Biomedicines (May 2021)

Occlusion of the Superior Mesenteric Artery in Rats Reversed by Collateral Pathways Activation: Gastric Pentadecapeptide BPC 157 Therapy Counteracts Multiple Organ Dysfunction Syndrome; Intracranial, Portal, and Caval Hypertension; and Aortal Hypotension

  • Mario Knezevic,
  • Slaven Gojkovic,
  • Ivan Krezic,
  • Helena Zizek,
  • Dominik Malekinusic,
  • Borna Vrdoljak,
  • Hrvoje Vranes,
  • Tamara Knezevic,
  • Ivan Barisic,
  • Katarina Horvat Pavlov,
  • Domagoj Drmic,
  • Miro Staroveski,
  • Antonija Djuzel,
  • Zoran Rajkovic,
  • Toni Kolak,
  • Ivica Kocman,
  • Eva Lovric,
  • Marija Milavic,
  • Suncana Sikiric,
  • Ante Tvrdeic,
  • Leonardo Patrlj,
  • Sanja Strbe,
  • Antonio Kokot,
  • Alenka Boban Blagaic,
  • Anita Skrtic,
  • Sven Seiwerth,
  • Predrag Sikiric

DOI
https://doi.org/10.3390/biomedicines9060609
Journal volume & issue
Vol. 9, no. 6
p. 609

Abstract

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Gastric pentadecapeptide BPC 157 therapy counteracts multiple organ dysfunction syndrome in rats, which have permanent occlusion of the superior mesenteric artery close to the abdominal aorta. Previously, when confronted with major vessel occlusion, its effect would rapidly activate collateral vessel pathways and resolve major venous occlusion syndromes (Pringle maneuver ischemia, reperfusion, Budd–Chiari syndrome) in rats. This would overwhelm superior mesenteric artery permanent occlusion, and result in local, peripheral, and central disturbances. Methods: Assessments, for 30 min (gross recording, angiography, ECG, pressure, microscopy, biochemistry, and oxidative stress), included the portal hypertension, caval hypertension, and aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis; ECG disturbances; MDA-tissue increase; and multiple organ lesions and disturbances, including the heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus). BPC 157 therapy (/kg, abdominal bath) (10 µg, 10 ng) was given for a 1-min ligation time. Results: BPC 157 rapidly recruits collateral vessels (inferior anterior pancreaticoduodenal artery and inferior mesenteric artery) that circumvent occlusion and ascertains blood flow distant from the occlusion in the superior mesenteric artery. Portal and caval hypertension, aortal hypotension, and, centrally, superior sagittal sinus hypertension were attenuated or eliminated, and ECG disturbances markedly mitigated. BPC 157 therapy almost annihilated venous and arterial thrombosis. Multiple organ lesions and disturbances (i.e., heart, lung, liver, and gastrointestinal tract, in particular, as well as brain) were largely attenuated. Conclusions: Rats with superior mesenteric artery occlusion may additionally undergo BPC 157 therapy as full counteraction of vascular occlusion-induced multiple organ dysfunction syndrome.

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