Increased blood flow through the portal system in cirrhotic rats

Portal venous pressure is the result of the interplay between portal venous blood flow and the vascular resistance offered to that flow. Whether portal hypertension is maintained only by an increased portal venous resistance or also by an increased blood flow within the portal venous system is still open to speculation. To resolve these differences, splanchnic and systemic hemodynamics were evaluated in cirrhotic rats, induced by CCl4. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. All cirrhotic rats had portal hypertension (portal venous pressure 13.5 +/- 1.1 vs. 9.0 +/- 0.5 mmHg, in normal control rats; p less than 0.01), but portal-systemic shunting in cirrhosis (31% +/- 13% vs. 0.2% +/- 0.02%; p less than 0.05) was variable, ranging from 1% to 97%. Portal venous inflow, the total blood flow within the portal system, was increased in cirrhotic rats (5.75 +/- 0.04 vs. 4.52 +/- 0.36 ml/min per 100 g; p less than 0.05). Total splanchnic arterial resistance was reduced in cirrhotic rats (3.3 +/- 0.2 vs. 5.8 +/- 0.5 dyn X s X cm-5 X 10(5); p less than 0.01). Portal venous resistance, however, was not abnormally elevated in cirrhotic rats (4.6 +/- 0.5 vs. 4.7 +/- 0.5 dyn X s X cm-5 X 10(4), p = NS). Splanchnic hemodynamics in cirrhotic rats demonstrate that portal hypertension is maintained, at least in part, by a hyperdynamic portal venous inflow. The hemodynamic data in cirrhotic rats provided evidence that supports the role of an increased portal blood flow in portal hypertension and gives a quantitative definition of splanchnic hemodynamics in intrahepatic portal hypertension.     

Hemodynamic effects of blood volume restitution following a hemorrhage in rats with portal hypertension due to cirrhosis of the liver: influence of the extent of portal-systemic shunting

The present study investigated whether, in rats with portal hypertension due to cirrhosis of the liver induced by carbon tetrachloride, blood volume restitution following a hemorrhage produces an increase of portal pressure beyond control values, as observed in rats with prehepatic portal hypertension. Since carbon tetrachloride-induced cirrhosis caused mild portal-systemic shunting, in some of the cirrhotic rats (12 of 29 rats) portal-systemic shunting was enhanced by a transient (4 days) partial constriction of the portal vein, which was removed 1 week prior to the study. After baseline measurements of portal pressure and arterial pressure, 15 ml per kg of blood were withdrawn at a rate of 0.3 ml per min and reinfused 15 min later. After blood reinfusion, portal pressure and arterial pressure were measured again, and cardiac output, regional blood flows and portal-systemic shunting were determined using radioactive microspheres. Portal-systemic shunting was 78 +/- 11% of total blood flow in the cirrhotic rats that had temporary portal vein constriction, but only 5 +/- 2% (p less than 0.001) in those that did not. Blood volume restitution in low-portal-systemic shunting rats did not produce any significant modification in splanchnic or systemic hemodynamics. However, in rats with high portal-systemic shunting, blood volume restitution produced a significant increase in portal pressure (from 9.9 +/- 0.9 to 13.5 +/- 0.9 mmHg, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperdynamic circulation in a chronic murine schistosomiasis model of portal hypertension

Chronic murine schistosomiasis is a natural disease model of portal hypertension closely mimicking the clinical and histological features of human hepatic schistosomiasis. We studied the splanchnic and systemic hemodynamics in the murine model of schistosomiasis by radioactive microsphere technique. Mice infected with 60 cercariae of Schistosoma mansoni (n = 8) were studied hemodynamically 11 wk after the infection and were compared with age-matched healthy controls (n = 11). Mean portal venous inflow in the infected mice (3.82 +/- 0.32 ml/min) was 61% higher than in the healthy animals (2.37 +/- 0.25 ml/min; p less than 0.01). A twofold increase in hepatic arterial flow was also seen in mice with schistosomiasis (0.47 +/- 0.14 ml/min) as compared with controls (0.16 +/- 0.03 ml/min; p less than 0.05), whereas splanchnic arteriolar resistance (60.91 +/- 7.64 vs. 101.21 +/- 11.06 mm Hg.min.ml-1.gm; p less than 0.05) and peripheral vascular resistance (112.05 +/- 14.05 vs 254.53 +/- 29.86 mm Hg.min.ml-1.gm; p less than 0.01) were reduced. There was a significant increase in cardiac index (752 +/- 99 vs. 453 +/- 55 ml.min-1.kg body weight-1; p less than 0.05) and reduction in mean arterial pressure (81.37 +/- 3.09 vs. 101.45 +/- 5.85 mm Hg; p less than 0.05) in the infected animals compared with controls. These observations clearly demonstrate the existence of a hyperdynamic circulatory state in this model of portal hypertension.     

Effects of ritanserin, a selective and specific S2-serotonergic antagonist, on portal pressure and splanchnic hemodynamics in portal hypertensive rats

Serotonergic mechanisms have recently been implicated in the pathogenesis of portal hypertension; this suggests that blockade of serotonin S2 receptors may be a new approach for the pharmacological therapy of portal hypertension. This study was aimed at investigating the effects of ritanserin, a selective S2-serotonergic antagonist, in portal-hypertensive rats whose condition was due to partial portal vein ligation. The animals were randomized under double-blind conditions into two groups: the first received ritanserin (0.7 mg/kg body wt, intravenously), and the second received the same volume of placebo (isotonic saline solution). The hemodynamic studies were performed using radiolabeled microspheres 60 min after drug administration. Ritanserin administration significantly reduced portal pressure (from 11.8 +/- 0.8 mm Hg to 9.4 +/- 0.6 mm Hg; p less than 0.05). This was associated with lower portocollateral resistance (1.8 +/- 0.2 mm Hg/ml/min 100 gm in the ritanserin group vs. 2.3 +/- 0.2 mm Hg/ml/min 100 gm in rats receiving placebo; not significant), but we saw no changes in portal-vein inflow (5.5 +/- 0.7 ml/min 100 gm vs. 5.4 +/- 0.5 ml/min 100 gm), mean arterial pressure (95.9 +/- 3.5 mm Hg vs. 94.0 +/- 4.0 mm Hg) and cardiac index (31.9 +/- 3.5 ml/min 100 gm vs. 28.5 +/- 2.6 ml/min 100 gm). Hepatic arterial and kidney blood flows were not modified by ritanserin. In summary, our results demonstrate that ritanserin infusion decreases portal pressure without causing systemic hemodynamic changes. This effect is probably due to a decrease in portocollateral resistance in portal-hypertensive rats. These results provide further for a role of serotonin in the pathogenesis of portal hypertension.     

Alterations in endocardial vascular resistance after reperfusion in a low flow, high demand model of ischemia: effects of dipyridamole and WEB-2086, a platelet-activating factor antagonist

To determine if alterations in regional coronary vascular resistance could occur in the type of myocardial ischemia present in severe angina pectoris, regional perfusion and function were studied in 35 conscious sedated dogs. A stenosis producing severe hypokinesia of the perfused segment was created for 2 h on the left anterior descending coronary artery and 10 episodes of 1 min of high demand ischemia (atrial pacing at a rate sufficient to induce dyskinesia in the hypoperfused segment) were superimposed before reperfusion. The dogs were randomized into three treatment groups: control (n = 13), dipyridamole (n = 10) or WEB-2086 (n = 12), an antagonist of the effects of the endogenous platelet-activating factor. During stenosis, residual endocardial blood flow in the ischemic but nonnecrotic area averaged 0.72 +/- 0.14, 0.38 +/- 0.13 and 0.68 +/- 0.17 ml/min per g in the control, WEB-2086 and dipyridamole groups, respectively. Twenty-four hours after reperfusion, endocardial blood flow in the ischemic area was significantly lower in control dogs (1.04 +/- 0.15 ml/min per g) than in dogs treated with WEB-2086 (1.44 +/- 0.28 ml/min per g; p less than 0.03) or dipyridamole (3.00 +/- 0.83 ml/min per g; p less than 0.01). Accordingly, in control dogs, endocardial coronary vascular resistance in the ischemic area was increased after reperfusion from 85 +/- 11 to 124 +/- 27 mm Hg/(ml/min per g) (p less than 0.05) after 24 h. In contrast, coronary vascular resistance in the ischemic area remained unchanged in dogs receiving WEB-2086 (77 +/- 8 to 79 +/- 9 mm Hg/(ml/min per g); p = NS) and it decreased significantly in dogs receiving dipyridamole (72 +/- 8 to 44 +/- 8 mm Hg/(ml/min per g); p less than 0.01). Regional function after 24 h remained depressed in all three groups. These data indicate that low flow, high demand ischemia induces alterations in the subendocardial microvasculature. Such alterations in regional coronary vascular resistance might play a role in several forms of ischemic heart disease such as in severe angina, but they appear susceptible to improvement by therapeutic interventions that influence granulocyte and platelet activation.     

Systemic hypotension and decreased pressor response in dogs with chronic bile duct ligation

Vascular instability as defined by systemic hypotension and unresponsiveness to endogenous or exogenous vasoactive substances is a feature of both patients and experimental animals with obstructive jaundice. In this study, we have attempted to dissect the possible mechanisms for these abnormalities using both in vivo and in vitro methods. In vivo cumulative pressor responses (Rmax) to intravenous and intraarterial infusions of norepinephrine and angiotensin II and to intravenous infusion of angiotensin I were studied pre- and postoperatively in chronic bile duct-ligated dogs and compared to sham-operated dogs. Preoperatively, the pressor responses to the cumulative infusion of six doses of vasoactive substances in the pre-sham operated and pre-chronic bile duct-ligated dogs were not significantly different. Postoperatively, in the sham-operated dogs, there was no significant change in systemic blood pressure at 1 and 3 weeks, and only in isolated instances were significantly different pressor responses found compared to the preoperative result. In chronic bile duct-ligated dogs, the mean systemic blood pressure fell significantly from 117.2 +/- 3.1 to 107.2 +/- 3.0 mm Hg (p less than 0.01) at 1 week and remained significantly lower at 3 weeks [109.7 +/- 2.6 mm Hg (p less than 0.05)]. The Rmax to intravenous, but not intraarterial norepinephrine, was significantly decreased. In contrast, the Rmax to both intravenous and intraarterial angiotensin II infusions were significantly depressed at both 1 and 3 weeks. Similarly, the response to intravenous angiotensin I was significantly depressed. Cardiac output rose moderately in two sham-operated dogs from an average of 3.1 to 3.5 liters per min by 3 weeks associated with a decrease of 14.8% in peripheral vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures

To study the mechanism and hemodynamic significance of myocardial ischemia in hypertrophic cardiomyopathy, 20 patients (nine with resting left ventricular outflow tract obstruction greater than or equal to 30 mm Hg) with a history of angina pectoris and angiographically normal coronary arteries underwent a pacing study with measurement of great cardiac vein flow, lactate and oxygen content, and left ventricular filling pressure. Compared with 28 control subjects without hypertrophic cardiomyopathy, their resting coronary blood flow was higher (91 +/- 27 vs 66 +/- 17 ml/min; p less than .001) and their coronary resistance was lower (1.13 +/- 0.38 vs 1.55 +/- 0.45 mm Hg/ml/min; p less than .001). Left ventricular end-diastolic pressure (16 +/- 6 vs 11 +/- 3 mm Hg; p less than .001) and pulmonary arterial wedge pressure (13 +/- 5 vs 7 +/- 3 mm Hg; p less than .001) were significantly higher in patients with hypertrophic cardiomyopathy. During pacing, coronary flow rose in both groups, although coronary and myocardial hemodynamics differed greatly. In contrast to the linear increase in flow in control subjects up to heart rate of 150 beats/min (66 +/- 17 to 125 +/- 28 ml/min), patients with hypertrophic cardiomyopathy demonstrated an initial rise in flow to 133 +/- 31 ml/min at an intermediate heart rate of 130 beats/min. At this point, 12 of 20 patients developed their typical chest pain. With continued pacing to a heart rate of 150 beats/min, mean coronary flow fell to 114 +/- 29 ml/min (p less than .002), with 18 of 20 patients experiencing their typical chest pain and metabolic evidence of myocardial ischemia. This fall in coronary flow was associated with a substantial rise in left ventricular end-diastolic pressure (30 +/- 9 mm Hg immediately after peak pacing). In the 14 patients whose coronary flow actually fell from intermediate to peak pacing, the rise in left ventricular end-diastolic pressure in the same interval was greater than that of the six patients whose flow remained unchanged or increased (11 +/- 8 vs 2 +/- 2 mm Hg; p less than .01). In addition, despite metabolic and hemodynamic evidence of myocardial ischemia, the arteriovenous O2 difference actually narrowed at peak pacing. Thus most patients with hypertrophic cardiomyopathy achieved maximum coronary vasodilation and flow at modest increases in heart rate. Elevation in left ventricular filling pressure, probably related to ischemia-induced changes in ventricular compliance, was associated with a decline in coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS)     

Interrelationship between splenic and superior mesenteric venous circulation manifested by transient splenic arterial occlusion using a balloon catheter

We examined the hemodynamic changes induced by transient splenic arterial occlusion using a balloon catheter to investigate the hemodynamic effect of transcatheter splenic arterial embolization--a procedure that has been used since its introduction in 1973 as therapy for hypersplenism and more recently for portal hypertension. The blood flow volume was measured in 20 patients with liver disease using an ultrasonic duplex system (Toshiba SAL50A/SDL-01A). The portal venous pressure was also measured via a 3F catheter using a transducer. The catheter was placed in position by substituting it for a 25-gauge needle that had been inserted into the portal vein under ultrasonic guidance percutaneously and transhepatically. Splenic arterial occlusion caused a drop in splenic venous blood flow from 708 +/- 487 to 241 +/- 155 ml per min, in portal venous blood flow from 993 +/- 439 to 807 +/- 419 ml per min and in portal venous pressure from 17.4 +/- 7.2 to 14.4 +/- 6.1 mm Hg. The latter two reductions were less than expected from the decrease in the splenic venous blood flow volume. This phenomenon was caused by an increase in the mesenteric venous blood flow from 475 +/- 126 to 630 +/- 270 mm per min. This increase may be due to a compensatory mechanism under the control of a regulatory loop in the liver or portal vein, and there seems to be a relationship between splenic and intestinal circulation in portal hypertension that maintains hepatic circulation.     

Acute and chronic hemodynamic effects of propranolol in unselected cirrhotic patients

Different and contradictory results concerning the use of propranolol in the treatment of portal hypertension have been reported. This study was designed to investigate the hemodynamic effects of short- and long-term administration of propranolol in portal hypertensive patients. Portal pressure, cardiac index, heart rate and blood pressure were obtained in 18 unselected alcoholic cirrhotic patients with esophageal varices before and 60 min after the oral administration of 40 mg propranolol and again after 106 +/- 35 days of continuous oral administration (mean dose = 158 +/- 63 mg per day). Baseline portal pressure was 21.7 +/- 7.2 mm Hg. It decreased after 60 min to 17.2 +/- 5.5 mm Hg (p less than 0.01) and after long-term administration of propranolol to 16.1 +/- 5.7 mm Hg (p less than 0.01). No decrease in portal pressure was noted in 9 of 18 (50%) patients after acute administration and 5 of 17 (30%) patients after long-term administration. Baseline cardiac index was 5.1 +/- 1.2 liters X min-1 X m-2. It decreased after 60 min to 3.9 +/- 1.4 liters X min-1 X m-2 (p less than 0.01) and to 3.6 +/- 1.0 liters X min-1 X m-2 after long-term administration (p less than 0.001). Baseline heart rate was 85 +/- 11 beats per min. It decreased after 60 min to 75 +/- 9 (p less than 0.001) and after long-term administration to 62 +/- 6 (p less than 0.001) beats per min. Baseline mean arterial pressure was 108 +/- 11 Hg. It decreased after 60 min to 97 +/- 14 mm Hg (p less than 0.01) and after long-term administration to 103 +/- 14 mm Hg (not statistically significant).(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of tolerance to nitroglycerin in the arterial and venous circulation of dogs

The purpose of this study was to define the effects of nitroglycerin on venous tone and to investigate the time course of nitroglycerin tolerance in the peripheral circulation. The changes in the arterial and venous circulation resulting from an intravenous infusion of nitroglycerin (5 micrograms/kg per min) after 5 minutes (acute infusion) were compared with those changes that occurred after 2 hours (chronic infusion) of the same infusion in six splenectomized, ganglion-blocked dogs. Hemodynamics, blood volume and venous and arterial compliance were measured during each infusion. Nitroglycerin initially decreased mean arterial pressure from 81.5 +/- 2.0 to 57.6 +/- 2.7 mm Hg (p less than 0.01). Central blood volume decreased from 21.1 +/- 1.4 to 15.9 +/- 1.1 ml/kg (p less than 0.01), while total blood volume and unstressed vascular volume did not change. In the acute study, nitroglycerin increased venous compliance 33% from 1.75 +/- 0.14 to 2.32 +/- 0.16 ml/mm Hg per kg (p less than 0.01) and arterial compliance 33% from 0.049 +/- 0.007 to 0.065 +/- 0.007 ml/mm Hg per kg (p less than 0.01). At the end of the 2 hour infusion, arterial pressure increased and was now unchanged from control. Central blood volume had returned to baseline, 17.8 +/- 0.9 ml/kg. Total blood volume and unstressed vascular volume remained unchanged. With the long-term infusion, both arterial and venous compliance decreased (p less than 0.02) to 0.050 +/- 0.006 and 1.50 +/- 0.06 ml/mm Hg per kg, respectively, such that neither value was different from control. Nitroglycerin levels remained constant throughout.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bradykinin contribution to renal blood flow effect of angiotensin converting enzyme inhibitor in the conscious sodium-restricted dog

We examined the relative contribution of renin-angiotensin system blockade and bradykinin potentiation to the renal hemodynamic effect of the angiotensin converting enzyme inhibitor enalaprilat in sodium-deprived dogs. Six conscious dogs instrumented for monitoring of blood pressure (BP) and renal blood flow (RBF) were employed in five groups of experiments. In group 1, enalaprilat alone was administered, and it decreased BP by -24 +/- 3 mm Hg and increased RBF by 135 +/- 15 ml/min. During a constant intravenous infusion of saralasin (group 2), enalaprilat decreased BP by -7 +/- 3 mm Hg and increased RBF by 84 +/- 7 ml/min (delta BP and delta RBF, p less than 0.01 vs. group 1 by analysis of variance). During a constant intrarenal arterial infusion of saralasin (group 3), the respective changes in BP and RBF after enalaprilat were -10 +/- 3 mm Hg and 69 +/- 12 ml/min, and these results did not differ from those of group 2. The infusion of saralasin intravenously or intrarenal arterially decreased BP slightly and increased RBF. In the presence of an intravenous infusion of a specific bradykinin antagonist, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg.TFA (B5630) (group 4), enalaprilat decreased BP by -28 +/- 4 mm Hg and increased RBF by 82 +/- 24 ml/min (delta RBF, p less than 0.01 vs. group 1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic studies in long- and short-term portal hypertensive rats: the relation to systemic glucagon levels

It is not known whether the hyperdynamic state which has been observed in several experimental models and in patients with portal hypertension reflects a temporary phase during the evolution of the portal hypertensive syndrome or is an expression of a permanent steady state. A hemodynamic study was performed in a group of rats with long-standing portal hypertension induced by portal vein constriction performed 6.2 +/- 0.1 months earlier. A group of rats matched by age and weight with short-term (20.7 +/- 0.9 days) portal hypertension and a group of long-term (6.2 +/- 0.1 months) sham-operated rats were used as controls. Cardiac output and regional blood flows were measured using a radioactive microsphere technique. Arterial blood levels of glucagon, a known vasodilator that was implicated in the etiology of the hyperdynamic circulation, were also measured. Portal pressure in long- and short-term portal hypertensive groups (12.3 +/- 0.4 and 13.7 +/- 0.4 mm Hg; not statistically significant) was higher than in the sham group (9.0 +/- 0.3 mm Hg; p less than 0.01). Cardiac output in the long-term portal hypertensive rats was similar to the sham-operated group and lower than in the short-term portal hypertensive group (19.4 +/- 1.0 and 20.6 +/- 1.5 vs. 32.7 +/- 2.0 ml X min-1 X 100 gm body weight-1; p less than 0.01). Portal venous inflow in the long-term portal hypertensive group was also similar to the sham group and lower than in the short-term portal hypertensive group (4.51 +/- 0.36 and 4.58 +/- 0.39 vs. 6.72 +/- 0.48 ml X min-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: a double-blind, placebo-controlled study.

The aim of this study was to determine the effects of the long-acting somatostatin analog, octreotide, on portal venous pressure and collateral blood flow in cirrhotic patients with portal hypertension during fasting and postprandial states. In a double-blind, placebo-controlled study, we investigated the effects of octreotide on the hepatic venous pressures and azygos blood flow of 21 patients before and after a standard liquid meal containing 40 gm of protein in 250 ml. Octreotide significantly reduced azygos blood flow from a mean of 499 +/- 65 ml/min to a mean of 355 +/- 47 ml/min (p < 0.01), but it had no effect on the hepatic venous pressure gradient. The hepatic venous pressure gradient of patients in the placebo group increased significantly, from a fasting mean of 16.4 +/- 1.6 mm Hg to a mean of 20.0 +/- 1.7 mm Hg 30 min after the meal (p < 0.01). In a second protocol hepatic venous pressures were measured in 20 patients at 30-min intervals for 2 hr after ingestion of the mixed meal. Again the placebo group showed a significant increase in the hepatic venous pressure gradient 30 min after the meal (20.4 +/- 1.5 mm Hg vs. 18.2 +/- 1.2 mm Hg; p < 0.05), but the group receiving octreotide showed no significant changes during the 2 hr of observation. We conclude that octreotide significantly reduces azygos blood flow, with little effect on portal venous pressure, and that it appears to inhibit postprandial increases in portal pressure in cirrhotic patients with portal hypertension.     

Hemodynamic, left ventricular structural and hormonal changes after discrete myocardial damage in the dog.

Transmyocardial direct-current (DC) shock produces localized left ventricular myocardial necrosis without obstruction to coronary blood flow. In 43 dogs sequential measurements of hemodynamic, neuroendocrine and myocardial structural changes were made at baseline and for 16 weeks after DC shock. Six dogs (14%) died in the peri-shock period. By 1 week after shock, left ventricular mass, as measured by nuclear magnetic resonance imaging, had increased from a mean value +/- SD of 67.9 +/- 10.1 to 82.5 +/- 12.9 g (p = 0.0001). Left ventricular end-diastolic volume was unchanged at 1 week but increased at 16 weeks from 56.1 +/- 10.3 to 70.3 +/- 10.7 ml (p = 0.0003). Left ventricular mass demonstrated a further increase at 12 months (107.8 +/- 14.8 g). Rest cardiac output was significantly decreased at 4 months (3.67 +/- 1.23 to 3.18 +/- 0.81 liters/min, p less than 0.01) as was stroke volume (43 +/- 9 to 37 +/- 7 ml, p less than or equal to 0.01). Left ventricular ejection fraction decreased progressively from 73% to 38% at 1 year. At 4 months there were increases in mean pulmonary artery pressure (18 +/- 4 to 23 +/- 4 mm Hg, p less than 0.01), pulmonary capillary wedge pressure (9 +/- 3 to 15 +/- 3 mm Hg, p less than 0.01) and right atrial pressure (5 +/- 4 to 9 +/- 3 mm Hg, p less than 0.01). Plasma norepinephrine was increased at 4 months (318 +/- 190 to 523 +/- 221 pg/ml, p = 0.0003), whereas plasma renin activity was not significantly changed (4.3 +/- 2.6 vs. 5.2 +/- 3.4 ng/ml per h). Microsphere regional blood flow studies demonstrated a 50% reduction in skeletal muscle blood flow at 4 months (0.06 +/- 0.06 ml/min per g compared with 0.12 +/- 0.09 in normal dogs, p = 0.05), and a reduction in the endocardial/epicardial blood flow ratio (1.11 +/- 0.13 compared with 1.24 +/- 0.13 in normal dogs, p = 0.02). Therefore, in this model of acute left ventricular damage, left ventricular hypertrophy precedes progressive left ventricular dilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of volume expansion on hemodynamics, capillary permeability and renal function in conscious, cirrhotic rats

General and splanchnic hemodynamics (radioactive microspheres), renal function, spontaneous and histamine-mediated vasopermeability and albumin distribution space were studied in conscious control and nonascitic cirrhotic rats, before and after a moderate and sustained saline infusion (3% of body weight per 30 min + repletion of urinary losses). In basal conditions, cirrhotic rats showed lower fractional sodium excretion than did control rats (0.09 +/- 0.01 vs. 0.15 +/- 0.01%, p less than 0.005). In addition, cirrhotic animals showed higher cardiac output (161.4 +/- 12.8 ml per min) and lower total peripheral resistance (0.63 +/- 0.05 mm Hg . min per ml) and mean arterial pressure (102.9 +/- 3.9 mm Hg) than did control rats (cardiac output: 89.0 +/- 7.6; total peripheral resistance: 1.31 +/- 0.11; mean arterial pressure: 117.5 +/- 5.11; p less than 0.005). No differences in portal-systemic shunt rate or vasopermeability between both groups were observed. After saline infusion, fractional sodium excretion increased to 4.31 +/- 0.16% in controls but only 2.11 +/- 0.02% in cirrhotic animals. In this group, cardiac output decreased by 49.6 +/- 5.1% whereas mean arterial pressure and total peripheral resistance increased by 7.1 +/- 0.6 and 112 +/- 10%, respectively. In control rats, no significant hemodynamic changes were observed. Blood gases did not change after expansion in any group. Saline infusion induced an increase in histamine-mediated vasopermeability in cirrhotic rats but not in control rats. Also albumin distribution space increased more in cirrhotic than in control animals. Heart weight was higher in cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic and renal vascular responses to dietary calcium and vitamin D

To assess the consequences of hypercalcemia on systemic and renal hemodynamics, vasoactive hormones, and water and electrolyte excretion in intact, conscious mongrel dogs, measurements in 10 dogs receiving 100 mg/kg calcium gluconate and 10,000 U/kg vitamin D daily for 2 weeks were compared with measurements made in 10 time-control dogs not receiving calcium or vitamin D. Hypercalcemia induced by dietary supplementation with calcium and vitamin D resulted in profoundly reduced glomerular filtration rate (40 vs 78 ml/min in controls; p less than 0.005), estimated renal plasma flow (145 vs 267 ml/min in controls; p less than 0.005), and renal blood flow (254 vs 441 ml/min in controls; p less than 0.005). Renal resistance was significantly increased in the hypercalcemic dogs (0.57 +/- 0.07 vs 0.28 +/- 0.01 mm Hg/ml/min; p less than 0.005). Hypercalcemia also resulted in increased fractional excretion of water (4.8 vs 1.4% in controls; p less than 0.005), sodium (1.4 vs 0.6% in controls; p less than 0.005), calcium (1.7 vs 0.7% in controls; p less than 0.01), and magnesium (10.2 vs 4.1% in controls; p less than 0.005). Systolic blood pressure (160 vs 172 mm Hg in controls; p less than 0.05) and stroke volume were lower (0.024 vs 0.036 L/beat in controls; p less than 0.005) in hypercalcemic dogs, presumably because of the diuresis, while total peripheral resistance was higher (36 vs 31 mm Hg/L/min; p less than 0.05) in controls. Magnesium levels were significantly lower in the experimental group (1.3 vs 1.7 mg/dl in controls; p less than 0.0005). Aldosterone levels, plasma renin activity, and urinary prostaglandin excretion were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of therapeutic paracentesis on systemic and hepatic hemodynamics and on renal and hormonal function

Thirteen patients with cirrhosis and tense ascites (six with and seven without peripheral edema) underwent 4- to 15-liter paracentesis without intravenous "colloid" replacement. Cardiac output increased from 6.6 +/- 0.7 liters per min at baseline to 8.2 +/- 0.7 liters per min (p less than 0.003) 1 hr after large-volume paracentesis completion and fell to 7.5 +/- 0.69 liters per min (p less than 0.05 vs. baseline, p less than 0.02 vs. 1 hr) 24 hr after large-volume paracentesis completion. There was no change in mean arterial pressure or mean pulmonary artery pressure. Central venous pressure fell from 9.1 +/- 0.8 mm Hg at baseline to 8.6 +/- 1.4 mm Hg 1 hr post-large-volume paracentesis to 6.8 +/- 1.0 mm Hg (p less than 0.005 vs. baseline, p less than 0.02 vs. 1 hr value) at 24 hr, and pulmonary capillary wedge pressure fell from 13.1 +/- 0.9 to 11.1 +/- 1.3 mm Hg 1 hr after large-volume paracentesis and to 9.89 +/- 1.2 (p less than 0.01 vs. baseline, p less than 0.03 vs. 1 hr after large-volume paracentesis) at 24 hr. Heart rate fell from 90 +/- 3.0 to 85 +/- 2.9 beats per min (p less than 0.01) 1 hr after large-volume paracentesis completion, but increased to 89 +/- 2.5 beats per min (p less than 0.02 vs. 1 hr after large-volume paracentesis) at 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic changes in patients with portal venous obstruction

Splanchnic and systemic hemodynamics were evaluated in five adult patients with portal hypertension due to portal venous obstruction and were compared with those of patients with cirrhosis and those of a control group. In patients with portal venous obstruction, the gradient between wedged and free hepatic venous pressures ranged from 2 to 3 mm Hg, as in the control group, and was significantly lower than in patients with cirrhosis. Hepatic blood flow averaged 0.521 +/- 0.127 liter per min per m2 (mean +/- S.D.) and was significantly lower than that measured in cirrhotic and normal patients. Cardiac index averaged 3.788 +/- 0.629 liters per min per m2; this high value for cardiac index was not significantly different from that measured in cirrhotic patients, but was significantly higher than in patients of the control group. It is suggested that a hyperkinetic circulatory state may result from the development of portal-systemic venous collateral circulation in patients with portal venous obstruction having normal liver and hepatic venous pressures.     

Transcapillary water and protein flux in the canine intestine with acute and chronic extrahepatic portal hypertension

Intestinal transcapillary water and total protein flux were determined in dogs with chronic extrahepatic portal hypertension after construction of an aortic-portal shunt combined with hilar portal vein constriction and compared to acute portal vein constriction. Measurements were made of thoracic duct lymph flow, portal venous pressure, and total protein concentration in plasma, thoracic duct lymph, intestinal and liver lymph. From these data and calculations based on the dual visceral origin of thoracic duct lymph from liver and intestine, intestinal transcapillary water flux in chronic extrahepatic portal hypertension (portal venous pressure = 21.4 +/- 2 mm Hg; mean +/- SEM), increased 5-fold (93 +/- 12 from 17 +/- 4 microliters/min/kg, P less than 0.001), while intestinal total protein flux expressed as protein clearance (intestinal transcapillary water flux X intestinal lymph/plasma total protein concentration) was unchanged (13 +/- 3 from 10 +/- 2 microliters/min per kg; P greater than 0.4), a finding supported by unaltered whole body plasma albumin "leak rate" (83 +/- 16 from 80 +/- 2 microliters/min per kg; P greater than 0.9). In acute portal vein constriction (portal venous pressure = 26 +/- 1 mm Hg) intestinal transcapillary water flux was similarly increased (58 +/- 16 from 9 +/- 2; P less than 0.014) but intestinal total protein flux was increased 3-fold (16 +/- 4 from 5 +/- 2; P less than 0.032). Calculated permeability surface area product and protein reflection coefficient (cross-point method) increased similarly in both preparations. In accord with earlier findings in patients with hepatic cirrhosis, chronic elevation in portal pressure increased intestinal transcapillary water flux but not total protein flux.