Oral midodrine for prophylaxis against post-spinal anesthesia hypotension during hip arthroplasty in elderly population: a randomized controlled trial.

BACKGROUND: We aimed to evaluate the efficacy of midodrine as a prophylaxis against post-spinal hypotension in elderly patients undergoing hip arthroplasty. METHODS: This randomized controlled trial included elderly patients undergoing hip arthroplasty under spinal anesthesia. Ninety minutes before the procedure, patients were randomized to receive either 5-mg midodrine or placebo (metoclopramide). After spinal anesthesia, mean arterial pressure (MAP) and heart rate were monitored every 2 min for 20 min then every 5 min until the end of the procedure. Post-spinal hypotension (MAP < 80% baseline) was treated with 10 mg ephedrine. The primary outcome was intraoperative ephedrine consumption. Secondary outcomes were the incidence of post-spinal hypotension, bradycardia, and hypertension (MAP increased by > 20% of the baseline reading). RESULTS: We analyzed 29 patients in the midodrine group and 27 in the control group. The intraoperative ephedrine consumption was lower in the midodrine group than in the control group (median [quartiles]: 10 [0, 30] mg versus 30 [20, 43] mg, respectively, P-value: 0.002); and the incidence of intraoperative hypotension was lower in the midodrine group than that in the control group. The incidence of hypertension and bradycardia were comparable between the two groups. CONCLUSION: The use of 5 mg oral midodrine decreased the vasopressor requirements and incidence of hypotension after spinal anesthesia for hip surgery in elderly patients. CLINICAL TRIAL REGISTRATION: This study was registered on September 22, 2022 at clinicaltrials.gov registry, NCT05548985, URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05548985 .

Atropine does not prevent hypoxemia and bradycardia in tracheal intubation in the pediatric emergency department: observational study.

OBJECTIVE: The benefit of atropine in pediatric tracheal intubation is not well established. The objective of this study was to evaluate the effect of atropine on the incidence of hypoxemia and bradycardia during tracheal intubations in the pediatric emergency department. METHODS: This is a single-center observational study in a tertiary pediatric emergency department. Data were collected on all tracheal intubations in patients from 31 days to incomplete 20 years old, performed between January 2016 and September 2020. Procedures were divided into two groups according to the use or not of atropine as a premedication during intubation. Records with missing data, patients with cardiorespiratory arrest, cyanotic congenital heart diseases, and those with chronic lung diseases with baseline hypoxemia were excluded. The primary outcome was hypoxemia (peripheral oxygen saturation ≤88%), while the secondary outcomes were bradycardia (decrease in heart rate >20% between the maximum and minimum values) and critical bradycardia (heart rate <60 bpm) during intubation procedure. RESULTS: A total of 151 tracheal intubations were identified during the study period, of which 126 were eligible. Of those, 77% had complex, chronic underlying diseases. Atropine was administered to 43 (34.1%) patients and was associated with greater odds of hypoxemia in univariable analysis (OR: 2.62; 95%CI 1.15-6.16; p=0.027) but not in multivariable analysis (OR: 2.07; 95%CI 0.42-10.32; p=0.37). Critical bradycardia occurred in only three patients, being two in the atropine group (p=0.26). Bradycardia was analyzed in only 42 procedures. Atropine use was associated with higher odds of bradycardia in multivariable analysis (OR: 11.00; 95%CI 1.3-92.8; p=0.028). CONCLUSIONS: Atropine as a premedication in tracheal intubation did not prevent the occurrence of hypoxemia or bradycardia during intubation procedures in pediatric emergency.

A mix of aminophylline and heparin plus nitroglycerin can reduce bradycardia during rotational atherectomy on the right coronary artery and dominant circumflex artery.

BACKGROUND: Rotational atherectomy (RA) may cause bradyarrhythmias and transitory atrioventricular block when performed in the right coronary artery (RCA) or a dominant circumflex (CX) coronary artery. However, there are no studies of a solution that can prevent coronary flow deterioration and bradycardia complications that may occur during RA. We aimed to create an alternative rota-flush solution to minimize the risk of bradycardia and complete atrioventricular block (AVB) that can occur during RA. MATERIALS AND METHODS: The study comprised 60 patients who were randomly divided into two groups: 30 received rotaphylline (= 240 mg aminophylline, 10,000 U unfractionated heparin, and 2000 mcg nitroglycerin to 1000 mL saline), and 30 received the traditional rota-flush (= 10,000 U unfractionated heparin, 2000 mcg nitroglycerin, and 1000 mL saline). The incidence of bradycardia or high-grade AVB (HAVB) during RA, coronary slow-flow phenomenon or no-reflow phenomenon, and coronary spasm were the primary endpoints of the study. Procedure success and RA-related procedural complications were secondary endpoints. RESULTS: The use of rotaphylline was an independent predictor of bradycardia and HAVB after accounting for all other factors (OR: 0.47, 95% CI: 0.24-0.79, p < 0.001). Lesion length (OR: 2.17, 95% CI: 1.24-3.04, p < 0.001), burr-to-artery ratio (OR: 0.59, 95% CI: 0.39-1.68, p < 0.001), and total run duration (OR: 0.79, 95% CI: 0.35-1.43, p < 0.001) were additional independent predictors. CONCLUSION: Bradycardia and the development of HAVB may be avoided by rotaphylline intracoronary infusion during RA applied to the RCA and dominant CX lesions. Multicenter studies including sizable patient populations should be conducted to validate the present findings.

Effect of initial and subsequent mask applications on breathing and heart rate in preterm infants at birth.

OBJECTIVE: Application of a face mask may provoke the trigeminocardiac reflex, leading to apnoea and bradycardia. This study investigates whether re-application of a face mask in preterm infants at birth alters the risk of apnoea compared with the initial application, and identify factors that influence this risk. METHODS: Resuscitation videos and respiratory function monitor data collected from preterm infants <30 weeks gestation between 2018 and 2020 were reviewed. Breathing and heart rate before and after the initial and subsequent mask applications were analysed. RESULTS: In total, 111 infants were included with 404 mask applications (102 initial and 302 subsequent mask applications). In 254/404 (63%) applications, infants were breathing prior to mask application, followed by apnoea after 67/254 (26%) mask applications. Apnoea and bradycardia occurred significantly more often after the initial mask application compared with subsequent applications (apnoea initial: 32/67 (48%) and subsequent: 44/187 (24%), p<0.001; bradycardia initial: 61% and subsequent 21%, p<0.001). Apnoea was followed by bradycardia in 73% and 71% of the initial and subsequent mask applications, respectively (p=0.607).In a logistic regression model, a lower breathing rate (OR 0.908 (95% CI 0.847 to 0.974), p=0.007) and heart rate (OR 0.935 (95% CI 0.901 to 0.970), p<0.001) prior to mask application were associated with an increased likelihood of becoming apnoeic following subsequent mask applications. CONCLUSION: In preterm infants at birth, apnoea and bradycardia occurs more often after an initial mask application than subsequent applications, with lower heart and breathing rates increasing the risk of apnoea in subsequent applications.

Efficacy Of Sub-Tenon's Block In Paediatric Strabismus Surgery In Terms Of Reduction In Oculocardiac Reflex.

Background: Strabismus is a common disease entity in paediatric age group usually requiring surgical intervention under general anaesthesia and Oculocardiac reflex is the most dangerous complications intraoperatively. Various anaesthetic options have been evaluated to mitigate this complication. The objective of this study was to assess the efficacy of sub-tenon's block in paediatric strabismus surgery in terms of reduction in oculocardiac reflex. Methods: This prospective Randomized control trial was conducted at Department of ophthalmology, MTI, Hayatabad Medical complex, Peshawar over a period of six months from 1st July to 31st December 2021. A total of 124, were equally divided in subtenon's group (Group A) and placebo group (Group B). Intraoperatively, patients were assessed for Bradycardia and development of OCR. Data including demographics, intraoperative BP, HR and OCR development were noted and analysed with SPSS version 22. Results: The total number of patients were 124, 62 in each group with a mean age of 9.45±1.61. Sixty-six (53.22%) patients were males and 58 (46.87%) patients were females. At 10-, 20- and 30-minutes interval, the SBP and DBP has no significant difference. At 10, 20, 30 minutes interval, the HR differed significantly (79.33±7.36 vs 66.65±6.83 (p˂0.05), 79.78±7.63 vs 66.57±7.06 (p˂0.05), 79.80±7.78 vs 66.52±7.01 (p˂0.05), respectively. Intraoperative OCR was recorded in 13 (21%) patients in sub-tenon's (Group A) versus 56 (90.30%) patients in placebo (Group B) with statistically significant difference between the two (p<0.05). Conclusion: Sub-tenon's injection of bupivacaine reduces the incidence of Bradycardia and OCR in squint surgery patients after general anaesthesia induction and usage is recommended in routine.

Preventing Spinal Hypotension During Cesarean Birth With Two Initial Boluses of Norepinephrine in Chinese Parturients: A Randomized, Double-Blind, Controlled Trial.

BACKGROUND: Norepinephrine is effective in preventing spinal hypotension during cesarean birth; however, an optimal regimen has not been determined. We hypothesized that an initial bolus of norepinephrine improves efficacy of spinal hypotension prophylaxis beyond continuous norepinephrine alone. METHODS: In this double-blind, controlled study, 120 patients scheduled for cesarean birth under spinal anesthesia were randomly allocated to receive a norepinephrine bolus at 0.05 or 0.10 µg/kg, followed by norepinephrine infusion at a rate of 0.05 µg·kg -1 ·min -1 . The primary outcome was the frequency of spinal hypotension during cesarean birth. The doses of the rescue drug (phenylephrine), frequency of nausea or vomiting, duration of hypotension, frequency of intraoperative hypertension, frequency of bradycardia, and fetal outcomes were also compared. RESULTS: One-hundred-fifteen patients were included in the analysis. Compared with the 0.05 µg/kg group, the frequency of spinal hypotension was lower in the 0.10 µg/kg group (20.7% vs 45.6%; odds ratio [OR], 0.31; 95% confidence interval (CI), 0.14-0.71; P = .004). Fewer rescue doses of phenylephrine (0 [0,0] vs 0 [0,80]; 95% CI for the difference, 0 (0-0); P = .006) were required, and the frequency of nausea or vomiting was lower (5.2% vs 17.5%; OR, 0.26; 95% CI, 0.07-0.99; P = .04) in the 0.10 µg/kg group. The duration of hypotension was shorter in the 0.10 µg/kg group than that in the 0.05 µg/kg group (0 [0,0] vs 0 [0,2]; 95% CI for the difference, 0 [0-0]; P = .006). The incidence of intraoperative hypertension, frequency of bradycardia, and fetal outcomes were comparable between the 2 groups. CONCLUSIONS: With a fixed-rate norepinephrine infusion of 0.05 µg·kg -1 ·min -1 , the 0.10 µg/kg initial bolus was more effective in reducing the incidence of spinal hypotension compared with the 0.05 µg/kg initial bolus.

Effect of glycopyrrolate on vasopressor requirements for non-elective cesarean section under spinal anesthesia: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The study aimed to investigate whether prophylactic use of glycopyrrolate decreases the vasopressor requirements to prevent hypotension following spinal anesthesia during non-elective cesarean section. METHOD: In this double-blind randomized clinical trial, 258 patients undergoing non-elective cesarean section were randomly assigned (1:1) to receive intravenous 0.2 mg glycopyrrolate or normal saline (placebo) before spinal anesthesia. The primary outcome was phenylephrine equivalent needed intraoperatively. Secondary outcomes included incidences of maternal hypotension, reactive hypertension, bradycardia, need for atropine, tachycardia, intraoperative nausea/vomiting, shivering, pruritus, dry mouth, dizziness; neonatal APGAR score at 1 min and 5 min, neonatal resuscitation needed, NICU admission and neonatal death. RESULTS: Three patients withdrew from the study due to failed spinal anesthesia. 128 patients in the glycopyrrolate group and 127 patients in the placebo group were analyzed. The mean phenylephrine equivalent needed was 1108.96 µg in the glycopyrrolate group and 1103.64 µg in the placebo group (mean difference, 5.32 µg [95% CI - 67.97 to 78.62]; P = 0.88). Hypotension occurred in 38 patients (30%) in the glycopyrrolate group as compared with 49 patients (39%) in the placebo group (P = 0.13). Tachycardia was reported in 70% of the participants in the glycopyrrolate group and 57% of those in the placebo group (P = 0.04). No statistically significant difference was noted in hypotensive episodes > 1, reactive hypertension, bradycardia, need for atropine, nausea, vomiting, shivering, and dry mouth between the two groups. Neonatal outcomes were similar in the two groups. CONCLUSION: Prophylactic use of glycopyrrolate does not decrease the requirements of vasopressor to prevent hypotension in non-elective cesarean section under spinal anesthesia. TRIAL REGISTRATION: Registration number: NCT04401345. Date of registration: 26/05/2020. Website: https://clinicaltrials.gov.

Hemodynamic and antiemetic effects of prophylactic hyoscine butyl-bromide during cesarean section under spinal anesthesia: a randomized controlled trial.

BACKGROUND: Abrupt bradycardia and hemodynamic instability during spinal anesthesia for cesarean section are not uncommon and are considered as one of the primary causes of intraoperative nausea and vomiting (IONV). We hypothesized that prophylactic use of hyoscine butyl-bromide (HBB) could improve hemodynamics and reduce IONV in parturients undergoing cesarean section. METHODS: A randomized, double-blind placebo-controlled trial was carried out in a tertiary university hospital, patients scheduled for elective cesarean section were equally randomized to receive either IV HBB 20 mg in 1 ml (Hyoscine group) or the same volume of 0.9% saline (Control group), one minute after spinal anesthesia. The primary endpoint was the incidence of intraoperative bradycardia (HR < 50 beats min-1). Secondary endpoints included changes in mean arterial blood pressure (MAP), the incidence of Intraoperative and Postoperative nausea or vomiting (IONV & PONV), the fetal heart rate and, Apgar score. RESULTS: Of the 160 subjects randomized, 80 received HBB and 80 received placebo. There was a significant reduction in the incidence of the primary endpoint of intraoperative bradycardia (HR < 50 beats min-1) in the Hyoscine group (0% vs 10%; OR = 0.05, 95% CI = [0.003, 0.93]; P = 0.004) compared with placebo. MAP showed an insignificant difference between groups over time. HBB significantly decreased incidences of IONV and PONV (p = 0.002 & 0.004) respectively. CONCLUSIONS: In parturients undergoing cesarean section under spinal anesthesia, pretreatment with intravenous HBB was a safe measure for both the mother and the baby to reduce the risk of severe intraoperative bradycardia, but not hypotension. Furthermore, it was associated with less incidence of both IONV and PONV. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04069078.

Ondansetron reduces the incidence of hypotension after spinal anaesthesia in non-caesarean delivery: A systematic review and meta-analysis.

The incidence rates of spinal anaesthesia-induced hypotension vary depending on the surgical procedures. This systematic review and meta-analysis evaluates the efficacy of prophylactic ondansetron in reducing the incidence of spinal anaesthesia-induced hypotension in non-caesarean delivery. Thirteen trials consisting of 1166 patients were included for analysis. Compared to placebo, there is a low quality of evidence that ondansetron was effective in reducing the incidence of spinal anaesthesia-induced hypotension (RR 0.62, 95% CI 0.44 to 0.87; p = 0.005) and bradycardia (RR 0.54, 95% CI 0.32 to 0.90; p = 0.02). We also found a moderate quality of evidence that ondansetron lowered the number of rescue ephedrine (RR 0.61, 95% CI 0.43 to 0.87; p = 0.007). Patients treated with ondansetron have higher mean arterial pressure 15 to 20 minutes after spinal anaesthesia induction and higher systolic arterial pressure 5, 10, 15 and 20 minutes after spinal anaesthesia. The evidence suggests that prophylactic administration of ondansetron results in the reduction of the incidence of spinal anaesthesia-induced hypotension, bradycardia and rescue ephedrine in patients undergoing non-caesarean delivery under spinal anaesthesia.

Standardizing premedication for non-emergent neonatal tracheal intubations improves compliance and patient outcomes.

OBJECTIVE: We sought to standardize and improve compliance with evidence-based premedication for non-emergent neonatal intubations in two academic-affiliated Neonatal Intensive Care Units. STUDY DESIGN: A multidisciplinary team created guidelines and electronic medical record order sets for intubation. Compliance with recommended premedication, number of intubation attempts, and frequency of bradycardia and desaturation were assessed. RESULTS: 387 intubation procedures were reviewed. Provision of recommended premedication increased by 36% and 75% at the level III and IV units, respectively. Decreased frequency of bradycardia during intubation (p = 0.0003) occurred in the level III unit. A reduction in number of intubation attempts (p ≤ 0.001), improvement in first-attempt intubation success (p ≤ 0.001), and decreased frequency of bradycardia (p = 0.01) and desaturation (p = 0.02) during intubation occurred in the level IV unit. CONCLUSIONS: This quality improvement initiative improved standardized premedication compliance and decreased adverse events associated with non-emergent neonatal intubations in two separate units.

Effect of Dexmedetomidine on Tachyarrhythmias After Cardiac Surgery: A Systematic Review and Meta-Analysis.

ABSTRACT: Tachyarrhythmias after cardiac surgery is a common occurrence in clinical practice, which can be life threatening. We searched 6 databases, including Embase, PubMed, Cochrane, CNKI, Wanfang, and Sinomed, to evaluate the effect of dexmedetomidine on tachyarrhythmias after adult cardiac surgery. The primary end point was the number of patients with atrial fibrillation (AF) after cardiac surgery. The secondary end points included the number of patients with supraventricular tachycardia or with ventricular tachycardia or with ventricular fibrillation or with myocardial infarction or deceased patients, the duration of mechanical ventilation, the intensive care unit stay, hospital stay, and the number of patients with bradycardia and those with hypotension. Among the 1388 retrieved studies, 18 studies (n = 3171 participants) met our inclusion criteria. Dexmedetomidine reduced the incidence of AF by 17% [relative risk (RR) = 0.83; 95% confidence interval (CI), 0.73-0.93; P = 0.002]. Through subgroup analysis, we found that when the maintenance dose of dexmedetomidine was >0.7 µg·kg-1·h-1, the effect of preventing AF was obvious (RR = 0.58; 95%CI 0.43-0.78; P = 0.0003). Dexmedetomidine also reduced the incidence of supraventricular tachycardia by approximately 70% (RR = 0.29; 95% CI, 0.11-0.77; P = 0.01) and the incidence of ventricular tachycardia by approximately 80% (RR = 0.23; 95% CI, 0.08-0.63; P = 0.004) but had no effect on ventricular fibrillation (RR = 1.02; 95% CI, 0.14-7.31; P = 0.99). The major side effect of dexmedetomidine was bradycardia. Dexmedetomidine can reduce the incidence of AF (especially high dosages), supraventricular tachycardia, and ventricular tachycardia after cardiac surgery in adults, but it does not affect the occurrence of ventricular fibrillation.

Transplantation of Pluripotent Stem Cell-Derived Cardiomyocytes into a Myocardial Infarction Model of Cynomolgus Monkey.

Recent evidence has provided exciting proof of concepts for the use of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) for cardiac repair; however, large animal studies, which better reflect human disease, are required for clinical application. Here, we describe how to create myocardial infarction in cynomolgus monkey followed by transplantation of PSC-CMs. This method ensures the establishment of a myocardial infarction model and enables reliable PSC-CM transplantation.

Glycopyrrolate does not ameliorate hypothermia associated bradycardia in healthy individuals: A randomized crossover trial.

BACKGROUND: Hypothermia improves outcomes following ischemia-reperfusion injury. Shivering is common and can be mediated by agents such as dexmedetomidine. The combination of dexmedetomidine and hypothermia results in bradycardia. We hypothesized that glycopyrrolate would prevent bradycardia during dexmedetomidine-mediated hypothermia. METHODS: We randomly assigned eight healthy subjects to premedication with a single 0.4 mg glycopyrrolate intravenous (IV) bolus, titrated glycopyrrolate (0.01 mg IV every 3 min as needed for heart rate <50), or no glycopyrrolate during three separate sessions of 3 h cooling. Following 1 mg/kg IV dexmedetomidine bolus, subjects received 20 ml/kg IV 4 °C saline and surface cooling (EM COOLS, Weinerdorf, Austria). We titrated dexmedetomidine infusion to suppress shivering but permit arousal to verbal stimuli. After 3 h of cooling, we allowed subjects to passively rewarm. We compared heart rate, core temperature, mean arterial blood pressure, perceived comfort and thermal sensation between groups using Kruskal-Wallis test and ANOVA. RESULTS: Mean age was 27 (SD 6) years and most (N = 6, 75%) were male. Neither heart rate nor core temperature differed between the groups during maintenance of hypothermia (p > 0.05). Mean arterial blood pressure was higher in the glycopyrrolate bolus condition (p < 0.048). Thermal sensation was higher in the control condition than the glycopyrrolate bolus condition (p = 0.01). Bolus glycopyrrolate resulted in less discomfort than titrated glycopyrrolate (p = 0.04). CONCLUSIONS: Glycopyrrolate did not prevent the bradycardic response to hypothermia and dexmedetomidine. Mean arterial blood pressure was higher in subjects receiving a bolus of glycopyrrolate before induction of hypothermia. Bolus glycopyrrolate was associated with less intense thermal sensation and less discomfort during cooling.

[Life-threatening cardiac arrhythmias]. / Akut lebensbedrohliche Herzrhythmusstörungen.

Cardiac arrhythmias are a common phenomenon and can be a challenge for the treating physicians in the acute situation. The article presents the different bradycardic and tachycardic cardiac arrhythmias and their treatment with practical advices for diagnosis.

Outcomes after Introduction of Minimally Invasive Surfactant Therapy in Two Australian Tertiary Neonatal Units.

OBJECTIVE: To assess the procedural and clinical outcomes associated with the introduction of minimally invasive surfactant therapy (MIST) into standard care at 2 tertiary Australian neonatal intensive care units. STUDY DESIGN: A prospective audit was designed before the introduction of MIST in 2018, with data collected over a period of 18 months. Procedural data were completed by the clinical team performing MIST, including clinical observations, medication use, and adverse events. The audit team collected demographic data and subsequent clinical outcomes from medical records. RESULTS: There were 135 MIST procedures recorded in 122 infants. For the included infants, the median gestation was 302/7 weeks (IQR, 276/7 to 322/7 weeks) and birth weight was 1439 g (IQR, 982-1958 g). During the MIST procedure, desaturation to a peripheral oxygen saturation of <80% was common, occurring in 75.2% of procedures. Other adverse events included need for positive pressure ventilation (10.6%) and bradycardia <100 beats per minute (13.3%). The use of atropine premedication was associated with a significantly lower incidence of bradycardia: 8.6% vs 52.9% (P < .01). Senior clinicians demonstrated higher rates of procedural success. The majority of infants (63.9%) treated with MIST did not require subsequent intubation and mechanical ventilation. CONCLUSIONS: MIST can be successfully introduced in neonatal units with limited experience of this technique. The use of atropine premedication decreases the incidence of bradycardia during the procedure. Success rates can be optimized by limiting MIST to clinicians with greater competence in endotracheal intubation.

Efficacy of an Oxycodone-Propofol Combination versus a Fentanyl-Propofol Combination in Conscious Sedation during Therapeutic Endoscopic Retrograde Cholangiopancreatography in Elderly Patients.

BACKGROUND: With a rapidly aging population, the need for endoscopic retrograde cholangiopancreatography (ERCP) is increasing. The commonly used sedation anesthesia in ERCP is a combination of propofol and fentanyl, even though fentanyl may cause some adverse reactions such as respiratory depression. OBJECTIVES: This study aimed to evaluate the efficacy of oxycodone combined with propofol versus fentanyl combined with propofol for sedation anesthesia during ERCP. METHODS: A total of 193 patients aged from 65 to 80 years undergoing ERCP were enrolled and randomized into two groups: an "oxycodone combined with propofol" group (group OP, n = 97) and a "fentanyl combined with propofol" group (group FP, n = 96). The rate of perioperative adverse events as well as the recovery time, patients' satisfaction, and endoscopists' satisfaction were noted. RESULTS: There was no difference in the frequency of hypotension or bradycardia between the two groups, but there were more episodes of desaturation (SpO2 <90% for >10 s in 8.3%), postoperative nausea (7.3%), and vomiting (5.2%) in group FP than in group OP. Patients' satisfaction in group FP was lower than that in group OP. The recovery time was longer in group FP than in group OP. CONCLUSIONS: Oxycodone combined with propofol was effective in ERCP, with a low incidence of perioperative adverse events.

The protective role of SOD1 overexpression in central mediation of bradycardia following chronic intermittent hypoxia in mice.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with many cardiovascular complications. Similar to OSA, chronic intermittent hypoxia (CIH) (a model for OSA) leads to oxidative stress and impairs baroreflex control of the heart rate (HR) in rodents. The baroreflex arc includes the aortic depressor nerve (ADN), vagal efferent, and central neurons. In this study, we used mice as a model to examine the effects of CIH on baroreflex sensitivity, aortic baroreceptor afferents, and central and vagal efferent components of the baroreflex circuitry. Furthermore, we tested whether human Cu/Zn Superoxide Dismutase (SOD1) overexpression in transgenic mice offers protection against CIH-induced deficit of the baroreflex arc. Wild-type C57BL/6J and SOD1 mice were exposed to room air (RA) or CIH and were then anesthetized, ventilated, and catheterized for measurement of mean arterial pressure (MAP) and HR. Compared with wild-type RA control, CIH impaired baroreflex sensitivity but increased maximum baroreceptor gain and bradycardic response to vagal efferent stimulation. Additionally, CIH reduced the bradycardic response to ADN stimulation, indicating a diminished central regulation of bradycardia. Interestingly, SOD1 overexpression prevented CIH-induced attenuation of HR responses to ADN stimulation and preserved HR responses to vagal efferent stimulation in transgenic mice. We suggest that CIH decreased central mediation of the baroreflex and SOD1 overexpression may prevent the CIH-induced central deficit.