First place winner of the Conrad Jobst Award in the gold medal paper competition. Nitric oxide synthase inhibitors N-monomethylarginine and aminoguanidine prevent the progressive and severe hypotension associated with a rat model of pancreatitis.
The objective of this study was to determine whether the observed vascular collapse and other pathologic features of severe pancreatitis may be related to the induction of nitric oxide synthase (NOS). The rat model of pancreatitis reported by Schmidt et al. was employed. Rats in the experimental groups received pretreatment with known NOS inhibitors, N-Monomethylarginine (NMMA) or Aminoguanidine (AG). Controls included sham-operated rats without pancreatic insult and a diseased control group which received pretreatment with normal saline (NS). Arterial blood pressure was continuously recorded with a femoral arterial catheter connected to a transducer and monitor. Fluid resuscitation for hypotension followed a strict protocol with the administration of 5.0 cc NS for sustained decreases in systolic blood pressure (SBP) below 90 mm Hg at 5-minute intervals. Laboratory parameters and histopathology confirmed the induction of pancreatitis, with 6 to 15-fold increases in serum amylase levels and an average of approximately 20% decrease in serum ionized Ca++ levels. Immunohistochemical studies of the pancreas revealed that pancreatic insult resulted in the induction of NOS. Rats in the saline control group (n = 5) became hypotensive (SBP less than 90 mm Hg) between 3 and 4 hours post pancreatic insult and required an average of 110.0 cc (3-4 x blood volume) of NS fluid resuscitation. Rats which were not resuscitated (n = 5) did not survive.(ABSTRACT TRUNCATED AT 250 WORDS)
Lomis
T J
TJ
Department of Surgery, York Hospital, Pennsylvania.
Siffring
C W
CW
Chalasani
S
S
Ziegler
D W
DW
Lentz
K E
KE
Stauffer
K E
KE
McMillan
A
A
Agarwal
N
N
Lowenstein
C J
CJ
Rhoads
J E
JE
D000681:Amylases / Q000097:blood; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002985:Clinical Protocols; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005440:Fluid Therapy; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007022:Hypotension / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009102:Multiple Organ Failure / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D010195:Pancreatitis / Q000150:complications*; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012720:Severity of Illness Index; D019323:omega-N-Methylarginine
D006146:Guanidines; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000681:Amylases; C004479:pimagedine; D002118:Calcium