Anaphylactic shock and mitochondria

Abstract

Introduction Anaphylactic shock (AS) is a rare but potentially lethal complication during anaesthesia even in previously apparently healthy individuals. While anaphylaxis is a clear trigger for activation of multiple downstream pathways, the precise mechanisms underlying the development of organ failure, shock and death remain elusive. Our team observed that muscle partial pressure in oxygen (PtiO2) decreased rapidly after AS. This rapid drop in skeletal muscle PtiO2 was unexpected since muscles were at rest and was unusual as against the other types of shock. Mitochondrial oxidative capacities have not been investigated during AS. The aim of this study was to assess mitochondrial oxidative capacity during anaphylactic shock in skeletal muscle and in other organs. Methods Ovalbumin-sensitized anaphylactic shock rats (n = 7) were compared to control rats (n = 7) for systemic hemodynamics. Mitochondrial oxidative capacity was assessed in 6 different organs or tissues: we used isolated mitochondria for the brain, the lung and the liver and permeabilized fibers for 3 different muscles (gastrocnemius, soleus skeletal muscles and heart left ventricle). Free radical leak (H2O2 production/O2 consumption) was also calculated in the 3 muscles. Results AS provoked an early and profound arterial hypotension. Mitochondrial oxidative capacities were not altered in the liver, the lung, the brain and in the soleus. Maximal mitochondrial oxidative capacities significantly decreased in the heart (−36%, 399 ± 131 vs. 144 ± 33 O2 μmol/min/mg, P = 0.04) and increased in the gastrocnemius (+24%, 99 ± 55 vs. 173 ± 45 O2 μmol/min/mg, P = 0.03) during AS. The free radical leak was not modified by AS in left ventricle and in soleus muscle but was significantly decreased in gastrocnemius (−50%: 8/10,000 vs. 16/10,000, P = 0.046). Discussion Heart mitochondria were significantly altered, this mitochondrial dysfunction could participate to the myocardial dysfunction observed during AS. Gastrocnemius paradoxical mitochondria behaviour can directly participate to the rapidity and the severity of AS. Conclusion In our model of AS, mitochondrial oxidative capacity was not altered in most of the organs studied but was separate in 2 different types of muscle.