Sikiric Predrag, Seiwerth Sven, Skrtic Anita, Staresinic Mario, Strbe Sanja, Vuksic Antonia, Sikiric Suncana, Bekic Dinko, Penovic Toni, Drazenovic Dominik, Becejac Tomislav, Tepes Marijan, Madzar Zrinko, Novosel Luka, Beketic Oreskovic Lidija, Oreskovic Ivana, Stupnisek Mirjana, Boban Blagaic Alenka, Dobric Ivan
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
Pharmaceuticals (Basel). 2025 Jun 10;18(6):866. doi: 10.3390/ph18060866.
In this study, pharmacotherapies of abdominal compartment syndrome (ACS) and intra-abdominal hypertension (IAH) in animal studies were reviewed from the perspective of ACS/IAH as failed cytoprotection issues, as non-specific injuries, and from the point of view of the cytoprotection concept as resolution. Therefore, this review challenges the unresolved theoretical and practical issues of severe multiorgan failure, acknowledged significance in clinics, and resolving outcomes (i.e., open abdomen). Generally, the reported agents not aligned with cytoprotection align with current pharmacotherapy limitations and have (non-)confirmed effectiveness, mostly in only one organ, mild/moderate IAH, prophylactic application, and provide only a tentative resolution. Contrarily, stable gastric pentadecapeptide BPC 157 therapy, as a novel and relevant cytoprotective mediator having pleiotropic beneficial effects, simultaneously resolves many targets, resolving established disturbances, specifically compression/ischemia (grade III and grade IV), and decompression/advanced reperfusion. BPC 157 therapy rapidly activates collateral bypassing pathways, and, in ACS and IAH, and later, in reperfusion, there is a "bypassing key" (i.e., azygos vein direct blood flow delivery). This serves to counteract multiorgan and vessel failure, including lesions and hemorrhages in the brain, heart, lung, liver, kidney and gastrointestinal tract, thrombosis, peripherally and centrally, intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, occlusion/occlusion-like syndrome, advanced Virchow triad circumstances, and free radical formation acting as a membrane stabilizer and free radical scavenger. Likewise, not only in ACS/IAH resolving, but also in other occlusion/occlusion-like syndromes, this "bypassing key" could be an effect of the essential endothelial cytoprotective capacity of BPC 157 and a particular modulatory effect on the NO-system, and a rescuing impact on vasomotor tone.
在本研究中,从腹腔间隔室综合征(ACS)/腹腔内高压(IAH)作为细胞保护失败问题、非特异性损伤以及细胞保护概念作为解决方案的角度,对动物研究中ACS和IAH的药物治疗进行了综述。因此,本综述对严重多器官功能衰竭尚未解决的理论和实际问题、在临床上公认的重要性以及解决结果(即开放腹腔)提出了挑战。一般来说,所报道的与细胞保护不一致的药物与当前药物治疗的局限性相符,并且具有(未)证实的有效性,大多仅在一个器官、轻度/中度IAH、预防性应用中有效,并且仅提供初步的解决方案。相反,稳定的胃十五肽BPC 157治疗作为一种具有多效有益作用的新型相关细胞保护介质,同时解决了许多靶点,解决了已有的紊乱,特别是压迫/缺血(III级和IV级)以及减压/晚期再灌注。BPC 157治疗迅速激活侧支旁路途径,并且在ACS和IAH中,以及随后在再灌注中,存在一个“旁路关键”(即奇静脉直接血流输送)。这有助于对抗多器官和血管功能衰竭,包括脑、心、肺、肝、肾和胃肠道的损伤和出血、外周和中枢的血栓形成、颅内(上矢状窦)、门静脉和腔静脉高压以及主动脉低血压、闭塞/类闭塞综合征、晚期魏尔啸三联征情况以及作为膜稳定剂和自由基清除剂的自由基形成。同样,不仅在ACS/IAH的解决中,而且在其他闭塞/类闭塞综合征中,这种“旁路关键”可能是BPC 157基本的内皮细胞保护能力、对NO系统的特定调节作用以及对血管运动张力的挽救作用的结果。