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The Journal of Thoracic and Cardiovascular Surgery, Vol 105, 353-363, Copyright © 1993 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
P Menasche, F Pradier, C Grousset, J Peynet, C Mouas, G Bloch and A Piwnica
In the course of cardiac transplantation, donor hearts undergo a four- step
sequence of events (arrest, cold storage, global ischemia during
implantation, and reperfusion) during which myocardial damage can occur. We
tested the hypothesis that the functional recovery of these hearts could be
improved by exposure to two interdependently formulated preservation
solutions throughout this four-step sequence. Solution I was used as a
perfusion and storage medium during the first three steps, and solution II
served as a modified reperfusate. The two solutions share the following
principles of formulation: prevention of cell swelling (high concentrations
of mannitol, a myocardium-specific impermeant) calcium overload (ionic
manipulations), and oxidative damage (reduced glutathione) and enhancement
of anaerobic energy production (glutamate). The two solutions differ with
respect to the calcium content and buffering capacity. One hundred rat
hearts perfused with isolated isovolumic buffer were subjected to
cardioplegic arrest; cold (2 degrees C) storage for 5 hours, global
ischemia at 15 degrees C for 1 hour, and normothermic reperfusion for 1
additional hour. In a first series of experiments (70 hearts), our kit of
solutions was compared with six clinical preservation regimens that
involved cardiac arrest with St. Thomas' Hospital or University of
Wisconsin solutions followed by storage of the hearts in saline,
Euro-Collins, St. Thomas' Hospital, or University of Wisconsin solutions.
In a second series of experiments (30 hearts), the effects of the kit were
more specifically investigated in relation to two types of
additive--oncotic agents (dextran) and thiol-based antioxidants (reduced
glutathione and N- acetyl-L-cysteine). According to comparisons of maximal
rate of ventricular pressure increase and left ventricular compliance after
reperfusion, the best myocardial protection was afforded by our kit of
solutions. The addition of dextran during storage did not provide
additional protection. Conversely, the omission of reduced glutathione was
clearly detrimental; the replacement of reduced glutathione with N-
acetyl-L-cysteine failed to improve recovery beyond that provided by
antioxidant-free solutions, thereby suggesting the importance, in this
model, of an anti-free radical compound that, like reduced glutathione, is
operative extracellularly. We conclude that the preservation of heart
transplants can be improved with the sequential use of two closely
interrelated solutions, the formulations of which integrate the basic
principles of organ preservation with those of myocardium- specific
metabolism.
ARTICLES
Improved recovery of heart transplants with a specific kit of preservation solutions
Department of Cardiovascular Surgery, Hopital Lariboisiere, Paris, France.
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