Neuronal adrenergic and muscular cholinergic contractile hypersensitivity in canine jejunum after extrinsic denervation

Extrinsic denervation may be responsible for motor dysfunction after small bowel transplantation. The aim of this study was to examine the role of extrinsic innervation of canine jejunum on contractile activity. An in vitro dose response of cholinergic and adrenergic agonists was evaluated in canine jejunal strips of circular muscle at 0, 2, and 8 weeks in a control group and after jejunoileal extrinsic denervation (EX DEN). Neurons in circular muscle were quantitated by means of immunohistochemical techniques. Adrenergic and cholinergic responses did not differ at any time in the control group. However, at 2 and 8 weeks, extrinsic denervation caused an increased sensitivity to the procontractile effects of the cholinergic agonist bethanechol at the level of the smooth muscle cells, and increased sensitivity to the inhibitory effects of the adrenergic agent norepinephrine mediated at the level of the enteric nervous system. Immunohistochemical analysis showed a reduction in all neurons and a complete lack of adrenergic fibers in the EX DEN group after 2 and 8 weeks. Extrinsic denervation induces enteric neuronal cholinergic and adrenergic smooth muscle hypersensitivity in canine jejunal circular muscle. Presented in part at the annual meeting of the American Gastroenterological Association, Orlando, Florida, May 18, 1999 (poster presentation), and published as an abstract in Gastroenterology 116:A1075, 1999. Supported by United States Public Health Service grant DK39337 from the National Institutes of Health (M.G.S.); the Swiss National Science Foundation; the Swiss Society of Gastroenterology and Hepatology; the Swiss Foundation for Medical and Biological Science; the Novartis Foundation; Astra Zeneca Pharmaceuticals, Switzerland; and the Department of Visceral and Transplantation Surgery, University of Bern, Switzerland.     

Low energy charge and high adenosine content in smooth muscle of human bladder in comparison with striated muscle

Summary This study determined the energy charge, adenosine and inosine content of human bladder smooth muscle in comparison with striated muscle of the same individual. Biopsies were obtained from 21 women who were subjected to urethrocystopexy because of urinary stress incontinence. We found that the ATP content of bladder smooth muscle was only about one-eighth of that of striated muscle. The energy charge of bladder smooth muscle was 0.78±0.13, which is low compared with striated muscle (0.92±0.02). The adenosine content of bladder smooth muscle was 6.7 times higher than striated muscle and the adenosine/ATP ratio was 1∶9 compared with 1∶450 for striated muscle. These findings were in accordance with our previous studies on uterine smooth muscle.     

人心和山羊心脏上、下腔静脉肌袖大体解剖

目的:观测人和山羊上、下腔静脉肌袖结构特点,为治疗局灶性心房颤动积累解剖学资料。方法:采用大体解剖方法观测人心(20例)和羊心(40例)的上、下腔静脉及其表面的心肌纤维。结果:人心上腔静脉肌袖的长和宽分别为(1.91±0.39)cm、(2.41±0.26)cm,下腔静脉肌袖的长和宽分别为(1.32±0.32)cm,(3.06±0.52)cm;羊心上(前)腔静脉肌袖的长和宽分别为(1.41±1.00)cm、(1.05±0.26)cm,下(后)腔静脉肌袖的长和宽分别为(0.81±0.48)cm,(1.03±0.28)cm。人和羊心脏的上腔静脉肌袖出现率均为100%;下腔静脉肌袖的出现率分别为88.89%和98%。肌纤维多数来源于右心房前后壁,也有来自于左心房或左右心房的。结论:①上腔静脉肌袖是人和羊普遍存在的解剖结构,人的下腔静脉肌袖出现率明显低于羊,可能是上腔静脉肌袖引起局灶性心房颤动多于下腔静脉肌袖的解剖学基础。②上腔静脉肌袖是构成左右房的又一重要通路。     

Cross talk in surface electromyograms of human hamstring muscles.

Signals generated from muscles other than the muscle(s) of interest (cross talk) can confound the interpretation of surface electromyograms (EMGs). In this study, the amount of cross talk in surface EMGs of human hamstring muscles was estimated using a protocol in which the quadriceps femoris was electrically stimulated via the femoral nerve. EMGs were recorded from the vastus lateralis and the medial and lateral hamstring muscle groups. The amplitude of the EMG response of the vastus lateralis to electrical stimulation was adjusted to match that of its maximum voluntary effort (MVE) under isometric conditions. Subsequent power density spectrum analysis showed that the median frequencies of the signals generated by electrical stimulation and MVE were not significantly different. In conventional bipolar recordings, cross talk in lateral hamstring EMGs averaged 17.1% MVE and in medial hamstring EMGs 11.3% MVE (average-rectified values). The double differential technique significantly reduced cross talk to 7.6% MVE for the lateral hamstrings, and to 4.2% MVE for the medial hamstrings. The double differential technique appears to be more selective than the bipolar technique when recording EMGs from muscles with highly active neighbors and thus should be used in such situations. Software simulations of the double differential technique also appear to be more selective than the bipolar technique and may be used when the number of amplifiers available is limited.     

The use of coaxially aligned freeze-thawed skeletal muscle autografts in the repair of the cauda equina — in the sheep

Summary The aim was to develop a model for study of nerve regeneration in nerve roots above the level of the dorsal root ganglion and to investigate the use of freeze-thawed muscle autografts for repair of nerve roots at this level.Four adult sheep were used for the experiment. A laminectomy was performed at the lumbosacral junction and the S2 root identified. Both the dorsal and ventral S2 roots were divided unilaterally within the dura and a freeze-thawed muscle graft was inserted into the nerve gap.When assessed at 6 months an action potential was recordable from the ventral root in one sheep. Histological examination of the nerve roots showed evidence of regeneration across the graft in the ventral roots of all the sheep and the dorsal roots of some.This preliminary work indicates a capacity for regeneration of the cauda equina and that freeze-thawed muscle can support this. It provides a useful model for further study of nerve root repair.     

Electrical responses of the muscularis externa to distension of the isolated guinea-pig distal colon

Abstract Enteric reflex pathways were studied in isolated segments of guinea-pig distal colon by recording the electrical responses to distension from the muscularis externa with suction electrodes. The end of the electrode wire were in the circular muscle and thus the recordings discussed below are deduced to be primarily from this layer. Moreover, intracellular microelectrodes in circular muscle cells and suction electrodes recorded similar events. Spontaneous activity consisted of myogenic slow waves at about 25 min ^-1 and transient biphasic potentials at about 6 min^-1 and 3-sec duration which were dependent on a stimulus from the enteric nervous system as they were blocked by tetrodotoxin (0.5 μM), d-tubocurarine (30 μM) and hexa-methonium (100 μM). Atropine (0.8 μM) blocked the depolarizing part of the biphasic potentials and unmasked transient spontaneous inhibitory junction potentials (IJPs) (～2-sec duration) which appeared to be responsible for the hyperpolarizing part of the biphasic potential. Three different responses were observed at sites oral to distension of the colon: a transient depolarizing response that was cholinergic (blocked by atropine (0.8 μM); ascending cholinergic excitation) and, after atropine, a transient IJP (ascending inhibition) which was followed by a transient non-cholinergic depolarizaton (ascending non-cholinergic excitation) that was sometimes followed by several cycles of slow wave activity. The oral responses to anal distension were also blocked by the nicotinic antagonists and were similar to the neurogenic spontaneous events, which also appeared to originate from activity in ascending nervous pathways. Four different responses were observed following distension of the oral end of the segment: an IJP followed by a prolonged phase of hyperpolarization that lasted for the duration of the distension (descending inhibition); a burst of depolarizing potentials (for up to 30 sec) that followed the termination of distensions up to 25 sec and was blocked by atropine (0.8 μM) (delayed cholinergic excitation), and a transient non-cholinergic response that immediately followed the termination of distension (non-cholinergic ‘off’ response). Apamin (0.5 μM) reduced the amplitude of the spontaneous IJPs and evoked IJPs. After apamin, distension evoked a small transient hyperpolarization at oral sites, which was similar to spontaneous events, and the prolonged hyperpolarization at anal sites. A second distension given within 20 sec of the first evoked an IJP of reduced amplitude at oral sites in every preparation. In contrast, the amplitudes of the oral Cholinergic excitation and descending inhibition were relatively unaffected by reducing the interval between distensions. Thus distension stimulates excitatory and inhibitory motor neurons supplying the circular muscle both oral and anal to the stimulus. The polarity of the reflex relies in part on the differences in timing and duration of responses as well as the transmission characteristics of the nervous pathways.     

Pharmacological evaluation of natural product analogues. I. Preliminary pharmacological evaluation of O-methylgortschakoine and O-methylpetaline

The synthesis of O-methylgortschakoine and O-methylpetaline was achieved through an unambiguous route. Pharmacological testing of O-methylgortschakoine in comparison to papaverine and 7,8-dimethoxy-N-methyltetrahydroisoquinoline, indicated that it possesses hypotensive, neuromuscular blocking and smooth muscle relaxant activities. 7,8-Dimethoxy-N-methyltetrahydroisoquinoline showed only nonspecific smooth muscle relaxation in our testing system. The 1-(p-methoxybenzyl)-substituent of O-methylgortschakoine appears to be required for this hypotensive and neuromuscular blocking effect. The quaternary analogue O-melthylpetaline was found to possess a more potent neuromuscular blocking activity.