Preventive effects of phenoxybenzamine on nitrous oxide-induced reproductive toxicity in Sprague-Dawley rats

In previous studies, we have shown that the reproductive toxicity of N2O in rats is prevented by the co-administration of either halothane or isoflurane, whereas treatment with folinic acid, which should reverse the effects of N2O on DNA production, does not prevent toxicity. These results cast doubt on the commonly held theory that inactivation of methionine synthase is the sole cause of N2O-induced reproductive toxicity, and suggest the need for other hypotheses. One such possibility is that N2O causes adverse reproductive toxicity secondary to its sympathomimetic effects. As a first step to test this theory, we studied the effects of phenoxybenzamine (PX), an alpha-1 adrenergic antagonist, on N2O-induced reproductive toxicity using a well-established in vivo rat model. On day 8 of gestation (plug day = day 0), 130 timed-pregnant Sprague-Dawley rats were injected s.c. with either 0.5 ml of either 0.9% saline (control and N2O alone groups) or PX (0.5, 5, or 50 micrograms/kg) in 0.9% saline, the latter the maximum tolerated PX dose. They were then exposed to either air (control) or 60% N2O for 24 hours (all other groups). On day 20 of gestation, cesarean sections were performed and the fetuses were removed and examined for either visceral of skeletal abnormalities. Compared with control, treatment with N2O alone resulted in increased incidences of fetal resorptions, major and minor visceral abnormalities, and minor skeletal abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physical activity in acute cerebrovascular insufficiency]

It was noted that physical activity of 1052 patients hospitalized for the acute cerebral flow failure due to atheromatosis is an important indicator of the cerebral ischemia. Extension of ischemia evaluated on the basis of physical activity enables to foresee possible improvement and survival. Authors' own classification of physical activity may be helpful in the monitoring of cerebral flow failure therapy.     

Effect of ornid on the regulation of cerebrovascular circulation]

An investigation of ornid, using radioisotopic, electromagnetic and resistographic methods, has shown the drug to diminish cerebral circulation and to abolish completely the constriction of the brain vessels induced by stimulation of the sympathetic and somatic nerves. Ornid prevented the development of experimental disturbances of the cerebral circulation of adrenergic nature.     

Affinity labelling of alpha-adrenoceptors in intact liver cells by [3H]phenoxybenzamine.

[³H]phenoxybenzamine of high specific activity (5.3 Ci/mmol) was synthesized and its binding to isolated, viable rat liver cells was studied. Phentolamine suppressible binding of [³H]phenoxybenzamine was irreversible and saturable (EC50: 10 nM, b_max: 200 fmol/mg wet cell weight). Competition-inhibition studies showed structural and stereoselectivity compatible with α-receptors. The IC50 of unlabelled phenoxybenzamine to reduce specific binding (9 nM) or to block adrenaline-induced phosphorylase activation in the same cells (2 nM) was similar, whereas the IC50 of agonists to suppress binding was higher than their EC50's for phosphorylase activation. The results represent the first example of labelling α-adrenoceptors in intact liver cells. The sites labelled by [³H]phenoxybenzamine mediate the block of phosphorylase activation by α-adrenoceptor antagonists. However, the relationship of these sites to receptors that mediate responses to physiological, low concentrations of catecholamines remains to be clarified.     

Prevention of cerebrovascular disorders with adrenergic substances]

The author suggests an experimental model of cerebrovascular disorders of the neurogenic (adrenergic) nature following the administration of KCl into the lateral ventricles of the brain of cats or dogs. Surgical desympathization considerably reduced the spasms of the cerebral vessels caused by the central effect of KCl. Dihydroergotoxin, phenoxybenzamine, tropaphene, guanethidine and nialamide produced both the therapeutic and the prophylactic influence under the mentioned experimental disorders of the cerebral circulation.     

Effect of phenoxybenzamine, propranolol and guanethidine after repeated administration on nutritional blood flow in rats]

In anesthetized rats, after i.p. treatment during 4 days: phenoxybenzamine and guanethidine were hypotensive and increased nutritional blood flow in squeletal muscles; propranolol had a poor hypotensive effect and decreased nutritional circulation in heart, skin and intestine.     

Cost of the treatment of acute cerebrovascular insufficiency causing cerebral infarction]

Many countries are interested in the cost of therapy of the acute cerebral flow insufficiency leading to brain infarction. Total costs include: drugs, laboratory tests, nursing care, the cost of patients' food, equipment, amortization, hospital administration etc. The total expenditure for a 10-15-day treatment of the acute neurological incident depended on the severity of the disease and was 8 million ++ z?oty in case of mildly ill patient, 9 million in case of moderately severe disease, and 21 million z?oty in case of severely ill patient. If the costs of such tests as CT and TCD-scanning will be added, total cost will increase significantly.     

Effect of phenoxybenzamine on luteinizing hormone release in the female rat

To clarify the mode of action of phenoxybenzamine, an alpha adrenergic blocking agent, its effects upon plasma LH levels in ovariectomized rats and upon the ovulatory LH surge expected between 1400 and 1600, the critical period, on the day of proestrus in normal rats were studied. A single injection of phenoxybenzamine, 20 mg/kg, given at 1300 on the day of proestrus bokced ovulation (1 out of 7 ovulating), while plasma LH did not differ from controls between 1500 and 1600. An additional injection of 20 iu HCG at 1500 prevented the ovulation block (83% ovulating). A single phenoxybenzamine injection at 1700 failed to prevent ovulation (5 out of 7 ovulating). The beta adrenergic blocking agents, propanolol and MJ 1999, did not affect ovulation. Treatment with phenoxybenzamine for 2 days, 20mg/kg/day, for 8 days, 10mg/kg/day, were did not prevent the rise causing a reduction in blood flow through the ovary rather than acting as a neurogenic stimulus in the hypothalamus.     

NMR simulation analysis of statistical effects on quantifying cerebrovascular parameters

Determining tissue structure and composition from the behavior of the NMR transverse relaxation during free induction decay and spin echo formation has seen significant advances in recent years. In particular, the ability to quantify cerebrovascular network parameters such as blood volume and deoxyhemoglobin concentration from the NMR signal dephasing has seen intense focus. Analytical models have been described, based on statistical averaging of randomly oriented cylinders in both the static and slow diffusion regimes. However, the error in estimates obtained from these models when applied to systems in which the statistical assumptions of many, randomly oriented perturbers are violated has not been systematically investigated. Using a deterministic simulation that can include diffusion, we find that the error in estimated venous blood volume fraction and deoxyhemoglobin concentration obtained using a static dephasing regime statistical model is inversely related to the square root of number of blood vessels. The most important implication of this is that the minimum imaging resolution for accurate deoxyhemoglobin and blood volume estimation is not bound by hardware limitations, but rather by the underlying tissue structure.     

Naloxone antagonism of phenoxybenzamine antinociception in the mouse tail stimulation test.

Phenoxybenzamine was antinociceptive in the mouse tail electrical stimulation assay (ED50, 36.8 mg/kg) with a peak effect at $\text{2}\text{1}\text{2}$ hours after subcutaneous injection. Naloxone antagonized this antinociception action of phenoxybenzamine in a dose-related manner. Dose-ratio analysis of naloxone's antagonism of phenoxybenzamine antinociception gave a pA₂ value of 6.15, similar to that found for the benzomorphinan mixed agonist-antagonists. This is in agreement with the sodium response ratio found for phenoxybenzamine, 4.3, in $\text{in vitro}$ assays of phenoxybenzamine inhibition of ³H-naloxone binding to mouse brain homogenate (5). These findings suggest that phenoxybenzamine binds to the opiate receptor both $\text{in vivo}$ as well as $\text{in vitro}$ in a manner similar to the mixed agonist-antagonists.     

Effect of phenoxybenzamine on mesenteric blood flow in irradiated rats

Reactivity of the superior mesenteric artery has been studied in rat Wistar by infusion of biogenic amines (noradrénaline, dopamine, serotonin, acetylcholine and histamine) in presence of phenoxybenzamine. A decrease in reactivity of the post-synaptic alpha receptor located on the mesenteric vascular smooth muscle cell was seen three days after irradiation by 2 Kr.     

Liver blood flow during haemorrhagic shock in the dog treated with phenoxybenzamine

The liver blood flow has been extensively studied in hemorrhagic shock, but considerable disagreement exists as to the nature of hemodynamic changes and their controlling mechanism. The present investigation was undertaken in order to determine the effects of hemorrhage and phenoxybenzamine (PBZ) on the participation of hepatic artery (HAF) and portal vein flow (PVF) in total liver blood flow (LBF) changes. The dynamics of LBF (H2 washout method), HAF and PVF (electromagnetic flowmeter) during 3-hours posthemorrhagic hypotension (90 min. = 50-60 mmHg; 90 min. = 25-30 mmHg) and one-hour postretransfusion period were investigated on 20 mongrel dogs under chloralose anesthesia. All animals were divided into 2 groups (control and PBZ-treated--5 mg/kg b.w. 30 minutes following first bleeding). Half an hour following bleeding there occurred a significant decrease of LBF (P less than 0.001) in dogs of both experimental groups. This degree of decrease was due to equal decrease in the PVF and HAF. The infusion of PBZ caused a slight tendency towards increase of LBF, while the subsequent decrease in blood flow values during second hypotensive period in the treated dogs was not so pronounced as in the untreated dogs. Although retransfusion led to an increase of LBF, HAF and PVF in both groups, the restauration was significantly better in PBZ-treated animals. The degree of metabolic acidosis was more pronounced in the untreated dogs than in PBZ-treated.     

A new model of computerized encephalovolumeter for monitoring of acute cerebrovascular insufficiency]

A new model of the computerized encephalovolumeter (EVM.IR) is presented. Infrared light is used as an information carrier enabling to follow the dynamics of intracerebral equilibrium and blood flow disorders. The authors suggest that this model would help clinical examination in the acute cerebral flow failure, and increase better evaluation of the efficiency of drugs improving cerebral blood flow. It should also help to foresee the outcome and prognosis. A new model of EVM.IR and its programs require further constructional and experimental studies before the routine use at ICUs.     

Respiratory effects of PGI-2 in the pig]

In anaesthetised pig the intravenous perfusion of 2 micrograms/Kg/min/4 min of PGI2 induces within 30' respiratory changes that spontaneously disappear after perfusion. The PGI2 induces a decrease of respiratory frequency while total pulmonary resistance increases significantly. This changes of pattern of breathing are correlated to tonus of vagus nerve and after vagosimpathectomy are not present. The relationship of tidal volume/frequency has been evaluated according to the blood pressure variation.