Pędzińska-Betiuk Anna, Schlicker Eberhard, Weresa Jolanta, Malinowska Barbara
Department of Experimental Physiology and Pathophysiology, Medical University of Bialystok, Bialystok, Poland.
Department of Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
Front Pharmacol. 2024 May 30;15:1382995. doi: 10.3389/fphar.2024.1382995. eCollection 2024.
Ischemic heart disease, associated with high morbidity and mortality, represents a major challenge for the development of drug-based strategies to improve its prognosis. Results of pre-clinical studies suggest that agonists of cannabinoid CB receptors and multitarget cannabidiol might be potential cardioprotective strategies against ischemia-reperfusion injury. The aim of our study was to re-evaluate the cardioprotective effects of cannabinoids against ischemia-reperfusion injury according to the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria published recently by the European Union (EU) CARDIOPROTECTION COST ACTION. To meet the minimum criteria of those guidelines, experiments should be performed (i) on healthy small animals subjected to ischemia with reperfusion lasting for at least 2 hours and (ii) confirmed in small animals with comorbidities and co-medications and (iii) in large animals. Our analysis revealed that the publications regarding cardioprotective effects of CB receptor agonists and cannabidiol did not meet all three strict steps of IMPACT. Thus, additional experiments are needed to confirm the cardioprotective activities of (endo)cannabinoids mainly on small animals with comorbidities and on large animals. Moreover, our publication underlines the significance of the IMPACT criteria for a proper planning of preclinical experiments regarding cardiac ischemia-reperfusion injury.
缺血性心脏病发病率和死亡率高,是开发改善其预后的药物策略面临的一项重大挑战。临床前研究结果表明,大麻素CB受体激动剂和多靶点大麻二酚可能是对抗缺血再灌注损伤的潜在心脏保护策略。我们研究的目的是根据欧盟心脏保护成本行动最近发布的改善心脏保护疗法临床前评估(IMPACT)标准,重新评估大麻素对缺血再灌注损伤的心脏保护作用。为满足这些指南的最低标准,实验应在健康的小动物身上进行,缺血后再灌注至少持续2小时,并且应在患有合并症和同时服用其他药物的小动物身上得到证实,以及在大动物身上进行。我们的分析表明,关于CB受体激动剂和大麻二酚心脏保护作用的出版物未满足IMPACT的所有三个严格步骤。因此,需要进行额外的实验,主要在患有合并症的小动物和大动物身上证实(内源性)大麻素的心脏保护活性。此外,我们的出版物强调了IMPACT标准对于正确规划关于心脏缺血再灌注损伤的临床前实验的重要性。