Biomedical subjects

H C Lin

Publications and source records attributed to H C Lin.

At least 253 records · Page 14Linked to original sources

PubMed1996

Synthesis and antithrombotic effect of xanthone derivatives.

A series of xanthone derivatives was synthesized and tested in-vitro for their ability to inhibit aggregation of rabbit washed platelets and human platelet-rich plasma (PRP) induced by various inducers. 2-Prenyloxyxanthone showed the most potent inhibition of rabbit washed platelet aggregation induced by arachidonic acid (1C50 = 10.2 microM). Of the compounds tested in human PRP, 2-[3 (propylamino)-2-hydroxypropoxy]xanthone (4) hydrochloride salt exhibited the most potent inhibition of platelet aggregation induced by adrenaline (IC50 = 4.4 microM), whereas in evaluation of mouse antithrombotic activity, compound 4 exhibited the most potent protection of mice from thrombotic challenge. Compound 4, 2-[3-(isopropylamino)-2-hydroxypropoxylxanthone hydrochloride salt and 2,5 dihydroxyxanthone suppressed the secondary aggregation induced by adrenaline in human PRP. We conclude that the antiplatelet effects of these compounds are mainly due to an inhibitory effect on thromboxane formation.

Animals↗

PubMed1996

Frequency of gastric pacesetter potential depends on volume and site of distension.

Little is known about the response of the frequency of gastric pacesetter potential (PP) to luminal distension. When volume distension occurs as a result of a meal, gastric emptying may play an important role, since the site of distension shifts as the meal is displaced from the stomach to the small bowel. In this study, using does equipped with duodenal fistulas and serosal electrodes on the antrum, we compared the frequency of gastric PP during the course of gastric emptying while isolating the volume distension to either the stomach or the small bowel. We found that 1) the frequency of gastric PP decreased linearly with greater initial meal volume when volume distension was isolated to either the stomach -P<0.05, analysis of variance (ANOVA)- or small bowel (P<0.01, ANOVA), and 2) the frequency of gastric PP decreased linearly with increased volume remaining in the stomach or increased volume entering the small intestine. We conclude that the frequency of gastric PP depends on the volume and site of distension.

Analysis of Variance↗

PubMed1996

Fat absorption is not complete by midgut but is dependent on load of fat.

Since the intubation study of B. Borgstrom, A. Dahlqvist, and G. Lundh (J. Clin. Invest. 36: 1521-1536, 1957) in humans, the completion of fat absorption within the proximal small intestine has been widely accepted. Based on this report, it has been assumed that the distal small intestine is exposed to fat only in the setting of pathology. This concept may be flawed, since completeness of fat absorption was calculated from the recovery of a water-soluble marker but the aqueous phase is now known to move independently from fat. To reexamine the question of whether fat absorption is complete by midgut, we measured the recovery of a fat-specific marker, 99mTc-thiocyanate, in a canine model equipped with duodenal and midgut fistulas. The fistulous output allowed for the measurement of the amount of fat entering the small intestine and the amount of fat entering the distal one-half of the small intestine. Emulsion meals containing 15 or 60 g of corn oil were tested. The importance of fat exposure of the distal one-half of the small intestine was further confirmed by comparing the fistulous fat recovery under two different patterns of exposure [allowing (ALL) or denying (150 cm) access to the distal small intestine]. We found that fat recovery depended on 1) the dose of fat (15 vs. 60 g; P < 0.0005), 2) the pattern of exposure (150 cm vs. ALL; P < 0.01), and 3) the fistulous position (duodenal vs. midgut; P < 0.005). Specifically, under a 150-cm exposure pattern, whereas 8.8 +/- 1.8 g (means +/- SE) of fat emptied into the duodenum after the 15-g fat meal, 32.6 +/- 3.2 g emptied after the 60-g fat meal. Correspondingly, although 3.5 +/- 1.5 g of fat were recoverable from the midgut fistulous output after the 15-g meal, a much larger amount, 17.1 +/- 5.6 g of fat, was recoverable and therefore not absorbed by the proximal one-half of the small intestine after the 60-g meal. The amount of fat recovery at each fistula was reduced when chyme was allowed access to the whole gut (by triggering fat-induced ileal brake). We conclude that the intestinal length required for fat absorption depends on the load of fat in the meal so that, even after usual meals, absorption of fat is not complete by midgut.

Absorption↗

PubMed1996

Cardiovascular effects of nitric oxide in the brain stem nuclei of rats.

Nitric oxide, synthesized from the semiessential amino acid L-arginine by nitric oxide synthase, is a remarkable regulatory molecule and plays an important role in physiological functions. However, the physiological role of nitric oxide in cardiovascular regulation by the central nervous system is not well understood. In this study we investigated the cardiovascular effects of nitric oxide in the lateral ventricle, nucleus tractus solitarii, area postrema, and rostral ventrolateral medulla in urethane-anesthetized male Sprague-Dawley rats. Microinjection of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, into the cerebral ventricle of rats elicited a dose-dependent increase in blood pressure and heart rate. This suggests that nitric oxide may be involved in central cardiovascular regulation. Unilateral microinjection (60 nL) of L-arginine (1 to 100 nmol) into the nucleus tractus solitarii and rostral ventrolateral medulla produced prominent dose-related depressor and bradycardic effects and reduced renal sympathetic nerve activity. However, L-arginine had no significant cardiovascular effects in the area postrema. In addition, 4 to 6 hours after intravenous injection of bacterial endotoxin-lipopolysaccharide (10 mg/kg), there was a time-related potentiation of the L-arginine-induced depressor and bradycardic effects in the nucleus tractus solitarii. These results indicate that nitric oxide is involved in central cardiovascular regulation. The depressor effect of nitric oxide in the nucleus tractus solitarii and rostral ventrolateral medulla may be through inhibition of renal sympathetic nerve activity.

Animals↗

PubMed1996

Bile salt inhibits acid-promoting feeding tube occlusion.

Occlusion of feeding tubes is a common and costly complication of enteral feeding. Although the composition of feeding formulas, the size, design, and material of the feeding tube, and the rate of delivery have been considered as factors that determine the rate of tube occlusion, little information is available on the effect of the luminal content of the gut on tube occlusion. Enteral feeding tubes are placed either in the stomach or postpylorically, in the small intestine. The chemical composition of these regions including acidity and bile salt concentration may vary. Since acidity has been shown to promote tube occlusion and bile salts have detergent-like properties, these chemical differences in the luminal environment may be important to tube occlusion. To test the idea that bile salt inhibits acid-promoted occlusion of feeding tubes, in an in vitro study, we compared the time-to-complete occlusion of four groups of formula-filled feeding tubes (six tubes in each group) immersed in an acidic solution (pH 3.0) containing 0 (control), 10, 20, or 40 mM of taurocholate. We found that although 33% of the feeding tubes were occluded within 12 hours in the absence of exposure to bile salt, none were occluded when 20 or 40 mM of taurocholate was added to the acidic solution. After 24 hours, 40 mM of taurocholate inhibited acid-promoted occlusion of 67% of the feeding tubes. Thus 0 to 40 mM of taurocholate still inhibited acid-promoted tube occlusion in a dose-dependent fashion (p < .05). Acidity and the concentration of bile salt may work together, but in opposite directions, as luminal factors that determine the rate of occlusion of feeding tubes.

Cholagogues and Choleretics↗

PubMed1996

Differential effects of nasal continuous positive airway pressure on reversible or fixed upper and lower airway obstruction.

Our study was to assess whether there were differential effects of nasal continuous positive airway pressure (nCPAP) on different kinds of obstruction in either upper or lower airways in patients with chronic obstructive pulmonary disease (COPD). nCPAP (6 cmH2O for ten minutes) was applied to 7 patients with reversible extrathoracic upper airway obstruction (RUAO) and 3 patients with fixed extrathoracic upper airway obstruction (FUAO). Eighteen stable asthmatics, receiving methacholine challenge to induce a more than 20% reduction in FEV1, were randomly investigated for the effect of nCPAP or sham pressure on reversible lower airway obstruction. Nine stable COPD patients were enrolled to study the effect on irreversible lower airway obstruction. Maximal expiratory and inspiratory flow volume curves and dyspnoea scores were obtained before and after immediate withdrawal of nCPAP. In the RUAO group, nCPAP significantly improved stridor and dyspnoea scores, decreased the ratio of FEF50/FIF50 from 2.05 +/- 0.25 to 1.42 +/- 0.16, and increased peak inspiratory flow (PIF) as well as forced inspiratory vital capacity by 26 +/- 8% and 9 +/- 4%, respectively. In expiratory phase, there was no significant change in pulmonary functions. In asthmatics, nCPAP significantly reversed methacholine-induced bronchoconstriction increasing forced vital capacity by 10 +/- 3%, FEV1 by 15 +/- 4% and PIF by 32 +/- 11%. nCPAP significantly increased the response to bronchodilators. The improvement in airflow rate persisted for at least 5 min after nCPAP withdrawal and was highly correlated with the response to bronchodilators. There was no significant effect of nCPAP on airflow rate in COPD patients. Subjective dyspnoea score changes paralleled the pulmonary function improvement. We conclude that there are differential effects of nCPAP on airflow rates in patients with different nature of airway obstruction. Patients with airway obstruction caused by structural changes may not benefit from the use of nCPAP in improving airflow rates.

Adolescent↗

PubMed1996

Portal hypertensive colopathy in patients with cirrhosis.

BACKGROUND: Colonic vascular ectasias and colorectal varices have been observed in patients with cirrhosis. However, the pathogenesis of these vascular lesions has not been established. METHODS: We enrolled 35 cirrhotic patients and 20 normal controls in this study. All received colonoscopic examinations and measurements of plasma glucagon levels. Portal pressure measurements were performed in all the cirrhotic patients. RESULTS: Colonic vascular ectasias occurred more commonly in cirrhotic patients than in controls (17 of 35 versus 0 of 20; p = 0.009) and more commonly in cirrhotic patients with ascites than in those without (15 of 24 versus 2 of 11; p = 0.038). However, the presence of colonic vascular ectasias was not related to the hepatic venous pressure gradient or plasma glucagon levels. Colorectal varices also occurred more commonly in cirrhotic patients than in controls (16 of 35 versus of 1 of 20; p = 0.034), but the hepatic venous pressure gradient, plasma glucagon levels, and severity of cirrhosis were not related to the presence of colorectal varices. CONCLUSIONS: Portal hypertension per se and increased plasma glucagon levels may not play an important role in the pathogenesis of colonic vascular ectasias or colorectal varices in patients with cirrhosis.

Aged↗

PubMed1996

Plasma interleukin-6 levels in patients with cirrhosis. Relationship to endotoxemia, tumor necrosis factor-alpha, and hyperdynamic circulation.

BACKGROUND: Liver cirrhosis with portal hypertension is associated with hyperdynamic circulation characterized by generalized vasodilatation and increased cardiac output and regional blood flows. Patients with liver cirrhosis present with increased levels of interleukin-6 (IL-6), which may inhibit vascular smooth-muscle contraction. We investigated whether increased plasma IL-6 levels contribute to the pathogenesis of hyperdynamic circulation observed in cirrhotic patients and whether they are correlated with plasma tumor necrosis factor-alpha (TNF-alpha) and endotoxin concentrations. METHODS: In 58 consecutive cirrhotic patients and 34 healthy subjects the plasma concentrations of TNF-alpha and IL-6 were measured with enzyme-linked immunosorbent assay, and endotoxin determinations with a limulus assay. In addition, 52 cirrhotic patients underwent a hemodynamic study using Swan-Ganz catheterization. RESULTS: Plasma TNF-alpha, IL-6, and endotoxin levels were significantly higher in cirrhotic patients than in healthy subjects (7.3 +/- 0.2 versus 5.8 +/- 0.1 pg/ml, 6.4 +/ 0.8 versus 2.0 +/- 0.2 pg/ml, and 7.6 +/- 1.2 versus 2.8 +/- 0.3 pg/ml, respectively; p < 0.01). In cirrhotic patients the plasma levels of TNF-alpha IL-6, and endotoxin progressively increased in relation to the severity of liver dysfunction (graded by Pugh's classification). A significant correlation was observed between plasma TNF-alpha and IL-6 levels (r = 0.48, p < 0.001), whereas no correlation was observed between plasma endotoxin levels and plasma TNF-alpha and IL-6 levels. Plasma IL-6 levels correlated negatively with systemic vascular resistance in patients with cirrhosis (r = 0.5, p < 0.01). CONCLUSIONS: Plasma IL-6 levels are increased in patients with cirrhosis. The severity of liver cirrhosis is an important factor for the occurrence of increased IL-6 levels. IL-6 may play a role in the hyperdynamic circulation observed in patients with cirrhosis.

Blood Circulation↗

PubMed1996

Lack of autoantibody expression in children born to mothers with silicone breast implants.

OBJECTIVE: We determined systematically the prevalence of autoantibodies in children born to mothers with silicone breast implants and the relationships with clinical symptoms and methods of exposure. METHODS: Autoantibody expression was determined in 80 children born to mothers with silicone implants and in 42 controls. A clinical assessment score was assigned to each patient. Antinuclear antibodies as well as antibodies to mitochondrial, smooth muscle, striational, myocardial, parietal cell, reticulin tissues, or subcellular compartments were measured by indirect fluorescent assay. Antibodies to nRNP (U1-RNP/snRNP); Sm; SS-A; SS-B; Scl-70; thyroid microsome; immunoglobulin (Ig)G, IgM, and IgA antibodies to cardiolipin; and antibodies to native and denatured human types I and II collagen were measured by enzyme-linked immunosorbent assay. Serum complement components C3 and C4 and IgM rheumatoid factor were measured by nephelometry. RESULTS: Autoantibody prevalence was not significantly different between children born to mothers with silicone implants and controls. The presence of autoantibodies was not related to the children's clinical symptoms or to the method of exposure. CONCLUSIONS: Determination of autoantibody production is of limited clinical utility in the evaluation of children born to mothers with silicone breast implants.

Adolescent↗

PubMed1996

Cytokeratin fragment 19 (CYFRA 21-1) as a tumor marker in non-small cell lung cancer.

To evaluate the diagnostic value of the serum cytokeratin 19 fragment (CYFRA 21-1) in bronchogenic carcinoma, we investigated the sera of 138 patients (58 with benign pulmonary disease and 80 with non-small cell lung cancer (NSCLC)) using immunoradiometric assay. The mean (SD) value of serum CYFRA 21-1 in NSCLC (13.26 (16.54)) was significantly higher than in benign lung diseases (1.74 (1.55)) (p < 0.0001). Sensitivity for CYFRA 21-1 (using 3.5 ng/ml, a cut-off value corresponding to a 95% specificity for benign pulmonary disease) in NSCL was 62%. Positive CYFRA 21-1 levels were significantly higher in 75% of patients with squamous cell carcinoma (n = 36) than in 53% with other NSCLC (n = 44) (p < 0.05). CYFRA 21-1 levels were significantly different between squamous cell carcinoma (17.28 (19.94)) and the other NSCLC (9.96 (12.44)) (P < 0.05). Elevated CYFRA 21-1 levels in patients with stage III and IV disease (n = 64, 18.19 (26.51)) were significantly higher than in stage I and II (n = 16, 4.41 (5.76)) (p < 0.02). The positive rate of CYFRA 21-1 in tumor stage I and II was only 37%. Our results indicate that CYFRA 21-1 may be a useful tumor marker in NSCLC, especially in squamous cell carcinoma. However, CYFRA 21-1 cannot be used for the diagnosis of early stage disease of NSCLC. CYFRA 21-1 may also contribute to the monitoring of NSCLC.

Adolescent↗

PubMed1996

Vascular hyporesponsiveness in aorta from portal hypertensive rats: possible sites of involvement.

Vascular hyporesponsiveness in portal hypertension has been proposed to be due to postreceptor defect. The present study was aimed to investigate possible sites of involvement in such hyporesponsiveness. Portal hypertension was induced by partial portal vein ligation (PVL). Concentration-response curves to KCI and phenylephrine in both groups showed that the Emax values were significantly lower in the PVL group. The EC50 values were not different between the two groups. In Ca++ free condition, phenylephrine induced a phasic contraction, which was significantly smaller in the aorta from PVL rats. Cumulative readdition of CaCl2 (1.0-2.5 mM) induced tension increases, which were all significantly lower in the PVL group. Basal contents of [3H]inositol phosphates in the aorta were similar between the two groups. Phenylephrine induced concentration-dependent increase of [3H]inositol phosphates in the aorta from both groups. The responses at 10(-8), 10(-7), 10(-6) and 10(-5) M were significantly smaller in the PVL group than in the sham-operated group. Both okadaic acid and phorbol 12,13-dibutyrate induced slowly developing contractile responses in the aorta. The responses were similar between the two groups at all time points. Our results suggested that in the aorta from PVL rats, vascular hyporesponsiveness was observed, together with decreased contractile responses due to: voltage- and receptor-dependent calcium influx as well as intracellular calcium release, and decreased receptor-coupled inositol phosphate formation. Contractile responses due to activation of protein kinase C or phosphatase inhibition were not impaired.

Animals↗

PubMed1996

Immunohistochemical analysis of an equine model of synovitis-induced arthritis.

OBJECTIVES: To use lipopolysaccharide (LPS) to create synovitis in the midcarpal joint of ponies, and to assess the morphologic, histochemical, and immunohistochemical effects of synovitis on articular cartilage of the third carpal bone. ANIMALS: 2- to 3-year-old ponies, 6 control (group 1) and 6 treated (group 2). PROCEDURE: Synovitis was induced in 1 midcarpal joint of group-2 ponies by intra-articular injections of LPS (0.02 micrograms/kg of body weight), morphine (0.1 mg/kg), and saline solution (group 2a) and a morphine and saline solution alone in the contralateral midcarpal joint (group 2b). Articular cartilage sections and attached synovial membrane from the third carpal bones were examined by immunohistochemical distribution of interleukin 1 beta, tumor necrosis factor (TNF)-alpha, TNF receptors (P55, P75) and 3-B-3(-) epitopes, and by localization of proteoglycans (metachromatic staining). Proteoglycan extracts were assessed by metachromatic staining or western blotting and immunohistochemical staining, using anti-3-B- antibodies. RESULTS: Enhanced immunoreactivity for the cytokines and receptors was found in inflamed synovial membrane and noncalcified cartilage (group 2a more than 2b). Metachromasia of the noncalcified cartilage was greater in group-1 than in group-2a and group-2b specimens. In group 2a, chondrocyte hypertrophy and enhanced immunoreactivity for 3-B-3(-) epitope in areas of increased cytokine immunoreactivity suggested possible phenotypic change of the chondrocytes in response to synovitis. Immunohistochemical analysis by western blotting of proteoglycan extracts indicated strong 3-B-3(-) epitope immunolocalization in group-2a, weaker staining in group-2b, and barely detectable stain in group-1 specimens, which correlated with in situ immunolocalization. CONCLUSIONS: Intra-articular administration of LPS may be used to induce a synovial environment conductive to increased immunoreactivity of interleukin 1 beta, TNF-alpha, and its receptors in equine synovial membrane and articular cartilage. These cytokines may be involved in the early phenotypic change of chondrocytes that is believed to occur in osteoarthritis and is characterized in this study by enhanced 3-B-3(-) epitope immunoreactivity and chondrocyte hypertrophy.

Animals↗

PubMed1996

Quantification of proliferating cell nuclear antigen in large intestinal crypt by computer-assisted image analysis.

Measurements of proliferating cell nuclear antigen (PCNA) labeling of the large intestinal crypts scored by experienced observers were compared with those generated by computer-assisted image analysis (CAIA). (CAIA was performed at Pathology Expertise, Inc., Newton, MA, by A. V. Sotnikov.) Serial sections (3 microns) of the rectal biopsy specimens from 32 patients were immunostained for PCNA and then counterstained with hematoxylin. The same set of slides and rules for the location/acquisition of complete crypts was used to assess a minimum of ten complete crypts/patient. Each crypt was subdivided longitudinally into five equal compartments. With CAIA, the images were stored digitally, and once the color references were set, the areas occupied by labeled and counterstained nuclei were quantified automatically. The labeling index (LI) was calculated from the PCNA-labeled nuclei area/total nuclei area in CAIA and from the number of labeled cells/total number of cells in visual scoring. The LI of whole crypts averaged 1.04 +/- 0.18 by CAIA and 3.91 +/- 0.46 by the visual method, and the Spearman correlation (rs) between the two methods was 0.89. The different modes of evaluation and color reference selection are likely to have contributed to the differences in the LI ranges observed in the two methods. The high correlation between PCNA quantification by CAIA and visual scoring by experienced technicians indicates that CAIA can reliably rank individual subjects. Thus, measurement of PCNA labeling by CAIA is a practical alternative for evaluating colorectal epithelial cell proliferation.

Adult↗

PubMed1996

Clinical implications of the white nipple sign and its role in the diagnosis of esophageal variceal hemorrhage.

OBJECTIVE: Differentiation of esophageal variceal hemorrhage from other sources of the GI tract is often difficult. This is a prospective investigation of the significance of the white nipple sign in patients with recent esophageal variceal hemorrhage. METHODS: One hundred sixty-six patients with recent variceal hemorrhage were prospectively studied with respect to presence or absence of the white nipple sign and other stigmata of hemorrhage and compared with 100 patients with known varices but without a clinical history of bleeding. RESULTS: The white nipple sign correlated positively with severity of bleeding (patients required more blood transfusion), hematemesis, and signs of shock. Patients with the white nipple sign also tended to undergo emergency endoscopy and have active bleeding at the time of endoscopy. There was no correlation between rebleeding rate after endoscopic therapy and presence of the white nipple sign. Appearance of the white nipple sign was closely related to the timing of endoscopy (p < 0.0001). The sensitivity and specificity of the white nipple sign in the diagnosis of esophageal variceal hemorrhage were 21 and 100%, respectively, compared with 100 and 54% for the red color sign. Furthermore, the sensitivity of the white nipple sign increased with shorter times between bleeding and endoscopy. CONCLUSIONS: In patients with upper GI bleeding, the white nipple sign suggests that the varices bled recently and that the bleeding was severe. However, it has no predictive value for rebleeding after endoscopic therapy. Earlier endoscopy (i.e., within 24 h of bleeding) is suggested to improve the diagnostic rate of esophageal variceal hemorrhage.

Case-Control Studies↗

PubMed1996

Modulatory effects of nitric oxide on baroreflex activation in the brainstem nuclei of rats.

It has been shown that nitric-oxide (NO) was synthesized in the central nervous system as well as in vascular endothelial cells. We reported recently that nitric oxide was involved in central cardiovascular regulation of rat brainstem nuclei. In the present study, we evaluated further the baroreflex response of NO in the nucleus tractus solitarii (NTS) of rats. Male Sprague-Dawley rats were anesthetized with urethane, blood pressure and heart rate was monitored intra-arterially. Intramedullary microinjection (60 nl) of NO synthase inhibitor NG-methyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester(L-NAME) or normal saline was made into the NTS. Baroreflex response were elicited by increasing doses of phenylephrine (10-30 micrograms/Kg i.v.) before and after intra-NTS administration of L-NMMA, L-NAME or normal saline. The reflex bradycardia elicited by phenylephrine was significantly inhibited by the pretreatment of L-NMMA or L-NAME. Furthermore, the inhibitory effects on baroreflex activation by L-NMMA were significantly reversed by pretreatment with L-arginine. These results suggested that central endogenous NO was involved in the medullary regulation of blood pressure and that NO synthase inhibitor attenuated baroreflex activation.

Animals↗

PubMed1996

Decreased bone mineral density in premenopausal patients with systemic lupus erythematosus.

To study bone mineral density (BMD) in premenopausal adult female patients with systemic lupus erythematosus (SLE) and its relation with clinical parameters, 56 SLE patients (mean age 31 years, mean disease duration 6.3 years) and 15 normal controls were studied. BMD at the lumbar vertebrae (L2-L4) was measured by dual energy X-ray absorptiometry (DEXA). Classification of BMD was made according to the WHO criteria in 1994. Correlation between BMD and clinical parameters was calculated. It was found BMD in the SLE patients (0.942 +/- 0.136 g/cm2) was lower than in the control group (1.055 +/- 0.080 g/cm2) (P < 0.01). According to the WHO criteria, 17 patients (30%) had normal BMD, 22 patients (40%) had osteopenia and 17 patients (30%) had osteoporosis. BMD was inversely correlated with disease duration in SLE patients (p < 0.005). The minimal disease duration for a female SLE patient to develop osteopenia was 3.5 years. In conclusion, SLE patients have lower lumbar BMD than normal controls. SLE patients with longer disease duration have lower BMD. In order to achieve early prevention of osteoporosis, we suggest that female SLE patients with disease duration for more than 3.5 years should take a BMD examination.

Adult↗

PubMed1996

Effects of captopril on renal functions, renal and portal hemodynamics in patients with cirrhosis.

Renin-angiotensin system plays a prominent role in the sodium and water homeostasis. In addition, activation of renin-angiotensin system frequently occurs in patients with cirrhosis and ascites. Theoretically, administering of angiotensin converting enzyme inhibitors can enhance sodium and water retention in cirrhotic patients with ascites. In this study, we evaluate the role of low-dose captopril on renal function changes, renal plasma flow and hemodynamics in patients with cirrhosis and ascites. Fifty patients are randomly assigned to receive captopril or placebo for 14 days. Renal functions, renal plasma flow, plasma renin activity, plasma aldosterone concentration and systemic and hepatic hemodynamics are measured before and after treatment. Our results indicate that placebo administration did not affect any of the parameter measured in this study. The finding that low-dose captopril significantly increases plasma renin activity suggests that the dose used in this study effectively blocks the enzyme activity. However, low-dose captopril does not affect renal plasma flow, renal functions and systemic and hepatic hemodynamics. Results in this study demonstrate that inhibition of angiotensin converting enzyme alone may not improve sodium and water retention in cirrhotic patients with ascites.

Aldosterone↗

PubMed1996

Sequential hemodynamic changes for large volume paracentesis in post-hepatitic cirrhotic patients with massive ascites.

Large volume paracentesis (4.8 to 15.5 liters) was performed in 42 patients with post-hepatitic cirrhosis and massive ascites, not only to derive parameters capable of predicting the development of severe clinical hypotension after large volume paracentesis, but also to determine the optimal time to introduce preventive volume expanders. Systemic hemodynamics were sequentially measured for 72 hours in thirty-two patients. Severe clinical hypotension occurred in 13 (31.0%) patients 4-62 hours from the start of paracentesis. Univariate analysis, with the Mantel-Cox test used to compare Kaplan-Meier curves, and the subsequent multivariate analysis by stepwise Cox regression procedure were utilized to identify two variables, withdrawn ascitic fluid greater than 7.5 liters (p = 0.0121) and the absence of peripheral edema (p = 0.0148), reaching statistical significance to predict the occurrence of severe clinical hypotension. Compared to the baseline value, the cardiac output of patients not developing severe clinical hypotension increased (6.26 +/- 0.66 vs. 6.65 +/- 0.69 liter/min, p < 0.01) one hour from the start of paracentesis and right atrial pressure decreased (11.2 +/- 2.4 vs. 8.7 +/- 2.3 mmHg, p < 0.05). The cardiac output returned to the baseline value at the 9th hour. Based on the results presented herein, we can conclude that severe clinical hypotension occurs in a high percentage of patients with post-hepatitic cirrhosis and massive ascites within 72 hours from the start of large volume paracentesis. At potential risk of this occurring are those patients without peripheral edema and withdrawn ascitic fluid greater than 7.5 liters. Volume expanders should be introduced before 4th hour from the start of large volume paracentesis.

Adult↗