Reduction In Liver Blood Flow Research Articles

The Shock Liver

Five patients with severe heart disease developed cardiogenic shock of more than 24 hours' duration. As a sequela to the shock, severe liver affection was demonstrated. Serum aspartate aminotransferases and serum lactate dehydrogenases showed very high activities. The prothrombin-proconvertin index was reduced to less than 25% of the normal. Four of the patients were jaundiced. The condition gave rise to some differential diagnostic problems. Liver biopsies were available from four of the patients, and histological examination of an autopsy specimen of the liver was performed in each case. The liver histology showed centrilobular necrosis and haemorrhage in all patients. It seems that centrilobular fibrosis develops later in the condition. The pathogenesis of this liver affection is probably hypoxic injury to the centrilobular areas of the liver lobule due to reduced liver blood flow.

Effect of Portacaval Shunt and Arterialization of the Liver on Bile Acid Metabolism

The effect on bile acid clearance of portacaval end-to-side shunt, with and without arterialization of the hepatic portal venous bed, was studied in dogs. Portacaval shunt reduced liver blood flow by 75%, and peripheral serum bile acid concentration rose from 3 to 239 muM. Arterialization maintained total liver blood flow within physiological range and serum bile acid concentration was only 19 muM. Since hepatic bile acid extraction was similar in both groups, bile acid clearance was determined largely by total liver blood flow. The results of this study indicate that hepatic clearance of substances originating from portal blood is impaired in portacaval shunt and can be restored by increasing the arterial blood supply to the liver.

Clinical Physiology of the Capillary Circulation

There is evidence suggesting that spinal cord injury (SCI) may induce pharmacokinetic alterations; in particular, changes in drug metabolic clearance. We have therefore launched a research line on the characterization of drug disposition of test drugs eliminated mainly by hepatic clearance. Thus, we have characterized the pharmacokinetics of phenacetin and naproxen in experimental SCI. Phenacetin is submitted to high-hepatic extraction and hence its clearance depends on liver blood flow. Naproxen is a low-extraction drug and thus its clearance depends on enzyme activity in liver cells. In animals with SCI, clearance of phenacetin, but not of naproxen, was significantly impaired. We have also observed that SCI significantly impairs liver blood flow but does not produce any significant alteration in biochemical indicators of liver function. Our observations suggest that SCI induces hemodynamic changes resulting in a reduction in liver blood flow, but has no significant effect on intrinsic liver function. Such alterations affect the metabolic clearance of high-extraction drugs, but not of low-extraction drugs.