Role of protein kinase C in preconditioning with ischemia against lethal cell injury

The PKC hypothesis and its variants are attractive but unproved. The chief difficulty is the lack of an objective means to assess whether or not PKC has been activated in hearts preconditioned in vivo with ischemia or in hearts preconditioned by pharmacologic means. The strongest evidence is supporting the PKC hypothesis in vivo is the prevention of preconditioning with antagonists such as staurosporine. However, these data are weakened by the failure of these agents to eliminate PC in large animal hearts. Since hearts of virtually all mammalian species can be preconditioned, it seems likely that the general mechanism causing it is similar in each and should respond to a strong inhibitor. More work needs to be done.