Influence of inhibition of nitric oxide synthesis on cardiac function in the newborn lamb after hypoxic-ischemic injury.
The aim of the present study was to investigate the effect of immediate post-hypoxic-ischemic (HI) inhibition of nitric oxide synthesis by N(omega)-nitro-L-arginine (NLA) on cardiac function and reactive oxygen species production. Fifteen newborn lambs were subjected to severe HI. Upon resuscitation 5 received 10 mg NLA/kg, 4 40 mg NLA/kg and 6 a placebo. Left ventricular (LV) contractility, cardiac output (CO), non-protein-bound iron (NPBI), ratio of reduced/oxidized ascorbic acid, alpha-tocopherol, sulfhydryl groups and malondialdehyde were measured before and 15, 60 and 120 min after resuscitation. There was a significant decrease in CO in all 3 groups at 60 min post-HI (p < 0.05). Reactive oxygen species production was also highest at 60 min post-HI (significantly increased NPBI and decrease in sulfhydryl groups in control lambs; p < 0.05). These results suggest neither a positive nor a negative effect of nitric oxide synthesis inhibition on post-HI myocardial performance but may suggest a positive effect of NLA on reactive oxygen species-mediated post-HI damage.
Dorrepaal
C A
CA
TNO Prevention and Health, Leiden, The Netherlands. CA.Dorrepaal@pg.tno.nl
van Bel
F
F
Steendijk
P
P
Shadid
M
M
van de Velde
E T
ET
Moison
R M
RM
Berger
H M
HM
Baan
J
J
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002302:Cardiac Output; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000503:physiopathology*; D009200:Myocardial Contraction; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D012756:Sheep; D014684:Venae Cavae
D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D019335:Nitroarginine; D019001:Nitric Oxide Synthase