Heat stress protects the perfused rabbit heart from complement-mediated injury.
We determined if heat stress induction of heat shock protein (HSP) 70 modulates complement activation in an experimental model of xenograft rejection. Male New Zealand White rabbits were heat stressed (core body temperature to 42 degrees C for 15 min; n = 9). Control rabbits (n = 13) were not exposed to heat stress. Hearts were removed 18 h later and perfused by the Langendorff method. After equilibration, human plasma (source of human complement) was added to the perfusion medium. Hemodynamic variables recorded during perfusion with human plasma were improved in hearts from heat-stressed animals compared with control hearts. Assembly of the soluble membrane attack complex was reduced in the interstitial fluid effluent from the heat-stressed hearts. Electron microscopic evidence of ultrastructural changes was attenuated in the hearts from heat-stressed rabbits. Myocardial tissue from heat-stressed animals exhibited an increase in inducible HSP 70 that was virtually absent in the hearts of control rabbits. Previous whole body hyperthermia protects the rabbit heart against the detrimental effects of heterologous plasma, suggesting that heat-stress induction of HSP 70 limits the extent of complement activation by a discordant vascularized tissue (xenograft). Induction of heat stress proteins by the donor organ might be an important mechanism affecting the outcome of xenograft transplants.
Gralinski
M R
MR
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0632, USA.
Black
S C
SC
Stancato
L F
LF
Kilgore
K S
KS
Campau
P A
PA
Park
J L
JL
Ozeck
M J
MJ
Pratt
W B
WB
Lucchesi
B R
BR
D000818:Animals; D015153:Blotting, Western; D003167:Complement Activation / Q000502:physiology; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D018882:Heat Stress Disorders / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000473:pathology; D010477:Perfusion; D011817:Rabbits
D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D018840:HSP70 Heat-Shock Proteins; C047610:SC5b-9 protein complex; D003165:Complement System Proteins