mmHg (60 min), 30 mmHg (30 min), 40 mmHg (30 min), and 50 mmHg (15 min) and in esketamine-anesthetized rats (25 mmHg for 120 min)) as a model of multiple occlusion syndrome. By improving the function of the venous system with BPC 157, we reversed the chain of harmful events. Rats with intra-abdominal hypertension (grade III, grade IV) received BPC 157 (10 µg or 10 ng/kg sc) or saline (5 ml) after 10 min. BPC 157 administration recovered the azygos vein via the inferior–superior caval vein rescue pathway. Additionally, intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were reduced, as were the grossly congested stomach and major hemorrhagic lesions, brain swelling, venous and arterial thrombosis, congested inferior caval and superior mesenteric veins, and collapsed azygos vein; thus, the failed collateral pathway was fully recovered. Severe ECG disturbances (i.e., severe bradycardia and ST-elevation until asystole) were also reversed. Microscopically, transmural hyperemia of the gastrointestinal tract, intestinal mucosa villi reduction, crypt reduction with focal denudation of superficial epithelia, and large bowel dilatation were all inhibited. In the liver, BPC 157 reduced congestion and severe sinusoid enlargement. In the lung, a normal presentation was observed, with no alveolar membrane focal thickening and no lung congestion or edema, and severe intra-alveolar hemorrhage was absent. Moreover, severe heart congestion, subendocardial infarction, renal hemorrhage, brain edema, hemorrhage, and neural damage were prevented. In conclusion, BPC 157 cured primary abdominal compartment syndrome.

Highlights

We suggest that abdominal compartment syndrome (Depauw et al, 2019) is a multiple occlusion syndrome
Despite permanently increased intraabdominal hypertension, a perilous syndrome occurred peripherally and centrally, the reversal of the abdominal compartment syndrome induced by the stable gastric pentadecapeptide BPC 157 application was quite consistent
All increased intra-abdominal pressures (i.e., 25, 30, 40, and 50 mmHg) produced a highly noxious syndrome, which occurred both peripherally and centrally. This noxious syndrome resembled the major vessel occlusion-induced syndromes (Vukojevic et al, 2018; Gojkovic et al, 2020; Kolovrat et al, 2020; Gojkovic et al, 2021a; Knezevic et al, 2021a; Knezevic et al, 2021a; Knezevic et al, 2021b) or “occlusion-like” syndromes that appear after intragastric application of absolute alcohol (Gojkovic et al, 2021b) and intraperitoneal application of lithium overdose (Strbe et al, 2021), in particular, similar to the acute Budd–Chiari syndrome and acute suprahepatic inferior caval vein occlusion (Gojkovic et al, 2020)

Summary

Introduction

We suggest that abdominal compartment syndrome (Depauw et al, 2019) is a multiple occlusion syndrome. Considering the effects of BPC 157 therapy peripherally and centrally (Vukojevic et al, 2018; Gojkovic et al, 2020; Kolovrat et al, 2020; Gojkovic et al, 2021a; Knezevic et al, 2021a; Knezevic et al, 2021a; Gojkovic et al, 2021b; Knezevic et al, 2021b; Strbe et al, 2021), in rats with severely increased intra-abdominal pressure, i.e., primary abdominal compartment syndrome, we attempted to introduce a therapy for compressed essential vessel tributaries, both arterial and venous (peripherally and centrally), due to occluded major veins and arteries, in order to prevent the consequent noxious syndrome, both peripherally and centrally. It was found that systemic and splanchnic blood flow and afferent hepatic flow were reduced as the intra-abdominal pressure rose; i.e., liver blood flow decreased by 39% when pneumoperitoneum increased from 10 to 15 mmHg and liver ischemic injury occurred (Chen et al, 2017)

Methods

Results

Conclusion