Chronic heart failure is associated with vascular remodeling of the brachial artery

AIMS: Endothelial dysfunction has been shown to correlate with severity of congestive heart failure (CHF) and recent data suggest morphological changes of peripheral vasculature to be associated with the syndrome. We therefore investigated the hypothesis that vascular remodeling is associated with functional changes in peripheral conduit arteries and with systemic overexpression of ET-1 in patients suffering from CHF. METHODS AND RESULTS: 57 consecutive patients referred to the Innsbruck Heart Failure and Transplantation Program (EF=23+/-7%) and 16 matched controls (EF=60+/-5%) were studied. Flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), wall thickness (WT), and incremental elastic modulus (Einc) were assessed by high-resolution ultrasound of the brachial artery. FMD (P=0.004) and NMD (P=0.02) were significantly higher in controls as compared to moderate and severe CHF patients. In contrast, brachial artery-wall thickness (BA-WT) was increased in severe CHF patients (P=0.038). BA-WT was significantly correlated with both FMD (r=-0.28; P=0.049) and NMD (r=-0.38; P=0.003), and with the Einc (r=0.45, P=0.001). Lumen diameter was not different among groups. In patients with BA-WT>0.31 mm, bigET-1 was higher compared to BA-WT<0.31 mm (P<0.05). CONCLUSION: CHF is associated with remodeling of the brachial artery, which is characterized by morphological, mechanical and functional changes of the vessel wall. Endothelin-1 may play a role in the vascular remodeling process.     

Urinary albumin excretion is associated with impaired flow- and nitroglycerin-mediated brachial artery dilatation in hypertensive adults

We investigated whether the urinary albumin/creatinine ratio (UACR), a measure of albuminuria, is associated with non-invasive measures of arterial function in hypertensive adults without known coronary heart disease (CHD) or stroke. UACR was measured in the first voided morning urine sample in 469 non-Hispanic white hypertensive individuals (mean age 62.2+/-9.8 years, 41% men) belonging to hypertensive sibships. High-resolution ultrasonography of the brachial artery was used to assess flow-mediated dilatation (FMD)--an endothelium-dependent response--and nitroglycerin-mediated dilatation (NMD)--an endothelium-independent response. Because of skewed distribution, UACR was log transformed after addition of 0.1. The association of log (UACR+0.1) with FMD and NMD, before and after adjustment for CHD risk factors, serum creatinine, and hypertension medication and statin use was assessed using linear regression analyses. In univariable analyses, variables associated with lower FMD were greater age, male sex, history of smoking, lower high-density lipoprotein (HDL) cholesterol, higher serum creatinine and higher log (UACR+0.1); variables associated with lower NMD were greater age, male sex, higher systolic blood pressure, lower HDL cholesterol, higher serum creatinine and higher log (UACR+0.1). In separate stepwise multivariable regression analyses that adjusted for conventional CHD risk factors, serum creatinine and hypertension medication and statin use, higher log (UACR+0.1) was associated with lower brachial artery FMD (P=0.035) and NMD (P=0.0002). These findings highlight the association of increased urinary albumin excretion with impaired vascular reactivity in hypertensive individuals.     

Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation

Adiponectin may have an antiatherogenic effect by reducing endothelial activation. We hypothesized that plasma adiponectin levels were correlated with endothelial function. Plasma adiponectin level was determined by an in-house RIA assay using a rabbit polyclonal antibody in 73 type 2 diabetic patients and 73 controls. Endothelium-dependent and independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound. Plasma adiponectin level was lower in diabetic patients than in controls (4.73 +/- 1.96 vs. 7.69 +/- 2.80 microg/ml, respectively; P < 0.001), and they also had impaired endothelium-dependent (5.6 +/- 3.6 vs. 8.6 +/- 4.5%, respectively; P < 0.001) and -independent vasodilation (13.3 +/- 4.9 vs. 16.5 +/- 5.6%, respectively; P < 0.001). Plasma adiponectin correlated with endothelium-dependent vasodilation in controls (P = 0.02) and diabetic patients (P = 0.04). On general linear-model univariate analysis, brachial artery diameter, the presence of diabetes, plasma adiponectin, and high-density lipoprotein were significant independent determinants of endothelium-dependent vasodilation. In vitro experiments showed that endothelial cells expressed adiponectin receptors, and adiponectin increased nitric oxide production in human aortic endothelial cells. In conclusion, low plasma adiponectin level is associated with impaired endothelium-dependent vasodilation, and the association is independent of diabetes mellitus. Adiponectin may act as a link between adipose tissue and the vasculature.     

充血性心力衰竭患者肱动脉流量介导性舒张功能异常及生脉液的治疗作用

目的 :观察充血性心力衰竭 （CHF）患者肱动脉流量介导性舒张 （FMD）功能变化及生脉液的干预作用。方法 :CHF患者 6 0例随机分两组 :常规治疗组 （2 8例 ） ,予常规抗心衰治疗。生脉液组 （32例 ） ,在常规治疗的基础上加用生脉液 2 0～ 4 0 m l静滴 ,1次 / d。疗程 14 d。疗程前后分别进行肱动脉血管超声检测及运动耐量试验。正常对照组2 0例 ,不予任何治疗。结果 :1生脉液组临床总有效率显著高于常规治疗组 （P<0 .0 1） ,心衰纠正时间较常规治疗组显著缩短 （P<0 .0 1） ,运动耐受时间较常规治疗组显著延长。 2 CHF患者肱动脉 FMD活性较正常对照组显著减弱 （P<0 .0 1）。3生脉液组生脉液干预后肱动脉 FMD活性显著增强 ,与常规治疗组比较有显著差异 （P<0 .0 1）。结论 :CHF患者存在明显的血管内皮依赖性舒张功能障碍。生脉液通过增强 FMD活性 ,对该病具有治疗作用。     

青年长期吸烟者血管内皮依赖性舒张功能的改变

目的:探讨青年长期吸烟血管内皮依赖性舒张功能的改变。方法:测定20例长期吸烟青年及15例正常对照者血流介导的和硝酸甘油介导的肱动脉内径改变。结果:两组肱动脉内径基础值(3.75±0 61mm:3.81±0.55mm)及硝酸甘油介导的肱动脉舒张[(22.13±7.65)％:(23.45±8.21)％]无显著差异(P>0.05),而血流介导的血管扩张存在显著差异.为[(3.61±2.90)％:(8.32±4.75)％]、P<0.01。单因素相关分析表明,肱动脉内皮依赖件舒张与吸烟量呈显著负相关(r=0.523.P<0.001).结论:青年长期吸烟者血管内皮依赖性舒张功能明显受损,受损程度与吸烟量有关。     

Impaired flow-mediated endothelium-dependent and endothelium-independent vasodilation of the brachial artery in patients with atherosclerotic peripheral vascular disease

A flow-mediated endothelium-dependent vasodilation and endothelium-independent nitroglycerin-induced vasodilation were carried out in 70 patients and 15 age-matched adults without any atherosclerotic risk factors to clarify vascular responsiveness in patients with atherosclerotic peripheral vascular disease. The percent change in flow-mediated vasodilation was significantly lower in patients than in controls (5.4 +/- 0.7% vs 12.8 +/- 2.2%, P < .001). Moreover, the percent change in nitroglycerin-induced vasodilation measured after sublingual administration of nitroglycerin was lower in patients than in controls (5.8 +/- 0.6% vs 10.2 +/- 1.5%, P < .01). On multiple regression analysis, none of the determinant factors showed a significant correlation with flow-mediated vasodilation. In contrast, Fontaine classification was found to be a significant predictor for nitroglycerin-induced vasodilation (r = -0.307, P < .05). There is a significant positive correlation between nitroglycerin-induced vasodilation and ankle-brachial pressure index in the patients. The data showed that vasoditation function were markedly impaired in end-stage patients with peripheral vascular disease.     

Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease

OBJECTIVE: Flow-mediated, endothelium-dependent dilatation (FMD) of the coronary and peripheral circulation is impaired by increased oxidative stress in patients with coronary artery disease (CAD). Carvedilol is a novel beta-blocker that also shows an antioxidant effect in vitro. However, the effect of carvedilol on endothelial dysfunction associated with established coronary atherosclerosis has not been examined in the clinical setting. METHODS: We studied 29 patients with CAD, including 17 with recent myocardial infarction and 12 with stable effort angina pectoris. Nineteen patients received carvedilol (10 with infarction and 9 with angina), and 10 were treated with placebo (7 with infarction and 3 with angina). We also studied 13 age- and sex-matched control subjects. Brachial FMD during reactive hyperemia and nitroglycerin-induced, endothelium-independent dilatation were assessed by high-resolution ultrasound. RESULTS: FMD was smaller in patients with CAD compared with controls, although nitroglycerin-induced dilatation was similar. Carvedilol significantly improved FMD after long-term treatment (5. 1% +/- 0.4% at baseline to 7.8% +/- 0.3% after 4 months; P <.01) but not after short-term treatment (5.1% +/- 0.4% at baseline to 5.0% +/- 0.7% after 2 hours). Placebo therapy had no effect on endothelial dysfunction. Neither carvedilol nor placebo had an effect on nitroglycerin-induced dilatation after short- and long-term treatment. Long-term carvedilol therapy also significantly decreased the plasma level of thiobarbituric acid-reactive substances compared with placebo (carvedilol, 5.8 +/- 0.4 nmol/mL to 4.6 +/- 0.3 nmol/mL, P <.01; placebo, 5.9 +/- 0.4 nmol/mL to 5.8 +/- 0.4 nmol/mL, P = not significant). CONCLUSION: These findings suggest that the improvement of endothelial function by carvedilol may be caused by its antioxidant activity.     

Daytime Cheyne-Stokes respiration in ambulatory patients with severe congestive heart failure is associated with increased mortality

BACKGROUND: Cheyne-Stokes respiration (CSR) frequently occurs in patients with severe heart failure during sleep and may increase mortality. Daytime CSR supposedly poses an even greater risk, but its prevalence and prognostic importance remain elusive. Therefore, we investigated the circadian prevalence of CSR and its influence on survival in patients with heart failure. METHODS: In 60 consecutive ambulatory patients (mean age+/-SE, 58.0+/-1.5 years; 6 women) with stable severe heart failure (left ventricular ejection fraction, 26+/-1%; New York Heart Association [NYHA] class, 2.6+/-0.1), the breathing pattern was unobtrusively monitored during 24 h of usual activities with a portable respiratory inductive plethysmograph. RESULTS: During nights, 62% of patients had >or=15 periodic breathing cycles per hour; during days, the corresponding prevalence was 16%. CSR prevailed in 32+/-3% of the night and in 10+/-2% of the day, with peaks at 4:00 am, 2:00 pm, and 6:00 pm. Eighteen patients with CSR during >or=10% of the daytime lived shorter without heart transplantation than 42 patients with <10% of daytime CSR (p<0.05) during 836+/-27 days of follow-up. CSR during >or=10% of the daytime was an independent predictor of mortality (hazard ratio, 3.8; 95% confidence interval, 1.1 to 12.7; p<0.05) when controlling for age, sex, brain natriuretic peptide, left ventricular ejection fraction, and NYHA class. CONCLUSIONS: CSR occurs in 62% of patients with severe heart failure at night and in 16% during the day. Since daytime CSR is associated with reduced survival, solely performing sleep studies may not allow to adequately assess prognosis and tailor treatment in patients with severe heart failure.     

Role of antidiuretic hormone in impaired water excretion of patients with congestive heart failure

Plasma antidiuretic hormone (ADH), PRA, plasma osmolality, and the parameters of renal water excretion were measured after overnight dehydration and for 5 h after an oral load in 14 patients with congestive heart failure (CHF) treated with diuretics (group 1), 8 hypertensive patients without CHF also treated with diuretics (group 2), and 11 patients with coronary artery disease but without CHF who were not treated with diuretics (group 3). Under basal conditions, mean plasma osmolality was lower in group 1 than in group 3, but was not different in groups 1 and 2. Mean plasma ADH was higher in group 1 than in group 2 or 3. In response to the water load, plasma osmolality and plasma ADH levels decreased in the 3 groups. ADH levels remained significantly greater in group 1 than in groups 2 and 3 from 2-4 h after the water load despite more marked hypoosmolality in group 1 compared with that in either of the 2 control groups. Plasma ADH was significantly correlated with plasma osmolality only in the 2 control groups. Mean PRA was greater in patients with CHF and patients without CHF treated with diuretics than in untreated patients. Cumulative water excretion was lower in patients with CHF than in patients in the 2 control groups from 2-5 h after the water load. At 5 h, the mean percentage excretion of the ingested loads was 56.8%, 90.7%, and 91.2% in the patients of groups 1, 2, and 3 respectively. Free water clearance was lower and minimal urinary osmolality was greater in the patients with CHF than in those in the 2 control groups. Two patients with CHF, who excreted more than 75% of the water load, also had low plasma basal ADH levels. These data show that patients with CHF have an inappropriate response of plasma ADH to a marked fall in plasma osmolality. This disorder is not due to the diuretic therapy, since hypertensive patients treated with diuretics behaved similarly to untreated patients without CHF. The reasons for this inappropriate response of plasma ADH during a water load in patients with CHF are probably multifactorial.     

Pro-inflammatory cytokines and endothelium-dependent vasodilation in the forearm. Serial assessment in patients with congestive heart failure

Background In patients with heart failure endothelium-dependent vasodilationof the forearm conduit vessels is impaired possibly becauseof elevated plasma levels of pro-inflammatory cytokines. Theeffect of elevated plasma cytokines on endothelium-dependentvasodilation of forearm conduit vessels was therefore seriallyinvestigated in 16 patients with congestive heart failure duringan episode of acute failure and at the time of recompensation. Methods and Results Pro-inflammatory cytokine levels and hyperaemic brachial arterydiameters were obtained shortly after admission for an episodeof acute heart failure and 11±3 days later at the timeof recompensation, which was obtained using diuretic therapywithout changing other cardiovascular medications. Serum concentrations(Mean±SD) of tumour necrosis factor alpha (TNF-) (decompensationvs recompensation: 25±23pg.ml^–1vs 26±17pg.ml^–1)and interleukine 6 (IL-6) (decom-pensation vs recompensation:27±24pg.ml^–1vs 20±18pg.ml^–1), determinedin venous blood using immunoradiometric assays were elevatedbut remained unaltered following recompensation. Brachial arterydiameter, derived from high-resolution ultrasound scans at restand during reactive hyperaemia, 90s after forearm cuff deflation,increased significantly during reactive hyperaemia at the timeof admission (3·4±0·7mm vs 4·0±0·5mm;P=0·014)and following recompensation (3·4±0·5mmvs 3·8±0·2mm;P=0·032). The brachialartery diameter during recompensation expressed as a percentageof the baseline value was similar at both intervals (decompensationvs recompensation: 117±14% vs 116±10%;P=ns). Atthe time of decompensation, the correlation between TNF- andthe percentage change in brachial artery diameter followingreactive hyperaemia was absent (r=0·098;P=0·719).The same correlation became significant at the time of recompensation(r=0·750;P=0·001). Conclusions In patients with congestive heart failure, plasma levels ofpro-inflammatory cytokines correlate with endothelium-dependentvasodilation of the brachial artery following recompensation,but not during an acute episode of heart failure.     

Biomechanical efficiency is impaired in patients with chronic heart failure

INTRODUCTION: Patients with chronic heart failure (CHF) have a lower peak oxygen consumption (pVO2) than normal subjects, and for a given quantity of work, have a lower total oxygen consumption (VO2) than controls. This apparent increase in biomechanical efficiency (BE) might be due to a higher proportion of anaerobic metabolism which, although leading to lower VO2 during steady state exercise, must be compensated for during recovery. METHODS: 13 patients with stable CHF and 12 controls underwent peak cycle exercise testing followed by three separate steady state exercise tests at 15%, 25% and 50% of the peak workload in random order. Oxygen consumption at steady state, deficit (during onset) and debt (during recovery) were calculated. BE was estimated as the total oxygen required to perform a given quantity of work. RESULTS: Patients had lower pVO2 and peak workload than control subjects. Absolute oxygen deficit and debt as a percentage of total oxygen consumed during the steady state tests was the same in both groups. However, once controlled for workload, VO2 deficit, debt and uptake at steady state were greater in patients than controls for the tests at 15% and 25% of peak. BE was inversely related to peak oxygen consumption in controls and patients. CONCLUSIONS: Patients with CHF have impaired BE at low work loads when compared with normal subjects.     

Association of coronary risk factors and endothelium-dependent flow-mediated dilatation of the brachial artery.

Impaired endothelial function has been reported to be the initial step in atherosclerosis. Some coronary risk factors independently relate to impaired endothelial function. However, few studies have examined the association between coronary risk factors and endothelial function in patients who have multiple risk factors without clinical atherosclerosis. This study was undertaken to elucidate the relationship between accumulation of coronary risk factors and vascular endothelial dysfunction. We examined 101 subjects with one or more coronary risk factors 56.8 +/- 1.0 years old and 40 age-matched control subjects without coronary risk factors. We measured brachial artery diameter non-invasively using a 7.5-MHz ultrasound machine at rest, during reactive hyperemia caused by endothelium-dependent vasodilatation, and after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. The percentage change in flow-mediated diameter (%FMD; deltaD/D x 100), in subjects with one or more coronary risk factors was significantly lower than that in control subjects(4.8 +/- 0.3% vs. 6.7 +/- 0.5%, p < 0.01). Endothelium-independent vasodilatation by nitroglycerin did not differ between the two groups. Endothelial function was impaired according to the accumulation of coronary risk factors. On multiple regression analysis, the number of risk factors, age, and brachial artery diameter at rest showed significant correlation with %FMD. Our results suggest that an accumulation of coronary risk factors was significantly related to impairment of endothelial function.     

Female sex is associated with a better long-term survival in patients hospitalized with congestive heart failure.

AIMS: Results of previous studies on the influence of gender on prognosis in heart failure have been conflicting and most studies have been conducted in selected populations. The aim of this study was determine whether mortality risk in women and men hospitalized with congestive heart failure is different. METHODS AND RESULTS: Survival analysis of 5491 consecutive patients admitted with congestive heart failure to 34 Danish hospitals between 1993-1996. Follow-up time was 5-8 years. Forty percent of the patients were female. Females were older, had less evidence of ischaemic heart disease and their left ventricular systolic function was preserved to a greater extent than in males. Men were more often treated with ACE inhibitors. During the follow-up period 1569 women (72%) and 2386 (72%) of the men died. When the age difference between men and women was adjusted for, male gender was associated with an increased risk of death (RR 1.25 (1.17-1.34)) and the increased risk was confirmed in a multivariate model containing several covariates. CONCLUSIONS: In patients hospitalized with congestive heart failure male gender is an independent predictor of mortality. Female heart failure patients may be under-treated with ACE inhibitors.     

Pilot study of a Web-based compliance monitoring device for patients with congestive heart failure

BACKGROUND: Web-based home care monitoring systems can assess medication compliance, health status, quality of life, and physiologic parameters. They may help overcome some of the limitations associated with current congestive heart failure management models. OBJECTIVES: This pilot study compared the effects of a self-care and medication compliance device, linked to a Web-based monitoring system, to the effects of usual care alone on compliance with recommended self-care behaviors; medication taking; quality of life; distance walked during a 6-minute walk test; and New York Heart Association Functional Class. We also assessed patient experiences living with the compliance device. METHODS: We enrolled 18 patients with Functional Class II-III congestive heart failure in an urban VA Medical Center. The patients were randomized into 2 groups. Group A received usual care plus the compliance device. Group B (controls) received usual care only. Data were collected using the compliance device, the Heart Failure Self-Care Behavior Scale, pill counts, 6-minute walk test, and the Minnesota Living with Heart Failure Questionnaire at baseline and at 3 months follow-up. RESULTS: At baseline and at 3 months, there were no differences between the compliance device group and the usual care group in self-care behaviors, pill counts, 6-minute walk-test distance, or Functional Class. However, quality of life improved significantly from baseline to 3-month follow-up (ANOVA, P =.006). This difference was due to an improvement in quality of life for the monitor group (P =.002) but not the usual care only group (P =.113). Patients in the compliance device group had a 94% medication compliance rate, 81% compliance with daily blood pressure monitoring, and 85% compliance with daily weight monitoring as compared to 51% for blood pressure monitoring and 79% for weight monitoring in the usual care group (P = NS). CONCLUSION: These are promising pilot results that, if replicated in a larger sample, may significantly improve care and outcomes for patients with heart failure.     

Statins associated with reduced mortality in patients admitted for congestive heart failure

BackgroundStatins may be of potential benefit in patients with congestive heart failure (CHF) due to modulation of neurohormones and their antioxidant, antiinflammatory, and antifibrotic properties. To test this hypothesis, we performed a case-control study by using a prospective registry of patients admitted to our hospital for CHF.Methods and ResultsThe Maastricht Registry of Congestive Heart Failure consists of a cohort of all patients who were admitted to the University Hospital Maastricht because of CHF for the first time between 1998 and 2000. Elective admissions were not included in the database. Drug treatment was left at the discretion of the attending physician. From a total of 840 patients admitted, we selected patients with an uncomplicated survival for at least 1 month after hospital discharge. For each survivor a nonsurvivor was matched for age, sex, left ventricular ejection fraction, and renal function. Drugs were considered in use only if they were administered for at least 90% of follow-up time. Five hundred twenty-four patients were included with a mean follow-up after discharge of 31 ± 18 months. Twenty percent used statins. In Cox multivariate regression analysis, the use of statins remained significantly associated with decreased mortality independent of the cause of CHF. However, there appeared no additional benefit of statins in patients using beta-blockers. Mortality rates were constant over time after discharge. Statins were as effective in ischemic as in nonischemic heart failure and in patients with depressed as well as preserved LVEF.ConclusionStatins appear associated with improved survival in CHF independent of its etiology. No additional benefit was seen in patients treated with beta-blockers.     

Mineralocorticoid receptor is overexpressed in cardiomyocytes of patients with congestive heart failure

Mineralocorticoid receptors (MRs) have been identified in the human cardiovascular tissues. We determined MR expression in the failing heart to clarify the mechanism of action of aldosterone antagonist in the treatment of congestive heart failure. MR protein and MR mRNA content were detected by immunohistochemical staining and in situ hybridization in the cardiac tissues. Immunohistochemical staining of the receptor, as well as in situ hybridization of MR mRNA, was dense in cardiomyocytes of the failing left ventricle as compared with the controls. The staining ratio of the cytoplasm to the interstitium showed that MRs were located mainly in the cytoplasm. The cytoplasm to the interstitium in the failing left ventricle was 1.53+/-0.13, which was significantly higher than that of the controls 1.25+/-0.19 (p<0.05). These findings suggest that the efficacy of aldosterone antagonists in treating congestive heart failure may be in part through blocking the MRs, which are upregulated in the failing heart.     

Nitroprusside and regional vascular capacitance in patients with severe congestive heart failure.

BACKGROUND. This study investigates the effects of sodium nitroprusside on regional vascular capacitance in eight patients with severe congestive heart failure (New York Heart Association class IV) and pulmonary hypertension. METHODS AND RESULTS. Regional relative blood volumes in the splanchnic and pulmonary region were determined by equilibrium blood pool scintigraphy. Hepatic venous wedge pressure and the mean of pulmonary artery and pulmonary capillary wedge pressure were used to represent the distending pressures of the splanchnic and pulmonary capacitance vessels, respectively. The dose of sodium nitroprusside was increased stepwise until systolic pulmonary artery pressure decreased below 50 mm Hg. This caused reductions in mean aortic pressure from 89 +/- 5 to 66 +/- 3 mm Hg (p less than 0.005), in pulmonary capillary wedge pressure from 31 +/- 1 to 16 +/- 2 mm Hg (p less than 0.001), and in hepatic venous wedge pressure from 10.0 +/- 1.0 to 5.9 +/- 0.6 mm Hg (p less than 0.005). Intestinal blood volume increased by 26 +/- 7% (p less than 0.005), whereas hepatic blood volume decreased by 9 +/- 3% (p less than 0.02). Pulmonary blood volume was unchanged. Analysis of intestinal and pulmonary vascular pressure-volume relations showed larger or equal blood volumes contained at lower distending pressures, indicating that sodium nitroprusside reduced smooth muscle tone of the capacitance vessels in these regions. The reduction of hepatic blood volume was compatible with passive expulsion of blood subsequent to reduced venous pressure. There was no change in the count rate from the spleen. CONCLUSIONS. Nitroprusside reduced venous pressure in patients with congestive heart failure by active relaxation of intestinal and pulmonary capacitance vessels. Hepatic vascular volume was probably reduced by a passive mechanism.