[Depot novadral as a prophylactic in circulatory collapse after epidural anesthesia].
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Hypotension in pregnancy represents an often underestimated danger for mother and fetus. Several investigators have described an increased incidence of miscarriages, premature delivery and small for date babies. In a first study 10 pregnant women with hypotension and severe orthostatic dysregulation were treated with norfenefrine hydrochloride (3 x 45 mg p. os/day). To investigate the effects of this therapy we monitored maternal blood pressure, subjective well being, CTG and furthermore fetal circulation by using pulsed doppler sonography. An average 4.2 days of treatment were required for complete alleviation of symptoms. Blood flow volume and resistance-index were determined for the fetal aorta descendens, and were found to be the same as in normal pregnancies. In addition no difference in fetal outcome was seen and there was no occurrence of premature contractions.
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We investigated the effects of the calcium entry blocker nimodipine on cerebral autoregulation, BBB, and vasogenic edema in animal experiments. In the first series of rats, ICBF was measured with H2 clearance using a balanced multiwire surface electrode. Variations in blood pressure (SAP), which was measured via femoral catheter, were induced by infusion of norfenefrine (pressure increase) and by hemorrhage (pressure decrease). The effect of SAP on the cerebral microcirculation was evaluated. In control animals receiving nimodipine, a typical autoregulation plateau was found. In rats treated with nimodipine infusion (12-14 micrograms/kg/min), 1CBF was considerably elevated at all blood pressure levels above 50 mm Hg, and in the steep 1CBF/SAP correlation, the autoregulation plateau was almost suspended. In a second series of randomized rats, the effect of nimodipine on BBB was investigated after Evans blue infusion. When a SAP of 180 mm Hg systolic was maintained for 6 min, a diffuse Evans blue staining was seen in 70% of the nimodipine animals (break-through of BBB). In the third series of rats, the effect of nimodipine on cold injury edema was investigated. Nimodipine (1 mg i.p.) considerably decreased the SAP; Edema formation measured by water and Na+ content 24 hr after trauma was then reduced. However, if the decrease in SAP was in part prevented by norfenefrine application, the rats receiving nimodipine developed significantly more edema. Brain water and sodium contents were markedly increased in both hemispheres. The results indicate an interference of nimodipine with cerebral autoregulation, and a BBB disruption may occur at lower SAP. If the BBB is impaired, nimodipine may considerably intensify edema formation. Nimodipine and similar calcium entry blockers should therefore only be used with caution in acute brain damage.
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We have attempted to trace the development of the concept which stresses that the encephalopathy often seen with hepatic failure may be the result of derangement in amino acid metabolism in patients with failing livers. We have also proposed that the infusion of solutions which may normalize these plasma amino acids and decrease the amount of toxic aromatic amino acids within the circulation may help in the amelioration of the symptoms of hepatic encephalopathy. We believe that in our studies to date, the use of this solution has been a significant advantage in the care of these extremely ill patients. We would hope that when the solution becomes generally available, the provision of such solutions to such patients will result in the salvage of some lives lost at the present time because of hepatic failure and encephalopathy.
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Vasopressors are often used to counteract hypotension induced by sympathetic blockade during epidural or spinal anaesthesia. This study contains data of invasive haemodynamic investigations following single-shot applications of different vasoconstrictor agents (Akrinor, etilefrine, ephedrin, norfenefrin, amezinium) during a combination of epidural block and controlled ventilation with oxygen and nitrous oxide. In a preceding dose finding study equipotent dosage of the substances used was confirmed. Usually bolus application of these vasopressors causes only a short-lasting circulatory stimulation, which does not cover the whole period of sympathetic blockade (exception: amezinium). Even small doses of drugs acting only upon alpha-receptors, may cause unwanted peripheral vasoconstriction and decrease of the already lowered cardiac output (example: norfenefrine). The rise of blood pressure after betamimetics may be delayed by an initial vascular beta 2 stimulation (example: etilefrine). In other sympathetic stimulants venoconstriction and therefore improvement of cardiac output by increase of preload takes place after an interval of some minutes to cardiac stimulation (example: ephedrin, Akrinor). Though the use of vasopressor agents during central blockade cannot be recommended in general, substances with alpha- as well as beta-stimulation should be preferred, if necessary. When using substances with short duration of action continuous infusion has to be taken into consideration.
The influence of different vasopressors (Akrinor, etilefrine, ephedrine, norfenefrine, ameziniummetilsulfate) on arterial perfusion pressure and oxygenator volume during extracorporeal circulation was compared to a control group. All substances led to an increase in perfusion pressure, thus demonstrating a direct influence on arterial vessels. The rise in arterial pressure after injection of ameziniummetilsulfate persisted during the investigation period, whereas norfenefrine led to a short-lasting, but massive increase. No rise in venous tone was noticed during the investigation period.
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The radioprotective effect (RPE) of some arylalkylamines (AAAs) was studied in experiments on mice. Mesaton and its close analogues were injected subcutaneously 15 minutes prior to irradiation at a dose of 800 rad. The protective effect is exerted by AAAs in low doses (25--50 mumole/kg), the compounds show stable and high RPE (80--80% survival, dose reduction factor being 1.3--1.4) and low toxicity (LD50 = 4--8 mumole/kg). AAAs studied are not less effective than aminothiols. Their pharmacological spectrum--K = LD50/ED50 (200--500) is superior to that of known aminothiols and indolylalkylamines.