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The evaluation of cardiac function alone from pressure and volume data can lead to misinterpretations. By linking of pressure and volume data a variety of new parameters can be calculated. Computer techniques allow the evaluation not only of cardiac work, but also of acceleration work and the efficiency of heart power. As an example of double blind study with CHD patients the measurement of such parameters under invasive diagnostics is demonstrated, facilitating a detailed evaluation of cardiac function.

The aim of the study was to demonstrate the possibility of transfemoral balloon occlusion of the coronary sinus and to detect changes of the left ventricular function during this occlusion in patients with angina pectoris. In 9 of 18 patients a stable occlusion over 15 seconds was performed. There were found only short term negative effects on the left ventricular contraction and relaxation. The coronary sinus pressure increased to 53 +/- 11 mm Hg. Numerous venous anastomoses made it difficult to occlude completely the sinus. The retrograde perfusion of the myocardium reached 20-30% of the antegrade one.

In 30 hypertensives with angina pectoris the acute action of beta-blockers Celiprolol and Metoprolol on the global and coronary haemodynamics was tested within cardiac catheter diagnostics. In accordance with no long-term effects Metoprolol acts negatively inotrope, chronotrope as well as pre- and post-load increasing. Celiprolol lowered the pre- and postload, and increased the cardiac output, but did not influence the heart rate. Both medicaments increased coronary flow and myocardiac oxygen consumption. From the mentioned effects important conclusions for therapy with both Beta-blockers can be derived.

In this study we propose a descriptive model of the events occurring in an excised lung during an inflation-deflation cycle. The model was developed by observing changes in small pressure-volume loops superimposed on quasistatic pressure volume curves. It was found that the shape of the small loops during lund inflation was a function of the previous end-expiratory pressure. These experimental results could most easily be explained by a model of the lung in which individual lung units open sequentially as the lung is inflated. During sequential recruitment, individual lung units open quickly to a volume determined by the transpulmonary pressure. The units then homogeneously increase and decrease in size according to pressure-volume curves similar to the defletion curve of the entire lung. Once lung units have been recruited, they remain open until the lung has been deflated to end-expiratory pressures below 3–4 cm H 2 O. Reducing the end-expiratory pressure to lower values causes additional derecruitment of lung units until a transpulmonary pressure of 0.0 to −1.0 cm H 2 O has been reached.

A modular ADC interface system for multi-parameter experiments with single NIM ADCs is described. 16 fast ADCs are handled by CAMAC modules and data buses in order to build up a sophisticated hardware system which is able to take coincidence data and singles spectra in parallel. The coincidence logic is handled by one of the interface modules; the interface allows online data reduction. The further expansion of the system will be discussed.

The relative abilities of 1--3 mg/kg of desipramine (DES), imipramine (IMIP), amitriptyline (AMI), and chlorimipramine (CI-IMIP) to enhance synaptic transmission mediated by either NE or 5-HT were determined by testing their effects directly on NE or 5-HT transmission to sympathetic preganglionic neurons in unanesthetized, spinal cats. Effects on NE transmission were assessed on intraspinal excitatory pathways which utilize NE as a transmitter. Effects on 5-HT transmission were assessed on 5-HT-mediated depression of spinal sympathetic reflexes produced by 30 mg/kg of 5-HTP. Both DES and IMIP markedly enhanced transmission through the intraspinal excitatory NE pathways whereas AMI and CI-IMIP depressed transmission. However, both AMI and CI-IMIP modestly enhanced transmission in cats depleted of central 5-HT by pretreatment with parachlorophenylalanine. The relative potencies of the four drugs on excitatory NE transmission were DES greater than IMIP greater than AMI greater than CI-IMIP. Each of the four drugs also enhanced the 5-HTP-induced depression of spinal sympathetic reflexes, but their relative potencies on 5-HT transmission were just the opposite to those found on NE transmission. Therefore, all four drugs enhanced transmission by both NE and 5-HT, but their relative selectivities for the two transmitters differed markedly and were complementary. In general, the results support those of previous studies based on less direct methods for assessing inhibition of amine reuptake by tricyclic antidepressants.

Two selective inhibitors of central epinephrine synthesis, LY 134046 and SKF 64139 (20 mg/kg, i.v.), gradually but markedly enhanced descending intraspinal transmission to sympathetic preganglionic neurons in spinal cats. Enhancement increased linearly to maximum values of 200% and 250%, respectively, at 4.5-5.5 h. Spinal sympathetic reflexes were not enhanced by either drug. The results support the proposal that bulbospinal epinephrine pathways depress the excitability of sympathetic preganglionic neurons by activating postsynaptic alpha 2-adrenergic receptors.

In this study the effect of temperature on gas trapping in excised lungs was examined with two types of experiments in rats. In the first, changes in gas trapping following ten successive inflation-deflation cycles at the same constant ventilation rate were examined at 17, 27, 37 and 42 degrees C. In the second, the effects of five different ventilation rates at temperatures of 17, 27 and 37 degrees C were determined. The fraction of gas trapped in lungs repeatedly ventilated for ten inflation-deflation cycles at constant ventilation rates remained nearly constant with time at 17 and 27 degrees C but decreased with time at 37 and 42 degrees C. The amount of gas trapped in the lung at 27 degrees C fell with the logarithm of increasing ventilation rate. Lowering the temperature shifted this relationship toward lower ventilation rates while increasing the temperatures caused an apparent shift toward higher ventilation rates.

1. The differential sensitivity of saphenous nerve fibres in the cat to block by procaine HCl was re-examined by recording identifiable unit action potentials from small nerve filaments. 2. Small myelinated axons were blocked more quickly than large myelinated axons, but this differential effect could not be accounted for by differences in anaesthetic concentration requirements. 3. The onset of block in non-myelinated axons was slower than or equal to that of small myelinated axons depending on anaesthetic concentration. 4. Absolute differential block of non-myelinated and small myelinated axons was obtained by limiting the length of axons exposed to procaine to 2 mm. 5. Differential rates of blocking among myelinated axons appear to depend on differences in the length of axons that must be exposed to blocking concentrations of procaine and to arise from the irregular distribution of such concentrations within an exposed nerve.

Summary Clinical and laboratory studies were carried out on 125 adults (81 males and 44 females) chosen at random and living in an area in which onchocerciasis was endemic. Special attention was given to skin changes, signs of eye pathology and the occurrence of miscarriage or abortion in the females and hydrocele in the males. Positive diagnoses were made by examination of 14 scarification smears from each subject and by palpation for onchocercomata. Overall infection rate for O. volvulus was 69 per cent and in the group 40 years and older it was 100 per cent. Specific skin changes were found in 14 per cent of the infected subjects. No ocular pathology attributable to onchocerciasis was seen. There was no evidence to suggest that in Liberia onchocerciasis was responsible for an increased rate of miscarriages or abortions or that it was a factor in hydrocele production in the male.

The dose-response effects of clonidine HCl (2.5-200 micrograms/kg i.v.) on transmission through somatospinal reflex, viscerospinal reflex, intraspinal, and spinal-bulbospinal reflex pathways were determined in spinal or chloralose-anesthetized cats to assess principle sites of drug action. Evoked sympathetic discharges were recorded from upper thoracic preganglionic rami. Clonidine rapidly produced parallel, dose-dependent depression of transmission through each pathway which was rapidly antagonized by tolazoline or yohimbine. The two spinal reflex pathways were least sensitive to depression which was identical and was limited to 60%. In contrast, both descending pathways could be depressed completely. Although the spinal-bulbospinal reflex pathway was more sensitive to depression than its efferent, descending intraspinal pathway alone, analysis of the relative depression of transmission at spinal and at brainstem levels indicates that the spinal site is more sensitive to clonidine that it is generally considered to be.

A model of Leptospira motility was recently proposed. One element of the model states that in translating cells the anterior spiral-shaped end gyrates counterclockwise and the posterior hook-shaped end gyrates clockwise. We tested these predictions by analyzing cells tethered to a glass surface. Leptospira illini was incubated with antibody-coated latex beads (Ab-beads). These beads adhered to the cells, and subsequently some cells became attached to either the slide or the cover glass via the Ab-beads. As previously reported, these cells rapidly moved back and forth across the surface of the beads. In addition, a general trend was observed: cells tethered to the cover glass rotated clockwise around the Ab-bead; cells tethered to the slide rotated counterclockwise around the Ab-bead. A computer-aided microcinematographic analysis of tethered cells indicated that the direction of rotation of cells around the Ab-bead was a function of both the surface of attachment and the shape of the cell ends. The results can best be explained by assuming that the gyrating ends interact with the glass surface to cause rotation around the Ab-beads. The analysis obtained indicates that the hook- and spiral-shaped ends rotate in the directions predicted by the model. In addition, the tethered cell assay permitted detection of rapid, coordinated reversals of the cell ends, e.g., cells rapidly switched from a hook-spiral configuration to a spiral-hook configuration. These results suggest the existance of a mechanism which coordinates the shape of the cell ends of L. illini.

The effects of acute and chronic lithium chloride administration on synaptic transmission between bulbospinal norepinephrine (NE) or 5-hydroxy-tryptamine (5-HT) pathways and sympathetic preganglionic neurons were tested in unanesthetized, spinal cats. Discharges recorded from sympathetic preganglionic white rami were evoked by stimulation of spinal reflex pathways or descending excitatory pathways in the cervical spinal cord. Acute lithium administration (2 meq/kg) produced insignificant depression of the reflex pathway but markedly depressed transmission through the intraspinal pathway, an effect that was prevented by depletion or blockage of 5-HT. These observations and the failure of lithium to alter the typical effects of L-dopa on both pathways indicate that lithium does not affect transmission through the excitatory NE pathway. L-Tryptophan (1,0 mg/kg) alone produced little or no depression of either pathway, but 3--4 hr after lithium, this dose of L-tryptophan gradually depressed transmission through both pathways by about 20%. After chronic lithium pretreatment (1 meq/kg twice a day for 3 days), L-tryptophan rapidly depressed transmission through spinal reflex and intraspinal pathways by 40% and 50% respectively. Chronic lithium pretreatment also more than doubled the depression of transmission through both pathways produced by 30 mg/kg of 5-HTP. The average of plasma lithium levels 8--10 hr after the last chronic dose was 1.5 meq/liter. These results support the proposal that lithium increases the uptake of L-tryptophan and 5-HTP by central 5-HT terminals and thereby enhances 5-HT synthesis which is reflected in increased transmission at central 5-HT synapses.

The systematic alterations of peripherally and intraspinally evoked sympathetic discharges in spinal cats by drugs affecting central catecholaminergic transmission indicate that bulbospinal norepinephrine neurons provide excitatory drive to sympathetic preganglionic neurons. Bulbospinal serotonergic neurons appear to be inhibitory.

The combination of coronary heart disease (CHD) with increased left ventricular wall mass (LVWM) appears associated with prolonged isovolumetric relaxation (IVR) and consequently, alterations in the rapid filling phase. Methylxanthine-substances may improve relaxation through inhibition of phosphodiesterase activity. Accordingly we examined multiple indexes of left ventricular diastolic function before and after administration of 200 mg pentoxifylline (Trental) intravenously to 18 patients (51.3 +/- 9.0 years, 15 males, three females) with stable angina pectoris and positive exercise-ECG in NYHA class I or II and LVWM greater than 160 g (n = 9) and less than or equal to 160 g (n = 9). Left ventricular pressure (P) and volume (V) measurements were made with a high-fidelity-micromanometer before and twelve minutes after administration of pentoxifylline. The time constant of left ventricular isovolumic relaxation (T), usual global left ventricular volumes and derived indexes such as peak filling rate (PFR), time to peak filling rate (TPFR), segmental (relaxation and rapid filling phases) and total pressure-volume relationship before and after pentoxifylline were calculated. Significant differences between these two groups (greater than/less than or equal to 160 g LVWM) were found for end-diastolic volume (68.7 +/- 19.0 to 90.8 +/- 22.6 ml/sqm), end-systolic volume (21.7 +/- 16.0 to 36.1 +/- 14.7 ml/sqm), end-diastolic pressure (15.0 +/- 4.8 to 15.7 +/- 5.1 mm Hg), PFR (3.25 +/- 1.18 to 2.66 +/- 0.71 s-1), T (46.0 +/- 5.7 to 52.7 +/- 7.2 ms), the linear regression of lnP-V (lny = -0.117 x + 4.59 to lny = -0.091 x + 4.75) in the IVR-phase (dp/dtmin less than or equal to x less than or equal to 80 ms) (leftward shift in p-V-relationship when less than or equal to 160 g) and the complet p-V-areas. After pentoxifyl-line-administration there were significant decreases in T in patients with increased LVWM (52.7 +/- 7.2 to 47.7 +/- 5.9 ms) and the P-V-product over the time in the rapid filling phase in patients with LVWM less than or equal to 160 g. Total peripheral resistance and heart rate did not change. These changes in parameters of left ventricular diastolic function in combination with significant improvement of pump function especially in patients with LVWM greater than 160 g after administration of pentoxifylline suggest that improved diastolic function is the result of a direct myocardial effect of pentoxifylline.

Unilateral injection of 5,7-dihydroxytryptamine (DHT) into the rat neostriatum markedly reduced not only striatal tryptophan hydroxylase (TPH) activity but also striatal tyrosine hydroxylase (TH) activity and dopamine (DA) concentration measured 10--15 days later. The decrease in striatal TH activity was dose related over the range of 8--32 micrograms of DHT; a dose of 16 micrograms reduced striatal TH activity to 40--50% of control, DA concentration to 38% of control, and TPH activity to 5--20% of control. Intrastriatal injection of 16 micrograms of DHT reduced TH activity in the ipsilateral substantia nigra to 51% of control. Pretreatment with amfonelic acid, a potent DA uptake inhibitor, significantly reduced the effect of DHT on striatal and nigral TH activity and striatal DA concentration without affecting the DHT-induced decrease in striatal TPH activity. Desmethylimipramine (5 and 25 mg/kg) had no effect on the DHT-induced decrease in striatal TH activity. Striatal choline acetyltransferase and glutamic acid decarboxylase activities were not decreased by 16 micrograms of DHT. The results indicate that DHT can alter dopaminergic function in the rat neostriatum through a direct effect of the drug on DA neurons.

The diastole is frequently neglected in the assessment of the heart function, though for a long while has been known that in the diastole active, energy-requiring processes take place. After a description of the various definitions and fundaments of the diastolic function of the ventricle the essential criteria and the methodological possibilities are mentioned. The most exact informations are to be obtained from simultaneous analyses of pressure dimensions (and volumes, respectively) with regional differentiation. In this case we are particularly interested in the early (isovolumetric) relaxation phase, since here the essential energetic processes take place, which may early be changed and which also first to all may be influenced medicamentously. By means of a listing of parameters of the diastolic ventricular function depending upon the methodological possibilities impulses shall be given to take into consideration the diastole more for diagnosis, prognosis and above all for therapy.

The effects of 3 phosphodiesterase inhibitors, aminophylline, isobutylmethylxanthine (IBMX), and RO 20-1724, were tested on descending intraspinal and spinal reflex transmission to sympathetic preganglionic neurons in unanesthetized spinal cats. Sympathetic discharges, recorded from upper thoracic preganglionic white rami, were evoked by stimulation (0.1 Hz) of descending excitatory pathways in the cervical dorsolateral funiculus (intraspinal) or of adjacent intercostal nerves (spinal reflex). Each phosphodiesterase rapidly and markedly enhanced transmission through intraspinal pathways but only slowly and modestly enhanced transmission through spinal reflex pathways. Pretreatment with a methyltyrosine-reserpine combination, chlorpromazine, or prazosin markedly restricted the enhancement of intraspinal transmission by IBMX to levels typically produced on spinal reflex pathways. Clonidine markedly depressed transmission through both pathways and prevented enhancement by the phosphodiesterase inhibitors. Yohimbine or tolazoline antagonized the depressant effects of clonidine and restored the ability of the phosphodiesterase inhibitors to enhance transmission. Somatic spinal reflexes were not affected by the phosphodiesterase inhibitors. The results suggest that descending norepinephrine pathways to sympathetic preganglionic neurons activate adenylate cyclase to generate cyclic AMP which increases neuronal excitability, possibly by phosphorylating membrane proteins. Clonidine appears to depress neuronal excitability by inhibiting adenylate cyclase through activation of alpha 2-adrenergic receptors.

In studies designed to determine the respective functional roles of two bulbospinal monoaminergic pathways to sympathetic preganglionic neurons, both L-dopa and precursors of 5-HT depressed transmission through excitatory spinal reflex and bulbospinal sympathetic pathways. Transmission through spinal reflex pathways was secondarily enhanced after L-dopa. Pharmacological tests indicated mediation of these effects by monoamines. After antagonism or depletion of central 5-HT, L-dopa only enhanced transmission through both pathways. The results indicate that hypotension and other sympathoinhibitory effects of L-dopa are produced at the spinal level by release of 5-HT from terminals of bulbospinal 5-HT pathways that are inhibitory to sympathetic preganglionic neurons. The excitatory effects of L-dopa are apparently mediated by release of catecholamines from bulbospinal noradrenergic pathways that are excitatory.

Enzyme-linked immunosorbent assays were developed to measure serum antibody specific for Pseudomonas elastase, alkaline protease, and exotoxin A. Antibody responses to each Pseudomonas antigen were measured in cystic fibrosis (CF) patients who were not colonized with Pseudomonas aeruginosa, in those who were colonized, in those who were chronically infected with this organism, and in control subjects. Antibody levels for each antigen in the colonized and infected CF patients were higher than levels in uncolonized CF patients or non-CF control subjects. The antibody responses to elastase were similar in patients of the colonized and infected groups. However, infected CF patients had significantly elevated levels of antibody to exotoxin A (P less than 0.01) and alkaline protease (P less than 0.05) when compared with patients simply colonized with P. aeruginosa. These findings confirm that Pseudomonas alkaline protease, elastase, and exotoxin A are produced by Pseudomonas strains which colonize and infect CF patients. As an adjunct to established procedures (X-ray, microbiological culture, etc.), the antitoxin and anti-protease enzyme-linked immunosorbent assays may be clinically useful tests for differentiating colonized CF patients from those who have more severe Pseudomonas pulmonary infections.

Despite considerable progress in mapping the central monoaminergic pathways to sympathetic preganglionic neurons in the spinal cord, the respective functional roles of these pathways have not been resolved. Evidence for both excitation and inhibition has been advanced for each of the three monoamines, serotonin, norepinephrine, and epinephrine. Our previous studies on spinal sympathetic pathways to sympathetic preganglionic neurons support the prevailing opinion that serotonin pathways are inhibitory but did not satisfactorily resolve the functional role of the norepinephrine pathways. However, more recent studies showing that intraspinally evoked sympathetic discharges were rapidly and markedly enhanced by phosphodiesterase inhibitors and that this effect was prevented by clonidine have led to formulation of a coherent hypothesis which accommodates much of the conflicting evidence regarding norepinephrine. In addition, evidence for the role of the epinephrine pathways has been obtained by using a selective inhibitor of epinephrine synthesis. The results of these recent studies complement our previous results and suggest that the excitability of sympathetic preganglionic neurons is regulated by excitatory norepinephrine pathways and inhibitory epinephrine pathways that activate or suppress adenylate cyclase to control intraneuronal levels of cyclic AMP.

Preganglionic sympathetic discharges, evoked by cervical stimulation in spinal cats, were rapidly and markedly enhanced for 1–2 h by aminophylline or isobutylmethylxanthine. Clonidine depressed intraspinal transmission and prevented enhancement by the xanthines; α 2 -receptor antagonists blocked the effect of clonidine and not only restored but also markedly prolonged the enhancement by the xanthines. The results suggest that the excitability of sympathetic preganglionic neurons is regulated by cyclic AMP through activation of different subtypes of adrenergic receptors that are either positively or negatively coupled to adenylate cyclase.

In 36 patients with angina pectoris during complex invasive diagnostic procedure the changes of global and regional systolic heart function by intravenous application of 200 mg pentoxifylline were examined. We observed a significant decrease of preload (reduction of LVEDP and MCS, LVEDV was not influenced) and an improvement of myocardial pump function, possibly combined with a favourable influence on alterated myocardial blood supply. In case of perfusion disturbances of the LV anterior wall the pentoxifylline injection was followed by signs of coronary-steal-mechanism in the LV posterior wall region. We did not found significant changes of afterload. Thus the acute hemodynamic effects of an intravenous application of pentoxifylline are comparable with those of nitrates and non-glycoside-cardiotonic substances with a predominant myocardial effect.

The pharmacological properties of centrally acting alpha2-receptor agonists such as clonidine suggest a potentially important role as ideal adjuvants for anesthesia since they produce sedation, analgesia anxiolysis, xerostomia and cardiovascular stability without respiratory depression, development of tolerance or addiction liability. Further clinical experience with this exciting development will undoubtedly establish the ultimate role and optimal use of alpha2 -receptor agonists in anesthetic practice. Beta-blockage can result in significant bradycardia, atrial ventricular conduction problems, bronchospasm and left ventricular contractile dysfunction. Thus, the use of long-acting beta-blockers is of limited value in the perioperative period. Esmolol, because of its ultrashort action, cardioselective properties and titratability, has been shown to be safe and effective for the treatment of tachycardia and hypertension. Doses from 50 to 300 micrograms/kg/min for up to 7 hours in the perioperative period have been shown to cause no apparent cumulative effect. It has been used in the treatment of asthmatic patients with tachycardia and hypertension without significant increases in airway resistance. Studies using esmolol during general anesthesia have demonstrated no significant interaction with several anesthetic regimens.

In unanesthetized spinal cats, clonidine HCl (5-50 microgram/kg, i.v.) rapidly and markedly depressed excitatory transmission through two spinal pathways to sympathetic preganglionic neurons. Depression through either pathway was dose-dependent and persisted for more than 3 hr but could be rapidly antagonized at any stage by tolazoline HCl in a dose-ratio of about 1:100. The two spinal pathways were also depressed transiently by L-dopa and for prolonged periods by 5-HTP; both precursors were shown to act by releasing 5-HT from bulbospinal 5-HT terminals and their depressant effects were also antagonized by tolazoline. In the absence of 5-HT-induced depression, L-dopa only enhanced transmission through both pathways by inducing release of catecholamines from bulbospinal NE terminals. These results indicate that clonidine depresses sympathetic activity by stimulating inhibitory 5-HT receptors on sympathetic preganglionic neurons, a mechanism that adequately accounts for its central vasodepressor effect.

In studies designed to determine the respective functional roles of two bulbospinal monoaminergic pathways to sympathetic preganglionic neurons, both L-dopa and precursors of 5-HT depressed transmission through excitatory spinal reflex and bulbospinal sympathetic pathways. Transmission through spinal reflex pathways was secondarily enhanced after L-dopa. Pharmacological tests indicated mediation of these affects by monoamines. After antagonism or depletion of central 5-HT, L-dopa only enhanced transmission through both pathways. The results indicate that hypotension and other sympathoinhibitory effects of L-dopa are produced at the spinal level by release of 5-HT from terminals of bulbospinal 5-HT pathways that are inhibitory to sympathetic preganglionic neurons. The excitatory effects of L-dopa are apparently mediated by release of catecholamines from bulbospinal noradrenergic pathways that are excitatory.

In 30 patients the influence of ionic (Amidotrizoate) and non-ionic (Iopromide) contrast agents on the heart parameters contractility, relaxation, perfusion and the rate of extrasystoles was investigated. They were significantly less influenced by Iopromide than by Amidotrizoate. A negative inotropic action was detectable only for Amidotrizoate. It is concluded that non-ionic contrast media should be used especially for critical patients.

The effects of clonidine HCI were compared with those of 5-HTP on transmission through two spinal sympathetic pathways, segmental spinal reflex pathways and descending intraspinal excitatory pathways, in unanesthetized spinal cats. Evoked sympathetic discharges were recorded from upper thoracic preganglionic rami. Clonidine (5-50 microgram/kg) produced a parallel, dose-dependent depression of transmission through each pathway. The intraspinal pathway was five time more sensitive than the spinal reflex pathway (ED50's, 6 and 30 microgram/kg), and the spinal reflex pathway could not be depressed by more than 60% even by higher doses. In contrast, 5-HTP was more effective in depressing the spinal reflex than the intraspinal pathway (ED50's 32 and 44 mg/kg), and both pathways could be depressed completely. Small doses of tolazoline or yohimbine rapidly antagonized the effects of clonidine but not 5-HTP. Clonidine and 5-HTP appear to depress the excitability of sympathetic preganglionic neurons by activating alpha2- and 5-HT receptors, respectively. Each mechanism may contribute independently to regulation of the sympathetic outflow.

Parasympathetic preganglionic discharges recorded from pelvic nerves in spinal cats were evoked by single-pulse stimulation of sacral afferent fibers of descending excitatory pathways in the thoracic spinal cord. Evoked responses were analyzed on-line by signal averaging. Discharges evoked by either pathway were increased in size by 2-10 times by coadministration of both picrotoxin and strychnine, but not by either drug alone. The combination also markedly enhanced evoked increases in bladder pressure. Strychnine was also effective with bicuculline and in cats depleted of central GABA stores by semicarbazide. The monoamine precursors, 5-HTP and L-dopa, only depressed evoked discharges in both untreated and convulsant-treated animals; this depression was enhanced by tricyclic antidepressants. The results indicate that sacral parasympathetic preganglionic neurons are controlled by an unusual type of strong, local tonic inhibition which is mediated by both GABA and glycine. Both amino acid transmitters must be blocked to unmask this inhibition. Interruption of supraspinal control of this local inhibition may account in part for loss of bladder function following spinal injuries. The 5-HT and NE bulbospinal pathways that terminate near the preganglionic neurons also appear to be inhibitory. Enhancement of this inhibitory monoaminergic transmission by tricyclic antidepressants may contribute to the efficacy of these drugs in treating nocturnal enuresis.