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Experimental Physiology Mar 2024The ability to increase cardiac output during dynamic exercise is paramount for the ability to maintain workload performance. Reflex control of the cardiovascular system... (Review)
Review
The ability to increase cardiac output during dynamic exercise is paramount for the ability to maintain workload performance. Reflex control of the cardiovascular system during exercise is complex and multifaceted involving multiple feedforward and feedback systems. One major reflex thought to mediate the autonomic adjustments to exercise is termed the muscle metaboreflex and is activated via afferent neurons within active skeletal muscle which respond to the accumulation of interstitial metabolites during exercise when blood flow and O delivery are insufficient to meet metabolic demands. This is one of the most powerful cardiovascular reflexes capable of eliciting profound increases in sympathetic nerve activity, arterial blood pressure, central blood volume mobilization, heart rate and cardiac output. This review summarizes the mechanisms meditating muscle metaboreflex-induced increases in cardiac output. Although much has been learned from studies using anaesthetized and/or decerebrate animals, we focus on studies in conscious animals and humans performing volitional exercise. We discuss the separate and interrelated roles of heart rate, ventricular contractility, ventricular preload and ventricular-vascular coupling as well as the interaction with other cardiovascular reflexes which modify muscle metaboreflex control of cardiac output. We discuss how these mechanisms may be altered in subjects with heart failure with reduced ejection fraction and offer suggestions for future studies.
PubMed: 38460125
DOI: 10.1113/EP091752 -
Neuromodulation : Journal of the... Jun 2024Implantation of stimulating electrodes into the basement of the vertebral spinous process allows the electrodes to be quickly and stably fixed relative to the spinal...
OBJECTIVES
Implantation of stimulating electrodes into the basement of the vertebral spinous process allows the electrodes to be quickly and stably fixed relative to the spinal cord. Using this approach, we have previously shown the selectivity of rat muscle activation during transvertebral stimulation (TS). In this work, we investigated the TS to induce forward stepping of the cat's hindlimbs in comparison with epidural stimulation (ES).
MATERIALS AND METHODS
TS was performed with an electrode placed in the VL3-VL6 vertebrae in five decerebrated cats. ES was performed on the same cats in L5-L7 segments. Kinematic parameters of stepping were recorded in addition to electromyographic activity of musculus (m.) iliopsoas (IP), m. tibialis anterior (TA), and m. gastrocnemius lateralis (GL) of both hindlimbs.
RESULTS
With VL3-VL4 TS, all five animals were capable of bipedal forward stepping, whereas VL5 and VL6 TS led to the forward stepping in 3 of 5 and 1 of 5 animals, respectively. Well-coordinated muscle activity led to a high level of intra- and interlimb coordination. Kinematic parameters of TS-induced stepping were similar to those obtained with ES. The TS of the VL3 vertebra causes the frequency lock with the integer multiple of the stimulation frequency. Similarly to the rat model, TS-evoked muscle responses were site specific. They were minimal during VL3 TS and were maximal during VL4-VL5 TS (IP) and VL5-VL6 TS (TA, GL).
CONCLUSIONS
The obtained results support hypotheses about the location of the central pattern generators in the upper lumbar spinal segments. The proposed approach of electrode placement is surgically easier to perform than is ES. This approach is useful for studying site-specific neuromodulation of the spinal sensorimotor networks and for investigating new strategies of locomotor recovery in animal models.
Topics: Animals; Cats; Decerebrate State; Electromyography; Muscle, Skeletal; Hindlimb; Biomechanical Phenomena; Spinal Cord Stimulation; Electrodes, Implanted; Electric Stimulation; Male; Female; Lumbar Vertebrae
PubMed: 36567242
DOI: 10.1016/j.neurom.2022.11.009 -
Journal of Orthopaedic Case Reports Apr 2022Isolated cerebral fat embolism syndrome (FES) is a rare complication that occurs within the first 3 days of the initial insult. We report a case of multiple long bone...
INTRODUCTION
Isolated cerebral fat embolism syndrome (FES) is a rare complication that occurs within the first 3 days of the initial insult. We report a case of multiple long bone fractures with isolated cerebral FES, despite undergoing early total care with definitive fixation.
CASE PRESENTATION
A 22-year-old female presented with type IIIA open femur shaft fracture on the right side (AO 32B2), closed femur shaft fracture (AO 32B2), comminuted patella fracture on the left side (AO 34C3), and undisplaced mandible fracture. She had a normal sensorium with a Glasgow Coma Scale (GCS) of E4V5M6. A whole body computed tomography (CT) scan was done to rule out other injuries. All initial scans were normal. After about 6 h in the ICU, she was noticed to have disconjugate gaze and was answering in monosyllables. A repeat CT scan of the brain was normal. The early total care and definitive fixation with titanium intramedullary nails for femur fractures and tension band wiring for patella was done under general anesthesia. On 1st post-operative day (POD), her GCS dropped to E1VTM1. On the 3rd POD, she developed decerebrate rigidity and generalized tonic clonic seizures. Fundoscopic examination showed multiple fat globules along the vessel in the entire field of both eyes. Since there were no other signs of FES in the lungs or on the skin, an MRI brain was done which revealed a hyperintensive starfield pattern on diffusion-weighted images, suggestive of cerebral fat embolism (CFE). At 4 weeks, her upper limb and lower limb muscle power improved. By 2 months, she was mobilized with support. Her Mini-Mental State Examination showed no cognitive impairment. At the latest follow-up at 1 year, her fractures are completely healed and she has no neurological or functional impairment.
CONCLUSION
We must always suspect isolated cerebral FES as a diagnosis in polytrauma patients even when the classical findings are not present. MRI compatible implants have to be used as far as possible as MRI may be required to confirm the diagnosis of CFE. The early total care with definitive fixation and supportive treatment helped us in this patient's complete recovery without cognitive impairment.
PubMed: 36380992
DOI: 10.13107/jocr.2022.v12.i04.2750 -
Experimental Physiology Jan 2020What is the central question of this study? What are the alterations in respiratory motor activity that may underlie ventilatory dysfunctions in juvenile and adult...
NEW FINDINGS
What is the central question of this study? What are the alterations in respiratory motor activity that may underlie ventilatory dysfunctions in juvenile and adult animals exposed to postnatal chronic intermittent hypoxia? What is the main finding and its importance? Postnatal chronic intermittent hypoxia modifies the motor activity to pumping and upper airway respiratory muscles in rats, mediated by epigenetic DNA hypermethylation, enhancing resting pulmonary ventilation and predisposing to collapse of the upper airways in juvenile and adult life.
ABSTRACT
Periods of apnoea, commonly observed in prematures and newborns, are an important risk factor for the development of cardiorespiratory diseases in adulthood. In the present study, we evaluated changes in pulmonary ventilation and respiratory motor pattern in juvenile and adult rats exposed to postnatal chronic intermittent hypoxia (pCIH). Newborn male Holtzman rats (P1) were submitted to pCIH (6% O for 30 s, every 9 min, 8 h a day (09.30-17.30 h)) during their first 10 days of life, while control animals were maintained under normoxic conditions (20.8% O ). Thereafter, animals of both groups were maintained under normoxia until the experiments. Unanaesthetized juvenile pCIH rats (n = 27) exhibited elevated tidal volume and respiratory irregularities (P < 0.05) compared to control rats (n = 7). Decerebrate, arterially perfused in situ preparations of juvenile pCIH rats (n = 11) displayed augmented phrenic nerve (PN) burst amplitude and reduced central vagus nerve activity in comparison to controls (n = 10). At adulthood, pCIH rats (n = 5) showed enhanced tidal volume (P < 0.05) and increased respiratory variability compared to the control group (n = 5). The pCIH-induced changes in ventilation and respiratory motor outputs were prevented by treatment with the DNA methyltransferase inhibitor decitabine (1 mg kg , i.p.) during the exposure to pCIH. Our data demonstrate that pCIH in rats impacts, in a persistent way, control of the respiratory pattern, increasing PN activity to the diaphragm and reducing the vagal-related activity to laryngeal muscles, which, respectively, may contribute to improve resting pulmonary ventilation and predispose to collapse of the upper airways during quiet breathing.
Topics: Aging; Animals; Animals, Newborn; DNA Methylation; Decitabine; Diaphragm; Epigenesis, Genetic; Hypoxia; Male; Phrenic Nerve; Pulmonary Ventilation; Rats; Rats, Sprague-Dawley; Respiratory Muscles; Respiratory System; Vagus Nerve
PubMed: 31605407
DOI: 10.1113/EP087928 -
Journal of Neurophysiology Sep 2020We recorded membrane potentialp changes in 45 pharyngeal motoneurons (PMs) including 33 expiratory modulated and 12 nonrespiratory neurons during breathing, swallowing,...
We recorded membrane potentialp changes in 45 pharyngeal motoneurons (PMs) including 33 expiratory modulated and 12 nonrespiratory neurons during breathing, swallowing, and coughing in decerebrate paralyzed cats. Four types of membrane potential changes were observed during swallowing: ) depolarization during swallowing ( = 27), ) depolarization preceded by a brief (≤ 0.1 s) hyperpolarization ( = 4), ) longer term (> 0.3 s) hyperpolarization followed by depolarization ( = 11), and ) hyperpolarization during the latter period of swallowing ( = 3). During coughing, PMs showed two types of membrane potential changes ( = 10). Nine neurons exhibited a ramp-like depolarization during the expiratory phase of coughing with the potential peak at the end of expiratory phase. This depolarization was interrupted by a transient repolarization just before the potential peak. The membrane potential of the remaining neuron abruptly depolarized at the onset of the expiratory phase and then gradually decreased even after the end of the expiratory phase. Single-shock stimulation of the superior laryngeal nerve (SLN) induced inhibitory postsynaptic potentials in 19 of 21 PMs. Two motoneurons exhibited an SLN-induced excitatory postsynaptic potential. The present study revealed that PMs receive the central drive, consisting of a combination of excitation and inhibition, from the pattern generator circuitry of breathing, swallowing, and coughing, which changes the properties of their membrane potential to generate these motor behaviors of the pharynx. Our data will provide the basis of studies of pharyngeal activity and its control from the medullary neuronal circuitry responsible for the upper airway motor activity. We have provided the first demonstration of the multifunctional activity of the pharyngeal motoneurons at the level of membrane potential during respiration, swallowing, and coughing.
Topics: Animals; Cats; Central Pattern Generators; Cough; Decerebrate State; Deglutition; Electric Stimulation; Female; Laryngeal Nerves; Male; Motor Neurons; Pharynx; Respiration; Synaptic Potentials
PubMed: 32727254
DOI: 10.1152/jn.00093.2020 -
Journal of Applied Physiology... Oct 2019The spontaneous or self-sustained discharge of spinal motoneurons can be observed in both animals and humans. Although the origins of this self-sustained discharge are...
The spontaneous or self-sustained discharge of spinal motoneurons can be observed in both animals and humans. Although the origins of this self-sustained discharge are not fully known, it can be generated by activation of persistent inward currents intrinsic to the motoneuron. If self-sustained discharge is generated exclusively through this intrinsic mechanism, the discharge of individual motor units will be relatively independent of one another. Alternatively, if increased activation of premotor circuits underlies this prolonged discharge of spinal motoneurons, we would expect correlated activity among motoneurons. Our aim is to assess potential synaptic drive by quantifying coherence during self-sustained discharge of spinal motoneurons. Electromyographic activity was collected from 20 decerebrate animals using a 64-channel electrode grid placed on the isolated soleus muscle before and following intrathecal administration of methoxamine, a selective α-noradrenergic agonist. Sustained muscle activity was recorded and decomposed into the discharge times of ~10-30 concurrently active individual motor units. Consistent with previous reports, the self-sustained discharge of motor units occurred at low mean discharge rates with low-interspike variability. Before methoxamine administration, significant low-frequency coherence (<2 Hz) was observed, while minimal coherence was observed within higher frequency bands. Following intrathecal administration of methoxamine, increases in motor unit discharge rates and strong coherence in both the low-frequency and 15- to 30-Hz beta bands were observed. These data demonstrate beta-band coherence among motor units can be observed through noncortical mechanisms and that neuromodulation of spinal/brainstem neurons greatly influences coherent discharge within spinal motor pools. The correlated discharge of spinal motoneurons is often used to describe the input to the motor pool. We demonstrate spinal/brainstem neurons devoid of cortical input can generate correlated motor unit discharge in the 15- to 30-Hz beta band, which is amplified through neuromodulation. Activity in the beta band is often ascribed to cortical drive in humans; however, these data demonstrate the capability of the mammalian segmental motor system to generate and modulate this coherent state of motor unit discharge.
Topics: Animals; Cats; Female; Hindlimb; Male; Motor Neurons; Muscle, Skeletal; Spine
PubMed: 31318619
DOI: 10.1152/japplphysiol.00110.2019 -
The Journal of Physiology May 2022Mechanical and metabolic signals associated with skeletal muscle contraction stimulate the sensory endings of thin fibre muscle afferents, which, in turn, generates...
Mechanical and metabolic signals associated with skeletal muscle contraction stimulate the sensory endings of thin fibre muscle afferents, which, in turn, generates reflex increases in sympathetic nerve activity (SNA) and blood pressure (the exercise pressor reflex; EPR). EPR activation in patients and animals with heart failure with reduced ejection fraction (HF-rEF) results in exaggerated increases in SNA and promotes exercise intolerance. In the healthy decerebrate rat, a subtype of acid sensing ion channel (ASIC) on the sensory endings of thin fibre muscle afferents, namely ASIC1a, has been shown to contribute to the metabolically sensitive portion of the EPR (i.e. metaboreflex), but not the mechanically sensitive portion of the EPR (i.e. the mechanoreflex). However, the role played by ASIC1a in evoking the EPR in HF-rEF is unknown. We hypothesized that, in decerebrate, unanaesthetized HF-rEF rats, injection of the ASIC1a antagonist psalmotoxin-1 (PcTx-1; 100 ng) into the hindlimb arterial supply would reduce the reflex increase in renal SNA (RSNA) evoked via 30 s of electrically induced static hindlimb muscle contraction, but not static hindlimb muscle stretch (model of mechanoreflex activation isolated from contraction-induced metabolite-production). We found that PcTx-1 reduced the reflex increase in RSNA evoked in response to muscle contraction (n = 8; mean (SD) ∫ΔRSNA pre: 1343 (588) a.u.; post: 816 (573) a.u.; P = 0.026) and muscle stretch (n = 6; ∫ΔRSNA pre: 688 (583) a.u.; post: 304 (370) a.u.; P = 0.025). Our data suggest that, in HF-rEF rats, ASIC1a contributes to activation of the exercise pressor reflex and that contribution includes a novel role for ASIC1a in mechanosensation that is not present in healthy rats. KEY POINTS: Skeletal muscle contraction results in exaggerated reflex increases in sympathetic nerve activity in heart failure patients compared to healthy counterparts, which likely contributes to increased cardiovascular risk and impaired tolerance for even mild exercise (i.e. activities of daily living) for patients suffering with this condition. Activation of acid sensing ion channel subtype 1a (ASIC1a) on the sensory endings of thin fibre muscle afferents during skeletal muscle contraction contributes to reflex increases in sympathetic nerve activity and blood pressure, at least in healthy subjects. In this study, we demonstrate that ASIC1a on the sensory endings of thin fibre muscle afferents plays a role in both the mechanical and metabolic components of the exercise pressor reflex in male rats with heart failure. The present data identify a novel role for ASIC1a in evoking the exercise pressor reflex in heart failure and may have important clinical implications for heart failure patients.
Topics: Acid Sensing Ion Channels; Animals; Blood Pressure; Heart Failure; Hindlimb; Male; Muscle Contraction; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Reflex
PubMed: 35343594
DOI: 10.1113/JP282923 -
Experimental Physiology Apr 2020What is the central question of this study? What is the contribution of the main acidic compounds accumulated during contractions, namely H , lactic acid and inorganic...
NEW FINDINGS
What is the central question of this study? What is the contribution of the main acidic compounds accumulated during contractions, namely H , lactic acid and inorganic phosphate, to evoke the metabolic component of the exercise pressor reflex? What is the main finding and its importance? We found that the pressor response to acidic stimuli is driven by the concentration of hydrogen ions and that lactate and inorganic phosphate act as potentiating agents.
ABSTRACT
H ions, lactate and inorganic phosphate are produced by contracting skeletal muscles and evoke, in part, the metabolic component of the exercise pressor reflex. Owing to their disparate dissociation constants (i.e. pK ), the contribution of each acid to the muscle metaboreflex is unclear. This lack of information prompted us to determine the reflex pressor responses to injection of acidic saline, lactate (24 mm) and inorganic phosphate (86 mm) at various values of pH (from 2.66 to 7.5), alone or in combination, into the arterial supply of hindlimb skeletal muscle of decerebrate rats. In particular, we tested the hypothesis that the pressor response to an injection of a combination of lactate and phosphate at an acidic pH is greater than that evoked by injection of either phosphate or lactate alone at the same pH. We found that injection of acidic saline produced a pressor response only at a pH of 2.66 (7 ± 4 mmHg), an effect that was potentiated when the solution contained lactate (50 ± 20 mmHg). At a pH of 6.0, however, this effect was lost. At a pH of 6.0, only the injection of inorganic phosphate produced a significant pressor response (23 ± 12 mmHg). A large potentiating effect was found when lactate was added to the inorganic phosphate solution (39 ± 18 mmHg), an effect that was lost at a pH >7.0. Our findings led to the conclusion that the pressor response to injection of acidic solutions was driven by H ions and that inorganic phosphate and lactate functioned as sensitizing agents.
Topics: Animals; Blood Pressure; Hindlimb; Lactic Acid; Male; Muscle Contraction; Muscle, Skeletal; Phosphates; Physical Conditioning, Animal; Physical Exertion; Rats; Rats, Sprague-Dawley; Reflex
PubMed: 31982004
DOI: 10.1113/EP088349 -
Undersea & Hyperbaric Medicine :... 2021Paroxysmal autonomic instability syndrome with dystonia (PAISD) is a possible complication that worsens the prognosis of hypoxic-ischemic encephalopathy related to...
Paroxysmal autonomic instability syndrome with dystonia (PAISD) is a possible complication that worsens the prognosis of hypoxic-ischemic encephalopathy related to non-fatal drowning. There are case reports of hyperbaric oxygen (HBO2) therapy enhancing recovery in such cases. We report a case of a 5-year-old boy admitted to the Pediatric Intensive Care Unit after a non-fatal drowning. He was transferred under mechanical ventilation and sedation, with hemodynamic instability and hypothermia. On admission he had a Glasgow Coma Score of 6. On the fifth day of admission he presented episodes of dystonia with decerebration posture, diaphoresis, tachycardia and hypertension, sometimes with identified triggers, suggesting PAISD. The episodes were difficult to control; multiple drugs were needed. Electroencephalography showed diffuse slow wave activity, and cranioencephalic magnetic resonance imaging showed hypoxia-related lesions, suggesting hypoxic-ischemic encephalopathy. Early after admission the patient started physiotherapy combined with normobaric oxygen therapy. Subsequently he started HBO2 therapy at 2 atmospheres, with a total of 66 sessions. Dystonia progressively subsided, with gradual discontinuation of therapy. He also showed improvement in spasticity, non-verbal communication and cephalic control. This case highlights the diagnostic and therapeutic challenges of PAISD and the potential benefit of HBO2 therapy, even in the subacute phase, in recovery of hypoxic-ischemic encephalopathy.
Topics: Child, Preschool; Decerebrate State; Drowning; Dystonia; Humans; Hyperbaric Oxygenation; Hypoxia-Ischemia, Brain; Male; Physical Therapy Modalities
PubMed: 33648033
DOI: 10.22462/01.03.2021.6 -
American Journal of Physiology.... Feb 2023We investigated the role played by bradykinin 2 (B2) receptors in the exaggerated exercise pressor reflex in rats with a femoral artery ligated for 72 h to induce...
We investigated the role played by bradykinin 2 (B2) receptors in the exaggerated exercise pressor reflex in rats with a femoral artery ligated for 72 h to induce simulated peripheral artery disease (PAD). We hypothesized that in decerebrate, unanesthetized rats with a ligated femoral artery, hindlimb arterial injection of HOE-140 (100 ng, B2 receptor antagonist) would reduce the pressor response to 30 s of electrically induced 1 Hz hindlimb skeletal muscle contraction, and 30 s of 1 Hz hindlimb skeletal muscle stretch (a model of mechanoreflex activation isolated from contraction-induced metabolite production). We hypothesized no effect of HOE-140 in sham-operated "freely perfused" rats. In both freely perfused ( = 4) and "ligated" ( = 4) rats, we first confirmed efficacious B2 receptor blockade by demonstrating that HOE-140 injection significantly reduced ( < 0.05) the peak increase in mean arterial pressure (peak ΔMAP) in response to hindlimb arterial injection of bradykinin. In subsequent experiments, we found that HOE-140 reduced the peak ΔMAP response to muscle contraction in ligated ( = 14; control: 23 ± 2; HOE-140: 17 ± 2 mmHg; = 0.03) but not freely perfused rats ( = 7; control: 17 ± 3; HOE-140: 18 ± 4 mmHg; = 0.65). Furthermore, HOE-140 had no effect on the peak ΔMAP response to stretch in ligated rats ( = 14; control: 37 ± 4; HOE-140: 32 ± 5 mmHg; = 0.13) but reduced the integrated area under the blood pressure signal over the final ∼20 s of the maneuver. The data suggest that B2 receptors contribute to the exaggerated exercise pressor reflex in rats with simulated PAD, and that contribution includes a modest role in the chronic sensitization of the mechanically activated channels/afferents that underlie mechanoreflex activation.
Topics: Rats; Animals; Reflex; Muscle, Skeletal; Receptors, Bradykinin; Rats, Sprague-Dawley; Bradykinin; Muscle Contraction; Peripheral Arterial Disease; Blood Pressure; Femoral Artery; Hindlimb
PubMed: 36534589
DOI: 10.1152/ajpregu.00274.2022