Investigation of Systemic Bupivacaine Toxicity using the In situ  Perfused Working Heart-Brainstem Preparation of the Rat

2002 ◽  
Vol 97 (6) ◽  
pp. 1550-1556 ◽  
Author(s):  
Anthony E. Pickering ◽  
Hidefumi Waki ◽  
P. Max Headley ◽  
Julian F.R. Paton
Keyword(s):  
Phrenic Nerve ◽  
Neural Control ◽  
Pressor Response ◽  
Ringer Solution ◽  
Cardiovascular Control ◽  
Cardiovascular Collapse ◽  
Sinus Arrhythmia ◽  
Cardiorespiratory Control ◽  
Aortic Depressor Nerve ◽  
Working Heart

Background The inadvertent systemic administration of bupivacaine has been associated with fatal cardiovascular collapse. Systemic bupivacaine may affect neural control of the cardiovascular system in addition to having toxic actions on the heart. The study tested the hypothesis that systemic bupivacaine has toxic effects on brainstem cardiorespiratory control. Methods The working heart-brainstem preparation (WHBP) of rat was used to examine the actions of bupivacaine administered either by arterial injection or brainstem microinjection. The WHBP is a decerebrate rostral-half of a bisected rat, which is artificially perfused with a carbogenated Ringer solution via the aorta. Phrenic nerve activity, perfusion pressure, and electrocardiographic results were recorded. Results Systemic bupivacaine (3 microg/ml) evoked a prolonged pressor response (10.5 +/- 5 mmHg) associated with marked bradycardia (-45 +/- 22 beats/min) and prolonged the PR and QRS intervals of the electrocardiogram. The amplitude of respiratory sinus arrhythmia was attenuated (64 +/- 15%) by bupivacaine without affecting activity recorded from the phrenic nerve. Bupivacaine selectively attenuated the baroreflex gain (55 +/- 19%) but had no effect on the peripheral chemoreflex-evoked bradycardia. The bradycardia elicited by stimulation of the aortic depressor nerve was inhibited by bupivacaine, indicating baroreflex inhibition within the brainstem. Furthermore, bilateral microinjections of bupivacaine in the nucleus of the solitary tract reversibly inhibited the baroreflex. Conclusions These results demonstrate that arterial concentrations of bupivacaine that previously were shown to be cardiotoxic can selectively affect key cardiovascular control processes within the brainstem. Such impairment of neural cardiovascular control may contribute to the cardiovascular collapse associated with systemic bupivacaine.

Daily acute intermittent hypoxia enhances phrenic motor output and stimulus-evoked phrenic responses in rats

2021 ◽  
Author(s):  
Raphael Rodrigues Perim ◽  
Michael D. Sunshine ◽  
Joseph F. Welch ◽  
Juliet Santiago ◽  
Ashley Holland ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Phrenic Nerve ◽  
Intermittent Hypoxia ◽  
Neural Control ◽  
Respiratory Cycle ◽  
Evoked Responses ◽  
Nerve Activity ◽  
Synaptic Inputs ◽  
Phrenic Nerve Activity ◽  
The Impact

Plasticity is a hallmark of the respiratory neural control system. Phrenic long-term facilitation (pLTF) is one form of respiratory plasticity characterized by persistent increases in phrenic nerve activity following acute intermittent hypoxia (AIH). Although there is evidence that key steps in the cellular pathway giving rise to pLTF are localized within phrenic motor neurons (PMNs), the impact of AIH on the strength of breathing-related synaptic inputs to PMNs remains unclear. Further, the functional impact of AIH is enhanced by repeated/daily exposure to AIH (dAIH). Here, we explored the effects of AIH vs. 2 weeks of dAIH preconditioning on spontaneous and evoked responses recorded in anesthetized, paralyzed (with pancuronium bromide) and mechanically ventilated rats. Evoked phrenic potentials were elicited by respiratory cycle-triggered lateral funiculus stimulation at C2 delivered prior to- and 60 min post-AIH (or an equivalent time in controls). Charge-balanced biphasic pulses (100 µs/phase) of progressively increasing intensity (100 to 700 µA) were delivered during the inspiratory and expiratory phases of the respiratory cycle. Although robust pLTF (~60% from baseline) was observed after a single exposure to moderate AIH (3 x 5 min; 5 min intervals), there was no effect on evoked phrenic responses, contrary to our initial hypothesis. However, in rats preconditioned with dAIH, baseline phrenic nerve activity and evoked responses were increased, suggesting that repeated exposure to AIH enhances functional synaptic strength when assessed using this technique. The impact of daily AIH preconditioning on synaptic inputs to PMNs raises interesting questions that require further exploration.

Interaction between thyrotrophin-releasing hormone and the muscarinic cholinergic system in rat brain

1992 ◽  
Vol 134 (2) ◽  
pp. 215-219 ◽  
Author(s):  
S. I. Garcia ◽  
S. M. Dabsys ◽  
D. Santajuliana ◽  
A. Delorenzi ◽  
S. Finkielman ◽  
...  
Keyword(s):  
Cholinergic System ◽  
Wistar Rats ◽  
Preoptic Area ◽  
Pressor Response ◽  
Acetylcholinesterase Inhibitor ◽  
Ringer Solution ◽  
Brain Areas ◽  
Thyrotrophin Releasing Hormone ◽  
Atropine Treatment ◽  
Muscarinic Cholinergic

ABSTRACT TRH increases the pressor response to acetylcholine through an increment in muscarinic receptors. As chronic atropinization produces a similar effect, we hypothesized that both phenomena may be related. The effect of chronic atropine treatment on the TRH content of several brain areas in Wistar rats was studied. Atropine produced significant increases in TRH content in the preoptic and septal areas, while decreases were observed in the hypothalamus and hypophysis. The concentration of TRH in cerebrospinal fluid rose significantly in atropine-treated rats compared with controls. A similar effect was observed with eserine, an acetylcholinesterase inhibitor. Finally, perfusion of brain preoptic area slices from normal rats with Krebs–Ringer solution in the presence of pilocarpine increased basal TRH release significantly and this effect was blocked by atropine. These results are compatible with a muscarinic control on the activity of the central TRH system. Journal of Endocrinology (1992) 134, 215–219

scholarly journals The effect of adenotonsillectomy for childhood sleep apnoea on cardiorespiratory control

2016 ◽  
Vol 2 (2) ◽  
pp. 00003-2016 ◽  
Author(s):  
Mathias Baumert ◽  
Yvonne Pamula ◽  
James Martin ◽  
Declan Kennedy ◽  
Anand Ganesan ◽  
...  
Keyword(s):  
Heart Rate ◽  
Respiratory Rate ◽  
Obstructive Sleep Apnoea ◽  
Respiratory Sinus Arrhythmia ◽  
Sleep Apnoea ◽  
Obstructive Sleep Apnoea Syndrome ◽  
Sinus Arrhythmia ◽  
Cardiorespiratory Control ◽  
Post Surgery ◽  
Obstructive Sleep

The efficacy of adenotonsillectomy for relieving obstructive sleep apnoea symptoms in children has been firmly established, but its precise effects on cardiorespiratory control are poorly understood.In 375 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either adenotonsillectomy (n=194) or a strategy of watching waiting (n=181), respiratory rate, respiratory sinus arrhythmia and heart rate were analysed during quiet, non-apnoeic and non-hypopnoeic breathing throughout sleep at baseline and at 7 months using overnight polysomnography.Children who underwent early adenotonsillectomy demonstrated an increase in respiratory rate post-surgery while the watchful waiting group showed no change. Heart rate and respiratory sinus arrhythmia were comparable between both arms. On assessing cardiorespiratory variables with regard to normalisation of clinical polysomnography findings during follow-up, heart rate was reduced in children who had resolution of obstructive sleep apnoea syndrome, while no differences in their respiratory rate or respiratory sinus arrhythmia were observed.Adenotonsillectomy for obstructive sleep apnoea increases baseline respiratory rate during sleep. Normalisation of apnoea–hypopnoea index, spontaneously orviasurgery, lowers heart rate. Considering the small average effect size, the clinical significance is uncertain.

scholarly journals Paced Breathing Increases the Redundancy of Cardiorespiratory Control in Healthy Individuals and Chronic Heart Failure Patients

Entropy ◽  
2018 ◽  
Vol 20 (12) ◽  
pp. 949 ◽  
Author(s):  
Alberto Porta ◽  
Roberto Maestri ◽  
Vlasta Bari ◽  
Beatrice De Maria ◽  
Beatrice Cairo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fault Tolerance ◽  
Chronic Heart Failure ◽  
Partial Information ◽  
Heart Period ◽  
Sinus Arrhythmia ◽  
Cardiorespiratory Control ◽  
Decomposition Approach ◽  
Heart Failure Patients ◽  
Young Subjects

Synergy and redundancy are concepts that suggest, respectively, adaptability and fault tolerance of systems with complex behavior. This study computes redundancy/synergy in bivariate systems formed by a target X and a driver Y according to the predictive information decomposition approach and partial information decomposition framework based on the minimal mutual information principle. The two approaches assess the redundancy/synergy of past of X and Y in reducing the uncertainty of the current state of X. The methods were applied to evaluate the interactions between heart and respiration in healthy young subjects (n = 19) during controlled breathing at 10, 15 and 20 breaths/minute and in two groups of chronic heart failure patients during paced respiration at 6 (n = 9) and 15 (n = 20) breaths/minutes from spontaneous beat-to-beat fluctuations of heart period and respiratory signal. Both methods suggested that slowing respiratory rate below the spontaneous frequency increases redundancy of cardiorespiratory control in both healthy and pathological groups, thus possibly improving fault tolerance of the cardiorespiratory control. The two methods provide markers complementary to respiratory sinus arrhythmia and the strength of the linear coupling between heart period variability and respiration in describing the physiology of the cardiorespiratory reflex suitable to be exploited in various pathophysiological settings.

Effect of hypoxia on neuromuscular transmission in the developing diaphragm

1994 ◽  
Vol 76 (2) ◽  
pp. 708-713 ◽  
Author(s):  
A. R. Bazzy
Keyword(s):  
Nerve Stimulation ◽  
Phrenic Nerve ◽  
Neuromuscular Transmission ◽  
Ringer Solution ◽  
Diaphragm Muscle ◽  
Control Force ◽  
Force Response ◽  
Direct Stimulation ◽  
Frequency Of Stimulation ◽  
Predominant Effect

To study the effects of hypoxia on neuromuscular transmission in the developing diaphragm, phrenic nerve-hemidiaphragm preparations were obtained from newborn (4–9 days) and older (22–30 days) rats. Diaphragms were stimulated directly or indirectly (via the nerve) for 1 s at frequencies of 10–80 Hz. Force generated in response to stimulation was measured during perfusion of oxygenated Ringer solution (control) and Ringer solution bubbled with 95% N2–5% CO2 (hypoxia). After 45 min of hypoxia, the force response of the older diaphragms to direct stimulation had decreased to approximately 50% of control at > or = 40 Hz; however, when stimulation occurred via the nerve at these frequencies only 15–20% of control force was generated. In the newborn diaphragms, the force decrement after similar or longer periods of hypoxia (< or = 90 min) was 30– 40% irrespective of the route or frequency of stimulation. After 15 min of reoxygenation, the force response to both muscle and nerve stimulation recovered completely in the older diaphragms but only partially in the newborn diaphragms (range 77% of control at 50 Hz to 95% of control at 10 Hz). These data suggest that in the newborn diaphragm 1) neuromuscular transmission is more resistant to the effects of hypoxia than the older diaphragm and 2) the predominant effect of hypoxia is peripheral in the diaphragm muscle fibers, whereas in the older diaphragm the effect is before or at the neuromuscular junction.

Inhibition of carotid pressor response by left aortic depressor nerve in dogs

1981 ◽  
Vol 240 (4) ◽  
pp. H555-H560 ◽  
Author(s):  
S. C. Walgenbach ◽  
D. E. Donald ◽  
A. Melcher
Keyword(s):  
Arterial Pressure ◽  
Pressor Response ◽  
The Other ◽  
Carotid Occlusion ◽  
Aortic Depressor Nerve ◽  
Vagal Nerves ◽  
Isolated Aorta ◽  
Anesthetized Dogs ◽  
The Mean ◽  
Aortic Baroreceptors

In 12 conscious dogs, the mean increase of 26 mmHg in arterial pressure during carotid occlusion was augmented by 52 mmHg after section of the left cervical vagus nerve and 6 mmHg after right vagal section. In 18 anesthetized dogs, in which the cervical vagal nerves were reversibly cold blocked, corresponding values were 33, 28, and 6 mmHg, respectively. In nine of these dogs, this left-sided dominance was present after bilateral section of the vagal cardiopulmonary afferents; it was absent after bilateral section of the aortic nerves in the other nine dogs. In five dogs on cardiopulmonary bypass with heart and lungs excluded, pressure within the isolated aorta and major intrathoracic arteries was raised from 120 to 220 mmHg. The resultant hypotension reflexly induced by activation of aortic baroreceptors was reduced by left but not by right vagal cold block. It was concluded that, in the dog, the left aortic nerve provided the major inhibition of the increase in arterial pressure after carotid occlusion.

Increased dietary sodium alters neural control of blood pressure during intravenous ANG II infusion

2003 ◽  
Vol 284 (2) ◽  
pp. H559-H565 ◽  
Author(s):  
Steven L. Bealer
Keyword(s):  
Blood Pressure ◽  
Neural Control ◽  
Tap Water ◽  
Pressor Response ◽  
Isotonic Saline ◽  
Dietary Sodium ◽  
Male Rats ◽  
Ang Ii ◽  
Blood Pressure Responses

Increased dietary sodium enhances both excitatory and inhibitory blood pressure responses to stimulation of the central sympathetic nervous system (SNS) centers. In addition, long-term (hours to days) administration of ANG II increases blood pressure by activation of the SNS. These studies investigated the effects of increased dietary sodium on SNS control of blood pressure during 0- to 24-h infusion of ANG II in conscious, male rats consuming either tap water or isotonic saline (Iso) for 2 to 3 wk. The SNS component (evaluated by ganglionic blockade with trimetaphan) of both control blood pressure and the pressor response to intravenous ANG II was reduced in Iso animals. Furthermore, although the pressor response to intravenous ANG II infusion was similar between groups, the baroreflex-induced bradycardia during the initial 6 h of ANG II infusion was significantly greater, whereas the tachycardia accompanying longer infusion periods was significantly attenuated in Iso animals. These data suggest that in normal rats increased dietary sodium enhances sympathoinhibitory responses during intravenous ANG II.

Effects of cadmium and lead on adrenergic neuromuscular transmission in the rabbit

1977 ◽  
Vol 232 (3) ◽  
pp. C128-C131 ◽  
Author(s):  
G. P. Cooper ◽  
D. Steinberg
Keyword(s):  
Electrical Stimulation ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Perfusion Pressure ◽  
Pressor Response ◽  
Ringer Solution ◽  
Bathing Solution ◽  
Sympathetic Nerve Stimulation ◽  
Fourfold Increase ◽  
Lead And Cadmium

The effects of inorganic lead (PbCl2) and cadmium (DdCl2) on the pressor response of rabbit saphenous arteries produced by sympathetic nerve stimulation were examined. A 1- to 3-cm length of artery was removed, placed in a bath containing mammalian Ringer solution, and perfused with the same solution at a constant rate sufficient to maintain a 40-60 mmHg perfusion pressure. Increases in perfusion pressure resulting from electrical stimulation -f periarterial nerve endings were reduced or completely blocked by the addition of 5-20 muM lead or cadmium to the bathing solution for a period of 15-30 min. Responses to norepinephrine or to direct electrical stimulation of the muscle remained relatively unaffected. During lead or cadmium blockade, the response to nerve stimulation could be restored by a fourfold increase in calcium concentration. It is concluded that lead and cadmium reduce the response to sympathetic nerve stimulation primarily through an effect on presynaptic nerve terminals.

scholarly journals The potency of different serotonergic agonists in counteracting opioid evoked cardiorespiratory disturbances

2009 ◽  
Vol 364 (1529) ◽  
pp. 2611-2623 ◽  
Author(s):  
M. Dutschmann ◽  
H. Waki ◽  
T. Manzke ◽  
A. E. Simms ◽  
A. E. Pickering ◽  
...  
Keyword(s):  
Respiratory Depression ◽  
Vascular Resistance ◽  
Phrenic Nerve ◽  
Sympathetic Activity ◽  
Nerve Activity ◽  
Cardiorespiratory Control ◽  
Conscious Rats ◽  
Phrenic Nerve Activity ◽  
Arterial Blood

Serotonin receptor (5-HTR) agonists that target 5-HT 4(a) R and 5-HT 1A R can reverse μ-opioid receptor (μ-OR)-evoked respiratory depression. Here, we have tested whether such rescuing by serotonin agonists also applies to the cardiovascular system. In working heart–brainstem preparations in situ , we have recorded phrenic nerve activity, thoracic sympathetic chain activity (SCA), vascular resistance and heart rate (HR) and in conscious rats, diaphragmatic electromyogram, arterial blood pressure (BP) and HR via radio-telemetry. In addition, the distribution of 5-HT 4(a) R and 5-HT 1A R in ponto-medullary cardiorespiratory networks was identified using histochemistry. Systemic administration of the μ-OR agonist fentanyl in situ decreased HR, vascular resistance, SCA and phrenic nerve activity. Subsequent application of the 5-HT 1A R agonist 8-OH-DPAT further enhanced bradycardia, but partially compensated the decrease in vascular resistance, sympathetic activity and restored breathing. By contrast, the 5-HT 4(a) R agonist RS67333 further decreased vascular resistance, HR and sympathetic activity, but partially rescued breathing. In conscious rats, administration of remifentanyl caused severe respiratory depression, a decrease in mean BP accompanied by pronounced bradyarrhythmia. 8-OH-DPAT restored breathing and prevented the bradyarrhythmia; however, BP and HR remained below baseline. In contrast, RS67333 further suppressed cardiovascular functions in vivo and only partially recovered breathing in some cases. The better recovery of μ-OR cardiorespiratory disturbance by 5-HT 1A R than 5-HT 4(a) R is supported by the finding that 5-HT 1A R was more densely expressed in key brainstem nuclei for cardiorespiratory control compared with 5-HT 4(a) R. We conclude that during treatment of severe pain, 5-HT 1A R agonists may provide a useful tool to counteract opioid-mediated cardiorespiratory disturbances.

Variation of respiratory sinus arrhythmia with age

1976 ◽  
Vol 41 (5) ◽  
pp. 734-738 ◽  
Author(s):  
J. B. Hellman ◽  
R. W. Stacy
Keyword(s):  
Heart Rate ◽  
Control Systems ◽  
Respiratory Sinus Arrhythmia ◽  
Linear Regression Analysis ◽  
Noninvasive Method ◽  
Sinus Arrhythmia ◽  
Cardiorespiratory Control ◽  
Cardiorespiratory Coupling ◽  
The Subject ◽  
Male Subjects

Respiratory sinus arrhythmia was measured on 24 male subjects whose agesranged from 21 to 65 yr, using a technique in which respiration was coupledto heart rate, so that there were 6 heartbeats per inspiration and 6 heartbeats per expiration. This voluntary cardiorespiratory coupling reduced the variance of heart rates measured at various points in the respiratory cycle. Fourier analysis was used to obtain the fundamental of heart rate and respiratory volume. A high correlation coefficient (-0.83) was found betweenpercent of variation of heart rate from the average heart rate (PB) and theage of the subject. Linear regression analysis performed on these data produced the equation: PB = 23.2–0.35 (age). Since sinus arrhythmia at thelow respiratory frequencies used probably reflects the viability of the cardiorespiratory control systems, we believe this provides a simple noninvasive method for the study of the overall competence of the system responsiblefor respiratory sinus arrhythmia.

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