Effects of acidic reperfusion on reperfusion arrhythmias and na+/k+
atpase activity in regionally ischemic rat hearts.
Avkiran, Metin, Chikao Ibuki, Yasuyuki Shimada, Peter S. Haddock.
Cardiovascular Research, The Rayne Institute, St Thomas' Hospital,
London SE1 7EH, United Kingdom
APStracts 2:0453H, 1995.
Transient (2 min) acidic (pH 6.6) reperfusion provides sustained
protection against reperfusion-induced ventricular fibrillation (VF),
possibly by inhibition of Na+ influx coupled to H+ extrusion. Our
objectives were to determine: (i) the minimum duration of acidic
reperfusion required to achieve such protection and (ii) the
potential role of ischemia- and reperfusion-induced changes in the
activity of Na+/K+ ATPase. Isolated rat hearts (n=12/group) were
subjected to independent perfusion of the left and right coronary
beds. After 15 min perfusion of both beds with pH 7.4 buffer, the
left coronary bed was subjected to 10 min of zero-flow ischemia. The
ischemic bed was then reperfused for 5 min, with pH 6.6 buffer for
the first 0 (control), 0.5, 1, 2 or 4 min and with pH 7.4 buffer
thereafter. In the control group, 92% of hearts developed VF within
20 s of the onset of reperfusion and remained in VF for the rest of
the reperfusion period. In the 0.5, 1, 2 and 4 min acidic reperfusion
groups, only 17*, 17*, 42* and 25%* of hearts exhibited VF during
acidic reperfusion (*p<0.05 v control). However, on returning to pH
7.4, VF occurred in a further 50, 58, 0 and 0% of hearts; thus, the
overall incidences of VF were 67, 75, 42* and 25%*. In a parallel
study, hearts (n=8/group) were frozen (-70 C), sectioned (10 [mu]m)
and, using quantitative cytochemistry, sarcolemmal Na+/K+ ATPase
activity was determined in both the ischemic/reperfused left
ventricular free wall (LV) and the non-ischemic right ventricular
free wall (RV). There was no inter-group difference in RV Na+/K+
ATPase activity. Ischemia (10 min) reduced LV Na+/K+ ATPase activity
from 110+/-8 to 25+/-3% of the RV value. Following 0.5, 1, 2, 3 and 4
min of acidic reperfusion, LV Na+/K+ ATPase activity was 24+/-3,
29+/-3, 37+/-5_, 55+/-6_ and 70+/-4%_, respectively (_ p<0.05 v
10 min ischemia). In contrast, no significant recovery of LV Na+/K+
ATPase activity occurred following up to 4 min of normal (pH 7.4)
reperfusion. In conclusion: (i) a minimum of 2 min of acidic
reperfusion is required to achieve sustained protection against VF,
and (ii) the protective mechanism may involve not only inhibition of
Na+ influx but also enhanced recovery of Na+/K+ ATPase activity from
ischemia-induced inhibition.
Received 4 November 1994; accepted in final form 30 August 1995.
APS Manuscript Number H989-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95