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

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.