Abstract 555: Heme-Oxygenase 1 Upregulation Attenuates Acute Myocardial Reperfusion Injury and Left Ventricular Remodeling in Rats
Background: Reperfusion injury occurring after reestablishment of blood flow after MI is thought to be mediated by reactive oxygen species and neutrophilic cellular damage. The Heme-Oxygenase-1 (HO-1) dependent decrease in oxidative stress may attenuate injury in part by inhibiting transcription factor NFκB-mediated inflammation. We tested the hypothesis that exogenous upregulation of HO-1 by hemin administration confers acute and chronic cardioprotection against I/R injury in rats and attenuates LV remodeling post-infarction.
Methods: Six week-old male Wistar rats were randomly assigned to sham, vehicle, or hemin-treated groups. Vehicle and hemin were administered i.p. once daily for 3 days prior to LAD occlusion, and 48 hours post-operatively once every 3 days. Infarct size was determined by H&E histological analysis and fibrosis was quantified by Masson’s Trichrome staining. We used transthoracic echocardiography to assess LV size, function and wall motion.
Results: Hemin increased HO-1 expression and decreased infarct size and fibrosis, and attenuated LV wall thinning and chamber dilatation in the short-term (4 days post-infarction). The decrease in infarct size and fibrosis in the hemin group was accompanied by a decrease in NF-κB activity. We observed no significant difference in infarct size and area of fibrosis between hemin and vehicle-treated groups at 3 months (p=0.6681, p=0.6382, respectively). Cavity dilatation did not differ between the two groups at 3 months, however attenuated interventricular septum thinning (p<0.05) was observed in the hemin group compared with the vehicle group.
Conclusion: HO-1 upregulation by hemin confers acute cardioprotection and decreased inflammation, possibly by inhibiting NF-κB activity, although chronic treatment with hemin does not prevent long-term LV remodeling post-MI. Future research should focus on optimal HO-1 upregulation to attenuate long-term LV remodeling due to reperfusion injury.