Response of isolated rat heart cells to hypoxia, re-oxygenation, and acidosis.

Abstract

SUMMARY Responses of isolated adult rat heart cells to conditions that emphasize various aspects of ischemia have been evaluated. Cells maintained in hypoxic media with limited gubstrate deteriorate mort rapidly than aerobic controls supplemented with glucose. Two distinct irreversible pathways for cell alteration can be distinguished as follows: (1) continued anaerobic aging in the absence of glucose results in the production of large numbers of cells which retain the rod-shaped morphology of heart cells in situ, but which have lost saxcolemmal integrity, and (2) after a period of anaerobic aging, reaeration of the cells produces large numbers of rounded cells in irreversible contracture. These cells maintain an intact sarcolemma and are indistinguishable from those produced by addition of 1 mM Ca 1+ to Na + -loaded, aerobic cells. Contracture of isolated cells on re-aeration is at least superficially analogous to the oxygen paradox in situ, but since the isolated cells maintain an intact sarcolemma, there is no loss of creatine phosphokinase or other components of the cytosol. Incubation of isolated heart cells at acid pH (pH 8.8 to 6.2) largely prevents both Ca I+ -dependent contracture and a Ca 1+ -dependent loss of respiratory capacity. The acidic conditions virtually eliminate the net influx of "Ca 1 * into isolated cells that occurs at neutral pH, and the inhibition appears to be localized at the sarcolemma.

Modification of the cardiac action potential by intracellular injection of adenosine triphosphate and related substances in guinea pig single ventricular cells.

“…This finding was explained by assuming that these substances were converted to ATP, which prolonged the action potential duration. This notion agrees well with the finding that isolated cells using collagenase retain their energy metabolism (Altschuld et al, 1981).…”

“…The ATP-ADP ratio of 3.9 was reported in the isolated ventricular cell by Altschuld et al (1981). Also, in perfused rat hearts, the approximate contents of ATP, ADP, and AMP were reported to be 25.6, 10.0 and 1.3 MM/g of wet weight, respectively (Grinwald et al, 1980).…”

Oxygen deprivation-induced injury to isolated rabbit kidney tubules.

“…A similar effect of pH on renal tubule cell Ca"+ levels has been reported for isolated rat tubules (29). Although the mechanism for this reduction of cell Ca"+ and the subcellular loci of the effect remain to be elucidated, this observation suggests that low pH has the potential to alter cellular Ca"+ dynamics in normal and prelethally injured tubules and is consistent with observations that low pH reduces transmembrane Ca"+ flux in myocardial cells (14,55) and that rises in cell pH appear to promote Ca"+-mediated events during cellular differentiation and replication (43). It has been reported that the kD for the binding of Ca"+ to calmodulin is -10-fold higher (0.25 ,uM) at pH 6.5 than at pH 7.5 (0.02 iM) (43,56 …”

“…Isolated tubule preparations studied both as individually perfused tubules and tubule suspensions have provided substantial insights into the normal physiology of the renal tubular epithelium (8)(9)(10). Freshly isolated intact cell preparations have been applied to the study of cell injury in a number of tissues including, to a limited extent, the kidney (11)(12)(13)(14)(15)(16). The present study establishes freshly isolated suspensions of rabbit tubules enriched in proximal segments as a highly versatile system for studying the effects ofoxygen deprivation on critical metabolic parameters involved in the pathogenesis of renal tubule cell injury, identifies major differences in the susceptibility of tubules to such injury as a function of whether oxygen deprivation is produced under hypoxic or under simulated ischemic conditions, and implicates pH as a major factor contributing to the differences between hypoxic and ischemic injury.…”

Intracellular pH during "chemical hypoxia" in cultured rat hepatocytes. Protection by intracellular acidosis against the onset of cell death.

“…In excitable tissue like myocardium, mild tissue acidosis may be protective early and injurious late during hypoxic or ischemic stress (1)(2)(3). The early protective effect of acidosis in myocytes is reported to be due to inhibition of ATP hydrolysis via the oligomycin-sensitive ATPase, thereby preventing ATP depletion (4).…”