Propensity Matched Analysis of del Nido Cardioplegia in Adult Coronary Artery Bypass Grafting: Initial Experience With 100 Consecutive Patients.

BACKGROUND: Del Nido cardioplegia (DC) offers prolonged cardiac protection with single-dose administration and has had a long safety record in pediatric cardiac surgery. However, its application in the adult population has thus far been limited. We evaluated the efficacy of cardiac protection and clinical outcomes of DC vs blood cardioplegia (BC) in adult coronary artery bypass graft (CABG) patients. METHODS: Clinical outcomes of 100 consecutive isolated CABG patients who received DC (May to September 2014) were compared with the previous 100 consecutive isolated CABG patients receiving BC (December 2013 to April 2014). Propensity matching yielded 82 pairs. The same surgeons operated on all patients. Clinical patient characteristics and data were extracted from our local The Society of Thoracic Surgeons database and the electronic medical record. RESULTS: Preoperative characteristics were similar between BC and DC patients before and after propensity matching. BC patients received anterograde and retrograde cardioplegia, whereas DC was delivered anterograde, with 92 of 100 patients receiving a single dose only. Inotropic support upon arrival to the recovery unit did not differ between BC and DC (0.28 ± 0.11 vs 0.27 ± 0.11 µg/kg/min milrinone [p = 0.8] and 0.05 ± 0.03 vs 0.05 ± 0.03 µg/kg/min norepinephrine [p = 0.7]), nor did postoperative troponin T levels (0.56 ± 0.48 vs 0.70 ± 1.27 ng/mL; p = 0.3). The peak intraoperative glucose level was higher in BC (209.8 ± 40.4 mg/dL) than in DC (161.4 ± 42.3 mg/dL) patients (p < 0.001). No patients died in either group, and the postoperative incidence of atrial fibrillation, stroke, reoperation for bleeding, and prolonged intubation did not differ between the groups before and after matching. There was also no difference in the postoperative ejection fraction between the groups (0.51 ± 0.13 vs 0.47 ± 0.13 for BC and DC, respectively; p = 0.17). CONCLUSIONS: In our initial experience, DC provided equivalent myocardial protection and clinical outcomes to BC in adult isolated CABG patients. DC was associated with lower cardiopulmonary bypass glucose levels than BC and demonstrated the feasibility of single-dose administration for routine coronary operations.

Dopamine D2 receptor modulation of human response inhibition and error awareness.

Response inhibition, comprising action cancellation and action restraint, and error awareness are executive functions of considerable clinical relevance to neuropsychiatric disorders. Nevertheless, our understanding of their underlying catecholamine mechanisms, particularly regarding dopamine, is limited. Here, we used the dopamine D2 agonist cabergoline to study its ability to improve inhibitory control and modulate awareness of performance errors. A randomized, double-blind, placebo-controlled, crossover design with a single dose of cabergoline (1.25 mg) and placebo (dextrose) was employed in 25 healthy participants. They each performed the stop-signal task, a well-validated measure of action cancellation, and the Error Awareness Task, a go/no-go measure of action restraint and error awareness, under each drug condition. Cabergoline was able to selectively reduce stop-signal RT, compared with placebo, indicative of enhanced action cancellation (p < .05). This enhancement occurred without concomitant changes in overall response speed or RT variability and was not seen for errors of commission on the Error Awareness Task. Awareness of performance errors on the go/no-go task was, however, significantly improved by cabergoline compared with placebo (p < .05). Our results contribute to growing evidence for the dopaminergic control of distinct aspects of human executive ability, namely, action cancellation and error awareness. The findings may aid the development of new, or the repurposing of existing, pharmacotherapy that targets the cognitive dysfunction of psychiatric and neurological disorders. They also provide further evidence that specific cognitive paradigms have correspondingly specific neurochemical bases.

Attentional asymmetries in a visual orienting task are related to temperament.

Spatial asymmetries are an intriguing feature of directed attention. Recent observations indicate an influence of temperament upon the direction of these asymmetries. It is unknown whether this influence generalises to visual orienting behaviour. The aim of the current study was therefore to explore the relationship between temperament and measures of spatial orienting as a function of target hemifield. An exogenous cueing task was administered to 92 healthy participants. Temperament was assessed using Carver and White's (1994) Behavioural Inhibition System and Behavioural Activation System (BIS/BAS) scales. Individuals with high sensitivity to punishment and low sensitivity to reward showed a leftward asymmetry of directed attention when there was no informative spatial cue provided. This asymmetry was not present when targets were preceded by spatial cues that were either valid or invalid. The findings support the notion that individual variations in temperament influence spatial asymmetries in visual orienting, but only when lateral targets are preceded by a non-directional (neutral) cue. The results are discussed in terms of hemispheric asymmetries and dopamine activity.

Neurochemical enhancement of conscious error awareness.

How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience. Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes (e.g., attention deficit hyperactivity disorder, drug addiction). These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing, but our understanding of the neurochemical drivers of these processes is limited. We conducted a randomized, double-blind, placebo-controlled, cross-over design of the influence of methylphenidate, atomoxetine, and citalopram on error awareness in 27 healthy participants. The error awareness task, a go/no-go response inhibition paradigm, was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram, significantly improved the ability of healthy volunteers to consciously detect performance errors. Furthermore, this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylphenidate condition for errors made with versus without awareness. Our results have implications for the understanding of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors.

Methylphenidate but not atomoxetine or citalopram modulates inhibitory control and response time variability.

BACKGROUND: Response inhibition is a prototypical executive function of considerable clinical relevance to psychiatry. Nevertheless, our understanding of its pharmacological modulation remains incomplete. METHODS: We used a randomized, double-blind, placebo-controlled, crossover design to examine the effect of an acute dose of methylphenidate (MPH) (30 mg), atomoxetine (ATM) (60 mg), citalopram (CIT) (30 mg), and placebo (PLAC) (dextrose) on the stop signal inhibition task in 24 healthy, right-handed men 18-35 years of age. Participants performed the task under each of the four drug conditions across four consecutive sessions. RESULTS: Methylphenidate led to a reduction in both response time variability and stop-signal reaction time (SSRT), indicating enhanced response inhibition compared with all other drug conditions. Crucially, the enhancement of response inhibition by MPH occurred without concomitant changes in overall response speed, arguing against a simple enhancement of processing speed. We found no significant differences between ATM and PLAC, CIT and PLAC, or ATM and CIT for either response time variability or SSRT. CONCLUSIONS: An acute dose of MPH but not ATM or CIT was able to improve SSRT and reduce response time variability in nonclinical participants. Improvements in response inhibition and response variability might underlie the reported clinical benefits of MPH in disorders such as attention-deficit/hyperactivity disorder.