Premuzic Mestrovic Ivica, Smoday Ivan Maria, Kalogjera Luka, Krezic Ivan, Zizek Helena, Vranes Hrvoje, Vukovic Vlasta, Oroz Katarina, Skorak Ivan, Brizic Ivan, Hriberski Klaudija, Novosel Luka, Kavelj Ivana, Barisic Ivan, Beketic Oreskovic Lidija, Zubcic Slavica, Strbe Sanja, Mestrovic Tomislav, Pavic Predrag, Staresinic Mario, Skrtic Anita, Boban Blagaic Alenka, Seiwerth Sven, Sikiric Predrag
Department of Pharmacology, School of Medicine University of Zagreb, 10000 Zagreb, Croatia.
Department of Surgery, School of Medicine University of Zagreb, 10000 Zagreb, Croatia.
Pharmaceuticals (Basel). 2023 Jul 7;16(7):977. doi: 10.3390/ph16070977.
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.
我们关注的首个证据是，抗心律失常药物，尤其是II类和III类抗心律失常药物以及β受体阻滞剂索他洛尔可在大鼠中诱发严重的闭塞/类闭塞综合征。在该综合征中，如同主要血管发生永久性闭塞的类似综合征、外周和中枢血管的情况以及其他严重损害内皮功能的类似有害过程一样，稳定的胃十五肽BPC 157激活侧支循环是一种有效的治疗方法。在180分钟的研究中，给予高剂量索他洛尔（80毫克/千克灌胃）后，出现了脑部的因果性病变（肿胀, 脑出血）、心脏、肺、肝、肾和胃肠道的充血、严重心动过缓以及颅内（上矢状窦）、门静脉和腔静脉高压、主动脉低血压，以及外周和中枢的广泛血栓形成。主要血管出现功能障碍（下腔静脉和肠系膜上静脉充血、奇静脉塌陷）。BPC 157治疗（在索他洛尔给药后5分钟或90分钟给予10微克、10纳克/千克灌胃）有效对抗了索他洛尔所致的闭塞/类闭塞综合征。特别是，心脏扩张、影响冠状动静脉和心肌血管的心肌充血消失；门静脉和腔静脉高压、肺实质充血以及静脉和动脉血栓形成消失，主动脉低血压减轻，在中枢，颅内（上矢状窦）高压、脑损伤和明显的脑出血减轻。此外，BPC 157消除和/或显著减轻了肝脏、肾脏和胃肠道的充血以及主要静脉的充血。因此，奇静脉激活和直接血液输送对于BPC 157的特定作用至关重要。因此，预防此类及类似事件，并在该事件有风险时做出充分反应，强烈支持进一步的BPC 157治疗。
