Canine stress syndrome/malignant hyperthermia susceptibility: calcium-homeostasis defect in muscle and lymphocytes

Abstract

This study provides the first comprehensive characterisation of the calcium (Ca) homeostasis defects found in muscle and lymphocytes of a malignant hyperthermia (MH)-susceptible dog. Novel findings regarding this dog are reported, compared to controls. First, a canine stress syndrome occurs, analogous to the porcine stress syndrome; susceptibility can be identified by exercise challenge testing. Secondly, caffeine causes Ca release from muscle sarcoplasmic reticulum in a greater amount and at a greater rate. Thirdly, there is a compensatory increase in Ca sequestration by sarcoplasmic reticulum. Fourthly, lymphocytes have lower cytosolic-free Ca and a greater ability to prevent Ca increase. Halothane increases Ca by a greater amount and rate. Fifthly, muscle is more resistant to the contracture-producing effects of caffeine, as occurs in the non-rigid variant of MH susceptibility in man. This resistance, despite increased caffeine-induced release through the Ca channel, may be attributable to increased Ca sequestration by sarcoplasmic reticulum. Finally, erythrocyte osmotic fragility and creatine kinase tests fail to distinguish between the MH-susceptible dog and controls.