Partial Curarization Research Articles

The rate of fatigue accumulation as a sensed variable

The rate of fatigue accumulation as a sensed variable

Effects of Ondansetron and Granisetron on Rocuronium-induced Neuromuscular Blockade in a Rat Phrenic Nerve-hemidiaphragm Preparation

Background: Both ondansetron and granisetron exert their antiemetic effects via a blockade of the 5-hydroxytryptamine 3 receptor (). Because the is a member of a superfamily of ligand-gated ion channels and has structural similarities to the nicotinic acetylcholine receptor (nAChR), a antagonist may also inhibit the nAChR. This study examined the effects of antagonists, ondansetron and granisetron, on rocuronium-induced neuromuscular blockade in vitro. Methods: Rat phrenic nerve-hemidiaphragm preparations were isolated and allocated randomly into seven groups (control, 1, 10, 100/ml of ondansetron, 0.1, 1, 10/ml of granisetron). Two studies were carried out using single twitch responses. In the cumulative dose-response study, rocuronium 1/ml and each doses of ondansetron or granisetron were administered simultaneously, and incremental 0.5/ml doses of rocuronium were added to obtain more than 95% neuromuscular twitch inhibition. , , , and of rocuronium in each group were calculated using a logistic model. In the partial curarization study, the twitch heights were measured after administering ondansetron or granisetron (10 minutes after administering 3/ml rocuronium) and were measured 10 minutes later. The 2 twitch heights were then compared. Results: In the cumulative dose-response study, ondansetron 100/ml and granisetron 10/ml significantly reduced the of rocuronium (P ＜ 0.05). There were no intergroup differences in the partial curarization study. Conclusions: High concentration of ondansetron and granisetron enhanced the neuromuscular blockade of rocuronium. Granisetron enhanced the neuromuscular blockade of rocuronium more potently than ondansetron.

Cardiovascular and catecholamine responses to static exercise in partially curarized humans.

Neural control of the circulation was evaluated during static exercise in 19 subjects by the determination of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO) and plasma catecholamines. Influence from central command was evaluated during contractions with weakened muscles following partial curarization and reflex influence from metaboreceptors was assessed by post-exercise muscle ischaemia. Static handgrip increased HR and more so MAP and CO and MAP remained elevated during post-exercise muscle ischaemia. With partial curarization plasma catecholamines were also increased (P < 0.05). Two-leg extension increased all variables and during post-exercise muscle ischaemia elevations of HR, MAP and CO were maintained (P < 0.05). With partial curarization HR, MAP and plasma noradrenaline were even greater during the contraction. With the involvement of both legs during static exercise, reflex influence from the muscles elevated blood pressure by way of HR and CO and the importance of central command was detectable for HR and MAP as plasma catecholamines became elevated. However, the results indicate a separation between a central command influence on HR and CO related to an increase in plasma catecholamines during a handgrip, while the reflex influence on blood pressure was directed towards total peripheral resistance.

Reactions of neurons of the posterior ventral nucleus of the thalamus of the rat during movements of the vibrissae.

The reactions of neurons of the posterior ventral nucleus of the thalamus were investigated during movements of the vibrissae, accomplished independently by the animal, in experiments on rats utilizing a technique of partial curarization proposed by the author. Differences were identified in the pattern of the reactions of the thalamic neurons to deviation of a vibrissa by the experimenter from the pattern of the reactions of the same neurons to deviation of the vibrissa elicited by its hitting against a barrier during a sweep. A dependence of the response of the sensory neurons on whether or not the barrier was mobile during the period of the sweep of the vibrissae was also demonstrated. The hypothesis is advanced that at the thalamic level the analysis of the parameters of the stimulus is accomplished in connection with information regarding movements of the vibrissae.

Partial curarization abolishes splitting of the inorganic phosphate peak in 31P‐NMR spectroscopy during intense forearm exercise in man

In this report using partial curarization, we present evidence suggesting that a mixture of active and inactive musle fibres does not provoke splitting the Pi peak during intense contraction.

Autonomic blockade and cardiovascular responses to static exercise in partially curarized man.

1. The cardiovascular responses, heart rate and mean arterial pressure, were followed in seventeen human subjects who performed static handgrip contractions for 2 min at the same absolute force (15% of the initial maximal voluntary contraction strength) before and during partial curarization. In control contractions the rate of perceived exertion was 10 exertion units, 16 units in contractions with tubocurarine which could be maintained and 20 units in contractions that could not be maintained. Control contractions increased mean arterial pressure by 6 mmHg from 89 mmHg while heart rate was unchanged from the resting value of 68 beats min-1. With tubocurarine, larger increases in mean arterial pressure of 11 mmHg and for heart rate of 8 beats min-1 were obtained during maintained contractions, and 15 mmHg and 16 beats min-1, respectively, during non-maintained contractions. 2. Atropine increased resting heart rate and blood pressure with tubocurarine to 107 beats min-1 and 98 mmHg, respectively, in seven subjects. The blood pressure response to exercise with tubocurarine was unaffected by atropine, but the heart rate increase was reduced from 15 to 4 beats min-1. 3. Propranolol reduced resting heart rate with tubocurarine to 56 beats min-1 with no effect on blood pressure in seven subjects. The cardiovascular responses to exercise with tubocurarine were unaffected by propranolol. In contrast, phentolamine reduced resting blood pressure with tubocurarine to 80 mmHg without affecting heart rate in seven subjects. Exercise responses with tubocurarine were unaffected by phentolamine. Combinations of atropine and propranolol in fourteen subjects or atropine and phentolamine in five subjects showed similar results during exercise with tubocurarine as with the sole use of the agents used to block autonomic receptors. 4. The results suggest that when partial curarization induces a disproportion between the signal from central command and that from exercising muscles, the larger signal arising from central command determines the magnitude of the cardiovascular responses. The centrally generated heart rate response is in part caused by vagal withdrawal. However, the blood pressure response cannot be attenuated by the sole use of alpha- or beta-receptor adrenergic blockade or combinations of these with atropine. This suggests that there may be greater redundancy in the autonomic control of blood pressure than in the vagal control of heart rate associated with central command during static exercise in man.

Cardiovascular responses at the onset of exercise with partial neuromuscular blockade in cat and man.

1. In decerebrated cats the cardiovascular, heart rate and blood pressure responses to static muscle contractions were followed from the onset of stimulation of the cut L7-S1 ventral roots. Heart rate and blood pressure were also followed during maximal voluntary and electrically induced static muscle contractions in man using one leg. In both cat and man contractions were performed under control conditions and tubocurarine-induced neuromuscular blockade. 2. In the cat, heart rate and blood pressure increased 1.7 s after the onset of the contraction. No cardiovascular responses were seen when the muscle contraction was blocked by tubocurarine. 3. In man, both heart rate and blood pressure increased at the onset of voluntary contractions. Partial curarization reduced strength to 39% of control. The heart rate response was unaffected by tubocurarine while the blood pressure response was reduced from 61 to 32 mmHg. 4. Electrical stimulation of the muscles resulted in 75% of voluntary strength in man. The heart rate response was delayed one R-R interval in the electrocardiogram but was as large as during voluntary contractions. During partial curarization the heart rate response was significantly smaller and the blood pressure response was reduced from 11 to 8 mmHg. 5. In conclusion, processes in active muscles elicit an increase in heart rate and blood pressure which depends on the intensity of the muscle contraction developed. However, the immediate cardiovascular responses at the onset of voluntary muscle contractions cannot be accounted for by reflexes generated in the working muscles alone.

Effect of respiratory muscle weakness on P0.1 induced by partial curarization.

Mouth occlusion pressure 0.1 s after onset of inspiration (P0.1) reflects central respiratory drive (CRD), but its dependence on respiratory muscle strength is unknown. To clarify this relationship, we produced progressive levels of respiratory muscle weakness by infusion of d-tubocurarine in eight supine spontaneously breathing normal subjects. Hypercapnic ventilatory response (HCVR) was measured before curarization and at mild (mean inspiratory effort 62 +/- 3% of control), moderate (42 +/- 3%), and severe (23 +/- 1%) weakness. At the severe level of weakness 1) supine functional residual capacity was not significantly changed from base line, 2) the percent of base-line slope of delta P0.1/delta PCO2 (122 +/- 27%) was significantly greater (P less than 0.01) than that for change in expired minute ventilation (delta VE)/delta PCO2 (39 +/- 10%), 3) the percent of base-line delta P0.1/delta VE (381 +/- 46%) during HCVR was significantly increased (P less than 0.01), 4) the P0.1 response was significantly increased from base line at two out of three specific levels of PCO2 while the VE was unchanged or significantly decreased, and 5) peak inspiratory resistance did not significantly change. Thus P0.1, unlike VE, did not decrease with even severe respiratory muscle weakness. Indeed, P0.1 increased at two out of three levels of PCO2 under circumstances when higher CRD is expected. One potential explanation for the results is that P0.1 may at least qualitatively reflect CRD up to the level of severe respiratory muscle weakness attained in this study.

Partial curarization in the postoperative period.

Forty-eight patients subjected to elective surgery were randomly selected for evaluation of neuromuscular transmission in the postoperative period. All patients were anaesthetized with thiopentone, nitrous oxide, fentanyl and pancuronium. On arrival in the postoperative ward, alertness, ability to sustain head lift and the train-of-four (TOF) ratio were estimated. Twenty-five percent of the patients had a markedly impaired neuromuscular transmission which was not acceptable from a clinical standpoint. The given dose of pancuronium was not excessively high and a fairly long time had elapsed between reversal and TOF-ratio measurement. There was a poor correlation between TOF ratio and ability to sustain head lift. The study indicates that residual curarization is a not uncommon fact which clinically is hard to assess. The only wat to avoid residual curarization seems to be to monitor the neuromuscular transmission during anaesthesia.

Breathing Patterns During Curare-Induced Muscle Weakness

This study examines the pattern of breathing used by normal subjects to compensate for an acute decrease in muscle strength. A continuous infusion of curare was used to reduce peak inspiratory pressure in six normal subjects from normal control levels to -45 cm H2O (moderate weakness) and to -70 cm H2O (mild weakness). Before administration of curare, inspiratory pressure exceeded -120 cm H2O. A canopy-computer-spirometer system was used for noninvasive spirometry and measurements of gas exchange. Partial curarization to a mild level of muscle weakness did not produce significant changes in the respiratory functions studied. With a moderate level of muscle weakness, there were significant increases in tidal volume from 166 to 186 ml/m2 and in inspiratory time from 1.51 to 1.71 sec (P less than 0.05). Minute ventilation and inspiratory flow did not change. However, when given 3% CO2, both normal and partially curarized subjects increased minute ventilation, from 2.3 to 5.7 L/min/m2 and from 2.5 to 6.7 L/min/m2, respectively. The increases in both conditions were secondary to increases in tidal volume. There was also a small increase in respiratory frequency from 15.4 to 18 breaths/min, P less than 0.01 in the partially curarized group given 3% CO2. Because minute ventilation was preserved while vital capacity decreased, it is proposed that respiration is maintained in the presence of muscle weakness associated with curare by diaphragmatic function which remains relatively unaffected by curarization.

Breathing Patterns during Curare-Induced Muscle Weakness

This study examines the pattern of breathing used by normal subjects to compensate for an acute decrease in muscle strength. A continuous infusion of curare was used to reduce peak inspiratory pressure in six normal subjects from normal control levels to −45 cm H2O (moderate weakness) and to −70 cm H2O (mild weakness). Before administration of curare, inspiratory pressure exceeded −120 cm H2O. A canopy-computer-spirometer system was used for noninvasive spirometry and measurements of gas exchange. Partial curarization to a mild level of muscle weakness did not produce significant changes in the respiratory functions studied. With a moderate level of muscle weakness, there were significant increases in tidal volume from 166 to 186 ml/m2 and in inspiratory time from 1.51 to 1.71 sec (P < 0.05). Minute ventilation and inspiratory flow did not change. However, when given 3% CO2, both normal and partially curarized subjects increased minute ventilation, from 2.3 to 5.7 L/min/m2 and from 2.5 to 6.7 L/min/m2, respectively. The increases in both conditions were secondary to increases in tidal volume. There was also a small increase in respiratory frequency from 15.4 to 18 breaths/min, P < 0.01 in the partially curarized group given 3% CO2. Because minute ventilation was preserved while vital capacity decreased, it is proposed that respiration is maintained in the presence of muscle weakness associated with curare by diaphragmatic function which remains relatively unaffected by curarization.

Relationship between respiratory muscle strength and vital capacity during partial curarization in awake subjects: T. J. Gal, S. K. Golberg. Anesth, 54:141–147, (February), 1981

Relationship between respiratory muscle strength and vital capacity during partial curarization in awake subjects: T. J. Gal, S. K. Golberg. Anesth, 54:141–147, (February), 1981

Relationship between Respiratory Muscle Strength and Vital Capacity during Partial Curarization in Awake Subjects

Departments of Anesthesiology and Internal Medicine, University of Virginia Medical Center, Charlottesville, Virginia

Respiratory mechanics in supine subjects during progressive partial curarization.

Respiratory mechanics were studied in six supine conscious volunteers during progressive muscle weakness produced by infusion of d-tubocurarine. Partial curarization was carried out to the point of abolishing head lift ability and handgrip strength. At all levels of partial paralysis, expiratory muscle strength was significantly more impaired than inspiratory strength. Despite this, subjects maintained relatively normal maximal expiratory flow rates, whereas inspiratory flows decreased significantly. The diminished inspiratory flows are not fully explained by decreased driving pressures during force inspiration, since inspiratory resistance increased significantly with the decreased flow. Inspiratory flow patterns suggest a variable extrathoracic obstruction most likely due to the absence of normal airway abductor activity during inspiration. Maximal respiratory muscle weakness decreased forced vital capacity by 29% and total lung capacity by 15%. The decreased level of lung inflation did not alter lung elastic recoil. Functional residual capacity was unchanged, but inspiratory capacity decreased by 25% and residual volume increased by 38%. These changes are in accord with predictions based on the decreased muscle strength and normal respiratory system recoil.

Diaphragmatic Function in Healthy Subjects during Partial Curarization

Diaphragmatic Function in Healthy Subjects during Partial Curarization

Centrally-generated commands and cardiovascular control in man.

It has long been established that neural activity generated wholly within the central nervous system can affect cardiovascular control. Even during complete paralysis the central cycling of respiratory neurones can impose respiratory rhythmicity on heart rate and vasomotion, and alter the effectiveness of purely cardiovascular reflexes. During muscular exercise centrally-generated voluntary motor command signals contribute to the stimulation of heart rate and the rise in blood pressure. This is seen, for example, when muscular weakness is induced by partial curarization, by fatigue, or by other means, so that a given level of muscular contraction is achieved only with an increased motor command, or 'effort'. Such command-related stimuli are essentially without cardiovascular feedback and are likely at most to provide coarse adjustments upon which finer controls are superimposed by well-known reflex mechanisms.

Changes in the perception of inspiratory resistive loads during partial curarization.

1. The ability of normal subjects to estimate the magnitude of resistive loads and to detect resistive loads was determined using standard psychophysical techniques. The experiments were repeated during maintained partial neuromuscular blockade with D-tubocurarine. 2. During curarization the ability to detect the presence of a small inspiratory resistive load was not significantly impaired. This finding is consistent with the view that changes in the usual breath-by-breath relation between pressure and flow mediate detection. 3. The size of resistive loads was over-estimated during partial curarization. Subjects thus placed more reliance on sensing the increased motor command required during curarization than on alternative peripheral signals related to pressure, flow or resistance. 4. The exponent for the power function relating the perceived magnitude of a resistive load to its actual size (Stevens, 1957) was reduced during partial neuromuscular blockade. 5. These results suggest that detection of resistive loads depends upon sensing apparent information arising from an unexpected pressure-flow disturbance but that estimation of the size of an added load depends, in part, on sensing the outgoing motor command.

Function of respiratory muscles during partial curarization in humans

The effects of submaximal neuromuscular blockade (SMNB) on the recruitment (or derecruitment) of the respiratory muscles during different types of respiratory maneuvers were studied in four healthy males infused slowly with pancuronium. The effects on lung mechanics were similar to those observed previously in that lung recoil pressure during inspiration did not change while the chest wall pressure-volume (PV) curve was shifted to the right (Rahn diagram). In each subject, SMNB produced a large increase in abdominal (gastric) and transdiaphragmatic pressures at any given lung volume during inspiration, reflecting greater diaphragmatic contribution to respiratory pressure swings. In addition, using concentric needle electrodes, we observed a marked fall in electrical (tonic and phasic) activity in the abdominal and in the intercostal/accessory muscles during SMNB but a slight increase in diaphragmatic activity. This pattern of changes was accentuated as ventilation increased. These findings indicate that the diaphragm is more resistant to curare than the other respiratory muscles in humans and that the transposition of the chest wall PV curve during SMNB is related to a loss of tonic activity in the intercostal musculature. The difference in sensitivity toward curare between the diaphragm and the other respiratory muscles is probably related to a difference in the safety margin at the neuromuscular synapses.

Diaphragmatic function in healthy subjects during partial curarization.

Diaphragmatic function estimated by transdiaphragmatic pressure (Pdi) was studied in eight normal subjects during progressive partial paralysis with d-tubocurarine (dTc). Dynamic Pdi was measured during quiet tidal breathing, maximum deep inspiration, and 12-s maximum voluntary ventilation (MVV). Maximum static transdiaphragmatic pressure (Pdimax) was also measured during maximum static inspiratory efforts at four lung volumes. The maximum effect of dTc at a cumulative dose of 0.2 mg/kg abolished head-lift and handgrip ability. Pdimax at functional residual capacity was decreased to 42% of its control value indicating significant diaphragmatic weakness at this level of curarization. The weakness had no inpact on quiet breathing and a moderate effect on maximum inspiration. In either case Pdi represented an increasing fraction of Pdimax. MVV fell significantly before the Pdi during the maneuver decreased. This decreased MVV in curarized subjects reflects upper airway obstruction caused by pharyngeal muscle weakness and the diminished contribution of the other respiratory muscles that are important at high levels of ventilatory effort but more sensitive to effects of dTc.

Changes in motor commands, as shown by changes in perceived heaviness, during partial curarization and peripheral anaesthesia in man.

1. The centrally generated ;effort' or direct voluntary command to motoneurones required to lift a weight was studied using a simple weight-matching task when the muscles lifting a reference weight were weakened. This centrally generated input to motoneurones was increased when the lifting muscles were partially paralysed with curare or decamethonium as judged by the increased perceived heaviness of a reference weight lifted by the weakened muscles.2. If subjects were asked simply to make matching isometric contractions when the lifting muscles were weakened the isometric tension produced by a weakened muscle was over-estimated.3. When subjects matched weights by flexing the distal joint of the thumb the perceived heaviness of a reference weight during a control partial curarization was compared with its perceived heaviness during a similar partial curarization when the thumb was also anaesthetized. At any level of maximal strength during curarization the perceived heaviness (which reflects the motor command to lifting motoneurones) was increased when the thumb was anaesthetized.4. This increased voluntary command to lifting motoneurones may be required because automatic reflex assistance provided by apparent servo action from the long flexor of the thumb is suppressed by anaesthesia of the thumb (Marsden, Merton & Morton, 1971, 1973, 1976a; Dyhre-Poulsen & Djørup, 1976).