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Cureus Apr 2024Hyponatremia is an adverse effect of many antiseizure medications (ASMs). It occurs with interference with the normal balance of electrolytes within the body. Various... (Review)
Review
Hyponatremia is an adverse effect of many antiseizure medications (ASMs). It occurs with interference with the normal balance of electrolytes within the body. Various risk factors associated with the development of hyponatremia in patients taking these medications include age, gender, dosage, and combinations with other drugs. ASMs such as carbamazepine (CBZ), oxcarbazepine (OXC), and valproic acid have a higher risk of hyponatremia. Hyponatremia induced by an antiseizure medication can occur through various mechanisms depending on the drug's specific mechanism of action. Hyponatremia can be a potentially fatal side effect. Patients taking these medications need to be monitored closely for the signs and symptoms of hyponatremia. Acute hyponatremia, defined as developing in <48 hours, is more likely to show symptoms than chronic hyponatremia. Signs of acute hyponatremia include delirium, seizures, decerebrate posturing, and cerebral edema with uncal herniation. Chronic hyponatremia, defined as developing in >48 hours, can cause lethargy, dizziness, weakness, headache, nausea, and confusion. Hyponatremia is associated with longer hospital stays and increased mortality. Treatment varies based on the degree of severity of hyponatremia. Choosing a treatment option should include consideration of the drug causing the electrolyte disturbance, the patient's risk factor profile, and the severity of symptoms as they present in the individual patient. Healthcare providers should be aware of hyponatremia as a potential side effect of ASMs, the signs and symptoms of hyponatremia, the different treatment options available, and the potential complications associated with rapid correction of hyponatremia.
PubMed: 38707045
DOI: 10.7759/cureus.57535 -
Scientific Reports Apr 2024Several neurologic diseases including spinal cord injury, Parkinson's disease or multiple sclerosis are accompanied by disturbances of the lower urinary tract functions....
Several neurologic diseases including spinal cord injury, Parkinson's disease or multiple sclerosis are accompanied by disturbances of the lower urinary tract functions. Clinical data indicates that chronic spinal cord stimulation can improve not only motor function but also ability to store urine and control micturition. Decoding the spinal mechanisms that regulate the functioning of detrusor (Detr) and external urethral sphincter (EUS) muscles is essential for effective neuromodulation therapy in patients with disturbances of micturition. In the present work we performed a mapping of Detr and EUS activity by applying epidural electrical stimulation (EES) at different levels of the spinal cord in decerebrated cat model. The study was performed in 5 adult male cats, evoked potentials were generated by EES aiming to recruit various spinal pathways responsible for LUT and hindlimbs control. Recruitment of Detr occurred mainly with stimulation of the lower thoracic and upper lumbar spinal cord (T13-L1 spinal segments). Responses in the EUS, in general, occurred with stimulation of all the studied sites of the spinal cord, however, a pronounced specificity was noted for the lower lumbar/upper sacral sections (L7-S1 spinal segments). These features were confirmed by comparing the normalized values of the slope angles used to approximate the recruitment curve data by the linear regression method. Thus, these findings are in accordance with our previous data obtained in rats and could be used for development of novel site-specific neuromodulation therapeutic approaches.
Topics: Animals; Cats; Male; Spinal Cord; Electric Stimulation; Spinal Cord Stimulation; Urinary Bladder; Decerebrate State; Urinary Tract; Urethra; Urination; Epidural Space
PubMed: 38670988
DOI: 10.1038/s41598-024-54209-3 -
Journal of Applied Physiology... May 2024Cyclooxygenase (COX) products of arachidonic acid metabolism, specifically prostaglandins, play a role in evoking and transmitting the exercise pressor reflex in health...
Cyclooxygenase (COX) products of arachidonic acid metabolism, specifically prostaglandins, play a role in evoking and transmitting the exercise pressor reflex in health and disease. Individuals with type 2 diabetes mellitus (T2DM) have an exaggerated exercise pressor reflex; however, the mechanisms for this exaggerated reflex are not fully understood. We aimed to determine the role played by COX products in the exaggerated exercise pressor reflex in T2DM rats. The exercise pressor reflex was evoked by static muscle contraction in unanesthetized, decerebrate, male, adult University of California Davis (UCD)-T2DM ( = 8) and healthy Sprague-Dawley ( = 8) rats. Changes (Δ) in peak mean arterial pressure (MAP) and heart rate (HR) during muscle contraction were compared before and after intra-arterial injection of indomethacin (1 mg/kg) into the contracting hindlimb. Data are presented as means ± SD. Inhibition of COX activity attenuated the exaggerated peak MAP (Before: Δ32 ± 13 mmHg and After: Δ18 ± 8 mmHg; = 0.004) and blood pressor index (BPi) (Before: Δ683 ± 324 mmHg·s and After: Δ361 ± 222 mmHg·s; = 0.006), but not HR (Before: Δ23 ± 8 beats/min and After Δ19 ± 10 beats/min; = 0.452) responses to muscle contraction in T2DM rats. In healthy rats, COX activity inhibition did not affect MAP, HR, or BPi responses to muscle contraction. Inhibition of COX activity significantly reduced local production of prostaglandin E in T2DM and healthy rats. We conclude that peripheral inhibition of COX activity attenuates the pressor response to muscle contraction in T2DM rats, suggesting that COX products partially contribute to the exaggerated exercise pressor reflex in those with T2DM. We compared the pressor and cardioaccelerator responses to static muscle contraction before and after inhibition of cyclooxygenase (COX) activity within the contracting hindlimb in decerebrate, unanesthetized type 2 diabetic mellitus (T2DM) and healthy rats. The pressor responses to muscle contraction were attenuated after peripheral inhibition of COX activity in T2DM but not in healthy rats. We concluded that COX products partially contribute to the exaggerated pressor reflex in those with T2DM.
Topics: Animals; Male; Diabetes Mellitus, Type 2; Muscle Contraction; Rats; Rats, Sprague-Dawley; Heart Rate; Reflex; Muscle, Skeletal; Blood Pressure; Physical Conditioning, Animal; Indomethacin; Cyclooxygenase Inhibitors; Arterial Pressure; Prostaglandin-Endoperoxide Synthases
PubMed: 38545661
DOI: 10.1152/japplphysiol.00879.2023 -
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 -
IDCases 2023We report a case of a 32-year-old male with a history of type 1 diabetes, inhaled drug use, and alcohol use disorder, who presented with encephalopathy, holocranial...
We report a case of a 32-year-old male with a history of type 1 diabetes, inhaled drug use, and alcohol use disorder, who presented with encephalopathy, holocranial headaches, neck pain, confusion, and generalized tonic-clonic seizures. The patient initially presented at a rural community hospital with a fever and was found to be in diabetic ketoacidosis (DKA). He was also hemodynamically stable but stuporous, prompting intubation to protect his airway. Despite initial treatment measures, his neurological condition worsened and he remained ventilator-dependent. Key findings include a high glucose level, presence of ketones, and evidence of drug use. Blood cultures showed no growth, but his febrile state persisted. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis, hyperglycorrhachia but normal protein, with no growth. Neuroimaging showed right hemispheric slowing on EEG and diffusion restriction in the right frontal lobe on MRI. The patient's neurological status worsened on the second day of admission, manifesting as sluggish pupillary reflexes, right third nerve palsy, and decerebrate posturing. Emergent MRI suggested cerebral edema, leading to initiation of hypertonic saline. This case highlights the diagnostic challenges and critical management considerations in a patient with multiple comorbidities presenting with unexplained neurological deterioration, emphasizing the importance of a comprehensive and timely approach to diagnosis and treatment.
PubMed: 37415782
DOI: 10.1016/j.idcr.2023.e01821 -
American Journal of Physiology. Heart... Aug 2023Stimulation of mechanically sensitive channels on the sensory endings of group III and IV thin fiber muscle afferents activates the mechanoreflex, which contributes to...
Stimulation of mechanically sensitive channels on the sensory endings of group III and IV thin fiber muscle afferents activates the mechanoreflex, which contributes to reflex increases in sympathetic nerve activity (SNA) and blood pressure during exercise. Accumulating evidence suggests that activation of the nonselective cation channel transient receptor potential vanilloid-1 (TRPV1) on the sensory endings of thin fiber afferents with capsaicin may attenuate mechanosensation. However, no study has investigated the effect of capsaicin on the mechanoreflex. We tested the hypothesis that in male and female decerebrate, unanesthetized rats, the injection of capsaicin (0.05 µg) into the arterial supply of the hindlimb reduces the pressor and renal SNA (RSNA) response to 30 s of 1 Hz rhythmic hindlimb muscle stretch (a model of isolated mechanoreflex activation). In male rats ( = 8), capsaicin injection significantly reduced the integrated blood pressure (blood pressure index or BPI: pre, 363 ± 78; post, 211 ± 88 mmHg·s; = 0.023) and RSNA [∫ΔRSNA; pre, 687 ± 206; post, 216 ± 80 arbitrary units (au), = 0.049] response to hindlimb muscle stretch. In female rats ( = 8), capsaicin injection had no significant effect on the pressor (BPI; pre: 277 ± 67; post: 207 ± 77 mmHg·s; = 0.343) or RSNA (∫ΔRSNA: pre, 697 ± 123; post, 440 ± 183 au; = 0.307) response to hindlimb muscle stretch. The data suggest that the injection of capsaicin into the hindlimb arterial supply to stimulate TRPV1 on the sensory endings of thin fiber muscle afferents attenuates the mechanoreflex in healthy male, but not female, rats. The findings may carry important implications for chronic conditions in which an exaggerated mechanoreflex contributes to aberrant sympathoexcitation during exercise. Recent evidence in isolated sensory neurons indicates that capsaicin-induced stimulation of TRPV1 attenuates mechanosensitivity. Here we demonstrate for the first time that capsaicin exposure/administration reduces the reflex pressor and renal sympathetic nerve response to mechanoreflex activation in male rats, but not female rats, in vivo. Our data may carry important clinical implications for chronic diseases which have been linked to an exaggerated mechanoreflex, at least in males.
Topics: Rats; Male; Animals; Muscle Contraction; Muscle, Skeletal; Capsaicin; Rats, Sprague-Dawley; Reflex; Blood Pressure; Hindlimb
PubMed: 37389947
DOI: 10.1152/ajpheart.00237.2023 -
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 -
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 -
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