Improvement of cardiac output and liver blood flow and reduction of pulmonary vascular resistance by intravenous infusion of L-arginine during the early reperfusion period in pig liver transplantation.
BACKGROUND
The release of liver arginase after orthotopic liver transplantation (OLT) causes a deficiency of L-arginine and nitrite in the plasma. This deficiency is possibly related to pulmonary hypertension and reduced hepatic blood flow, which are commonly observed in the immediate reperfusion period. The aim of this study was to evaluate the impact of L-arginine supplementation on metabolic and hemodynamic parameters during liver reperfusion after OLT in pigs.


METHODS
Thirteen pig OLTs (control group, n=6; arginine group, n=7) were performed by a standard technique. Cold ischemic time was 20 hr. L-Arginine was infused at a dosage of 500 mg/kg body weight into the donor pigs (30 min before liver explantation) and also into the recipients (over a period of 3 hr from the beginning of the reperfusion period). At the end of the experimental study, the pigs were killed with an overdose of potassium.


RESULTS
In the control group, liver revascularization increased plasma arginase concentrations (+615%) and reduced plasma levels of L-arginine (-87%), nitrite (-82%), and nitrate (-53%). Infusion of L-arginine increased plasma levels of L-arginine from 94+/-21 micromol/L to 1674+/-252 micromol/L (P<0.001), L-ornithine from 46+/-8 micromol/L to 2215+/-465 micromol/L (P<0.001), and L-citrulline from 58+/-8 micromol/L to 116+/-34 micromol/L (P<0.001), but had no effect on plasma levels of nitrite and nitrate. Administration of L-arginine in the donor pigs did not produce any systemic or organ-specific hemodynamic alterations. Infusion of L-arginine into the recipient pigs improved cardiac performance (increase in heart rate [+61%, P=0.017] and cardiac index [+53%, P=0.005], reduction in pulmonary capillary wedge pressure [-54%, P=0.014]). Moreover L-arginine infusion increased oxygen consumption (+65%, P=0.003), reduced pulmonary vascular resistance index (P=0.001), stimulated portal venous blood flow (P=0.014), and elevated body temperature during the reperfusion period (P=0.007).


CONCLUSIONS
From these data, we conclude that the infusion of L-arginine during OLT improves the hemodynamic performance of the heart, lung, and liver.
Längle
F
F
Department of Surgery, University of Vienna, Austria.
Steininger
R
R
Waldmann
E
E
Grünberger
T
T
Benditte
H
H
Mittlböck
M
M
Soliman
T
T
Schindl
M
M
Windberger
U
U
Mühlbacher
F
F
Roth
E
E
D000818:Animals; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D002302:Cardiac Output / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D007262:Infusions, Intravenous; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000097:blood; D015427:Reperfusion Injury / Q000188:drug therapy; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects*
D009566:Nitrates; D009573:Nitrites; D001120:Arginine; D010100:Oxygen