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An optimal experimental design for the development of preservative heart solutions
René Ferrera1, Pierre Michel, Guylaine Hadour
1INSERM IFR Cardiovasuculaire No. 39 and HCL, Bron, France. ferrera@lyon151.inserm.fr
Background:
The aim of this study was to determine the optimal composition of a new medium for long-term hypothermic heart preservation.
Methods:
The independent effects of 19 compounds were evaluated using an in vitro porcine model. Tissue viability was assessed by measuring the reduction of methyltetrazolium salt, oxygen consumption and energetic compound levels on myocardial biopsies after 24-, 48- or 72-hour incubation periods. Screening of several compounds at two concentrations was performed to greatly reduce the number of experiments.
Results:
Pyruvate, aspartic acid, chlorpromazine and polyethylene glycol displayed protective properties, whereas calcium (2 mmol/liter), nifedipine, mannitol, magnesium (16 mmol/liter) and reduced glutathione showed deleterious effects. On the basis of these data, the composition of a new preservation solution (Group 1, n = 6) was compared with St Thomas solution (Group II, n = 6) in an isolated, 24-hour pig heart preservation model. During reperfusion, left ventricular developed pressure and coronary blood flow were significantly higher (p <.01) in Group I, suggesting better preservation.
Conclusions:
Our technique allows for rapid and efficient screening of many compounds currently used in the composition of preservation solutions for cardiac surgery.