Protection of energy status of hypoxic cardiomyocytes by mild acidosis.
The question was investigated whether mild acidosis can provide energetic protection on the hypoxic myocardial cell by mechanisms other than negative inotropy. The experimental model used was quiescent ventricular cardiomyocytes isolated from the adult rat. The extracellular pH (pHe) in modified hypoxic Tyrode's solution was varied by changing the concentration of bicarbonate at constant PCO2. The intracellular pH (pHi) was determined with 2',7'-bis-(carboxyethyl)5-(6')-carboxyfluorescein. When the pHe was varied between 6.6 and 7.4, the pHi varied only between 6.91 and 7.14. At pH 7.0, pHi and pHe were identical. Around pHe 7.0, the rate of hypoxic energy loss was lowest. Energetic differences were most prominent after 90 min hypoxia. At this time loss of ATP was 57.1 +/- 2.9% at pHe 6.95 vs. 83.5 +/- 4.1% at pHe 7.4 and 73.9 +/- 2.8% at pHe 6.6; the free energy change of ATP hydrolysis was reduced from 58.8 +/- 0.4 kJ/mol under control conditions to 52.0 +/- 1.1 kJ/mol at pHe 6.95 vs. 45.8 +/- 1.2 and 47.3 +/- 1.4 kJ/mol at pHe 7.4 and 6.6, respectively (means +/- S.D.). Anaerobic lactate production was not significantly altered in the investigated pHe range, indicating that glycolytic energy production remained constant. The results of the present study demonstrate that mild acidosis (pHe around 7.0) has a prominent energy-saving effect on the hypoxic cardiomyocyte due to a reduction in the demand of energy.
Koop
A
A
Physiologisches Institut I, Universität Düsseldorf, Germany.
Piper
H M
HM
D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010100:Oxygen