Kenjiro Tanaka

Regional distribution of immunoreactive endothelin in porcine tissue: Abundance in inner medulla of kidney

A specific and sensitive radioimmunoassay for endothelin has been developed. Half maximal inhibition of binding of radioiodinated endothelin was observed at 37 pg/tube and endothelin was detectable as low as 1 pg/tube. With this assay, the regional distribution of endothelin was determined in porcine tissue. The highest concentration of immunoreactive endothelin was observed in inner medulla of kidney (6.2 +/- 1.1 pg/mg wet weight), while the concentration in kidney cortex was very low. Immunoreactive endothelin was also found in lung in relatively high concentration. The immunoreactive endothelin in porcine lung and inner medulla of kidney was further characterized by reverse phase high performance liquid chromatography combined with radioimmunoassay.

Immunoreactive endothelin in rat kidney inner medulla: marked decrease in spontaneously hypertensive rats

Using a specific and sensitive radioimmunoassay for endothelin, the regional distribution and molecular form of endothelin was investigated in rat tissue. The highest concentration was observed in the inner medulla of the kidney (8.7 +/- 2.2 pg/mg wet weight). On two kinds of reverse phase high performance liquid chromatography, immunoreactive endothelin in the inner medulla of the kidney was separated into two peaks at positions where authentic porcine/human and putative rat/human endothelin eluted. Furthermore, the concentration of immunoreactive endothelin in the inner medulla of the kidney was remarkably decreased in spontaneously hypertensive rats (SHR) compared with normotensive control Wistar Kyoto rats (WKY) but no difference was observed in lung immunoreactive endothelin.

Suppressive effect of captopril on platelet aggregation in essential hypertension

Effects of captopril on platelet aggregation were studied in 12 essential hypertensive subjects. At the same time, the effects of captopril and angiotensin II on platelet aggregation in vitro were examined in 20 volunteers. A 50-mg oral dose of captopril was administered daily to hypertensive subjects for 2 weeks; the dose was then increased to 100 mg daily for the next 2 weeks. Values of platelet aggregation induced by ADP, epinephrine, collagen, and arachidonic acid before captopril treatment were 71.9 ± 4.5, 77.3 ± 4.2, 72.4 ± 4.1, and 70.8 ± 4.3% (mean ± SE), respectively. Two weeks after daily administration of 50 mg captopril, these values were 56.7 ± 4.5, 50.8 ± 7.6, 64.0 ± 4.6, and 60.9 ± 3.9%, respectively, with significant reduction of platelet aggregation (p < 0.001, p < 0.01, p < 0.01. and p < 0.005, respectively). Daily administration of 100 mg captopril also had a significant suppressive effect on platelet aggregation. Changes of platelet count and serum lipids were not significant. In vitro, captopril and angiotensin II added to plateletrich plasma had no effect on platelet aggregation. These results show that the suppressive effect of captopril on platelet aggregation is a secondary action in vivo.

Angiographic features in the infarct-related artery after intracoronary urokinase followed by prolonged anticoagulation. Role of ruptured atheromatous plaque and adherent thrombus in acute myocardial infarction in vivo.

To unravel sequential morphological features in infarct-related coronary arteries (IRCA), we performed coronary angiography (CAG) before, during, and immediately after intracoronary urokinase infusion in 43 consecutive patients. After 1 month of rigorous anticoagulation by intravenous heparin and subsequent oral warfarin or after the same period of treatment by antiplatelet agents, we repeated CAG in all patients except for one, who died 6 days after thrombolytic therapy. Thirty-two IRCAs were totally occluded, and 11 were severely occluded at baseline. With recanalization and/or reduction in luminal narrowing at the site of the occlusion by progressive removal of the overlying thrombus and plaque content, we recognized the development of extraluminal contrast pooling in an ellipsoid shape (type A), single or paired linear radiolucency(ies) with or without outpouching (type B), and definite outpouching (type C). The development of type A, B, and C lesions occurred in 4, 6, and 0 IRCAs immediately after thrombolytic therapy and in 0, 18, and 3 IRCAs 1 month later, respectively. Throughout the study, at least one of type A-C lesions developed in 23 of 43 (53.5%) IRCAs. Lesion development proceeded from total or severe occlusion to type A, then to type B or C, both accompanied by progressive reduction in luminal narrowing and frequent enlargement of outpouching. A postmortem study in one patient whose CAG immediately after thrombolytic therapy was interpreted as a type B lesion demonstrated a ruptured plaque with paired ridges. Serial observations in vivo indicate that many IRCAs are associated with a complex underlying spatial structure, probably composed of some part of ruptured atheromatous plaque with or without adherent thrombus. Recognition and identification of such complex structures beneath the accumulated thrombus are of great importance in both CAG interpretation and elucidation of the pathophysiological sequence of acute myocardial infarction in vivo and may enable prevention or more effective therapy of acute coronary events.

Minimal Change Nephrotic Syndrome in Adults: Response to Corticosteroid Therapy and Frequency of Relapse

Rate of response to a corticosteroid and frequency of relapse were studied in 33 patients with adult-onset minimal change nephrotic syndrome (MCNS). Of these, 28 patients were treated with oral prednisolone (PSL) at 1 mg/kg/d for from 4 to 8 weeks depending on their response, followed by PSL, at gradually tapering doses for 1 year. Five severely nephrotic patients received 1 g of methylprednisolone intravenously (IV) for 3 days, followed by 40 mg/d oral PSL for 4 to 8 weeks and finally PSL in gradually reduced doses. Sixteen patients (48%) were free of proteinuria within 4 weeks, and 25 (76%) within 8 weeks. Two patients required cyclophosphamide for induction of remission. Age at presentation was not significantly correlated with response time to corticosteroid therapy. Thirty-two (97%) went into remission, and relapse occurred in 11 (34%) of these. As assessed by the life-table method, 84% of patients were still in remission at 6 months after induction of remission, 75% after 1 year, and 63% during the follow-up period (mean, 47.1 +/- 29.1 months; range, 6 to 123 months). Incidence of relapse was not correlated with remission induction time, ie, earlier (less than or equal to 4 weeks) or later (greater than 4 weeks), but was greater in younger (less than 30 years of age) patients than older (greater than or equal to 30 years) patients (P less than 0.03). At the last follow-up, 31 patients (94%) were in complete remission and had normal renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution and molecular forms of brain natriuretic peptide in porcine heart and blood

Although brain natriuretic peptide (BNP) is a novel natriuretic peptide originally identified in porcine brain, recent investigation has verified the presence of BNP in porcine heart. In order to identify BNP as a circulating hormone, we analyzed the regional distribution and molecular form of immunoreactive (ir-) BNP in heart and blood. Tissue concentration of ir-BNP was high in atrium, but low in ventricle, in a manner similar to that of atrial natriuretic peptide (ANP). However, the concentration of ir-BNP in atrium was only about 1/50 that of ir-ANP. In plasma, ir-BNP was found at a concentration of 1-3 fmol/ml, which was about 1/20 that of ir-ANP. Both ir-BNP and ir-ANP were present as low molecular weight forms. Three forms of ir-BNP of about 3K daltons, including BNP-26, BNP-29 and BNP-32, are thought to circulate in blood.

Holter Electrocardiogram Monitoring in Nephrotic Patients during Methylprednisolone Pulse Therapy

We assessed the effect of intravenous methylprednisolone pulse therapy (IMPT) on cardiac rhythm and electrolyte metabolism in patients with nephrotic syndrome. A total of 25 patients had valid evaluations with continuous ambulatory electrocardiograms, and 20 of these had simultaneous sodium and potassium clearances. No significant difference of frequency in complex ventricular arrhythmias (Lowns grades 3-5) between the control and the therapy period was observed; however, 4 patients showed complex ventricular arrhythmias including ventricular tachycardia (2 patients) during the course of therapy. Fractional excretion of potassium and serum potassium significantly increased from baseline after IMPT. Complex ventricular arrhythmias, sometimes leading to sudden death, might ensue from IMPT. These dysrhythmias may be related to an abrupt change in potassium reflux from the cell.

Involvement of sympathetic nerves in cardiosuppressive effects of α-human atrial natriuretic polypeptide (α-hANP) in anesthetized rats

In order to clarify the hypotensive mechanisms of α-human atrial natriuretic polypeptide (α-hANP), hemodynamic responses were investigated in anesthetized rats. Mean blood pressure (MBP), cardiac index (CI) and total peripheral resistance index (TPRI) were measured before and after infusion of α-hANP (30 ng/min per 100 g body weight) in intact, nephrectomized, atropinized or chemically sympathectomized rats. MBP was significantly reduced in all rats, associated with a decrease in CI. TRPI decreased slightly in sympathectomized rats but was unchanged in the other rats. The α-hANP-induced reduction in MBP of sympathectomized rats was significantly less than that of intact rats (9.5 ± 1.2 vs. 20.9 ± 2.6%; P < 0.01). Similarly, the decrease in CI of sympathectomized rats was significantly less than that of intact rats (5.0 ± 1.8 vs. 21.7 ± 5.3%; P < 0.05). Changes in MBP and CI of nephrectomized, atropinized or intact rats did not differ significantly. It is suggested that neither fluid loss nor parasympathetic nerves play an important role in the acute hemodynamic response. However, sympathetic nerves might be involved in the cardiosuppressive action of α-hANP.

Right Ventricular Apical Pacing Impairs Left Ventricular Twist as Well as Synchrony: Acute Effects of Right Ventricular Apical Pacing

BACKGROUND This study was designed to compare the rotation of the left ventricular (LV) apex and base, LV synchrony between LV apical and basal rotation, and LV twist, changing from intrinsic atrioventricular conduction to right ventricular apical (RVA) pacing. METHODS Thirty consecutive patients with sick sinus syndrome who had undergone DDD pacemaker implantation were studied. Changing from intrinsic atrioventricular conduction to RVA pacing, the acute effect on echocardiographic parameters, including LV rotation and twist and LV apical-basal rotation delay, was assessed. RESULTS During RVA pacing, values of peak rotation in the LV apex and base and LV twist were significantly lower than during intrinsic atrioventricular conduction (P=.007, P=.003, and P<.0001, respectively). Apical-basal rotation delay during RVA pacing was significantly longer than during intrinsic atrioventricular conduction (P=.02). CONCLUSIONS RVA pacing decreases apical and basal LV rotation and induces LV apical-basal rotation delay, resulting in impairment of LV twist.

Dobutamine stress echocardiography at 7.5 μg/kg/min using color tissue Doppler imaging M-mode safely predicts reversible dysfunction early after reperfusion in patients with acute myocardial infarction

Abstract Dobutamine stress echocardiography (DSE) is widely used to predict reversible left ventricular dysfunction, but evaluation by this method is subjective. The recently developed color tissue Doppler imaging (TDI) M-mode may permit objective and quantitative assessment of changes in wall motion induced by DSE. We tested the hypothesis that this new method can detect sensitively reversible dysfunction in the post–myocardial infarction setting. DSE with color TDI M-mode and conventional DSE were performed to predict reversible dysfunction in 53 patients at a mean of 3 days after infarction using 7.5 and 10 μg/kg/min of dobutamine. Follow-up regular echocardiography (4 weeks later) was used as the reference technique to define reversible dysfunction segments. To predict reversible dysfunction segments, the standard segmental wall motion score change on conventional DSE and the ratio of the segmental wall velocity difference at rest versus stress (7.5 and 10 μg/kg/min) on DSE with color TDI M-mode (7.5-TDI-M and 10-TDI-M, respectively) were used. With 7.5 μg/kg/min of dobutamine, the sensitivity for predicting reversible dysfunction using color TDI M-mode (7.5-TDI-M) was significantly higher than that of conventional DSE (89% vs 73%, p