Aims: 

Pretreatment with the a₁-adrenoceptor agonist phenylephrine (PE) has been shown to protect cardiac tissue from a subsequent period of ischaemia. This phenomenon, known as pharmacological preconditioning, decreases infarct size and increases the functional recovery of the intact heart. The present study investigated the role of protein kinase C (PKC) and ATP-sensitive K⁺ (K_ATP) channels in PE-dependent preconditioning of isolated myocytes.

Methods: 

Isolated adult rat ventricular myocytes were maintained at 35-37°C, stimulated at 1 Hz, and exposed to metabolic inhibition and reperfusion. Cells were pretreated with a 10 minute perfusion of substrate-free Tyrode solution containing PE (5 mM), the PKC inhibitor chelerythrine (5 mM), PE + chelerythrine, the K_ATP inhibitor glibenclamide (10 mM) or PE + glibenclamide. Contractions were recorded using video-microscopy and stored on DVD for later analysis. Recovery of contractile function and the times to contractile failure and rigor were used as indicators of protection.

Results: 

Phenylephrine pre-treatment caused a significant increase in the percentage of cell recovering contractile function compared to Tyrode-pretreated controls (43.8 ± 5.4% vs. 18.8 ± 2.3%, mean ± SEM). This effect was abrogated by chelerythrine or glibenclamide (14.2 ± 5.4% and 8.2 ± 6.9% respectively). However, glibenclamide also decreased recovery in the absence of phenylephrine (3.2 ± 2.2%). Substrate-free Tyrode solution alone increased functional recovery compared to control in 2 of 6 experiments, however average recovery was not significantly different from control.

Conclusion: 

Preconditioning of isolated cardiac myocytes by phenylephrine involves the activation of PKC and K channels.