Reinforcement therapy using nitric oxide synthase inhibitors against endotoxin shock in dogs.
OBJECTIVE
Nitric oxide synthase (NOS) inhibitors were confirmed to correct the hypotension associated with septic shock, but the overall prognosis is often pessimistic. The histological findings failed to show any improvement. In fact, some patients even exhibited signs of exacerbation. The purpose of this study was to investigate the therapeutic effects of NOS inhibitors and catecholamines in dogs suffering from endotoxin shock. The histological changes produced by these agents were also evaluated.


METHODS
Mongrel dogs were used under midazolam anesthesia. A PiCCO continuous cardiac output monitoring catheter was placed in the femoral artery, and a central venous monitoring catheter was placed in the external carotid artery.


RESULTS
Endotoxin (0.5 mg/kg, i.v.) was administered to cause shock. After this shock state was observed, the NOS inhibitors and catecholamines raised the blood pressure, and norepinephrine (NA, 2 microg/kg/h) was found to be more potent than S-methylisothiourea (SMT, 20 microg/kg/h). The combined effects of SMT-NA or SMT-DOB were greater than those of NA or dobutamine (DOB) alone. The histological changes induced by endotoxin shock were not ameliorated by the administration of NOS inhibitors but instead appeared to be exacerbated to some degree.


CONCLUSIONS
NOS inhibitors combined with cathecholamines were thus suggested to be able to reduce the cathecolamine dosage in patients suffering from septic shock; They are thus considered to be hemodynamically effective agents.
Suga
Hiroyasu
H
Department of Emergency Medicine, Tokyo Women's Medical University Daini Hospital, 2-1-10 Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan.
Nakagawa
Takao
T
Soga
Yukihiro
Y
Deguchi
Yoshizumi
Y
Suzuki
Tadashi
T
Miyoshi
Norio
N
Imamura
Yoshiaki
Y
Fukuda
Masaru
M
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D004731:Endotoxins / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000187:drug effects; D012772:Shock, Septic / Q000188:drug therapy* / Q000209:etiology; D019323:omega-N-Methylarginine / Q000494:pharmacology / Q000627:therapeutic use*
D002395:Catecholamines; D004731:Endotoxins; D004791:Enzyme Inhibitors; D007550:Isothiuronium; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium