Hypoxic preconditioning - A phenomenon increasing the tolerance of cardiomyocytes to hypoxia/reoxygenation

Most studies addressing the question of hypoxic preconditioning (HP) are performed on isolated cardiomyocytes. There are relatively few reports on delayed HP in vivo and only occasional studies have addressed early preconditioning in vivo. HP has been found to restrict necrosis and apoptosis of cardiomyocytes and to improve the contractility of the isolated heart in ischemia (hypoxia) and reperfusion (reoxygenation). Evidence has been obtained indicating that adenosine is a trigger for HP in vitro. NO is a trigger for HP in in vitro and in vivo experiments. Reactive oxygen species were also found to be triggers for hypoxic preconditioning. ERK1/2 and p38 kinase have been shown to play important roles in delayed HP in vitro. Data showing that Akt kinase and PI3 kinase are also involved in hypoxic preconditioning in vitro have been obtained. KATP channels and KCa channels may be mediators and, perhaps, end effectors of late HP. Hypoxic preconditioning activates the following transcription factors: HIF-1α, HIF-3α, GATA-4, and NF-κB. The end effectors of HP may be the proteins HSP90, GRP78, 14-3-3, Bcl-2, Bcl-xL, BAD, and iNOS.