Masaaki Takano

Renal Hemodynamic Changes Induced by Captopril and Angiotensin-Converting Enzyme Gene Polymorphism

We studied the relationship between renal hemodynamic changes induced by a single acute administration of captopril (50 mg p.o.) and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in 27 healthy human volunteers, 7 with DD genotype, 10 with ID, and 10 with II genotype. The increase in effective renal plasma flow (p < 0.02) and the fall in renal vascular resistance (p < 0.01) in response to captopril were significantly less in subjects with the DD genotype than in subjects with the other genotypes. These data suggest that intrarenal ACE inhibition by captopril differs according to ACE gene ID polymorphism in healthy humans.

Gastrointestinal transit of non-disintegrating solid formulations in humans

Abstract Gastrointestinal transit times of four non-disintegrating formulations, namely, heavy tablets (H-tablets; 8 × 4 mm; relative density 1.33), light tablets (L-tablets; 10 × 6 mm; relative density 0.86), pellets (2 × 5–6 mm; relative density 1.46) and micro-particles (420–590 μm; relative density 1.26), were studied in healthy subjects after a light breakfast using dual-isotope scintigraphy, and also under fasting conditions for H- and L-tablets. The gastrointestinal transit times of the tablets, pellets and micro-particles, which had a relative density of more than unity, were almost identical. The mean gastric emptying times (GET1/2; time for 50% activity to leave the stomach) of the formulations (H-tablets, pellets and micro-particles) were 2.7, 2.2 and 2.3 h, respectively, under non-fasting conditions. A large inter-subject difference was observed in arrival time to the colon (ATC1/2; time for 50% activity to arrive at the ascending colon after GET1/2) with a range of 1.5 h to more than 6.5 h with these formulations under non-fasting conditions. However, the time for 50% activity to arrive at the ileocecal junction after GET1/2 (small intestine transit time; SITT1/2) showed very small intersubject variations with mean values of 1.7, 2.6 and 1.9 h for H-tablets, pellets and micro-particles, respectively, under non-fasting conditions. The residence times for these formulations at the ileocecal junction were observed to be more than 2 h. Tablets having a relative density of less than unity (L-tablets) showed a significantly prolonged gastric emptying time in the non-fasting state in comparison with H-tablets, although both were emptied rapidly in the fasting state without any significant difference. The intestinal transit time of the L-tablets showed no difference from that of the H-tablets, irrespective of the administration conditions.

Effects of an oral protein load on glomerular filtration rate in healthy controls and nephrotic patients.

Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and humoral factors were simultaneously examined before and after a 50-gram oral protein load in 12 healthy controls and 12 nephrotic patients. The protein load led to rises in GFR with unchanged filtration fraction in both groups although the rate of increase in GFR was greater in the former. The levels of blood urea nitrogen, serum osmotic pressure, plasma glucagon and serum insulin, but not plasma angiotensin II, were significantly elevated following the protein load. The increase in GFR after the protein load appears to be mainly caused by increased ERPF and afferent arteriolar vasodilation.

Effect of Prostaglandins on Renal Function in Uninephrectomized Humans

We examined the effects of unilateral nephrectomy (UN) and administration of indomethacin in 15 healthy humans. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urine flow, sodium and potassium excretions, urinary excretion rate of prostaglandin E2 (PGE2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) in the remaining kidney were all significantly (p < 0.01) increased 10 days after UN. Indomethacin administered at 75 mg/day for 3 days abolished the increase in GFR, ERPF and sodium excretion with reduced urinary excretion rate of PGE2 and 6-keto PGF1 alpha but not the increase in urine flow and potassium excretion. These findings suggest that renal prostaglandins may play a role in renal functional adaptation following UN.

Evaluation of left ventricular wall motion and function in patients with previous myocardial infarction by three-dimensional99mTc-HSAD multigated cardiac pool imaging

To evaluate left ventricular (LV) wall motion stereoscopically from all directions and to calculate the LV volume by three-dimensional (3D) imaging,99mTc-DTPA human serum albumin-multigated cardiac pool-single photon emission computed tomography (99mTc-MUGA-SPECT) was performed. A new data processing program was developed with the Application Visualization System-Medical Viewer (AVS-MV) based on images obtained from99mTc-MUGA-SPECT. In patients with previous myocardial infarction, LV function and LV wall motion were evaluated by 3D-99mTc-MUGA imaging. The LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were obtained from 3D-99mTc-MUGA images by the surface rendering method, and the left ventricular ejection fraction (LVEF) was calculated at thresholds of 35% (T1), 40% (T2), 45% (T3), and 50% (T4). There was a strong correlation between the LV volume calculated by 3D-99mTc-MUGA imaging at a threshold of 40% and that determined by contrast left ventriculography (LVEDV: 194.7 ± 36.0ml vs. 198.7 ± 39.1ml, r = 0.791, p < 0.001; LVESV: 91.6 ± 44.5ml vs. 93.3 ± 41.3ml, r = 0.953, p < 0.001), respectively. When compared with the LVEF data obtained by left ventriculography, significant correlations were found for 3D images reconstructed at each threshold (T1: r = 0.966; T2: r = 0.962; T3: r = 0.958; and T4: r = 0.955). In addition, when LV wall motion obtained by 3D-99mTc-MUGA imaging (LAT and LAO views) was compared with the results obtained by left ventriculography (RAO and LAO views), there was good agreement.3D-99mTc-MUGA imaging was superior in allowing evaluation of LV wall motion in all directions and in assessment of LV function, since data acquisition and image reconstruction could be done within a short time with the three-detector imaging system and AVS-MV. This method appears to be very useful for the observation of both LV wall motion and LV function in patients with ischemic heart disease, because it is a noninvasive examination.

Clinical application of three-dimensional myocardial imaging: Evaluation of efficacy of medical treatment on myocardial perfusion

To investigate the clinical applicability of the three-dimensional (3D) myocardial imaging using a newly developed system (the Application Visualization System-Medical Viewer), thallium-201 myocardial single photon emission computed tomography was performed in 19 patients with previous myocardial infarction before and after treatment with nisoldipine. We have developed a new method for automatically reconstructing 3D imaging for the stereoscopic evaluation of myocardial perfusion. The left ventricular myocardial volume with a radioisotope count ≧ 50% of maximum was calculated by using the conventional surface rendering method. With these images, the effect of nisoldipine on myocardial perfusion was assessed and the myocardial volume with a radioisotope count ≧ 50% of maximum was compared. In fifteen (88%) of 19 patients, myocardial perfusion increased in the infarct areas after nisoldipine treatment. Nisoldipine significantly increased the myocardial volume with a radioisotope count ≧ 50% of maximum from 141 ± 17 to 153 ± 18 ml on the stress 3D imagings. These findings indicate that nisoldipine improved myocardial perfusion during exercise. 3D imaging provided stereoscopic assessment of the changes in myocardial perfusion following treatment with nisoldipine and also detected transient enlargement of the left ventricular lumen induced by exercise.