[Effect of anoxia, flow-stop and cardioplegic solutions on the liberation of noradrenaline from the isolated rabbit heart in comparison to clinical findings]. / Einfluss von Anoxie, Flow-Stop und cardioplegischen Lösungen auf die Freisetzung von Noradrenalin aus isolierten Kaninchenherzen im Vergleich zu klinischen Befunden.

Experiments with isolated hearts. The results include the effects of anoxia, flow-stop and cardioplegic solutions (CPL) on the efflux of noradrenaline (NA) from isolated rabbit hearts preperfused with 3H-noradrenaline. 1.) Anoxic Tyrode solution did not enhance 3H-NA efflux into the perfusion medium. 2.) 3H-NA efflux was greatly enhanced after a flow-stop period of 20 min in normothermia (34 degrees C), but only to a small amount after a flow-stop period of 30 min in hypothermia (10 degrees C). 3.) In flow-stop experiments in hypothermia all CPL solutions enhanced the 3H-NA efflux. This effect is due to sodium deprivation (most CPL) or to high potassium concentration.--Studies on cardiosurgical patients. NA-concentration was determined in blood samples from vena cava superior (zv), radial artery (art) and coronary sinus (cv). 1.) cv NA-level continuously rose from 0.27 ng/ml after induction of anaesthesia to 0.77 ng/ml at onset of complete extracorporeal circulation. 2.) In 19 patients cardioplegia was induced by CPL HTP Bretschneider. Immediately after the cardioplegic period art und cv samples were collected at short intervals. NA-concentrations were not elevated in cv samples. 3.) An increase of NA in cv blood was distinct in two patients with extremely long periods of cardioplegia. In summary, after perfusion of isolated rabbit hearts with hypothermic CPL and subsequent flow-stop, an enhanced NA efflux is evident during reperfusion with Tyrode's solution. The effect of CPL on the NA release seems of minor importance in patients undergoing cardiosurgical procedures.

[Presynaptic receptor systems in central noradrenergic neurons]. / Präsynaptische Rezeptor-Systeme an zentralen noradrenergen Neuronen.

Slices of rat occipital cortex, hypothalamus or cerebellar cortex were stimulated either electrically or by high potassium (in few experiments by tyramine). 1. Electrical or potassium stimulation elicit physiologically noradrenaline release in contrast to tyramine. 2. Stimulation-induced overflow of tritium, reflecting noradrenaline release, was diminished by a) alpha-adrenoceptor agonists, b) morphine and enkephaline, c) prostaglandin E1. The effect of agonists was abolished only by specific antagonists. Metabolism of 3H-noradrenaline was unchanged. 3. It is concluded that transmitter release from the noradrenergic neurones of several brain areas is modulated by drugs acting on alpha-adrenoceptors, opiate receptors and prostaglandin receptors. In contrast to other tissues there was no evidence obtained for presynaptic dopamine, beta-, muscarine, nicotine and angiotensin receptors. It seems likely that the receptors, involved in the modulation of noradrenaline release, are located at the noradrenergic nerve ending themselves, i.e. that they are presynaptic receptors.

[Vena cava superior thrombosis following placement of internal jugular vein catheter (author's transl)]. / Vena cava superior Thrombose nach Anlegen eines Jugularis interna Katheters.

Internal jugular vein puncture is suggested to be the safest route for placement of central venous catheter. One advantage is the lack of ensuing thrombosis. However, the case described demonstrates the occurrence of this complication. A 72-year old female developed severe thrombosis of the vena cava superior 5 days after placement of an internal jugular vein catheter. Thrombectomy was successfully performed during extracorporal circulation.

[Opiate receptors and endorphines (author's transl)]. / Opiatrezeptoren und Endorphine.

Recent progress in narcotic drug research is briefly reviewed. Several investigators were able, independently to identify stereospecific opiate receptors, which mediate the specific effects of narcotic analgesics. A possible physiological importance of opiate receptors is likely, since endogenous ligands could be detected. Especially from brain and from pituitary glands of several species, quite a number of peptides with morphine-like effects could be isolated. The chemical structure of some of these endorphines could be analyzed. Endorphines are suggested to be involved in pain perception, electroanalgesia, acupuncture analgesia, psychiatric disorders, synthesis and release of pituitary hormones.

[Anaesthesiological problems in donor-nephrectomie and kidney transplantation (author's transl)]. / Anästhesiologische Gesichtspunkte bei der Entnahme von Spendernieren und bei Nierentransplantation.

The quality of cadaver renal homografts is not at least dependent on the anaesthesiological management. The latter should include artificial ventilation with oxygen, correction of acidosis, abundant infusion of iso- and hyperosmolar solutions, phenoxybenzamine infusion, heparin i.v. Preoperative disorders and anaesthesiological problems in patients undergoing renal transplantation are discussed. Neuroleptanalgesia was performed in all 112 patients.

Presynaptic receptor systems on the noradrenergic neurones of the rabbit pulmonary artery.

A search was performed for presynaptic, release-modulating receptor systems on the post-ganglionic sympathetic nerves of rabbit pulmonary artery. Strips of the artery were preincubated with (-)-3H-noradrenaline and then superfused and stimulated transmurally. 1. Tetrodotoxin, guanethidine, and omission of calcium all suppressed the stimulation-evoked overflow of tritium, thus confirming selective release from noradrenergic neurones. 49% of the stimulation-evoked overflow of total consisted of 3H-noradrenaline, 22% of 3H-3,4-dihydroxyphenyglycol (DOPEG), and 9% of 3H-normetanephrine. Cocaine virtually abolished the evoked overflow of 3H-DOPEG; further addition of corticosterone also abolished that of 3H-normetanephrine. In the presence of cocaine plus corticosterone, unmetabolized 3H-noradrenaline accounted for 86% of the stimulation-evoked overflow of total tritium. The overflow evoked per pulse was 2.2 X 10(-5) of the tritium content of the tissue (1 Hz); it increased 2-fold when the frequency was raised to 8 Hz. 2. Presynaptic alpha-adrenoceptors have previously been demonstrated in this tissue (Starke et al., 1975b). High concentrations of isoprenaline reduced the stimulation-evoked overflow of tritium, presumably by alpha-adrenergic inhibiton. No presynaptic effect of up to 10(-5) M normetanephrine and metanephrine was found. 3. Dopamine slightly diminished the stimulation-evoked overflow of tritium, but only at 100 times the inhibitory threshold concentration of noradrenaline (which is 10(-8) M; Starke et al., 1975b), probably through activation of presynaptic alpha-adrenoceptors. Apomorphine failed to reduce the evoked overflow whether the superfusion medium contained cocaine and corticosterone or not. 4. Isoprenaline (10(-9) -10(-6) M) did not change the evoked overflow whether the medium contained cocaine and corticosterone or not, and whether the frequency was 1 or 2 Hz. Propranolol also had no effect. 5. Angiotensin II increased the stimulation-evoked overflow both in the absence and in the presence of cocaine and corticosterone. Equieffective concentrations of angiotensin I were 10 times higher. Saralasin had no effect, whereas 1-Sar,8-Ile-angiotensin produced a small increase. Both of the latter peptides behaved as presynaptic antagonists of angiotensin II. A presynaptically supramaximal concentration of the alpha-adrenergic agonist oxymetazoline prevented the facilitatory action of yohimbine, but not that of angiotensin II. Separation of 3H-compounds showed that angiotensin II caused a proportionate increase in stimulation-evoked overflow of 3H-noradrenaline, 3H-DOPEG, and 3H-normetanephrine; this finding rules out any inhibition of noradrenaline uptake mechanisms. 6. 10(-4) -10(-3) M acetylcholine caused hexamethonium-sensitive acceleration of basal tritium outflow. Much lower concentrations (10(-7) M and higher) reduced the overflow evoked by electrical stimulation. The evoked overflow of 3H-noradrenaline, 3H-DOPEG, and 3H-normetanephrine was proportionately decreased...

Enkephalin: a potential modulator of noradrenaline release in rat brain.

In slices of rat occipital cortex preincubated with 3H-noradrenaline, methioine-enkephalin diminished the overflow of tritium evoked by electrical field stimulation or by 20 mM potassium. The effect was not modified by phentolamine, but was antagonized by naloxone. Giver alone, naloxone slightly increased the potassium-evoked overflow. It is concluded that enkephalin reduces transmitter release from cerebrocortical noradrenergic nerve endings. One-function of endogenous opiate receptor ligands may be presynaptic inhibition of central noradrenergic transmission.

Relative pre- and postsynaptic potencies of alpha-adrenoceptor agonists in the rabbit pulmonary artery.

The rabbit pulmonary artery contains postsynaptic alpha-adrenoceptors which meidate smooth muscle contraction; its noradrenergic nerves contain presynaptic alpha-adrenoceptors which mediate inhibition of the release of the transmitter evoked by nerve impulses. Dose-response curves for the pre- and postsynaptic effects of eight alpha-receptor agonists were determined on superfused strips of the artery in the presence of cocaine, corticosterone and propranolo. 1. According to the concentrations which caused 20% of the maximal contraction (EC20 post), the postsynaptic rank order of potency was: adrenaline greater than noradrenaline greater than oxymetazoline greater than naphazoline greater than phenylephrine greater than tramazoline greater than alpha-methylnoradrenaline greater than methoxamine. The pA2 values of phentolamine againstoxymethazoline, phenylephrine, alpha-methylnoradrenaline and methoxamine were 7.43, 7.48, 7.59 and 7.69, respectively. 2. For the investigation of presynaptic effects, the arteries were preincubated with 3H-noradrenaline. All agonists inhibited the overflow of tritium evoked by transmural sympathetic nerve stimulation. According to the concentrations which reduced the stimulation-induced overflow by 20% (EC20 pre), the rank order of potency was: adrenaline greater than oxymetazoline greater than tramazoline greater than alpha-methylnoradrenaline greater than noradrenaline greater than naphazoline greater than phenylephrine greater than methoxamine. 10(-5) M phentolamine shifted the presynaptic dose-response curves for moradrenaline and oxymethazoline to the right. 3. The ratio EC20 pre/EC20 post was calculated for each agonist as an index of its relative post- and presynaptic potency. According to the ratios, the agonists were arbitrarily classified into three groups. Group 1 (ratio about 30: preferentially postsynaptic agonists) comprised methoxamine and phenylephrine; group 2 (ratio near 1; similar pre- and postsynaptic potencies) comprised noradrenaline, adrenaline and naphazoline; group 3 (ratio below 0.2; preferentially presynaptic agonists) comprised oxymetazoline, alpha-methylnoradrenaline and tramazoline (as well as clonidine). 4. Preferentially presynaptic and preferentially postsynaptic agonists had opposite effects on the basoconstrictor response to nerve stimulation. Methoxamine and phenylephrine either did not change or enhanced, but never reduced, the response. In contrast, oxymetazoline, alpha-methylnoradrenaline and tramazoline at low concentrations selectively inhibited the response to stimulation at low frequency (0.25-2Hz). 5. It is concluded that alpha-adrenoceptor agonists vary widely in their relative pre- and postsynaptic potencies, possibly because of structural differences between pre- and postsynaptic alpha-receptors. Pre- and postsynaptic components contribute to their overll postsynaptic effec in actively transmitting synapses. The preferential activation of presynaptic alpha-receptors results in alpha-adrenergic inhibition of synaptic transmission.

Phencyclidine and ketamine: comparison with the effect of cocaine on the noradrenergic neurones of the rat brain cortex.

In slices of rat occipital cortex, the influence of phencyclidine and ketamine on the accumulation of 3H-noradrenaline and the subsequent outflow of tritium was investigated, and was compared with the effect of cocaine.--All three drugs inhibited the accumulation of tritium during incubation of the slices with 3H-noradrenaline. Phencyclidine was slightly, whereas ketamine was much less effective than cocaine.--All three drugs accelerated the spontaneous outflow of tritium from slices preincubated with 3H-noradrenaline. The acceleration caused by low concentrations probably reflects an inhibition of the re-uptake of spontaneously released 3H-noradrenaline; in addition, high concentrations (10(-4) M phencyclidine, 3 X 10(-4)-10(-3) M cocaine and 10(-3)-3 X 10(-3) M ketamine) appear to release tritiated compounds from the neurones. The distance between uptake-inhibiting and releasing concentrations was much greater for cocaine than for phencyclidine and ketamine.--All three drugs enhanced the overflow of tritium evoked by electrical field stimulation. The increase probably reflects an inhibition of the re-uptake of released 3H-noradrenaline; in addition, phencyclidine appears to enhance the release of noradrenaline per pulse.--The actions of phencyclidine and ketamine on central noradrenergic neurones may contribute to the characteristic psychotropic side-effects of these general anaesthetics.

Morphine tolerance and dependence in noradrenaline neurones of the rat cerebral cortex.

By subcutaneous implantation of 2 or 13 morphine pellets (75 mg morphine/pellet), rats were made tolerant to, and dependent on narcotic analgesics. Occipital cortex slices from dependent animals and placebo-implanted controls were incubated with (-)-3H-noradrenaline and subsequently superfused with physiological salt solution. The accumulation of 3H-noradrenaline was not changed by pretreatment with 2, but was slightly decreased by pretreatment with 13 morphine pellets. The overflow of tritium evoked by electrical field stimulation was higher in slices from morphine-implanted rats than in those from placebo controls. Morphine and levorphanol, added in vitro, inhibited the stimulation-induced overflow of tritium at similar concentrations and to a similar degree in slices from morphineand placebo-pretreated animals.--It is concluded that, during chronic treatment with morphine, an adaptation takes place in the brain to compensate for the acute effect of narcotic analgesics, i.e. inhibition of the release of noradrenaline by nerve impulses. The chain of events from the drug-receptor interaction to the depression of the release process can be escluded as substrate of this adaptation. During withdrawal, the compensatory changes provoke an enhanced increase of extracellular noradrenaline during nerve impulses.

Influence of morphine and naloxone on the release of noradrenaline from rat cerebellar cortex slices.

In slices of rat cerebellar cortex preincubated with (-)-3H-noradrenaline, the influence of morphine and naloxone on the efflux of tritium was investigated. The spontaneous outflow was not changed by 10(-5) M of either morphine or naloxone. On the other hand, morphine caused a concentration-dependent decrease of the overflow of tritium evoked by electrical field stimulation. Naloxone did not change the stimulation-induced overflow, but prevented its inhibition by morphine. It is concluded that morphine, through an action on opiate receptors located on cerebellar noradrenergic neurones, inhibits the secretion of the transmitter in response to nerve impulses.