A new approach in the treatment of hypotension in human septic shock by NG-monomethyl-L-arginine, an inhibitor of the nitric oxide synthetase.
NG-monomethyl-L-arginine (L-NMMA) is an inhibitor of the enzyme nitric-oxide-synthetase. Nitric oxide (NO), produced by endothelial and vascular cells regulates physiological vascular tone, blood pressure and tissue perfusion via guanylate-cyclase and cGMP. In an advanced stage of therapy resistant septic shock in response to inflammatory mediators, NO is overproduced. This leads to vasodilatation, a fall in systemic blood pressure and an attenuated vasoconstriction-response to sympathetic-stimuli. Two episodes of severe and prolonged hypotension in a patient with sepsis were successfully treated twice by bolus therapy of L-NMMA within 4 weeks. On both occasions blood pressure was reversed to normal and the continuous use of high doses of catecholamines were stopped. In contrast to the immediate response of blood pressure, heart rate and central venous pressure remained stable. Cardiac output dropped to 68% and PaO2 increased. These findings indicate that NO-synthetase-inhibitors may be of value in the therapy of human septic shock.
Schilling
J
J
Department of Surgery, University Hospital Zürich, Switzerland.
Cakmakci
M
M
Bättig
U
U
Geroulanos
S
S
D000328:Adult; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003131:Combined Modality Therapy; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007022:Hypotension / Q000188:drug therapy*; D008297:Male; D009336:Necrosis; D019001:Nitric Oxide Synthase; D010195:Pancreatitis / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D012008:Recurrence; D012772:Shock, Septic / Q000188:drug therapy*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases