Effects of alpha human atrial natriuretic polypeptide on the systemic hemodynamics and coronary circulation in patients with ischemic heart disease

Alpha human atrial natriuretic polypeptide (alpha-hANP) was intravenously infused into 7 patients with ischemic heart disease who had almost normal cardiac function at a rate of 0.025 micrograms/kg/min for 15 min. During infusion of alpha-hANP, left ventricular (LV) systolic pressure decreased from 144 +/- 19 (SD) to 129 +/- 22 mmHg (p less than 0.01), LV end diastolic pressure (EDP) from 15 +/- 5 to 13 +/- 4 mmHg (p less than 0.05), mean aortic pressure from 102 +/- 14 to 91 +/- 14 mmHg (p less than 0.01), time constant of LV pressure fall (T) from 100 +/- 15 to 88 +/- 13 msec (p less than 0.05), systemic vascular resistance (SVR) from 1711 +/- 206 to 1424 +/- 340 dynes.sec.cm-5 (p less than 0.05) and coronary vascular resistance (CVR) from 8.5 +/- 1.2 to 7.4 +/- 1.3 x 10(4) dynes.sec.cm-5 (p less than 0.05). There was a linear correlation between percent changes in SVR and those of CVR (r = 0.92, p less than 0.01), and the fall in CVR was approximately 68% of that in SVR. Increases occurred in heart rate from 63 +/- 7 to 66 +/- 8 beats/min (p less than 0.05), LV dp/dt from 1558 +/- 266 to 1627 +/- 238 mmHg/sec (p less than 0.05), LV dp/dt/p from 22.9 +/- 3.2 to 25.6 +/- 3.7/sec (p less than 0.01), and myocardial oxygen consumption (from 7.9 +/- 2.4 to 9.8 +/- 2.1 ml/min, p less than 0.05), while mean right atrial and mean pulmonary arterial pressures and pulmonary vascular resistance were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Wallace direct versus anti-reflux Le Duc ureteroileal anastomosis: comparative analysis in modified Studer orthotopic neobladder reconstruction

Objectives: To investigate and compare Wallace direct ureteroileal anastomosis with Le Duc anti‐reflux procedure in modified Studer orthotopic neobladder reconstruction after radical cystectomy. Methods: A total of 72 consecutive patients who underwent modified Studer orthotopic bladder reconstruction after a radical cystectomy for bladder cancer were investigated. They were examined for vesicoureteral reflux, hydronephrosis, and pyelonephritis at 6 months after surgery according to the type of ureteroileal anastomosis. Results: Vesicoureteral reflux occurred in 29 ureters (38.2%) after the Wallace procedure compared to six ureters (9.6%) with the Le Duc (P < 0.05). Hydronephrosis was detected in 12 ureters (18.8%) in the Le Duc patients compared to seven (9%) in the Wallace patients (P > 0.05). Six months after the operation, all three patients with vesicoureteral reflux‐related hydronephrosis improved using clean intermittent catheterization in the Le Duc patients; five of seven patients were cured by clean intermittent catheterization and two improved without any treatment in the Wallace patients. Seven of nine cases of ureteroileal anastomosis stenosis causing hydronephrosis were cured without any treatment but one case resulted in a non‐functional kidney despite treatment of the stenosis. Conclusions: Direct ureteroileal anastomosis using the Wallace method is effective for minimizing ureteroileal anastomosis stenosis and it represents a simple surgical procedure when combined with a modified Studer procedure.     

Endovascular therapy for stenosis of the petrous or cavernous portion of the internal carotid artery: percutaneous transluminal angioplasty compared with stent placement

OBJECT: The effects of percutaneous transluminal angioplasty (PTA) and stent placement for stenosis of the petrous or cavernous portion of the internal carotid artery (ICA) were compared. METHODS: Twenty-four patients with symptomatic, greater than 60% stenosis of the petrous or cavernous portion of the ICA were treated using PTA or stent placement; 15 were treated with PTA and nine with stent insertion. Initial and follow-up results (> 3 months posttreatment) were compared in each group. Stenotic portions of the ICA were successfully opened in 13 of 15 patients in the PTA group, and in all nine patients in the stent-treated group. In one case in the PTA group stent delivery was attempted; however, the device could not pass through the vessel's tortuous curve, and PTA alone was performed in this case. Postoperatively, the mean stenotic ratio decreased from 72.1 to 29.6% in the PTA group, and from 75.6 to 2.2% in the stent-treated group. In four patients in the PTA group, stenoses greater than 50% were demonstrated on follow-up angiography performed at 3 to 6 months after PTA. In the stent-treated group, no restenosis was encountered, although in one case acute occlusion of the stent occurred; the device was recanalized with PTA and infusion of tissue plasminogen activator. This case was the only one of the 24 in which any neurological deficits related to the endovascular procedure occurred. Stent placement brought a greater gain in diameter than did PTA at the initial and late follow-up period; this gain was statistically significant. CONCLUSIONS: Stent placement is more effective than PTA for stenosis of the petrous or cavernous portion of the ICA from the viewpoint of initial and late gain in diameter.     

Quantitative autoradiography of the rat brain vesicular monoamine transporter using the binding of [3H]dihydrotetrabenazine and 7-amino-8-[125I]iodoketanserin

The binding of [3H]dihydrotetrabenazine, a specific ligand of the monoamine transporter present on serotonin and catecholamine synaptic vesicles, was studied on rat brain sections. The characteristics of binding (Kd = 5.0 nM, k1 = 0.13 x 10(6) M-1 s-1; k-1 = 0.66 x 10(-3) s-1) were similar to those previously observed on tissue homogenates. The rostrocaudal topographical distribution of dihydrotetrabenazine binding sites was analysed by quantitative autoradiography. High labelling was observed in regions richly innervated by monoaminergic systems: dopamine in the striatum and olfactory tubercles, noradrenaline in the striatal fissure and in the paraventricular and dorsomedial hypothalamus and serotonin in the lateral septum, islands of Calleja and suprachiasmatic nucleus. Cell bodies were also labelled in the substantia nigra and ventral tegmental area (dopamine), in locus coeruleus (noradrenaline) and in raphe nucleus (serotonin). The pituitary gland (particularly the neural lobe) and the pineal gland were also labelled. Low labelling was observed in various areas of the cerebral cortex and in the cerebellum. Unilateral 6-hydroxydopamine lesion of the substantia nigra dramatically reduced [3H]dihydrotetrabenazine labelling in the ipsilateral striatum. Moreover, ketanserin has recently been shown to possess a nanomolar affinity for the vesicular monoamine transporter, and autoradiographic localization of brain monoaminergic synaptic vesicles was also obtained by means of the derivative 7-amino-8-[125I]iodoketanserin in the presence of 5-hydroxytryptamine2 and alpha 1 antagonists, although the non-specific labelling was higher than with [3H]dihydrotetrabenazine. It is concluded that [3H]dihydrotetrabenazine may represent a valuable monoaminergic marker in in vitro autoradiographic studies.     

Effects of forskolin on canine congestive heart failure

Forskolin is a diterpene of the labdane family which activates adenylate cyclase. The effects of forskolin were investigated in a congestive heart failure (CHF) model that we newly established using anesthetized dogs. The model was made by the intramural injection of protease into the left ventricular free wall, saline loading, and dextran and methoxamine infusion. By this maneuver, aortic blood flow (AoBF) was decreased; left atrial pressure (LAP), systemic vascular resistance (SVR) and left ventricular endodiastolic pressure (LVEDP) were markedly increased; and systemic blood pressure was unchanged. A bolus injection of 5.0 micrograms/kg forskolin reversed the hemodynamic findings of CHF. It reduced LAP (17.5----7.9 mmHg) (mean, N = 7), SVR (19980----10390 dyne sec/cm5), time constant T (90.7----59.2 msec) and LVEDP (22.8----16.8 mmHg); and it increased Vmax (2.32----2.82 l/sec) and AoBF (0.50----0.72 l/min). Forskolin improved the CHF mainly through its vasodilator and positive inotropic actions.     

Circulating thrombomodulin levels are related to latent progression of atherosclerosis in hypertensive patients.

The present study was designed to test the hypothesis that circulating levels of thrombomodulin are elevated in patients with hypertension in proportion to the severity of the vascular damage. A cross-sectional study was carried out using a population consisting of 96 patients with essential hypertension without clinically evident cardiovascular disease (mean age: 65 +/- 10 years) and 99 healthy normotensive control subjects (64 +/- 9 years). Blood was sampled and serum concentrations of soluble thrombomodulin were measured using an enzyme immunoassay method. We calculated the ratio of the concentration of thrombomodulin to that of creatinine, because soluble thrombomodulin is excreted by the kidney and the serum level of thrombomodulin was correlated with that of creatinine (p < 0.05). The association between the ratio and other clinical variables was investigated. The ratio of the thrombomodulin to creatinine concentrations was higher in hypertensive (29.3 +/- 10.9) than in control subjects (24.4 +/- 5.9; p < 0.0001). Systolic blood pressure was correlated with the ratio but the ratio showed no correlation with serum lipid levels when analyzed using data from all subjects. In hypertensive patients, the ratio correlated with the grade of sclerotic, but not hypertensive, changes in the fundus oculi (Scheie's classification, p < 0.001). Furthermore, the ratio correlated with brachial-ankle pulse wave velocity (p < 0.001). However, no correlation was detected between the ratio and blood pressure. These results suggest that circulating levels of thrombomodulin are elevated in hypertensive patients as compared to normotensive subjects and that the thrombomodulin level may be a molecular marker of the latent progression of atherosclerosis in hypertensive patients.     

Preoperative management of Cushing's syndrome with metyrapone for severe psychiatric disturbances

Abstract:   A 56-year-old woman suffered from severe depression due to Cushing's syndrome with right adrenal adenoma. She had a normal mental state before developing Cushing's syndrome. Because of her depressive state, informed consent for the treatment could not be obtained, and oral administration of 1.5 g/day metyrapone was commenced. After two weeks, her mental state had markedly improved. She subsequently underwent a right adrenalectomy, and metyrapone administration was terminated on the day of surgery. Without modification on the replacement of corticosteroids, the postoperative course was uneventful. Preoperative management of Cushing's syndrome with metyrapone may be useful in cases of severe psychiatric disturbances due to hypercortisolism.     

Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats

Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2–32 mg/kg IP) as well as idebenone (10–100 mg/kg IP) and physostigmine (0.1–0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems.