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Biomedical subjects

Tokunori Yamamoto

Publications and source records attributed to Tokunori Yamamoto.

15 recordsLinked to original sources

Effects of calcium channel blockade on angiotensin II-induced peritubular ischemia in rats.

Recent studies have indicated that derangement of peritubular capillary (PTC) circulation with consequent tubulointerstitial hypoxia plays a pivotal role in the pathogenesis of renal injury. The present study was performed to determine whether azelnidipine, a new dihydropyridine calcium channel blocker, attenuates angiotensin II (AngII)-induced peritubular ischemia in anesthetized rats. The superficial PTCs were visualized directly using an intravital fluorescence videomicroscope system, and the PTC blood flow was evaluated by analyzing the velocity of fluorescein isothiocyanate-labeled erythrocytes. Intravenous infusion of AngII (50 ng/kg/min, 10 min) significantly increased mean arterial pressure (MAP) and renal vascular resistance (RVR) (by 35 +/- 3% and 110 +/- 32%, respectively), and decreased total renal blood flow (RBF) and PTC erythrocyte velocity (by -34 +/- 4 and -37 +/- 1%, respectively). Treatment with azelnidipine (5 microg/kg/min i.v., 10 min) had no effect on basal MAP, RBF, RVR, or PTC erythrocyte velocity. However, azelnidipine markedly attenuated the AngII-induced increases in MAP (7 +/- 3%) and RVR (40 +/- 4%) and decreases in RBF (-24 +/- 1%) and PTC erythrocyte velocity (-22 +/- 1%). Similar attenuation in the AngII-induced responses of MAP, RBF, RVR, and PTC erythrocyte velocity were observed in rats treated with a higher dose of azelnidipine (20 microg/kg/min i.v., 10 min), which significantly decreased basal MAP and RVR and increased RBF and PTC erythrocyte velocity. These data suggest that calcium channel blockade attenuates AngII-induced peritubular ischemia, which may be involved in its beneficial effects on renal injury.

Adenosine Triphosphate↗

Direct visualization of cortical peritubular capillary of transplanted human kidney with reperfusion injury using a magnifying endoscopy.

BACKGROUND: We developed a direct imaging system of renal microcirculation by a magnifying-endoscopy that enables visualization of the movement of erythrocyte in glomerular and cortical peritubular capillary (CPC). We investigated the microcirculation of CPC in the early phase of both living- and cadaveric-donor transplant kidneys. METHODS: Erythrocyte velocity in CPC were monitored and measured in 20 renal transplants at 20, 60, 90, and 120 minutes after reperfusion. The kidney grafts came from 11 living donors and 9 non-heart-beating cadaveric donors. RESULTS: In living-donor transplants, erythrocyte velocity in CPC at 20 minutes after revascularization declined to one third of baseline value just before nephrectomy and recovered to the prenephrectomy value 120 minutes after reperfusion. In contrast, it continued to be disturbed for 90 minutes in cadaveric-donor transplants. Erythrocyte velocity in CPC more significantly deteriorated in cadaveric transplants than in those of living transplants at 20 through 60 minutes after the revascularization. In living-donor transplants, erythrocyte velocity did not correlate with donor age, both warm (WIT) and cold ischemic time (CIT), time to the initial urination, and best creatine clearance. In the cadaveric transplants, ischemic time, both WIT and CIT, did not correlate with the erythrocyte velocity. However, donor age, duration of acute tubular necrosis, and best creatine clearance after transplantation significantly correlated with the erythrocyte velocity. CONCLUSION: The measurement of erythrocyte velocity in CPC is a reliable method for predicting the recovery of renal function and reserved renal function of kidney allografts undergoing prolonged ischemia.

Blood Flow Velocity↗

Laparoscopic pyeloplasty using endoscopic GIA stapler for ureteropelvic junction obstruction.

PURPOSE: We applied laparoscopic pyeloplasty in 10 patients with ureteropelvic junction (UPJ) obstruction. To evaluate the efficiency and safety of this procedure using an endoscopic GIA stapler, the clinical outcomes and our procedures are presented. PATIENTS AND METHODS: From August 1996 to March 2003, eight female and two male patients with a mean age of 22.3 years suffering from UPJ obstruction diagnosed by various combinations of ultrasonography, excretory urography, retrograde ureteropyelography, CT, and MRI were treated with laparoscopic dismembered Anderson-Hynes pyeloplasty with resection of a dilated redundant renal pelvis. In six cases, an endoscopic gastrointestinal automatic stapler (Endo-GIA) was used. The procedure was performed via an extraperitoneal approach in two cases and a transperitoneal approach in eight. RESULTS: Laparoscopic pyeloplasty was successful in all patients, including the six treated using an Endo- GIA stapler. The mean operating time was 291 minutes, and the mean anastomotic time was 105 minutes, with a mean estimated blood loss of 44 mL. Postoperative complications occurred in five cases: anastomotic urinary leakage in two and pyelonephritis in three. The mean time to full convalescence in the entire series was 22 days. No urolithiasis occurred in the patients treated with the Endo-GIA stapler during the follow-up period of 2 to 76 (mean 22) months. CONCLUSIONS: Laparoscopic dismembered pyeloplasty including the Endo-GIA stapler technique is an efficient and safe procedure that provides excellent results for extrinsic or complicated UPJ stenosis. The risk of stone formation has not yet been determined.

Adolescent↗

Pulse total-hemoglobinometer provides accurate noninvasive monitoring.

OBJECTIVE: Rapid noninvasive measurement of total hemoglobin would be extremely useful for various clinical situations. This study determined the clinical accuracy and utility for a pulse total-hemoglobinometer using four wavelengths: 660 nm (reduced hemoglobin), 805 nm (isosbestic point), 940 nm (oxygenated hemoglobin), and 1300 nm (water density). DESIGN: Clinical trial. SETTING: University school of medicine. PATIENTS: Patients were 122 individuals (age, 18-82 yrs; 49.4 +/- 16.0 yrs [mean +/- SD]), including 71 healthy volunteers, 24 patients undergoing surgery, and 27 patients undergoing hemodialysis. INTERVENTIONS: The hemoglobinometer probe, which simultaneously indicated peripheral oxygen saturation, pulse rate, and hemoglobin, was placed on the fingertip similarly to a regular pulse oximeter. The hemoglobin values were compared with those obtained by the co-oximeter or the sodium lauryl sulfate-methemoglobin method. Those hemoglobin values were assigned to either the training set or the validation set for statistical evaluation. MEASUREMENTS AND MAIN RESULTS: Multiple regression analysis including the ratio of the pulsatile optical density (phi(ij)) derived from the four wavelengths and other factors demonstrated that the mean value of the normalized pulse wave obtained from the photodiode at 805 nm (DC805) and the ratios of DC940 and DC1300 (DC940/DC1300) were the pivotal factors in the hemoglobinometer's increased accuracy in the clinically useful range. The coefficient of determination between both methods was r2 = .81 (p < .0001) in the training set and r2 = .75 (p < .0001) in the validation set. When the cutoff value of anemia was set at 10 g/dL, and anemia was defined as <10 g/dL, the respective sensitivity and specificity of hemoglobinometer values to detect anemia in intraoperative patients were 84.3% and 84.6% (n = 20). CONCLUSIONS: The data demonstrated the necessity for consideration of light scattering in red blood cells for pulse-spectrophotometric hemoglobin measurement. This was accomplished with additional factors, such as DC805 and DC940/DC1300. With these improvements, the pulse hemoglobinometer provided noninvasive, clinically acceptable measurement of hemoglobin. The pulse hemoglobinometer is a versatile tool that might be useful for routine health checkups of neonates and young children, intraoperative monitoring of bleeding, and emergency care.

Adult↗

Assessment of microheterogeneity of blood flow in the rat urinary bladder by high-resolution digital radiography.

OBJECTIVES: To assess high-resolution digital radiography for measuring blood flow and thus examine the microheterogeneity of bladder microcirculation in a rat model. MATERIALS AND METHODS: Microheterogeneity of blood flow in both mucosa and detrusor muscle of eight anaesthetized rats was investigated using an imaging technique with very high spatial resolution (0.1 x 0.1 mm(2)) using digital radiography combined with the deposition of (3)H-labelled desmethylimipramine. The spatial pattern of blood flow was quantified by the coefficient of variation of the regional flow (CV = sd/mean). RESULTS Muscle blood flow was less than mucous blood flow (muscle : mucosa, 2.9 : 5) in the empty bladder. In the muscle layer the blood flow distribution was more heterogeneous than that in the mucosa, with a mean (sd) CV in muscle and mucosa of 0.33 (0.033) and 0.16 (0.019), respectively (P < 0.001) at the capillary level. CONCLUSION: There was a heterogeneous distribution of blood flow in the microcirculation to capillary vessels in the muscular layer, possibly reflecting a difference in dynamic blood flow of regional perfusion of the emptied bladder.

Animals↗

Role of asymmetrical dimethylarginine in renal microvascular endothelial dysfunction in chronic renal failure with hypertension.

We examined whether endothelial function of the renal microcirculation was impaired in a model of chronic renal failure (CRF), and further assessed the role of asymmetrical dimethylarginine (ADMA) and its degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH), in mediating the deranged nitric oxide (NO) synthesis in CRF. CRF was established in male mongrel dogs by subtotal nephrectomy, and the animals were used in experiments after a period of 4 weeks. The endothelial function of the renal afferent and efferent arterioles was evaluated according to the response to acetylcholine, using an intravital needle-lens charge-coupled device camera. Intrarenal arterial infusion of acetylcholine (0.01 microg/kg/min) elicited 22+/-2% and 20+/-2% dilation of the afferent and efferent arterioles in normal dogs. In dogs with CRF, this vasodilation was attenuated (afferent, 12+/-2%; efferent, 11+/-1%), and the attenuation paralleled the diminished increments in urinary nitrite+nitrate excretion. In the animals with CRF, plasma concentrations of homocysteine (12.2+/-0.7 vs. 6.8+/-0.4 micromol/l) and ADMA were elevated (2.60+/-0.13 vs. 1.50+/-0.08 micromol/l). The inhibition of S-adenosylmethionine-dependent protein arginine N-methyltransferase by adenosine dialdehyde decreased plasma ADMA levels, and improved the acetylcholine-induced changes in urinary nitrite+nitrate excretion and arteriolar vasodilation. Acute methionine loading impaired the acetylcholine-induced renal arteriolar vasodilation in CRF, but not normal dogs, and the impairment in CRF dogs coincided with the changes in plasma ADMA levels. Real-time polymerase chain reaction revealed downregulation of the mRNA expression of DDAH-II in the dogs with CRF. Collectively, these results provide direct in vivo evidence of endothelial dysfunction in canine CRF kidneys. The endothelial dysfunction was attributed to the inhibition of the NO production by elevated ADMA, which involved the downregulation of DDAH-II. The deranged NO metabolic pathway including ADMA and DDAH is a novel mechanism for the aggravation of renal function.

Acetylcholine↗

Hypoperfusion of peritubular capillaries induces chronic hypoxia before progression of tubulointerstitial injury in a progressive model of rat glomerulonephritis.

Chronic hypoxia likely plays a pivotal role in chronic renal disease, but the specifics of its involvement remain unclear. To elucidate how chronic hypoxia occurs and whether hypoxia participates in the progression of renal disease, the authors established an irreversible glomerulonephritis model induced by uninephrectomy and repeated anti-Thy-1 antibody injections. Glomerulosclerosis with microvascular obliteration was complete at 2 wk after antibody injection and was not restored until 11 wk. Tubulointerstitial injury was mild at 2 wk and was gradually exacerbated until 11 wk, a pattern that was in accordance with the loss of peritubular capillaries. Immunohistochemical analysis using pimonidazole revealed the augmentation of hypoxia in the cortex before the aggravation of tubulointerstitial injury and subsequent peritubular capillary loss. The preexistence of hypoxia implies that it had substantial participation in the progression of tubulointerstitial injury. To test whether blood flow was inhibited in diseased kidneys, capillaries with intact blood flow were identified by tail vein injection of biotinylated lectin specific to endothelial cells. The renal microvasculature was well recognized by lectin in the controls, whereas lectin binding to peritubular capillaries was strikingly decreased in diseased kidneys, suggesting a disturbance of blood flow. Intravital microscopy analysis confirmed that blood flow in peritubular capillaries was decreased by approximately 40% in the disease group compared with the controls. In conclusion, stagnation of blood flow in peritubular capillaries induced chronic hypoxia at an early stage in this model, which was followed by progressive tubulointerstitial injury and a loss of peritubular capillaries.

Animals↗

A comparison of changes in cardiac preload variables during graded hypovolemia and hypervolemia in mechanically ventilated dogs.

We developed an online monitoring system to measure systolic blood pressure variation (SPV) and its down (dDown) and up components, along with pulse pressure variation (dPP). Using the system, we compared different cardiac preload indicators-such as stroke volume variation (SVV) and corrected flow time (FTc)-along with central venous pressure and pulmonary artery occlusion pressure in mechanically-ventilated dogs during normovolemia, graded hypovolemia (-200 and -350 mL), and hypervolemia (+200 and +350 mL). We simultaneously measured these preload indicators along with global hemodynamic variables and investigated their validity and limitations to access preload changes. SPV increased from 4.8 +/- 1.4 mm Hg at baseline to 11.2 +/- 1.8 mm Hg during hypovolemia (-350 mL), but it did not change significantly during hypervolemia. Similar changes were observed with dDown, dPP, and SVV. FTc, conversely, increased during hypervolemia but remained unchanged during hypovolemia. The results of this study indicate that SPV, dDown, dPP, and SVV are useful indicators of hypovolemia, but not of hypervolemia. Conversely, hypovolemia could not be detected reliably by FTc, but it does reflect blood volume changes during hypervolemia. Although SPV, dDown, and dPP measurements require no additional invasion and cost beyond arterial cannulation, their limits must be kept in mind for the monitoring of blood volume status in mechanically-ventilated patients.

Animals↗

Efficacy of preoperative donation of autologous blood in patients undergoing radical retropubic prostatectomy.

BACKGROUND: Radical retropubic prostatectomy (RRP) has resulted in substantial blood loss and the frequent need for homologous blood transfusion. In this study, the efficacy of autologous blood transfusion, from medical and financial perspectives, was evaluated in patients undergoing RRP. METHODS: Between 1994 and 2000, 80 patients with localized prostate cancer underwent RRP in our institute. Based on informed consent, preoperative donation of autologous blood (PDA) was performed in 65 out of 80 patienets. Four or six units were donated during the first 3 years; however, donation units were reduced to a maximum of 4 units since 1997 onwards. The discard rate of donated blood and frequency of homologous transfusion were examined. Changes of hematocrit (Ht) and hemoglobin (Hb) levels through donation and surgery and important factors that may affect postoperative levels of Ht and Hb were evaluated in 56 patients receiving 4-unit donations. RESULTS: Overall, 2 or 4 units of donated blood were discarded in four patients and homologous transfusion was required in two patients. In 56 patients receiving 4-unit donation, the mean Ht level at predonation was 43.3%. Following donation, this decreased to 35.7%. The administration of recombinant human erythropoietin (rHuEpo) relieved declining Ht levels following donation, but changes in Ht levels after surgery were minor. Important factors related to postoperative decline of Ht and Hb levels were operative time and blood loss. CONCLUSIONS: The program of 4-unit PDA can be performed safely without rHuEpo injection, and it is useful to reduce the risk of requiring homologous transfusion. However, more efficient programs to relieve patient burden and to reduce medical cost are needed.

Aged↗

Intravital videomicroscopy of peritubular capillaries in renal ischemia.

The recent refinement and computerization of intravital microscopy have permitted us to monitor microcirculation in vivo with minimal invasion. Here, we report on the first findings made with the use of a pencil-lens intravital microscope as applied to the ischemic rat kidney. Peritubular capillary and glomerular blood flow were monitored under basal conditions, during renal artery occlusion, and immediately after release of the clamp. Erythrocyte velocity was calculated as an angle in consecutive spatiotemporal images. Intravital videomicroscopy during the reperfusion period showed intermittent cessation and partial recovery of blood flow in both peritubular and glomerular capillaries. Blood flow was uniformly orthograde under control conditions; however, the retrograde flow occurred on reperfusion. The patency of peritubular capillaries was partially compromised during the early reperfusion period but rapidly recovered. The recovery of glomerular microcirculation occurred faster than that of peritubular capillaries. We suggest that a functional vasculopathy develops very early in the course of ischemia-reperfusion in superficial cortical microvasculature and is more pronounced in peritubular capillaries, thus accounting for the development of patchy injury of tubular epithelia.

Acute Kidney Injury↗

Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells.

There is accumulating circumstantial evidence suggesting that endothelial cell dysfunction contributes to the "no-reflow" phenomenon in postischemic kidneys. Here, we demonstrated the vulnerability of in vitro, ex vivo, and in vivo endothelial cells exposed to pathophysiologically relevant insults, such as oxidative and nitrosative stress or ischemia. All of these stimuli compromised the integrity of the endothelial lining. Next, we performed minimally invasive intravital microscopy of blood flow in peritubular capillaries, which provided direct evidence of the existence of the no-reflow phenomenon, attributable, at least in part, to endothelial injury. In an attempt to ameliorate the hemodynamic consequences of lost endothelial integrity, we transplanted endothelial cells or surrogate cells expressing endothelial nitric oxide synthase into rats subjected to renal artery clamping. Implantation of endothelial cells or their surrogates expressing functional endothelial nitric oxide synthase in the renal microvasculature resulted in a dramatic functional protection of ischemic kidneys. These observations strongly suggest that endothelial cell dysfunction is the primary cause of the no-reflow phenomenon, which, when ameliorated, results in prevention of renal injury seen in acute renal failure.

Acute Kidney Injury↗

Prostate-specific antigen levels and prognosis in patients with hormone-refractory prostate cancer treated with low-dose dexamethasone.

OBJECTIVE: The efficacy of low-dose dexamethasone (DXM) therapy in patients with hormone-refractory prostate cancer (HRPC) was evaluated. PATIENTS AND METHODS: Prostate-specific antigen (PSA) response and survival following DXM therapy were analyzed in 27 Japanese patients exhibiting HRPC. Concurrent therapies and antiandrogen withdrawal syndrome, which may affect PSA levels and palliative effects, were excluded from the study. A dose of 1.5 mg of DXM was administered, and androgen deprivation therapy was maintained during DXM therapy. A decline in PSA levels of at least 50% from baseline was considered a significant PSA response. Prognostic factors for PSA response and survival were examined by univariate and multivariate analyses. RESULTS: A significant PSA response was observed in 16 of the 27 cases (59.3%). Median survival period of patients exhibiting significant PSA response was 15.9 months and was significantly longer than that of patients demonstrating a decline in PSA of less than 50% (median 7.7 months, p < 0.0001). Effect on pain control also correlated with the significant PSA response. No meaningful prognostic factors for PSA response were detected; however, a PSA decline of greater than 50% was the prognostic factor for survival. CONCLUSION: DXM therapy remains one of the most beneficial treatment modalities in patients with HRPC.

Aged↗

Distinct modulation of superficial and juxtamedullary arterioles by prostaglandin in vivo.

Renal afferent (AFF) and efferent arteriolar (EFF) responsiveness to angiotensin II (ANG II) in superficial and juxtamedullary nephrons in vivo remains undetermined, nor has it been clarified what role intrarenal autocrines/paracrines play in modulating the renal microvascular response. The present study characterized the responsiveness to ANG II (1-30 ng/kg/min) of AFF and EFF of canine superficial and juxtamedullary nephrons under pentobarbital anesthesia, using intravital CCD-videomicroscopy that allowed direct in vivo visualization of the renal microcirculation. Furthermore, the effect of prostaglandins (PG) and nitric oxide (NO) on ANG II-induced tone was examined. In superficial nephrons, ANG II induced a similar dose-dependent constriction of both AFF (46 +/- 5% constriction) and EFF (53 +/- 3%). In juxtamedullary arterioles, ANG II induced a dose-dependent constriction of EFF, whereas AFF responses were diminished (17 +/- 4% vs. 37 +/- 4% at 10 ng/kg/min). The PG inhibition by indomethacin enhanced the ANG II-induced constriction of juxtamedullary AFF, whereas no augmentation was observed in other arterioles. In contrast, NO inhibition by nitro-L-arginine methylester (L-NAME) enhanced the ANG II-induced constriction, with greater augmentation in juxtamedullary AFF and EFF. Finally, renal interstitial PG and nitrite/nitrate contents were greater in the medulla than the superficial cortex under basal and ANG II-stimulated conditions. Taken together, the results of the intravital CCD-videomicroscopy reveal that the renal microvascular action of ANG II had both zonal (juxtamedullary vs. superficial nephrons) and segmental (AFF vs. EFF) heterogeneity under the present experimental conditions. This heterogeneity was associated with a difference in the intrarenal production of prostaglandin E2 (PGE2) and NO; PGE2 contributed to segmental and zonal differences whereas NO was responsible for the zonal heterogeneity in arteriolar responsiveness.

Angiotensin II↗