Effects hypoxia/reoxygenation on intracellular calcium ion homeostasis in ventricular myocytes during halothane exposure

In the experiments presented in this chapter, the researchers test the hypothesis that exposure of myocytes to halothane decreases the severity of hypoxia-reoxygenation injury to the myocardium by preventing the accumulation of Ca²⁺ in the intracellular organelles, primarily the sarcoplasmic reticulum (SR), during the hypoxic period. The object of the present study has been to explore the interaction of hypoxia and halothane on intracellular Ca²⁺ homeostasis, to examine possible mechanisms by which the anesthetic may protect the myocardium during hypoxic insult. These experiments demonstrate that concurrent exposure of individual myocytes to halothane during hypoxia is associated with a beneficial outcome based on indicies of structure and function. Hypoxia-reoxygenation of ventricular myocytes is associated with pathological changes in the way that myocytes handle Ca²⁺. Even apparently normal cells, with normal morphology and resting [Ca²⁺]_i are impaired. They have an inability to be electrically paced following hypoxia and difficulty in handling large sudden increases in the [Ca²⁺]_i produced by 10 mM caffeine. Exposure to halothane during hypoxia and reoxygenation appears to give some protection to the ventricular myocyte as demonstrated by a huge propensity for maintenance of normal morphology and resting [Ca²⁺]_i in the postischemia reoxygenation period and the ability to handle pacing-induced and caffeine-induced sudden increases in [Ca²⁺]_i. Furthermore, exposure of the myocytes to the anesthetic prevents the large increase in caffeine-releasable Ca²⁺ associated with hypoxia and reperfusion. These findings support the hypothesis that exposure of myocytes to halothane decreases the hypoxia-reoxygenation injury to the myocardium by preventing the accumulation of Ca²⁺ in the intracellular organelles, primarily the SR, during the hypoxic period. These anesthetic-induced changes in how the hypoxic myocytes handle Ca²⁺ can help explain the decrease in myocardial damage and irritability seen in vivo.