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Biomedical subjects

E H Forrest

Publications and source records attributed to E H Forrest.

27 records · Page 2Linked to original sources
PubMed1996

Acute haemodynamic changes after oral carvedilol, a vasodilating beta-blocker, in patients with cirrhosis.

BACKGROUND/AIMS: Combinations of beta-blockers and vasodilators have been assessed for their ability to lower portal pressure and so prevent variceal haemorrhage. However, reservations have been raised particularly with respect to renal function and perfusion after the use of these medicines in patients with chronic liver disease. We studied the acute effects of carvedilol, a new vasodilating beta-blocker which combines non-selective beta-blockade with alpha-1 receptor antagonism, upon the haemodynamics of patients with cirrhosis. METHODS: Sixteen patients completed the study which measured the changes approximately 1 h after the administration of 25 mg oral carvedilol. RESULTS: The hepatic venous pressure gradient fell from 16.7 +/- 0.9 to 13.6 +/- 1.0 mmHg (p < 0.00001), accounted for largely by reductions in the wedged hepatic venous pressure. Despite this, the azygos blood flow did not change. There was a significant fall in mean arterial pressure (94.8 +/- 4.4 cf. 84.6 +/- 4.3 mmHg; p = 0.0001), which was particularly apparent in the diastolic blood pressure of those patients with ascites. The heart rate only fell significantly in the ascitic subjects. No significant changes occurred in the cardiac output or systemic vascular resistance. Unilateral renal vein flow as measured by the reverse thermodilution technique remained constant. CONCLUSIONS: Carvedilol is therefore a potent acute portal hypotensive agent which does not appear to compromise renal perfusion. However, patients with ascites are at greater risk of its systemic hypotensive action.

Administration, Oral↗
PubMed1996

Clinical response after transjugular intrahepatic portosystemic stent shunt insertion for refractory ascites in cirrhosis.

BACKGROUND: Transjugular intrahepatic portosystemic stent shunts (TIPSS) have been used successfully to reduce portal pressure in the context of variceal haemorrhage. Recent interest has focused on the possible use of TIPSS to manage refractory ascites. AIM: To study the effect of TIPSS insertion in 18 patients with refractory ascites. RESULTS: Response rates were 33.3%, 50%, 33.3% and 26.7% at 1 week, 4 weeks, 3 months and 6 months, respectively. Overall mortality was 50% with a new or worsening encephalopathy rate also of 50%. Patients with lower serum bilirubin and serum creatinine prior to TIPSS insertion had greater response at 1 and 4 weeks, respectively. There was no improvement in either liver or renal function after TIPSS insertion by standard laboratory tests, although serum sodium increased in the responders after 1 month. CONCLUSION: TIPSS improves refractory ascites in only a minority of patients, and is associated with high encephalopathy and mortality rates.

Ascites↗
PubMed1996

Differing actions of the acute administration of propranolol and isosorbide-5-mononitrate on the portal circulation.

BACKGROUND: The aim of this study was to clarify the actions of propranolol and isosorbide-5-mononitrate upon the portal circulation. METHODS: Portal haemodynamics were assessed in 16 patients with transjugular intrahepatic portosystemic stent shunts. A reverse thermodilution catheter was positioned in the portal vein, and portal vein pressure and portal vein flow were measured directly. The effects of propranolol 80 mg and isosorbide-5-mononitrate 20 mg over 1 h were determined independently. RESULTS: This demonstrated that propranolol reduced both portal pressure gradient (7.7 +/- 2.3 to 5.5 +/- 2.1 mmHg, P < 0.01) and portal vein flow (925 +/- 123 to 597 +/- 99 mL/min, P = 0.01) significantly, implying a reduction in splanchnic inflow as its main effect. In contrast, isosorbide-5-mononitrate tended to increase portal vein flow (814 +/- 186 to 911 +/- 211 mL/min; P = 0.06) whilst reducing portal pressure significantly (108 +/- 12 to 92 +/- 10 mmHg P = 0.014). This suggests a fall in intrahepatic resistance and provides no evidence for baroreceptor-mediated reflex splanchnic vasoconstriction. CONCLUSIONS: These drugs act upon different variables contributing to portal hypertension and so they may have a powerful synergistic effect in combination. Direct measurement of portal vein flow is a valuable method for assessing the pharmacological modulation of portal venous inflow.

Blood Pressure↗
PubMed1996

Review article: renal circulatory changes in cirrhosis--pathogenesis and therapeutic prospects.

Renal dysfunction in cirrhosis describes a spectrum of abnormalities which lead to the clinical manifestations of ascites, peripheral oedema and hepato-renal failure. This article reviews the processes underlying this dysfunction with particular regard to the disturbance in the renal circulation. Renal haemodynamic changes occur early in cirrhosis prior to the development of ascites. However, as the liver disease progresses these changes become more profound and lead ultimately to severe cortical hypoperfusion. Renal blood flow and glomerular filtration rate do not appear to correlate well with the presence of ascites, and a separate defect in tubular sodium handling is likely to be present. The development of portal hypertension is a possible trigger of increased renal vascular resistance, whereas a deterioration in liver function may relate to the impaired tubular handling of sodium. The peripheral vasodilatation hypothesis seeks to relate these renal changes to the activation of vasopressor systems after the development of arteriolar vasodilatation. Correlations between systemic vascular resistance and renal blood flow have been difficult to establish. A variety of substances may mediate the renal circulatory changes. The likelihood is that the increase in systemic vasoconstrictors is compensatory, and that it is the locally active vasoactive substances, particularly those derived from the endothelium, which play a major role in the development of renal vasoconstriction. The management of ascites is fraught with complications, and the treatment of hepato-renal syndrome inadequate. Liver transplantation is currently the only therapy which gives any hope of long-term response and survival. Methods of improving the renal circulation by mechanically lowering portal pressure or by antagonizing locally active renal vasoconstrictors may be beneficial.

Animals↗
PubMed1996

Longterm follow up of transjugular intrahepatic portosystemic stent shunt (TIPSS) for the treatment of portal hypertension: results in 130 patients.

BACKGROUND: Transjugular intrahepatic portosystemic stent shunts (TIPSS) are increasingly being used to manage the complications of portal hypertension. This study reports on the follow up on 130 patients who have undergone TIPSS. PATIENTS AND METHODS: One hundred and thirty patients (81 male), mean (SD) age 54.7 (12.5) years underwent TIPSS. The majority (64.6%) had alcoholic cirrhosis and 53.2% had Childs C disease. Indications were: variceal haemorrhage (76.2%), refractory ascites (13.1%), portal hypertensive gastropathy (4.6%), others (6.1%). Shunt function was assessed by Doppler ultrasonography and two then six monthly portography and mean follow up for survivors was 18.0 months (range 2-43.5). RESULTS: The procedure was successful in 119 (91.5%). Sixty three episodes of shunt dysfunction were observed in 45 (37.8%) patients. Variceal rebleeding occurred in 16 (13.4%) patients and was always associated with shunt dysfunction. Twenty (16.8%) patients had new or worse spontaneous encephalopathy after TIPSS and 11 (64.7%) patients had an improvement in resistant ascites. Thirty day mortality was 21.8% and one year survival 62.5%. CONCLUSION: TIPSS is an effective treatment for variceal bleeding, resistant ascites, and portal hypertensive gastropathy. Rebleeding is invariably associated with shunt dysfunction, the frequency of which increases with time, therefore regular and longterm shunt surveillance is required.

Acute Disease↗
PubMed1995

The effect of nitric oxide synthase inhibition on portal pressure and azygos blood flow in patients with cirrhosis.

It has been proposed that the hyperdynamic circulation found in cirrhosis is mediated by nitric oxide released through the induction of nitric oxide synthase. To investigate this the effect of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), was studied upon the portal circulation. After a 30-min infusion of 3 mg/kg of L-NMMA there was a significant fall in heart rate from 83.2 +/- 4.4 to 74.2 +/- 3.9 bpm (p = 0.005), and a significant rise in mean arterial pressure from 91.6 +/- 2.2 to 103.7 +/- 3.2 mmHg, p = 0.004). There was, however, no change in hepatic venous pressure gradient (16.7 +/- 1.5 to 16.1 +/- 1.7 mmHg, p = 0.477) nor in azygos venous blood flow (366 +/- 126 to 368 +/- 145 ml/min, p = 0.683). On subgroups analysis by Child-Pugh grade, significant changes occurred in heart rate and mean arterial pressure only in grade A and B patients (p = 0.0061 and p = 0.0068, respectively). Regional peripheral blood flow was studied using hand thermography. All patients who had an isothermic hands (relatively cold fingers compared to palmar temperature) at the start of the study developed an isothermic pattern after the L-NMMA infusion. This study demonstrates a significant systemic effect of nitric oxide synthase inhibition in patients with cirrhosis but no effect upon the portal or portosystemic collateral circulations at this dose.

Adult↗
PubMed1995

Relationship between directly measured portal pressure gradient and variceal hemorrhage.

OBJECTIVE: It is commonly believed that variceal hemorrhage in patients with cirrhosis and portal hypertension does not occur below a portal pressure gradient (PPG) of 12 mm Hg. The aim of this study was to assess the relationship between directly measured portal pressure gradient and variceal hemorrhage. METHODS: The procedure of insertion of the transjugular intrahepatic portosystemic stent-shunt (TIPSS) for variceal hemorrhage provides access to the portal vein and allows direct measurement of the portal pressure. Right atrial, inferior vena caval, and portal pressure were recorded, and the PPG was calculated (portal pressure-inferior vena caval pressure) in 48 patients undergoing TIPSS for variceal hemorrhage. RESULTS: PPG was reduced from a mean of 21.4 (6.4) before TIPSS to 10.6 (3.1) mm Hg after the procedure. Seven patients (14.7%) had a baseline portal pressure gradient of < 12 mm Hg. CONCLUSION: The results of this study do not support the concept of a discrete bleeding threshold.

Atrial Function, Right↗
PubMed1988

Influence of cyclosporin A on growth of an acute T-cell leukaemia in PVG rats.

Our objective was to examine the effect of cyclosporin A (CsA; 25 or 12.5 mg/kg) on growth of an acute (Roser) T-cell leukaemia in male PVG rats. The leukaemic blasts were shown (by immunocytochemical analysis) to have a mature, T-helper-cell phenotype, i.e., OX-19 (CD5) +/- , W3/25 (CD4)+, OX44+, MHC-class I+, OX-26+, corresponding to a population comprising 5% of normal rat medullary thymocytes. Animals received 20 X 10(3) viable tumour cells intramuscularly (day 0) and were given either CsA (25 or 12.5 mg/kg) or drug vehicle by gavage from day 0 or day 14, by which latter time leukaemic blasts normally appeared in the circulation. Administration of the higher dose of CsA from day 0 or day 14 significantly delayed the appearance of leukaemic cells in the peripheral circulation, whereas treatment with 12.5 mg/kg was without significant effect. CsA whole blood levels on day 17 were twice as high in leukaemic rats as in normal controls. Leukaemic infiltration of the spleen and the liver was reduced on day 17 after 25 mg/kg CsA, but no such effect was observed in lymph nodes or kidneys. A heterogeneous, host "reactive" cell population, which developed in response to the leukaemia, was inhibited by CsA, indicating that the effect of the drug was probably not mediated by host defence mechanisms. In CsA-treated leukaemic animals, there was biochemical evidence of synergistic impairment of glomerular and tubular function.

Animals↗