Effect of 3-aminotriazole on hyperthermia-mediated cardioprotection
in rabbits.
Kingma, J. G., D. Simard, J. R. Rouleau, R. M. Tanguay, R. W. Currie,.
Quebec Heart Institute and Department of Medicine, Faculty of
Medicine, Laval University, Ste-Foy, Qu[acute]ebec G1V 4G5, Centre de
Recherche du CHUL and Laboratory of Cellular and Developmental
Genetics, Pav. C.-E Marchand, RSVS, Laval University, Ste-Foy,
Qu[acute]ebec G1K 7P4, Department of Anatomy and Neurobiology,
Faculty of Medicine, Dalhousie University, Halifax, N.S. B3H 4H7
APStracts 2:0516H, 1995.
Hyperthermia-induced cardioprotection during myocardial ischemia may
involve increased activity of antioxidative enzymes. In this study we
investigated the effects of 3-amino-1,2,4-triazole (3-AT), an
irreversible catalase inhibitor, in heat shocked (HS) rabbits
subjected to ischemia-reperfusion injury. Rabbits underwent whole
-body hyperthermia at 42oC for 15 minutes. Twenty-four hours later,
rabbits were administered either saline vehicle or 3-AT (1 or 2 g/Kg;
i.p.), 30 minutes before undergoing 30 minutes of regional coronary
occlusion and 3 hours reperfusion. Controls did not undergo whole
-body hyperthermia and were given either saline or 3-AT. Heart rate
and LV pressure were recorded continuously during these experiments.
Infarct area (tetrazolium staining) was normalized to anatomic risk
zone size (microsphere autoradiography). Expression of HSP71 was
verified using Western blot analysis; myocardial catalase activity
was determined in tissue biopsies. Infarct size was significantly
reduced in HS rabbits (25.1+/-2.8%, p=0.02; mean+/-SEM) compared to
controls (53.6+/-4.7%). Treatment with 1 g/Kg 3-AT attenuated HS
-mediated cardioprotection (36.9+/-4.9%, p=0.08 vs HS); protection was
abolished with 2 g/Kg 3-AT (48.9+/-6.6%). Myocardial catalase
activities were higher in tissue biopsies from HS rabbits (47.0+/-4.5
U/mg protein, p=0.02) compared to controls (33.4+/-1.9 U/mg
protein); catalase activities were significantly reduced in rabbits
treated with 3-AT. In conclusion, whole-body hyperthermia increases
expression levels of HSP71; myocardial catalase activity is also
significantly increased. Myocardial protection in HS rabbits
subjected to ischemia-reperfusion injury was reversed with 3-AT.
These data suggest that increased intracellular activities of
catalase and possibly other antioxidant enzymes is an important
mechanism for hyperthermia-mediated cellular protection.
Received 18 July 1995; accepted in final form 11 September 1995.
APS Manuscript Number H677-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95