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Biomedical subjects

L Malmberg

Publications and source records attributed to L Malmberg.

34 records · Page 2Linked to original sources

Transient supersensitivity in the hypertrophied rat urinary bladder.

The presence of a paraffin bolus intravesically for 1 or 4 weeks was accompanied by an approximate three-fold increase in bladder weight. A supersensitivity to methacholine was demonstrated in these hypertrophied bladders at 1 week but not at 4 weeks. At the earlier time of observation, the contractile responses in vitro to nerve stimulation were reduced, while at the later time of observation the responses were the same as those of controls; the atropine-sensitive fraction of the response was entirely responsible for the recovery. The concentration of choline acetyltransferase, indicating cholinergic nerve density and initially reduced by about 50%, rose in course of time. It is suggested that in the beginning of the experimental period, the muscle cells of the hypertrophied bladders in situ are exposed to 'subnormal' transmitter concentration. An extension of the field of innervation of the cholinergic nerves may explain the disappearance of the supersensitivity.

Animals↗

Disuse as cause of supersensitivity in the rat urinary bladder.

Ureterostomia in situ was performed to reduce the nervous reflex activation of the bladders without concomitant hypertrophy. In muscle strips of these disused and non-hypertrophied bladders, supersensitivity to methacholine was demonstrated, which did not increase between 1 and 3 weeks. The supersensitivity did not increase further by combining urinary diversion with section of the preganglionic bladder nerves (decentralization). From the present results it may be concluded that in decentralized and hypertrophied bladders not only hypertrophy per se, previously studied (Ekström et al. 1985), but also loss of nerve impulse traffic (cf. urinary diversion) contribute to the development of supersensitivity.

Animals↗

Unilateral denervation of the rat urinary bladder and reinnervation: a predominance for ipsilateral changes.

Unilateral removal of the pelvic ganglion affected the bladder-half on the denervated side more profoundly than that on the non-denervated side. At an early stage (3-7 days) the former was heavier, had a lower choline acetyltransferase activity, developed less tension to nerve stimulation and, in course of time, became more sensitized to methacholine in vitro than the latter. At a late stage (30-60 days) the nerve-evoked contractile responses on the denervated side had increased, which was almost wholly attributed to the atropine-sensitive part of the contraction, but the recovery was not complete. On the non-denervated side the nerve-evoked responses were not significantly changed. It was calculated that in the normally innervated bladders 25-30% of the cholinergic nerves of each half were of contralateral origin. The figure was lower (18%) for the nerves mediating the atropine-resistant response.

Animals↗

Supersensitivity to methacholine in rat urethra following hypertrophy or disuse.

It has been possible to sensitize the rat urethra without cutting its nerves. This was achieved by hypertrophy or disuse. Hypertrophy of the urethra (2-4-fold weight increase) was caused by the presence of an intraluminal paraffin bolus. Disuse was caused by diverting the flow of urine from the lower urinary tract. When examined in vitro after an experimental period of 1 to 4 weeks the EC50 value of the parasympathomimetic drug methacholine was in both cases half of that of controls. The common cause of the development of supersensitivity in the two types of experiments is thought to be decreases in the local concentration of transmitter at the muscle cells. The present findings favour the idea of a parasympathetic motor control of the rat urethra.

Animals↗

On a cholinergic motor innervation of the rat urethra.

Choline acetyltransferase activity was demonstrated in the proximal part of the male rat urethra, indicating a cholinergic innervation of this tissue. The cholinergic nerve fibres emanated evidently from the pelvic nerves, since bilateral removal of the pelvic ganglion caused a major fall in the activity of this enzyme. The muscle activity of the circular layer of the proximal urethra was recorded in vitro. The basal activity of this segment was low. The parasympathomimetics acetylcholine and methacholine, evoked rapid and marked contractile responses; the maximal responses to these drugs were 36 and 44%, respectively, of that to potassium. The corresponding figures for phenylephrine and noradrenaline were found to be 79 and 88%, respectively. The responses evoked by the parasympathomimetics were unaffected by the ganglion blocker hexamethonium, the alpha-adrenoceptor blocker dihydroergotamine and the beta-adrenoceptor blocker propranolol. Atropine, however, abolished the responses completely. Following degeneration of adrenergic or cholinergic nerves of the urethra the parasympathomimetics still evoked contractions. Taken together these findings indicate that the parasympathomimetics exert their contractile effect through a direct action on muscarinic receptors. Parasympathectomy but not sympathectomy (caused by 6-hydroxydopamine treatment) gave rise to a supersensitivity to methacholine, as judged by a leftward shift of the dose-response curve for this drug, the ED50-value being ten times less than that of the controls. The observations seem to suggest that the proximal urethra normally is under the influence of cholinergic activity beside that of adrenergic activity previously demonstrated.

Animals↗

Force development in muscle strips of the disused and nondistended rat urinary bladder.

In rats the flow of urine was diverted from the bladder over a period of 7-10 days. Active length-tension curves of muscle strips of such disused bladders did not differ from those of controls, provided lengths were related to optimum length for force development. When, however, lengths were related to length in situ the active length-tension curves were shifted to the left. The muscle strips of the disused bladders showed a higher degree of stiffness than those of controls. The present findings are related to previous ones made on disused but distended bladders showing changes in the opposite direction. Taken together they demonstrate the importance of filling and periodic emptying for the preservation of normal length-tension relations in the bladder.

Animals↗

Functional evidence for sprouting or decentralized parasympathetic neurons in rat urinary bladder.

The pelvic nerve, carrying parasympathetic nerve fibres, distributes bilaterally in the rat urinary bladder. Preganglionic parasympathetic denervation (decentralization) on one side and postganglionic parasympathetic denervation on the other are followed by an initial decrease in acetylcholine forming capacity and in number of acetylcholinesterase positive nerves in the bladder. However, within a few weeks a marked recovery in acetylcholine synthesis and in number of nerves, based on collateral sprouting, occurs. In this study muscle strips of the rat urinary bladder exposed to the combined surgical procedure was studied. The strips were taken from "denervated" and "decentralized" halves of the bladder. Their contractile responses to methacholine and transmural electrical field stimulation were isometrically recorded in vitro. A supersensitivity to methacholine was found to have developed, of about the same degree, in the two halves 1 week postoperatively. In the denervated halves 4 weeks postoperatively, the supersensitivity was even more marked, whereas in the decentralized halves it tended to be less than after 1 week. The responses of denervated halves to electrical stimulation were reduced 1 week postoperatively. This was also the case for decentralized halves, although the reduction was not large enough to be significant. When examined 4 weeks postoperatively the responses, in particular in denervated halves, were enlarged compared to those 1 week postoperatively. The atropine-sensitive portion of the responses increased with time. Increases in contractile responses to electrical stimulation accompanied by a tendency to desensitization to methacholine are taken as functional evidence for outgrowth of decentralized parasympathetic neurones in the decentralized halves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hyperplasia and hypertrophia in the denervated and distended rat urinary bladder.

The parasympathetically denervated and distended rat urinary bladder was found to have increased fourfold in weight when examined 3 weeks postoperatively. Both in muscularis and mucosa of such a bladder the synthesis of proteins, RNA and DNA was increased severalfold. An increase in the polyamines putrescine, spermidine and spermine was also found; these polyamines are usually linked to protein synthesis. The results suggest that the cells of the two layers increase both in size and number. Hyperplasia was, in a previous study, suggested as a possible explanation for a right-ward shift of the active length-tension curve of muscle strips in the denervated rat urinary bladder.

Animals↗

Development of supersensitivity to methacholine in the rat detrusor following either parasympathetic denervation or decentralization.

The male rat urinary bladder belongs to those few structures where both the post- and preganglionic parasympathetic nerves are accessible for severance. In the present study the sensitivity to the parasympathomimetic drug methacholine of muscle strips of either denervated or decentralized bladders was examined in vitro. One week postoperatively denervated and decentralized bladders were sensitized to the same degree, the ED50 values being 4 times less than ED50 of unoperated control bladders. In contrast to the decentralized bladders the supersensitivity in the denervated ones was found to have increased further when tested four weeks postoperatively, the ED50 value being about 20 times less than that of controls. The present findings are in agreement with Cannon's "law of denervation". The results are discussed in relation to possible mechanisms behind the phenomenon of supersensitivity.

Animals↗

Peripheral vasodilatation in the treatment of hypertension. Prazosin compared with hydralazine in patients not responding to beta-receptor blockade.

Prazosin was compared with hydralazine in 39 patients (mean age 49 years), who were already on beta-blockade for arterial hypertension. They all had a resting DBP greater than 100 mm Hg on propranolol 80 mg b i d. They were randomly allocated to prazosin or hydralazine treatment. Blood pressure was measured after 4, 8 and 12 weeks. We noted a significant fall in blood pressure in both groups, in most cases to normotensive levels. Side-effects and other variables of interest are discussed. Together with beta blockade, i e propranolol, both prazosin and hydralazine give good blood-pressure control and no important differences could be found.

Adult↗

Preponderance for either alpha- or beta-adrenoceptor mediated sensitization in the rat submaxillary gland.

The sensitivity of the rat submaxillary gland was examined 3-4 weeks after either parasympathetic decentralization or sympathetic decentralization or denervation. The threshold doses for secretion of saliva of parasympathomimetic (methacholine) and sympathomimetic (noradrenaline, adrenaline, phenylephrine and isoprenaline) drugs were estimated and the amount of saliva secreted in response to supraliminal doses of these drugs was measured. Each type of operation caused the development of a supersensitivity that involved all three types of receptors, i.e. muscarinic cholinoceptors, alpha-adrenoceptors and beta-adrenoceptors. Following parasympathetic decentralization the sensitization was predominantly mediated via alpha-adrenoceptors, and also via cholinoceptors. Following sympathetic decentralization or denervation the postjunctional sensitization was predominantly mediated via beta-adrenoceptors; most of the supersensitivity to noradrenaline, adrenaline and phenylephrine found after sympathetic denervation was of the prejunctional type. An increase in receptor density and an intracellular arrangement where the response of cholinoceptors and alpha-adrenoceptors is mediated via one pathway and the response of beta-adrenoceptors via another are suggested as factors that may be of importance for the development of the postjunctional supersensitivity. The present study shows that the traffic of secretory impulses in the sympathetic nerve is of importance for the level of sensitivity of the secretory cells. Since postjunctional supersensitivity following sympathetic denervation did not exceed that following sympathetic decentralization it is suggested that under normal conditions a continuous release of noradrenaline from the nerve endings is of little importance for the level of sensitivity.

Animals↗

Patient survival with pacemaker therapy at regional hospital, Orebro, Sweden, 1964-1974.

The results of pacemaker therapy in the Regional Hospital, Orebro, during its first 10 years are presented. In general, patients with a history of temporary heart failure either before or at the time of implantation, had a better prognosis than those with such a history. Myocardial infarction had a detrimental effect on the prognosis in the first year of the patients pacing, but not thereafter.

Aged↗