Biomedical subjects

K Chiba

Publications and source records attributed to K Chiba.

At least 217 records · Page 12Linked to original sources

PubMed1995

[Extracorporeal shock wave lithotripsy for urinary calculi in an ileal reservoir following reconstruction of the urinary bladder].

A new method for reconstruction of the urinary bladder was introduced by Taguchi in 1977. It consisted of two components; making of pseudo-urethra and the reconstruction of urinary reservoir in the pelvis. The latter was made of the ileum and the peritoneum with temporary use of Japanese paper. This operative method was applied to a 28-year-old female patient when she had cystectomy and bilateral ureterostomy. Thereafter she had has no trouble for 13 years. However, her recent rentogenogram showed urinary tract calculi in the reservoir. Endoscopic treatment was not indicated because of the deformed reservoir and the inflexible pseudourethra. Thus, extracorporeal shock wave lithotripsy (ESWL) was applied to the case with successful results. We herrin reported the case and discussed the usefulness of ESWL for urinali calculi in the ileal reservoir.

Adult↗

PubMed1995

Traumatic neuroma of the common hepatic duct after laparoscopic cholecystectomy.

Jaundice and stricture of the common hepatic duct were detected in a 53-yr-old woman 2 months after she had laparoscopic cholecystectomy for a gallstone. Then she underwent resection of the stricture part of the duct and hepaticojejunostomy which was effective. Pathological examination showed that traumatic neuroma, probably caused by bile leakage after cauterization, led to stricture of the common bile duct.

Bile Duct Neoplasms↗

PubMed1995

[Dysarthria due to small cerebral infarction--the localization of lesion and clinical characteristics].

We compared locations of infarctions and clinical characteristics for patients with dysarthria and those without dysarthria. Subjects were 40 patients with a small infarction in the corona radiata or junctional zone to the capsule and 13 patients with infarctions in the internal capsule. Left corona radiata/junctional zone infarctions were significantly smaller than right sided lesions. Dysarthria was associated more frequently with the corona/junctional lesions on the left side than the right sided lesions. Asymptomatic infarctions on the contralateral side were seen in 41% of the patients with dysarthria. In these cases, dysarthria continued longer and dysphagia occurred more frequently than the cases without right sided lesions. Corona radiata/junctional zone infarctions with dysarthria were located significantly more anteriorly than those without dysarthria. The corona radiata/junctional zone infarctions presenting with dysarthria alone, upper limb dominant hemiparesis, and lower dominant hemiparesis were located in the anterior, middle, and posterior areas, respectively. In conclusion, dysarthria may occur with unilateral small cerebral infarctions, more frequently with left sided lesions than with right sided lesions. It is assumed that the left corona radiata/junctional zone infarction may interrupt simultaneously the corticobulbar pathway and callosal fibers to the right hemisphere which transmit motor information for speech to the right hemisphere. It is also possible that there are individual variations in the proportion of crossed and uncrossed corticobulbar innervation, which may explain dysarthria with unilateral cerebral lesions in some patients. It was suggested that there is an anterior-posterior somatotopy in the corona radiata/junctional zone as well as in the internal capsule.

Cerebral Infarction↗

PubMed1995

[A case of middle ureteral tumor treated by end-to-end anastomosis following resection of 6.7 cm segment].

A 71-year-old male with a right ureteral tumor in the midportion and contracted kidney of the opposite side, due to complete vesicoureteral reflux, underwent end-to-end anastomosis after partial ureterectomy 6.7 cm in length. Our experience in this case led us to conclude that end-to-end anastomosis of the upper or mid-portion of the ureter was possible for the maximal 7.0 cm length of the ureteral loss, when the kidney could be fixed downward as much as possible.

Aged↗

PubMed1995

A desk top computer program for visualized statistical analysis of lesional images in intracerebral hemorrhage.

Statistically identified information on the relationships between the sites of lesions in intracerebral hemorrhage (ICH), risk factors such as a smoking or drinking habit, anamnesis, and biochemical data through blood tests will extend assistance to neuromedical clinicians on their daily clinical duties. It will provide them with a useful guide to determine the method of treatment. Also, it will be a basic research material for their clinical studies on diagnosis, progress, or prognosis in ICH. In order to obtain such statistics with the help of the computer, we need to have a computationally effective image database system. As is generally known, medical image data especially requires a great amount of storage; high-speed processing techniques are therefore also needed to deal with such data effectively. In addition, it is desired that we have outputs from the analysis edited with well-visualized effect, using 3D computer graphics, etc. These are why most existing image processing systems have been designed to work on comparatively large-scale computers. So far as we know, it is hard to find a practical and inexpensive personal computer-based application system for visualized statistical analysis of lesional images in ICH. We have developed a desk top computer-based program for statistical analysis of lesional image data of ICH. With this system, we can organize a medical image database that consists of the personal data of patients with ICH (sex, age, occupation, diagnosis, symptoms, part of physical disorder, etc.), risk factors, anamnesis (cerebral apoplexy, hypertension, hypotension, corpulence, diabetes, hyperlipidemia, atrial fibrillation, valvular endocarditis, etc.), biochemical data of blood, and lesional image data from CT or MRI. This system consists of the following components: 1) database management, 2) information retrieval (IR), 3) lesional image processing, 4) statistical analysis, and 5) prognostic prediction. The images are drawn manually on prescribed data sheets by tracing CT or MRI films and are read through the image scanner; then the compressed data of the digitized images is recorded in the database. Each recorded image data consists of the following two components: the frame image that corresponds to the contour of tissues of interest on the corresponding sliced section, and the actual image that corresponds to the lesion itself. In our system, these two images are separately stored and managed so that we can effectively perform subsequent image analysis. Other variables in the database (risk factors, anamnesis, etc.) are mainly used as search keys for making the aggregate of image data by the IR subsystem. In any aggregate, its elements, namely image data, have common medical background descriptions with the search keys. These aggregates can be used as input for the lesional image processing subsystem. With this subsystem, we can obtain the accumulated distribution of frequencies within a specified range of any sliced section, display planar color maps and profiles associated with the distribution, reconstruct it in 3D form, perform transformations of 3D images (zooming, enhancement, rotation, etc.), and test the significant difference of frequencies between any two different sites. We have been making practical use of this system to find the neurological relationship between the symptom (dysarthria, and paralysis of upper/lower limbs) and the site of lesion with cerebral infarction in pons. This study is quite important since the distributions of pyramidal tract related to the above symptom in pons are not well-known compared to those in cerebral cortex, internal capsule, or cerebral peduncle. With our system, we have obtained several findings expected to be helpful for this study. However, since this study is still in the initial phases, we will only present the outcome as a working example of our system. Our system was originally developed for analyzing lesional images with ICH. However, it could

Cerebral Hemorrhage↗

PubMed1994

Realignment of postoperative cervical kyphosis in children by vertebral remodeling.

STUDY DESIGN: This study analyzed radiographically change in the sagittal curvature of the cervical spine after atlantoaxial (C1-C2) posterior fusion in children. OBJECTIVES: This study clarified the process of spinal remodeling after postoperative cervical deformation in children. SUMMARY OF BACKGROUND DATA: Postoperative spinal deformations in children are observed frequently. However, there have been only a few reports on postoperative changes in the sagittal curvature of the cervical spine and spinal remodeling after those changes. METHODS: Between 1979 and 1991, there was a total of 12 children who underwent C1-C2 posterior fusions. The average age at the time of surgery was 9.8 years. The alignment of the cervical spine was classified into four groups (lordosis, straight, kyphosis, and swan-neck deformity). Radiographic findings suggestive of the remodeling were as follows: 1) new bone formation on the anterior vertebral cortex, and 2) increase in body/canal ratio (BCR). The follow-up period averaged 6.2 years. RESULTS: Postoperative cervical malalignment (kyphosis or swan-neck deformity) occurred in four patients. In all four patients, new bone formation and increase in BCR at the apex of kyphosis were observed. Therefore, there was gradual improvement of the malalignment by vertebral remodeling. This phenomenon was not observed in eight patients with normal alignment. CONCLUSION: Realignment of postoperative cervical kyphosis by vertebral remodeling was observed in children. The results of this study suggested that remodeling occurred even in the spine, which was similar to the remodeling in long bones.

Atlanto-Axial Joint↗

PubMed1994

Effects of tilisolol on ischemic myocardial metabolism in dogs.

The effects of tilisolol on ischemic myocardial energy and carbohydrate metabolism were examined, and compared with those of propranolol. Ischemia was induced by ligating the left anterior descending coronary artery for 3 or 30 min in anesthetized open-chest dogs, 5 min after saline, tilisolol (0.2 mg.kg-1, i.v.), or propranolol (1 mg.kg-1, i.v.) injection. During ischemia, the myocardial energy stores were depleted, and the levels of glycolytic intermediates were altered, associated with ST segment elevation and TQ segment depression of the epicardial electrocardiogram. Tilisolol prevented the myocardial energy depletion and alterations of carbohydrate metabolism caused by 3 min of ischemia, to the same extent as did propranolol. Even 30 min after ischemia, the prevention of these ischemic changes was sustained by tilisolol, but not by propranolol. Tilisolol briefly reduced the ST segment elevation and TQ segment depression induced by ischemia. These results suggest that the protective effects of tilisolol on the ischemic myocardium are more potent and long-lasting than those of propranolol.

Adrenergic beta-Antagonists↗

PubMed1994

Kinetic study on myoglobin refolding monitored by five optical probe stopped-flow methods.

The refolding kinetics of horse cyanometmyoglobin induced by concentration jump of urea was investigated by five optical probe stopped-flow methods: absorption at 422 nm, tryptophyl fluorescence at around 340 nm, circular dichroism (CD) at 222 nm, CD at 260 nm, and CD at 422 nm. In the refolding process, we detected three phases with rate constants of > 1 x 10(2) s-1, (4.5-9.3) s-1, and (2-5) x 10(-3) s-1. In the fastest phase, a substantial amount of secondary structure (approximately 40%) is formed within the dead time of the CD stopped-flow apparatus (10.7 ms). The kinetic intermediate populated in the fastest phase is shown to capture a hemindicyanide, suggesting that a "heme pocket precursor" recognized by hemindicyanide must be constructed within the dead time. In the middle phase, most of secondary and tertiary structures, especially around the captured hemindicyanide, have been constructed. In the slowest phase, we detected a minor structural rearrangement accompanying the ligand-exchange reaction in the fifth coordination of ferric iron. We present a possible model for the refolding process of myoglobin in the presence of the heme group.

Animals↗

PubMed1994

Characterization of monkey cytochrome P450, P450 CMLd, responsible for S-mephenytoin 4-hydroxylation in hepatic microsomes of cynomolgus monkeys.

We isolated a new form of cytochrome P450 (P450) which was able to catalyze S-mephenytoin 4'-hydroxylation from hepatic microsomes of cynomolgus monkeys. The final preparation (referred to as P450 CMLd) was apparently homogenous judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and the estimated minimum molecular weight of this protein was 53 kDa. The N-terminal amino acid sequence of P450 CMLd (identified 16 residues) was identical with that of protein encoded by P450 2C9 cDNA. P450 CMLd was cross-reactive with both antibodies raised against P450 2C11 and P450 2C9 which were purified from hepatic microsomes of male rats and humans, respectively. In hepatic microsomes of cynomolgus monkeys, both antibodies recognized two proteins showing different mobilities on SDS-PAGE (50 and 53 kDa). P450 CMLd was a good catalyst for S-mephenytoin 4'-hydroxylation in a reconstituted system. Anti-P450 2C9 antibody inhibited the activity of S-mephenytoin 4'-hydroxylase, but not the activities of R-mephenytoin 4'-hydroxylase and R- and S-mephenytoin N-demethylases in liver microsomes from cynomolgus monkeys. From these lines of evidence we conclude that P450 CMLd is classified into the P450 2C subfamily and acts as one of the S-mephenytoin 4'-hydroxylases in hepatic microsomes of cynomolgus monkeys.

Amino Acid Sequence↗

PubMed1994

The surgical technique of retroperitoneal lavage for the treatment of extended necrotizing pancreatitis.

For cases of extended necrotizing pancreatitis which involve the spread of infectious or hemorrhagic necrotic lesions to the retroperitoneal tissue, we recommend sequestrectomy and subsequent retroperitoneal lavage via the retroperitoneal access. For successful retroperitoneal lavage, as much liquefactive infectious necrotic tissue as possible should be removed from the retroperitoneal cavity during the operation. In addition, the necrotic cavity should be opened, adequately washed out, and catheters placed in the retroperitoneal cavity by retroperitoneal access. Although we have only applied this ideal technique in two patients so far, the details are presented herein. The significance of retroperitoneal lavage lies in the fact that it cleans the retroperitoneal foci of infection and necrosis, and that it eliminates the necrotic material, bacterial deposits, and biologically active substances produced after surgery. Ultimately, wound healing is markedly promoted, leading to improvement in the systemic condition.

Acute Disease↗

PubMed1994

Development and preliminary application of a high-performance liquid chromatographic assay for omeprazole metabolism in human liver microsomes.

A high-performance liquid chromatography assay was developed to measure the enzymatic activities of the 5-hydroxylation and sulphoxidation of omeprazole, a proton pump inhibitor, in human liver microsomes. The preliminary study was also undertaken to assess the assay's applicability for the enzyme kinetic analysis of omeprazole metabolism by human liver microsomes. The recovery of 5-hydroxyomeprazole, omeprazole sulphone and phenacetin (internal standard) after the precipitation of microsomal protein by acetonitrile was nearly complete. The intra-assay relative standard deviations (n = 6) were 8.2 and 12.8% for quantitation of the 5-hydroxylation and sulphoxidation activities of omeprazole, respectively. Eadie-Hofstee plots for the formation of 5-hydroxyomeprazole and omeprazole sulphone gave a biphasic relationship for all the microsomal samples studied (n = 6). The respective mean (+/- SD) high- and low-affinity component kinetic parameters for the 5-hydroxylation and sulphoxidation of omeprazole estimated by a two-enzyme kinetic analysis were: Km1 = 6.3 +/- 1.7 and 10.4 +/- 6.3 microM, Km2 = 183.2 +/- 180.4 and 671.2 +/- 639.4 microM, Vmax1 = 109.8 +/- 75.4 and 77.5 +/- 46.1 pmol mg-1 min-1, and Vmax2 = 163.3 +/- 94.1 and 318.3 +/- 163.3 pmol mg-1 min-1. The results suggest that the assay is reproducible, accurate and applicable for studying the metabolism of omeprazole in human liver microsomes.

Chromatography, High Pressure Liquid↗

PubMed1994

Dapsone N-acetylation, metoprolol alpha-hydroxylation, and S-mephenytoin 4-hydroxylation polymorphisms in an Indonesian population: a cocktail and extended phenotyping assessment trial.

We examined dapsone N-acetylation and metoprolol alpha-hydroxylation and S-mephenytoin 4-hydroxylation phenotypings using the respective test probes (dapsone and racemic metoprolol and mephenytoin) administered separately and in a cocktail manner to an Indonesian subject group (n = 30). After ascertaining that the separate and cocktail phenotyping tests of the probe drugs correlated with each other (all rs values > 0.84; p < 0.001), the cocktail phenotyping assessment was extended to the other 74 Indonesians. In a total of 104 Indonesians phenotyped with the cocktail test, a visual antimode was apparent only in the dapsone N-acetylation and S-mephenytoin 4-hydroxylation polymorphisms: the frequencies of slow acetylators and poor hydroxylators were 43.3% (95% confidence interval, 33.7% to 52.8%) and 15.4% (95% confidence interval, 8.5% to 22.3%), respectively. The distribution histogram and probit plots of the metabolic ratio of metoprolol gave no clear evidence for bimodality, and therefore no poor alpha-hydroxylator of metoprolol was considered to exist in the present sample size. The findings indicate that the Indonesian subjects have a greater incidence of slow acetylator phenotype compared with Japanese and Chinese, as well as a frequency of poor metabolizer phenotype of S-mephenytoin similar to that of Korean and Chinese subjects. They resemble an African population (Nigerians) in metoprolol alpha-hydroxylation polymorphism, with no apparent antimode derived from white populations.

Acetylation↗

PubMed1994

The kinetic profiles of enalapril and enalaprilat and their possible developmental changes in pediatric patients with congestive heart failure.

Enalapril and enalaprilat concentrations were measured after enalapril maleate (0.05 to 0.3 mg/kg) was administered orally to 12 pediatric patients (age range, 10 days to 6 1/2 years) with congestive heart failure caused by congenital heart disease and compared with those obtained from seven normal adults (age range, 21 to 39 years). When normalized to the oral 1 mg/m2 dose of enalapril maleate, the mean +/- SD area under the serum concentration-time curve (AUC) of enalaprilat, a pharmacologically active angiotensin-converting enzyme inhibitor, did not differ significantly between the pediatric group aged > 20 days and adult group (83.1 +/- 47.0 versus 64.6 +/- 17.8 ng.hr/ml per 1 mg/m2). When normalized to the oral 0.1 mg/kg dose, the mean AUC was significantly (p < 0.05) smaller in this pediatric group than in the adult group (138.4 +/- 69.2 versus 245.7 +/- 61.8 ng.hr/ml per 0.1 mg/kg). The AUC observed in three younger (age < 20 days) subjects tended to be much greater compared with infants aged > 20 days. The mean AUC ratio of enalaprilat to enalapril was significantly (p < 0.05) lower in the older pediatric subgroup (2.0 +/- 1.0) than in the adult group (3.4 +/- 1.6), whereas the mean ratios were comparable between the two subdivided pediatric groups. The results suggest that the oral enalapril dose would be better determined on a body surface area rather than on a body weight basis in pediatric patients with congestive heart failure aged > 20 days. The oral dosage should be much reduced in infants with congestive heart failure aged < 20 days compared with those aged > 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Intravesical instillation of oxybutynin hydrochloride therapy for patients with a neuropathic bladder.

Intravesical oxybutynin hydrochloride was administered to 17 patients with a neuropathic bladder (myelomeningocele in 15 and spinal cord tumour in two) and urinary incontinence refractory to intermittent catheterisation. Therapy consisted of instillation of a 10 ml solution containing 5 mg oxybutynin hydrochloride twice daily. The cystometric bladder capacity before and after 1 hour of intravesical oxybutynin hydrochloride was 132 +/- 45 ml and 193 +/- 71 ml (mean +/- 1 standard deviation, p < 0.01) in all 17 patients. In 13 patients with low compliant bladders, the mean bladder compliance before and after 1 hour of instillation was 4.2 +/- 2.4 ml/cmH2O and 8.5 +/- 6.4 ml/cmH2O respectively (p < 0.01). The period of the intravesical oxybutynin hydrochloride treatment ranged from 2 to 16 months (mean 11.1 months). The improvement rate of 'moderately improved' and better response was 76.5% in all 17 patients. One patient complained of slight lower abdominal pain, which receded as treatment continued. Since the pH value of the solution appeared to be so low as to irritate the vesical mucosa, the value was adjusted to 5.85. No local or systemic side effects were observed thereafter. These encouraging results suggest that intravesical instillation of oxybutynin hydrochloride is an attractive alternative in patients with a neuropathic bladder, who are either unresponsive to or have intolerable side effects from oral medications.

Adolescent↗

PubMed1994

Inhibitory effect of perindopril, a novel angiotensin-converting enzyme inhibitor, on neointima formation after balloon injury in rats and cholesterol-fed rabbits.

We investigated the effect of perindopril, a novel angiotensin-converting enzyme (ACE) inhibitor, on neointima formation in vessel walls after balloon injury in rats (carotid artery) and cholesterol-fed rabbits (thoracic aorta). Continuous treatment with perindopril significantly reduced neointima formation in both species, as compared with the control group: intima/media (I/M) ratio (rats -62%; p < 0.001; rabbits -25%, p < 0.05); neointima area (rats -65%, p < 0.01; rabbits -24%, p < 0.05). These changes involved reduction of intimal smooth muscle cells (SMC) in rats and of macrophages in rabbits. Furthermore, perindopril also significantly decreased ACE activity in both aortic tissue and serum [11.38 +/- 0.87 vs. 34.93 +/- 6.44 pmol His-Leu (HL)/mg/min (p < 0.01) and 2.79 +/- 0.28 vs. 38.50 +/- 5.41 pmol HL/mg/min (p < 0.001), respectively], aortic contraction evoked by angiotensin I (AI) and mean blood pressure (BP, 84.9 +/- 3.5 vs. 109.3 +/- 3.8 mm Hg, p < 0.001) as compared with control values. These results indicate that perindopril may reduce neointima formation by suppressing the aortic renin-angiotensin system (RAS). These findings indicate that perindopril may be capable of preventing restenotic lesions after angioplasty in humans [corrected].

Angioplasty, Balloon↗

PubMed1994

Interethnic differences in omeprazole metabolism in the two S-mephenytoin hydroxylation phenotypes studied in Caucasians and Orientals.

Two independent studies showed that the 5-hydroxylation, but not the sulfoxidation, of omeprazole is more rapid in extensive metabolizers (EMs) than in poor metabolizers (PMs) of S-mephenytoin. In Caucasian, Chinese, and Korean PMs, the mean oral clearances were similar and not significantly different (85, 73, and 59 ml h-1 kg-1, respectively). However, the geometric mean clearance in Caucasian EMs (950 ml h-1 kg-1) was higher than in both Chinese EMs (426 ml h-1 kg-1, p < 0.05) and Korean EMs (446 ml h-1 kg-1, p < 0.01). The incidence of PMs of S-mephenytoin is higher in Chinese (14.6%) and Koreans (12.6%) than in Swedish Caucasians (3.3%). Therefore, the proportion of heterozygous compared to homozygous EMs is higher in Orientals than in Caucasians. This might explain the higher clearance of omeprazole in Caucasian EMs compared to the clearance of omeprazole in Chinese and Korean EMs of S-mephenytoin.

Aryl Hydrocarbon Hydroxylases↗

PubMed1994

The role of S-mephenytoin 4'-hydroxylase in imipramine metabolism by human liver microsomes: a two-enzyme kinetic analysis of N-demethylation and 2-hydroxylation.

1. The metabolism of imipramine (N-demethylation and 2-hydroxylation) was studied in relation to the activity of S-mephenytoin 4'-hydroxylase in human liver microsomes. 2. Eadie-Hofstee plots for the formation of despiramine and 2-hydroxyimipramine were biphasic, suggesting that at least two enzymes are involved in both the N-demethylation and 2-hydroxylation of imipramine by human liver microsomes. 3. The respective mean (+/- s.d.) kinetic parameters for the N-demethylation and 2-hydroxylation of imipramine derived from a two-enzyme kinetic analysis were: Km1 = 1.1 +/- 0.4 and 1.6 +/- 0.6 microM, Vmax1 = 0.11 +/- 0.03 and 0.15 +/- 0.07 nmol mg-1 min-1, and Vmax1/Km1 = 0.10 +/- 0.02 and 0.09 +/- 0.04 ml mg-1 min-1; Km2 = 214 +/- 84 and 257 +/- 148 microM, Vmax2 = 2.22 +/- 0.69 and 0.53 +/- 0.15 nmol mg-1 min-1, and Vmax2/Km2 = 0.011 +/- 0.001 and 0.003 +/- 0.002 ml mg-1 min-1. 4. With regard to imipramine N-demethylation and 2-hydroxylation at 2 microM (representing high-affinity reactions) and at 400 microM (representing low-affinity reactions), only N-demethylation at 2 microM showed a close correlation with the 4'-hydroxylation of S-mephenytoin (rs = 0.952, P < 0.01; n = 10 livers). 5. Concentrations up to 250 microM S-mephenytoin inhibited the N-demethylation of imipramine (2 microM), but no further inhibition was observed using concentrations from 250 to 750 microM. 6. Imipramine inhibited S-mephenytoin 4'-hydroxylation competitively with a Ki value of 12.5 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aryl Hydrocarbon Hydroxylases↗

PubMed1994

Lack of correlation of hypotensive effects with prevention of cardiac hypertrophy by perindopril after ligation of rat coronary artery.

1. The present study was designed to test the hypothesis that beneficial effects of angiotensin converting enzyme (ACE)inhibitors are independent of a fall in blood pressure in rat experimental heart failure following coronary ligation. 2. The animals were assigned randomly to six groups; sham operation, controls subjected to coronary ligation (control), coronary ligation plus chronic treatment with ACE inhibitors at non- and hypotensive doses; perindopril (0.2 or 2 mg kg-1 day-1) or enalapril (2 or 20 mg kg-1 day-1) for three weeks starting one week after the ligation. 3. Systemic blood pressure was measured every week during the experiments. At the end of the treatments, cardiac function and heart weight (an index of myocardial hypertrophy) were determined. In the other animals, ACE activities in plasma and tissues including heart, kidney, lung and blood vessels were measured. 4. In the controls, cardiac ACE activity, weight of right ventricle and left ventricular end-diastolic pressure (LVEDP) were higher compared to those in the sham-operated animals four weeks after the coronary ligation. However, ACE activities were not changed in plasma, kidney, lung and aorta by ligation of the coronary artery. 5. The chronic treatment with perindopril at a dose of 0.2 mg kg-1 day-1 inhibited the increase in ACE activity in cardiac tissue and suppressed the right ventricular hypertrophy without affecting systemic haemodynamics. In contrast, enalapril at a dose of 20 mg kg-1 day-1, but not 2 mg kg-1 day-1, prevented the development of the right ventricular hypertrophy. Enalapril at 20 mg kg-1 day-1 also lowered systemic blood pressure. 6. There is no significant correlation between systemic blood pressure and right ventricular hypertrophy at the end of the treatment with perindopril (r = 0.06) or enalapril (r = 0.1).7. These findings demonstrate that perindopril, an ACE inhibitor, prevents cardiac hypertrophy without affecting systemic blood pressure in the rat with heart failure after coronary ligation, and suggest that selective augmentation of ACE activity in cardiac tissue is involved in the progression of hypertrophy in this model.

Angiotensin-Converting Enzyme Inhibitors↗