A decrease of both [Ca2+]e and [H+]e produces cell damage in the perfused rat heart.
Cell damage of the Langendorff-perfused rat heart in response to a decrease of both [Ca2+]e and [H+]e is described. At pHe = 7.7, lactate dehydrogenase (LDH) release could be induced during perfusion with media of reduced [Ca2+]e (0.1-0.4 mmol/l). Decreasing pHe to normal abolished LDH release. The gap junction channel blocker heptanol (2 mmol/l) also reduced enzyme release, and polyethylene glycol (9% PEG6000) totally prevented cell damage. Elevation of buffer capacity of perfusion media or perfusion flow both increased LDH release. Cell damage could also be aggravated by substituting 10 mmol/l of [Na+]e by foreign cations. At [Ca2+]e = 0.1 mmol/l and pHe = 7.7, [Ca2+]i and [Na+]i of non-lysed cells were markedly increased (in HCO3/CO2 buffered media to about 7.0 micromol/l and 36 mmol/l, respectively; in HEPES-buffered media, to about 5.0 micromol/l and 55 mmol/l; physiological values of [Ca2+]i and [Na+]i are around 0.1 micromol/l and 10 mmol/l, respectively), whereas pHi was not appreciably elevated. In contrast to myocytes in the intact heart, [Ca2+]i of isolated cardiomyocytes under similar conditions was decreased to about 75 nmol/l and LDH release was negligible; pHi of isolated cardiomyocytes, as in intact myocardium, did not change appreciably. The results indicate that Ca2+ overload is produced at lowered [Ca2+]e and [H+]e by an influx of Ca2+ through gap junctional leaks.
Diederichs
F
F
Institute of Clinical Biochemistry, Hannover Medical School, Germany.
D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002412:Cations; D006321:Heart / Q000187:drug effects*; D006859:Hydrogen / Q000378:metabolism* / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium
D002021:Buffers; D002412:Cations; D006859:Hydrogen; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D002118:Calcium