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 diffusible precursors, may help to explain age-related differences in tolerance of global myocardial ischemia. Postischemic function and high-energy 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 old (adult). Hearts in each age group were subjected to 60 minutes of ischemia 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 inhibitor. These groups were compared with one another and with control hearts that were continuously perfused for 1 hour. In adults, addition of pentoxifylline to St. Thomas' Hospital cardioplegic solution restored adenosine triphosphate and total nondiffusible nucleotide levels to control values and improved recovery of cardiac output and developed pressure compared with results with unmodified St. Thomas' Hospital cardioplegic solution. In contrast, biochemical and functional parameters in neonatal hearts were not affected by either unmodified St. Thomas' Hospital cardioplegic solution cardioplegia or St. Thomas' Hospital cardioplegic solution with pentoxifylline. Functional recovery in neonatal hearts subjected to unprotected ischemia was superior to that in the older age groups. In 1-month-old hearts, St. Thomas' Hospital cardioplegia improved recovery compared with recovery after unprotected ischemia, but no incremental improvement in function or high-energy stores was seen with addition of pentoxifylline. The lack of effect of pentoxifylline on neonatal hearts suggest that there is a relative deficiency of 5'-nucleotidase in this age group. This may contribute to the improved functional recovery observed in unprotected hearts. Furthermore, addition of pentoxifylline to adult hearts appears to confer the benefits of low 5'-nucleotidase activity occurring naturally in the neonate.
Pridjian
A K
AK
Department of Surgery, University of Michigan School of Medicine, Ann Arbor.
Bove
E L
EL
Bolling
S F
SF
Childs
K F
KF
Brosamer
K M
KM
Lupinetti
F M
FM
D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors*; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001639:Bicarbonates / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002302:Cardiac Output; D002314:Cardioplegic Solutions / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology*; D010431:Pentoxifylline / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011685:Purine Nucleotides / Q000032:analysis / Q000378:metabolism*; D011817:Rabbits; D012965:Sodium Chloride / Q000494:pharmacology
D001639:Bicarbonates; D002314:Cardioplegic Solutions; D011685:Purine Nucleotides; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D011189:Potassium Chloride; D015720:5'-Nucleotidase; D008274:Magnesium; D002122:Calcium Chloride; D010431:Pentoxifylline