DEVELOPMENTAL DIFFERENCES IN MYOCARDIAL PROTECTION IN RESPONSE TO 5'-NUCLEOTIDASE INHIBITION

Age-related differences in the activity of 5'-nucleotidase, an enzyme responsible for conversion of high-energy phosphates to their the diff usible precursors, may help to explain age-related differences in tole rance of global myocardial ischemia. Postischemic function and high-en ergy phosphate content were measured in the hearts of rabbits 7 to 10 days old (neonate), 30 to 40 days old (1 month), and 6 to 12 months ol d (adult). Hearts in each age group were subjected to 60 minutes of is chemia at 34 degrees C either with no cardioplegia, with unmodified St . Thomas' Hospital cardioplegic solution, or with St. Thomas' Hospital cardioplegic solution with pentoxifylline, a 5'-nucleotidase inhibito r. These groups were compared with one another and with control hearts that were continuously perfused for 1 hour. In adults, addition of pe ntoxifylline to St. Thomas' Hospital cardioplegic solution restored ad enosine triphosphate and total nondiffusible nucleotide levels to cont rol values and improved recovery of cardiac output and developed press ure compared with results with unmodified St. Thomas' Hospital cardiop legic solution. In contrast, biochemical and functional parameters in neonatal hearts were not affected by either unmodified St. Thomas' Hos pital cardioplegic solution cardioplegia or St. Thomas' Hospital cardi oplegic solution with pentoxifylline. Functional recovery in neonatal hearts subjected to unprotected ischemia was superior to that in the o lder age groups. In 1-month-old hearts, St. Thomas' Hospital cardiople gia improved recovery compared with recovery after unprotected ischemi a, but no incremental improvement in function or high-energy stoles wa s seen with addition of pentoxifylline. The lack of effect of pentoxif ylline on neonatal hearts suggests that there is a relative deficiency of 5'-nucleotidase in this age group. This may contribute to the impr oved functional recovery observed in unprotected hearts. Furthermore, addition of pentoxifylline to adult hearts appears to confer the benef its of low 5'-nucleotidase activity occurring naturally in the neonate .