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In cirrhosis, arterial vasodilatation leads to central hypovolemia and activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. As the liver disease and circulatory dysfunction may affect baroreflex sensitivity (BRS), we assessed BRS in a large group of patients with cirrhosis and in controls who were all supine and some after 60[degrees] passive head-up and 30[degrees] head-down tilting in relation to central hemodynamics and activity of the sympathetic nervous and renin-angiotensin-aldosterone systems. One-hundred and five patients (Child classes A/B/C: 21/55/29) and 25 (n = 11 + 14) controls underwent a full hemodynamic investigation. BRS was assessed by cross-spectral analysis of variabilities between blood pressure and heart rate time series. The median BRS was significantly lower in the supine cirrhotic patients, 3.7 (range 0.3-30.7) ms/mmHg than in matched controls (n = 11): 14.3 (6.1-23.6) ms/mmHg, P < 0.001. A stepwise multiple-regression analysis revealed that serum sodium (P = 0.044), heart rate (P = 0.027), and central circulation time (P = 0.034) independently correlated with BRS. Head-down tilting had no effects on BRS, but, after head-up tilting, BRS was similar in the patients (n = 23) and controls (n = 14). In conclusion, BRS is reduced in cirrhosis in the supine position and relates to various aspects of cardiovascular dysfunction, but no further reduction was observed in parallel with the amelioration of the hyperdynamic circulation after head-up tilting. The results indicate that liver dysfunction and compensatory mechanisms to vasodilatation may be involved in the low BRS, which may contribute to poor cardiovascular adaptation in cirrhosis. cardiovascular dysfunction; central circulation time; hyperdynamic circulation; renin-angiotensin-aldosterone system; sympathetic nervous system doi:10.1152/ajpheart.01227.2006

Our aim was to measure whole body energy expenditure after a mixed liquid meal, with and without simultaneous propranolol infusion, in patients with cirrhosis. We also wanted to investigate the effect of propranolol on substrate fluxes and oxygen uptake in the tissues drained by the hepatic vein and azygos vein in the postprandial period in these patients. Whole-body oxygen uptake, hepatic blood flow, hepatic venous pressure gradient and net-hepatic fluxes of oxygen, lactate, glucose, glycerol, and free fatty acids (FFA) were measured in 12 patients with alcoholic cirrhosis before and for 2 h alter ingestion of a mixed liquid meal (700 kcal). Half of the patients (n = 6) were randomized to a treatment group receiving intravenous infusion of propranolol in combination with the meal. The meal-induced energy expenditure was significantly lower in patients given propranolol [15.0 [+ or -] 18.9 vs. 67.0 [+ or -] 26.1 kJ/120 min (means [+ or -] SD), P < 0.01]. Meal-induced whole body oxygen uptake was lower in patients receiving propranolol (19.2 [+ or -] 38 vs. 135.7 [+ or -] 61 mmol/120 min, P < 0.01), and the meal-induced increase in splanchnic oxygen uptake was nonexistent when propranolol was administered in combination (-13.2 [+ or -] 34.8 vs. 110.4 [+ or -] 34.8 mmol/120 min, P = 0.04). Postprandially, the propranolol group had a tendency toward a reduced splanchnic glucose output, and the FFA uptake was significantly reduced. Propranolol reduces meal-induced whole body oxygen uptake and energy expenditure as well as splanchnic oxygen uptake. The splanchnic reduction in oxygen consumption can explain almost the entire reduction in whole body oxygen consumption. calorimetry; catheterization; azygos vein; portal hypertension

Patients with cirrhosis have hyperdynamic circulation with abnormally distributed blood volume and widespread arteriovenous communications. We aimed to detect possible very early (i.e., before 4 s) and early (i.e., after 4 s) central circulatory transits and their potential influence on determination of central and arterial blood volume (CBV). Thirty-six cirrhotic patients and nineteen controls without liver disease undergoing hemodynamic catheterization were given central bolus injections of albumin with different labels. Exponential and gamma variate fits were applied to the indicator dilution curves, and the relations between flow, circulation times, and volumes were established according to kinetic principles. No significant very early central circulatory transits were identified. In contrast, early (i.e., 4 s to maximal) transits corresponding to a mean of 5.1% (vs. 0.8% in controls; P < 0.005) of cardiac output (equivalent to 0.36 vs. 0.05 1/min; P < 0.01) were found in cirrhotic patients. These early transits averaged 7.7 vs. 12.7 and 17.2 s of ordinary central transits of cirrhotic patients and controls, respectively (P < 0.001). Early transits were directly correlated to the alveolar-arterial oxygen difference in the cirrhotic patients (r = 0.46, P < 0.01) but not in controls (r = 0.04; not significant). There was good agreement between the CBV determined by the conventional indicator dilution method and that determined by separation of early and ordinary transits by the gamma variate fit method (1.51 vs. 1.53 liter; not significant). In conclusion, no very early central circulatory transits were identified in cirrhotic patients. A significant part of the cardiac output undergoes an early transit, probably through pulmonary shunts or areas with low ventilation-perfusion ratios in cirrhotic patients. Composite determination of CBV by the gamma variate fit method is in close agreement with established kinetic methods. The study provides further evidence of abnormal central circulation in cirrhosis. central blood volume; exponential fit; indicator dilution technique; kinetic principles; pulmonary shunts; ventilation-perfusion ratio

The size of the central and arterial blood volume (CBV) is essential in the understanding of fluid retention in cirrhosis. Previously, it has been reported decreased, normal, or increased, but no reports have analyzed CBV with respect to gender and lean body mass. The aim of the present study was by means of an optimized technique to reassess it in a large group of patients with cirrhosis compared with healthy controls and matched controls in relationship to their body dimensions and gender. Eighty-three patients with cirrhosis (male/female, 60:23), 67 patients without liver disease (male/ female, 22:45), and 14 young healthy controls (male/female, 6:8) underwent a hemodynamic investigation with determination of cardiac output, central circulation time, and CBV determined according to kinetic principles. Related to gender, CBV was lower in male cirrhotics (1.48 [+ or -] 0.30 liter) than in matched and young controls (1.68 [+ or -] 0.33 and 1.72 [+ or -] 0.33 liter, respectively; P < 0.05-0.01). No significant differences in CBV were seen between female cirrhotics and controls. Absolute and adjusted CBVs were lower in the females than in men with cirrhosis (P < 0.001), and men with cirrhosis had lower absolute and body weight-adjusted CBVs than matched controls (P < 0.01). Normalized values of CBV (%total blood volume) were significantly lower in patients with cirrhosis (25 [+ or -] 4%) than in matched controls (31 [+ or-] 7%) and young controls (28 [+ or -] 4%; P < 0.02). CBV correlated significantly with anthropometrics, including lean body mass (r = 0.68-0.82; P < 0.0001). In conclusion, the CBV of patients with cirrhosis was lower than that of controls when adjusted for body dimensions and gender. There are significant gender differences, and signs of underfilling are more pronounced in male than in female patients. The results emphasize the importance of adjustments of blood volumes for anthropometrics and gender. central circulation time; hyperdynamic circulation; lean body mass; peripheral vasodilatation; portal hypertension; systemic vascular resistance

The formation of type III collagen of granulation tissue in experimental and clinical studies is effectively marked by the amino-terminal propeptide of type type III procollagen. (PIIINP). The PIIINP's disposal kinetics is not known. The I 125 labelled PIIINP is injected intravenouslly in the thoracic ductvenous of the concious pigs. After injection the initial distribution was 2.2 litres. There was a rapid intact of PIIINP in the lymphatic recirculation and the constancy of the lymphatic serum ratio after one hour of injection.

This review describes the development of single‐photon emission tomography (SPECT) in the Copenhagen area under the leadership of the internationally renown scientist, Niels A. Lassen, and the history leading up to construction of the tomograph. Measurements of global cerebral blood flow (CBF) in the 1940s and 1950s were performed by Kety & Schmidt and Lassen & Munck. Determination of regional cerebral blood flow (rCBF) by intra‐arterial injection of 133Xe and measurement with a 254‐multicrystal scintillation detector and a computer system was a major step forward in the study of physiology and pathophysiology of cortical cerebral blood flow. Tomography with radioisotope ligands, including non‐invasive administration, was advanced in different centres during the 1970s. An emission tomograph, the Tomomatic 64, was developed as a result of a multidisciplinary Danish and international collaboration. It was the first emission tomograph to provide dynamic data that could produce cross‐sectional rCBF images. The present description of the construction and function of the Tomomatic 64 includes comparison with other contemporary and later brain‐dedicated SPECT systems. Basic and clinical application of the Tomomatic 64 in Copenhagen resulted in several hundred important scientific publications and improved diagnostics for patients with a variety of neurological disorders. It is concluded that the development of the Tomomatic 64 was a major step forward in the study and examination of rCBF and brain function related to several brain disorders, in addition to vascular diseases. [ABSTRACT FROM AUTHOR]