Hemodynamic and hepatic microcirculational changes in endotoxemic rats treated with different NOS inhibitors.
OBJECTIVE
Severe septic shock may produce hypotension, which is due to the vasodilatational effect of nitric oxide. The effects of different nitric oxide synthase inhibitors on the hemodynamic and hepatic microcirculation of the endotoxemic rats were studied.


METHODS
A prospective controlled study was performed. Eighteen Sprague-Dawley male rats (250-300 g) were anesthetized and studied. The rats were divided into three groups. The rats in group A (n = 6) were injected with lipopolysaccharide (50 mg/kg BW) and L-NAME (5 mg/kg BW). The rats in group B (n = 6) were injected with the same dose of lipopolysaccharide and aminoguanidine (400 mumole/kg BW). The rats in group C rats (n = 6) were injected with same dose of lipopolysaccharide and normal saline as a control. The rats were cannulated with femoral arterial, venous, and jugular venous catheters. Cardiac output was measured using a thermodilutional method, and liver sinusoidal microcirculation was measured with Laser Doppler Flowmetry. The cardiac output, stroke volume, heart rate, blood pressure, and microcirculational flux of the liver in the three groups were measured and compared at 0, 20, 40, 60 and 80 minutes after injection.


RESULTS
The rats of group A showed significant decrease of their cardiac output, stroke volume and hepatic microcirculation after the drugs were infused though their blood pressure increased. The rats of group B showed decrease of their blood pressure and stroke volume initially, but no significant change of their cardiac output and hepatic microcirculation. At the 80th min, the rats of group B had the significantly highest cardiac output, stroke volume and hepatic microcirculation among three groups.


CONCLUSIONS
The aminoguanidine prevents the hypotensive effect as well as L-NAME during severe sepsis, but it can maintain cardiac output, stroke volume and hepatic microcirculation better than L-NAME.
Hwang
Tsann-Long
TL
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
Yeh
Chin-Cheh
CC
D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology*; D008102:Liver Circulation / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000209:etiology / Q000503:physiopathology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D006146:Guanidines; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester