Intravascular and intraparenchymatous hepatic segmentary sclerosis

Abstract Purpose: To evaluate the morphological effects of injected sclerosing agents into the liver. Methods: This study was performed on twenty dogs, distributed into five groups: Group 1 (n = 5) - control, Group 2 (n = 5) - injection of 50% glucose solution inside hepatic parenchyma and animals followed during seven days, Group 3 (n = 10) - injection of ethanol inside hepatic parenchyma and animals distribution into two subgroups Subgroup 3A (n = 5) - followed during 24 hours and subgroup 3B (n = 5) - followed during seven days (group 3B), Group 4 (n = 5) - ethanol injection inside left portal vein branch and followed during 24 hours. Livers were macroscopically evaluated, submitted to hepatic arteriography and portography, then histology. Results: All animals in Group 4 died within 23 hours due to diffuse hepatic necrosis. The animals of groups 2 and 3 had a satisfactory evolution. Fibrosis formed in the segment reached by the sclerosant solution and interruption of the contrast flow injected into the portal system. Conclusion: Intrahepatic parenchymal ethanol injection is well tolerated and causes sclerosis restricted to a specific segment; however, intraportal ethanol injection causes massive hepatic necrosis and can lead to death.

Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis

Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic perfusion in distinct shock states. We hypothesized that enalaprilat potentiates the benefits of early fluid resuscitation in severe experimental sepsis, particularly in the splanchnic region. Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over a period of 30 min. Thereafter, two interventions were performed: fluid infusion (normal saline, 32 mL/kg over 30 min) and enalaprilat infusion (0.02 mg kg-1 min-1 for 60 min) in randomized groups. The following groups were studied: controls (fluid infusion, N = 4), E1 (enalaprilat infusion followed by fluid infusion, N = 5) and E2 (fluid infusion followed by enalaprilat infusion, N = 5). All animals were observed for a 120 min after bacterial infusion. Mean arterial pressure, cardiac output (CO), portal vein blood flow (PVBF), systemic and regional oxygen-derived variables, and lactate levels were measured. Rapid and progressive reductions in CO and PVBF were induced by the infusion of live bacteria, while minor changes were observed in mean arterial pressure. Systemic and regional territories showed a significant increase in oxygen extraction and lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were also detected. Fluid replacement promoted transient benefits in CO and PVBF. Enalaprilat after fluid resuscitation did not affect systemic or regional hemodynamic variables. We conclude that in this model of normotensive sepsis inhibition of angiotensin-converting enzyme did not interfere with the course of systemic or regional hemodynamic and oxygen-derived variables.

Assessment of effects of propranolol on portal hemodynamics in cirrhosis by duplex ultrasonography.

OBJECTIVE: To study the effect of propranolol on portal hemodynamics in cirrhotics using duplex ultrasonography. METHODS: Portal venous flow was measured by duplex ultrasonography in 12 healthy volunteers and ten men with cirrhosis. The cirrhotics were evaluated prior to and after ingestion of propranolol (60 mg twice daily for seven days) or placebo in a randomized cross-over fashion. Variations in heart rate, blood pressure, portal vein diameter, and portal venous flow and velocity were evaluated. RESULTS: The mean (SD) portal venous flow in the volunteers was 746 (280) mL/min, portal flow velocity was 18.5 (3.6) cm/s and portal vein diameter was 9.2 (1.4) mm. In cirrhotics, propranolol decreased portal blood flow from 586 (220) to 413 (120) mL/min (p < 0.03), the overall reduction being 29.5%. This effect was due to decrease in portal flow velocity, from 12.5 (3.3) to 9.7 (2.3) cm/s (p < 0.03) without significant change in portal vein diameter. No changes were observed with placebo. CONCLUSIONS: Propranolol decreases portal flow velocity and thus portal venous flow in cirrhotics.

Blockade of Na+/H+ exchanger contracts the portal vein of spontaneously hypertensive and Wistar Kyoto rats.

It has been claimed that the activity of Na+/H+ exchanger (NHE) is altered in spontaneously hypertensive rats (SHR) suggesting a possible role for it in the pathophysiology of hypertension. The purpose of this study has been to investigate the effect of blockade of NHE on the noradrenaline (NA) and 26K+ induced tone and on the recovery of tone from acid induced contractions in the portan vein of spontaneously hypertensive rats (SHR) as compared to their controls of Wistar Kyoto rats (WKY). Blockade of NHE by 10(-4) dimethylamiloride (DMA) raised the tone of NA and 26K+ activated preparation of both strains, the contractions being higher with NA activation. Total blockade of NHE by replacement of Na in solution with N-methy-D-Glucamine (NMDG) raised the tone of the NA activated preparations by 45+/-10%, n=8, P<0.01 and 33+/-4%, n=12, P < 0.01 in SHR and WKY respectively. The time for 50% relaxation from NH4Cl washout contraction was significantly prolonged by 10(-5) and 10(-4) M DMA in both strains under NA or 26K+ activation. DMA effect was greater on NA than on 26K+ activated preparations, and was not significantly different when comparing SHR to WKY results. In conclusion the results reported in this study indicate that NHE has similar activity in WKY and SHR portal veins and that its blockade contracts both preparations. Therefore, it is unlikely that increased NHE activity, acting directly on vascular smooth muscle tone, could be a primary cause for hypertension.

Response of the portal vein of spontaneous hypertensive rats to intracellular pH.

The effect of intracellular pH perturbations on the portal vein preparations of spontaneously hypertensive rats and their control Wistar Kyoto rats was investigated. Intracellular alkalinity induced by application of 20 mM NH4Cl or 20 mM trimethylamine produced dilatation of both preparations. Intracellular acidity induced by washout of the previous ammonium and trimethylamine solutions or by application of 20 mM sodium propionate solution caused constriction of both preparations. These responses of the portal veins of both animals to intracellular pH variations were qualitatively the same in nonactivated preparations and in preparations precontracted with 26 mM K+ or 1 microM norepinephrine. Recovery from acidic constrictions induced by washout of ammonium and trimethylamine solutions was significantly slower in spontaneous hypertensive rats than in Wistar Kyoto rats preparations. Conceivably, a lower intracellular pH in the vascular smooth muscle of the resistance vessels of hypertensive patients, as compared to normotensive individuals, may partly account for the hypertensive phenomena.

Effects of sodium nitroprusside on potassium induced contracture in isolated vascular smooth muscle

Se investigaron los efectos de nitroprusiato de sodio sobre la actividad contráctil isométrica (TCI) y sobre la contractura inducida por ClK 60 mM en vena porta aislada de rata e incubada en condiciones en que se modifican el influjo y eflujo de calcio. En condiciones control (medio (KRB) la TCI fue de 10.61ñ0.56mN(n=13). La adición de concentraciones crecientes de NPS (no acumulativas) disminuyó la TCI de manera dosis dependente directa. El componente tónico de la contractura inducida por ClK 60 mM decayó en un 27.04ñ10.9% (n=6) depués del agregado de NPS 10-4M. El efecto relajante de la droga fue más pronunciado en presencia de nifedipina 10-10M (72.35ñ7.5% de inhibición). La sensibilidad de la preparación a NPS se redujo fuertemente en condiciones en que el eflujo de Ca+2 estaba disminuido (medio pobre en sodio = KRB sucrosa). Los experimentos aquí presentados apoyan la hipótesis de que el efecto vasodilatador de NPS podría ser atribuido a un incrementado eflujo del catión

Effects of buphenin on the rat portal vein.

The vasodilator and tocolytic substance buphenin (10 mumol/l) stimulated the spontaneous phasic activity of some (8 out of 18) isolated rat portal vein preparations; 0,1-1 mmol/l buphenin diminished or abolished the activity in all preparations. The isotonic and isometric tonic contractions of portal vein in response to adrenaline, noradrenaline and phenylephrine (0,1-1 mumol/l) disappeared almost completely after addition of buphenin in equimolar concentrations, whereas acetylcholine contractions persisted. The beta-adrenergic blocking agents propranolol and dichloisoprenaline (10 mumol/l) only slightly antagonized the inhibitory effect of buphenin on the contractile responses to catecholamines. It is concluded that buphenin exerts dual action upon rat portal vein: the drug partially stimulates the beta-receptors and partially blocks the alpha-adrenergic receptors.