The Annals of Thoracic Surgery, Vol 58, 409-415, Copyright © 1994 by The Society of Thoracic Surgeons
Orotic acid improves left ventricular recovery four days after heterotopic transplantation
T Yeh Jr, IM Rebeyka, ER Jakoi, DE Johnson, RJ Dignan, CM Dyke and AS Wechsler
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
Orotic acid accelerates compensatory myocardial hypertrophy after regional
ischemia and improves left ventricular function acutely after global
ischemia. In this study, the effect of orotic acid on left ventricular
function was investigated 4 days after global ischemia (75 minutes, 21
degrees C) using heterotopically transplanted rabbit hearts (n = 18).
Experimental animals received daily 100-mg/kg doses of intraperitoneally
administered orotic acid, starting 1 day before transplantation, and showed
a threefold increase in the serum level of orotic acid by 4 days. After 1
hour of reperfusion, the developed pressure was equally depressed in both
the control and experimental groups; however, 4 days later, the developed
pressure in control animals was decreased by 3 +/- 3 mm Hg (versus the
developed pressure measured at 1 hour) while the developed pressure in
experimental animals was significantly increased by 25 +/- 8 mm Hg.
Heterotopically transplanted hearts manifested diminished systolic function
(stemming from ischemia and unloading) as well as decreased expression of
adult myosin. Because orotic acid has been observed to produce an increase
in protein synthesis in other models, we investigated whether this
improvement in systolic function resulted from an orotic acid-mediated
augmentation (or preservation) or normal adult myosin expression. Both
orotic acid-treated and untreated hearts manifested decreased expression of
the beta-myosin heavy chain protein and steady-state messenger RNA levels.
Because function improved with decreased beta- myosin heavy chain
expression, an alternate mechanism underlying orotic acid-mediated
improvement in function is implicated. Nevertheless, orotic acid may be a
therapeutic agent facilitating long-term recovery from global ischemia.
