We assessed the effect of acidosis on cell killing during anoxia and reoxygenation in cultured rat neonatal cardiac myocytes. After 4.5 hours of anoxia and glycolytic inhibition with 2-deoxyglucose, loss of viability was >90% at pH 7.4. In contrast, at pH 6.2-7.0, viability was virtually unchanged. To model changes of pH and oxygenation during ischemia and reperfusion, myocytes were made anoxic at pH 6.2 for 4 hours, followed by reoxygenation at pH 7.4. Under these conditions, reoxygenation precipitated loss of viability to about half the cells. When pH was increased to 7.4 without reoxygenation, similar lethal injury occurred. No cell killing occurred after reoxygenation at pH 6.2. We conclude that acidosis protects against lethal anoxic injury, and that a rapid return from acidotic to physiologic pH contributes significantly to reperfusion injury to cardiac myocytes-a 'pH paradox'.
|Original language||English (US)|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Sep 16 1991|
Bibliographical noteFunding Information:
Reperfusion injury is the exacerbation of tissue damage when blood flow is restored to an ischemic organ. A marked reperfusion injury occurs to ischemic myocardium, whose mechanisms remain unclear. Generation of free radicals (9), critical depletion of ATP lev- National ‘This Institutes work was of supported, Health, and in t Ii e art, Gustavus by Grants and from Louise the Pfeiffer Office of Research Naval Research, Foundation. the Portions of this work were presented at the 74th Annual Meetin of the Federation of American Societies for Experimental Biology, Washington, DC, Apt-i B l-5,1990 (24).