FUROSEMIDE FOR PORTAL HYPERTENSION. AN OLD DRUGFOR A NEW INDICATION? J.M. Cereda, D. Roulot, A. Braillon, R. Moreau, A. Koshy, D. Lebrec INSERM U24, HSpital Beaujon, Clichy, France. In patients with cirrhosis, it has been demonstrated that body fluid volume and the degree of portal hypertension are correlated. Hence, a reduction of blood volume by furosemide could decrease portal presure and thereby be useful in the treatment of portal hypertension. Therefore, we studied splanchnic and systemic hemodynamics, before and I h after i.v. administration of furosemide (0.75 mg/kg) in I0 patients with cirrhosis. Furosemide significantly increased hemoglogin from 12.4 to 13.0 mg/L and patients passed more than I L of urine within the 3 h following furosemide administration; these findings indicate that blood volume decreased after furosemide administration. Cardiac output significantly decreased from 6.6 ± 2.3 to 5.5 ± 2.2 L/min while arterial pressure and heart rate did not change significantly; therefore, systemic vascular resistance increased. Furosemide significantly decreased wedged hepatic venous pressure from 31.1 ± 6.2 to 27.7 ± 5.2 mmHg but not free hepatic venous pressure (9.0 ± 4.4 vs 8.2 ± 4.6, respectively). Accordingly, hepatic venous pressure gradient significantly decreased from 22.1 ± 5.4 to 19.5 ± 4.0 mmHg. Azygos blood flow significantly decreased from 0.40 ± 0.17 to 0.31 ± 0.13 L/min as well as hepatic blood flow from 1.49 ± 0.50 to 0.82 ± 0.30 L/min, respectively. It is suggested that this effects of furosemide on splanchnic circulation is due to a reflex vasconstriction in response to the decrease in blood volume. These findings show that blood volume change is a new approch to modulate splanchnic hemodynamics in patients with cirrhosis. Further studies are necessary to investigate the potential beneficial effect of furosemide in the treatment of the complications of portal hypertension. EFFECT OF LIVER TRANSPLANTATION ON BASAL HKMODYNA/~CS AND ON RESPONSE TO HEMOgRHACE IN AWAKE RATS. P. Chaland, D. Lebrec, A. Braillon, C. Gaudin, C. Girod, H. Bismuth, J.P. Benhamou INSERM U24, HSpital Beaujon, Clichy and Unit~ de Chirurgie H~patobiliaire, HSpital Paul Brousse, Villejuif, France Splanchnic vascular bed plays a major role in cardiovascular homeostasis. Therefore, circulation control might be compromised after liver transplantation through removal of afference and efference of hepatic nerves. Hence, hemodynamic studies (radioactive microsphere method in conscious rats) were performed i wk after either liver transplantation (n=5) or sham operation (various vessels were only clamped, n=8). Measurements were repeated after a 2 ml/100 g body wt hemorrhage at the nadir of arterial pressure changes. Transplanted rats, when compared to sham operated rats, exhibited a significant increase in cardiac index (65 ± 7 vs 51 ± 9 ml.min-l.100 g-i body wt) and decrease in mean arterial pressure (92 ± 9 vs 107 ± I0 mmHg); blood flows in splanchnic and vital organs were normal. These changes were associated with an increase in plasma epinephrine without change in norepinephrine concentration. After hemorrhage, arterial pressure significantly decreased to 78 mmHg in both groups with a trend for a lesser decrease in cardiac output in transplanted rats than in sham operated (-27 vs -45%, respectively). The fraction of cardiac output to portal vascular bed significantly decreased from 18 to 8% in sham operated rats, whereas, in transplanted rats this fraction was unchanged. Liver denervation was confirmed by undetectable concentration of liver tissue norepinephrine. It is concluded that rats with liver transplantation exhibit: a) a hyperkinetic circulatory syndrome, probably stress related; b) an improved tolerance to hemorrhage, probably due to the lack of splanchnic vasoconstriction improving venous return. Sl13

Furosemide for portal hypertension. An old drug for a new indication?

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Page 1: Furosemide for portal hypertension. An old drug for a new indication?

FUROSEMIDE FOR PORTAL HYPERTENSION. AN OLD DRUGFOR A NEW INDICATION? J.M. Cereda, D. Roulot, A. Braillon, R. Moreau, A. Koshy, D. Lebrec INSERM U24, HSpital Beaujon, Clichy, France.

In patients with cirrhosis, it has been demonstrated that body fluid volume and the degree of portal hypertension are correlated. Hence, a reduction of blood volume by furosemide could decrease portal presure and thereby be useful in the treatment of portal hypertension.

Therefore, we studied splanchnic and systemic hemodynamics, before and I h after i.v. administration of furosemide (0.75 mg/kg) in I0 patients with cirrhosis.

Furosemide significantly increased hemoglogin from 12.4 to 13.0 mg/L and patients passed more than I L of urine within the 3 h following furosemide administration; these findings indicate that blood volume decreased after furosemide administration. Cardiac output significantly decreased from 6.6 ± 2.3 to 5.5 ± 2.2 L/min while arterial pressure and heart rate did not change significantly; therefore, systemic vascular resistance increased. Furosemide significantly decreased wedged hepatic venous pressure from 31.1 ± 6.2 to 27.7 ± 5.2 mmHg but not free hepatic venous pressure (9.0 ± 4.4 vs 8.2 ± 4.6, respectively). Accordingly, hepatic venous pressure gradient significantly decreased from 22.1 ± 5.4 to 19.5 ± 4.0 mmHg. Azygos blood flow significantly decreased from 0.40 ± 0.17 to 0.31 ± 0.13 L/min as well as hepatic blood flow from 1.49 ± 0.50 to 0.82 ± 0.30 L/min, respectively. It is suggested that this effects of furosemide on splanchnic circulation is due to a reflex vasconstriction in response to the decrease in blood volume.

These findings show that blood volume change is a new approch to modulate splanchnic hemodynamics in patients with cirrhosis. Further studies are necessary to investigate the potential beneficial effect of furosemide in the treatment of the complications of portal hypertension.

EFFECT OF LIVER TRANSPLANTATION ON BASAL HKMODYNA/~CS AND ON RESPONSE TO HEMOgRHACE IN AWAKE RATS. P. Chaland, D. Lebrec, A. Braillon, C. Gaudin, C. Girod, H. Bismuth, J.P. Benhamou INSERM U24, HSpital Beaujon, Clichy and Unit~ de Chirurgie H~patobiliaire, HSpital Paul Brousse, Villejuif, France

Splanchnic vascular bed plays a major role in cardiovascular homeostasis. Therefore, circulation control might be compromised after liver transplantation through removal of afference and efference of hepatic nerves.

Hence, hemodynamic studies (radioactive microsphere method in conscious rats) were performed i wk after either liver transplantation (n=5) or sham operation (various vessels were only clamped, n=8). Measurements were repeated after a 2 ml/100 g body wt hemorrhage at the nadir of arterial pressure changes.

Transplanted rats, when compared to sham operated rats, exhibited a significant increase in cardiac index (65 ± 7 vs 51 ± 9 ml.min-l.100 g-i body wt) and decrease in mean arterial pressure (92 ± 9 vs 107 ± I0 mmHg); blood flows in splanchnic and vital organs were normal. These changes were associated with an increase in plasma epinephrine without change in norepinephrine concentration.

After hemorrhage, arterial pressure significantly decreased to 78 mmHg in both groups with a trend for a lesser decrease in cardiac output in transplanted rats than in sham operated (-27 vs -45%, respectively). The fraction of cardiac output to portal vascular bed significantly decreased from 18 to 8% in sham operated rats, whereas, in transplanted rats this fraction was unchanged. Liver denervation was confirmed by undetectable concentration of liver tissue norepinephrine.

It is concluded that rats with liver transplantation exhibit: a) a hyperkinetic circulatory syndrome, probably stress related; b) an improved tolerance to hemorrhage, probably due to the lack of splanchnic vasoconstriction improving venous return.

Sl13