The contractions of the isolated guinea-pig vas deferens in response to stimulation of the sympathetic hypogastric nerve were potentiated by low concentrations and inhibited by high concentrations of the antiadrenaline agents tolazoline, yohimbine, ergotamine, phenoxybenzamine and piperoxan. Eserine potentiated the contractions of the vas deferens produced by hypogastric nerve stimulation. The cholinesterase activity of an extract of vas deferens was decreased by the antiadrenaline agents. The potentiation of responses to sympathetic stimulation by antiadrenaline drugs, which also possess anticholinesterase activity, can be explained on the basis of a cholinergic sympathetic mechanism.The effects of antiadrenaline agents on the taining 2 adjacent platinum rings. Stimulation was responses to stimulation of a sympathetic nerve do by 2 msec. pulses at a frequency of 10/sec. applied not always run parallel to their effects on responses at supramaximal strength (usually 3.0 mA.) for 10 sec.induced by noradrenaline. Thus Varagic (1956b) in every 2 min. The time cycle of stimulation was found that tolazoline potentiated the response of automatically controlled. Contractions were recorded the rabbit uterus to sympathetic nerve stimulation, by an isotonic frontal writing lever. and Hukovic (1959) reported that phenoxybenzIsolated Vas Deferens.-For experiments in which amine increased the response to sympathetic nerve nerve stimulation was not required the vas deferens stimulation in the isolated atria of the rabbit. was suspended in a 5 ml. bath. We have investigated the effects of tolazoline Cholinesterase Activity.-The vasa deferentia from and other antiadrenaline agents on the a guinea-pig were ground with Tyrode solution responses of the isolated vas deferens to (11 ml.) in a mortar. The whole extract was divided sympathetic nerve stimulation, noradrenaline and into 2 ml. aliquots to serve as source of enzyme in acetylcholine-and on the cholinesterase activity of each reaction mixture. The drugs examined for acetylcholine, and on anticholinesterase activity were mixed with the enzyme the vas deferens. 10 min. before the addition of substrate and brought METHODSto 32°. Acetylcholine as substrate was added to reach Isolated Innervated Vas Deferens.-The isolated vas a final concentration of 0.5 lxg. /ml. in a final volume deferens with intact hypogastric nerve was prepared of reaction mixture of 5 ml. At various time intervals by the method of Hukovic (personal communication). after this, the reaction mixture was agitated and 0.1 Guinea-pigs weighing about 500 g. were killed by a ml-samples were withdrawn and assayed for acetylblow on the head. The abdomen was opened in the choline on a strip of guinea-pig ileum suspended in midline and the distal colon retracted to one side. Tyrode solution in a 5 ml. bath. A dose-response The hypogastric nerves were identified and dissected curve for acetylcholine was obtained upon the ileum free. The vasa deferentia were cut from their attach-at the beginning and the end of each exp...
Studies systematically comparing the performance of health-related quality-of-life (HRQL) instruments in pulmonary arterial hypertension (PAH) are lacking. We sought to address this gap by comparing cardiac and respiratory-specific measures of HRQL in PAH. We prospectively assessed HRQL in 128 patients with catheterization-confirmed PAH at baseline and at 6, 12, and 24+ months. Cardiac-specific HRQL was assessed using the Minnesota Living with Heart Failure Questionnaire (LHFQ); respiratory-specific HRQL using the Airways Questionnaire 20 (AQ20); and general health status using the 36-item Short Form physical component summary (SF-36 PCS). The LHFQ and AQ20 were highly intercorrelated. Both demonstrated strong internal consistency and converged with the SF-36 PCS. Both discriminated among patients based on World Health Organization functional class (FC), 6-minute walk distance (6MWD), and Borg Dyspnea Index (BDI), except for a potential floor effect associated with low 6MWD. The LHFQ was more responsive than the AQ20 to changes over time in FC, 6MWD, and BDI. In multivariate analyses, the LHFQ and AQ20 were each longitudinal predictors of general health status, independent of FC, 6MWD and BDI. In conclusion, both cardiac-specific and respiratory-specific measures appropriately assess HRQL in most patients with PAH. Overall, the LHFQ demonstrates stronger performance characteristics than the AQ20.
It has been shown by others that hemicholinium (α,α′‐dimethylethanolamino‐4,4′‐biacetophenone) inhibits the synthesis of acetylcholine, an effect which is reversed by choline. Hemicholinium produces a failure of response to nerve stimulation in the following sympathetically innervated preparations: guinea‐pig isolated vas deferens, rabbit isolated uterus, rabbit isolated colon, perfused rabbit ear, cat isolated atria and the piloerector muscles in the cat's tail. The blocking action of hemicholinium on the responses to postganglionic sympathetic stimulation resembles its blocking action against cholinergic nerve stimulation observed on rabbit isolated atria with vagus nerves, rabbit isolated vagina with pelvic nerves, and guinea‐pig isolated diaphragm with phrenic nerve. The failure of transmission produced by hemicholinium in sympathetic nerves and in cholinergic nerves can be reversed by choline. It is suggested that if there were a cholinergic junction at sympathetic nerve endings the mechanism of the blocking action of hemicholinium at these endings could be explained by inhibition of acetylcholine synthesis.
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