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.     

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.     

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)     

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.     

Vasopressin and vasopressin plus nitroglycerin for portal hypertension. Effects on systemic and splanchnic hemodynamics and coronary blood flow

We measured the coronary, systemic, and splanchnic effects of vasopressin and vasopressin plus nitroglycerin in 8 stable patients with alcoholic cirrhosis. Vasopressin (0.1-0.8 U/min) increased pressure in the hepatic vein, pulmonary artery and pulmonary capillaries. Wedged hepatic (portal) vein pressure was unchanged; the hepatic venous pressure gradient (wedged-free hepatic vein pressure) fell. Insignificant declines occurred in cardiac output, gastroesophageal collateral (azygous) blood flow, hepatic blood flow and coronary sinus (cardiac) blood flow. The addition of nitroglycerin (40-70 micrograms/min) reduced pressure in the hepatic vein, pulmonary artery and pulmonary capillaries, while increasing the hepatic venous pressure gradient. Wedged hepatic vein pressure did not change. Gastroesophageal collateral (azygous) flow increased markedly; cardiac output rose to a lesser degree. Coronary sinus and hepatic blood flow did not change. Nitroglycerin ameliorated the increases in systemic and pulmonary artery pressure produced by vasopressin but also tended to reverse the decline in the hepatic venous pressure gradient and markedly increased gastroesophageal flow. Neither drug significantly affected coronary blood flow.     

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.     

Haemodynamic effects of enalaprilat on portal hypertension in patients with HBsAg-positive cirrhosis

Abstract It has been suggested that enalaprilat inhibits the renin-angiotensin-aldosterone system in plasma and tissue; it may therefore reduce portal vascular pressure owing to secondary hyperaldosteronism in patients with liver cirrhosis. In order to evaluate this concept, 20 patients with hepatitis B surface antigen (HBsAg)-positive liver cirrhosis and portal hypertension received an intravenous infusion of 2.5 mg of enalaprilat. Wedged hepatic venous pressure, free hepatic venous pressure and cardiac index were measured before, immediately after, and then 15 min, 30 min and 1 h after intravenous enalaprilat infusion. The mean pressure gradient between wedged hepatic venous pressure and free hepatic venous pressure was significantly decreased, by 13% immediately after, 18% at 15 min, 23% at 30 min and 13% at 1 h after infusion of enalaprilat. Thirteen patients experienced a decrease of hepatic venous pressure gradient (HVPG) greater than 5 mmHg, another three 3-5 mmHg and the remaining four patients exhibited no significant change in HVPG. Systemic haemodynamic indices, including pulmonary arterial pressure, pulmonary capillary wedge pressure and central venous pressure, decreased significantly at 15 and 30 min after enalaprilat infusion ( P < 0.01). Liver function, renal function and blood routine before and after enalaprilat infusion showed no significant changes. There were no adverse effects during or after enalaprilat infusion. We conclude that enalaprilat infusion can quickly and safely reduce the hepatic venous pressure gradient in patients with HBsAg-positive cirrhosis.     

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.     

Lack of effects of isosorbide-5-mononitrate on hepatic hemodynamics in HBsAg-positive cirrhosis

We conducted a randomized controlled hemodynamic study to evaluate the effect of placebo and 20 mg isosorbide-5-mononitrate, a long-acting organic nitrate, in 19 patients with HBsAg-positive cirrhosis by the simultaneous measurement of portal venous pressure and wedged hepatic venous pressure. Baseline values for the two groups were similar. One hour after oral administration of 20 mg isosorbide-5-mononitrate in 10 patients, mean arterial pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure significantly decreased from 92 +/- 13 (mean +/- S.D.) to 82 +/- 14 mmHg, from 12.9 +/- 4.5 to 9.3 +/- 2.4 mmHg and from 6.9 +/- 3.4 to 4.3 +/- 1.8 mmHg, respectively. However, both portal venous pressure gradient (from 18.1 +/- 3.6 to 17.5 +/- 3.0 mmHg) and hepatic venous pressure gradient (from 17.8 +/- 5.2 to 16.6 +/- 5.3 mmHg) remained unchanged during the study. In six patients who received 20 mg isosorbide-5-mononitrate twice daily for 7 days, hepatic venous pressure gradient remained unaltered as compared to basal and 1-hr values. There was no significant change in cardiac index, heart rate or systemic vascular resistance in either immediate (1-hr) or delayed (7-day) studies. Three patients (30%) developed mild headache or dizziness and two patients (20%) demonstrated systolic hypotension (less than mmHg) during the immediate study. This study shows that isosorbide-5-mononitrate appears to have no effect in treating portal hypertension in patients with HBsAg-positive cirrhosis. In addition, the isosorbide-5-mononitrate may affect the systemic circulation more than the portal circulation.     

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.     

Action of Nitroglycerin and amyl nitrite in labile and essential hypertension: hemodynamic differences.

Seventeen patients with labile hypertension received nitroglycerin and 18 received amyl nitrite. Twelve patients with established essential hypertension received nitroglycerin and 12 received amyl nitrite. Nitroglycerin reduced the systolic and mean arterial pressures and cardiac output in both groups, but had no effect on diastolic pressure and total peripheral resistance. Amyl nitrite decreased systolic, diastolic, and mean arterial pressures and peripheral vascular resistance and increased heart rate and cardiac output in labile hypertensives. In established hypertensive patients, amyl nitrite decreased systolic, diastolic, and mean arterial pressures and cardiac output, and had little effect on peripheral vascular resistance. Nitroglycerin reduced arterial pressure in labile and established hypertensives through venodilation and peripheral venous pooling. Amyl nitrite and effects similar to nitroglycerin in established hypertensives; in labile hypertensives it reduced arterial pressure through arterial dilation and a decrease in peripheral vascular resistance.     

Haemodynamic response to intravenous vasopressin and nitroglycerin in portal hypertension.

We have evaluated the haemodynamic effects of intravenous (iv) nitroglycerin (NG) and vasopressin (VP) alone and in combination, in 12 patients with cirrhosis and recent variceal haemorrhage (two to seven days). Nitroglycerin infusion alone (200 micrograms/min) produced a significant fall in portal pressure (WHVP-FHVP) (from 16.4 (0.6) to 13.3 (1.2) mmHg; p less than .001) associated with hypotension (mean arterial pressure from 95 (7) to 78 (9) mmHg; p less than 0.005). Vasopressin alone (0.4 IU/min) reduced portal pressure (20.7 (1.3) to 14.0 (1.3) mmHg; p less than 0.001), but there was considerable variation in the systemic haemodynamic changes with increased cardiac output in four of six patients. The combination of vasopressin and nitroglycerin corrected all systemic haemodynamic disturbances produced by either agent alone. This combination led, however, to a further reduction in portal pressure (from 13.7 (0.9) to 11.7 (0.7) mmHg p less than 0.01). These results show that: (1) intravenous nitroglycerin reduces portal pressure, and (2) the combination of nitroglycerin and vasopressin reverses systemic haemodynamic disturbances produced by either agent alone and leads to a further decrease in portal pressure.     

Low dose of nitroglycerin failed to improve splanchnic hemodynamics in patients with cirrhosis: evidence for an impaired cardiopulmonary baroreflex function

High doses of nitroglycerin may decrease portal pressure in patients with cirrhosis with untoward effects such as arterial hypotension and a decrease in systemic O2 uptake. In the present study, low doses of nitroglycerin (7 to 15 micrograms per min, i.v.) were administered in 11 patients with cirrhosis in order to unload cardiopulmonary baroreceptor--one of the possible mechanisms by which nitroglycerin may improve splanchnic hemodynamics--and moreover to avoid deleterious systemic effects. Nitroglycerin significantly decreased right atrial pressure (-35%) and pulmonary wedged pressure (-27%) with significant increase in plasma norepinephrine concentration (+23%), which indicated that cardiopulmonary baroreceptor unloading was achieved. Changes in systemic hemodynamics were slight, although significant, with a decrease in arterial pressure (-8%) and an increase in heart rate (+8%); this indicates a minimal effect on high-pressure baroreflexes. In contrast, no significant change was observed in hepatic venous pressure gradient, hepatic blood flow and azygos blood flow. However, the fraction of cardiac output reaching the azygos system significantly increased by 18%. Plasma renin activity did not change significantly. Moreover, O2 transport and uptake were significantly decreased. These findings show that low doses of nitroglycerin failed to improve splanchnic hemodynamics in patients with cirrhosis. These results suggest an impaired cardiopulmonary baroreflex function which is probably located on the efferent arch.     

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.     

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.     

Potentiation of the hemodynamic effects of acutely administered nitroglycerin by methionine

It is believed that nitroglycerin causes vasodilatation by interacting with sulfhydryl groups present in vascular smooth muscle. This study was performed to assess whether methionine, an amino acid capable of increasing sulfhydryl availability, would potentiate the hemodynamic effects of nitroglycerin. Nitroglycerin was initially infused in incremental doses from 1 to 50 micrograms/min in all patients to determine the dose required to reduce mean arterial pressure by 10% and pulmonary capillary wedge pressure by 30%. After a washout period, 10 patients received 5 g methionine i.v. and five patients received an equal volume of 5% dextrose in water (control). Nitroglycerin dose titration was then repeated. Methionine alone induced no hemodynamic effects, but after methionine infusion, there was a significant reduction in the nitroglycerin infusion rate required to reach each hemodynamic endpoint (p less than 0.01). In the control group, there was no significant change in responsiveness to nitroglycerin between infusions. Thus, methionine potentiates the hemodynamic effects of acutely administered intravenous nitroglycerin.     

Effect and mechanism of action of isosorbide-5-mononitrate.

Nitrates have been shown to decrease portal pressure in cirrhotic patients with portal hypertension and this has been attributed to decreased portal venous resistance. We studied the effect and mechanism of action of oral administration of isosorbide-5-mononitrate (Is-5-Mn) (20 mg), which, unlike the dinitrate, does not require hepatic biotransformation to a vasoactive metabolite on portal and systemic haemodynamics in 11 patients with portal hypertension complicating cirrhosis. A significant reduction in portal pressure gradient (WHVP-FHVP) (from 23.9 (3.4) to 21.8 (3.4) mmHg: p less than 0.005) occurred 60 minutes after Is-5-Mn due entirely to a fall in WHVP, associated with decreased estimated liver blood flow (from 1940 (159) to 1639 (179) ml/min: p less than 0.05). Right atrial and pulmonary artery pressures and cardiac index fell significantly whilst mean arterial pressure remained unaffected. Heart rate and the calculated systemic vascular resistance index increased significantly. Significant correlations existed between the reduction in portal pressure gradient and fall in cardiac index (r = 0.65, p less than 0.05) and increase in systemic vascular resistance index (r = 0.72, p less than 0.02). The observed decrease in estimated liver blood flow, in association with an increase in systemic vascular resistance index, suggests that baroreceptor mediated splanchnic vasoconstriction may be one of the factors responsible for the fall in portal pressure, rather than portal venous dilatation.     

Effect of intravenous administration of nitroglycerin and regitine on hemodynamics in mitral valve insufficiency

During exercise in subjects with congestive heart failure and mitral regurgitation the rise in systemic arterial pressure is usually accompanied by increase in systemic vascular resistance. That could cause decrease of cardiac output not only because of a lack of myocardial reserve, but also because of an increase of mitral regurgitant volume. In such situation decrease in left ventricular preload could further increase the regurgitant volume and cardiac output. Whether changes in pre-or afterload can cause significant changes in mitral regurgitation, nitroglycerin and phentolamine was assessed in that group of patients. 22 patients with significant mitral regurgitation (3+,4+) was randomly divided into two groups. The first one received short intravenous infusion of nitroglycerin at a rate of 170 micrograms/min. The second one received phentolamine intravenously 1-1,5 mg/min. Patients underwent right heart catheterization with Swan-Ganz thermodilution catheter. Mean pulmonary, pulmonary capillary wedge, and right atrial pressure were monitored and recorded. Cardiac output was determined by thermodilution technique using iced 5% dextrose. If there were no contraindications (PWP greater than 30 mm Hg) an effort test was performed (cycloergometer, supine position). The same protocol was repeated during administration of nitroglycerin and phentolamine. Nitroglycerin significantly decreased right atrial and capillary wedge pressure (from 22.9 to 15.6 mm Hg). There were no significant differences in cardiac output, pulmonary and systemic vascular resistance. Pulmonary artery pressure decreased after nitroglycerin but the difference was not significant. All above effects of nitroglycerin persisted during effort. Phentolamine decreased significantly right atrial, pulmonary and capillary wedge pressure with simultaneous increase of cardiac output (30%) and decrease of pulmonary and systemic vascular resistance. In summary, nitroglycerin decreases only symptoms and theoretically could worsen forward flow in patients with mitral regurgitation and heart failure, especially in subjects with a significant increase of systemic vascular resistance during effort.     

Long-term hemodynamic effects of ketanserin, a 5-hydroxytryptamine blocker, in portal hypertensive patients

Ketanserin, a 5-hydroxytryptamine-2 receptor blocker, has been shown to decrease portal pressure in recent acute hemodynamic studies that have been performed both in experimental animals and portal hypertensive patients. The present study was designed to investigate the effects of chronic oral administration of ketanserin in portal hypertensive patients with cirrhosis. The mean baseline hepatic venous pressure gradient in the 13 patients with alcoholic cirrhosis who completed the study was 15.7 +/- 2.7 mmHg. It decreased significantly to 13.3 +/- 2.0 mmHg (p less than 0.001) after ketanserin was administered at a mean dose of 51 mg per day for a mean period of 32 days. This 14.6% reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure (from 22.2 +/- 4.0 to 20.1 +/- 3.6 mmHg) and was accompanied by significant decreases in cardiac index (18.8%) and in mean arterial pressure (8.1%). However, changes in cardiac index or in mean arterial pressure were not predictive of modifications in the hepatic venous pressure gradient. Eight of 16 patients entered in the study developed side effects, the most significant being a reversible portosystemic encephalopathy, which occurred in three patients who had poor liver function. This study confirms evidence in favor of a role for 5-hydroxytryptamine in portal hypertension and adds a new group of agents for the chronic treatment of portal hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of nitroglycerin on pulmonary vascular capacitance in dogs

In this study we investigated the hypothesis that the decrease in pulmonary vascular pressures observed after administration of nitroglycerin is in part due to a shift in the pulmonary vascular pressure-volume relationship. The experiments were done in six closed-chest dogs anesthetized with pentobarbital, in which pulmonary, cardiac, and intestinal relative blood volumes were determined by equilibrium blood pool scintigraphy. Nitroglycerin (30 micrograms/kg/min) caused 7% (p less than 0.02) and 12% (p less than 0.02) reductions in pulmonary and total cardiac blood volume, respectively, and a 7% (p less than 0.01) increase in intestinal blood volume. This shift of blood from the heart and the pulmonary circulation to the systemic (intestinal) circulation was accompanied by reductions in mean pulmonary artery pressure from 16 +/- 2 mm Hg to 12 +/- 1 mm Hg (p less than 0.01), in mean pulmonary capillary wedge pressure from 11 +/- 2 mm Hg to 6 +/- 1 mm Hg (p less than 0.01), and in mean portal pressure from 9 +/- 1 mm Hg to 8 +/- 1 mm Hg (p less than 0.01). The position of the pulmonary vascular pressure-blood volume relationship was unaffected by nitroglycerin, whereas the portal pressure-intestinal blood volume relationship was shifted to the left and upward. These changes suggest that pulmonary vascular tone remained unchanged, whereas intestinal vascular tone decreased during administration of nitroglycerin. In conclusion, nitroglycerin decreased pulmonary vascular pressures through a passive emptying of the pulmonary circulation as a result of increased systemic (intestinal) vascular capacitance.