Hydroxyl radical production during myocardial ischemia and
reperfusion in the cat.
O'neill, Charles A., Liang-Wu Fu, Barry Halliwell* and John C.
Longhurst.
Department of Internal Medicine, Division of Cardiovascular
Medicicne, University of California, Davis, Davis, CA 95616
APStracts 3:0022H, 1996.
We previously have shown that generation of reactive oxygen species
during myocardial ischemia and reperfusion stimulates cardiac
sympathetic afferent nerve endings. We hypothesized that, in this
feline model of brief ischemia and reperfusion, the rate and
concentration of production of hydroxyl radical (HO x ) during
reperfusion is dependent upon the duration of myocardial ischemia.
Additionally, we hypothesized that HO x is produced during ischemia.
Therefore, we evaluated the time dependency of production of HO x
during reperfusion following 2, 5 and 10 min of reversible occlusion
of the left anterior descending (LAD) coronary artery to induce
ischemia in cats (n=10). Blood samples collected from the coronary
vein at 0.25, 1, 2 and 4 min following 2 min of ischemia revealed net
cumulative rate of production of p-, m- and o-tyrosine of 99+/-31,
10+/-5.1 and 0.8+/-0.2 nmol/min/g, respectively. Following 5 min of
ischemia, net cumulative rates of production of p-, m- and o-tyrosine
during reperfusion were 177+/-63, 74+/-26 and 1.6+/-0.8 nmol/min/g,
respectively, while following 10 min of ischemia production rates
were 153+/-42, 78+/-29 and 2.1+/-0.5 nmol/min/g, respectively. The
highest rate of production of tyrosines was observed immediately
following ischemia, perhaps indicating a washout of HO x derived
products, which had accumulated in the myocardium during ischemia. To
evaluate production of HO x during ischemia, deoxygenated saline
(PO2: 10+/-0.9 mm Hg) containing phenylalanine was perfused into the
ischemic coronary vascular bed through a cannula placed in the LAD
(n=16). Perfusate was collected from the coronary vein during the 10
min of ischemia. Net production of HO x during ischemia, measured by
the production of p-, m- and o-tyrosines, was 82+/-11, 6.6+/-0.4 and
1.7+/-0.3 nmol/min/g, respectively. Pretreatment with deferoxamine
(10 mg/kg, n=7) or dimethylthiourea (10 mg/kg, n=6) decreased net
production of HO x during ischemia and reperfusion. These results
demonstrate that HO x is produced during brief ischemia and
reperfusion with the greatest amount being produced immediately after
ischemia. Additionally, we have shown that the duration of brief
ischemia determines the rate of production of HO x during
reperfusion.
Received 21 April 1995; accepted in final form 18 December 1995.
APS Manuscript Number H380-5.
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