Role of heme oxygenase-1 in remifentanil cardiac preconditioning in rats

Abstract

INTRODUCTION: Remifentanil preconditioning (RPC) can protect the heart from ischemia-reperfusion injury (IRI). Heme oxygenase-1 (HO-1) can also reduce the cardiac infarct size during ischemia reperfusion in vivo. Our aim was to investigate whether HO-1 expression participates in RPC cardio protection. METHODS: IRI was induced in male Sprague-Dawley rats (300g) by occluding the left coronary artery for 30 minutes followed by 2 hours of reperfusion. 6μg/kg/min remifentanil as administered in three infusion cycles of 5-min (RPC group). Hemin, an agonist of HO-1, 30mg/kg/d was given intraperitoneally for 2 days before RPC (RPC+hemin group). Tin Protoporphyrin IX (SnPP), which can inhibit HO-1 expression, was injected 0.7 mg/kg/day subcutaneously for 2 days before RPC (RPC+SnPP group). The non-operation group was marked as sham. In the control group, 0.9% saline replaced remifentanil. After the operation, the heart infarct size was determined by 2, 3, 5-triphenyltetrazolium staining. Expression of HO-1, phosphorylated extracellular single regulated kinase (P-Erk), nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNFα) were also measured. RESULTS: Infarct size was significantly attenuated from 48.47±2.0% (Control, n=6) to 35.09±0.3% (RPC, n=6). The RPC protective effect was enhanced by hemin (6.08±1.4%, n=6) and inhibited by Snpp (39.37±1.1%, n=6). The expression of HO-1 in the RPC group (149.02±34.6) and RPC+hemin group (232.94±133.5) were higher than in the control group (109.15±60.3). The expression of HO-1 in the RPC+Snpp group was 72.52±19.2 vs 109.15±60.3 in the control group. The RPC group (326.98±199.6) and RPC+hemin (261.91±274.8) group had an increase in P-Erk concentration compared with control (202.61±120.6). The effect of RPC was blocked by Snpp (P-Erk 184.11±171.7). In addition, both the expression of iNOS and TNFα were decreased significantly in RPC (iNOS 54.86±9.5; TNFα 88.35±11.5) and RPC+hemin (iNOS 52.59±9.8; TNFα 71.93±23.2) but increased in RPC+SnPP (iNOS 82.00±10.8; TNFα 136.11±81.8) compared with control (iNOS 116.75±59.9; TNFα 170.65±71.4). CONCLUSION: Remifentanil protects the heart from IRI through activation of HO-1.