Proton and calcium concentration

Apart from activation of protein kinases, increases in the intracellular proton and calcium concentrations or a decrease in the intracellular ATP concentration gradually decrease cell-cell conductance (for review, see27). However, while acidosis in normal hearts reduces dye transfer between cardiomyocytes, the same level of acidosis during ischemia does not,72 pointing to an interaction of several of the above regulatory mechanisms. 

MYOCARDIAL ISCHEMIA/REPERFUSION INJURY AND ITS MODIFICATION BY ISCHEMIC PRECONDITIONING 

Cardiomyocyte death occurs during ischemia as well as during the subsequent reperfusion,69 with both necrosis and apoptosis contributing to cell death.70 Loss of cardiomyocyte volume regulation contributes to irreversible ischemic tissue injury,71 and open hemichannels might contribute to the ischemia/reperfusion-induced osmotic imbalance in cardiomyocytes.72,73 

Brief episodes of ischemia/reperfusion delay the development of irreversible tissue damage induced by a subsequent more prolonged ischemic period.74 Apart from the delay in infarct development, ischemic preconditioning also reduces the extent of apoptosis.75 77 The signal transduction cascade of ischemic preconditioning has been discussed in detail elsewhere.71,78 

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