Shigehiro Miki

Total and Split Renal Function Assessed by Ultrasound Doppler Techniques

We evaluated total and split renal functions from the pattern for renal arterial blood flow detected by ultrasound Doppler in healthy subjects and patients with varying degrees of renal function and disorders other than renovascular hypertension or severe aortic valvular disease. A renal-time pulsed ultrasonic echo-Doppler device at 2.5 MHz was used with a translumbar approach. The ratio of peak diastolic (D) to systolic (S) velocity correlated well with both p-aminohippurate clearance and creatinine clearance. Acceleration time was correlated with the clearance of neither compound. To evaluate the clinical usefulness of ultrasound Doppler in the assessment of split renal function, we compared the D/S ratio with the renal function obtained by radionuclide methods for individuals. The split renal glomerular filtration rate, calculated by a method which makes use of the early renal uptake of 99mTc-diethylenetriam-inepentaacetic acid, correlated well with the D/S ratio. These results indicate that the ultrasonic measurement of renal arterial blood flow by the pulsed Doppler method should be useful for assessment of total and split renal functions.

Sodium Sensitivity And Sympathetic Nervous System In Hypertension Induced By Long-Term Nitric Oxide Blockade In Rats

1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to produce acute and chronic hypertension in many animal species, but the underlying mechanisms mediating the hypertension are not completely understood. In particular, the pathogenetic roles of sodium sensitivity and the sympathetic nervous system in this model of hypertension are controversial. The present study was designed to test the hypothesis that long‐term administration of the NO synthesis inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME) to male Sprague‐Dawley rats would produce a sodium‐sensitive hypertension and that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity.

Successful Resection of Pheochromocytoma in a Hemodialysis Patient

A 45-year-old woman with a pheochromocytoma who had been on regular hemodialysis for 4 years and underwent successful surgery is described. Careful preoperative management, including the use of prazosin and weight control, was carried out to prevent severe intraoperative and postoperative cardiovascular complications. Prazosin was given at an initial dose of 0.5 mg/day, and the dosage was increased to 20 mg/day prior to surgery. The increase in intravascular volume led to a gain of 3 kg in body weight. No deterioration of the cardiovascular or respiratory function was caused by these maneuvers, and surgery was performed without significant complications except for a rapid rise of blood pressure during tumor resection. To our knowledge, only one similar case report could be found in the English literature.

Sensitive detection of myocardial contraction abnormality in chronic hemodialysis patients by ultrasonic tissue characterization with integrated backscatter

Since acoustic properties of the myocardium are sensitive to the myocardial structure and the contractile conditions of myocyte, the authors evaluated cardiac dysfunction based on the integrated ultrasonic backscatter in 18 hemodialysis (HD) patients (duration: 102 ±84 months, mean age: 57.6 ±9.7 years) and 11 age-matched normals. The cyclic variation of integrated backscatter (CV-IB) at interventricular septum (IVS) and left ventricular posterior wall (PW) was measured and compared with percent fractional short ening (%FS) and percent wall thickening (%Th). The CV-IB of HD patients was smaller than that of control subjects (IVS: 6.2 ± 1.1 dB vs 8.2 ± 1.1 dB, p = 0. 0003 and PW: 8.4 ±2.2 vs 10.3 ±1.3, p = 0.025). No significant difference was observed in %FS and %Th between HD patients and control subjects. In HD, the ratio of velocities of early diastolic inflow (E) to late atrial inflow was decreased (0.7 ±0.2 vs 1.1 ±0.7, p = 0.049) and decel eration time of E was prolonged significantly (200 ±28 msec vs 159 ±30 msec, p = 0.0082). In the absence of overt cardiac systolic dysfunction, myocardial damage indicated as a decrease in CV-IB and diastolic dysfunction identified on transmitral velocity waveform were detected, which may reflect from the myocardial fibrosis. As a mechanism, pressure overload, hyperparathyroidism, and anemia were neglected, and the other humoral factors may contribute to the myocardial damage in chronic renal failure.

Pharmacokinetics and Efficacy of Carvedilol in Chronic Hemodialysis Patients with Hypertension

The efficacy, safety, and pharmacokinetics of carvedilol were investigated in an open trial performed on six patients with hypertension and chronic renal failure requiring hemodialysis. The plasma level of unchanged carvedilol after a single dose of 10 mg reached a peak 1–5 h after administration both on days with and without hemodialysis. The drug was gradually metabolized thereafter and had almost disappeared from the plasma after 24 h. Blood pressure was lowered by carvedilol both on days with and without hemodialysis. No carvedilol passed through the dialysis membrane. During the 4-week administration period of carvedilol at 10 mg/day, assessment of plasma samples taken just prior to early morning administration demonstrated no drug accumulation. Blood pressure was well controlled during the administration period. Tolerance to the antihypertensive effect was not observed. Heart rate was not significantly changed at any time. There were no side effects in any of the patients during the trial, and laboratory parameters remained unchanged. These results indicate that carvedilol is a safe and effective antihypertensive agent for use in patients on chronic hemodialysis.

Dopaminergic modulation of the pressure???natriuresis response in rats

Objective The present study was carried out to examine the involvement of dopamine in the pressure-natriuresis phenomenon which has been postulated as a major regulator of extracellular fluid volume and thereby arterial pressure. Design Dopaminergic modulation of the pressure-natriuresis response was studied in the innervated and denervated rat kidney, to allow a distinction between the effects of neural and extraneural dopamine. Methods The pressure-natriuresis response was studied in anesthetized Sprague-Dawley rats, in which neural and hormonal influences on the kidney were fixed by denervating the kidney and by intravenous infusion of aldosterone, hydrocortisone, vasopressin and norepinephrine. The innervation to the kidney remained intact in some experiments with the selective dopamine-1 antagonist SCH 23390. Urinary excretion of dopamine during the pressure-natriuresis response was also examined in the innervated and denervated rat kidney. Results Although infusion of dopamine at a dose of 2 (μ/kg per min had no effect on the pressure-natriuresis response in rats in which neural and hormonal influences on the kidney were fixed, the slopes of the relations between urine flow, sodium excretion and mean arterial pressure in rats given 10 μ/kg per min dopamine were significantly greater than those found in the control rats. Renal plasma flow increased significantly in the dopamine-treated rats whilst glomerular filtration rate did not differ between the control and dopamine-treated rats. The dopamine-induced increase in the slope of pressure-natriuresis relationship and renal plasma flow were completely blocked by 0.5 μ/kg per min SCH 23390. However, infusion of SCH 23390 alone at 0.5 μ/kg per min did not significantly alter the pressure-natriuresis response in rats with either denervated or innervated kidney. In addition, urinary excretion of dopamine derived from neither neural nor extraneural origins was altered in parallel with variations in mean arterial pressure. Conclusion These results suggest that exogenous administration of dopamine may affect the pressure-natriuresis response by altering the magnitude of arterial pressure-induced changes in tubular sodium reabsorption, via an action of dopamine-1 receptors. However, endogenous dopamine does not appear to be capable of modulating the pressure-natriuresis response.

Effect of low dietary calcium intake on blood pressure and pressure natriuresis response in rats: a possible role of the renin-angiotensin system.

Dietary Ca is an important modulator of blood pressure in humans and rats. Since the kidney plays a key role in the pathogenesis of hypertension, the effects of a low Ca diet (0.01% Ca) on blood pressure and pressure natriuresis response were studied in normotensive Sprague-Dawley rats. In addition, a possible role of the renin-angiotensin system in the development of hypertension and an altered pressure natriuresis response resulting from low dietary Ca intake was examined. In the low Ca diet group, systolic blood pressure measured by the tail-cuff method was significantly higher than in the normal Ca diet group (1,1% Ca) 1 week after the diet (1 13.0 +/- 7.1 vs. 105.0 +/- 9.5mmHg, p < 0.05). After 4 weeks, the hypertension was more pronounced. Low dietary Ca intake significantly inhibited the water and sodium excretory responses to acute elevation of renal perfusion pressure by tightening an infrarenal aortic constriction. Treatment with an inhibitor of angiotensin-converting enzyme, captopril (30 mg/kg/day), completely abolished the elevation of blood pressure and attenuated the reduced pressure natriuresis response observed in Ca-deficient rats. Although plasma renin activity was not different between the low and normal Ca diet groups after the 2-week dietary regimen, the pressor response to angiotensin II was enhanced by 30% in the low Ca diet group and there was a significant difference in the pressor response between the two groups. These results suggest a possible involvement of the renin-angiotensin system in the development of hypertension and an inhibitory effect on the pressure natriuresis response caused by low dietary Ca intake, via an enhanced sensitivity to angiotensin II.

Noninvasive detection and monitoring of renal arteriovenous fistula by color Doppler

The diagnosis of a renal arteriovenous fistula is usually confirmed by angiography. Described is the utilization of color Doppler ultrasound to monitor a renal arteriovenous fistula before and after treatment by transcatheter steel coil embolization in a 63-year-old woman. Using color Doppler, the arteriovenous fistula with an aneurysmal lesion was clearly visualized. A pulsed-wave Doppler analysis showed increased flow velocity and decreased pulsatility in the supplying artery. After successful transcatheter occlusion of the fistula, these findings disappeared. The Doppler ultrasound technique is likely to be useful to detect and monitor a renal arteriovenous fistula noninvasively, simply, and quickly.

Clinical Evaluation of the Immunoadsorbent Therapy of Immunoneuropathies.

難治性免疫性神経疾患患者に対し免疫吸着療法 (IAT) を施行し, その臨床的有用性を検討した.対象は慢性多発性根神経炎 (CIDP) 5例, ギランバレー症候群 (GBS) 1例で, CIDP症例についてはステロイド療法などの薬物治療に反応しないものとした. 血液浄化法は膜分離法による血漿吸着法とし, 吸着カラムにはポリビニールアルコールゲルにフェニルアラニンをリガンドとして固定した疎水性カラムを使用した. IATは症例により1-35回施行した. 全例で活動力低下, 異常知覚, 歩行障害などの自他覚症状の改善を認め, 握力検査においても筋力増強が確認された. IAT施行前後の血中蛋白分画の比較では免疫グロブリン分画の有意の減少がみられたが, アルブミンは不変であった. また, CIDP症例においてはIAT施行前, 全例に髄液蛋白濃度の増加がみられたが, IAT施行後はほとんどの症例で蛋白濃度の明らかな減少を認めた. 副作用としてIAT施行中の-過性の血圧低下と施行後の発熱を認めたが, いずれも重篤なものではなかった. 以上より, 本療法は難治性免疫性神経疾患に対し有用かつ安全に施行可能な治療法と思われた.

Pharmacokinetics and clinical effects of carvedilol in chronic hemodialysis patients with hypertension.

血液透析を施行している高血圧を伴う慢性腎不全患者6例を対象にcarvedilolの有効性, 安全性および体内動態について検討した.透析時および非透析時におけるcarvedilol 10mg単回投与後の血漿中未変化体はいずれも投与1-5時間で最高濃度に達し, 以後徐々に代謝され24時間後にはほぼ消失した. 血圧は透析日および非透析日のいずれにおいてもcarvedilolの投与により緩徐に下降した. また, carvedilolの透析による体外除去は極めて少なく, 本薬の血中濃度への透析の影響はほとんどなかった.Carvedilol 10mg 1日1回4週間の連続投与により, 早朝服薬前の血漿中未変化体濃度の上昇はみられず, 本薬の蓄積性は認められなかった. 血圧は, 投与期間中良好にコントロールされ, 耐薬性もみられなかった. また, 心拍数は, いずれの時点においても有意な変化を示さなかった. 副作用および臨床検査値の異常は認められなかった.以上より, carvedilolは血液透析患者における血圧管理に有効かつ安全な降圧薬であると考えられた.