Simultaneous study of metabolism and function following cardioplegic arrest: a novel method of evaluation of the transplanted heart in the rat.
BACKGROUND
Limitations of the isolated perfused rat heart model for heart preservation studies include short study time due to the lack of stability of the preparation. We aimed to develop a new experimental model based on heterotopic heart transplantation in the rat to achieve simultaneous (31)P magnetic resonance spectroscopy (MRS) and functional study of the transplanted heart during early and late blood reperfusion.


METHODS
Twenty-five Lewis rats underwent heterotopic abdominal isograft heart transplantation and were randomized in two groups. Hearts were harvested after cardioplegic arrest induced with Centre de Résonance Magnétique Biologique et Médicale (CRMBM) solution and then stored at 4 degrees C for a total ischemic time of 3 hours. Graft contractility measurement and simultaneous (31)P MRS were performed after 1 hour and 24 hours of blood reperfusion, respectively, in groups I (n = 12) and II (n =13).


RESULTS
Contractility improved during reperfusion. The mean rate pressure product plus or minus standard error of mean increased from 11,373 +/- 1,377 mm Hg/min in group I to 24,363 +/- 3,860 mm Hg/min in group II (P = 0.003), while mean dP/dtmax increased from 1,642 +/- 173 mm Hg/sec to 2,571 +/- 333 mm Hg/sec, respectively (p = 0.03). Simultaneously, both the phosphocreatine/adenosine triphosphate (ATP) and inorganic phosphate/ATP ratios decreased from group I to group II (p = 0.025 and p = 0.015, respectively), suggesting regeneration of the intracellular pool of ATP in group II.


CONCLUSIONS
Simultaneous functional and metabolic studies of the transplanted heart are feasible in rats. Improvement in contractility during late reperfusion is contemporary with significant changes in energetic metabolism. Our model should be useful for the further improvement of heart preservation, which may result in significant clinical progress.
Caus
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Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR CNRS 6612, Faculté de Médecine de Marseille, 27 Bd Jean Moulin, 13005 Marseille, France.
Izquierdo
M
M
Lan
C
C
Le Fur
Y
Y
Confort-Gouny
S
S
Cozzone
P J
PJ
Bernard
M
M
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects; D000818:Animals; D006321:Heart / Q000502:physiology*; D006324:Heart Arrest, Induced; D006339:Heart Rate / Q000502:physiology; D016027:Heart Transplantation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects; D010758:Phosphorus; D051381:Rats; D011917:Rats, Inbred Lew; D015424:Reperfusion; D013997:Time Factors; D017725:Ventricular Pressure / Q000502:physiology
D010725:Phosphocreatine; D010758:Phosphorus; D000255:Adenosine Triphosphate