Cardioprotective Effect of Losartan Alone or in Combination with Remote Ischemic Preconditioning on the Biochemical Changes Induced by Ischemic/Reperfusion Injury in a Mutual Prospective Study with a Clinical and Experimental Animal Arm
DOI:
https://doi.org/10.17140/HROJ-4-142Keywords:
Ischemic reperfusion; Losartan, Remote ischemic preconditioning, Biochemical markers; PCI.Abstract
Background and Aims: Losartan is an angiotensin receptor II antagonist used clinically to reduce
blood pressure and treat hypertension or hypertrophic cardiomyopathy. It is also proposed
to suppress cardiac injury following reperfusion. We evaluated the potential effect of Losartan
alone and in combination with remote ischemic preconditioning (RIPC), an established treatment,
on the biochemical changes induced by ischemic/reperfusion injury (I/R) in both humans
and rabbits.
Methods: Thirty consecutive patients undergoing elective percutaneous coronary intervention
(PCI) were divided into three groups (10 each): group 1 (control group without any preconditioning),
group 2 (patients who were maintained on losartan (50-100 mg /day) for one month
before PCI), group 3 (similar to group 2 but PCI was preceded by RIPC). On the other hand,
sixty adult male New Zealand white rabbits were divided into 6 groups (10 each): group I
(control), group II (sham), group III (I/R as 30 min ischemia followed by 120 min reperfusion),
group IV (regular losartan 20 mg/kg for 40 days orally followed by I/R), group V (I/R preceded
by RIPC) and group VI (similar to groups IV but I/R was preceded by RIPC). Tumor necrosis
factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), troponin I (cTnI), creatine kinase MB
(CK-MB) and C-reactive protein (CRP) were measured in blood for all study groups.
Results: Clinical and experimental parts showed that groups with RIPC combined with losartan
pretreatment enhanced cardioprotective effects of RIPC against I/R injury as evidenced
by significant reduction (p<0.001) in the levels of IL-6 and cTnI; also the level of NO was
significantly (p<0. 0.001) increased compared with other groups. However, this effect was not
significant regarding the level of TNF-α, CK-MB nor CRP.
Conclusions: Pretreatment with losartan enhances the cardioprotective effects of RIPC in ischemic
reperfusion injury.
References
Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfu-sion injury: A neglected therapeutic target. J Clin Invest. 2013; 123(1): 92-100. doi: 10.1172/JCI62874
Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012; 298: 229-317. doi: 10.1016/B978-0-12-394309-5.00006-7
Levitsky J, Gurell D, Frishman WH. Sodium ion/hydrogen ion exchange inhibition: A new pharmacologic approach to myocar-dial ischemia and reperfusion injury. J Clin Pharmacol. 1998; 38(10): 887-897. doi: 10.1002/j.1552-4604.1998.tb04383.x
Frank A, Bonney M, Bonney S, Weitzel L, Koeppen M, Eckle T. Myocardial ischemia reperfusion injury: From basic science to clinical bedside. Semin Cardiothorac Vasc Anesth. 2012; 16(3): 123-132. doi: 10.1177/1089253211436350
Luo SJ, Zhou YJ, Shi DM, Ge HL, Wang JL, Liu RF. Remote ischemic preconditioning reduces myocardial injury in patients undergoing coronary stent implantation. Can J Cardiol. 2013; 29(9): 1084-1089. doi: 10.1016/j.cjca.2012.11.022
Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocar-dium. Circulation. 1986; 74(5): 1124-1136. doi: 10.1161/01. CIR.74.5.1124
Eisen A, Fisman EZ, Rubenfire M, et al. Ischemic precon-ditioning: Nearly two decades of research. A comprehensive review. Atherosclerosis. 2004; 172(2): 201-210. doi: 10.1016/ S0021-9150(03)00238-7
Candilio L, Hausenloy DJ, Yellon DM. Remote ischemic conditioning: A clinical trial’s update. J Cardiovasc Pharmacol Ther. 2011; 16(3-4): 304-312. doi: 10.1177/1074248411411711
Hausenloy DJ, Kharbanda R, Rahbek SM, et al. Effect of re-mote ischaemic conditioning on clinical outcomes in patients presenting with an ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Eur Heart J. 2015; 36(29): 1846-1848.
Jaffe MD, Quinn NK. Warm-up phenomenon in angina pec-toris. Lancet. 1980; 2(8201): 934-936.
Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Cir-culation. 1993; 87(3): 893-899. doi: 10.1161/01.CIR.87.3.893
Tong B, Lin Z, Xie L, Xu C. Atorvastatin inhibits platelet aggregation and activation following carotid balloon injury in cholesterol-fed rabbits. Nan Fang Yi Ke Da Xue Xue Bao. 2014; 34(8): 1162-1166.
Lunder M, Ziberna L, Janic M, et al. Low-dose atorvastatin, losartan, and particularly their combination, provide cardiovas-cular protection in isolated rat heart and aorta. Heart Vessels. 2013; 28(2): 246-254. doi: 10.1007/s00380-012-0259-0
Yellon DM, Downey JM. Preconditioning the myocardium: From cellular physiology to clinical cardiology. Physiol Rev. 2003; 83(4): 1113-1151. doi: 10.1152/physrev.00009.2003
EL Desoky ES, Hassan AK, Salem SY, Fadil SA, Taha AF. Cardioprotective effect of atorvastatin alone or in combina-tion with remote ischemic preconditioning on the biochemical changes induced by ischemic/reperfusion injury in a mutual pro-spective study with a clinical and experimental animal arm. Int J Cardiol. 2016; 222: 866-873. doi: 10.1016/j.ijcard.2016.07.178
Kharbanda RK, Mortensen UM, White PA, et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2002; 106(2326): 2881-2883. doi: 10.1161/01.CIR. 0000043806.51912.9B
Han J, Wang D, Yu B, et al. Cardioprotection against ischemia/ reperfusion by licochalcone B in isolated rat hearts. Oxid Med Cell Longev. 2014; 2014: 134862. doi: 10.1155/2014/134862
Zhao ZG, Tang ZZ, Zhang WK, Li JG. Protective effects of embelin on myocardial ischemia-reperfusion injury following cardiac arrest in a rabbit model. Inflammation. 2015; 38(2): 527- 533. doi: 10.1007/s10753-014-9959-1
Yaghooti H, Firoozrai M, Fallah S, Khorramizadeh MR. An-giotensin II induces NF-kappaB, JNK and p38 MAPK activa-tion in monocytic cells and increases matrix metalloproteinase-9 expression in a PKC- and Rho kinase-dependent manner. Braz J Med Biol Res. 2011; 44(3): 193-199. doi: 10.1590/S0100- 879X2011007500008
Meng Y, Chen C, Tian C, Du J, Li HH. Angiotensin II-induced Egr-1 expression is suppressed by peroxisome prolif-erator-activated receptor-gamma ligand 15d-PGJ(2) in mac-rophages. Cell Physiol Biochem. 2015; 35(2): 689-698. doi: 10.1159/000369729
Li M, Liu J, Han C, Wang B, Pang X, Mao J. Angioten-sin II induces the expression of c-reactive protein via MAPK-dependent signal pathway in U937 macrophages. Cell Physiol Biochem. 2011; 27(1): 63-70. doi: 10.1159/000325206
Maning J, Negussie S, Clark MA, et al. Biased agonism/ antagonism at the AngII-AT1 receptor: Implications for adre-nal aldosterone production and cardiovascular therapy. Phar-macol Res. 2017; pii: S1043-6618(17)30352-3. doi: 10.1016/j. phrs.2017.05.009
Lymperopoulos A, Aukszi B. Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldo-sterone production: Implications for heart failure therapy. World J Cardiol. 2017; 9(3): 200-206. doi: 10.4330/wjc.v9.i3.200
Lymperopoulos A, Sturchler E, Bathgate-Siryk A, et al. Dif-ferent potencies of angiotensin receptor blockers at suppressing adrenal β-arrestin1–dependent post-myocardial infarction hy-peraldosteronism. J Am Coll Cardiol. 2014; 64(25): 2805-2806. doi: 10.1016/j.jacc.2014.09.070
Mason RP, Jacob RF, Kubant R, et al. Effects of angiotensin receptor blockers on endothelial nitric oxide release: The role of eNOS variants. Br J Clin Pharmacol. 2012; 74(1): 141-146. doi: 10.1111/j.1365-2125.2012.04189.x
Zhang YJ, Bai XJ, Qi ZM, Wang HX. Mechanism of car-dioprotection against ischemia/reperfusion injury by valsartan: An experiment with isolated rat hearts. Zhonghua Yi Xue Za Zhi. 2005; 85(47): 3350-3353. doi: 10.1155/2014/134862
Thygesen K, Alpert JS, Jaffe AS, et al. Third universal defini-tion of myocardial infarction. J Am Coll Cardiol. 2012; 60(16): 1581-1598. doi: 10.1161/CIR.0b013e31826e1058
Konstantinov IE, Arab S, Kharbanda RK, et al. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genomics. 2004; 19(1): 143-150. doi: 10.1152/physiolgenomics.00046.2004
Gassanov N, Nia AM, Caglayan E, Er F. Remote ischemic preconditioning and renoprotection: From myth to a novel thera-peutic option? J Am Soc Nephrol. 2014; 25(2): 216-224. doi: 10.1681/ASN.2013070708
Kang SW, Kim OK, Seo B, et al. Simultaneous, real-time measurement of nitric oxide and oxygen dynamics during cardi-ac ischemia-reperfusion of the rat utilizing sol-gel-derived elec-trochemical microsensors. Anal Chim Acta. 2013; 802: 74-81. doi: 10.1016/j.aca.2013.09.029
Zhou W, Zeng D, Chen R, et al. Limb ischemic precondition-ing reduces heart and lung injury after an open heart operation in infants. Pediatr Cardiol. 2010; 31(1): 22-29. doi: 10.1007/ s00246-009-9536-9
D’Ascenzo F, Moretti C, Omede P, et al. Cardiac remote ischaemic preconditioning reduces periprocedural myocar-dial infarction for patients undergoing percutaneous coronary interventions: A meta-analysis of randomised clinical trials. EuroIntervention. 2014; 9(12): 1463-1471. doi: 10.4244/EI-JV9I12A244
Hassan AKM, Shams-Eddin H, Abdel-Rahim MHM, El-Hafeez HAA, Edroos S. Cardio- and reno-protective effect of remote ischemic preconditioning in patients undergoing percu-taneous coronary intervention. A prospective, non-randomized controlled trial. The Egyptian Heart Journal. 2015; 67(4): 315- 323. doi: 10.1016/j.ehj.2015.08.001
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content published in Heart Research (HROJ) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.