Increase In Portal Flow Research Articles

Hormonal and Splanchnic Hemodynamic Alterations Following Hepatic Resection

Reported hemodynamic changes after partial hepatectomy (PH) include elevations in portal blood flow and pressure (Ppv). The etiology of these changes is unknown. We studied degree of portosystemic shunt (PSS), splanchnic artery blood flow and resistance (Qspl, R spl) as well as prostacyclin (PGI2), glucagon, and insulin response in rats undergoing 75% hepatectomy. The results showed that following an immediate threefold rise in portal PGI2, a hemody namically significant PSS developed at 48 hr. The PGI2 changes paralleled the increase in portal flow (Qpv), pressure (Ppv), PSS, and the decrease in Rspl. Glucagon levels also rose immediately postresection, but fell to normal prior to resolution of both PSS and hyperemia. There was no significant change in insulin or glucose levels after resection. This implies a relationship between PSS and the release of a prostanoid effecting Qpv, Qspl , and Rspl which relates to, and possibly mediates, the hemodynamic changes following liver resection. We conclude that PH is a model of acute PHT, and that the altered splanchnic hemodynamics could relate to hepatic regeneration.

Increase in portal flow induces c-myc expression in isolated perfused rat liver.

We examined expression of the c-myc oncogene in isolated perfused livers to elucidate the mechanisms involved in triggering the proliferation of hepatocytes after partial hepatectomy (PH). During perfusion with a 1:1 mixture of Dulbecco's modified Eagle's medium and the oxygen transport fluid FC-43, rat livers were two-thirds resected (PH), and further perfused for 1 1/2 hours at the physiological portal flow throughout the perfusion. Expression of c-myc in the perfused livers with PH(+) was ten times higher than in those with PH(-). Furthermore, expression of c-myc in the PH(-) livers perfused with a threefold volume of the physiological portal flow was 5-10 times higher than that in the livers perfused with the physiological portal flow. The perfusates that passed through the livers did not induce DNA synthesis of primary cultured hepatocytes. These results suggest that an increase in the portal flow volume may act as a trigger for hepatocyte proliferation after PH.

Hepatic blood flow during cardiopulmonary bypass

To establish the effects of different modes of cardiopulmonary bypass on hepatic blood flow, with the aim of increasing understanding of the hemodynamic factors that may lead to hepatic dysfunction in patients after cardiopulmonary bypass. The anatomical and physiologic characteristics that are unique to the hepatic circulation are also reviewed, together with an account of the known specific effects on the liver of several hemodynamic stimuli that are commonly present during cardiopulmonary bypass. The entire world literature on the subjects of clinical and experimental cardiopulmonary bypass, extracorporeal circulation, blood gas tensions, hypothermia, hypotension, and hepatic blood flow was searched via Index Medicus, up to and including 1991. Data are presented only from those studies that employed sound cardiopulmonary bypass or blood flow measurement technique. For investigations on hypothermia, data for temperatures < 28 degrees C are not included. Details of one recent experimental study in the dog by the author are highlighted, in which the relative effects of pump flow rate, temperature, and type of perfusion (pulsatile or nonpulsatile) are presented; the data are critically compared and contrasted with those data obtained by earlier workers. Hepatic hemodynamics are characterized by a dual supply of blood from the hepatic artery, actively controlled within the liver, and the portal vein, principally regulated by prehepatic resistance vessels. Portal flow may modulate the hepatic arterial circulation through the "hepatic arterial buffer response." Hypotension caused by hemorrhage causes a decrease in portal blood flow but hepatic arterial flow is maintained by autoregulation and by the "buffer" response. Hypothermia (28 degrees C) has little effect on hepatic arterial flow, but portal flow may increase. During cardiopulmonary bypass, total liver blood flow is better maintained at a pump flow rate of 2.4 than at 1.2 L/min/m2. Perfusion at 28 degrees C causes an increase in portal flow and a slight decrease in hepatic arterial flow. Total hepatic blood flow is better preserved during cardiopulmonary bypass at 1.2 L/min/m2 by pulsatile than by nonpulsatile flow; however, no significant difference was noted between pulsatile and nonpulsatile perfusion at a bypass flow rate of 2.4 L/min/m2, particularly at 28 degrees C. During cardiopulmonary bypass, hepatic blood flow is better maintained by high pump flow than by low pump flow rates. Hypothermic cardiopulmonary bypass may benefit the hepatic circulation, although the additional advantages usually gained by the use of pulsatile perfusion may be partly lost when hypothermia is combined with a high pump flow rate.

New insights on the mechanism of the alcohol-induced increase in portal blood flow.

Acute administration of ethanol increases portal blood flow by 40-60%. This increase in blood flow compensates for the increase in O2 consumption that follows alcohol intake and may play a protective role against hypoxic hepatocellular necrosis. We have investigated the mechanism of this hemodynamic effect of ethanol in the rat using the labeled microsphere technique. We ruled out a direct role of systemic glucagon and of acetaldehyde in mediating the increase in portal flow. However, the increase in flow is maximal at a blood ethanol concentration of 3.5 mM, corresponding to that required to achieve the Vmax of alcohol dehydrogenase, and is suppressed by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Alcohol ingestion results in zonal liver hypoxia and in increases in acetate, both of which have been shown to increase the levels of adenosine, a potent vasodilator, in blood and tissues. Ethanol produces a 400% increase in arterial adenosine. Adenosine infusion leads to a dose-dependent increase in portal blood flow of up to 100%, an effect that is suppressed by administration of 8-phenyltheophylline, an antagonist of adenosine at A1 and A2 receptors. Similarly, the ethanol-induced increase in portal blood flow is fully suppressed by 8-phenyltheophylline. In conclusion, adenosine appears to play an important role in the mechanism by which ethanol increases portal blood flow.

IMPROVED ARTERIAL PORTOGRAPHY IN PORTAL HYPERTENSION

Visualization of portosystemic venous collaterals with arterial portography is often unsatisfactory even when vasodilator drugs are used. In this investigation arterial portography performed during reactive hyperemia following a temporary SMA occlusion is compared to currently used clinical methods in cirrhotic dogs with stable portal hypertension induced by fractionated polyvinyl alcohol embolization of the portal vein. Following a 2-minute balloon occlusion of the SMA a maximum increase in portal blood flow of 240% over the pre-occlusion value was found while the maximum increase in portal flow after 1 mg/kg tolazoline injected into the SMA amounted to only 110%. Compared to arterial portography performed with 32 ml diatrizoate 76% injected at a rate of 8 ml/sec into the SMA with and without a preceding 5 mg/kg tolazoline SMA injection, a significant earlier and better opacification of the portal system and portosystemic venous collaterals was found after a 2-minute SMA balloon occlusion. Simultaneous portal vein blood sampling revealed a 50–100% higher peak blood iodine concentration after SMA occlusion when compared to the other 2 investigated techniques. Encountered complications were all related to the used balloon catheter that is commercially available for human use and included interluminal leak, balloon rupture and detachment, failure to deflate the balloon and perforation. It is concluded that a significant improvement in arterial portography over currently used clinical methods can be achieved when performed immediately after a temporary occlusion of the SMA, provided a safe diagnostic balloon catheter is (becomes) available. Supported by NIH Grant AM-19474.

Control of hepatic and intestinal blood flow: effect of isovolaemic haemodilution on blood flow and oxygen uptake in the intact liver and intestines.

1. Limited isovolaemic haemodilution was produced in cats by addition of dextran 75-Ringer solution to an extracorporeal blood reservoir connected in series with the cat. Total hepatic venous outflow was neasured using a hepatic venous long-circuit and hepatic arterial flow was measured with an electromagnetic flow probe. Oxygen uptake was monitored in the guts and liver. Na-pentobarbitone anaesthesia was used. 2. Following reduction of the haematocrit (from 31 to 22) the oxygen uptake of the gut segment and liver were maintained. Gut conductance increased to 125% of control while the oxygen extraction ratio increased to only 109%. The hepatic arterial conductance did not change in spite of a greatly reduced (to 68%) oxygen delivery. Hepatic extraction increased to 140% of control. 3. The hepatic artery did not dilate to maintain constant oxygen supply to the liver thus confirming our previous observation that blood flow is not coupled to hepatic metabolism. 4. Oxygen extraction in the gut correlated well with changes in portal blood flow but not with changes in vascular conductance, arterial blood pressure or oxygen delivery. 5. The blood flow of the gut (vascular beds draining into the portal vein in the splenectomized preparation) was controlled in a manner that prevented changes in portal venous PO2 in spite of a reduction in oxygen content. Local PO2 and perhaps pH, are suggested as the factors controlling gut blood flow following haemodilution. 6. Changes in portal blood flow correlated with changes in portal vascular (intrahepatic) conductance such that increased portal flow produced an increased portal conductance thereby maintaining portal venous pressure constant.

Esophageal Varices in Agnogenic Myeloid Metaplasia: Disappearance After Splenectomy

A patient with massive splenomegaly secondary to agnogenic myelofibrosis and extramedullary myeloid metaplasia was found to have esophageal varices. No intra- or extrahepatic obstruction to portal blood flow was present. Splenectomy immediately reduced portal venous pressure to normal, and 2 months postoperatively no varices were demonstrable by barium swallow. Portal hypertension in certain cases of agnogenic myelofibrosis and extramedullary myeloid metaplasia may be mainly due to increased portal flow rather than increased resistance, and these individuals may benefit from splenectomy alone.

Pathogenesis of Portal Hypertension

ABSTRACT To the Editor:— The article, Contrasting Patterns of Ascites Formation in Hepatic Cirrhosis, by Witte et al (208:1661, 1969) shows well how to distinguish between portal hypertension with stagnant portal flow and portal hypertension with high portal flow. An increase in portal blood flow may be the principal cause of portal hypertension, or associated with splenomegaly, and may be treated by splenectomy without the creation of a porta-caval venous shunt.The idea that splenomegaly and increase in portal flow may cause portal hypertension had been postulated on the basis of painstakingly gathered clinical, anatomic, and pathologic observations, but has not yet been generally accepted. Thus the existence of portal hypertension primarily due to increased portal flow has been either ignored or admitted almost furtively.Much more work is needed, but the article shows clearly how to explore this subject with arteriograms, using portal flow and pressure determinations and the

Portal hypertension without cirrhosis or extrahepatic obstruction: Report of a case

A fifty-two year old man with bleeding esophageal varices secondary to portal hypertension but without evidence of intrahepatic or extrahepatic obstruction is presented. Although there was no arteriovenous fistula found, there was indirect evidence that in this case the portal hypertension was secondary to increased portal flow. He was treated successfully by portacaval anastomosis.A discussion of the pathology of the liver with increased portal flow is presented.