Computer Aided Monitor-Data Processing (CAMP)

A computer aided monitor-data processing system (CAMP-System) was developed in order to get a consistent and comprehensive database which can very precisely reflect intra-operative haemodynamic courses. The goal of the present study was to introduce a new method to scan and to gauge haemodynamic courses and to demonstrate its superiority over the traditional way of data processing based on a handwritten anaesthesia protocol. Methods. The computerized system was applied to a study which was designed to investigate the influence of ketanserin (K) vs. urapidil (U) on haemodynamic stability during cardiac operations. Twenty male patients scheduled for myocardial revascularization received either 20 mg K or 30 mg U. Heart rate, central venous, arterial and pulmonary artery pressures were measured and on-line recorded every 20 seconds by the computer record system. In the handwritten protocol these variables were registered at eight pre-defined time points. Computerized data processing (including artifact depletion and data condensation) was compared to the results evaluated from the handwritten protocol. Results. While the only significant differences in the handwritten protocol were slightly higher values of pulmonary artery pressures in group K, the computer analysis revealed a number of further differences. Higher maximum and a less stable time course of HR in group K in the pre-bypass phase and lower mean and standard deviation of MAP during cardiopulmonary bypass. Conclusion. Computerized data processing including automatic artifact suppression and data condensation was able to reveal differences in the course of haemodynamic variables that cannot be detected in a conventional handwritten protocol.     

Absence of effects of ketanserin on renal prostacyclin and thromboxane A2 in essential hypertension

The anti-hypertensive effect of ketanserin, a new antagonist of 5-HT2-serotonergic receptors, was evaluated in 10 patients with uncomplicated essential hypertension. At the end of 2 weeks of placebo wash-out and following 2 and 4 weeks of treatment with ketanserin (20 mg twice daily), blood pressure and heart rate were measured both in the supine and standing position. In addition, before and at the end of treatment, plasma renin activity (PRA), plasma concentration of aldosterone and the nocturnal urinary excretion of 6-keto-PGF1 alpha and TXB2, the two metabolites that largely reflect the renal synthesis of prostacyclin and thromboxane, respectively, were determined. The study was carried out in a metabolic ward where the intake of sodium was adjusted to 100-120 mmol day-1. Ketanserin significantly reduced blood pressure both in the supine and standing position with no significant change of heart rate. The treatment did not produce any variation of PRA, aldosterone, urinary excretion of 6-keto-PGF1 alpha or TXB2. These results indicate that ketanserin reduces blood pressure without interfering with the renin-angiotensin-aldosterone system or the renal synthesis of prostacyclin and thromboxane.     

Effect of the acute sublingual administration of ketanserin in hypertensive patients

The purpose of this study has been to compare the acute antihypertensive effect of a dose of 20 mg of ketanserin in 18 patients after sublingual administration and in 19 after oral administration. In three patients ketanserin and ketanserin-ol plasma levels were measured after both sublingual and oral administration. The results showed a more rapid, considerable antihypertensive effect after sublingual administration. In addition, the high plasma levels of ketanserin-ol, the metabolite produced by hepatic reduction of ketanserin, reached after sublingual administration, rather than transmucosal absorption, indicate that the clinical effect observed is due to more rapid dissolution of the tablet formulation and liberation of the active drug.     

Effect of intravenous ketanserin on the human action potential duration at fixed heart rate

Summary In this study any changes in action potential duration or Q-T interval due to acute doses of ketanserin were monitored. The effect of a bolus dose (10 or 20 mg) followed by an infusion (10 or 20 mg over 20 minutes) of ketanserin on the Q-T interval and action potential duration was studied in six patients undergoing routine cardiac catheterization. Action potential duration was measured with a silver-silver chloride electrode catheter while heart rate was kept constant by atrial pacing and reflex effects avoided by -adrenergic blockade. There were some prolongations of the action potential duration but they were not in excess of 40 msec and did not reach statistical significance (control 263±46.0 msec; bolus 269±52.1 msec; infusion 262±53.6 msec; nor were there any significant changes in Q-T interval. Thus acute intravenous doses of ketanserin, in the absence of hypokalaemia or other Q-T interval-prolonging drugs, have no consistent effect on Q-T interval or action potential duration; prolongation of the action potential, when it occurs, is small.     

Effects of ketanserin on neuronal responses to serotonin in the prefrontal cortex, lateral geniculate and dorsal raphe nucleus

The ability of the putative serotonin2 (5-HT2) antagonist ketanserin, to alter serotonin (5-HT)-induced responses in cell firing was examined in the prefrontal cortex, the lateral geniculate nucleus and the dorsal raphe nucleus of the rat by microiontophoretic extracellular single unit recording techniques. In the prefrontal cortex, ketanserin failed to antagonize the inhibitory effects of 5-HT recorded in cerveau isolé or preparations anesthetized with chloral hydrate (pure excitatory responses to 5-HT were not observed in either of these preparations). Paradoxically, the inhibitory response produced by 5-HT (but not gamma-aminobutyric acid, tryptamine or norepinephrine) was potentiated, even in cells where ketanserin alone did not alter spontaneous firing rates. The systemic administration of ketanserin (5 mg/kg, i.p.) had effects similar to those observed in the microiontophoretic experiments in the prefrontal cortex. In the dorsal raphe nucleus of animals anesthetized with chloral hydrate, ketanserin neither attenuated nor potentiated the inhibition of serotonergic neurons by 5-HT. In the lateral geniculate nucleus, as in the prefrontal cortex, ketanserin potentiated rather than attenuated, the inhibitory effect of 5-HT. Ketanserin was found to attenuate the excitatory responses produced by norepinephrine, an alpha 1-adrenoceptor-mediated response, in the lateral geniculate nucleus. The observed potentiation by ketanserin of inhibitory responses to 5-HT but not those of gamma-aminobutyric acid, tryptamine or norepinephrine, recorded in the prefrontal cortex, may be consistent with the proposed interaction between ketanserin and a specific 5-HT2 binding site.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactions between the serotoninergic and noradrenergic systems of the brain and their role in the regulation of animal behavior

Studies were carried out using DBA/2 mice on the relationship between the behavioral effects of antagonists of different types of 5-HT receptors and the level of activity of α₂-adrenoceptors. The 5-HT_1c receptor antagonists mianserin (2 mg/kg) and cyproheptadine (2 mg/kg) and the 5-HT₂ receptor antagonist ketanserin (3 mg/kg) had no effect on movement activity, while the 5-HT₃ and 5-HT₄ receptor antagonists zacopride (1 mg/kg) and ICS 205-930 (1 mg/kg) reduced movement behavior in intact animals. On a background of treatment with the α₂-adrenoceptors blocker yohimbine (0.5 mg/kg), mianserin, cyproheptadine, and ketanserin inhibited movement activity and significantly reduced the sensitivity of animals to audiogenic convulsions. These data indicate that administration of α₂-adrenoceptors antagonists increases the efficiency with which serotonin receptors regulate behavior. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia; Department of Pharmacology, Scientific Health Center, University of Texas, San Antonio, USA. Translated from Fiziologicheskii Zhurnal im.I. M. Sechenova, Vol. 81, No. 8, pp. 101–103, August, 1995.     

Ketanserin降低清醒自发性高血压大鼠血压波动性的机理初探

应用计算机化清醒大鼠血流动力学测定技术，观察５－ＨＴ２受体阻滞剂Ｒｉｔａｎｓｅｒｉｎ（Ｒｉｔ）和α１受体阻滞剂哌唑嗪对清醒自发性高血压大鼠（ＳＨＲ）的血压、血压波动性（ＢＰＶ）和动脉压力感受性反射血压控制部分（ＡＢＲ－ＢＰ）的效应，旨在初步探讨兼具５－ＨＴ２受体和α１受体阻滞作用地新型抗高血压药Ｋｅｔａｎｓｅｒｉｎ降低ＢＰＶ的机制。结果表明：Ｒｉｔ对ＳＨＲ无降压作用，但侧脑室给药明显提高ＡＢＲ－Ｂ     

SEROTONIN ENHANCES SYMPATHETIC VASOCONSTRICTOR RESPONSES IN RAT ISOLATED PERFUSED TAIL ARTERY BY ACTIVATION OF POSTJUNCTIONAL SEROTONIN-2 RECEPTORS

1. The effects of serotonin and the selective serotonin-2 receptor antagonist ketanserin have been investigated on sympathetic vasoconstrictor responses in rat isolated perfused/superfused proximal tail artery segments. 2. Serotonin (6 nmol/l) markedly enhanced responses to low frequency, short duration electrical stimulation (0.1 ms pulses at 1 Hz for 10 s). 3. Serotonin (6 nmol/1) had a very slight (<10 mmHg) direct vasconstrictor effect. 4. Both the enhancing effect of serotonin on responses to electrical stimulation and the slight direct vasoconstrictor effect were blocked by ketanserin (3 nmol/l). 5. Ketanserin (3 nmol/l) had no significant effect on resting tone or on responses to electrical stimulation. 6. It is concluded that serotonin enhances sympathetic vasoconstrictor responses in rat tail artery by activation of postjunctional serotonin-2 receptors. Blockade of this effect by ketanserin is entirely consistent with its antihypertensive effect in vivo.     

Effect of ketanserin tartrate on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts

In man ketanserin tartrate reduces plasma LDL cholesterol. To clarify the mechanism of this effect the effect of ketanserin on 3-hydroxy-3-methylglutaryl (HMG) CoA reductase and LDL receptor activity in cultured human skin fibroblasts has been examined. After incubation with ketanserin for 14 h HMG CoA reductase activity was decreased in a dose-dependent manner up to 300 ng/ml (550 nM) without changing the free cholesterol content in the cells. Ketanserin increased specific binding and specific internalization of 125I-LDL dose-dependently. There was a significant inverse relationship between the percentage changes in HMG CoA reductase and LDL receptor activity. It appears that ketanserin induces up-regulation of LDL receptor activity by direct suppression of HMG CoA reductase, and this may be one mechanism by which plasma LDL-cholesterol is reduced by ketanserin.     

The effect of ketanserin upon postoperative blood pressure, cerebral blood flow and oxygen metabolism in patients subjected to craniotomy for cerebral tumours

Hypertension and cerebral hyperperfusion are often seen in the immediate postoperative period after craniotomy for supratentorial tunours. This study was performed to evaluate the effect of ketanserin, given at the end of the peroperative period, upon cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO₂) before extubation. Mean arterial blood pressure (MABP), cerebral arterio-venous oxygen content difference (AVDO₂), PaO₂, and PaCO₂ were repeatedly measured during the operation, and 180 minutes after extubation. Ten patients were included in this study. The results were compared to those from a recent study in which ten patients served as control. All patients were anaesthetized with thiopentone, fentanyl, nitrous oxide 67%, halo-thane 0.5% anesthesia. Ten patients were given ketanserin 10–20 mg (mean 18,5 mg) before extubation. There was no significant difference in CBF- and CMRO₂ values between the two groups. During the period between closure of the dura and 5 minutes after extubation, an increase in MABP was observed in the control group ( P <0.05) but not in the ketanserin group. During the same period, a decrease in AVDO₂ was observed in both groups ( P <0.05) and during the next 10 minutes an increase was observed. However, no difference in AVDO₂ values between the two groups was found.
These findings suggest that peroperative treatment with ketanserin reduces postoperative hypertension without influencing the cerebral blood flow or metabolism.