Inducible nitric oxide synthase inhibition improves intestinal microcirculatory oxygenation and CO2 balance during endotoxemia in pigs.
OBJECTIVE
We examined whether selective inhibition of inducible nitric oxide synthase (iNOS) promotes intestinal microvascular oxygenation (microPO2) and CO2 off-load after endotoxic shock.


METHODS
Prospective, controlled experimental study in a university animal research laboratory.


METHODS
13 domestic pigs.


METHODS
After baseline measurements shock was induced by 1 microg kg-1 h-1 endotoxin until mean arterial pressure fell below 60 mmHg. After 30 min in shock the animals were resuscitated with either fluid alone (control, n=6) or fluid and the iNOS inhibitor N-[3-(aminomethyl)benzyl]acetamidine hydrochloride (1400W, n=7). As final experimental intervention all animals received the nonselective NOS inhibitor L-NAME.


RESULTS
Systemic and regional hemodynamic and oxygenation parameters were measured at baseline, during endotoxemia and shock, hourly for 3 h of 1400W therapy, and 30 min after the final L-NAME administration. microPO2 was assessed by the Pd-porphyrin phosphorescence technique, and the arterial to intestinal PCO2 gap was determined by air tonometry. Endotoxemia and shock resulted in a decrease in ileal mucosal and serosal microPO2 and a rise in PCO2 gap. The combination of 1400W and fluid resuscitation, but not fluid alone, normalized both the serosal microPO2 and the intestinal PCO2 gap. Administration of L-NAME decreased cardiac output and oxygen delivery and intestinal microPO2 and blood flow in both groups.


CONCLUSIONS
Partial blockade of NO production by 1400W increased serosal microvascular oxygenation and decreased the intestinal CO2 gap. This findings are consistent with the idea that 1400W corrects pathological flow distribution and regional dysoxia within the intestinal wall following endotoxic shock.
Siegemund
Martin
M
Department of Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
van Bommel
Jasper
J
Schwarte
Lothar A
LA
Studer
Wolfgang
W
Girard
Thierry
T
Marsch
Stephan
S
Radermacher
Peter
P
Ince
Can
C
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007422:Intestines / Q000098:blood supply; D008833:Microcirculation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D010101:Oxygen Consumption; D013552:Swine
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester