JM Gordon*, RH Ritchie & GJ Dusting.

Howard Florey Institute, University of Melbourne, Vic, 3010

Cardiac myocytes (CM) can be protected from a potentially lethal ischaemic insult by preconditioning with transient ischaemia. Although the mechanisms of the protection are still poorly understood, adenosine is a known trigger. We have recently reported that an N-terminal fragment of the annexin peptide lipocortin-1 (LC-1_2-26) protects rat myocardium from endotoxin and cytokine-induced depression of inotropic responsiveness¹. However, the cardioprotective potential of lipocortin against ischaemia/reperfusion injury has not been determined. We tested the hypothesis that lipocortin protects isolated CM against cellular injury in a model of simulated ischaemia. Adult rat CM were incubated in a simulated ischaemia buffer² (10 mM 2-deoxy-D-glucose, 20 mM D,L-lactic acid in a HEPES buffer, pH 6.5) for 4h at 37°C. Paired control CM were incubated in normal HEPES buffer (pH 7.4). CM were then allowed to recover in normal medium for 2.5h. The protective effects of adenosine or LC-1_2-26 (0.3 mM) during simulated ischaemia were assessed as the reduction in lactate dehydrogenase (LDH) and creatine kinase (CK) activity as a percent of that induced by simulated ischaemia alone (mean±SE). Simulated ischaemia significantly increased LDH activity by 463±111 IU/10⁵ cells (n=13, P<0.05 vs control) and CK activity by 5125±1500 IU/10⁵ cells (n=13, P<0.05 vs control).

* P<0.05, ^# P < 0.001 (both vs simulated ischaemia alone)

These data indicate that lipocortin protects CM from cellular injury during simulated ischaemia: we now plan to elucidate the intracellular signalling pathways mediating this effect.

1. Ritchie RH et al (1999) Clin Exp Pharmacol Physiol, 26, 522-524

2. Gordon JM et al (1999) Proc Aust Soc Clin Exp Pharmacol Toxicol, 6, 94

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