Hemodynamic effects of a combination of vasopressin and ketanserin in patients with hepatitis b-related cirrhosis.

We measured the hemodynamic effects of intravenous vasopressin, ketanserin (a 5-hydroxytryptamine-2 receptor blocker), and vasopressin plus ketanserin in 33 patients with hepatitis B-related cirrhosis. Thirteen patients received vasopressin alone (0.66 units/min), ten patients ketanserin alone (10 mg), and ten patients vasopressin followed by vasopressin plus ketanserin. Vasopressin alone reduced the hepatic venous pressure gradient (from 18 +/- 5, mean +/- S.D., to 9 +/- 3 mmHg, p less than 0.0001) and cardiac output (p less than 0.0001), but increased mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.0001), pulmonary capillary wedge pressure (p less than 0.0001), and systemic vascular resistance (p less than 0.001). There was no significant change in heart rate. Ketanserin alone produced a significant fall in the hepatic venous pressure gradient (from 16 +/- 4 to 13 +/- 3 mmHg, p less than 0.0001), mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.005), and pulmonary capillary wedge pressure (p less than 0.005). Heart rate, cardiac output, and systemic vascular resistance were not significantly changed. The addition of ketanserin to vasopressin corrected most of the systemic hemodynamic disturbances produced by vasopressin. This combination did not lead to a further reduction in the hepatic venous pressure gradient. We conclude that intravenous ketanserin reduces portal pressure in patients with hepatitis B-related cirrhosis. The addition of ketanserin to vasopressin improves the detrimental systemic hemodynamic effects of vasopressin without further reducing the portal pressure.     

Systemic and portal haemodynamic changes following triglycyllysine vasopressin plus nitroglycerin administration in patients with hepatitis B-related cirrhosis

We measured the haemodynamic changes following triglycyllysine vasopressin administration and after addition of nitroglycerin in twelve patients with portal hypertension due to hepatitis B-related cirrhosis. A bolus i.v. injection of triglycyllysine vasopressin at a dose of 2 mg reduced the hepatic venous pressure gradient from 18.5 +/- 3.7 (mean +/- S.D.) to 15.6 +/- 4.0 mmHg, p less than 0.001. However, the cardiac index decreased from 4.8 +/- 1.0 to 3.7 +/- 0.8 l/min m2, p less than 0.001; the heart rate decreased from 79 +/- 15 to 71 +/- 13, p less than 0.01; the right atrial pressure increased from 3.2 +/- 1.9 to 5.3 +/- 2.3 mmHg, p less than 0.001; the mean arterial pressure increased from 92 +/- 13 to 103 +/- 13 mmHg, p less than 0.05; and the systemic vascular resistance rose from 939 +/- 182 to 1367 +/- 310 dyn/s cm-5, p less than 0.001. Furthermore, both mean pulmonary arterial pressure and pulmonary capillary wedge pressure showed a significant increase following triglycyllysine vasopressin administration as compared with baseline values (p less than 0.005). The addition of sublingual nitroglycerin at a dose of 0.6 mg returned all the systemic haemodynamic parameters to baseline levels. On the other hand, nitroglycerin administration caused no further change in the hepatic venous pressure gradient. We concluded that although triglycyllysine vasopressin significantly reduced portal pressure in patients with hepatitis B-related cirrhosis, it produced untoward systemic haemodynamic changes similar to those seen with vasopressin. The addition of nitroglycerin improved the detrimental systemic haemodynamic effects produced by triglycyllysine vasopressin without further reducing the hepatic venous pressure gradient.     

Nitroglycerin improves the hemodynamic response to vasopressin in portal hypertension

This study was designed to investigate whether the addition of nitroglycerin to vasopressin infusion could avoid the deleterious systemic effects of vasopressin while maintaining or enhancing the therapeutic benefits of portal pressure reduction. The effect of nitroglycerin on splanchnic and systemic hemodynamics was studied in cirrhotic patients and portal hypertensive dogs receiving i.v. vasopressin. During i.v vasopressin infusion (0.4 units per min), the cardiac output decreased in patients by 14% from 7.6 +/- 0.9 (mean +/- S.E.) to 6.5 +/- 0.7 liters per min, p less than 0.01, the mean arterial pressure increased 21% from 87 +/- 2 to 105 +/- 4, p less than 0.01, and the heart rate decreased 11% from 79 +/- 3 to 71 +/- 3, p less than 0.01. The administration of sublingual nitroglycerin (0.4 mg) returned all the systemic hemodynamic parameters to baseline values. In dogs, vasopressin infusion significantly reduced portal pressure and flow while increasing portal venous resistance. Nitroglycerin when added to the vasopressin infusion reduced portal venous resistance and further decreased portal pressure in dogs. In patients, vasopressin reduced the hepatic blood flow (44%), wedged hepatic venous pressure (11%), and the gradient between wedged and free hepatic venous pressures (23%). Nitroglycerin administration caused a further reduction of the wedged hepatic venous pressure (23.6 +/- 2.3 to 21.1 +/- 2.0, 11%, p less than 0.01). There was a small but not significant further decline (7%) in the hepatic venous pressure gradient. These results provide evidence that the addition of nitroglycerin to an i.v. infusion of vasopressin reversed the detrimental effects of vasopressin while preserving the beneficial effects.     

Portohepatic Pressures, Hepatic Function, and Blood Gases in the Combination of Nitroglycerin and Vasopressin: Search for Additive Effects in Cirrhotic Portal Hypertension

We studied the effects of the combination of nitroglycerin and vasopressin on portohepatic hemodynamics, hepatic function, and blood gases in nine patients with cirrhosis and portal hypertension. Vasopressin infusion at a dose of 0.4 U/min caused a significant fall in portal pressure, which is evaluated by portal venous pressure gradient (-34%, p less than 0.01), associated with a decrease in hepatic perfusion (-33%, p less than 0.01) and intrinsic clearance (-20%, p less than 0.01) after 30 min. The arterial oxygenation, however, was not modified (paO2; from 73 +/- 8 to 72 +/- 7 mm Hg, NS). Nitroglycerin infusion at a dose of 100 micrograms/min was then administered for 20 min. The addition of nitroglycerin produced a further reduction in free portal venous pressure (-12%, p less than 0.01), but this was not associated with a significant improvement in both hepatic perfusion (+16%, NS) and intrinsic clearance (-7%, NS). In addition, there was a significant fall in arterial oxygenation (paO2; from 72 +/- 7 to 59 +/- 5 mm Hg, p less than 0.01). We conclude that the addition of nitroglycerin to vasopressin has a beneficial effect on free portal venous pressure, but does not have hepatic benefit. Moreover, sufficient care must be taken, when treating portal hypertension with this combination, to avoid arterial hypoxemia.     

Portal hemodynamics during nitroglycerin administration in cirrhotic patients

Nitroglycerin is a potent venous dilator and a mild arterial vasodilator that has been shown to improve the hemodynamic response to vasopressin in portal hypertensive patients and to decrease portal pressure in experimental animals. In order to determine the effect of nitroglycerin on portal venous hemodynamics, we studied 11 patients with alcoholic cirrhosis before and during the administration of sublingual nitroglycerin (0.4 and 0.6 mg). The hepatic venous pressure gradient (which was obtained by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure) decreased from 17.9 +/- 6.5 mm Hg (mean +/- S.D.) to 15.1 +/- 5.1 mm Hg (p less than 0.02) at the peak of the effect, which occurred from 2 to 12 min after nitroglycerin administration. The mean arterial pressure was reduced from 96 +/- 10 mm Hg to a peak decrease of 76 +/- 18 mmHg (p less than 0.001). The peak change in the hepatic venous pressure gradient induced by nitroglycerin correlated directly with the peak change in mean arterial pressure (r = 0.79, p less than 0.01). There was a moderate increase in heart rate in response to the decrease in blood pressure (73 +/- 15 to 83 +/- 15 beats per min, p less than 0.001). Two of the 11 patients did not reduce their hepatic venous pressure gradient after 0.6 mg nitroglycerin. Reductions in portal pressure were observed with both increases and moderate decreases in azygos blood flow, suggesting that, as observed in experimental animals, the portal-pressure-reducing effect of nitroglycerin could be due to two different and independent mechanisms, a reduction in portal blood flow or portal-collateral vasodilatation.     

Long-term haemodynamic effects of isosorbide 5-mononitrate in patients with cirrhosis and portal hypertension

Since it is well known that pharmacological tolerance may rapidly occur on continuous administration of organic nitrates, in this study we attempted to investigate whether isosorbide 5-mononitrate (Is-5-Mn), a long-acting vasodilator that decreases portal pressure in acute haemodynamic studies, causes a significant reduction in portal pressure following long-term oral administration. Eleven patients with cirrhosis and portal hypertension were studied prior to and following 3 months of continuous administration of Is-5-Mn, 40 mg b.i.d. The hepatic venous pressure gradient decreased significantly following long-term Is-5-Mn treatment (from 18.6 +/- 3.4 to 17.2 +/- 3.1 mmHg; p less than 0.01). This was associated with a moderate increase in hepatic blood flow. Azygos blood flow and portal blood flow did not change. There were significant decreases in mean arterial pressure (from 89.4 +/- 13.7 to 82.6 +/- 10.8 mmHg; p less than 0.05) and heart rate (from 77 +/- 10 to 73 +/- 10 b.p.m.; p less than 0.05). In contrast, there were no changes in portal pressure or hepatic and systemic haemodynamics in a control group of 17 patients receiving placebo. Repeated nitroglycerin cross-tolerance studies in five patients receiving Is-5-Mn indicated the development of a partial pharmacological tolerance (as shown by blunted haemodynamic response to nitroglycerin after long-term Is-5-Mn administration). This study shows that Is-5-Mn continues to cause a significant decrease in portal pressure during long-term therapy, with only partial pharmacological tolerance to this compound.     

Hemodynamic effects of the administration of terlipressin alone or combined with nitroglycerin in patients with cirrhosis]

Terlipressin (Glypressin), a synthetic analog of vasopressin, induces arteriolar vasoconstriction which causes both a portal hypotensive effect and certain side-effects on the systemic circulation (elevated arterial pressure and reduced cardiac output). The combination of nitroglycerin with terlipressin might accentuate the portal hypotensive effect and prevent the side-effects on the systemic circulation. The aim of this study was to examine the systemic and splanchnic hemodynamic responses to terlipressin administered alone or combined with nitroglycerin in patients with cirrhosis. Systemic and splanchnic hemodynamics were measured before and 1 h after a bolus of terlipressin (1 to 2 mg IV) given alone (n = 10) or in association with nitroglycerin infusion (25 micrograms/min, n = 9). Terlipressin alone significantly increased the arterial pressure by 21%, systemic vascular resistance by 60%, and significantly decreased cardiac output by 23%. The right atrial and pulmonary pressures significantly increased and the wedged hepatic venous pressure and hepatic venous pressure gradient significantly decreased by 8% and 16%, respectively. The combined therapy decreased the cardiac output by 20%, but did not significantly modify the other systemic and splanchnic hemodynamic values. No significant differences were found between terlipressin and the combined therapy concerning changes in wedged hepatic venous pressure or hepatic venous pressure gradient. We conclude that in patients with cirrhosis, nitroglycerin prevents the deleterious vasoconstrictor and vasopressor effects of terlipressin. However, the combined therapy, as terlipressin alone, decreases the cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative haemodynamic effects of transdermal vs intravenous nitroglycerin in acute myocardial infarction with elevated pulmonary artery wedge pressure

The comparative haemodynamic effects of transdermal and intravenous nitroglycerin were evaluated in 16 patients with haemodynamic and radiographic left heart failure following a recent myocardial infarction. After the control period patients were randomized to transdermal (10 mg(24 h)-1) or intravenous (mean dose: 40 +/- 9 micrograms min-1) nitroglycerin. Haemodynamic parameters were recorded after 0.5,1,2,6,12,18 and 24 h during administration of the drug and 2 h after drug discontinuation. After the washout period the alternate system of nitroglycerin administration was adopted, according to a cross-over design. No differences were found in baseline measurements. Transdermal nitroglycerin reduced the pulmonary artery wedge pressure after 0.5 h (from 21 +/- 5 to 16 +/- 5 mmHg; P less than 0.05). The peak effect occurred at 2 h (12 +/- 5 mmHg). The improvement was sustained over 24 h. Transdermal nitroglycerin also significantly reduced mean pulmonary arterial and right atrial pressures (from 28 +/- 3 to 20 +/- 5 mmHg and from 6 +/- 3 to 2 +/- 2 mmHg at peak effect, respectively). Cardiac index increased from 2.5 +/- 0.6 to 2.8 +/- 0.8 l min-1 m-2 (P less than 0.05). There was no change in heart rate. Similar haemodynamic changes were observed after the intravenous infusion of nitroglycerin. Thus transdermal nitroglycerin is a safe and effective treatment of acute myocardial infarction with signs of left ventricular failure when an intravenous nitroglycerin infusion cannot be properly implemented.     

Dose-response relation of intravenous enoximone in congestive cardiac insufficiency

Enoximone (MDL 17043) is a new generation inotropic drug which acts by inhibiting phosphodiesterase and is endowed with both inotropic and vasodilator properties. The purpose of this study, which involved 23 patients aged from 18 to 75 years in NYHA class III or IV and with evidence of severe haemodynamic disturbances (cardiac index below 2.5 1/mn/m2, pulmonary wedge pressure above 15 mmHg), was to evaluate the acute haemodynamic responses to doses of enoximone that ranged from 0.25 to 2.50 mg/kg administered by bolus intravenous injection. Heart failure was either of ischaemic origin (6 cases) or idiopathic (10 cases) or due to various causes (7 cases). Group A patients (n = 11) received the drug in low doses (less than or equal to 1 mg/kg) as opposed to group B patients (n = 12) who were given high doses (greater than 1 mg/kg). Results were evaluated from the amplitude and duration of the haemodynamic response at maximum effect time (30 min). The following parameters were measured: cardiac index, pulmonary wedge pressure, systemic vascular resistance, mean arterial pressure and heart rate. Cardiac index and pulmonary wedge pressure were significantly improved in both groups (P less than 0.005): cardiac index +39 p. 100 in group A, +55 p. 100 in group B; pulmonary wedge pressure -36 p. 100 in group A, -48 p. 100 in group B; systemic vascular resistance -46 p. 100 in group B. Heart rate and arterial pressure were not significantly altered. The duration of response was 1 to 3 hours in group A patients and 4 to 8 hours in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intraportal nitroglycerin on portosystemic hemodynamics in patients with cirrhosis: comparison with i.v. route

We observed 18 patients with portal hypertension and cirrhosis to compare the effects of intraportal nitroglycerin on portosystemic hemodynamics with the i.v. route. Patients received 1 microgram/kg/min of nitroglycerin intravenously (n = 9) or the same dose of nitroglycerin directly into the portal vein (n = 9). Both routes of nitroglycerin significantly reduced mean arterial pressure and this effect was higher with the i.v. route (-28.0% versus -19.3%, p less than 0.02). The portal pressure, as evaluated by the portal venous pressure gradient or hepatic venous pressure gradient, was also reduced significantly in both groups. The fall in portal pressure was higher in the intraportal group, but the difference was not significant (intravenous versus intraportal, -23.9 versus -25.1% in portal venous pressure gradient, -25.2 versus -33.4% in hepatic venous pressure gradient). The hepatic blood flow was maintained despite the significant reduction in portal pressure by both routes. These results indicate that intraportal nitroglycerin decreases portal pressure with a smaller effect on systemic hemodynamics than the i.v. route. We conclude that the oral administration of nitroglycerin, which is a pathway equivalent to the intraportal route, may be more useful than the i.v. (i.e., sublingual) route in the treatment of portal hypertension.     

The hypotensive effect of oral nitroglycerin on portal venous pressure in patients with cirrhotic portal hypertension

Abstract Nitroglycerin was administered orally to seven patients with cirrhosis and portal hypertension, to determine whether portal venous pressure (PVP) may be lowered without the systemic effects associated with its intravenous or sublingual use. PVP was measured via direct cannulation of the portal vein transhepatically using a Chiba needle. PVP decreased from 29 (s.d. = 4) to 22.7 (s.d. = 3.7) mmHg (22% mean fall) following 1.2 mg nitroglycerin with onset 7–15 min following ingestion, and the response persisted for up to 150 min. This was not associated with headache in any patient. Although a decrease in blood pressure was seen in most patients, this temporally followed the fall in PVP suggesting that it was a secondary response. Sublingual nitroglycerin was given to two patients without change in PVP yet both experienced severe headache. These findings support the hypothesis that oral nitroglycerin is delivered differentially to the portal venous bed with differential effects on PVP. Further studies are needed to evaluate this agent and this strategy for their potential role in long-term control of portal pressure.     

Additive effects of dobutamine and amrinone on myocardial contractility and ventricular performance in patients with severe heart failure

The effects of amrinone, dobutamine, and a combination of the two drugs on peak positive left ventricular dP/dt and left ventricular performance were evaluated in 11 patients with chronic congestive heart failure. When administered alone, both dobutamine (10.9 micrograms/kg/min) and intravenous amrinone (1.9 mg/kg/min) significantly increased left ventricular dP/dt and performance. When compared with dobutamine alone, the addition of amrinone resulted in further increases in left ventricular dP/dt and cardiac index (to 1319 +/- 419 from 1202 +/- 376 mm Hg/sec, p less than .002, and to 3.56 +/- 0.78 from 3.04 +/- 0.67 liters/min/m2, p less than .01, respectively). The combination also induced a further reduction in left ventricular end-diastolic pressure (to 15.3 +/- 11.3 from 18.2 +/- 10.3 mm Hg, p less than .05) when compared with amrinone alone. The combination of dobutamine and amrinone increased heart rate slightly when compared with either drug alone, but did not further reduce systemic arterial pressure when compared with amrinone alone. The dose-response curve of left ventricular dP/dt and performance during titration of dobutamine with and without the addition of intravenous amrinone was evaluated in seven patients. The addition of amrinone to any dose of dobutamine produced higher cardiac index and lower systemic vascular resistance than dobutamine or amrinone alone. Thus, when compared with dobutamine alone in patients with chronic congestive heart failure, the addition of intravenous amrinone to dobutamine results in an additive improvement in left ventricular performance throughout the dose range.     

Effects of vasopressin on haemodynamics in portal hypertensive rats receiving clonidine

Abstract: The effects of clonidine, vasopressin or a combination of both substances on splanchnic and systemic haemodynamics were measured in conscious rats with portal vein stenosis. Clonidine alone significantly decreased portal pressure, portal tributary blood flow and cardiac index, but did not change arterial pressure. Vasopressin alone significantly increased arterial pressure and significantly decreased portal pressure, portal tributary blood flow and cardiac index. Changes in portal tributary blood flow, arterial pressure and cardiac index were significantly higher with vasopressin than with clonidine alone. Vasopressin infusion in rats pretreated with clonidine significantly increased arterial pressure and significantly decreased portal pressure, portal tributary blood flow and cardiac index. Changes in arterial and portal pressures and portal tributary blood flow were significantly higher with combined therapy than with clonidine alone. Changes in arterial and portal pressures and portal tributary blood flow did not differ between combined therapy and vasopressin alone. Changes in cardiac index were significantly higher with combined therapy than with clonidine or vasopressin alone. Hepatic artery blood flow was not affected by either clonidine or vasopressin but significantly declined with combined therapy. In conclusion, this study suggests that a combination of vasopressin and clonidine accentuates the portal hypotensive action of clonidine but not the action of vasopressin. Moreover, this study suggests that a combination of vasopressin and clonidine may have deleterious effects on systemic and hepatic artery vascular beds.     

Effects of somatostatin on hepatic and systemic hemodynamics in patients with cirrhosis of the liver: comparison with vasopressin

The effects of somatostatin on hepatic and systemic hemodynamics were investigated in 17 patients with chronic liver disease and severe portal hypertension during the hemodynamic assessment before elective portal-systemic shunt surgery. The injection of somatostatin (1.0 microgram/kg) caused a decrease of the wedged hepatic venous pressure, from 19.5 +/- SE 1.3 mmHg to 14.0 +/- 1.0 mmHg (p < 0.001). Injections of 0.5 and 2.0 microgram/kg had similar effects. During somatostatin infusion at a constant rate (7.5 microgram/min) there was a reduction of the wedged hepatic venous pressure (-17.0%, p < 0.001) and estimated hepatic blood flow (-17.5%, p < 0.01) but no significant changes in hepatic vascular resistance, cardiac output, systemic blood pressure, peripheral resistance, or cardiopulmonary pressures. In marked contrast to the selective action of somatostatin on splanchnic hemodynamics, vasopressin infusion (0.3 U/min) in 6 patients caused not only significant falls in the wedged hepatic venous pressure and estimated hepatic blood flow (-28.6% and -31.8%, respectively), but also significant changes in the systemic circulation, including a reduction of the cardiac output (-19.7%, p < 0.01) and heart rate (-12.6%, p < 0.01) and an increase of the arterial pressure (+18.8%, p < 0.01) and peripheral resistance (+46.8%, p < 0.01). These results show that somatostatin effectively reduces hepatic blood flow and portal pressure in patients with cirrhosis and severe portal hypertension, without altering the systemic circulation.     

Effects of Intravenous Nitroglycerin and Nitroglycerin and Metoclopramide on Intravariceal Pressure: A Double Blind, Randomized Study

Objective : Effective and safe reduction of variceal pressure by pharmacological means. Methtds : Twenty patients with portal hypertension and large esophagcal varices. Ten patients received i.v . nitroglycerin (300 μg-bolus) and an equal number received a combination of i.v . nitroglycerin (150 μg) and metoclopramide (20-mg bolus). Continuous measurement of variceal pressure and systemic hemodynamics was carried out. Results : Compared with the baseline, the variceal pressure was reduced at 10 min after injection of 300 μg nitroglycerin (22.3 ± 7.9 vs . 17.3 ± 7 mm Hg, p , not significant); the percentage reduction was 23.5 ± 15.8%. With the combination of low dose (150 μ) nitroglycerin and metoclopramide, variceal pressure significantly decreased from 23.1 ± 4.7 to 15.9 ± 5.9 mm Hg ( p < 0.01) (a reduction of 29.5 ± 24.1%), There was no significant alteration in the heart rate or mean arterial pressure with either regimen, Conclusiuns : Our results suggest that a combination of i.v . metoclopramide and low-dose nitroglycerin reduces variceal pressure more effectively man high-dose nitroglycerin used alone. This combination should be further evaluated in the control of acute variceal bleeding.     

Intestinal microvascular adaptation to chronic portal hypertension in the rat

Microvascular pressures, diameters, and flow velocities were measured in the small intestine of rats with chronic stenosis of the portal vein. Ten days after portal vein stenosis, portal venous pressure increased (13.8 +/- 0.4 mmHg vs, 7.3 +/- 0.5 mmHg; p less than 0.05) whereas systemic arterial pressure decreased (94.2 +/- 2.0 mmHg vs. 106.5 +/- 1.6 mmHg; p less than 0.05). Red blood cell centerline velocity, measured in first-order arterioles, was significantly higher in portal hypertensive rats (24.3 +/- 1.2 mm/s vs. 19.6 +/- 1.3 mm/s), yet there was no significant change in the diameters of these vessels. Microvascular pressures and diameters of first- and second-order arterioles were not different between control and portal hypertensive rats. However, both pressure (34.3 +/- 2.7 mmHg vs. 28.0 +/- 1.8 mmHg) and diameter (30.4 +/- 0.6 microns vs. 21.4 +/- 2.1 microns) were significantly increased in the third-order arterioles of portal hypertensive rats. A consistent elevation in pressure was observed throughout the distal segments (capillaries to first-order venules) of the intestinal microcirculation of portal hypertensive rats. The results of these studies indicate that the increased intestinal vascular pressures associated with chronic portal hypertension result from a combination of reduced arteriolar resistance and venous congestion.     

The effect of the combination of nitroglycerin and propranolol on splanchnic and systemic hemodynamics in a portal hypertensive rat model

Present investigations support major contributions from increases in both portal blood flow and portal vascular resistance in the mechanism that maintains portal hypertension. beta-Adrenergic blockers have been shown to reduce the elevated portal blood flow component. The possibility that nitroglycerin administration could reduce the elevated portal vascular resistance component is investigated here. Portal hypertension was induced in rats by a calibrated constriction of the portal vein. Portal hypertensive rats receiving placebo exhibited significant (p less than 0.05) elevations over normal rats receiving placebo in cardiac index, portal venous inflow and portal pressure. Portal hypertensive rats were then divided into groups receiving nitroglycerin infusion, propranolol (beta-adrenergic blockade) and combined administration of nitroglycerin and propranolol. Significant reductions (p less than 0.05) in portal blood flow of 30, 32 and 44%, respectively, were accompanied by significant portal pressure reductions of 2.7 +/- 0.2, 1.7 +/- 0.3 and 3.6 +/- 0.4 mm Hg in all groups, respectively (p less than 0.05). Nitroglycerin failed to prevent a 46% rise in portal-collateral resistance accompanying the portal blood flow reduction, similar to resistance rises also found in propranolol-treated (33%) and combination nitroglycerin-propranolol-treated (49%) groups. We conclude that nitroglycerin infusion can significantly reduce portal pressure, alone or in combination with beta-blockade, by reducing portal venous inflow. It appears that nitroglycerin reduces portal blood flow through the effect of baroreceptor sympathetic reflexes that constrict the splanchnic bed in response to vasodilatation and venous pooling.     

Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis.

In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+/- SD) wedged hepatic (25.8 +/- 6.4 mmHg), intrahepatic (24.5 +/- 6.2 mmHg) and intrasplenic (25.0 +/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with intravariceal (25.2 +/- 6.7) pressure measurements. In patients with NCPF, mean (+/- SD) wedged hepatic (9.1 +/- 3.7 mmHg) and intraphepatic (15.4 +/- 5.8 mmHg) pressures were significantly (p less than 0.01) lower than the intrasplenic (24.5 +/- 4.2 mmHg) and intravariceal (23.96 +/- 5.6 mmHg) pressures. Two independent pressure gradients, one between intrasplenic and intrahepatic pressure (8.9 +/- 6.5 mmHg) and another between intrahepatic and wedged hepatic venous pressure (6.2 +/- 5.6 mmHg) were seen in non-cirrhotic portal fibrosis patients, indicating the likelihood of both pre- and perisinusoidal resistance to flow of portal venous blood in these patients. A highly significant (p less than 0.001) correlation between intravariceal and intrasplenic pressures was found in patients with cirrhosis of liver (r = 0.93), as well as in patients with non-cirrhotic portal fibrosis (r = 0.85). No correlation was found between the size of oesophageal varices and wedged hepatic and intrahepatic pressures. Patients with grade 4 varices had significantly higher intravariceal (p less than 0.01) and intrasplenic (p less than 0.05) pressure than patients with grade 2 varices. It can be concluded that intravariceal pressure is representative of portal pressure in patients with cirrhosis of liver as well as in non-cirrhotic portal fibrosis patients and it can be recommended as the single haemodynamic investigation in patients with portal hypertension and oesophageal varices.     

Effects of prostaglandin inhibition on systemic and hepatic hemodynamics in patients with cirrhosis of the liver

The role of prostaglandins in the pathogenesis of the circulatory abnormalities of cirrhosis was investigated by studying the effects of prostaglandin inhibition with indomethacin (50 mg/8 h for 24 h) on the systemic and splanchnic hemodynamics in 13 patients with cirrhosis of the liver. Indomethacin administration significantly reduced cardiac output (from 7.44 +/- 0.7 to 6.78 +/- 0.7 L/min, p less than 0.05) and increased peripheral vascular resistance (from 990 +/- 104 to 1155 +/- 140 dyn X s X cm-5, p less than 0.05). Arterial pressure was not modified. These changes in systemic hemodynamics were associated with a significant reduction in hepatic blood flow (from 1.88 +/- 0.43 to 1.48 +/- 0.3 L/min, p less than 0.05) and with a slight decrease of portal pressure (from 18.8 +/- 1.3 to 17.5 +/- 1.4 mmHg, p less than 0.05). These results suggest that endogenous prostaglandins contribute to the increased cardiac output and diminished vascular resistance observed in cirrhosis of the liver. In addition, by promoting splanchnic vasodilation, prostaglandins may contribute to increased portal pressure in these patients.     

Effects of vaso-active agents on hepatic function and blood gases in patients with cirrhosis: A study of vasopressin and nitroglycerin

The effects of vaso-active agents on hepatic function and splanchnic oxygenation were studied in 17 patients with cirrhosis and portal hypertension. Eight patients received vasopressin (0.3 iu/min) and nine patients received nitroglycerin (50 micrograms/min). Both drugs caused a significant reduction in the portal venous pressure gradient. Vasopressin infusion significantly decreased intrinsic clearance of indocyanine green (-23%, P less than 0.01). This may be due to a decreased hepatic perfusion (-28%, P less than 0.01) and portal venous oxygenation (-15% in portal venous oxygen tension, P less than 0.05). In contrast, no changes in hepatic perfusion and portal venous oxygenation were observed after nitroglycerin infusion. Nitroglycerin did not decrease intrinsic clearance of indocyanine green. These results suggest that vasodilators, rather than vasoconstrictors, might be welcome in the treatment of patients with cirrhosis and portal hypertension.