BACKGROUND Nikethamide,a respiratory stimulant,is used to treat hypoxemia caused by coronavirus disease 2019(COVID-19),but it carries a risk of convulsions.Magnesium sulfate(MgSO_(4)),a seizure inhibitor,might serve a...BACKGROUND Nikethamide,a respiratory stimulant,is used to treat hypoxemia caused by coronavirus disease 2019(COVID-19),but it carries a risk of convulsions.Magnesium sulfate(MgSO_(4)),a seizure inhibitor,might serve as a rescue agent against nikethamide-induced seizures.AIM To investigate the therapeutic effect of MgSO_(4)on nikethamide-induced seizures in COVID-19 patients through animal experiments,providing experimental support for the clinical application of MgSO_(4)in preventing and treating seizures caused by nikethamide.METHODS Forty mice were randomly divided into four groups:(1)Physiological saline;(2)Low-dose MgSO_(4)(50 mg/kg);(3)Medium-dose MgSO_(4)(100 mg/kg);and(4)High-dose MgSO_(4)(200 mg/kg).After 15 minutes of intraperitoneal injection of different doses of MgSO_(4)or an equal volume of physiological saline,the mice were injected with nikethamide(250 mg/kg).RESULTS Compared to the normal saline group,all doses of MgSO_(4)significantly prolonged the seizure latency and reduced the severity of convulsions.However,they also extended the duration of seizures and correspondingly increased survival time(P<0.05).The incidence of seizures and mortality rate in the MgSO_(4)-treated groups were significantly lower than those in the normal saline group(P<0.05).CONCLUSION MgSO_(4)can prevent and treat seizures caused by nikethamide in mice.This finding has implications for the application of MgSO_(4)in treating and preventing seizures caused by nikethamide in COVID-19 treatment.展开更多
BACKGROUND： Nikethamide, a respiratory center stimulant, is widely used in China. However, its effects on the central nervous system and medullary respiratory center remain poorly understood. OBJECTIVE： To investiga...BACKGROUND： Nikethamide, a respiratory center stimulant, is widely used in China. However, its effects on the central nervous system and medullary respiratory center remain poorly understood. OBJECTIVE： To investigate the influence of nikethamide on inspiratory neuron discharge in the medial region of the nucleus retrofacialis in neonatal rats, based on the observations addressing rhythmic respiratory discharge generated by the basic medullary respiratory center and various respiration neuron discharges in brain slices. DESIGN, TIME AND SETTING： A controlled, observational study utilizing in vitro neuroelectrophysiology was performed at the Department of Physiology in Southern Medical University between September and December in 2007. MATERIALS： Nikethamide was purchased from Sigma, USA; BL-420E biological signal collection and manaclement system was provided by Chengdu TME Technology, China.METHODS： Isolated medulla-spinal cord preparations were collected from neonatal Sprague Dawley rats, aged 1-3 days. Tissues were divided to include the medial region of the nucleus retrofacialis, ventral respiratory, and dorsal respiratory groups. Subsequently, modified Kreb＇s solution and 5 μg/mL nikethamide-containing modified Kreb＇s solution were consecutively perfused into the medial region of the nucleus retrofacialis in neonatal rat brain slices. MAIN OUTCOME MEASURES： Hypoglossal nerve root respiratory-related rhythmic discharge activities and inspiratory neuron discharges were recorded with an adsorption electrode and microelectrode. RESULTS Nikethamide resulted in prolonged inspiratory neuron discharge time, shortened respiratory cycle and expiratory time. Nikethamide intervention resulted in enhanced integral amplitude of some inspiratory neurons with no changes in discharge frequency or increased discharge frequency in remaining inspiratory neurons with no changes in integral amplitude. CONCLUSION： Nikethamide excites inspiratory neurons in the basic rhythmic respiration and medullary respiratory center, in addition to increased inspiratory neuron and neural network excitability.展开更多
基金Supported by The Zhejiang Provincial Health Commission,No.2022KY1391.
文摘BACKGROUND Nikethamide,a respiratory stimulant,is used to treat hypoxemia caused by coronavirus disease 2019(COVID-19),but it carries a risk of convulsions.Magnesium sulfate(MgSO_(4)),a seizure inhibitor,might serve as a rescue agent against nikethamide-induced seizures.AIM To investigate the therapeutic effect of MgSO_(4)on nikethamide-induced seizures in COVID-19 patients through animal experiments,providing experimental support for the clinical application of MgSO_(4)in preventing and treating seizures caused by nikethamide.METHODS Forty mice were randomly divided into four groups:(1)Physiological saline;(2)Low-dose MgSO_(4)(50 mg/kg);(3)Medium-dose MgSO_(4)(100 mg/kg);and(4)High-dose MgSO_(4)(200 mg/kg).After 15 minutes of intraperitoneal injection of different doses of MgSO_(4)or an equal volume of physiological saline,the mice were injected with nikethamide(250 mg/kg).RESULTS Compared to the normal saline group,all doses of MgSO_(4)significantly prolonged the seizure latency and reduced the severity of convulsions.However,they also extended the duration of seizures and correspondingly increased survival time(P<0.05).The incidence of seizures and mortality rate in the MgSO_(4)-treated groups were significantly lower than those in the normal saline group(P<0.05).CONCLUSION MgSO_(4)can prevent and treat seizures caused by nikethamide in mice.This finding has implications for the application of MgSO_(4)in treating and preventing seizures caused by nikethamide in COVID-19 treatment.
基金the National Natural Science Foundation of China,No.30570670the Natural Science Foundation of Guangdong Province,No.5004714
文摘BACKGROUND： Nikethamide, a respiratory center stimulant, is widely used in China. However, its effects on the central nervous system and medullary respiratory center remain poorly understood. OBJECTIVE： To investigate the influence of nikethamide on inspiratory neuron discharge in the medial region of the nucleus retrofacialis in neonatal rats, based on the observations addressing rhythmic respiratory discharge generated by the basic medullary respiratory center and various respiration neuron discharges in brain slices. DESIGN, TIME AND SETTING： A controlled, observational study utilizing in vitro neuroelectrophysiology was performed at the Department of Physiology in Southern Medical University between September and December in 2007. MATERIALS： Nikethamide was purchased from Sigma, USA; BL-420E biological signal collection and manaclement system was provided by Chengdu TME Technology, China.METHODS： Isolated medulla-spinal cord preparations were collected from neonatal Sprague Dawley rats, aged 1-3 days. Tissues were divided to include the medial region of the nucleus retrofacialis, ventral respiratory, and dorsal respiratory groups. Subsequently, modified Kreb＇s solution and 5 μg/mL nikethamide-containing modified Kreb＇s solution were consecutively perfused into the medial region of the nucleus retrofacialis in neonatal rat brain slices. MAIN OUTCOME MEASURES： Hypoglossal nerve root respiratory-related rhythmic discharge activities and inspiratory neuron discharges were recorded with an adsorption electrode and microelectrode. RESULTS Nikethamide resulted in prolonged inspiratory neuron discharge time, shortened respiratory cycle and expiratory time. Nikethamide intervention resulted in enhanced integral amplitude of some inspiratory neurons with no changes in discharge frequency or increased discharge frequency in remaining inspiratory neurons with no changes in integral amplitude. CONCLUSION： Nikethamide excites inspiratory neurons in the basic rhythmic respiration and medullary respiratory center, in addition to increased inspiratory neuron and neural network excitability.
