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The liver receives about 25% of cardiac output. Portal blood accounts for about two-thirds of total flow, and although the liver does not regulate portal flow, it does regulate portal pressure. The hepatic arterial flow is regulated by a unique intrinsic regulatory system, the hepatic arterial buffer response, that is dependent on an adenosine washout mechanism and serves to hold total hepatic blood flow constant. Hepatic arterial flow is not regulated by liver metabolic demands, but rather subserves the hepatic role as a regulator of blood levels of nutrients and hormones by maintaining blood flow and thereby hepatic clearance, as steady as possible. The arterial buffer also plays a role in maintenance of intrahepatic pressures and liver volume. About 30% of hepatic volume is blood (12% of total body blood volume). This total capacitance consists of stressed and unstressed volumes. Stressed volume depends upon intrahepatic pressure and vascular compliance (distensibility). Unstressed volume is the theoretical volume remaining in an organ at zero pressure. Pressures and flows would not be altered if unstressed volume was absent. Active constriction of the capacitance vessels results in transfer of unstressed volume to stressed volume, which maintains or increases venous pressure and venous return. Passive volume changes, secondary to flow changes and thus intrahepatic pressure, are also dramatic in the liver and represent changes in stressed volume. Intrahepatic pressure is virtually equal to portal venous pressure in the normal basal state and is regulated by hepatic venous sphincters. Active hepatic vasoconstriction can result in contraction of these sphincters and also in some presinusoidal constriction. The sphincters appear to be passively distensible, and this characteristic serves to maintain portal and intrahepatic pressures at quite constant levels such that, if inflow decreases, the sphincter resistance increases, and pressure is prevented from a precipitous fall. The intrahepatic pressure maintains sinusoidal patency and allows all sinusoids to be uniformly perfused, even at quite low flows. Fluid and solute exchange between blood and the parenchymal cell is affected by the

SUMMARY1. In anaesthetized cats, the hepatic artery, portal vein and inferior vena cava pressures and the hepatic artery and portal vein flows were recorded using pressure transducers and electro-magnetic flowmeters.2. The hepatic nerves were stimulated with maximal stimuli for periods of 2-5 min. The magnitude of the response varied with the frequency of stimulation over the range 1-10 impulses/sec. The resistance to flow increased in both the hepatic artery and the portal vein.3. In the hepatic artery, mean pressure remained virtually constant, while the flow showed an initial marked decrease followed by a return towards the control level. In the portal vein, the flow remained constant while portal pressure showed a maintained increase. These responses were unaffected by previous administration of atropine and propranolol, but were blocked by phenoxybenzamine.4. Infusions of noradrenaline into the hepatic artery produced changes similar to those following stimulation of the nerves. In contrast, when the hepatic arterial pressure was maintained constant, intravenous infusions of noradrenaline produced a maintained decrease in hepatic artery flow.5. The occurrence of autoregulation of the hepatic artery flow at arterial pressures above 80-100 mm Hg was confirmed.6. Occlusion of the carotid arteries caused a rise in arterial pressure with little change in hepatic artery flow, but when the hepatic artery pressure was maintained at the pre-occlusion level the flow showed an abrupt decrease, usually followed by a recovery towards the control level. This decrease was abolished by section of the hepatic nerves and removal of the adrenal glands.

SU-MMAMY1. These experiments were designed to measure how much blood is mobilized from or pooled in the liver, spleen and gastro-intestinal tract to compensate for a haemorrhage or infusion of blood.2. Hepatic volume, splenic weight and intestinal volume were recorded in cats anaesthetized with sodium pentobarbitone. Whole blood was removed or infused at rates of 0-5-0-6 ml. kg-'. min-1 until 10 ml./kg (1 9 % blood volume) had been removed or 18 ml./kg (34 % blood volume) had been infused. These blood volume changes produced only small changes in arterial and portal pressures except after removal of 8 ml.fkg (1 5 % blood volume) when arterial pressure began to decrease rapidly.

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Cardiac output is determined by heart rate, by contractility (maximum systolic elastance, Emax) and afterload, and by diastolic ventricular compliance and preload. These relationships are illustrated using the pressure-volume loop. Diastolic compliance and Emax place limits determined by the heart within which the pressure-volume loop must lie. End-diastolic and end-systolic pressures and hence the exact position of the loop within these limits are determined by the peripheral circulation. In the presence of minimal sympathetic tone, some 60% of total blood volume is hemodynamically inactive and constitutes a blood volume reserve (the unstressed volume). The remainder of the blood volume (the stressed volume) and the compliance of the venous system determine the venous pressure. This venous pressure together with venous resistance determines venous return, right atrial pressure, cardiac preload, and hence cardiac output. Venoconstriction causes conversion of unstressed volume to the stressed volume, the blood volume reserve is converted into hemodynamically active blood volume. After hemorrhage this replaces the lost stressed volume, while in other situations where total blood volume is not reduced, it allows a sustained increase in cardiac output. The major blood volume reserve is in the splanchnic bed: the liver and intestine, and in animals but not man, the spleen. A major unsolved problem is how the conversion of unstressed volume to stressed volume by venoconstriction is reflexly controlled.

Experiments were performed to determine the validity of the indocyanine green (ICG) clearance technique, with and without allowances for incomplete hepatic extraction, as an estimate of hepatic plasma flow. This technique was compared with that of directly measured hepatic blood flow using a hepatic venous long-circuit preparation in the anesthetized cat. This preparation allowed direct measurement and alteration of hepatic blood flow and collection of arterial, portal, and hepatic venous blood samples without depletion of the animal's blood volume. Measurements of ICG by spectrophotometry and high-pressure liquid chromatography (HPLC) were equally accurate, but the HPLC was 100 times more sensitive and allowed smaller sample volumes. It was determined that systemic clearance of ICG after a bolus dose (1.3 mumol/kg) was much smaller than hepatic blood flow. Allowance must be made for the incomplete extraction. When the clearance was multiplied by extraction, mean estimated hepatic plasma flow exceeded the measured flow values by 20-30%, and this difference was attributed to temporary extrahepatic distribution. In all experiments estimated hepatic plasma flows were highly variable, and reasons for this are discussed. In hepatectomized cats ICG was found to be distributed into extrahepatic tissues.

Hemodynamic relationships between flows, pressures, and blood volume have been examined in the denervated liver of cats anesthetized with pentobarbital. Portal and hepatic lobar venous pressures, portal and total hepatic flows, and hepatic blood volume were recorded when portal flow was varied from 0 to 240 ml X min-1 X 100 g liver-1 and when hepatic outflow pressure was varied from 0 to 9.5 mmHg, before, during, and after intravenous infusion of norepinephrine (2 micrograms X min-1 X kg body wt-1). Portal pressure was 1-2 mmHg higher than lobar venous pressure and 8-9 mmHg higher than inferior vena caval pressure, showing that the major site of resistance in the portal circuit was in the large hepatic veins. Intrahepatic pressure was linearly related to total hepatic flow, and norepinephrine increased the intercept but not the slope of this relationship. Hepatic blood volume was linearly related to intrahepatic pressure with a calculated compliance of 2.5-3.0 ml X mmHg-1 X 100 g liver-1 and a calculated unstressed volume at zero pressure of 10-15 ml/100 g liver. Norepinephrine did not significantly change vascular compliance but caused a marked reduction of 15-20 ml/100 g liver in calculated unstressed volume. Thus norepinephrine reduced hepatic blood volume by 15-20 ml/100 g liver at any given intrahepatic pressure. It is concluded that venoconstriction in the hepatic bed occurs by a decrease in unstressed volume with little change in compliance. Unstressed volume represents a true blood volume reserve, independent of passive influences, which can be mobilized by the central nervous system.