Heat stress contributes to the enhancement of cardiac mitochondrial complex activity.
Hyperthermic stress is known to protect against myocardial dysfunction after ischemia-reperfusion injury. It is unclear however, what energetic mechanisms are affected by the molecular adaptation to heat stress. We hypothesized that mild hyperthermic stress can increase mitochondrial respiratory enzyme activity, affording protection to mitochondrial energetics during prolonged cardiac preservation for transplantation. Rat hearts were excised after heat-stress or sham treatment and subjected to cold cardioplegic arrest and ischemia followed by reperfusion in an ex vivo perfusion system. Cardiac function, mitochondrial respiratory, and complex activities were assessed before and after ischemia. Heat shock protein (Hsp 32, 60, and 72) expression was increased in heat-stressed hearts. This was associated with increased mitochondrial complex activities in heat-stress versus sham-treated groups for complex I-V. During reperfusion, higher complex activities and respiratory control ratios were observed in heat-stressed versus sham-treated groups. Recovery of ventricular function was improved in heat-stressed hearts. Furthermore, mitochondria in reperfused heat-stressed myocardium exhibited intact membranes with packed, parallel, lamellar cristae, whereas in sham-treated myocardium, mitochondria were severely disrupted. This study provides the first evidence of heat-stress-mediated enhancement of mitochondrial energetic capacity. This is associated with increased tolerance to ischemia-reperfusion injury. Protection by heat stress against myocardial dysfunction may be partially due to enhancement of mitochondrial energetics.
Sammut
I A
IA
Departments of Cardiothoracic Surgery, and Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Jayakumar
J
J
Latif
N
N
Rothery
S
S
Severs
N J
NJ
Smolenski
R T
RT
Bates
T E
TE
Yacoub
M H
MH
D000818:Animals; D018834:Chaperonin 60 / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology; D005334:Fever / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D018834:Chaperonin 60; D002950:Citrate (si)-Synthase