Antiarrhythmic Sotalol, Occlusion/Occlusion-like Syndrome in Rats, and Stable Gastric Pentadecapeptide BPC 157 Therapy
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Published:2023-07-07
Issue:7
Volume:16
Page:977
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ISSN:1424-8247
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Container-title:Pharmaceuticals
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language:en
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Short-container-title:Pharmaceuticals
Author:
Premuzic Mestrovic Ivica1ORCID, Smoday Ivan Maria1, Kalogjera Luka1ORCID, Krezic Ivan1, Zizek Helena1, Vranes Hrvoje1ORCID, Vukovic Vlasta1ORCID, Oroz Katarina1, Skorak Ivan1, Brizic Ivan1, Hriberski Klaudija1, Novosel Luka1, Kavelj Ivana1, Barisic Ivan1, Beketic Oreskovic Lidija1, Zubcic Slavica1, Strbe Sanja1, Mestrovic Tomislav2, Pavic Predrag2, Staresinic Mario2, Skrtic Anita3ORCID, Boban Blagaic Alenka1, Seiwerth Sven3, Sikiric Predrag1
Affiliation:
1. Department of Pharmacology, School of Medicine University of Zagreb, 10000 Zagreb, Croatia 2. Department of Surgery, School of Medicine University of Zagreb, 10000 Zagreb, Croatia 3. Department of Pathology, School of Medicine University of Zagreb, 10000 Zagreb, Croatia
Abstract
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.
Funder
University of Zagreb
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
Reference99 articles.
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