Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding.

Psilocybin and its active metabolite psilocin have been shown to elicit rapid and long-lasting symptom improvements in a variety of affective psychiatric illnesses. However, the region-specific alterations underlying these therapeutic effects remain relatively unknown. The central amygdala (CeA) is a primary output region within the extended amygdala that is dysregulated in affective psychiatric disorders. Here, we measured CeA activity using the activity marker c-Fos and CeA reactivity using fiber photometry paired with an aversive air-puff stimulus. We found that psilocin administration acutely increased CeA activity in both males and females and increased stimulus specific CeA reactivity in females, but not males. In contrast, psilocin produced time-dependent decreases in reactivity in males, but not in females, as early as 2 days and lasting to 28 days post administration. We also measured behavioral responses to the air-puff stimulus and found sex-dependent changes in threat responding but not exploratory behavior or general locomotion. Repeated presentations of the auditory component of the air-puff were also performed and sex-specific effects of psilocin on CeA reactivity to the auditory-alone stimulus were also observed. This study provides new evidence that a single dose of psilocin produces sex-specific, time-dependent, and enduring changes in CeA reactivity and behavioral responding to specific components of an aversive stimulus.

Transthoracic echocardiography for right ventricular function late after the Mustard operation.

The aim of the study was to assess echocardiographic measurements of right ventricular function in 24 patients aged 10.7 to 28.9 years (mean 18.9 years) receiving the Mustard baffle repair for transposition of the great arteries. Right ventricular ejection fraction (RVEF) from single-plane areas and area length volumes, pulsed Doppler mean aortic acceleration, and tricuspid annular plane systolic excursion were correlated with first-pass radionuclide RVEF. The mean radionuclide RVEF was 39%, the mean echocardiographic apical four-chamber RVEF was 41%, and the mean short-axis RVEF was 37%. Echocardiographic apical four-chamber right ventricular end-diastolic volumes were 102 +/- 24 ml/m2, and RVEF interobserver and intraobserver correlation coefficients were 0.73 and 0.81, respectively. Radionuclide and echocardiographic RVEF correlation coefficients were short axis, 0.40; apical four-chamber, 0.24; average four-chamber and short axis, 0.38; mean aortic acceleration, 0.26; and tricuspid annular plane systolic excursion, 0.06. The range of echocardiographic right ventricular volumes for young adults receiving the Mustard repair is established allowing serial observation of dilatation. However, simple and reliable echocardiographic prediction of RVEF remains elusive in this age group.

End-systolic volume and long-term survival after coronary artery bypass graft surgery in patients with impaired left ventricular function.

BACKGROUND: Left ventricular function is the main predictor of long-term survival in patients with coronary artery disease. In patients with impaired left ventricular function after myocardial infarction, end-systolic volume is a better predictor than the global ejection fraction. We analyzed long-term follow-up of patients with impaired left ventricular function undergoing coronary artery bypass graft surgery to evaluate preoperative predictors of survival. METHODS AND RESULTS: Consecutive patients with ejection fractions < or = 40% (n = 193) who had undergone surgical revascularization were followed to assess the predictive value of preoperative baseline characteristics and catheterization findings for long-term survival. Patients were followed for 133 +/- 30.7 months. At the time of surgery, patient age was 56 +/- 7.9 years and 169 patients (87.6%) had a history of previous myocardial infarction. Thirty-one patients (16%) were female. The ejection fraction was 32 +/- 7%, and the end-systolic volume was 147.4 +/- 52.6 mL. One hundred sixty-four patients (84.9%) had three-vessel disease, and 44 (22.8%) had a left main stenosis with > 50% diameter loss. Follow-up was complete in 99%. Fourteen patients died (7.3%) within the first 30 days after surgery. Twelve-month actuarial survival was 86%, 4-year survival was 80%, and 10-year survival was 40%. Predictors of poor long-term survival on multivariate analysis were end-systolic volume index (chi 2 = 14.02, P = .002), number of previous myocardial infarctions (chi 2 = 6.47, P = .001), preoperative stenosis score (chi 2 = 4.97, P = .02), and age at the time of surgery (chi 2 = 4.45, P = .03). CONCLUSIONS: End-systolic volume index is the major predictor of survival after coronary artery bypass graft surgery in patients with impaired left ventricular function. Strategies to prevent ventricular dilatation, such as angiotensin-converting enzyme inhibitors, may improve the long-term outcome in these patients.

Efficacy and dosage of enalapril in congenital and acquired heart disease.

In a tertiary referral centre 63 patients underwent 67 treatment periods with enalapril. The median age was 5.4 months. All children had signs of heart failure: congestive cardiac failure with breathlessness at rest was present in 88%. Haemodynamic groups were left-to-right shunt (n = 15), impaired ventricular function (n = 14), after cardiac surgery (n = 23), valvar regurgitation (n = 12), and hypertension (n = 3). Serial clinical, radiological, and laboratory data were used to judge outcome. The mean (SD) maximal dose was 0.30 (0.21) mg/kg/day. Thirty nine (58%) patients improved, 20 (30%) showed no improvement, and eight (12%) had side effects requiring discontinuation of enalapril. Renal failure in eight patients was related to young age, low weight, and left-to-right shunt group. Three patients died in congestive heart failure with renal failure. Enalapril was clinically safe and effective for children with cardiac failure secondary to ventricular impairment, valvar regurgitation, or after cardiac surgery. Renal failure was a problem in young infants with left-to-right shunts.

First-time coronary artery bypass grafting: the anaesthetist as a risk factor.

We have investigated the contribution of the anaesthetist and surgeon to outcome after 1301 consecutive coronary artery bypass grafting operations (first operation). The mean + 1 SD aspartate amino transferase concentration on the day after surgery (AST-D1) was 134 u litre-1 (or, after logarithmic transformation, 94 u litre-1). Twenty patients were selected at random from each of three groups having AST-D1 less than 100 u litre-1, 100-134 u litre-1 or greater than 134 u litre-1; positive ECG diagnoses of perioperative myocardial infarction were significantly more frequent with AST-D1 values greater than 100 u litre-1 than with smaller values, but no more frequent with AST-D1 greater than 134 u litre-1. Because several deaths occurred before AST-D1 could be measured, an "adverse outcome" was defined as either hospital death or AST-D1 greater than 100 u litre-1. Univariate analysis implicated both anaesthetist and surgeon as significant predictors of adverse outcome but, after allowing for 12 patient-related factors, only cardiopulmonary bypass time (or ischaemic cross-clamp time) (P less than 0.01) and anaesthetist (P = 0.05) were associated significantly with outcome.