Optimal Time Duration for Low-Pressure Controlled Reperfusion to
Efficiently Protect Ischemic Rat Heart
J.C. Bopassa, C. Nemlin, L. Sebbag, C. Rodriguez, M. Ovize, and R. Ferrera
ABSTRACT
Previous studies have shown the capacity of low-pressure (LP) reperfusion to protect the
ischemic heart. The present study sought to determine the optimal time for the application
of LP reperfusion. Isolated rat hearts (n = 30) were exposed to 40 minutes of global warm
ischemia followed by 70 minutes of reperfusion. Reperfusion was performed under LP (LP =
70 cm H
2
O) for 0 (control group), 5 (group LP-5), 10 (group LP-10), 30 (group LP-30), or
60 (group LP-60) minutes. Following the LP period the hearts were reperfused with
normal pressure (100 cm H
2
O) until the end of reperfusion. Cardiac function was assessed
during reperfusion using the Langendorff model. Myocardial necrosis was assessed by
measuring LDH leakage in the coronary effluents. Functional recovery was reduced among
the control and LP-5 groups with rate-pressure products (RPP) averaging 3788 499 and
5333 892 mm Hg/min, respectively. RPP was significantly improved in other groups with
RPP averaging 7363 1159, 7441 863, and 7269 692 mm Hg/min in LP-10, LP-30, and
LP-60 (P .01). Similarly, necrosis measured by LDH leakage was significantly reduced
in LP-10, LP-30, and LP-60 hearts (P .01). This study demonstrated that LP reperfusion
improves postischemic contractile dysfunction and attenuates necrosis when applied for at
least 10 minutes.
M
ANY STUDIES USING animal preparations or clin-
ical models have attempted to modify reperfusion
conditions in order to attenuate its deleterious effects.
Controlled reperfusion following an ischemic insult has
been proposed to protect the reperfused myocardium.
1,2
Our group recently demonstrated that low-pressure (LP)
reperfusion may protect the heart at the time of reperfusion
after an irreversible normothermic ischemic insult.
3
Further-
more, the protection afforded by LP reperfusion seemed to act
the same way (PI3-kinase Akt pathway) as postcondition-
ing.
4
However, the optimal conditions for the application of
this cardioprotective maneuver have remained unknown.
The present study sought to determine the optimal duration
for application of LP reperfusion.
METHODS
This investigation conformed to the Guide for the Care and Use of
Laboratory Animals published by the US National Institutes of
Health (NIH Publication No. 85-23, revised 1996). Male Wistar
rats, weighing 350 to 450 g, were anesthetized with pentobarbital
(50 mg/kg). After removal, isolated rats hearts (n = 30) were
exposed to 40 minutes of global warm ischemia followed by 70
minutes of reperfusion. Reperfusion was performed under LP (LP =
70 cm H
2
O) for 0 (control group), 5 (group LP-5), 10 (group
LP-10), 30 (group LP-30), or 60 (group LP-60) minutes. Following
the LP period, hearts were reperfused at normal pressure (100
cm H
2
O) until the end of reperfusion. It should be noted that
100 cm H
2
O is considered to be the normal perfusion pressure
for a rat heart under physiologic conditions. Cardiac function
was assessed during reperfusion using a Langendorff model. The
heart rate (HR), left ventricular systolic pressure (LVSP), and
left ventricular end-diastolic pressure (LVEDP) were measured
using a latex balloon introduced on the left. We calculated the
rate-pressure product (RPP = (LVSP-LVEDP) HR). Myo-
cardial necrosis was assessed by measuring lactate dehydroge-
nase (LDH) release in the coronary effluent, as previously
described.
4
Statistical comparisons were performed using anal-
ysis of variance and Fisher PLSD test.
From the INSERM U886, Université de Lyon (J.C.B., C.N.,
L.S., M.O., R.F.), and Hôpital Cardiologique de Lyon (L.S., C.R.,
M.O.), Lyon, France.
This work was supported by the Agence de la Biomédecine,
France.
Address reprint requests to René Ferrera, INSERM U 886,
Laboratoire de Physiologie, Faculté de Médecine Lyon-Nord, 8,
Avenue Rockefeller, 69373 Lyon Cedex 08, France. E-mail:
ferrera@lyon.inserm.fr
© 2007 by Elsevier Inc. All rights reserved. 0041-1345/07/$–see front matter
360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2007.08.024
Transplantation Proceedings, 39, 2615–2616 (2007) 2615