Roberto Groszmann | Yale University (original) (raw)
Uploads
Papers by Roberto Groszmann
Hepatology, 1991
In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric... more In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and 12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity.
Portal hypertension is the main complication of cirrhosis, regardless of its etiology. Variceal b... more Portal hypertension is the main complication of cirrhosis, regardless of its etiology. Variceal bleeding and ascites are direct consequences of portal hypertension and to a large extent, account for the high mortality and the high cost associated with the treatment of patients with cirrhosis 1 . Practically all patients with cirrhosis will eventually develop portal hypertension. Initially, portal pressure increases as a consequence of an increased resistance to portal flow due to scarring, compression and narrowing of the sinusoids. Later on, in addition to this elevated resistance to blood flow, there is an increase in portal blood inflow. When both resistance and flow are elevated, portal pressure increases even further and when a minimal pressure threshold is reached, the clinical complications of portal hypertension appear. Studies from our and other laboratories support the contention that a minimal portal pressure gradient of around 10-12mmHg is necessary for the development of varices and variceal bleeding, which is the most lethal consequence of portal hypertension. In portal hypertensive states, portal-systemic collaterals develop in an attempt to decompress the portal system and reduce portal pressure. In man, these communications occur throughout the abdominal cavity and through gastroesophageal varices that drain mostly into the azygos venous system. The extensive collateralization of the portal system which accompanies portal hypertension, shunts large amounts of portal blood away from the liver and reduces effective liver perfusion. This porto-systemic shunting induces in itself detrimental hepatic and systemic metabolic effects and plays a major role in the pathogenesis of another complication of cirrhosis, porto-systemic encephalopathy. Preventing the collateralization of the portal system may have beneficial effects not only because it may prevent or delay the formation of varices but also because it may reduce portal-systemic shunting. Studies performed in our laboratory using different experimental models of chronic liver disease (cirrhosis and schistosomiasis), have shown that propranolol, administered in the early stages of the portal hypertensive process ameliorates the progressive increase in portal pressure associated with chronic liver diseases and prevents the development of porto-systemic collaterals 2, 3 . Based on these studies a study has been developed in cirrhotic humans evaluating the use of betablockers for the prevention of variceal development. Hopefully this study will provide further insight regarding the efficacy of beta-blocker use in the earliest stages of cirrhosis. This study will be completed by September 2002.
Acta gastroenterologica Latinoamericana
Revista de gastroenterologia de Mexico
Digestion
... Intrahepatic Modulation of Portal Pressure and Its Role in Portal Hypertension Anthony M. Whe... more ... Intrahepatic Modulation of Portal Pressure and Its Role in Portal Hypertension Anthony M. Wheatley, Xing-yi Zhang Microcirculation Research Laboratory ... Bluhm RE, Frazer MG, Vore M, Pinson CW, Badr KF: Endothelins 1 and 3: Potent cholestatic agents secreted and excreted ...
Acta gastroenterologica Latinoamericana
The American Journal of Digestive Diseases
Two patients with spontaneous bacterial peritonitis caused by Neisseria meningitidis are describe... more Two patients with spontaneous bacterial peritonitis caused by Neisseria meningitidis are described. In both cases immediate diagnosis was possible by examination of the ascitic fluid. Meningococcal peritonitis supports the hypothesis that the hematogenous spread of bacteria into the ascitic fluid may be one of the mechanisms of spontaneous bacterial peritonitis.
Gastroenterology
In an effort to avoid the potentially dangerous side effects of vasopressin infusions, we attempt... more In an effort to avoid the potentially dangerous side effects of vasopressin infusions, we attempted to reproduce mechanically the splanchnic hemodynamic changes induced by vasopressin without its systemic effects. Superior mesenteric arterial pressure was reduced to 50 to 70 mm Hg for 30 to 60 min in 10 normal dogs by partial balloon obstruction of the superior mesenteric artery. Balloon inflation caused a decrease in portal venous pressure (5.6 +/- 0.6 versus 2.8 +/- 0.7 mm Hg), hepatic vein wedge pressure (4.8 +/- 0.4 versus 2.3 +/- 0.5 mm Hg), and portal vein flow 424 +/- 53 versus 275 +/- 52 ml per min), and an increase in hepatic arterial blood flow (172 +/- 19 versus 217 +/- 29 ml per min). Total hepatic blood flow and oxygen delivery to the liver were unchanged. Partial balloon obstruction caused an increase in cardiac output (1950 +/- 203 versus 2317 +/- 376 ml per min) and mean arterial pressure 138 +/- 6 versus 151 +/- 7 mm Hg), whereas heart rate did not change. Partial balloon obstruction of the superior mesenteric artery caused similar changes in splanchnic hemodynamics to those of vasopressin infusions into the superior mesenteric artery, but without the potential deleterious effects of vasopressin on systemic hemodynamics.
Gastroenterology
Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown ... more Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown to be effective in controlling hemorrhage from esophagogastric varices. Intravenous infusions of vasopressin (IVV), which can be initiated rapidly and require less sophisticated equipment and personnel, have also been reported to control variceal hemorrhage. We undertook a controlled clinical trial to compare these two routes of administration. Twenty-two cirrhotic patients with massive hemorrhage from varices were randomized to receive either IVV or IAV. Intraarterial vasopressin was begun at 0.1 U/min and increased progressively as needed to 0.2, 0.3, 0.4, and 0.5 U/min. Intravenous vasopressin was begun at 0.3 U/min and increased progressively as needed to 0.6, 0.9, 1.2, and 1.5 U/min. Hemorrhage was controlled in 5 of 10 episodes (50%) with IVV and in 6 of 12 episodes (50%) with IAV. Seven of the ten episodes treated with IVV (70%) ended fatally compared with 9 of 12 treated with IAV (75%). Side-effects and complications occurred with similar frequency in the two groups. The two routes of administration are equal in effects, side-effects, and complications. We recommend that IVV, which can be administered more easily, be given a brief therapeutic trial early in the management of hemorrhage from varices.
Gastroenterology
The accuracy and reliability of a balloon catheter for measuring wedged hepatic venous pressure (... more The accuracy and reliability of a balloon catheter for measuring wedged hepatic venous pressure (WHVP) were evaluated in 82 simultaneous determinations using the balloon catheter technique and the direct measurement of portal venous pressure. These measurements showed a close positive correlation (r = 0.97) over a wide range of pressures in 12 normal and 4 cirrhotic dogs. Studies were then performed in 13 cirrhotic patients in whom the balloon catheter was introduced using the Seldinger technique. Free hepatic venous pressure (FHVP) was measured with the balloon undistended. By distending the balloon to occlude the hepatic vein, the WHVP was recorded. Comparison of FHVP and WHVP with the conventional and balloon techniques revealed a close positive correlation (r = 0.89 and 0.93, respectively). The correlation was virtually perfect for the hepatic venous pressure gradient (WHVP-FHVP, r = 0.98). The balloon technique offers many advantages over the conventional approach, including the ease of achieving and demonstrating the wedged position from the femoral approach, the ability to measure the free and wedged pressure repeatedly without manipulating the catheter, and the measurement of pressure in a larger, more representative segment of the liver.
The American journal of physiology
The American journal of physiology
A method for determining the extent of portal-systemic shunting (PSS) is described and evaluated ... more A method for determining the extent of portal-systemic shunting (PSS) is described and evaluated in lightly anesthetized (ketamine) rats. This method relies on the intrasplenic injection of 15-micrometers gamma-labeled spheres and the subsequent measurement of liver and lung radioactivities. After the splenic injection of the microspheres, a fraction of microspheres shunting the hepatic sinusoidal bed will be entrapped in the lungs. Thus, the ratio, lung/(lung + liver) radioactivities, will indicate the degree of PSS. The percent of PSS was determined in normal (n = 13; 1.2 +/- 0.3%), in cirrhotic (n = 9; 15.0 +/- 4.5%; P less than 0.01), and in portal vein-ligated animals (n = 14; 95.0 +/- 0.9%; P less than 0.001 for normal and cirrhotic). In addition, PSS was sequentially quantitated (n = 3) before (3.0%) and after (89%) partial portal vein ligation. The variability of PSS found in cirrhotic rats (0.7-41.0%) is in agreement with the reported data for PSS in patients. This technique, which is simple, rapid, and reproducible, allows the quantitation of PSS in small laboratory animals.
Hepatology
A method to quantitate blood flow through the gastroesophageal collaterals in portal hypertensive... more A method to quantitate blood flow through the gastroesophageal collaterals in portal hypertensive patients was developed. Since gastroesophageal collaterals drain into the azygos system, it is postulated that measurement of blood flow in the azygos vein should provide a quantitative measurement of gastroesophageal collateral blood flow changes in portal hypertensive patients. Azygos blood flow was measured using a double thermodilution catheter directed under fluoroscopy to the azygos vein. Ten patients with alcoholic cirrhosis were studied. Five of these patients had a history of repeated bleeding from gastroesophageal varices (Group I). The azygos blood flow in these patients was 596 f 78 ml per min. The other five patients all had decompressive surgery of the portal system (Group 11). In these patients the azygos venous blood flow was 305 k 29 ml per min (p < 0.01). The coefficient of variation of repeated baseline measurements was of 4.4 f 0.6%.
Hepatology
We have recently shown that maintenance of portal hypertension in rats is highly dependent on hig... more We have recently shown that maintenance of portal hypertension in rats is highly dependent on high portal blood flow. This study attempts to determine whether portal hypertension, induced in the rat by partial constriction of the portal vein, can be reduced by lowering portal blood flow with a beta blocking agent. Portal hypertensive rats treated with propranolol had a reduction in portal blood floC to 0.89 f 0.13 ml-min-'.gm-' accompanied by reduction in portal pressure to 12.6 k 1.00 mm Hg, disproportionately small because of a rise in portal-collateral vascular resistance ,to 12.52 f 1.63 dyne. sec. cm-'. gm .lo' accompanying the portal blood flow reduction.
Hepatology, 1991
In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric... more In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and 12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity.
Portal hypertension is the main complication of cirrhosis, regardless of its etiology. Variceal b... more Portal hypertension is the main complication of cirrhosis, regardless of its etiology. Variceal bleeding and ascites are direct consequences of portal hypertension and to a large extent, account for the high mortality and the high cost associated with the treatment of patients with cirrhosis 1 . Practically all patients with cirrhosis will eventually develop portal hypertension. Initially, portal pressure increases as a consequence of an increased resistance to portal flow due to scarring, compression and narrowing of the sinusoids. Later on, in addition to this elevated resistance to blood flow, there is an increase in portal blood inflow. When both resistance and flow are elevated, portal pressure increases even further and when a minimal pressure threshold is reached, the clinical complications of portal hypertension appear. Studies from our and other laboratories support the contention that a minimal portal pressure gradient of around 10-12mmHg is necessary for the development of varices and variceal bleeding, which is the most lethal consequence of portal hypertension. In portal hypertensive states, portal-systemic collaterals develop in an attempt to decompress the portal system and reduce portal pressure. In man, these communications occur throughout the abdominal cavity and through gastroesophageal varices that drain mostly into the azygos venous system. The extensive collateralization of the portal system which accompanies portal hypertension, shunts large amounts of portal blood away from the liver and reduces effective liver perfusion. This porto-systemic shunting induces in itself detrimental hepatic and systemic metabolic effects and plays a major role in the pathogenesis of another complication of cirrhosis, porto-systemic encephalopathy. Preventing the collateralization of the portal system may have beneficial effects not only because it may prevent or delay the formation of varices but also because it may reduce portal-systemic shunting. Studies performed in our laboratory using different experimental models of chronic liver disease (cirrhosis and schistosomiasis), have shown that propranolol, administered in the early stages of the portal hypertensive process ameliorates the progressive increase in portal pressure associated with chronic liver diseases and prevents the development of porto-systemic collaterals 2, 3 . Based on these studies a study has been developed in cirrhotic humans evaluating the use of betablockers for the prevention of variceal development. Hopefully this study will provide further insight regarding the efficacy of beta-blocker use in the earliest stages of cirrhosis. This study will be completed by September 2002.
Acta gastroenterologica Latinoamericana
Revista de gastroenterologia de Mexico
Digestion
... Intrahepatic Modulation of Portal Pressure and Its Role in Portal Hypertension Anthony M. Whe... more ... Intrahepatic Modulation of Portal Pressure and Its Role in Portal Hypertension Anthony M. Wheatley, Xing-yi Zhang Microcirculation Research Laboratory ... Bluhm RE, Frazer MG, Vore M, Pinson CW, Badr KF: Endothelins 1 and 3: Potent cholestatic agents secreted and excreted ...
Acta gastroenterologica Latinoamericana
The American Journal of Digestive Diseases
Two patients with spontaneous bacterial peritonitis caused by Neisseria meningitidis are describe... more Two patients with spontaneous bacterial peritonitis caused by Neisseria meningitidis are described. In both cases immediate diagnosis was possible by examination of the ascitic fluid. Meningococcal peritonitis supports the hypothesis that the hematogenous spread of bacteria into the ascitic fluid may be one of the mechanisms of spontaneous bacterial peritonitis.
Gastroenterology
In an effort to avoid the potentially dangerous side effects of vasopressin infusions, we attempt... more In an effort to avoid the potentially dangerous side effects of vasopressin infusions, we attempted to reproduce mechanically the splanchnic hemodynamic changes induced by vasopressin without its systemic effects. Superior mesenteric arterial pressure was reduced to 50 to 70 mm Hg for 30 to 60 min in 10 normal dogs by partial balloon obstruction of the superior mesenteric artery. Balloon inflation caused a decrease in portal venous pressure (5.6 +/- 0.6 versus 2.8 +/- 0.7 mm Hg), hepatic vein wedge pressure (4.8 +/- 0.4 versus 2.3 +/- 0.5 mm Hg), and portal vein flow 424 +/- 53 versus 275 +/- 52 ml per min), and an increase in hepatic arterial blood flow (172 +/- 19 versus 217 +/- 29 ml per min). Total hepatic blood flow and oxygen delivery to the liver were unchanged. Partial balloon obstruction caused an increase in cardiac output (1950 +/- 203 versus 2317 +/- 376 ml per min) and mean arterial pressure 138 +/- 6 versus 151 +/- 7 mm Hg), whereas heart rate did not change. Partial balloon obstruction of the superior mesenteric artery caused similar changes in splanchnic hemodynamics to those of vasopressin infusions into the superior mesenteric artery, but without the potential deleterious effects of vasopressin on systemic hemodynamics.
Gastroenterology
Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown ... more Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown to be effective in controlling hemorrhage from esophagogastric varices. Intravenous infusions of vasopressin (IVV), which can be initiated rapidly and require less sophisticated equipment and personnel, have also been reported to control variceal hemorrhage. We undertook a controlled clinical trial to compare these two routes of administration. Twenty-two cirrhotic patients with massive hemorrhage from varices were randomized to receive either IVV or IAV. Intraarterial vasopressin was begun at 0.1 U/min and increased progressively as needed to 0.2, 0.3, 0.4, and 0.5 U/min. Intravenous vasopressin was begun at 0.3 U/min and increased progressively as needed to 0.6, 0.9, 1.2, and 1.5 U/min. Hemorrhage was controlled in 5 of 10 episodes (50%) with IVV and in 6 of 12 episodes (50%) with IAV. Seven of the ten episodes treated with IVV (70%) ended fatally compared with 9 of 12 treated with IAV (75%). Side-effects and complications occurred with similar frequency in the two groups. The two routes of administration are equal in effects, side-effects, and complications. We recommend that IVV, which can be administered more easily, be given a brief therapeutic trial early in the management of hemorrhage from varices.
Gastroenterology
The accuracy and reliability of a balloon catheter for measuring wedged hepatic venous pressure (... more The accuracy and reliability of a balloon catheter for measuring wedged hepatic venous pressure (WHVP) were evaluated in 82 simultaneous determinations using the balloon catheter technique and the direct measurement of portal venous pressure. These measurements showed a close positive correlation (r = 0.97) over a wide range of pressures in 12 normal and 4 cirrhotic dogs. Studies were then performed in 13 cirrhotic patients in whom the balloon catheter was introduced using the Seldinger technique. Free hepatic venous pressure (FHVP) was measured with the balloon undistended. By distending the balloon to occlude the hepatic vein, the WHVP was recorded. Comparison of FHVP and WHVP with the conventional and balloon techniques revealed a close positive correlation (r = 0.89 and 0.93, respectively). The correlation was virtually perfect for the hepatic venous pressure gradient (WHVP-FHVP, r = 0.98). The balloon technique offers many advantages over the conventional approach, including the ease of achieving and demonstrating the wedged position from the femoral approach, the ability to measure the free and wedged pressure repeatedly without manipulating the catheter, and the measurement of pressure in a larger, more representative segment of the liver.
The American journal of physiology
The American journal of physiology
A method for determining the extent of portal-systemic shunting (PSS) is described and evaluated ... more A method for determining the extent of portal-systemic shunting (PSS) is described and evaluated in lightly anesthetized (ketamine) rats. This method relies on the intrasplenic injection of 15-micrometers gamma-labeled spheres and the subsequent measurement of liver and lung radioactivities. After the splenic injection of the microspheres, a fraction of microspheres shunting the hepatic sinusoidal bed will be entrapped in the lungs. Thus, the ratio, lung/(lung + liver) radioactivities, will indicate the degree of PSS. The percent of PSS was determined in normal (n = 13; 1.2 +/- 0.3%), in cirrhotic (n = 9; 15.0 +/- 4.5%; P less than 0.01), and in portal vein-ligated animals (n = 14; 95.0 +/- 0.9%; P less than 0.001 for normal and cirrhotic). In addition, PSS was sequentially quantitated (n = 3) before (3.0%) and after (89%) partial portal vein ligation. The variability of PSS found in cirrhotic rats (0.7-41.0%) is in agreement with the reported data for PSS in patients. This technique, which is simple, rapid, and reproducible, allows the quantitation of PSS in small laboratory animals.
Hepatology
A method to quantitate blood flow through the gastroesophageal collaterals in portal hypertensive... more A method to quantitate blood flow through the gastroesophageal collaterals in portal hypertensive patients was developed. Since gastroesophageal collaterals drain into the azygos system, it is postulated that measurement of blood flow in the azygos vein should provide a quantitative measurement of gastroesophageal collateral blood flow changes in portal hypertensive patients. Azygos blood flow was measured using a double thermodilution catheter directed under fluoroscopy to the azygos vein. Ten patients with alcoholic cirrhosis were studied. Five of these patients had a history of repeated bleeding from gastroesophageal varices (Group I). The azygos blood flow in these patients was 596 f 78 ml per min. The other five patients all had decompressive surgery of the portal system (Group 11). In these patients the azygos venous blood flow was 305 k 29 ml per min (p < 0.01). The coefficient of variation of repeated baseline measurements was of 4.4 f 0.6%.
Hepatology
We have recently shown that maintenance of portal hypertension in rats is highly dependent on hig... more We have recently shown that maintenance of portal hypertension in rats is highly dependent on high portal blood flow. This study attempts to determine whether portal hypertension, induced in the rat by partial constriction of the portal vein, can be reduced by lowering portal blood flow with a beta blocking agent. Portal hypertensive rats treated with propranolol had a reduction in portal blood floC to 0.89 f 0.13 ml-min-'.gm-' accompanied by reduction in portal pressure to 12.6 k 1.00 mm Hg, disproportionately small because of a rise in portal-collateral vascular resistance ,to 12.52 f 1.63 dyne. sec. cm-'. gm .lo' accompanying the portal blood flow reduction.