AHEART May 47/5

Schäfer, C., Y. V. Ladilov, B. Siegmund, and H. M. Piper. Importance of bicarbonate transport for protection of cardiomyocytes against reoxygenation injury. Am J Physiol Heart Circ Physiol 278: H1457–H1463, 2000.—Isolated cardiomyocytes from adult rats were incubated in anoxic bicarbonate-buffered media at extracellular pH (pHo) 6.4 until a cytosolic Ca21 overload and intracellular pH (pHi) of 6.4 were reached. On reoxygenation, the pH of the medium was changed to 7.4 to activate the Na1/H1exchanger (NHE) and the Na-HCO3 2 symporter (NBS). The reoxygenation was performed in the absence or presence of the NHE inhibitor HOE-642 (3 μmol/l) and/or the NBS inhibitor DIDS (0.5 mmol/l), as in bicarbonate-free media. In reoxygenated control cells pHi rapidly recovered to the preanoxic level, and a burst of spontaneous oscillations of cytosolic Ca21 occurred, accompanied by the development of hypercontracture. When NBS and NHE were simultaneously inhibited during reoxygenation, pHi recovery was prevented, Ca21 oscillations were attenuated, and hypercontracture was abolished. Sole inhibition of NBS or NHE showed no protection against hypercontracture. In the absence of cytosolic acidosis, HOE-642 or DIDS did not prevent hypercontracture induced by Ca21 overload. The results demonstrate that simultaneous inhibition of NHE and NBS is needed to protect myocardial cells against reoxygenation-induced hypercontracture.