Heat stress protects the perfused rabbit heart from complement
mediated injury: an experimental model of hyperacute xenograft
rejection.
Gralinski, Michael R., Shawn C. Black[acute]a, Louis F. Stancato,
Kenneth S. Kilgore, Patricia A. Campau, James L. Park, Mark J. Ozeck,
William B. Pratt, and Benedict R. Lucchesi.
Department of Pharmacology and Department of Pathology, University
of Michigan Medical School, 1301C Medical Science Research Building
III, Ann Arbor, Michigan 48109-0632, [acute]aMerck Frosst Canada
Inc., P.O. Box 1005, Pointe-Claire - Dorval, Quebec H9R 4P8
APStracts 3:0021H, 1996.
Complement activation is implicated in the hyperacute rejection
phenomenon occurring with transplantation of a vascularized
discordant xenograft. The purpose of this study was to determine if
heat stress and the associated induction of hsp70 could modulate
complement activation in an experimental model of xenograft
rejection. Male, New Zealand White rabbits were heat-stressed (n=9)
by increasing their core body temperature to 42[square root]C for 15
minutes. Control rabbits (n=13) were instrumented, but not exposed to
heat-stress. The hearts were removed eighteen hours later and
perfused by the Langndorff method. After equilibration normal human
plasma, a source of human complement, was added to the perfusion
medium. Hemodynamic variables were obtained for both groups before
(baseline) and after the addition of normal human plasma. Hemodynamic
variables recorded during perfusion with human plasma were improved
in hearts removed from heat stressed animals when compared to hearts
from the control group. Assembly of the soluble membrane attack
complex was reduced significantly in the interstitial fluid effluent
from the heat-stressed hearts as compared to the controls. Electron
microscopic evidence of ultrastructural changes were attenuated in
the hearts from heat stressed rabbits. Immunoblotting analysis
revealed that myocardial tissue from heat stressed animals exhibited
a marked increase in the inducible form of hsp70 which was virtually
absent in the hearts of control rabbits. Thus, previous whole body
hyperthermia protects the rabbit isolated heart against the
detrimental effects resulting from exposure to heterologous plasma.
The results suggest that heat-stress induction of hsp70 limits the
extent of complement activation (human) by a discordant vascularized
tissue (xenograft). The induction and expression of heat-stress
proteins by the donor organ might be an important mechanism affecting
the outcome of xenograft transplants
Received 1 November 1995; accepted in final form 13 December
1995.
APS Manuscript Number H1027-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96