Abstract
In ex vivo whole heart studies temperature preconditioning (TP) has been found to confer cardioprotection (Khaliulin et al. 2007). Here we have investigated the molecular effects of TP in freshly isolated adult rat cardiac myocytes. To assess the affect of TP we measured; contractile function, Ca2+ homeostasis and mitochondrial permeability transition pore (MPTP) opening. TP consisted of three cycles of 2 minutes at 12°C and 3 minutes at 37°C. Contraction of myocytes was synchronized by electrical field stimulation (1Hz) and recovery of contractile function was measured following simulated ischaemia/reperfusion injury. This consisted of 7 minutes perfusion with substrate-free Tyrode solution containing cyanide (2mM) and iodoacetic acid (1mM) followed by 10 minutes reperfusion with Tyrode solution. A significant increase in contractile function after TP (52%±6 n=225, 3) was observed compared to control (29%±5 n=229, 3) (p<0.05). To identify whether this protection was linked to changes in Ca2+ handling, we analysed Ca2+ levels at 10 minutes reperfusion. We found that TP myocytes had significantly lower Ca2+ levels (131nM n=67, 3) compared to controls (301nM n=69, 3) (p<0.005). MPTP opening is thought to be a critical event in the determination of myocyte fate following ischaemia/reperfusion injury. Therefore we investigated the effects of TP on the time to induce MPTP opening in response to photodamage using TMRM, a mitochondrial selective dye. We found that TP myocytes significantly delayed time to MPTP opening (15.2±0.6 n=126, 3) compared to controls (11.9±0.4 n=168, 3) (p<0.0001). TP confers protection to isolated myocytes by significantly increasing recovery of contractile function and preventing calcium overload in response to simulated ischaemia/reperfusion. TP also significantly delays MPTP opening after simulated ischaemia/reperfusion injury. Data presented as mean±SEM, n=myocytes, animals. Khaliulin et al., J physio 581.3 (2007) 1147-1161. Funded by The British Heart Foundation.
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