Search PubMed⌕ Search

Biomedical subjects

Y Sawa

Publications and source records attributed to Y Sawa.

At least 145 records · Page 8Linked to original sources
PubMed1998

Changes in the enzymatic activities of beagle liver during maturation as assessed both in vitro and in vivo.

1. We have examined changes in caffeine and trimethadione (TMO) metabolism in vivo, agents which are used as probe drugs. In this study the total body clearance (Cl) of caffeine and TMO was low 1 week after birth (week 1), increased rapidly from week 3, peaked and then decreased gradually until reaching the level for the mature, adult dog. The elimination half-life (t1/2) of caffeine and TMO was prolonged during week 1; however, it then gradually became shorter. Gradually it became longer and reached the level for the adult dog. The apparent volume of distribution (Vd) of caffeine did not change throughout the study. However, the Vd of TMO was only high during week 1. 2. The in vitro changes in a variety of typical substrates for seven different cytochrome P450 (CYP) isozymes were examined. In this study three different patterns of metabolism can be identified: (1) activity is low immediately after birth, increases, peaks and then decreases to the adult dog level (p-nitroanisole; CYP1A1, caffeine; CYP1A2, benzphetamine; CYP3A/2B(?), aniline; 2E1 and TMO; CYP2C9/2E1/3A4); (2) activity generally increases rapidly soon after birth, continues to increase, peaks and then gradually decreases to the adult level (phenytoin; CYP2C9); and (3) activity is high (about the same level as the adult) immediately after birth, decreases and then gradually increases to the adult level (erythromycin; CYP3A4/5). 3. The results of these in vivo and in vitro studies suggest that changes in enzyme activity are due to differences in P450 isoenzymes during development.

Alanine Transaminase↗
PubMed1998

Pulmonary disease models induced by in vivo hemagglutinating virus of Japan liposome-mediated endothelin-1 gene transfer.

Overproduction and overexpression of endothelin-1 (ET-1) have been reported to contribute to the pathophysiology of pulmonary diseases, including pulmonary fibrosis, obliterative bronchiolitis, and primary pulmonary hypertension. To determine whether ET-1 contributes to the pathogenesis of pulmonary disease, we locally overexpressed ET-1 using an in vivo UV-inactivated hemagglutinating virus of Japan (HVJ) liposome-mediated gene transfer system. Plasmid DNA of ET-1 (pME18fc preproET-1) and high mobility group 1 (HMG1) protein were co-encapsulated in liposomes. Then the plasmid DNA and liposome complexes were introduced into the lung via the trachea in Wistar rats, using HVJ-mediated membrane fusion. Control animals received instillation of HVJ liposome with an empty cassette. Two weeks after in vivo transfection of the preproET-1 gene, hyperplastic connective tissue plaques were seen in the alveolar duct and small conducting airways, indicating histologically distinctive obliterative bronchiolitis. No histopathologic changes were seen in the control animals. These results suggested that local overexpression of ET-1 may play an important role in the pathogenesis of obliterative bronchiolitis.

Animals↗
PubMed1998

[Minimally invasive cardiac surgery--the efficacy of right parasterna approach].

The recent concepts of minimally invasive surgery have affected even cardiovascular surgery. Especially, the desire to lessen incisional pain and hospital stay has made minimally invasive cardiac surgery (MICS) desirable. However, its efficacy is still controversial. To investigate this goal, we assessed the efficacy of avoidance of median sternotomy through right parasternal approach in view of the postoperative bleeding, % transfusion, postoperative intubation period, degree of incisional pain and serum level of cytokines. Patients with mitral valve disease or atrial septal defects were divided into the MICS (M) group and the control (C) group. In the M group, operations were performed through right parasternal incision under cardiopulmonary bypass (CPB) instituted by placing a venous cannula directly into superior vena cava and arterial and the other venous cannulae into femoral artery and vein. On the other hand, in the C group, operations were performed through median sternotomy under conventional CPB. There were no significant differences in CPB and AXC time between two groups. The M group showed significantly lower value in the postoperative bleeding volume, % transfusion, postoperative intubation time. Patients in the M group showed higher satisfaction of small incision as compared with those in the C group. Serum level of IL-8 after CPB was significantly lower in the M group than in the C group. These results suggested that MICS for mitral disease or ASD appears to be less invasive when median sternotomy is avoided. This suggest that MICS is a promising and contributed approach for open heart surgery to improve the QOL of the patients.

Adult↗
PubMed1998

[Non-real-time computed tomography-guided percutaneous ethanol injection therapy for hepatocellular carcinoma undetectable by ultrasonography].

The purpose of this study was to evaluate the feasibility of non-real-time CT-guided percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC, 37 lesions) untreatable by ultrasonography-guided (US)-PEIT. The HCC lesion was localized on the lipiodol CT image with a graduated grid system. We advanced a 21 G or 22 G needle in a stepwise fashion with intermittent localization scans using a tandem method to position the tip of the needle in the lesion. Ethanol containing contrast medium was injected with monitoring scans obtained after incremental volumes of injection, until perfusion of the lesion was judged to be complete. A total of 44 CT-PEIT procedures were performed. The average number of needle passes from the skin to the liver in each CT-PEIT procedure was 2.3, the average amount of ethanol injected was 14.4 ml, and the average time required was 49.3 minutes. Complete perfusion of the lesion by ethanol on monitoring CT images was achieved in all lesions with only a single or double CT-PEIT procedure without severe complication. Local recurrence was detected only in 5 lesions. At present, it is more time-consuming to perform CT-PEIT than US-PEIT because conventional CT guidance is not real-time imaging. However, it is expected that this limitation of CT-PEIT will be overcome in the near future with the introduction of CT fluoroscopy. In conclusion, CT-PEIT should prove to be a feasible, acceptable treatment for challenging cases of HCC undetectable by US.

Aged↗
PubMed1997

C-Myc expression and its role in patients with chronic aortic regurgitation.

BACKGROUND: Proto-oncogenes have been implicated in the pathogenesis of gene-mediated myocardial remodeling. In the human heart, however, it has not been clarified whether these proto-oncogenes are related to contractile impairment and structural alteration of the myocardium. The present study is designed to investigate the relationship between the c-Myc protein expression in the myocardium and the myocardial contractile dysfunction in patients with chronic aortic regurgitation who underwent indicated for aortic valve replacement. METHODS AND RESULTS: Twelve patients (11 males and one female) with an average age of 55 years who underwent aortic valve replacement for isolated chronic aortic regurgitation were studied. The preoperative New York Heart Association class was II in four patients and III in eight. Ejection fraction, end-systolic volume index, end-systolic stress (Mirsky's form), and mass index of the left ventricle before surgery were 47+/-13%, 93+/-37 mL/m2, 223.2+/-44.4 Kdyn/cm2, and 210+/-38 g/m2, respectively. A left ventricular endomyocardial biopsy was performed to assess the myocardial cell diameter, fibrous content, and c-Myc protein expression in the myocardium. Cell diameter and fibrous content were significantly higher than those in five normal controls. C-Myc was detected in 9 of 12 present patients but in none of the normal controls. The degree of c-Myc expression had significant positive correlations with ejection fraction (r=0.93; P<.01) and end-systolic stress/end-systolic volume index (r=0.96; P<.01) and significant negative correlations with end-systolic volume index (r=-0.90; P<.01), cell diameter (r=-0.97; P<.01), and fibrous content (r=-0.92; P<.01), which suggested that the degree of c-Myc expression may have a significant negative correlation with myocardial contractility and myocardial hypertrophy. CONCLUSIONS: C-Myc expression may be related to the pathogenesis of myocardial remodeling in patients with chronic aortic regurgitation.

Adult↗
PubMed1997

A novel strategy for myocardial protection using in vivo transfection of cis element 'decoy' against NFkappaB binding site: evidence for a role of NFkappaB in ischemia-reperfusion injury.

BACKGROUND: NFkappaB, an important transcriptional factor, has been reported to play a significant role in the coordinated transcription of cytokine and adhesion molecule genes. Therefore, blocking the NFkappaB may attenuate ischemia reperfusion injury in the myocardium. For blocking transcriptional factors, gene therapy, such as cis element "decoy," appears to be an innovative and useful therapy. This study aimed to prove the efficacy of cis element decoy against NFkappaB binding site for myocardial protection. METHODS AND RESULTS: Rat hearts were transfected with fluorescence isothiocyanate-labeled cis element decoy against NFkappaB (NF)-binding site (NF group, n=6) and scrambled decoy (SD) group (n=6) by coronary infusion of hemagglutinating virus of Japan (HVJ)-liposome during cardioplegic arrest. Both the NF and SD groups showed marked FITC-staining in the nuclei of myocytes, demonstrating the efficacy of gene transfer into the nuclei of cardiac myocytes as compared with the control group transfected with empty liposomes. After 3 days of transfection, the NF group showed significantly higher percentages of recovery of left ventricular developed pressure (NF versus SD, 87+/-11 versus 54+/-12%) and coronary flow (97+/-16 versus 61+/-15%) than did the control hearts when exposed to ischemia (30 minutes, 37 degrees C) and reperfusion (30 minutes, 37 degrees C). The NF group showed a significantly lower percentage of neutrophil adherence to endothelial cells (38+/-6 versus 81+/-3%) and a lower tissue level of interleukin-8 (109+/-48 versus 210+/-55 ng/mg) than did the SD group. CONCLUSION: The hearts transfected with cis element decoy against NFkappaB binding site showed significant improvement in tolerance against ischemia-reperfusion injury in association with the inhibition of neutrophil adherence and tissue IL-8 production. This suggests that NFkappaB plays a significant role in ischemia-reperfusion injury. This method, using in vivo gene transfection of cis element decoy against NFkappaB binding site, appears to be a novel and future strategy for myocardial protection.

Animals↗
PubMed1997

Antioxidant activity of polyphenolics in diets. Rate constants of reactions of chlorogenic acid and caffeic acid with reactive species of oxygen and nitrogen.

Phenolic non-flavonoid compounds in diets, such as chlorogenic acid and caffeic acid are widely recognized to be antioxidants. However, it is not known how these phenolics scavenge reactive species of oxygen and nitrogen. We determined the rate constants of the reactions between the phenolics with superoxide and hydroxyl radical with a pulse radiolysis. The second-order rate constants of the reactions of chlorogenic acid with superoxide and hydroxyl radical were 1.67 +/- 0.14 x 10(6) M(-1) s(-1) and 3.34 +/- 0.19 x 10(9) M(-1) s(-1), respectively, while those of caffeic acid with superoxide and hydroxyl radical were 0.96 +/- 0.01 x 10(6) M(-1) s(-1) and 3.24 +/- 0.12 x 10(9) M(-1) s(-1), respectively. By scavenging peroxy radical chlorogenic acid inhibited the initiation of chain lipid peroxidations by organic free radical. The second-order rate constant of the reaction of chlorogenic acid with peroxy radical was estimated to be 1.28 +/- 0.11 x 10(5) M(-1) s(-1). Chlorogenic acid was rapidly oxidized by peroxynitrite in concentration- and pH-dependent manners and its rate constant was determined to be 1.6 +/- 0.7 x 10(5) M(-1) s(-1), using competitive inhibitions by glutathione and methionine.

Antioxidants↗
PubMed1997

In vivo gene transfection with heat shock protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat.

Heat shock protein 70 (HSP70) has been reported to be involved in the myocardial self-preservation system. To obtain the evidence that HSP70 plays a direct role in the protection from myocardial ischemia-reperfusion injury, rat hearts were transfected with human HSP70 gene by intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome containing human HSP70 gene. The control hearts were infused with HVJ-liposome without the HSP70 gene. The hearts from whole-body heat-stressed or nontreated rats were also examined. Western blot and immunohistochemical analysis showed that apparent overexpression of HSP70 occurred in the gene transfected hearts and that gene transfection might be more effective for HSP70 induction than heat stress. In Langendorff perfusion, better functional recovery as well as less creatine phosphokinase leakage after ischemia were obtained in the gene transfected hearts with HSP70 than in the control or nontreated hearts. Furthermore, the gene transfected hearts showed better functional recovery than the heat-stressed hearts. These results indicated that overexpressed HSP70 plays a protective role in myocardial injury, suggesting the possibility that gene transfection with HSP70 may become a novel method for myocardial protection through enforcing the self-preservation systems.

Animals↗
PubMed1997

Identification of lymphatic vessels by using a monoclonal antibody specific for the human thoracic duct.

Light microscopic identification of lymphatic vessels of the human small intestine was studied immuno-histochemically with a monoclonal antibody specific for human thoracic duct (mAb-D) and rabbit anti-human laminin antibody (anti-L). Two types of vessels were observed with anti-L; one strongly reacted with regularly outlined vessels and the other weakly reacted with irregularly outlined vessels and thin walls. Immunoreactivity to mAb-D was strong in the weakly reacting vessels, and the strongly reacting vessels did not react to mAb-D. Immunoreactivity of lymphatic vessels to anti-L has been reported to be weaker than that of the blood vessels; only irregularly outlined vessels which were weakly immunostained with anti-L reacted to mAb-D and no cross-reaction to mAb-D was observed in the regularly outlined vessels. This indicates that the vessels strongly reacting with anti-L are blood vessels and the vessels immunostained with mAb-D must be lymphatics. The study shows that it is possible to identify lymphatic vessels light microscopically by mAb-D. This method will be useful in studying the fine distribution of lymphatic vessels in normal tissue and also in pathological tissue such as metastasis of malignant tumors.

Aged↗
PubMed1997

Myocardial histological changes in dilated cardiomyopathy during a long-term left ventricular assist device support.

As the myocardium in patients with dilated cardiomyopathy (DCM) is deteriorating progressively, resulting in a decrease in left ventricular function, patients with end-stage DCM may require implantation of a left ventricular assist device (LVAD) unless they undergo heart transplantation. Although LVAD has been reported to provide excellent hemodynamic support, no data are currently available about the effects of long-term LVAD support on the myocardium in patients with DCM. We describe two patients with end-stage DCM who underwent LVAD implantation and were supported with LVAD for 524 and 245 days, respectively. Serial myocardial biopsies showed increases in myocardial cell diameter and intercellular fibrosis, despite excellent hemodynamic support by LVAD. These data suggest that the myocardium in patients with end-stage DCM deteriorates progressively, even if the pre-load of the left ventricle is reduced by LVAD.

Adult↗
PubMed1997

The contribution of Na+/H+ exchange to ischemia-reperfusion injury after hypothermic cardioplegic arrest.

BACKGROUND: Na+/H+ exchange has been reported to be one of the key mechanisms in myocardial ischemia-reperfusion injury. However, the effect of temperature on Na+/H+ exchange is not fully understood. METHODS: Sodium-propionate-induced cell swelling, an indicator of the function of the Na+/H+ exchanger, was measured in rat thymic lymphocytes. A Langendorff perfused rat heart model was also employed to investigate the effect of the pharmacologic inhibition of Na+/H+ exchange on the recovery of cardiac function after hypothermic ischemia. This was done using FR168888, an inhibitor of Na+/H+ exchange. RESULTS: In the in vitro study, rat lymphocytes were observed to swell at 17 degrees, 22 degrees, and 27 degrees C, indicating that the Na+/H+ exchanger remains functional even under hypothermic conditions. FR168888 was found to significantly inhibit Na+/H+ exchange-induced cell swelling, even at 17 degrees C. In the in vivo study, pretreatment with FR168888 was found to prevent the deterioration of ventricular function, even after 5 hours of hypothermic cardioplegic arrest. This was associated with a decrease in the reperfusion-induced elevation in resting tension. CONCLUSIONS: These results suggest that Na+/H+ exchange in the heart still occurs, even under hypothermic conditions, and contributes to reperfusion injury, even after hypothermic cardioplegic arrest.

Animals↗
PubMed1997

Experimental bronchiolitis obliterans induced by in vivo HVJ-liposome-mediated endothelin-1 gene transfer.

BACKGROUND: Bronchiolitis obliterans (OB) is a lesion that results when injury to small conducting airways is repaired by a proliferation of fibrous granulation tissue. Bronchiolitis obliterans has emerged as a main cause of morbidity and mortality in the setting of lung and heart-lung transplantation. Endothelin-1 (ET-1), initially discovered as a vasoconstrictive peptide, has a mitogenic activity on vascular smooth cells and airway epithelial cells. Overproduction of endothelin has been reported in patients with OB or chronic rejection after lung transplantation. It is still undetermined whether locally overexpressed ET-1 has a potential impact in the pathogenesis of OB. METHODS: We locally overexpressed ET-1 using ultraviolet irradiation-inactivated hemagglutinating virus of Japan (HVJ)-liposome-mediated in vivo gene transfer. Plasmid DNA of prepro-ET-1 and high mobility group 1 protein were coencapsulated in liposomes, and were introduced into airway epithelial cells by HVJ-mediated membrane fusion. Control animals received instillation of HVJ-liposome with an empty expression cassette. To confirm the efficiency of transfection, HVJ liposome with beta-galactosidase gene was introduced. The expression of ET-1 and beta-galactosidase was assessed by immunohistochemistry. RESULTS: Bronchial epithelium alveolar cells and alveolar macrophage were stained blue (X-Gal) 1 week after in vivo gene transfer of beta-galactosidase gene, indicating beta-gal activity. In animals 1 to 2 weeks after in vivo transfection of prepro-ET-1 gene, hyperplastic connective tissue plaque was seen in the alveolar duct and small conducting airway, indicating histologically distinctive bronchiolitis obliterans. Strong ET-1-like immunoactivities were seen in the airway epithelial, hyperplastic connective tissue, and alveolar cells. No histopathologic changes were seen in the control animals. CONCLUSIONS: These results suggested that ET-1 may play an important role in the pathogenesis of OB. The effective pharmacologic antagonist or inhibitor may possibly control the progression of disease in patients of OB.

Animals↗
PubMed1997

Effect of cardiopulmonary bypass under tepid temperature on inflammatory reactions.

BACKGROUND: Cardiopulmonary bypass (CPB) causes inflammatory reactions and abnormal responses of vascular resistance. Theoretically, the difference in the blood temperature during CPB may influence the degree of CPB-induced inflammatory reactions. METHODS: To elucidate the effect of the perfusate temperature during CPB, serum levels of inflammatory cytokines, neutrophil elastase, complements, and vasoactive substances were measured in 18 patients undergoing elective coronary artery bypass grafting under tepid temperature (34 degrees C) and moderate hypothermia (28 degrees C). Respiratory index and systemic vascular resistance index during and after CPB and intubation time after postoperative course were also analyzed. RESULTS: The patterns of the change in interleukin-8 and neutrophil elastase were significantly different between the two groups. The tepid group showed an earlier decrease in interleukin-8 and neutrophil elastase levels as compared with the hypothermic group. The prostaglandin E2 level just after CPB was significantly higher in the tepid group than in the hypothermic group. Systemic vascular resistance index and respiratory index and intubation time were significantly lower in the tepid group than in the hypothermic group. CONCLUSIONS: These results demonstrated that tepid CPB affected the inflammatory cytokine release and neutrophil activation compared with hypothermic CPB, resulting in the attenuation of respiratory dysfunction. This may suggest a beneficial effect of tepid temperature in CPB with possible attenuation of the postperfusion syndrome.

Bradykinin↗
PubMed1997

Idiopathic iliac arterial aneurysms in a child.

Arterial aneurysms are very rare in children, especially those who have no history of cardiac or vascular malformation, connective tissue disorder, or trauma. We describe a 3-year-old boy who had multiple arterial aneurysms of the left external iliac artery with a maximal diameter of 67 mm, with no history of these disorders. The iliac artery distal to the aneurysm and superficial femoral artery were occluded causing the growth disturbances of his left leg. He underwent graft replacement of the left iliac artery using a ringed Gore-Tex graft (6 mm in diameter). Postoperative angiogram showed a patent graft without any residual aneurysm in the left iliac artery. His ankleibrachial index improve from 0.2 to 0.6 after surgery.

Anastomosis, Surgical↗
PubMed1997

Efficient gene transfer method into the whole heart through the coronary artery with hemagglutinating virus of Japan liposome.

OBJECTIVE: To confirm gene transfer techniques especially into the whole heart, we tried out a gene transfer method involving liposome with the viral envelope hemagglutinating virus of Japan liposome as an alternative to existing techniques such as cationic lipofection or other viral vectors. METHOD: For this study, hemagglutinating virus of Japan liposome (H group) or cationic liposome (L group) was used to compare the efficacy of gene transfection of oligonucleotide labeled with fluorescein isothiocyanate and cDNA of beta-galactosidase and human manganese-superoxide dismutase. Fluorescein-labeled oligonucleotide, cDNA of beta-galactosidase, or manganese-superoxide dismutase was complexed with liposomes, DNA-binding nuclear protein, and the viral protein coat of hemagglutinating virus of Japan. After donor rat hearts arrested by cardioplegia had been harvested, the coronary artery during cardioplegic arrest was infused via an aortic cannula with the liposome-gene complex. Next, the hearts were transplanted into the abdomen of recipient rats of the same strain, and all recipients were put to death after 3 days of transfection. RESULTS: Fluorescein isothiocyanate was detected in the nuclei of more than 70% of the myocytes (75% +/- 14%, n = 5) in the H group compared with fewer than 10% in the L group (7% +/- 5%, n = 5). The intensity of fluorescein isothiocyanate was significantly higher in the H group (979 +/- 112 FI) than in the L group (116 +/- 68 FI). beta-Galactosidase was expressed in the cytosol of more than 50% of the myocytes in the H group (61% +/- 7%, n = 5) compared with none in the L group (0%, n = 5). After 3 days of gene transfection, and when exposed to ischemia (30 minutes, 37 degrees C) and reperfusion (30 minutes, 37 degrees C) with Langendorff apparatus, the hearts transfected with manganese-superoxide dismutase (S group, n = 5) showed a significantly higher percentage of recovery of left ventricular end-diastolic pressure (S vs C, 86% +/- 3% vs 54% +/- 12%) and coronary flow (98% +/- 2% vs 66% +/- 12%) than did the control hearts (C group, n = 5). Western blotting analysis showed an apparent increased expression of manganese-superoxide dismutase in the hearts transfected with manganese-superoxide dismutase compared with the control hearts. These results clearly demonstrated that the donor hearts were transfected with fluorescein-labeled oligonucleotide and the beta-galactosidase gene as a result of coronary infusion of the hemagglutinating virus of Japan liposome during cardioplegic arrest at the time of harvest. Furthermore, the hearts transfected with manganese-superoxide dismutase showed significant improvement in tolerance against ischemia reperfusion injury. CONCLUSION: We believe that this method represents a novel in vivo gene transfer technique for the heart and thus may provide a new tool for research and therapy of heart transplantation.

Animals↗
PubMed1997

Pulsed intravenous methylprednisolone therapy for inflammatory myopathies: evaluation of the effect by comparing two consecutive biopsies from the same muscle.

To examine the effect of pulsed intravenous methylprednisolone (IVMP) on polymositis (PM) and dermatomyositis (DM), two biopsies were taken from the same muscle before and after IVMP in one case each of PM and DM. After IVMP, numerous muscle fibers were seen undergoing regeneration. Among all subsets of infiltrating cells that decreased in number, macrophages in the perivascular area decreased markedly. Also conspicuous was decrease of CD8+ cells in the endomysium in PM and that of B-cells in the perivascular area in DM. Among infiltrating cells, frequency of those which expressed the signal transducers and activators of transcription 1 (STAT-1) fell considerably, but remained still abnormally high. Regions on the endothelial cells of blood vessels that expressed MHC antigens and intercellular adhesion molecules 1 (ICAM-1) also decreased but remained more widespread than normal. These results agreed with the favorable clinical effect of IVMP, but showed that many of the immunological parameters remained abnormal.

Adult↗
PubMed1997

Role of calcitonin gene-related peptide in the vascular system on the development of the hyperdynamic circulation in conscious cirrhotic rats.

BACKGROUND/AIMS: Calcitonin gene-related peptide (CGRP), a potent vasodilator; plays an important role in modulating vascular tone, acting as a noncholinergic nonadrenergic neurotransmitter. The aim of this study was to assess the role of CGRP, present in the vascular system, in the development of the hyperdynamic circulation observed in liver cirrhosis. METHODS: Two doses of human alpha-CGRP [8-37], a specific antagonist of CGRP, were administered to cirrhotic and controls rats. Hemodynamics were evaluated using radioactive microspheres in conscious animals. To investigate the arterial depressor effect of exogenous CGRP, we constructed a dose-response curve for mean arterial pressure in cirrhotic and control rats by administering human alpha-CGRP. RESULTS: The administration of high-dose human alpha-CGRP [8-37] (300 nmol.kg body weight-1.min-1) significantly increased both the mean arterial pressure (21 +/- 2 vs. 13 +/- 1%, p < 0.01) and total vascular resistance (76 +/- 5 vs. 54 +/- 5%, p < 0.01) in cirrhotic rats, compared to control rats. The splanchnic hemodynamic effects induced by human alpha-CGRP [8-37] were a significant decrease in percent change of portal venous inflow -42 +/- 3 vs. -33 +/- 3%, p < 0.05) and a significant increase in percent change of splanchnic arterial resistance (110 +/- 9 vs. 76 +/- 5%, p < 0.01) in cirrhotic rats, compared to control rats. Low-dose human alpha-CGRP [8-37] (60 nmol.kg body weight-1. min-1) caused similar hemodynamic changes, but the degree of change was much less than for the high-dose administration. The vascular response to human alpha-CGRP was significantly reduced in cirrhotic rats as compared to controls (ANOVA, p < 0.01). Plasma concentrations of CGRP were significantly elevated in cirrhotic rats. CONCLUSIONS: CGRP in the vascular system was involved in the modulation of vasodilatation in rats with liver cirrhosis, as demonstrated by the administration of a selective CGRP antagonist and exogenous CGRP.

Animals↗