Integration of vascular, contractile and metabolic responses to
hypoxia: effects of maturation and the role of adenosine.
Matherne, G. Paul, Stuart S. Berr, and John P. Headrick.
Departments of Pediatrics & Radiology, University of Virginia
Health Sciences Center, Charlottesville, Virginia 22908, U.S.A and
Division of Biochemistry & Human Physiology, Department of
Molecular Sciences, James Cook University of North Queensland,
Townsville 4811, Australia
APStracts 2:0323R, 1995.
We examined myocardial responses to reduced arterial PO2, and the role
of endogenous adenosine, in constant-pressure perfused hearts from
immature (IMM) and mature (MAT) rabbits. During normoxia coronary
flow and MVO2 were similar in both groups. With moderate hypoxia
coronary perfusate flow increased by 125+/-16% in IMM but by only
68+/-12% in MAT hearts. IMM hearts displayed better maintenance of
contractile function (87% vs. 67% in MAT hearts) and metabolic state.
Blockade of cardiac adenosine receptors with 25 _M 8-_-sulfophenyl
-theophylline attenuated vasodilation during hypoxia, reduced
contractile function, and abolished age-related differences in l
responses to hypoxia. Myocardial purine release and extracellular
purine levels were 3-fold higher in MAT compared to IMM hearts and
was associated with higher cytosolic [5_-AMP] (and lower
[ATP]/[ADP].[Pi]) in MAT hearts. In summary: i) IMM hearts are
functionally and metabolically more tolerant of hypoxic perfusion,
largely due to improved hypoxia-induced coronary vasodilation, ii)
endogenous adenosine mediates this beneficial vasodilation, enhancing
hypoxic tolerance, and iii) improved vascular sensitivity to
adenosine allows for enhanced vasodilatory responses in the face of
lower adenosine levels and higher energy state in immature hearts.
Received 18 May 1995; accepted in final form 30 October 1995.
APS Manuscript Number R302-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95