Calpain inhibition reduces infarct size and improves global hemodynamics and left ventricular contractility in a porcine myocardial ischemia/reperfusion model - PubMed (original) (raw)
Comparative Study
. 2005 Dec 28;528(1-3):124-31.
doi: 10.1016/j.ejphar.2005.10.032. Epub 2005 Dec 1.
Affiliations
- PMID: 16324693
- DOI: 10.1016/j.ejphar.2005.10.032
Comparative Study
Calpain inhibition reduces infarct size and improves global hemodynamics and left ventricular contractility in a porcine myocardial ischemia/reperfusion model
Philipe N Khalil et al. Eur J Pharmacol. 2005.
Abstract
Calpains, a family of Ca2+-dependent cysteine proteases, are activated during myocardial ischemia and reperfusion. This study investigates the cardioprotective effects of calpain inhibition on infarct size and global hemodynamics in an ischemia/reperfusion model in pigs, using the calpain inhibitor A-705253. The left anterior descending coronary artery was occluded for 45 min and reperfused for 6 h. A bolus of 1.0 mg/kg A-705253 or distilled water was given intravenously 15 min prior to induction of ischemia and a constant plasma level of A-705253 was maintained by continuous infusion of 1.0 mg/kg A-705253 during reperfusion. Infarct size was assessed histochemically using triphenyltetrazolium chloride staining. Macromorphometric findings were verified by light microscopy on hematoxylin-eosin- and Tunel-stained serial sections. Global hemodynamics, including the first derivate of the left ventricular pressure (dP / dtmax), were measured continuously throughout the experiment. A-705253 reduced the infarct size by 35% compared to controls (P < 0.05). Hemodynamic alterations, including heart rate, aortic blood pressure, central venous pressure and left atrial pressure, were attenuated mainly during ischemia and the first 2 h during reperfusion by A-705253. Cardiac function improved, as determined by dP / dtmax, after 6 h of reperfusion (P < 0.003). Our results demonstrate that myocardial protection can be achieved by calpain inhibition, which decreases infarct size and improves left ventricular contractility and global hemodynamic function. Hence, the calpain-calpastatin system might play an important pathophysiological role in porcine myocardial ischemia and reperfusion damage and A-705253 could be a promising cardioprotective agent.
Similar articles
- Cardioprotective effects of angiotensin II type 1 receptor blockade with olmesartan on reperfusion injury in a rat myocardial ischemia-reperfusion model.
Dai W, Hale SL, Kay GL, Jyrala AJ, Kloner RA. Dai W, et al. Cardiovasc Ther. 2010 Spring;28(1):30-7. doi: 10.1111/j.1755-5922.2009.00108.x. Cardiovasc Ther. 2010. PMID: 20074257 - Sustained protective effects of 7-monohydroxyethylrutoside in an in vivo model of cardiac ischemia-reperfusion.
De Celle T, Heeringa P, Strzelecka AE, Bast A, Smits JF, Janssen BJ. De Celle T, et al. Eur J Pharmacol. 2004 Jun 28;494(2-3):205-12. doi: 10.1016/j.ejphar.2004.05.017. Eur J Pharmacol. 2004. PMID: 15212976 - Poly(ADP-ribose) polymerase inhibition improves postischemic myocardial function after cardioplegia-cardiopulmonary bypass.
Khan TA, Ruel M, Bianchi C, Voisine P, Komjáti K, Szabo C, Sellke FW. Khan TA, et al. J Am Coll Surg. 2003 Aug;197(2):270-7. doi: 10.1016/S1072-7515(03)00538-6. J Am Coll Surg. 2003. PMID: 12892811 - Contribution of calpains to myocardial ischaemia/reperfusion injury.
Inserte J, Hernando V, Garcia-Dorado D. Inserte J, et al. Cardiovasc Res. 2012 Oct 1;96(1):23-31. doi: 10.1093/cvr/cvs232. Epub 2012 Jul 10. Cardiovasc Res. 2012. PMID: 22787134 Review. - Calpains and Coronary Vascular Disease.
Potz BA, Sabe AA, Abid MR, Sellke FW. Potz BA, et al. Circ J. 2016;80(1):4-10. doi: 10.1253/circj.CJ-15-0997. Epub 2015 Oct 21. Circ J. 2016. PMID: 26489456 Free PMC article. Review.
Cited by
- Calpain inhibition decreases oxidative stress via mitochondrial regulation in a swine model of chronic myocardial ischemia.
Potz BA, Sabe SA, Scrimgeour LA, Sabe AA, Harris DD, Abid MR, Clements RT, Sellke FW. Potz BA, et al. Free Radic Biol Med. 2023 Nov 1;208:700-707. doi: 10.1016/j.freeradbiomed.2023.09.028. Epub 2023 Sep 23. Free Radic Biol Med. 2023. PMID: 37748718 - Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.
Aluja D, Delgado-Tomás S, Ruiz-Meana M, Barrabés JA, Inserte J. Aluja D, et al. Int J Mol Sci. 2022 Apr 7;23(8):4103. doi: 10.3390/ijms23084103. Int J Mol Sci. 2022. PMID: 35456920 Free PMC article. Review. - Reperfusion Cardiac Injury: Receptors and the Signaling Mechanisms.
Maslov LN, Popov SV, Mukhomedzyanov AV, Naryzhnaya NV, Voronkov NS, Ryabov VV, Boshchenko AA, Khaliulin I, Prasad NR, Fu F, Pei JM, Logvinov SV, Oeltgen PR. Maslov LN, et al. Curr Cardiol Rev. 2022;18(5):63-79. doi: 10.2174/1573403X18666220413121730. Curr Cardiol Rev. 2022. PMID: 35422224 Free PMC article. Review. - Spatio-temporal regulation of calpain activity after experimental myocardial infarction in vivo.
Zhang K, Cremers MM, Wiedemann S, Poitz DM, Pfluecke C, Heinzel FR, Pieske B, Adams V, Schauer A, Winzer R, Strasser RH, Linke A, Quick S, Heidrich FM. Zhang K, et al. Biochem Biophys Rep. 2021 Oct 28;28:101162. doi: 10.1016/j.bbrep.2021.101162. eCollection 2021 Dec. Biochem Biophys Rep. 2021. PMID: 34761128 Free PMC article. - Calpain inhibition decreases myocardial fibrosis in chronically ischemic hypercholesterolemic swine.
Potz BA, Sabe AA, Sabe SA, Lawandy IJ, Abid MR, Clements RT, Sellke FW. Potz BA, et al. J Thorac Cardiovasc Surg. 2022 Jan;163(1):e11-e27. doi: 10.1016/j.jtcvs.2019.11.150. Epub 2020 Mar 29. J Thorac Cardiovasc Surg. 2022. PMID: 32359903 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous