Cardiotrophin-1 can protect cardiac myocytes from injury when added both prior to simulated ischaemia and at reoxygenation

Objective: The cytokine cardiotrophin-1 (CT-1) has previously been shown to protect cultured cardiocytes from cell death induced by serum removal or hypoxia when administered prior to the damaging stimulus. We wished to test whether a similar protective effect could be observed if CT-1 was added after the ischaemic period and to investigate the signalling pathways involved in the protective effect when CT-1 is given prior to or after ischaemia. Methods: We therefore examined the protective effect of CT-1 in cultured rat cardiocytes exposed to simulated ischaemia followed by reoxygenation when CT-1 was administered either prior to simulated ischaemia or at reoxygenation. Results: We show that CT-1 can exert a protective effect against the damaging effects of simulated ischaemia/reoxygenation both when added after the simulated ischaemia at reoxygenation ( P <0.05 in trypan blue, TUNEL and annexin V assays) or when added prior to the simulated ischaemia ( P <0.05). In both cases, these protective effects are blocked by an inhibitor of the p42/p44 MAPK pathway ( P <0.05 in all assays). Conclusion: CT-1 can protect cardiac cells when added either prior to simulated ischaemia or at the time of reoxygenation following simulated ischaemia and these effects are dependent upon its ability to activate the p42/p44 MAPK pathway. Hence CT-1 may have therapeutic potential when added at the time of reperfusion following ischaemic damage.