Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the relationship between oxygen transport and uptake in cirrhosis, we studied the effects of three vasoactive drugs that change O2 transport. Systemic hemodynamics, blood gases and lactate concentration were measured in patients with alcoholic cirrhosis before and after intravenous dobutamine, propranolol and nitroglycerin. Nine patients received successively dobutamine and then propranolol. Ten patients received nitroglycerin. Three other patients without cirrhosis (controls) received dobutamine. In patients with cirrhosis, dobutamine infusion was accompanied by a significant increase in cardiac output (+21%), systemic O2 transport (+21%) and O2 uptake (+12%), whereas O2 extraction ratio and arterial lactate concentration did not change significantly. Propranolol administration was followed by a significant decrease in cardiac output (-24%) and systemic O2 transport (-25%) and a significant increase in O2 extraction ratio (+19%), whereas O2 uptake and arterial lactate concentration did not change. Nitroglycerin infusion was accompanied by a significant decrease in cardiac output (-21%), systemic O2 transport (-26%) and O2 uptake (-10%), whereas O2 extraction ratio (+18%) and arterial lactate concentration (+31%) significantly increased. In control patients, dobutamine infusion was accompanied by an increase in cardiac output and in systemic O2 transport and by a decrease in O2 extraction ratio, whereas O2 uptake was not modified. These results suggest that O2 uptake may be abnormally dependent on O2 transport in patients with cirrhosis.
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PMID:Relationship between oxygen transport and oxygen uptake in patients with cirrhosis: effects of vasoactive drugs. 249 14

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.
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PMID:Low dose of nitroglycerin failed to improve splanchnic hemodynamics in patients with cirrhosis: evidence for an impaired cardiopulmonary baroreflex function. 250 Mar 89

We studied the effects of a series of vasodilators on intrahepatic vascular resistance of isolated perfused cirrhotic rat livers in basal conditions and during norepinephrine-induced vasoconstriction. Cirrhosis was induced by repeated intraperitoneal injections of carbon tetrachloride. The vasodilators were a nonselective beta-adrenergic antagonist (propranolol), an alpha 1-adrenergic antagonist (prazosin), a nonselective beta-adrenergic agonist (isoproterenol), an alpha 2-agonist (clonidine), nitrovasodilators (nitroglycerin and nitroprusside), calcium channel blockers (verapamil, diltiazem, nifedipine), papaverine, diazoxide and pentoxifylline. In basal conditions, isoproterenol, nitroglycerin, papaverine, pentoxifylline and nitroprusside demonstrated significant vasodilatory activity. However, the response was weak and isoproterenol was the only drug active in the therapeutic range of concentrations. Propranolol, prazosin, verapamil, diltiazem, nifedipine and diazoxide were ineffective. Prazosin, papaverine and pentoxifylline reduced norepinephrine-induced vasoconstriction, whereas isoproterenol, clonidine and propranolol were ineffective. We conclude that several vasodilators can reduce resistance in the cirrhotic rat liver, but their potency is low and few are effective at therapeutic concentrations. Furthermore, their activity may be blunted when resistance is increased by norepinephrine.
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PMID:Effect of vasodilators on hepatic microcirculation in cirrhosis: a study in the isolated perfused rat liver. 271 34

Bleeding from esophageal varices is a feared complication of liver cirrhosis with high mortality. Pharmacotherapy of the acute bleeding episode with vasopressin has been shown to be effective in controlled studies, but side effects of this therapy are high and therefore replacement of vasopressin with somatostatin is under investigation. Another potential lead is the combination of vasopressin with vasodilators such as nitroglycerin. While acute pharmacotherapy of the patient with esophageal varices is well accepted, chronic or prophylactic pharmacotherapy is still in the investigative stage. Prophylactic therapy with beta-blockers, e.g. propranolol, has been shown to be effective in compensated patients with alcoholic cirrhosis. In patients with more advanced stages of the disease, or with cirrhosis of other etiology, the effectiveness of propranolol has not been proven. The mechanism of propranolol is similar to that of vasopressin, i.e. it lowers portal pressure by reducing portal flow. To maintain function of the affected organ, an alternative approach--namely lowering of portal pressure through reduction of the pathologically elevated resistance--should be actively investigated.
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PMID:[Pharmacological therapy of portal hypertension]. 286 82

Thirty-nine patients admitted during a 16-month period for acute bleeding from varices confirmed by emergency endoscopy were randomized to receive either continuous intravenous infusions of vasopressin alone (0.66 units per min) (Group I: 19 patients) or vasopressin plus sublingual nitroglycerin (0.6 mg every 30 min for 6 hr) (Group II: 20 patients). The two groups of patients were similar in the type and severity of their cirrhosis. Bleeding was controlled initially in 47% (9/19) of the patients in Group I and 55% (11/20) of the patients in Group II after 6 hr of infusion (not statistically significant). Complete control of bleeding during 24 hr of infusion was achieved in only 4 of 19 patients in Group I (21%) but in 9 of 20 in Group II (45%). This difference is not statistically significant. The total number of patients with complications during infusions were significantly different statistically in the vasopressin and vasopressin-nitroglycerin groups, respectively (17/19 vs. 7/20, p less than 0.001). Major complications requiring immediate cessation of infusions were observed in 6 of 19 of the patients in Group I (32%) and in 2 of 20 in Group II (10%) (p less than 0.05). Mortality (58% in Group I, 55% in Group II) and transfusion requirements were similar in the two groups. This study shows that the addition of sublingual nitroglycerin to intravenous vasopressin does not alter the efficacy of vasopressin alone in controlling hemorrhage from esophageal varices, but it does significantly reduce the complications.
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PMID:Controlled trial of vasopressin plus nitroglycerin vs. vasopressin alone in the treatment of bleeding esophageal varices. 308 3

1. Basal forearm haemodynamics were studied by venous occlusion plethysmography in three groups of subjects: group I, healthy controls, group II, patients with cirrhosis age- and sex-matched with group I, and group III, an older group of patients with cirrhosis. Subsequently, responses to sublingual nitroglycerin were measured in group I and II subjects. 2. Controls responded to nitroglycerin with an increase in venous distensibility; group II patients had higher initial venous distensibility but did not respond to nitroglycerin. No other variables in either group were affected by nitroglycerin. 3. Group II and III patients differed in forearm blood flow and vascular resistance and venous distensibility. A significant inverse correlation was found between age and forearm blood flow (r = 0.57, P less than 0.001) in all patients with cirrhosis. 4. We conclude that (a) venous tone is reduced in cirrhosis, possibly as a result of chronic venodilatation; (b) this venodilatation impedes further dilatory response to a small dose of nitroglycerin; (c) cirrhosis is also associated with age-related decreases in peripheral haemodynamics.
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PMID:Effects of nitroglycerin on forearm haemodynamics in patients with cirrhosis. 312 20

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.
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PMID:Haemodynamic response to intravenous vasopressin and nitroglycerin in portal hypertension. 312 65

We used transesophageal real-time two-dimensional Doppler echography (TE2DD) to assess the effects of propranolol (n = 18, 6 mg each) and nitroglycerin (n = 18, 0.5 mg each) on blood flow in the intercostal veins, azygos vein, thoracic aorta, and esophagogastric varices. The primary disease in all of the patients was liver cirrhosis. Propranolol infusion markedly reduced the flow velocity in the varices, intercostal vein, azygos vein, and thoracic aorta (-24%, -41%, -34%, and -24%, respectively). It also significantly reduced the blood flow volume index (BFVI), defined as mean velocity in cm/sec X the square of the diameter in cm2 of both the azygos vein and the aorta (-34%, -21%, respectively). Nitroglycerin infusion did not cause significant changes in the hemodynamics of the above vessels, because the hemodynamic responses to the drug differed from individual to individual. The BFVI of the azygos vein correlated well with the azygos venous flow measured by the conventional thermodilution technique (r = 0.79, p less than 0.01). TE2DD appears to be a useful method for studying the hemodynamics of ascending collaterals in patients with portal hypertension.
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PMID:Effects of propranolol and nitroglycerin on cephalad collateral venous flow in patients with cirrhosis: evaluation using transesophageal real-time two-dimensional Doppler echography. 314 50

We studied the effects of a series of 16 vasodilators on the intrahepatic vasoconstriction induced by norepinephrine in the isolated perfused rat liver. The vasodilators were nonselective alpha-adrenergic antagonists (phentolamine, ifenprofil, isoxsuprine and buflomedil), a nonselective beta-adrenergic antagonist (propranolol) and an agonist (isoproterenol), an alpha 2-adrenergic agonist (clonidine), calcium channel blockers (verapamil and diltiazem), nitrovasodilators (nitroglycerin, sodium nitroprusside), papaverine and other unclassified vasodilators, some of them with rheological properties (diazoxide, vincamine, cinepazide, naftidofuryl and pentoxifylline). The most potent drugs were ifenprofil, phentolamine, isoxsuprine, clonidine, sodium nitroprusside and buflomedil. Diazoxide, papaverine, pentoxifylline and trinitrine were less powerful. Verapamil, diltiazem, propranolol, isoproterenol, vincamine, cinepazide and naftidofuryl were ineffective. We conclude that different classes of pharmacological agents have significant vasodilatory properties on the hepatic microvasculature. This offers interesting perspectives in the treatment of cirrhosis and stressful states where high levels of circulating norepinephrine may contribute to the altered liver perfusion.
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PMID:Effect of vasodilators on hepatic microcirculation: a study of the inhibition of norepinephrine-induced vasoconstriction in the isolated perfused rat liver. 335 3

Upper gastrointestinal bleeding (GIB) is a major complication in cirrhotic patients. Endoscopy and oesophageal sclerosis are reference treatments and must be done as soon as possible. However, such treatment is not possible unless the patient is admitted to hospital. In a prospective, randomised, double-blind trial, we compared the efficacy of terlipressin combined with glyceryl trinitrate (TER-GTN), administered as early as possible to 76 patients with cirrhosis who had active GIB (84 bleeding episodes). Infusion was done at the patient's home by the physician on the emergency team (a mobile intensive care unit) if the patient had GIB and a history and clinical signs of cirrhosis. Patients received either an intravenous injection (1 to 2 mg) of TER-GTN or a double-placebo injection, and then another injection at 4 and 8 h. Control of bleeding, rebleeding, and mortality rate at days 15 and 42 were evaluated. In most patients, endoscopy confirmed the rupture of oesophageal varices (75.7%). Bleeding control was significantly better in the TER-GTN group (n = 41) than in the double-placebo group (n = 43) (p = 0.034). Mortality due to bleeding episodes was significantly lower in the TER-GTN group than in the double-placebo group at day 15 (p = 0.035) and at day 42 (p = 0.06). There were no serious side-effects. Early administration of TER-GTN lowers the deleterious consequences of prolonged hypovolaemia on the hepatic function of these patients.
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PMID:Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients. 756 70


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