Systemic and splanchnic hemodynamics following hemorrhage and volume restitution with Haemaccel in portal hypertensive rats: the effect of propranolol.
OBJECTIVE
Recently, we found in a portal hypertensive rat model that hemorrhage and volume restitution with Haemaccel, a low viscosity plasma expander, induced an increase in cardiac output and portal venous inflow. The present study was conducted to evaluate whether pretreatment with propranolol will attenuate these hyperdynamic changes.


METHODS
Portal hypertension was induced by portal vein constriction. Treatment was initiated 14--21 days later. Propranolol (30 mg/kg per day) or water were administered for 7 days via a gastric gavage. Under ketamine anesthesia, 18 h after the last given dose, blood was withdrawn at a constant rate of 0.3 mL/min for 15 min followed by a 15-min stabilization. Haemaccel was infused at the same rate and volume used for withdrawal. Hemodynamic measurements were performed after volume restitution in both groups by using radioactive microspheres.


RESULTS
Eight rats were studied in each group. In the propranolol-treated animals, portal venous inflow was decreased (2.4 +/- 0.8 vs 3.8 +/- 0.7 mL/min per 100 g bodyweight; P < 0.01), while splanchnic arteriolar and porto-collateral resistance were increased (52.8 +/- 21.0 vs 32.8 +/- 13.0 and 6.0 +/- 1.4 vs 4.1 +/- 0.7 mmHg x min x 100 g bodyweight/mL; P < 0.05, respectively). Cardiac output, mean arterial pressure, heart rate, total peripheral resistance and portal pressure were not significantly different between the two groups.


CONCLUSIONS
In this model, pretreatment with propranolol prevented the increase in portal venous inflow, which occurs following hemorrhage and volume restitution with Haemaccel. Although caution should be taken in extrapolating data from animal models to humans, our results suggest that volume replacement during a portal hypertensive-related bleeding episode may be safer in a patient treated with non-selective beta-adrenoreceptor antagonists.
Hilzenrat
N
N
Liver Research Laboratory and Department of Medicine B', The Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Arish
A
A
Yaari
A
A
Sikuler
E
E
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000503:physiopathology*; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D010952:Plasma Substitutes / Q000494:pharmacology*; D011097:Polygeline / Q000494:pharmacology*; D011168:Portal System / Q000503:physiopathology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D010952:Plasma Substitutes; D011097:Polygeline; D011433:Propranolol