PubMed Health⌕ Search

Biomedical subjects

E van Lunteren

Publications and source records attributed to E van Lunteren.

At least 19 recordsLinked to original sources

Auxotonic contractile responses of rat tracheal and bronchial airway smooth muscle.

The purposes of the present study were to directly compare: (1) the degree of trachealis muscle shortening and changes in tracheal dimensions and (2) ACh-mediated auxotonic contraction of trachea and intraparenchymal bronchi. The auxotonic contractile properties of tracheal and bronchial airway smooth muscle were assessed from 1-2 mm thick tracheal sections and;1 mm thick lung slices using videomicrometry in vitro at 37 degrees C. Acetylcholine resulted in reductions in luminal area, perimeter, mean radius, length, and breadth (22.0, 10.0, 11.9, 10.7 and 12.0%, respectively). Trachealis muscle shortening reached a maximum of 39.8+/-4.3%. The K(+)channel blocker 4-aminopyridine significantly augmented the ACh-mediated reductions in tracheal luminal dimensions. In response to ACh (10(-3)m), reductions in bronchial dimensions were significantly greater than those of the trachea for luminal area, perimeter and mean radius (44.6 vs. 18.6, 32.0 vs. 8.0 and 28.9 vs. 9.9%, respectively). These data indicate that auxotonic contractile responses of rat tracheal smooth muscle differ from those previously reported in the dog and guinea pig, that ACh-mediated auxotonic contraction of tracheal smooth muscle is augmented by 4-aminopyridine, and that proportionate reductions in luminal dimensions in response to ACh are considerably greater for bronchial than tracheal airways.

4-Aminopyridine↗

Heterogeneity within geniohyoid motor unit subpopulations in firing patterns during breathing.

Respiratory motor units (MU) segregate into subpopulations, which differ in firing patterns during resting and stimulated breathing. For phrenic/diaphragm MUs, diversity also exists within subpopulations, and is greater for late than early-onset MUs. The present study characterized the extent of diversity within upper airway respiratory MU subpopulations by recording geniohyoid MUs in anesthetized cats. Inspiratory MUs (I-MU, n=21) had a wide range of firing durations (coefficient of variation (CV)=42%). In contrast, inspiratory-expiratory MUs (I/E-MU, n=19) had a narrow range of firing durations during inspiration (CV=13%), but a wide range of firing durations during expiration (CV=36%). Mean firing frequency had similar degrees of diversity among units for I-MU and I/E-MU (CV=31-40%). For I-MU firing duration correlated with mean firing frequency, whereas no such relationship was apparent for I/E-MU. Single-breath end-expiratory airway occlusion decreased heterogeneity in firing duration during inspiration and increased it during expiration, whereas end-inspiratory airway occlusion decreased heterogeneity during expiration. In conclusion, (a) there is considerable diversity within geniohyoid MU subpopulations receiving respiratory drive; (b) the degree of diversity within subpopulations differs for I-MU and I/E-MU; and (c) diversity within subpopulations in timing of activity is modulated by single-breath airway occlusion.

Airway Obstruction↗

Modulation of diaphragm action potentials by K(+) channel blockers.

K(+) channels regulate diaphragm contractility. The present study examined the electrophysiological mechanisms accounting for diversity among K(+) channel blockers in their inotropic actions on the diaphragm. Rat diaphragmatic muscle fibers were recorded intracellularly in vitro at 37 degrees C. Apamin and charybdotoxin (Ca2+)-activated K(+) channel blockers) did not alter resting membrane potential or action potentials. Glibenclamide (ATP-sensitive K(+) channel blocker) slowed action potential repolarization by 12% (P<0.05) and increased action potential area by 25% (P<0.005). Tetraethylammonium (which blocks several types of K(+) channels) increased action potential overshoot by 20% (P<0.01) and prolonged action potential rise time by 17% (P<0.02). 4-Aminopyridine and 3,4-diaminopyridine (which also block several types of K(+) channels) slowed action potential repolarization by 163% (P<0.0001) and 253% (P<0.0001), and increased action potential area by 183% (P<0.0001) and 298% (P<0.0001), respectively. Slowing of repolarization for the aminopyridines was especially marked at voltages approaching resting membrane potential, thereby changing action potential repolarization from a first to a second order decay. Previously reported variability in inotropic effects among K(+) channel blockers correlated significantly with the extent to which they slowed action potential repolarization and increased action potential area, but not with changes in other action potential properties.

Action Potentials↗

Inotrophic effects of the K(+) channel blocker TEA on dystrophic (mdx and dy/dy) mouse diaphragm.

K(+) channels regulate diaphragm resting membrane potential and action potential duration, and hence force. Certain blockers of these channels, e.g. tetraethylammonium (TEA), increase twitch force of normal diaphragm. To further address whether these agents may be useful in the treatment of diaphragm weakness, studies examined the effects of TEA on force of overtly diseased muscle. Diaphragm from two mouse models of muscular dystrophy (mdx and dy/dy) was studied in vitro. Diaphragm from both models was significantly weaker than diaphragm from control animals. TEA (10 mM) increased twitch force of both mdx diaphragm (P<0.005) and dy/dy diaphragm (P<0.0005), as well as force of diaphragm from non-diseased animals. The percent force increase of mdx diaphragm was at least as great as that of non-diseased muscle (15.3 vs 9.2%, P=0.14), and the percent force increase of dy/dy diaphragm was significantly greater than that of non-diseased muscle (22.7 vs 10.2%, P<0.02). Absolute force increases normalized for cross-sectional area were comparable for healthy and diseased diaphragm, however. These findings indicate that TEA increases force of both dystrophin-deficient and merosin-deficient dystrophic mouse diaphragm muscle.

Animals↗

Effect of temperature on endplate potential rundown and recovery in rat diaphragm.

The amplitude of neuromuscular junction end-plate potentials (EPPs) decreases quickly within a train but recovers nearly completely from train to train during intermittent stimulation. Rundown has been shown to be dependent not only on the rate of transmitter release but also on the rate of replenishment of the depleted neurotransmitter at the site of release. Two groups of processes have been proposed for synaptic vesicle recycling, both of which involve multiple energy-requiring steps and enzymatic reactions and which therefore would be expected to be very temperature-sensitive. The present study tested the hypothesis that low temperature therefore increases the rate of EPP amplitude rundown. Studies were performed in vitro on rat diaphragm and used micro-conotoxin to allow normal-sized EPPs to be recorded from intact fibers. EPP amplitude rundown during intermittent stimulation at 20 and 50 Hz (duty cycle 333 ms) was greater at 20 degrees C than it was at 37 degrees C. Initially, temperature affected only intra-train rundown but, over longer periods of stimulation, both intra- and inter-train rundown were significantly accelerated by cold temperature. Cumulative EPP amplitudes were calculated by successively adding the amplitudes of each EPP during the stimulation period to provide an estimate of total neurotransmitter release in the neuromuscular junction. The cumulative EPP amplitude was significantly lower at 20 degrees C than it was at 37 degrees C during both 20 and 50 Hz stimulation. These data indicate that the mechanism involved in EPP amplitude rundown and recovery is temperature-sensitive, with a greater decrement in EPP amplitude at cold than at warm temperatures.

Action Potentials↗

Effects on dystrophic (dy/dy) limb muscle of the K+ channel blocker tetraethylammonium.

K(+) channel blockers, such as tetraethylammonium (TEA) and 4-aminopyridine, increase force of normal skeletal muscle. To determine whether they also increase force of diseased muscle, effects of TEA were examined on limb muscles of dy/dy dystrophic mice in vitro. TEA significantly increased isometric twitch force of normal and dystrophic soleus muscle by 29.9+/-5.8 and 30.0+/-5.0%, respectively, and significantly increased force of normal and dystrophic extensor digitorum longus muscle by 18.3+/-1.9 and 34. 9+/-10.4%, respectively. Force increases could be attributed only partially to a prolongation of contraction time. These data indicate that TEA augments force of overtly diseased (dystrophic) limb muscle to an extent comparable with that of normal limb muscle.

Animals↗

Catchlike property of rat diaphragm: subsequent train frequency effects in variable-train stimulation.

A high-frequency burst of pulses at the onset of a subtetanic train of stimulation allows skeletal muscle to hold force at a higher level than expected from the extra pulses alone because of the catchlike property of muscle. The present study tested the hypothesis that the presence and degree of force increase induced by a high-frequency burst are strongly modulated by the subsequent train frequency. Rat diaphragm muscle strips (studied in vitro at 37 degrees C) underwent two-, three-, or four-pulse bursts [interpulse interval (IPI) of 5 or 10 ms] at the onset of 10- to 50-Hz subtetanic trains. Force was quantified during the train with respect to its peak value (F(peak)), mean value (F(mean)), and force-time integral (F(area)), and it was compared with that produced during subtetanic trains of an equal number of pulses without preceding pulse bursts (Diff-F(peak), Diff-F(mean), Diff-F(area)). F(peak) and F(mean) increased with two-, three-, and four-pulse bursts, and Diff-F(peak) and Diff-F(mean) increased progressively with decreasing frequency of the subtetanic train. F(area), the best reflection of catchlike force augmentation, was increased mainly by the four-pulse bursts with an IPI of 10 ms, and Diff-F(area) was maximal at subsequent train frequencies of 15-25 Hz. The use of incorrect patterns of burst stimulation could also precipitate F(area) decreases, which were observed with the four-pulse, 5-ms IPI paradigm. The time required to reach 80% of maximal force (T(80%)) became shorter for each of the pulse burst stimulation patterns, with maximal reduction of Diff-T(80%) occurring at a subsequent train frequency of 20 Hz in all cases. These data indicate that extra-pulse burst stimulation paradigms need to incorporate the optimal combinations of extra-pulse number, IPI, and the frequency of the subsequent subtetanic train to take greatest advantage of the catchlike property of muscle.

Analysis of Variance↗

Attenuation of rat diaphragm low-frequency fatigue by vanadate in vitro.

Sodium vanadate inhibits protein tyrosine phosphatases, including in skeletal muscle. Vanadate increases contractile force of airway, vascular and gastrointestinal smooth muscle. The present study tested the hypothesis that vanadate augments skeletal muscle contractility. Rat diaphragm muscle strips (n=26 from 12 animals) were studied in vitro at 37 degrees C. Muscles contracted isometrically while stimulated supramaximally with one of two protocols: 30 min of continuous 0.1 Hz stimulation, or 5 min of intermittent 20 Hz stimulation (duty cycle 0.33). Vanadate (500 microM)-treated muscle strips were compared with untreated muscle. Vanadate did not affect force or isometric twitch kinetics of otherwise quiescent muscle. During prolonged 0.1 Hz stimulation, force of control muscles declined by 17 +/- 4% over 30 min, whereas muscles incubated with vanadate maintained force virtually unchanged. Force over time was significantly greater with than without vanadate (P = 0.03), with values being significantly different during the last 10 min of the 30 min stimulation period. In the absence of vanadate force declined at a rate of approximately 0.6% per min, whereas with vanadate the rate of force decline was less than 0.1% per min (P < 0.02). During intermittent 20 Hz stimulation, the degree of force decline was not affected by vanadate at any time over a course of 5 min. Isometric contractile kinetics were not altered by vanadate during either 0.1 or 20 Hz stimulation. These data suggest that vanadate ameliorates low- but not higher-frequency fatigue in diaphragm, suggesting a role for protein tyrosine phosphorylation in the regulation of muscle fatigue resistance.

Animals↗

Peptide toxin blockers of voltage-sensitive K+ channels: inotropic effects on diaphragm.

Agents that block many types of K+ channels (e.g., the aminopyridines) have substantial inotropic effects in skeletal muscle. Specific blockers of ATP-sensitive and Ca2+-activated K+ channels, on the other hand, do not, or minimally, alter the force of nonfatigued muscle, consistent with a predominant role for voltage-gated K+ channels in regulating muscle force. To test this more directly, we examined the effects of peptide toxins, which in other tissues specifically block voltage-gated K+ channels, on rat diaphragm in vitro. Twitch force was increased in response to alpha-, beta-, and gamma-dendrotoxin and tityustoxin Kalpha (17 +/- 6, 22 +/- 5, 42 +/- 14, and 13 +/- 5%; P < 0.05, < 0.01, < 0.05, < 0.05, respectively) but not in response to delta-dendrotoxin or BSA (in which toxins were dissolved). Force during 20-Hz stimulation was also increased significantly by alpha-, beta-, and gamma-dendrotoxin and tityustoxin Kalpha. Among agents, increases in twitch force correlated with the degree to which contraction time was prolonged (r = 0.88, P < 0.02). To determine whether inotropic effects could be maintained during repeated contractions, muscle strips underwent intermittent 20-Hz train stimulation for a duration of 2 min in presence or absence of gamma-dendrotoxin. Force was significantly greater with than without gamma-dendrotoxin during repetitive stimulation for the first 60 s of repetitive contractions. Despite the approximately 55% higher value for initial force in the presence vs. absence of gamma-dendrotoxin, the rate at which fatigue occurred was not accelerated by the toxin, as assessed by the amount of time over which force declined by 25 and 50%. These data suggest that blocking voltage-activated K+ channels may be a useful therapeutic strategy for augmenting diaphragm force, provided less toxic blockers of these channels can be found.

Animals↗

Effect of phasic activation on endplate potential in rat diaphragm.

Neuromuscular junction endplate potentials (EPPs) decrease quickly and to a large extent during continuous stimulation. The present study examined the hypothesis that EPP rundown recovers rapidly, thereby substantially preserving neurotransmission during intermittent compared with continuous stimulation. Studies were performed in vitro on rat diaphragm, using mu-conotoxin to allow recording of normal-sized EPPs from intact fibers. During continuous 5- to 100-Hz stimulation, EPP amplitude declined with a biphasic time course. The initial fast rate of decline was modulated substantially by stimulation frequency, whereas the subsequent slow rate of decline was relatively frequency independent. During intermittent 5- to 100-Hz stimulation (duty cycle 0.33), EPP amplitude declined rapidly during each train, but recovered substantially by the onset of the following train. The intra-train declines were substantially greater than the inter-train declines in EPP amplitude. Intra-train reductions in EPP amplitude were stimulation frequency dependent, based on both the total decline and rate constant of EPP decline. In contrast, the degree of recovery from train to train was independent of stimulation frequency, indicating low frequency dependence of inter-train rundown. The substantial recovery of EPP amplitude in between trains resulted in greater cumulative EPP size during intermittent compared with continuous stimulation. During continuous stimulation, EPP drop-out was only seen during 100-Hz stimulation; this was completed mitigated during intermittent stimulation. Miniature EPP size was unaffected by either continuous or intermittent stimulation. The pattern of rapid intra-train rundown and slow inter-train rundown of EPP size during intermittent stimulation is therefore due to rapid changes in the magnitude of neurotransmitter release rather than to axonal block or postsynaptic receptor desensitization. These findings indicate considerable rundown of EPP amplitudes within a stimulus train, with near complete recovery by the onset of the next train. This substantially attenuates the decrement in EPP amplitude during intermittent compared with continuous stimulation, thereby preserving the integrity of neurotransmission during phasic activation.

Animals↗

Metabolic profiles of cat and rat pharyngeal and diaphragm muscles.

Pharyngeal muscles play important roles in the maintenance of upper airway patency during sleep. The present study determined the extent of heterogeneity among pharyngeal muscles and the diaphragm in their metabolic profiles, and examined whether differences among muscles may account for previously described differences in their fatigue resistance. Cat and rat sternohyoid, geniohyoid, genioglossus (cat only) and diaphragm muscle were assayed for activities of the mitochondrial enzyme citrate synthase (CS), the glycolytic enzyme phosphofructokinase (PFK) and the cytosolic enzyme lactate dehydrogenase (LDH). CS activity varied among muscles in both species, being highest for genioglossus in cat and highest for diaphragm in rat. PFK activity was highest for genioglossus in cat, but did not differ among muscles in rat. LDH activity was lower for the genioglossus than the sternohyoid and diaphragm in cat. CS and PFK activities correlated positively, and LDH activity correlated negatively, with in vitro fatigue resistance assessed after 5 min of repetitive stimulation in cat. These data indicate close relationships between metabolic profiles, particularly oxidative capacity, and fatigue resistance of pharyngeal muscles in relationship to each other and to the diaphragm.

Animals↗

Effects of theophylline on pharyngeal dilator and diaphragm muscle contractile properties.

Theophylline alleviates central and obstructive apneas of prematurity, and may improve adult obstructive sleep apnea. One mechanism of action appears to be a stimulatory effect on the motor output to upper airway dilator muscles. The purpose of the present study was to determine whether theophylline might have a second mechanism of action, namely that of improving the force and/or endurance of the pharyngeal dilator musculature. Rat sternohyoid muscle strips were studied in vitro and compared to diaphragm strips. The isometric twitch force and twitch kinetics of neither muscle were altered by theophylline (100 mg/l). Theophylline significantly slowed the rate at which the diaphragm fatigued during intermittent 40-Hz stimulation (p < 0.001). In contrast, theophylline produced no improvement in the fatigue resistance of the sternohyoid muscle. The degree of force potentiation during the early portion of the fatigue protocol was not altered by theophylline for either muscle. These results suggest that the mechanism by which theophylline improves obstructive apnea is unlikely to be due to a beneficial effect on pharyngeal dilator muscle force or endurance.

Animals↗

Effects of genetic obesity on rat upper airway muscle and diaphragm contractile properties.

The contractile properties of pharyngeal respiratory muscle are altered in sleep apnoea and in conditions associated with sleep apnoea, such as ageing. We hypothesized that the contractile properties of the pharyngeal musculature are also altered by obesity, another factor associated with sleep apnoea. Studies compared a pharyngeal muscle, the sternohyoid, with the diaphragm. These were chosen as representative muscles whose contraction has opposing effects on upper airway patency. Both muscles were removed from nine lean and nine obese male Zucker rats (a genetic model of obesity), and isometric contractile properties were studied in vitro at 37 degrees C. For the sternohyoid muscle, in obese compared to lean animals there were no significant differences in isometric contraction time (15.2 +/- 0.3 vs 14.2 +/- 0.6 ms, respectively), half-relaxation time (13.6 +/- 0.5 vs 12.6 +/- 0.9 ms, respectively), twitch-to-tetanic tension ratio (0.22 +/- 0.02 vs 0.24 +/- 0.02, respectively), force-frequency relationship, fatigue resistance (2 min fatigue index 0.20 +/- 0.03 vs 0.18 +/- 0.02, respectively), or maximal degree of force potentiation during repetitive stimulation (52 +/- 11 vs 74 +/- 20% increase, respectively). For the diaphragm, the only significant effect of obesity was a lowering of the twitch-to-tetanic tension ratio (0.25 +/- 0.01 vs 0.29 +/- 0.02, respectively). In obese, as in lean animals, the sternohyoid had faster isometric twitch kinetics, a larger degree of force potentiation, and lower resistance to fatigue, than the diaphragm. In lean, but not obese, animals the sternohyoid twitch-to-tetanic tension ratio was lower than and the force frequency relationship was located to the right of that of the diaphragm. In this study, genetic obesity in rats was not associated with any significant alterations in the contractile properties of the pharyngeal muscle, and only small changes in the relationship between the contractile properties of the sternohyoid and diaphragm muscle.

Aging↗

Comparative effects of aging on pharyngeal and diaphragm muscles.

We hypothesized that aging is associated with alterations in pharyngeal muscle structural and contractile properties. Sternohyoid and geniohyoid muscles from young (3-4 months) and old (20-21 months) Fischer 344 rats were compared with diaphragm muscle. The pharyngeal muscles had significantly lower proportions of slow oxidative (SO) fibers compared to the diaphragm, and the percentage of fast glycolytic (FG) fibers was significantly higher in the sternohyoid than in both the geniohyoid and the diaphragm. With senescence, there was a small but significant increase in the proportion of FG fibers and a corresponding reduction in the proportion of fast oxidative glycolytic (FOG) fibers in all three muscles. The sternohyoid muscle had significantly faster isometric contractile kinetics and lower fatigue indexes than the diaphragm. Aging was associated with significant worsening of sternohyoid endurance, but no significant alterations in sternohyoid twitch kinetics or diaphragm properties. These results indicate that in rats the pharyngeal dilator muscles have larger proportions of fast fibers, fast contractile kinetics and worse endurance than the diaphragm. Furthermore, aging was associated with a shift to a higher proportion of FG fibers with a concomitant reduction in proportion of FOG fibers, as well as a decline in pharyngeal muscle endurance.

Aging↗

Changes in pharyngeal respiratory muscle force produced by K+ channel blockade.

The purpose of the present study was to determine whether the contractility of pharyngeal respiratory muscles can be augmented by altering membranous K+ channel conductance. The effects on twitch force of two K+ channel blockers, tetraethylammonium (TEA, 10 mM) and 4-aminopyridine (4-AP, 0.3 mM), were examined in vitro for sternohyoid and diaphragm muscle strips. Both agents augmented isometric twitch force of both muscles. In response to TEA twitch force of the sternohyoid muscle increased significantly more than that of the diaphragm (by 33 +/- 7 vs. 9 +/- 1%, P = 0.004), whereas with 4-AP the increase in twitch force of the sternohyoid muscle was comparable to that of the diaphragm (55 +/- 15 vs. 64 +/- 6%, P = 0.50). 4-AP shifted the force-frequency relationship of both muscles leftward but did not alter peak tetanic force, so that force with 4-AP exceeded that without drug at stimulation frequencies below 60 Hz. In contrast TEA reduced force at stimulation frequencies > 20 Hz. The isometric contraction times of both muscles was variably prolonged, more so with 4-AP (by 30 +/- 15% for the sternohyoid and 32 +/- 3% for the diaphragm) than with TEA (by 9 +/- 2% for the sternohyoid and 5 +/- 2% for the diaphragm). For the group of muscles and K+ channel blockers, the degree of augmentation of twitch force correlated with the degree of prolongation of contraction time (r = 0.82, P < 0.001), consistent with blocking delayed rectifier K+ channels as the mechanism of increasing muscle force.

4-Aminopyridine↗

Pharyngeal dilator muscle contractile and endurance properties in neonatal piglets.

Pharyngeal dilator muscles are critical for maintaining upper airway patency in the neonatal period. The present study examined in vitro the contractile properties of a pharyngeal dilator muscle, the sternohyoid, in 1-7-day-old piglets (n = 24). Isometric contraction and half-relaxation times were 36.7 +/- 1.1 and 30.9 +/- 1.2 msec, respectively. Twitch potentiation ('staircase phenomenon') and post-tetanic potentiation were noted following repetitive stimulation. During prolonged repetitive stimulation with a standard (40 Hz) fatigue test, muscle force declined gradually over time, with loss of half of the initial force occurring over 138 +/- 11 sec, and a 2-min fatigue index (ratio of force at 2 min to initial force) of 0.52 +/- 0.03. An additional 10 piglets were studied at ages of 14-20 days. Muscle from older piglets had comparable isometric twitch kinetics as that of younger animals. However, sternohyoid muscle from the older piglets had worse endurance than muscle from the younger animals, as indicated by a shorter time required for force to decrease by half (86 +/- 10 sec, P < 0.01) and a lower 2-min fatigue index (0.36 +/- 0.03, P < 0.01). These data indicate that for the sternohyoid muscle of the newborn piglet (a) physiological properties are consistent with moderate to fast contraction with good endurance, (b) force potentiates during repetitive twitch stimulation and following a brief period of tetanic stimulation, and (c) there is worsening of endurance but no change in isometric twitch kinetics with increasing age during the first weeks of life.

Aging↗

Central and spinal effects of sodium cyanide on respiratory activity.

The pharmacological actions of cyanide on respiratory activity have been known for some time and are attributed mainly to effects on peripheral chemoreceptors. In the studies reported here, we have examined the acute central effects of cyanide when applied topically to the ventral surface of the medulla (VMS) and when administered into the spinal intrathecal space at the C5-T3 level on activities of the phrenic nerve, diaphragm, parasternal intercostal, triangularis sterni, and transversus abdominis muscles. Topical application of 10-100 micrograms (10 microliters of 1-10 mg/ml) cyanide to the intermediate area of the VMS decreased respiratory activity by > 50%, and expiratory muscles were more sensitive to inhibition than inspiratory muscles. The onset of depression of phrenic nerve or respiratory muscle activity occurred within 20 s of administration, and the effects reversed after washout. In contrast, intrathecal administration of cyanide in doses of 10-100 micrograms (100 microliters of 0.1-1 mg/ml) increased electrical activity of the respiratory muscles. Diaphragm activity changed from 17 +/- 2 to 42 +/- 8 (SE) units (P < 0.01), parasternal intercostal activity increased from 18 +/- 3 to 46 +/- 9 units (P < 0.01), and expiratory activity of the chest wall and abdominal muscles increased from 9 +/- 2 to 39 +/- 10 units (P < 0.05). Both topical application on the VMS and intrathecal administration of cyanide caused an increase in arterial blood pressure and a slight insignificant acceleration of heart rate. These data suggest that cyanide acting on the VMS causes respiratory depression and enhancement of sympathetic outflow.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗