Pharmaceuticals (Jul 2023)

Antiarrhythmic Sotalol, Occlusion/Occlusion-like Syndrome in Rats, and Stable Gastric Pentadecapeptide BPC 157 Therapy

  • Ivica Premuzic Mestrovic,
  • Ivan Maria Smoday,
  • Luka Kalogjera,
  • Ivan Krezic,
  • Helena Zizek,
  • Hrvoje Vranes,
  • Vlasta Vukovic,
  • Katarina Oroz,
  • Ivan Skorak,
  • Ivan Brizic,
  • Klaudija Hriberski,
  • Luka Novosel,
  • Ivana Kavelj,
  • Ivan Barisic,
  • Lidija Beketic Oreskovic,
  • Slavica Zubcic,
  • Sanja Strbe,
  • Tomislav Mestrovic,
  • Predrag Pavic,
  • Mario Staresinic,
  • Anita Skrtic,
  • Alenka Boban Blagaic,
  • Sven Seiwerth,
  • Predrag Sikiric

DOI
https://doi.org/10.3390/ph16070977
Journal volume & issue
Vol. 16, no. 7
p. 977

Abstract

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We focused on the first demonstration that antiarrhythmics, particularly class II and class III antiarrhythmic and beta-blocker sotalol can induce severe occlusion/occlusion-like syndrome in rats. In this syndrome, as in similar syndromes with permanent occlusion of major vessels, peripheral and central, and other similar noxious procedures that severely disable endothelium function, the stable gastric pentadecapeptide BPC 157-collateral pathways activation, was a resolving therapy. After a high dose of sotalol (80 mg/kg intragastrically) in 180 min study, there were cause-consequence lesions in the brain (swelling, intracerebral hemorrhage), congestion in the heart, lung, liver, kidney, and gastrointestinal tract, severe bradycardia, and intracranial (superior sagittal sinus), portal and caval hypertension, and aortal hypotension, and widespread thrombosis, peripherally and centrally. Major vessels failed (congested inferior caval and superior mesenteric vein, collapsed azygos vein). BPC 157 therapy (10 µg, 10 ng/kg given intragastrically at 5 min or 90 min sotalol-time) effectively counteracted sotalol-occlusion/occlusion-like syndrome. In particular, eliminated were heart dilatation, and myocardial congestion affecting coronary veins and arteries, as well as myocardial vessels; eliminated were portal and caval hypertension, lung parenchyma congestion, venous and arterial thrombosis, attenuated aortal hypotension, and centrally, attenuated intracranial (superior sagittal sinus) hypertension, brain lesions and pronounced intracerebral hemorrhage. Further, BPC 157 eliminated and/or markedly attenuated liver, kidney, and gastrointestinal tract congestion and major veins congestion. Therefore, azygos vein activation and direct blood delivery were essential for particular BPC 157 effects. Thus, preventing such and similar events, and responding adequately when that event is at risk, strongly advocates for further BPC 157 therapy.

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