Circulation, Vol 80, 983-993, Copyright © 1989 by American Heart Association
C Indolfi, BD Guth, T Miura, S Miyazaki, R Schulz and J Ross Jr
In anesthetized swine, the left anterior descending coronary artery was
cannulated and perfused at constant blood flow levels during two grades of
ischemia. In one group (n = 10), moderate ischemia reduced percent systolic
wall thickening (by sonomicrometry) from 25 +/- 7% to 6 +/- 2%, whereas in
the other group (n = 7), severe ischemia reduced percent wall thickening
from 24 +/- 6% to -0.5 +/- 4%. Heart rate was paced in both groups at 91
beats/min. After reperfusion and complete return to control conditions,
administration of the bradycardic agent UL-FS 49 (0.37 mg/kg i.v.)
decreased the heart rate to 55 +/- 5 beats/min. During subsequent ischemia
at the same coronary inflow as before bradycardia, percent wall thickening
in the ischemic zone during moderate ischemia was increased from 6 +/- 2%
to 25 +/- 6% (p less than 0.01) (not significantly different from control
without ischemia), and during severe ischemia, percent wall thickening
increased from -0.5 +/- 4% to 13 +/- 7% (p less than 0.01). During moderate
ischemia, bradycardia caused an increase in the subendocardial blood flow
from 0.24 +/- 0.60 to 0.42 +/- 0.17 (ml/min)/g (p less than 0.009) and
during severe ischemia, bradycardia caused an increase from 0.14 +/- 0.08
to 0.2 +/- 0.1 (ml/min)/g (p less than 0.001). At each level of ischemia, a
more marked improvement occurred in subendocardial blood flow per beat
([(ml/min)/g]/heart rate). The relation between myocardial blood flow and
wall function at a heart rate of 55 beats/min (n = 14) was plotted and
compared with that studied at a heart rate of 122 beats/min in another
group of pigs (n = 14). The increase in subendocardial blood flow per
minute during bradycardia was not sufficient to explain the striking
increase in function; thus, an independent relation (p less than 0.05)
between blood flow per minute and contractile function (percent wall
thickening) was found for for each heart rate. In contrast, when myocardial
blood flow was normalized for heart rate and expressed per beat, data from
both heart rate groups could be described by a single relation. Thus, the
subendocardial blood flow per beat predicted wall function independently of
heart rate and accounted for changes in both oxygen supply and demand.
ARTICLES
Mechanisms of improved ischemic regional dysfunction by bradycardia. Studies on UL-FS 49 in swine
Department of Medicine, University of California, San Diego, La Jolla 92093.
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