Biomedical subjects

H Shinohara

Publications and source records attributed to H Shinohara.

At least 127 records · Page 7Linked to original sources

PubMed1998

Right heart flow dynamics after tricuspid valve annuloplasty. Characteristics and time course.

To evaluate the effect of tricuspid annuloplasty (TAP) on right heart flow dynamics, we analyzed tricuspid inflow velocity pattern, jugular venous pulse and color Doppler flow signal of tricuspid regurgitation (TR) before and after surgery in 16 patients who underwent TAP (TAP group). Cardiac rhythm was atrial fibrillation in all patients. Twelve patients with lone atrial fibrillation served as controls (AF group). Patients in the TAP group were studied before and serially after surgery with a mean follow-up period of 2.7 years. TAP was performed according to the modified De Vega technique in all patients. In a comparison of the most recent data in the TAP group and the data in the AF group, the maximum tricuspid inflow velocity was significantly increased, and both the deceleration time of the tricuspid inflow velocity wave and the y-h interval of the jugular venous pulse were significantly prolonged in the TAP group compared to the AF group. Immediately after surgery, in the TAP group, the area of the TR jet was markedly decreased, and the deceleration time of the tricuspid inflow velocity wave was significantly prolonged compared to those before surgery. The area of the TR jet was dramatically decreased and remained small during the follow-up period. Thus, TAP may produce mild tricuspid stenosis but may also confer sustained preventive effects against TR.

Adult↗

PubMed1998

The effects of nicorandil on electrophysiological changes in acute myocardial ischemia and reperfusion.

This study was undertaken to clarify the effects of nicorandil on electrophysiological changes during acute ischemia and following reperfusion. We prepared an acute ischemic heart model by ligating the left anterior descending coronary artery in 27 dogs. After 10 minutes, reperfusion was performed. The changes in ventricular effective refractory period (ERP) and intramyocardial conduction time (ICT) were compared between the nicorandil group (n = 12) which received nicorandil intravenously before the coronary ligation and the control group (n = 15). In the control group, the ERP was shortened during ischemia, and rapidly shortened immediately after reperfusion, but was slightly prolonged 10 minutes after reperfusion. The ICT was prolonged during ischemia, but returned to the pre-ischemia value after reperfusion. In the nicorandil group, the changes in ERP and ICT were significantly inhibited compared to those in the control group. The incidence of ventricular fibrillation (VF) during reperfusion was 42% in the control group. However, there was no VF during reperfusion in the nicorandil group. Therefore, nicorandil may correct both the delayed conduction and the uneven ventricular effective refractory period detected during acute ischemia and following reperfusion, inhibiting the development of ventricular arrhythmia during reperfusion.

Acute Disease↗

PubMed1998

Relationship between flow dynamics in the left atrium and hemostatic abnormalities in patients with nonvalvular atrial fibrillation.

To investigate the relationship between left atrial (LA) flow dynamics and hemostatic markers in nonvalvular atrial fibrillation (AF), 45 patients with nonvalvular AF who had not received anticoagulants were evaluated by transesophageal echocardiography. We determined the LA appendage flow and the presence of LA spontaneous echo contrast (SEC) or thrombus. We measured plasma levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A, D-dimer, beta-thromboglobulin, and platelet factor 4 in peripheral blood as hemostatic markers. The patients were divided into a low-velocity group (n = 19; sum of peak emptying and filling LA appendage flow velocities < 40 cm/s) and a high-velocity group (n = 26; > or = 40 cm/s). The maximum LA diameter was significantly greater and the LA expansion fraction was significantly smaller in the low-velocity group than in the high-velocity group. LA SEC or thrombus was observed in 11 patients (58%) in the low-velocity group, but not in any patients in the high-velocity group (p < 0.001). The plasma levels of TAT, fibrinopeptide A, D-dimer, beta-thromboglobulin, and platelet factor 4 were significantly higher in the low-velocity group than in the high-velocity group. The plasma levels of TAT, fibrinopeptide A, beta-thromboglobulin, and platelet factor 4 were significantly higher in 8 patients without LA SEC or thrombus in the low-velocity group than in 26 patients in the high-velocity group. Patients with nonvalvular AF accompanied by an enlarged and dysfunctioning LA and a decreased LA appendage flow velocity had increased intravascular coagulation-fibrinolysis activity and platelet activation. These abnormalities may be closely related to the thrombogenetic state in patients with nonvalvular AF.

Adult↗

PubMed1998

Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by 123I-MIBG imaging.

To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62 +/- 11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n = 7), hypertension (n = 2), and atrial fibrillation (n = 1). Radioiodinated metaiodobenzyl guanidine (123I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, (1) left ventricular ejection fraction (LVEF) increased significantly from 38.3 +/- 6.9% to 47.5 +/- 14.7%; (2) sub-maximal exercise time increased significantly from 205 +/- 112 to 272 +/- 120 seconds; (3) the heart to mediastinum (H/M) ratio of 123I-MIBG increased significantly (early image: 1.99 +/- 0.38 versus 2.20 +/- 0.50; delayed image: 1.86 +/- 0.44 versus 2.09 +/- 0.51); and (4) the washout rate of 123I-MIBG decreased slightly from 29.1 +/- 9.1% to 25.4 +/- 7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure.

3-Iodobenzylguanidine↗

PubMed1998

[Effect of the skull on brain perfusion SPECT imaging].

Because attenuation gradually decreases reconstructed counts from the periphery to the center portion of the object, the deep region far from the detector is not clearly observed if attenuation is not compensated. In brain perfusion SPECT, diagnosis is sometimes made using filtered back projection images without attenuation compensation (FBP). Brain perfusion SPECT has the unique characteristic that the radiopharmaceutical accumulates only within the brain and is never taken up by the surrounding skull. This study investigated the effect of skull on brain perfusion SPECT reconstructed with FBP. We theoretically derived the relation between the counts of brain and the linear attenuation coefficient of skull. It was found that the difference in reconstructed counts between the deep gray matter and peripheral gray matter decreased due to the existence of the skull. This result indicated that the deep gray matter was inclined to be visible if the FBP images were displayed according to relative counts normalized to the maximum count of each image. In order to confirm this, we made a numerical phantom with realistic human brain and skull contours on the basis of MR images from a normal volunteer. The linear attenuation coefficient of brain was assumed to be 0.15 cm-1, while that of skull was assumed to be 0.26 cm-1 (denoted as BONE+) or 0 cm-1 (BONE-). In accordance with the theoretical results, the deep gray matter of BONE+ images was more clearly observed than that of BONE- images, if these were displayed using the relative counts of each images. The physical phantom experiments also supported the theoretical and numerical phantom studies.

Cerebrovascular Circulation↗

PubMed1998

[Efficacy of combination of ondansetron injection and tablet in CAF-induced emesis in breast cancer patients].

Efficacy of combination of ondansetron injection and tablet on CAF (cyclophosphamide, adriamycin, 5-fluorouracil) induced emesis were investigated in 10 breast cancer patients (33 courses). Complete suppression rate of nausea or vomiting were approximately 75%, approximately 90% respectively for every treatment day. According to judgement criteria, antiemetic rate of approximately 100% was achieved during the study period. As to food intake of each treatment day, in approximately 70% of treatment courses was assessed as '(patient was) able to eat most of the meal'. Trend in emetic episodes and food intake in each patient receiving several courses of CAF therapy were evaluated. As a result, those patients experiencing nausea or vomiting or had effect on their food intake, were found to be in the similar condition in the following course (s) of CAF. No adverse drug reaction nor clinical laboratory test abnormalities due to ondansetron was observed. In this investigation, combination of ondansetron injection and tablet was shown to sufficiently suppress CAF-induced nausea and vomiting, and their efficacy was confirmed. Still, the study suggested that number of emetic episodes or degree of anorexia differs according to each individual. Therefore we regard additional administration of ondansetron or concomitant use of steroids should be considered when necessary.

Administration, Oral↗

PubMed1998

[Evaluation of cardiac function by various cardiac imaging techniques in mitochondrial cardiomyopathy: a case report].

A 39-year-old man with cardiomyopathy due to point mutation of mitochondrial DNA(3243) was admitted to our hospital because of exertional dyspnea accompanied by hearing disturbance and diabetes mellitus. Echocardiography revealed asymmetric hypertrophy of the anterolateral and posterior walls and systolic dysfunction of the left ventricle (fractional shortening = 18%). Pulsed Doppler mitral inflow velocity wave showed a pseudonormalized pattern. Iodine-123 betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) myocardial scintigraphy showed decreased accumulation in the anterolateral, posterior, and apical walls. Left ventriculography showed moderately decreased ejection fraction (43%), and left ventricular end-diastolic pressure was mildly elevated (18 mmHg). Angiography showed normal coronary arteries, but coronary flow reserve measured by administering intravenous adenosine triphosphate was impaired in the left anterior descending and left circumflex arteries compared to the right coronary artery. Intracellular accumulations of abnormal mitochondria were detected by histologic examination of the cardiac and skeletal muscles. Evaluation of cardiac function showed that the area of myocardial hypertrophy was nearly consistent with the region of decrease in 123I-BMIPP accumulation and coronary flow reserve.

Adult↗

PubMed1998

Calbindin-D 28 kD and parvalbumin in the horizontal cells of rat retina during development.

PURPOSE: Calbindin-D 28K (CaD) and parvalbumin (PV) are calcium-binding proteins thought to act as an intraneural calcium ion buffering system in the central nervous system. We previously reported that PV appears at birth in some cells in the outer portion of the nuclear layer of the retina that can differentiate into horizontal cells. CaD is also distributed in horizontal cells; however, it is not clear at which developmental stage CaD appears. METHODS: The development of horizontal cells and the distribution of CaD and PV was examined ultrastructurally and immunohistochemically in rat retinas from birth (P0) to postnatal day 50 (P50). RESULTS: Our ultrastructural data showed clear differentiation of horizontal cells from other retinal cells in the early postnatal days. These cells became nearly mature around P10 to P12. PV appeared in the outer nuclear layer at birth (P0) and, by P7, was observed in the ganglion cell layer, amacrine cells, and horizontal cells. CaD-immunoreactive cells, however, were not seen in any portions of the retina until P7. At P10, CaD-immunoreactivity was faintly observed in horizontal cells, and its immunoreactivity gradually increased in the horizontal cells from P10 to P15 when the eyes of the rats opened. CaD was not found in the ganglion cell layer or in amacrine cells at any period examined. CONCLUSION: In the horizontal cells, PV appeared when they were ultrastructurally distinguished from other retinal cells, while CaD appeared when they already had some structure for endocytosis and synaptic transmission, suggesting that PV and CaD may be good morphological and functional markers for horizontal cells, respectively.

Animals↗

PubMed1998

[Cardiac amyloidosis with atrioventricular valve thickening and left atrial dysfunction: a case report].

A 70-year-old man with cardiac amyloidosis was referred to our hospital because of exertional chest pain accompanied by ischemic changes on electrocardiography on April 2, 1997. Transthoracic echocardiography revealed a normal size and normally contracted left ventricle without hypertrophy and "granular sparkling" quality of the myocardium, thickening of the mitral and tricuspid valves, and enlargement of the left atrium with reduced booster pump function. Pulsed Doppler mitral inflow velocity wave showed a pseudonormalized pattern, and pulmonary venous flow velocity wave showed a non-compliant pattern. Transesophageal echocardiography revealed thickening and reduced movement of the interatrial septum and reduced flow velocity in the left atrial appendage, suggesting left atrial dysfunction. Adenosine triphosphate (ATP) stress thallium-201 myocardial scintigraphy showed reversible patchy defect mainly in the posterolateral wall. Left ventricular end-diastolic and pulmonary capillary wedge pressures were mildly elevated. Angiography showed normal coronary arteries, but coronary flow reserve measured by administering intravenous ATP in the left anterior descending artery was severely impaired. A rectal biopsy specimen was positive by Congo red staining. Thus, angina pectoris in this patient may be due to amyloid infiltration of the small intramural coronary arteries. Atrioventricular valve thickening and left atrial dysfunction are important clues to diagnose cardiac amyloidosis.

Adenosine Triphosphate↗

PubMed1998

Prevention of intestinal toxic effects and intensification of irinotecan's therapeutic efficacy against murine colon cancer liver metastases by oral administration of the lipopeptide JBT 3002.

The induction of severe diarrhea limits the usefulness of the DNA topoisomerase I inhibitor irinotecan (CPT-11) in the treatment of advanced colon cancer. We investigated whether oral administration of the new synthetic bacterial lipopeptide, JBT 3002, encapsulated in phospholipid liposomes could prevent damage to the intestinal epithelium and lamina propria and thus allow for the parenteral administration of high-dose irinotecan to mice with established syngeneic CT-26 colon cancer liver metastases. Treatment of mice with four daily i.p. injections of 100 mg/kg irinotecan was effective against liver metastases but also resulted in loss of body weight and early death. Histopathological examination of the intestines after this treatment revealed loss of villi, epithelial vacuolation, decrease in the number of cells in the crypts in S-phase, increase in the number of apoptotic cells, and reduction in the number of lymphocytes in the lamina propria. In contrast, treatment of mice with the same irinotecan regimen after oral administration of JBT 3002 produced highly significant inhibition of liver metastases without detectable damage to the intestines. Studies that used irinotecan administered once a week for 3 weeks after pretreatment with oral JBT 3002 demonstrated significantly intensified eradication of established CT-26 liver metastases compared with treatment with once-weekly irinotecan alone. Histological studies revealed that the liver metastases in mice treated with oral JBT 3002 and i.p. irinotecan contained a higher number of macrophages than metastases in mice treated with either drug alone. In vitro studies revealed that irinotecan produced direct antiproliferative effects but JBT 3002 did not. Tumor cells exposed to both irinotecan and macrophages activated by JBT 3002 were highly susceptible to lysis. These data show that oral administration of JBT 3002 can prevent irinotecan-induced gastrointestinal toxic effects and maintain the integrity of the lamina propria, thus allowing for intensification of irinotecan therapy against liver metastases from colon cancer.

Adjuvants, Immunologic↗

PubMed1998

Correlation of the peripapillary atrophy area with optic disc cupping and disc hemorrhage.

PURPOSE: To investigate the association of the peripapillary atrophy area with disc cupping area and disc hemorrhage in subjects who underwent ocular examination as part of a routine physical examination. METHODS: We reviewed plain color fundus photographs taken of 12,140 eyes of 6,070 subjects as part of a routine health examination. The refractive error in these eyes was not known. Using a computerized image analysis system, we measured the area of peripapillary atrophy (zone beta), the optic disc, and optic disc cupping by means of planimetry in 8,842 eyes of 4,421 subjects with fundus images of good quality. RESULTS: The ratio of cup area to disc area was significantly greater in eyes with peripapillary atrophy (0.36 + 0.09) than in eyes without peripapillary atrophy (0.34 + 0.07), and the ratio of peripapillary atrophy area to disc area was significantly greater in eyes with disc hemorrhage (0.26 + 0.34) than in those without disc hemorrhage (0.09 + 0.18). Moreover, in eyes with peripapillary atrophy, the ratio of cup area to disc area was significantly larger in eyes with disc hemorrhage (0.48 + 0.08) than in those without disc hemorrhage (0.36 + 0.09). These results remained statistically unchanged even after "glaucomatous" eyes were excluded from the study. CONCLUSION: Peripapillary atrophy appears to be associated with a higher degree of cupping of the optic disc and disc hemorrhage, and the results suggest an association between peripapillary atrophy and glaucomatous optic neuropathy.

Female↗

PubMed1998

[Results of surgical treatment in patients with T3 non-small cell lung cancer].

To investigate the prognosis of pathological proven T3N0-1M0 non-small cell lung cancer (NSCLC), 73 patients who underwent pulmonary resection between 1975 and 1993 were reviewed. The 5-year survival rate for all patients was 46.3%. The subject included chest wall invasion in 34 (parietal pleura 17, intercostal muscle or ribs 17), invasion to another lobe in 30, main bronchus involvement less than 2 cm distal to the carina in 12, invasion to pericardium in 6 and invasion to diaphragm in 3. The 5-year survival rates was as follows: chest wall invasion 46.7%, invasion to another lobe 51.7%, main bronchus involvement 41.7%, invasion to pericardium and diaphragm 33.3% respectively. The 5-year survival rate was 58.8% when invasion was limited within parietal pleura, whereas 35.3% when invasion extended outside intercostal muscle. Patients invaded within parietal pleura had better prognosis than that of outside intercostal muscle. In conclusion, good outcome would be expected in patients with T3N0-1M0 non-small cell lung cancer when the invasion limited within parietal pleura.

Adult↗

PubMed1998

Characteristics of Helicobacter pylori strains isolated from patients with different gastric diseases.

The pathogenesis of chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis is considered to be related to infection by Helicobacter pylori. The purpose of this study was to investigate the characteristics of H. pylori strains isolated from patients with various gastric diseases. Fifty strains of H. pylori were clinically isolated at Keio University Hospital and were assessed for (i) vacuolating cytotoxin (VT) production, by cytotoxic assay using rabbit kidney (RK) 13 cells; (ii) the expression of cytotoxin associated gene (cagA), by polymerase chain reaction; and (iii) motility on a semi-solid plate. Positivity for VT production by H. pylori strains isolated from patients with chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis, was 100%, 89%, 92%, 100%, and 60%, respectively. There was no significant difference in the incidence of positivity for cagA among the strains isolated from different gastric diseases. Swarming distances, which indicate motility of H. pylori strains, were 12.7, 13.2, 12.8, 16.6 and 9.2mm in strains from chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis, respectively, with H. pylori isolated from remnant gastritis showing significantly less motility than H. pylori isolates from other diseases. There were no significant differences in VT production and cagA positivity among the H. pylori strains.

Animals↗

PubMed1998

[Combined scatter and attenuation correction for 201Tl myocardial perfusion SPECT using OS-EM algorithm].

There are two possible ways to obtain scatter-corrected images with the ML-EM (maximum likelihood expectation maximization) algorithm: one is the subtraction of scatter estimate si from projection data pi, and then (pi-si) is used for scatter-corrected projection data (denoted as SC(T)); the other method is the addition of scatter estimate si to the projections calculated from the reconstructed image without performing data subtraction (SC(E)). This paper investigated these two ML-EM algorithms of combined scatter and attenuation correction on 201Tl myocardial perfusion SPECT imaging. Scatter windows were placed one full width at half maximum (FWHM) below and above the photopeak centerline. The scatter fraction in the primary peak was estimated using trapezoidal approximation by the triple energy window method. Phantom and clinical images were reconstructed using 6 iterations of ordered subsets EM algorithm (OS-EM). A cylindrical phantom with a cold-rod insert and a heart/thorax phantom with liver insert were used to evaluate scatter and the attenuation compensation technique. A cylindrical phantom filled with uniform 201Tl solution was used to evaluate statistical noise. The percent root-mean-square uncertainty (%RMSU) was used as a quantitative measure of noise amplification. %RMSU showed that the SC(E) method amplified noise less in comparison with the SC(T) method, however, no significant difference in image quality was observed between the two methods. In conclusion, both the SC(T) and SC(E) methods provided significant and similar improvement in the removal of scatter in 201Tl myocardial perfusion SPECT imaging.

Absorption↗

PubMed1997

Humoral injury in porcine livers perfused with human whole blood.

BACKGROUND: We investigated the influence of humoral injury during xenoperfusion of porcine livers by human blood. METHODS: The porcine livers were perfused under physiological conditions for 9 hr. The perfusates consisted of porcine whole blood in group 1, human whole blood in group 2, and human whole blood with soluble complement receptor type 1 (300 microg/ml) in group 3. RESULTS: Liver enzyme release and serum hemoglobin in group 2 increased significantly after 3 hr of xenoperfusion, compared with those in group 1 and group 3 (P<0.05). Severe histological damage with minimal cellular infiltration was observed in group 2 after 6 hr of xenoperfusion, but was present only at trace levels in group 1 and group 3. In group 2, von Willebrand factor, a possible target of natural antibodies, was induced on sinusoidal endothelial cells after 3 hr of xenoperfusion, correlating with diffuse deposition of human IgM and membrane attack complex. In group 3, von Willebrand factor, human IgM, and membrane attack complex staining in the intralobular region were present at trace levels. In group 3, the indocyanine green removal capacity, representing hepatocyte function, was significantly higher than in group 2 (P<0.05). CONCLUSIONS: Based on these results, we suggest that humoral injury is a major cause of liver damage during liver xenoperfusion. The pattern of humoral injury in xenoperfused livers may be attributed to anatomical features of the liver and unique responses of sinusoidal endothelial cells to xenoperfusion.

Animals↗

PubMed1997

Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation.

Conventional assessment of left ventricular (LV) relaxation by calculating the time constant of LV pressure decay during the isovolumic diastole requires an invasive approach. Conversely, noninvasive parameters obtained by measuring isovolumic relaxation time and transmitral flow velocity often give inaccurate information. Using LV pressure curve, pulsed Doppler echocardiography, and pulsed Doppler tissue imaging in 38 patients with heart disease and 12 control subjects, we calculated the time constant and recorded transmitral flow velocity and motion velocities at the endocardial portions of the ventricular septum and LV posterior wall. Compared with the controls, patients exhibited a prolonged time constant, a decreased peak early diastolic velocity of the LV posterior wall, and a prolonged time interval from the second heart sound to the peak of the early diastolic wave. The time constant correlated well with the isovolumic relaxation time and various parameters calculated from the transmitral flow velocity, except in patients with elevated LV end-diastolic pressure. In all subjects, the time constant correlated negatively with the peak early diastolic velocity of the posterior wall and positively with the time from the second heart sound to the peak of the early diastolic wave. Thus, early diastolic parameters derived from the motion velocity of the LV posterior wall by pulsed Doppler tissue imaging were closely related to the time constant. This technique may allow noninvasive evaluation of abnormal LV relaxation in patients with various heart diseases.

Blood Flow Velocity↗

PubMed1997

Successful long-term xenoperfusion of the pig liver: continuous administration of prostaglandin E1 and insulin.

For clinical utilization of extracorporeal liver perfusion as an artificial liver assist device, we examined the possibility of long-term xenoperfusion of the pig liver by the continuous administration of prostaglandin E1 (PGE1) and insulin. After a 3-hr perfusion period, pig livers that were xenoperfused with human blood exhibited a drastic decrease in the perfusate volume, a progressive elevation of the hepatic artery pressure, a gradual deterioration of bile production, and a marked increase in the release of creatine kinase-BB component. The continuous administration of PGE1 (25 microg/hr) and insulin (1 U/hr) significantly improved these derangements (P<0.05) and allowed stable perfusion for up to 9 hr. This manipulation also inhibited leukocyte aggregation in the graft, the characteristic perfusate hemolysis, and acceleration of ketogenesis. Histological examination revealed that the interlobular edema and hemorrhage, characteristics of tissue injuries in xenogeneic hyperacute rejection, were markedly alleviated in the PGE1 and insulin-treated group. This study clarifies the finding that the combined administration of PGE1 and insulin is effective for long-term xenogeneic extracorporeal liver perfusion, with the graft viability well maintained.

Alprostadil↗

PubMed1997

Prostaglandin E1 resuscitates hepatic organic anion transport independent of its hemodynamic effect after warm ischemia.

Prostaglandin E1 (PGE1) is a promising agent against ischemic liver damage, but direct evidence of the benefit to intrinsic hepatocyte function has been lacking. We demonstrate here that organic anion transport can be supported by treatment with PGE1 even at a lower dose which does not affect hepatic microcirculation in rabbits with liver inflow occlusion. Near-infrared spectroscopy was applied to directly measure hepatic clearance of indocyanine green (ICG), an exogenous organic anion, and to estimate microcirculation as measured by oxygen saturation and the content of hemoglobin in the sinusoid. Also, morphological changes in microtubules, the cytoskeleton which is known to be associated with organic anion transport, and energy status, as measured by adenine nucleotide levels, were observed. ICG removal rate in hepatocytes decreased significantly from 0.100 +/- 0.018 to 0.027 +/- 0.019 min-1 (mean +/- SD, P < 0.01) by 60-min warm ischemia, whereas the value increased to 0.082 +/- 0.030 min-1 (P < 0.05) when PGE1 was given at a dose of 0.05 microgram/kg/min. The treated livers also showed early reorganization of microtubules, as well as amelioration of ATP resynthesis after reperfusion. However, there were no significant differences in intraoperative changes in oxygen saturation and the content of hemoglobin in the sinusoid between PGE1-treated and untreated groups, indicating that the influence of PGE1 at this dose on hemodynamic changes is not considerable. These results indicate that PGE1 resuscitates an inherent hepatocyte function of organic anion transport on reperfusion after warm ischemia and suggest that the benefit could be attributed solely to direct action on hepatocytes.

Adenine Nucleotides↗