Splanchnic Arterial Resistance Research Articles

Inspiratory Increases in Systolic Blood Pressure (“Delta-up”) and Pulse Pressure Are Not Equivalent

Inspiratory Increases in Systolic Blood Pressure (“Delta-up”) and Pulse Pressure Are Not Equivalent

Splanchnic hyperemia and hypervolemia during Valsalva maneuver in postural tachycardia syndrome

Prior work demonstrated dependence of the change in blood pressure during the Valsalva maneuver (VM) on the extent of thoracic hypovolemia and splanchnic hypervolemia. Thoracic hypovolemia and splanchnic hypervolemia characterize certain patients with postural tachycardia syndrome (POTS) during orthostatic stress. These patients also experience abnormal phase II hypotension and phase IV hypertension during VM. We hypothesize that reduced splanchnic arterial resistance explains aberrant VM results in these patients. We studied 17 POTS patients aged 15-23 yr with normal resting peripheral blood flow by strain gauge plethysmography and 10 comparably aged healthy volunteers. All had normal blood volumes by dye dilution. We assessed changes in estimated thoracic, splanchnic, pelvic-thigh, and lower leg blood volume and blood flow by impedance plethysmography throughout VM performed in the supine position. Baseline splanchnic blood flow was increased and calculated arterial resistance was decreased in POTS compared with control subjects. Splanchnic resistance decreased and flow increased in POTS subjects, whereas splanchnic resistance increased and flow decreased in control subjects during stage II of VM. This was associated with increased splanchnic blood volume, decreased thoracic blood volume, increased heart rate, and decreased blood pressure in POTS. Pelvic and leg resistances were increased above control and remained so during stage IV of VM, accounting for the increased blood pressure overshoot in POTS. Thus splanchnic hyperemia and hypervolemia are related to excessive phase II blood pressure reduction in POTS despite intense peripheral vasoconstriction. Factors other than autonomic dysfunction may play a role in POTS.

Effects of sustained-release lanreotide on hemodynamics in rats with portal vein stenosis

Background/Aims: Somatostatin and its analogue have been shown to provide beneficial effects in the management of portal hypertension and hyperdynamic circulation. The current study was undertaken to evaluate the effects of lanreotide, a sustained-release somatostatin analogue, on hemodynamics in rats with portal hypertension. Methods: Immediately after portal vein stenosis, rats were randomly assigned to receive vehicle or a single intramuscular injection of lanreotide 10 mg/kg. Hemodynamic measurements (radioactive microsphere technique) with portal systemic shunts determinations were performed on the 4th and 8th day after surgery, respectively. Results: On the 4th day after surgery, rats treated with lanreotide had significantly lower cardiac index and higher systemic vascular resistance than rats treated with vehicle, while these values were no different on the 8th day after portal vein stenosis. In contrast, the elevation of portal pressure, portal tributary blood flow, and splanchnic fraction of cardiac output had ameliorated following lanreotide administration associated with an increase in splanchnic arterial resistance. Portal systemic shunts were lower in rats receiving lanreotide than in rats receiving vehicle. Conclusion: The current study showed that a single injection of sustained-release lanreotide in rats with portal vein stenosis delayed the development of peripheral arterial vasodilatation and hyperdynamic circulation, while it modified the evolution of portal hypertension and splanchnic hyperemia. This treatment also prevents, in part, the development of portal systemic shunts in rats with portal vein stenosis.

Role of calcitonin gene-related peptide in the vascular system on the development of the hyperdynamic circulation in conscious cirrhotic rats

Background/Aims: Calcitonin gene-related peptide (CGRP), a potent vasodilator, plays an important role in modulating vascular tone, acting as a noncholinergic nonadrenegic neurotransmitter. The aim of this study was to assess the role of CGRP, present in the vascular system, in the developent of the hyperdynamic circulation observed in liver cirrhosis. Methods: Two does of human α-CGRP [8–37], a specific antagonist of CGRP, were administered to cirrhotic and control rats. Hemodynamics were evaluated using radioactive microspheres in conscious animals. To investigate the arterial depressor effect of exogenous CGRP, we constructed a dose-response curve for mean arterial pressure in cirrhotic and control rats by administering human α-CGRP. Results: The administration of high-dose human α-CGRP [8–37] (300 nmol · kg body weight −1 · min −1) significantly increased both the mean arterial pressure (21±2 vs. 13±1%, p<0.01) and total vascular resistance (76±5 vs. 54±5%, p<0.01) in cirrhotic rats, compared to control rats. The splanchnic hemodynamic effects induced by human α-CGRP [8–37] were a significant decrease in percent change of portal venous inflow −42±3 vs −33±3%, p<0.05) and a significant increase in percent change of splanchnic arterial resistance (110±9 vs 76±55, p<0.01) in cirrhotic rats, compared to control rats. Low-dose human α-CGRP [8–37] (60 nmol · kg body weight −1 · min −1) caused was much less than for the high-dose administration. The vascular response to human α-CGRP was significantly reduced in cirrhotic rats as compared to controls (ANOVA, p<0.01). Plasma concentrations of CGRP were significantly elevated in cirrhotic rats. Conclusions: CGRP in the vascular system was involved in the modulation of vasodilation in rats with liver cirrhosis, as demonstrated by the administration of a selective CGRP antagonist and exogenous CGRP.

AUGMENTED ENDOGENOUS NITRIC OXIDE PRODUCTION IN PARTIAL PORTAL VEIN‐LIGATED RATS

1. Endothelium-derived nitric oxide (NO) is a potent vasodilator. Because the body oxidizes it to nitrate ions, NO3-, measurement of the serum concentration and the urinary excretion of NO3- may be an index for endogenous NO. We investigated the role of NO on hyperdynamic circulation in cirrhotic and partial portal vein-ligated rats by measuring NO3. 2. Liver cirrhosis was induced by administration of thioacetamide. Systemic and splanchnic haemodynamics and splenic-systemic shunting were determined by tracer microspheres. The concentration of NO3- was measured by using high-performance liquid chromatography with an anioncolumn. 3. We found that systemic and splanchnic hyperdynamic circulation existed to almost the same extent in cirrhotic and in portal vein-ligated rats as compared to the controls and shamoperated rats, respectively. Splenic-systemic shunting was markedly greater in portal vein-ligated rats than in cirrhotic rats. 4. Serum NO3- levels and urinary excretion of NO3- in cirrhotic rats tended to increase as compared to the controls. On the other hand, the levels in portal vein-ligated rats were significantly increased as compared to those of the shamoperated rats, and were significantly and negatively correlated to the splanchnic arterial resistance and total vascular resistance. The amount of urinary excretion of NO3- significantly correlated to splenic-systemic shunting (r = 0.61, P < 0.05) only in portal vein-ligated rats. 5. We suggest that these high levels of NO3- in portal vein-ligated rats relate to the extensive formation of porto-collateral vasculature or acute changes in systemic and splanchnic haemodynamics due to portal vein-ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic characterization in experimental liver cirrhosis induced by thioacetamide administration

Systemic and splanchnic hemodynamics in experimental liver cirrhosis in rats induced by thioacetamide were evaluated by the radioactive microsphere method. Cardiac output and regional blood flow were measured in conscious and anesthetized control and cirrhotic rats. The conscious thioacetamide-treated rats had hyperdynamic circulation with an increased cardiac index (300 +/- 10 vs 258 +/- 3 ml/min/kg body weight, P < 0.001) and increased portal venous inflow compared with the controls (64.60 +/- 2.4 vs 48.39 +/- 0.88 ml/min/kg body weight, P < 0.001). Under pentobarbital anesthesia, the hyperdynamic circulation of the cirrhotic rats was maintained, with an increased cardiac index (276 +/- 7 vs 229 +/- 5 ml/min/kg body weight, P < 0.001) and increased protal venous inflow compared with the controls (72.47 +/- 3.0 vs 54.08 +/- 1.2 ml/min/kg body weight, P < 0.001). Portal pressure, portal venous resistance, and portal systemic shunting increased significantly while splanchnic arterial resistance decreased significantly in cirrhotic rats. Thioacetamide-induced cirrhosis is a useful model for the hemodynamic study of portal hypertension and remains useful in hemodynamic studies in the basal state under pentobarbital anesthesia.

Administration of Nω-nitro- l-arginine ameliorates portal-systemic shunting in portal-hypertensive rats

Background : Nitric oxide, a vasodilator synthesized from l-arglnine by vascular endothelial cells, may play a role in the development of portal-systemic collaterals. This study investigated the effect of long-term inhibition of NO secretion on portal systemic shunting. Methods : Systemic and splanchnic hemodynamics and the degree of portal-systemic shunting were evaluated in partial portal vein-ligated rats after administration of placebo (0.9% saline) or N ω-nitro- l-arginine (NNA) (~2 μg · kg −1 · min −1) intravenously for 6 days. Results : NNA treatment induced increases in splanchnic arterial resistance ( P < 0.001) and portal-collateral resistance ( P < 0.05) and a decrease in portal venous inflow ( P < 0.05). Portal pressure was not changed (NS). The splenic-systemic shunting was significantly decreased from 81% ± 5% in the placebotreated group to 69% ± 4% in the NNA-treated group ( P < 0.05), paralleled by an insignificant reduction in the mesenteric-systemic shunting (64% ± 7% vs. 50% ± 6%, NS). The attenuation of portal-systemic shunting by NNA was further shown by an increase in the vascular resistance of portal-systemic collateral venous bed using an in situ portal-systemic collateral perfusion model (1.27 ± 0.05 vs. 1.07 ± 0.03 cm H 2O · mL −1 · min −1; P < 0.001). Conclusions : The results show that in portal hypertensive rats, NNA reduces portal-systemic shunting without reducing portal pressure, suggesting that NO plays a role in the collaterallzation of the portal system. In addition, high flow through the portal-collateral bed is probably an important driving force that is independent of portal hypertension for the development of portal-systemic shunting in portal-hypertensive rats.

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.