Mental health and well-being of anaesthetists during the COVID-19 pandemic: a scoping review.

The COVID-19 pandemic has imposed substantial burdens on clinicians and there is a need to better understand the impact on mental health and well-being. This scoping review investigates the prevalence of mental health concerns in anaesthetists, risk and protective factors for mental well-being, and anaesthetists' pandemic-related concerns and support. We searched online databases for articles published between January 2020 and May 2022, using search terms related to: anaesthesia; burnout, well-being, mental health or stress; and COVID-19. We identified 20 articles comprising 19 different populations of anaesthetists (n = 8680) from 14 countries. Studies identified the prevalence of the following condition in anaesthetists: burnout (14-59%); stress (50-71%); anxiety (11-74%); depression (12-67%); post-traumatic stress (17-25%); psychological distress (52%); and insomnia (17-61%). Significant risk factors for poorer mental health included: direct COVID-19-related issues (fear of self and family exposure to infection; requirement for quarantine); practitioner health factors (insomnia; comorbidities); psychosocial factors (loneliness; isolation; perceived lack of support at home and work); demographic factors (female gender; non-white ethnicity; LGBTQIA+); and workplace factors (redeployment outside area of clinical practice; increased work effort; personal protective equipment shortages). Protective factors identified included: job satisfaction; perceived organisational justice; older age; and male sex. Anaesthetists' self-reported concerns related to: personal protective equipment; resource allocation; fear of infection; fear of financial loss; increased workload; and effective communication of protocols for patient treatment. Support from family, colleagues and hospital management was identified as an important coping mechanism. Findings from this review may support the design of interventions to enhance anaesthetists' psychological health during pandemic conditions and beyond. Future research should include consistent psychological outcome measures and rigorous experimental design beyond cross-sectional studies.

Effectiveness of enhanced pulse oximetry sonifications for conveying oxygen saturation ranges: a laboratory comparison of five auditory displays.

Background: Anaesthetists monitor auditory information about a patient's vital signs in an environment that can be noisy and while performing other cognitively demanding tasks. It can be difficult to identify oxygen saturation (SpO2) values using existing pulse oximeter auditory displays (sonifications). Methods: In a laboratory setting, we compared the ability of non-clinician participants to detect transitions into and out of an SpO2 target range using five different sonifications while they performed a secondary distractor arithmetic task in the presence of background noise. The control sonification was based on the auditory display of current pulse oximeters and comprised a variable pitch with an alarm. The four experimental conditions included an Alarm Only condition, a Variable pitch only condition, and two conditions using sonifications enhanced with additional sound dimensions. Accuracy to detect SpO2 target transitions was the primary outcome. Results: We found that participants using the two sonifications enhanced with the additional sound dimensions of tremolo and brightness were significantly more accurate (83 and 96%, respectively) at detecting transitions to and from a target SpO2 range than participants using a pitch only sonification plus alarms (57%) as implemented in current pulse oximeters. Conclusions: Enhanced sonifications are more informative than conventional sonification. The implication is that they might allow anaesthetists to judge better when desaturation decreases below, or returns to, a target range.

Obesity-related health status is a better predictor of pregnancy with fertility treatment than body mass index: a prospective study.

This study assessed whether an obesity-related health status instrument (Edmonton obesity scoring system - EOSS) or body mass index (BMI) better predicted pregnancy rates in overweight women undergoing fertility treatments. A prospective cohort study was conducted on patients with a BMI ≥ 25 kg m(-2) undergoing a fertility treatment cycle (ovulation induction, superovulation, or in vitro fertilization). Obesity-related health status including blood pressure, blood work, health history, and functional assessment were assessed. A total of 101 patients were included in the study with an average age of 36.3 ± 4.2 years and a mean BMI of 31.8 ± 5.2 kg m(-2) . EOSS was found to be statistically predictive of pregnancy rate/cycle (OR 0.51, 95% CI 0.27-0.94; P = 0.03), whereas BMI was not (OR 0.95, 95% CI 0.86-1.05). A similar trend was seen for clinical pregnancy rate/cycle started. However, the association between clinical pregnancy rates and EOSS or BMI did not reach statistical significance (OR 0.53, P = 0.06 and OR 0.98, P = 0.62 respectively). Our results demonstrated that EOSS better predicted pregnancy rates after fertility treatments than BMI. In fact, for every EOSS stage increased by one unit, the odds of pregnancy were approximately halved. A multi-centre study powered for live birth is warranted to establish effective pre-fertility management of overweight women.

The effectiveness of pulse oximetry sonification enhanced with tremolo and brightness for distinguishing clinically important oxygen saturation ranges: a laboratory study.

UNLABELLED: Our study examined the effectiveness of pulse oximetry sonification enhanced with acoustic tremolo and brightness to help listeners differentiate clinically relevant oxygen saturation ranges. In a series of trials lasting 30 s each, 76 undergraduate participants identified final oxygen saturation range ( TARGET: 100% to 97%; Low: 96% to 90%; Critical: 89% and below), and detected threshold transitions into and out of the target range using conventional sonification (n = 38) or enhanced sonification (n = 38). Median (IQR [range]) accuracy for range identification with the conventional sonification was 80 (70-85 [45-95])%, whereas with the enhanced sonification it was 100 (99-100 [80-100])%; p < 0.001. Accuracy for detecting threshold transitions with the conventional sonification was 60 (50-75 [30-95])%, but with the enhanced sonification it was 100 (95-100 [75-100]%; p < 0.001. Participants can identify clinically meaningful oxygen saturation ranges and detect threshold transitions more accurately with enhanced sonification than with conventional sonification.

Reliability of skin-type self-assessment: agreement of adolescents' repeated Fitzpatrick skin phototype classification ratings during a cohort study.

BACKGROUND: The Fitzpatrick Skin Phototype Classification (FSPC) is the most commonly used measure of skin type. In questionnaire-based surveys, self-rated FSPC is often used as a measure of respondents' skin type. OBJECTIVE: The objective of this analysis was to assess test-retest reliability of the self-rated FSPC within a 12-month cohort study that examined the psychological sequelae of acne. METHODS: Participants were students aged 14-17 years in four Australian secondary schools; two-government system schools and two private schools. The primary outcomes were a number of psychological measures. The FSPC was assessed by a single concise questionnaire item. Test-retest agreement (as measured by quadratic weighted kappa) of participants' self-rated FSPC at three time-points (baseline, 6 and 12 months) was calculated. RESULTS: Of the 244 participating students, 209 students (86%) completed all three rounds of data collection. A further 26 students (11%) completed two rounds. Quadratic weighted kappa for Rounds 1 and 2 was 0.757 (95% CI 0.663-0.831). For Rounds 2 and 3 it was 0.805 (95% CI 0.659-0.893). Between Rounds 1 and 3 it was 0.767 (95% CI 0.698-0.832). This represents good-to-very-good agreement. Skin type was retained as an independent variable in 8 of the 16 regression models built to explain psychological outcomes in this study. CONCLUSION: Skin type appears to be a significant factor in psychological morbidity in acne. The FSPC is a reliable method for assessing skin phenotype, even when elicited via a concise questionnaire item suitable for assessing skin type as a potential confounder in studies of other outcome factors.

Predictors of pulmonary exacerbations in patients with cystic fibrosis infected with multi-resistant bacteria.

BACKGROUND: This study examined characteristics of adult and adolescent patients with cystic fibrosis (CF) to determine factors associated with an increased risk of pulmonary exacerbations. METHODS: 249 patients with CF infected with multidrug resistant bacteria were recruited and prospectively followed for up to 4.5 years until they experienced a pulmonary exacerbation severe enough to require intravenous antibiotics. Multivariable regression analyses were used to compare the characteristics of patients who experienced an exacerbation with those who did not. RESULTS: 124 of the 249 patients (50%) developed a pulmonary exacerbation during the first year and 154 (62%) experienced an exacerbation during the 4.5 year study period. Factors predictive of exacerbations in a multivariable survival model were younger age (OR 0.98, 95% CI 0.96 to 0.99), female sex (OR 1.45, 95% CI 1.07 to 1.95), lower forced expiratory volume in 1 second (FEV(1)) (OR 0.98, 95% CI 0.97 to 0.99), and a previous history of multiple pulmonary exacerbations (OR 3.16, 95% CI 1.93 to 5.17). Chronic use of inhaled corticosteroids was associated with an increased risk of exacerbation (OR 1.92, 95% CI 1.00 to 3.71) during the first study year. CONCLUSIONS: Patients who experience pulmonary exacerbations are more likely to be younger, female, using inhaled steroids, have a lower FEV(1), and a history of multiple previous exacerbations. It is hoped that knowledge of these risk factors will allow better identification and closer monitoring of patients who are at high risk of exacerbations.

The nicotinic antagonist methyllycaconitine has differential effects on nicotine self-administration and nicotine withdrawal in the rat.

Nicotinic acetylcholine receptor (nAChR) antagonists have been shown previously to decrease nicotine self-administration and precipitate elevations in brain reward thresholds and somatic signs of withdrawal in animals chronically exposed to nicotine. Both the positive-reinforcing effects of acute nicotine and the negative effects of nicotine withdrawal have been hypothesized to contribute to the development and maintenance of nicotine dependence. The aim of the present study was to use methyllycaconitine (MLA), an alpha 7 nAChR antagonist, to investigate the role of alpha 7 receptors in the reinforcing effects of nicotine and nicotine withdrawal. MLA was administered to animals allowed to self-administer nicotine intravenously, and also to animals that had been prepared with nicotine-containing osmotic mini-pumps and trained on a brain stimulation reward procedure. The results indicated that pretreatment with the highest doses of MLA used (3.9 and 7.8 mg/kg) significantly reduced nicotine self-administration at two doses of self-administered nicotine (0.03 and 0.06 mg/kg/infusion). Nevertheless, MLA administration, at all doses tested, had no effect on brain reward thresholds or the number of somatic signs of withdrawal observed in rats chronically exposed to either nicotine or saline. In conclusion, the alpha 7 nAChR subtype appears to play a significant role in the reinforcing effects of acute nicotine administered intravenously, but not in nicotine dependence, as reflected in the lack of precipitation of the nicotine withdrawal syndrome in nicotine-treated animals.

Pulmonary sequelae after electron spinal irradiation.

We measured pulmonary function in 21 patients, after craniospinal irradiation with a posterior spinal electron beam. The median age at treatment was 7.5 years. Nine patients (43%) demonstrated abnormal pulmonary function tests, five with restrictive changes, one with isolated diminished diffusion capacity, and three with obstructive disease. These changes were mild and predominantly asymptomatic.

Lithium monitoring before and after the distribution of clinical practice guidelines.

OBJECTIVE: To determine whether distribution of clinical practice guidelines improves lithium monitoring and whether standards of monitoring differed between patients in psychiatric contact and those seen only in primary care. METHOD: Standards of monitoring were assessed for patients on lithium in northeast Scotland throughout 1995 and/or throughout 1996. Guidelines were circulated in January 1996 to all local general practitioners and psychiatrists. Monitoring was compared between 1995 and 1996 and for patients with and without psychiatric contact. RESULTS: Both primary care and psychiatric records were scrutinized for 422 and 403 patients prescribed lithium throughout 1995 and 1996, respectively. While monitoring was poor on several parameters during both years, frequency of measurement of both thyroid and renal function improved in 1996. Standards of monitoring were better for patients in psychiatric care. CONCLUSION: Standards of lithium monitoring require further improvement. Locally agreed practice guidelines are helpful but patients on lithium should be in continuing contact with an experienced psychiatrist.

Effects of repeated withdrawal from continuous amphetamine administration on brain reward function in rats.

RATIONALE: The study of the effects of repeated amphetamine administration and withdrawal on brain reward function has relevance to both amphetamine dependence and non-drug-induced depressions. OBJECTIVES: The purpose of this study was to investigate the effects of continuous amphetamine administration and withdrawal on brain stimulation reward thresholds, and the changes that occur with repeated amphetamine exposures. METHODS: Rats were prepared with bipolar electrodes in the lateral hypothalamus and trained in a discrete-trial reward threshold procedure. Then, rats underwent two separate periods of amphetamine administration via subcutaneous osmotic mini-pumps. RESULTS: Continuous amphetamine administration was associated with lowering in brain reward thresholds and decreases in response latencies, while withdrawal was associated with threshold elevations. These effects changed with subsequent amphetamine administration and withdrawal. CONCLUSIONS: The results of this study indicated that with the amphetamine administration regime used here, rats developed increased sensitivity to the effects of acute amphetamine administration and tolerance to the effects of amphetamine withdrawal.

Theophylline for irreversible chronic airflow limitation: a randomized study comparing n of 1 trials to standard practice.

STUDY OBJECTIVE: To compare quality of life and exercise capacity (primary aim), and drug usage (secondary aim), between groups of patients with irreversible chronic airflow limitation (CAL) who were undergoing theophylline Theo-Dur; Key Pharmaceuticals; Kenilworth, NJ) therapy guided by n of 1 trials or standard practice. DESIGN: Randomized study of n of 1 trials vs standard practice. SETTING: Outpatient departments in two tertiary care centers. PATIENTS: Sixty-eight patients with irreversible CAL who were symptomatic despite the use of inhaled bronchodilators, and who were unsure whether theophylline was helping them following open treatment, were randomized into n of 1 trials (N=34) or standard practice. INTERVENTIONS: The n of 1 trials (single-patient, randomized, double-blind, multiple crossover comparisons of the effect on dyspnea of theophylline vs a placebo) followed published guidelines. Standard practice patients stopped taking theophylline but resumed it if their dyspnea worsened. If their dyspnea then improved, theophylline was continued. In both groups, a decision about continuing or stopping the use of theophylline was made within 3 months of randomization. MEASUREMENTS AND RESULTS: The primary outcomes (the chronic respiratory disease questionnaire [CRQ] and 6-min walk) were measured at baseline, 6 months, and 12 months by personnel blinded to treatment group allocation. No between-group differences (n of 1 minus standard practice) were seen in within-group changes over time (1 year minus baseline) in the CRQ Physical Function score (point estimate on the difference, -2.8; 95% confidence limits [CLs], -8.2, 2.5), CRQ Emotional Function score (point estimate on the difference, 0.5; 95% CLs, -4.7, 5.7), or 6-min walk (point estimate on the difference, 8 m; 95% CLs, -26, 44 m). No differences between groups were seen in the secondary outcome of the proportion of patients taking theophylline at 6 and 12 months. In 7 of 34 n of 1 trial patients (21%), dyspnea improved during theophylline treatment compared with placebo treatment. CONCLUSIONS: Using n of 1 trials to guide theophylline therapy in patients with irreversible CAL did not improve their quality of life or exercise capacity, or reduce drug usa e, over 1 year compared to standard practice. Under the objective conditions of an n of 1 trial, 21% of patients with CAL responded to theophylline. There remains a rationale for considering theophylline in patients with irreversible CAL who remain symptomatic despite the use of inhaled bronchodilators, but the use of n of 1 trials to guide this decision did not yield clinically important advantages over standard practice.

Differential effect of nitric oxide synthase inhibitors on acetylcholine-induced relaxation of rat pulmonary and celiac artery rings.

The effect of NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) on acetylcholine (ACh) induced relaxation of rat intrapulmonary artery and celiac artery ring segments was studied in vitro with and without meclofenamate pretreatment. L-NMMA, and to a lesser extent L-NAME, raised baseline tone more in pulmonary than celiac arteries. Pretreatment of pulmonary and celiac artery rings with meclofenamate did not alter this contractile effect. Pulmonary artery and celiac artery ring segments were precontracted with phenylephrine, and cumulative concentration-relaxation curves to ACh were obtained before and after incubation of the rings with L-NAME or L-NMMA. L-NAME inhibited the ACh-induced relaxation of pulmonary arterial rings at 10000 fold lower concentrations than those needed to only partly inhibit the ACh-induced relaxation of celiac artery rings. L-NMMA (10-300 microM) inhibited the ACh-induced relaxation of pulmonary arterial rings in a concentration-dependent manner, whereas L-NMMA (300 microM) only partially inhibited the ACh-induced relaxation of celiac artery rings. The inhibition of ACh-induced relaxation by L-NAME and to a lesser extent by L-NMMA was more when pulmonary and celiac artery rings were pretreated with meclofenamate (1.0 microM). These results suggest that in the pulmonary artery nitric oxide plays a greater role in the modulation of baseline vascular tone and ACh-induced relaxation than in the celiac artery. In addition, cyclooxygenase products do not contribute to the direct contractile responses to L-NAME and L-NMMA in both the pulmonary and celiac artery rings but do modulate the ACh-induced relaxation of these vessels.

Accuracy of asthma treatment in schoolchildren in NSW, Australia.

Insufficient use of anti-inflammatory drugs, such as inhaled corticosteroids and cromoglycate, may contribute to the disease burden associated with asthma. Conversely, aggressive treatment of mild disease may result in avoidable costs and/or adverse drug effects. The aim of this study was to determine the relationship between asthma severity and inhaled corticosteroid/cromoglycate use in a large (n=4,909) random sample of children, aged 8-11 yrs, in NSW, Australia. Asthma and its treatment were assessed by questionnaire responses. Asthma, defined as diagnosis plus current wheeze, was present in 901 children (18% of the sample), of whom 225 (5%) had moderate asthma, defined as asthma plus additional symptoms (sleep disturbance), utilization (hospital, casualty), or disability (reduced activity, school absence). Use of inhaled corticosteroid/cromoglycate was reported by 636 children (13% of the sample). Determinants of use included: asthma diagnosis, current wheeze, and troublesome dry nocturnal cough. There was also a strong relationship between anti-inflammatory treatment and a multicomponent asthma severity score constructed for each child. Inhaled corticosteroids and/or cromoglycate were used by 56% of the children with asthma (24% daily) and by 76% of children with moderate asthma (42% daily). Undertreatment, defined as less than daily inhaled corticosteroids/cromoglycate in moderate asthma, was identified in 130 children (14% of those with asthma or 3% of the sample). Conversely, apparently aggressive treatment, defined as inhaled corticosteroid/cromoglycate use in children with persistent minimal symptoms (asthma severity score of less than 3) was identified in 101 children (2% of the sample). Although there were significant differences between regions in the choice of anti-inflammatory drugs and in the prevalence both of undertreatment and apparently aggressive treatment, there was no clear relationship to regional utilization of emergency and hospital services for asthma. Nevertheless, the frequency of undertreatment suggests an opportunity to reduce asthma morbidity by more consistent application of current therapeutic guidelines.

Cyclooxygenase inhibition and vascular reactivity in a rat model of hyperdynamic sepsis.

We postulated that the attenuated pulmonary and systemic vascular contractility observed in sepsis was secondary to the release of vasodilator prostaglandins. We used the cyclooxygenase inhibitor meclofenamate to inhibit prostaglandin synthesis in an unanesthetized, chronically instrumented model of hyperdynamic sepsis. Sixteen male Sprague-Dawley rats (300-350 g) were randomized to either sepsis induced by cecal ligation and perforation (CLP, n = 8) or a sham procedure (Sham, n = 8). Vascular reactivity was assessed by measuring the hypoxic (FiO2 = 0.08) pulmonary pressor response (HPV), and the systemic pressor response to an intravenous infusion of phenylephrine (1.5-7.5 micrograms/kg/min) before and after the administration of meclofenamate (5 mg/kg intravenously, i.v.). Twenty-four hours postoperatively, CLP animals had significantly increased cardiac output (CO) as compared with Sham animals (204 +/- 12 vs. 148 +/- 5 ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP) (109 +/- 4 vs. 118 +/- 3 mm Hg, p < 0.05), and decreased total systemic vascular resistance (TSVR) (0.546 +/- 0.046 vs. 0.805 +/- 0.030 mm Hg.min.ml-1, p < 0.05). Mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (TPVR) were similar in both groups (p > 0.05). In response to hypoxia, the change in MPAP (delta MPAP) was 3.6 +/- 1.0 and 6.9 +/- 0.8 (mm Hg) in CLP and Sham animals, respectively (p < 0.05). Similarly, the change in TPVR (delta TPVR) during hypoxia was 0.012 +/- 0.006 and 0.038 +/- 0.009 mm Hg.min.ml-1 in CLP and Sham (p < 0.05). The pulmonary and systemic blood pressure (BP) response to phenylephrine was also attenuated in CLP as compared with Sham animals. After treatment with meclofenamate, differences were no longer apparent in the HPV response between CLP and Sham animals, due to a slight increase in the HPV response of CLP animals and a slight decrease in the HPV response in Sham animals. The attenuated pressor response to phenylephrine was not changed in either the pulmonary or the systemic circulation after the administration of meclofenamate. These data suggest that vasodilator prostaglandins may contribute to the attenuated pulmonary pressor response in sepsis. However, the mechanism of the attenuated HPV may be different than the attenuated response to exogenous catecholamines since meclofenamate had no effect on either the pulmonary or systemic response to a phenylephrine infusion in septic animals.

Calcitonin gene-related peptide does not mediate the abnormal vascular reactivity observed in a rat model of acute Pseudomonas pneumonia.

Abnormal systemic and pulmonary vascular reactivity has been demonstrated in numerous models of sepsis and pneumonia. Furthermore, the attenuated hypoxic pulmonary pressor response observed in these animals probably is responsible for the ventilation/perfusion (V/Q) mismatching and consequent arterial hypoxemia. We hypothesized that excess release of endogenous vasodilators such as calcitonin gene-related peptide (CGRP) in pneumonia was responsible for the diminished hypoxic pressor response. Using the CGRP receptor antagonist CGRP (8-37), we examined the role of CGRP in the attenuated hypoxic pulmonary response in a rat model of acute Pseudomonas pneumonia. Sixteen Sprague-Dawley rats were instrumented for chronic hemodynamic monitoring and subsequently randomized to either Pneumonia (n = 8), induced by the instillation of 0.2 ml broth containing 2 x 10(8) colony-forming units (CFU)/ml Pseudomonas aeruginosa into the right lower lobe, or Sham (n = 8) procedure. Hemodynamic measurements and the hypoxic (FiO2 = 0.08) pulmonary pressor response were recorded at baseline, 48 h after the pneumonia or sham procedure and after the administration of 250 micrograms CGRP (8-37) (post-CGRP(8-37)). The regional distribution of pulmonary blood flow was determined by the injection of radioactive microspheres. Forty-eight hours after the instillation of Pseudomonas, Pneumonia animals had significantly increased cardiac output (CO) as compared with Sham (193 +/- 7 vs. 154 +/- 7 ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP 109 +/- 4 vs. 118 +/- 3 mm Hg, p = NS), and reduced total systemic vascular resistance (TSVR 0.57 +/- 0.03 vs. 0.78 +/- 0.05 mm Hg.min.ml-1, p < 0.05). Pneumonia animals were further characterized by increased mean pulmonary artery pressure (MPAP) as compared with Sham (24 +/- 2 vs. 20 +/- 1 mm Hg, p < 0.05) animals, and an increased alveolar-arterial (A-a) oxygen gradient (31 +/- 3 vs. 20 +/- 4 mm Hg, p < 0.05). The administration of CGRP (8-37) did not alter baseline hemodynamic variables and did not change the pressor response to hypoxia in either group. Furthermore, CGRP receptor blockade did not alter the distribution of blood flow in the lung during normoxia or hypoxia. These data suggest that although this model of acute pneumonia is characterized by an attenuated hypoxic pressor response, the mechanism does not appear to be mediated by excess release of the vasodilator CGRP.

Vascular reactivity in sepsis: importance of controls and role of nitric oxide.

We have previously reported differential impairment of pulmonary and systemic vascular contractility in hyperdynamic sepsis. The objectives of this study were (1) to determine whether the magnitude of this phenomenon depends on the control group chosen for comparison, and (2) to examine the role of nitric oxide (NO) in this altered vascular contractility. Rats were randomized to sepsis induced by cecal ligation and perforation (CLP) or to one of two control procedures. The Sepsis group had a jugular venous line for fluid administration, laparotomy, and CLP. Control group 1 (Control) had only a jugular venous line inserted, while group 2 (Sham) had a jugular venous line inserted and an abdominal incision. All rats were killed 24 h after surgery. Vascular contractility of small pulmonary arterial and thoracic aortic rings was assessed in vitro by obtaining cumulative dose-response curves to the contractile agonists potassium chloride (KCl), phenylephrine (PE), and prostaglandin F2 alpha (PGF2 alpha). Pulmonary vessels from animals in the Sepsis and Sham groups exhibited significant attenuation of the contractile responses to KCl, PE, and PGF2 alpha compared with the Control group. In contrast, contractility of the aortic rings to KCl, PE, and PGF2 alpha was not significantly different in the three groups studied. Incubation of pulmonary and aortic vessels with NG-nitro-L-argine methyl ester (L-NAME, 10 microM) caused an increase in the response to KCl, PE, and PGF2 alpha in pulmonary vessels in Sepsis and Sham rats but not in Control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of inhibition of NO synthase on vascular reactivity in a rat model of hyperdynamic sepsis.

To evaluate the role of nitric oxide (NO) in the attenuated vascular reactivity observed in sepsis, we utilized the specific NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Male Sprague-Dawley rats (n = 16) were randomized to either sepsis induced by cecal ligation and perforation (CLP; n = 8) or sham procedure (Sham; n = 8). Vascular reactivity was assessed by measuring the pulmonary pressor response to hypoxia (HPV) (fractional inspired O2 concentration = 0.08) and the pulmonary and systemic pressor response to an intravenous infusion of phenylephrine (1.5-6.0 micrograms.kg-1.min-1). Twenty-four hours after surgery, CLP animals had significantly attenuated HPV compared with Sham animals. In response to hypoxia the change in total pulmonary vascular resistance during hypoxia was 0.008 +/- 0.004 and 0.021 +/- 0.006 mmHg.min-ml-1 in CLP and Sham animals, respectively (P < 0.05). The pulmonary and systemic blood pressure response to phenylephrine was also attenuated in CLP compared with Sham animals. After L-NAME infusion (15 mg/kg), there was a significant augmentation of the HPV response in Sham animals. In contrast, the HPV response in CLP animals was unchanged after L-NAME. The attenuated pressor response to phenylephrine in neither the pulmonary nor the systemic circulation was changed after the administration of L-NAME. These data suggest that in rats, excess NO is not an important mediator of the attenuated vascular reactivity observed in sepsis.