Introduction. There is a lack of information regarding outcomes after liver transplant in Latin A... more Introduction. There is a lack of information regarding outcomes after liver transplant in Latin America. Objectives. This study sought to describe outcomes after liver transplant in adult patients from Argentina. Methods. We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. Results. A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. Conclusions. We believe the information contained in this article might be of value for reviewing current practices and developing local policies. L IVER transplant (LT) is a well-established therapeutic practice in Argentina for patients with end-stage liver disease. In Argentina, the first LT was performed in 1988, and during past decades the annual number of LTs has increased steadily, placing Argentina at the top of Latin American LT rates [1]. This was possible due to the advances in surgical techniques, peritransplant intensive care, and immunosuppressive regimens, which resulted in significant improvements in short-term survival.
This study evaluated the clinical application of a pressure-sensitive gauge that allows the nonin... more This study evaluated the clinical application of a pressure-sensitive gauge that allows the noninvasive measurement of the pressure of esophageal varices at endoscopy. The study was performed in 70 patients with cirrhosis and portal hypertension. Among them, 47 had ...
Introducción: el examen histopatológico del hígado obtenido por biopsia percutánea es considerado... more Introducción: el examen histopatológico del hígado obtenido por biopsia percutánea es considerado tradicionalmente como el procedimiento de elección para evaluar el grado de fibrosis. Sin embargo, es un procedimiento invasivo y doloroso que tiene un pequeño riesgo de complicaciones. Recientemente se introdujo la elastografía de transición (Fibroscan ®), un nuevo método no invasivo para evaluar el grado de fibrosis que puede utilizarse en sustitución de la biopsia para diagnosticar (detectar o evaluar) la fibrosis hepática. La elastografía se ha evaluado en una serie de hepatopatías crónicas distintas a la hepatitis C para identificar la prevalencia de fibrosis, incluidas la hepatitis B, coinfección VIH-VHC, enfermedades colestásicas e hígado graso no alcohólico con una precisión diagnóstica que va de 75 a 93%. En el presente artículo se presenta la información más relevante sobre el uso del Fibroscan ® en la detección de la fibrosis hepática.
We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonis... more We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonist void of systemic effects, caused a significant reduction of portal pressure in conscious cirrhotic dogs. The mechanism by which ritanserin lowers portal pressure is poorly defined. We investigated the splanchnic and systemic hemodynamic effects of ritanserin (0.63 mg/kg body wt i.v., a dose known to completely inhibit binding of 5-hydroxytryptamine to its receptors), in conscious and unrestrained cirrhotic rats (n = 13). Heparinized catheters were placed into the portal vein, inferior vena cava, aorta, and left ventricle with exit from the neck. Hemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabeled microspheres and the reference sample method. Sixty minutes after administration, ritanserin caused a significant reduction of portal pressure (-17%) with minimal changes in portal venous inflow (+3%)...
Increased nitric oxide formation has been shown to be involved in the hyperdynamic circulation of... more Increased nitric oxide formation has been shown to be involved in the hyperdynamic circulation of portal hypertension. It has been proposed that it could be related to stimulation of the inducible nitric oxide synthase by endotoxin. Therefore, the aim of the present study was to evaluate whether dexamethasone treatment, an inhibitor of the expression of the inducible enzyme, ameliorates the hyperdynamic circulation observed in cirrhotic rats due to chronic bile duct ligation. Systemic and splanchnic hemodynamic parameters were measured after administration of dexamethasone (3 mg/kg/day during 3 days, i.p.) or its vehicle. In cirrhotic rats dexamethasone treatment caused a mild but not significantly higher mean arterial pressure in comparison with vehicle while similar values of cardiac output, peripheral vascular resistance, portal blood flow and portal pressure were observed in both group of animals. A significant body weight loss over the three days of treatment was observed in ra...
The validity of hemodynamic measurements by the reference sample method with microspheres injecti... more The validity of hemodynamic measurements by the reference sample method with microspheres injection into the aorta, via a carotid artery catheter, was evaluated in rats and compared with the results obtained after left ventricle injection. In the aorta injection group, a good mix of microspheres was observed in 83% of the animals. Moreover, a symmetrical distribution of microspheres was observed in 10 out of 12 rats (83%). An excellent correlation between right and left kidney-testes blood flows was observed (r = 0.93 and 0.96, respectively; P less than 0.01). Mean arterial pressure was not modified during microspheres injection into the aorta. Cardiac output (104 +/- 26 vs 101 +/- 23 ml/min, NS) and portal blood flow (14.2 +/- 3.3 vs 13.5 +/- 2.2 ml/min, NS) were similar after aorta and left ventricle injections series, respectively. Our results indicate that the injection of microspheres into the aorta is an adequate and easy approach to systemic and splanchnic hemodynamic measurements. This approach could be a good alternative to left ventricle injection of microspheres in experimental studies in rats.
Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The ai... more Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine...
Desmopressin (DDAVP), a synthetic analogue of vasopressin, has been shown to improve the bleeding... more Desmopressin (DDAVP), a synthetic analogue of vasopressin, has been shown to improve the bleeding time in patients with cirrhosis. The duration of this effect and the hemodynamic changes associated with DDAVP have not been studied so far. To evaluate these issues, 14 cirrhotics with portal hypertension were studied in basal conditions and after DDAVP (0.3 uk/kg). In 8 patients, hemostatic tests were done at basal conditions and 1, 3, 6 and 24 hs after drug administration. In the remaining 6 patients, mean arterial pressure, cardiac output, portal and femoral blood flows were evaluated. Hemodynamic parameters were measured by Doppler ultrasound. DDVP caused a marked decrease in bleeding time at 1, 3, 6 and 24 hs (14 +/- 9 vs 8 +/- 3, 7 +/- 4, 6 +/- 4 and 8 +/- 4 min, respectively); the decrease was maximal and statistically significant at 6 hs (55 +/- 15%, p < 0.02) after DDAVP infusion. Bleeding time reduction was observed in every patient studied. In the hemodynamic study, DDAVP...
The role of prostaglandins in the pathogenesis of the circulatory abnormalities of cirrhosis was ... more 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 ...
In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate... more In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate and cardiac output and diminishes portal pressure and collateral blood flow. However, there is little information on the possible effects of propranolol on hepatic artery blood flow. The present study addressed this question in 12 cirrhotic patients with end-to-side portacaval shunt, in whom all of the liver blood flow represents the hepatic artery blood flow. Hepatic artery blood flow (continuous infusion of indocyanine green), cardiac output (thermal dilution), heart rate and mean arterial pressure were measured before and 20 min after the intravenous infusion of 10 to 15 mg of propranolol. beta-Adrenergic blockade caused a significant reduction of cardiac output (from 9.1 +/- 2.1 to 7.1 +/- 1.4 liters per min, p less than 0.001) (mean +/- S.D.) and heart rate (from 85 +/- 10 to 71 +/- 7 beats per min, p less than 0.001), and a significant increase of systemic vascular resistance (fro...
We have recently shown that ventilation-perfusion (VA/Q) mismatching at rest in cirrhosis is due ... more We have recently shown that ventilation-perfusion (VA/Q) mismatching at rest in cirrhosis is due to an abnormal pulmonary vascular tone. It has been suggested that in patients with cirrhosis, O2 transfer might become diffusion-limited during exercise. This study examined pulmonary hemodynamics and mechanisms modulating gas exchange during exercise (60 to 70% VO2max) in six patients (41 +/- 5 yr, mean +/- SEM) with cirrhosis but with normal lung function tests. At rest, QT was high (8.4 +/- 0.5 L/min), pulmonary vascular resistance (PVR) was low (0.61 +/- 0.17 mm Hg/L/min), and there was mild to moderate VA/Q mismatching (LogSD Q, 0.79 +/- 0.09; normal range, 0.3 to 0.6). However, hyperventilation (PaCO2, 29 +/- 2 mm Hg) and high QT (thus, high PVO2, 41 +/- 2 mm Hg) contributed to the maintenance of PaO2 within normal values (99 +/- 7 mm Hg). Exercise VO2 (1,278 +/- 122 ml/min) was normal relative to work load, but, contrary to that in normal subjects, QT was higher and PVR did not fall. During exercise, PaO2 showed a trend to decrease (to 90 +/- 5 mm Hg) and PaCO2 to rise (to 35 +/- 2 mm Hg), but the differences failed to reach statistical significance (p = 0.07 each). PVO2 fell significantly with exercise (41 +/- 2 to 33 +/- 0.3 mm Hg, p less than 0.05), but neither AaPO2 (15 +/- 7 to 21 +/- 6 mm Hg) nor VA/Q inequality (LogSD Q, 0.82 +/- 0.11) changed. No systemic difference was noticed between predicted and measured PaO2 values, suggesting no O2 diffusion impairment during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to evaluate the relationship between plasma levels of von Willebrand fa... more The aim of this study was to evaluate the relationship between plasma levels of von Willebrand factor (vWF), a marker of endothelial cell activation, and nitric oxide, a powerful vasodilator synthesized by endothelial cells, in 27 patients with cirrhosis at different stages of the disease. These results were compared with those of age-matched normal, healthy subjects (n= 10). Methods: vWF:antigen was measured by electro-immunodiffusion test and serum nitrite and nitrate levels, the stable end products of nitric oxide metabolism, were determined by an enzymatic procedure. Results: vWF:antigen and nitrite/nitrate levels were significantly higher in cirrhotic patients (367+-185% and 29.3+-10.8 /anol/l) than in healthy subjects (92+-20% and 19.2+-8.3 /anol/l, p<0.05, respectively). Higher levels of vWF:antigen and nitrites/nitrates were observed in patients with more advanced degrees of liver failure, as reflected by quantitative Child-Pugh's score (516_ 154% and 38.3-7.8 #mol/l in Child-Pugh ->9 vs 227+-61% and 21.0-+6.1/anol/l in Child-Pugh <9, p<0.001, respectively). Moreover, both endothelial-related factors were higher in patients with ascites than those without ascites (543_+158% and 37.8+-8.9/anol/l vs 262+-103% and 24.4+-8.8/tmol/l, p<0.001, respectively). In the overall series, a highly significant linear correlation between nitrites/nitrates and vWF:antigen levels was observed in patients with cirrhosis (r=0.79, p<0.001). Conclusions: These results support a cirrhosis-related endothelial dysfunction and suggest that plasma vWF measurement could be useful as a marker of endothelial disturbance in patients with cirrhosis.
Introduction. There is a lack of information regarding outcomes after liver transplant in Latin A... more Introduction. There is a lack of information regarding outcomes after liver transplant in Latin America. Objectives. This study sought to describe outcomes after liver transplant in adult patients from Argentina. Methods. We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. Results. A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. Conclusions. We believe the information contained in this article might be of value for reviewing current practices and developing local policies. L IVER transplant (LT) is a well-established therapeutic practice in Argentina for patients with end-stage liver disease. In Argentina, the first LT was performed in 1988, and during past decades the annual number of LTs has increased steadily, placing Argentina at the top of Latin American LT rates [1]. This was possible due to the advances in surgical techniques, peritransplant intensive care, and immunosuppressive regimens, which resulted in significant improvements in short-term survival.
This study evaluated the clinical application of a pressure-sensitive gauge that allows the nonin... more This study evaluated the clinical application of a pressure-sensitive gauge that allows the noninvasive measurement of the pressure of esophageal varices at endoscopy. The study was performed in 70 patients with cirrhosis and portal hypertension. Among them, 47 had ...
Introducción: el examen histopatológico del hígado obtenido por biopsia percutánea es considerado... more Introducción: el examen histopatológico del hígado obtenido por biopsia percutánea es considerado tradicionalmente como el procedimiento de elección para evaluar el grado de fibrosis. Sin embargo, es un procedimiento invasivo y doloroso que tiene un pequeño riesgo de complicaciones. Recientemente se introdujo la elastografía de transición (Fibroscan ®), un nuevo método no invasivo para evaluar el grado de fibrosis que puede utilizarse en sustitución de la biopsia para diagnosticar (detectar o evaluar) la fibrosis hepática. La elastografía se ha evaluado en una serie de hepatopatías crónicas distintas a la hepatitis C para identificar la prevalencia de fibrosis, incluidas la hepatitis B, coinfección VIH-VHC, enfermedades colestásicas e hígado graso no alcohólico con una precisión diagnóstica que va de 75 a 93%. En el presente artículo se presenta la información más relevante sobre el uso del Fibroscan ® en la detección de la fibrosis hepática.
We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonis... more We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonist void of systemic effects, caused a significant reduction of portal pressure in conscious cirrhotic dogs. The mechanism by which ritanserin lowers portal pressure is poorly defined. We investigated the splanchnic and systemic hemodynamic effects of ritanserin (0.63 mg/kg body wt i.v., a dose known to completely inhibit binding of 5-hydroxytryptamine to its receptors), in conscious and unrestrained cirrhotic rats (n = 13). Heparinized catheters were placed into the portal vein, inferior vena cava, aorta, and left ventricle with exit from the neck. Hemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabeled microspheres and the reference sample method. Sixty minutes after administration, ritanserin caused a significant reduction of portal pressure (-17%) with minimal changes in portal venous inflow (+3%)...
Increased nitric oxide formation has been shown to be involved in the hyperdynamic circulation of... more Increased nitric oxide formation has been shown to be involved in the hyperdynamic circulation of portal hypertension. It has been proposed that it could be related to stimulation of the inducible nitric oxide synthase by endotoxin. Therefore, the aim of the present study was to evaluate whether dexamethasone treatment, an inhibitor of the expression of the inducible enzyme, ameliorates the hyperdynamic circulation observed in cirrhotic rats due to chronic bile duct ligation. Systemic and splanchnic hemodynamic parameters were measured after administration of dexamethasone (3 mg/kg/day during 3 days, i.p.) or its vehicle. In cirrhotic rats dexamethasone treatment caused a mild but not significantly higher mean arterial pressure in comparison with vehicle while similar values of cardiac output, peripheral vascular resistance, portal blood flow and portal pressure were observed in both group of animals. A significant body weight loss over the three days of treatment was observed in ra...
The validity of hemodynamic measurements by the reference sample method with microspheres injecti... more The validity of hemodynamic measurements by the reference sample method with microspheres injection into the aorta, via a carotid artery catheter, was evaluated in rats and compared with the results obtained after left ventricle injection. In the aorta injection group, a good mix of microspheres was observed in 83% of the animals. Moreover, a symmetrical distribution of microspheres was observed in 10 out of 12 rats (83%). An excellent correlation between right and left kidney-testes blood flows was observed (r = 0.93 and 0.96, respectively; P less than 0.01). Mean arterial pressure was not modified during microspheres injection into the aorta. Cardiac output (104 +/- 26 vs 101 +/- 23 ml/min, NS) and portal blood flow (14.2 +/- 3.3 vs 13.5 +/- 2.2 ml/min, NS) were similar after aorta and left ventricle injections series, respectively. Our results indicate that the injection of microspheres into the aorta is an adequate and easy approach to systemic and splanchnic hemodynamic measurements. This approach could be a good alternative to left ventricle injection of microspheres in experimental studies in rats.
Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The ai... more Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine...
Desmopressin (DDAVP), a synthetic analogue of vasopressin, has been shown to improve the bleeding... more Desmopressin (DDAVP), a synthetic analogue of vasopressin, has been shown to improve the bleeding time in patients with cirrhosis. The duration of this effect and the hemodynamic changes associated with DDAVP have not been studied so far. To evaluate these issues, 14 cirrhotics with portal hypertension were studied in basal conditions and after DDAVP (0.3 uk/kg). In 8 patients, hemostatic tests were done at basal conditions and 1, 3, 6 and 24 hs after drug administration. In the remaining 6 patients, mean arterial pressure, cardiac output, portal and femoral blood flows were evaluated. Hemodynamic parameters were measured by Doppler ultrasound. DDVP caused a marked decrease in bleeding time at 1, 3, 6 and 24 hs (14 +/- 9 vs 8 +/- 3, 7 +/- 4, 6 +/- 4 and 8 +/- 4 min, respectively); the decrease was maximal and statistically significant at 6 hs (55 +/- 15%, p < 0.02) after DDAVP infusion. Bleeding time reduction was observed in every patient studied. In the hemodynamic study, DDAVP...
The role of prostaglandins in the pathogenesis of the circulatory abnormalities of cirrhosis was ... more 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 ...
In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate... more In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate and cardiac output and diminishes portal pressure and collateral blood flow. However, there is little information on the possible effects of propranolol on hepatic artery blood flow. The present study addressed this question in 12 cirrhotic patients with end-to-side portacaval shunt, in whom all of the liver blood flow represents the hepatic artery blood flow. Hepatic artery blood flow (continuous infusion of indocyanine green), cardiac output (thermal dilution), heart rate and mean arterial pressure were measured before and 20 min after the intravenous infusion of 10 to 15 mg of propranolol. beta-Adrenergic blockade caused a significant reduction of cardiac output (from 9.1 +/- 2.1 to 7.1 +/- 1.4 liters per min, p less than 0.001) (mean +/- S.D.) and heart rate (from 85 +/- 10 to 71 +/- 7 beats per min, p less than 0.001), and a significant increase of systemic vascular resistance (fro...
We have recently shown that ventilation-perfusion (VA/Q) mismatching at rest in cirrhosis is due ... more We have recently shown that ventilation-perfusion (VA/Q) mismatching at rest in cirrhosis is due to an abnormal pulmonary vascular tone. It has been suggested that in patients with cirrhosis, O2 transfer might become diffusion-limited during exercise. This study examined pulmonary hemodynamics and mechanisms modulating gas exchange during exercise (60 to 70% VO2max) in six patients (41 +/- 5 yr, mean +/- SEM) with cirrhosis but with normal lung function tests. At rest, QT was high (8.4 +/- 0.5 L/min), pulmonary vascular resistance (PVR) was low (0.61 +/- 0.17 mm Hg/L/min), and there was mild to moderate VA/Q mismatching (LogSD Q, 0.79 +/- 0.09; normal range, 0.3 to 0.6). However, hyperventilation (PaCO2, 29 +/- 2 mm Hg) and high QT (thus, high PVO2, 41 +/- 2 mm Hg) contributed to the maintenance of PaO2 within normal values (99 +/- 7 mm Hg). Exercise VO2 (1,278 +/- 122 ml/min) was normal relative to work load, but, contrary to that in normal subjects, QT was higher and PVR did not fall. During exercise, PaO2 showed a trend to decrease (to 90 +/- 5 mm Hg) and PaCO2 to rise (to 35 +/- 2 mm Hg), but the differences failed to reach statistical significance (p = 0.07 each). PVO2 fell significantly with exercise (41 +/- 2 to 33 +/- 0.3 mm Hg, p less than 0.05), but neither AaPO2 (15 +/- 7 to 21 +/- 6 mm Hg) nor VA/Q inequality (LogSD Q, 0.82 +/- 0.11) changed. No systemic difference was noticed between predicted and measured PaO2 values, suggesting no O2 diffusion impairment during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to evaluate the relationship between plasma levels of von Willebrand fa... more The aim of this study was to evaluate the relationship between plasma levels of von Willebrand factor (vWF), a marker of endothelial cell activation, and nitric oxide, a powerful vasodilator synthesized by endothelial cells, in 27 patients with cirrhosis at different stages of the disease. These results were compared with those of age-matched normal, healthy subjects (n= 10). Methods: vWF:antigen was measured by electro-immunodiffusion test and serum nitrite and nitrate levels, the stable end products of nitric oxide metabolism, were determined by an enzymatic procedure. Results: vWF:antigen and nitrite/nitrate levels were significantly higher in cirrhotic patients (367+-185% and 29.3+-10.8 /anol/l) than in healthy subjects (92+-20% and 19.2+-8.3 /anol/l, p<0.05, respectively). Higher levels of vWF:antigen and nitrites/nitrates were observed in patients with more advanced degrees of liver failure, as reflected by quantitative Child-Pugh's score (516_ 154% and 38.3-7.8 #mol/l in Child-Pugh ->9 vs 227+-61% and 21.0-+6.1/anol/l in Child-Pugh <9, p<0.001, respectively). Moreover, both endothelial-related factors were higher in patients with ascites than those without ascites (543_+158% and 37.8+-8.9/anol/l vs 262+-103% and 24.4+-8.8/tmol/l, p<0.001, respectively). In the overall series, a highly significant linear correlation between nitrites/nitrates and vWF:antigen levels was observed in patients with cirrhosis (r=0.79, p<0.001). Conclusions: These results support a cirrhosis-related endothelial dysfunction and suggest that plasma vWF measurement could be useful as a marker of endothelial disturbance in patients with cirrhosis.
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