Disordered catecholamine release in pigs susceptible to malignant hyperthermia

Area of Science:

• Veterinary Medicine
• Physiology
• Pharmacology

Background:

• Malignant hyperthermia (MHS) is a genetic disorder affecting skeletal muscle response to anesthesia.
• Stress-susceptible pigs exhibit abnormal responses to anesthetic agents like halothane.
• Catecholamine (CA) levels and myocardial damage are potential indicators of stress response in pigs.

Purpose of the Study:

• To investigate the impact of different myorelaxant agents on catecholamine release and myocardial cell necrosis in normal and stress-susceptible pigs.
• To evaluate the protective effect of dantrolene against stress-induced cardiovascular complications in MHS pigs.

Main Methods:

• Experimental stress induced by succinylcholine or pancuronium in normal and stress-susceptible pigs.
• Measurement of blood catecholamines (noradrenaline and adrenaline) during stress.
• Morphological grading of myocardial cell necrosis 1-2 days post-stress.
• Assessment of dantrolene's effect on catecholamine levels and myocardial necrosis.

Main Results:

• Normal pigs showed similar noradrenaline levels and myocardial necrosis regardless of the myorelaxant used.
• Stress-susceptible pigs exposed to succinylcholine exhibited significantly elevated catecholamines and severe myocardial necrosis.
• Pancuronium induced lower catecholamine levels and reduced heart lesions in stress-susceptible pigs compared to succinylcholine.
• Dantrolene pretreatment prevented high catecholamine levels and myocardial necrosis in stress-susceptible pigs under succinylcholine stress.

Conclusions:

• Peripheral sympathetic neurons in MHS pigs may react abnormally, potentially due to defective calcium turnover.
• Succinylcholine exacerbates stress responses in MHS pigs, leading to cardiovascular damage.
• Dantrolene effectively mitigates succinylcholine-induced stress responses and myocardial injury in MHS pigs, likely by modulating calcium release.