Interleukin-1a Preconditioning Reduces Myocardial Ischemia Reperfusion Injury

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Abstract

Background

Interleukin-1 (IL-1) has been shown to induce superoxide dismutase (SOD) activity and to express heat shock protein (HSP). Since the reperfusion of ischemic heart is associated with the reduction of antioxidative enzymes including SOD and expression of HSP, it was hypothesized that IL-1 could be beneficial against ischemic reperfusion injury.

Methods and Results

Rats were injected with recombinant IL-1a (30 μg/kg IP); after 48 hours, they were anesthetized and hearts were removed, isolated, and perfused by the Langendorif technique. Myocardial functions were studied by measuring left ventricular developed pressure (LVDP) and its maximum first derivative (LV dP/dt), and cellular injury was studied by estimating creatine kinase (CK) release. Induction of the expression of HSP27 mRNA and HSP27 protein was examined by Western blot analysis and Northern blot analysis, respectively. Antioxidant enzymes were assayed by enzymatic analysis. Our results indicated reduction of ischemic reperfusion injury by IL-1a, as evidenced by better recovery in postischemic ventricular functions (LVDP [mm Hg]: control, 63±14; IL-1, 102+11; P<.05), increased coronary flow (mL/min) (control, 2.93± 0.58; IL-1, 5.17+0.43; P<.03), and reduced creatine kinase release (IU/L) (control, 110±5.78; IL-1, 81.76±7.71; P<.01). IL-1a induced the expression of HSP27 mRNA within 2 hours as examined by Northern blot analysis and the expression of HSP27 after 48 hours. In addition, hearts pretreated with IL-1a for 48 hours and then subjected to 30-minute ischemia and 60-minute reperfusion enhanced the activities (nmol/min/mg protein) of Cu/Zn SOD (control, 1.55±0.22; IL-ia, 2.92±0.04; P<.004), Mn-SOD (control, 4.54±0.19; IL-1a, 6.33±0.09, P<.001), catalase (control, 15.53±0.37; IL-la, 21.67±0.72; P<.002), glutathione peroxidase (control, 17.49±0.35; IL-1a, 25.87±0.58; P<.001), and glucose-6-phosphate dehydrogenase (control, 22.71±0.44; IL-ia, 29.53±0.48; P<.001).

Conclusions

The results of this study indicate that low doses of IL-la can be used as a therapeutic agent to precondition a heart from ischemia reperfusion injury.

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