Anticipatory perioperative management for patent ductus arteriosus surgery: Understanding postligation cardiac syndrome

Ligation of a hemodynamically significant ductus arteriosus results in significant changes in loading conditions which have predictable consequences. Postligation cardiac syndrome, defined as hypotension requiring inotropic support and failure of oxygenation and ventilation, may occur 6‐12 hours following ligation due to left ventricular systolic and diastolic failure, respectively. Afterload is the primary driver of this decompensation. In this review, we describe the pathophysiological changes in loading conditions associated with postligation cardiac syndrome and other contributors to cardiovascular dysfunction following ductal ligation. We present strategies for perioperative optimization and a physiology‐based algorithm for postoperative management guided by targeted neonatal echocardiography. The use of these strategies to reduce the frequency of postligation deterioration may be an avenue to improve outcomes for neonates in this vulnerable patient population.     

Exploring Coverage of the 2008 Irish Dioxin Crisis in the Irish and UK Newsprint Media

The 2008 dioxin crisis occurred as a result of contamination of Irish pork. The event had significant implications for Ireland’s economy and the reputation of its agricultural industry, as well as raising concerns for human health. This study describes the results of a content analysis of Irish and UK newspaper coverage of the 2008 Irish dioxin crisis, as this is likely to provide insight into how public perceptions of this issue were shaped. Articles from 16 print publications were systematically sampled for the period December 2008 to February 2009. The resulting data set of 141 articles was examined using a coding protocol developed based on previous research and refined during piloting. Results indicated that the dioxin crisis was primarily portrayed by the media as an industry/economic crisis, dominant in 26.9% of articles in the sample. Within this dominant portrayal, the agricultural industry was frequently cited as being in crisis (42.6%); however, the implications of the crisis on the wider economic environment also received attention (17.7%). Differences between Irish and UK-based media were also examined, revealing that while the Irish media most frequently described the crisis in terms of its impact on the industry and economy, the UK media were more likely to portray the crisis as a risk to health. These dominant media messages and message framings have implications for the public understanding of the issue in each country and potential consequences regarding perception of the adequacy of existing food policy and regulatory oversight.     

Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing.

Recent data suggest that Alzheimer's patients who discontinue treatment with cholinesterase inhibitors have a significantly delayed cognitive decline as compared to patients receiving placebo. Such observations suggest cholinesterase inhibitors to provide a disease-modifying effect as well as symptomatic relief and, moreover, that this benefit remains after drug withdrawal. Consistent with this suggestion, we now demonstrate that chronic administration of tacrine, nefiracetam, and deprenyl, drugs that augment cholinergic function, increases the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing. While both drug-treated and complex environment reared animals continue to exhibit memory-associated activation of hippocampal polysialylated neurons, the magnitude is significantly reduced suggesting that such interventions induce a more robust memory pathway that can acquire and consolidate new information more efficiently. This hypothesis is supported by our findings of improved learning behavior and enhanced resistance to cholinergic deficits seen following either intervention. Furthermore, the level of enhancement of basal neuroplastic status achieved by either drug or environmental intervention correlates directly with improved spatial learning ability. As a combination of both interventions failed to further increase basal polysialylated cell frequency, complex environment rearing and chronic drug regimens most likely enhanced cognitive performance by the same mechanism(s). These findings suggest that improved memory-associated synaptic plasticity may be the fundamental mechanism underlying the disease modifying action of drugs such as cholinesterase inhibitors. Moreover, the molecular and cellular events underpinning neuroplastic responses are identified as novel targets in the search for interventive drug strategies for the treatment of neurodegenerative and neuropsychiatric disorders.     

The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

Voltage-dependent calcium currents in Purkinje cells from rat cerebellar vermis.

Whole-cell patch clamp recording was used to characterize calcium currents in Purkinje cells dissociated from the cerebellar vermis of 1-3-week postnatal rats. A subset of Purkinje cells had a low-threshold, transient current similar to the T-type current in peripheral neurons. All Purkinje cells had a high-threshold, slowly inactivating current. Only a small component of the high-threshold current was sensitive to dihydropyridine (DHP) antagonists or to the dihydropyridine agonist BAY K8644. omega-Conotoxin had very little effect on the high-threshold current. The results suggest that these Purkinje cells have at least three types of calcium channels: T-type channels (present in only a fraction of cells), DHP-sensitive L-type channels (contributing a small fraction of the high-threshold current), and a predominant type of high-threshold channel that is pharmacologically distinct from L-type and N-type channels characterized in peripheral neurons.     

Behavior, genetics and biochemistry of an allele of the mutant mouse spastic, spaAlb

A new autosomal recessive mutation, characterized by an early defect in righting reflex and stiffened gait, progression to severe spasticity, tremor and rigidity, and death before weaning, appeared spontaneously on the C57BL/6 background. It was shown to be an allele of the mutant spastic spa, and shall be known as spaAlb. Mutant levels of [3H]strychnine binding are less than 10% of control levels in the brainstem and spinal cord. Autoradiographic examination of the distribution of [3H]strychnine binding sites in the mutant confirm a greatly reduced level of binding compared to control in all areas of the spinal cord, brainstem, and midbrain.     

Increased Ventricular Vulnerability in a Chronic Ethanol Model Despite Reduced Electrophysiologic Responses to Catecholamines

An increased incidence of sudden death has been reported in chronic alcoholism. To assess electrical vulnerability of the heart, action potential responses, and the role of the sympathetic system, a well-nourished canine model has been studied intact under chloralose anesthesia after 1 year of ethanol consumption at 36% of caloric intake. Two alcoholic groups were compared with controls (Group 1). In Group 2 myocardial vulnerability was assessed after chronic EtOH and superimposed acute administration. In Group 3 basal vulnerability was related to circulating norepinephrine and release of neurohormone from the myocardium. Subsequently the responsiveness to catecholamine infusion was determined. To assess vulnerability an electrode catheter was placed in the right ventricular apex. The basal ventricular fibrillation threshold (VFT) was reduced to 27 +/- 3 ma in Group 2 versus 43 +/- 1.0 in Group 1. Acute infusion of ethanol in Group 2 further reduced the threshold. Group 3 had a reduced basal VFT. Baseline arterial plasma levels of norepinephrine were 8-fold higher and coronary venous levels 13 times higher in the alcoholic group than in Group 1. However, VFT was not responsive to infused epinephrine, compared with Group 1 controls. In vitro study of superfused ventricular tissue from Group 3 revealed that basal action potential amplitude, overshoot, and resting potential were comparable with normals. Basal repolarization time (90%) was 198 +/- 12 msec in Group 3 versus 215 +/- 6 msec in Group 1 (p less than 0.05). After acute EtOH, repolarization time was shortened to 170 +/- 8.6 in Group 1 at 90 mg% ethanol (p less than 0.002), with minimal further change up to 280 mg%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholinergic and dopaminergic agents which inhibit a passive avoidance response attenuate the paradigm-specific increases in NCAM sialylation state

Summary The influence of cholinergic and dopaminergic agents on the acquisition of a passive avoidance response in the rat is demonstrated. Trifluoperazine (0.12 mg/kg), a dopamine antagonist, inhibited task acquisition when present during training or later, during consolidation, at the 10–12 h posttraining period and at no other intervening time point. Induction of amnesia was dose-dependent and was not apparent when the dose exceeded 0.12 mg/ kg. This effect appears to be due to an increase in dopamine release through presynaptic receptor antagonism as similar results could be obtained by the administration of apomorphine (0.5 mg/kg), a dopamine agonist, and this effect could be antagonized by the D 1 receptor selective antagonist SCH-23390. Scopolamine (0.15 mg/kg), a muscarinic antagonist, impaired acquisition of the passive avoidance response when administered during training and, separately, at the 6 h post-training period. This could not be attributed to presynaptic antagonism as oxotremorine (0.2 mg/kg), a muscarinic agonist, had no amnesic action. Administration of apomorphine or scopolamine during training and at the appropriate post-training period prevented subsequent paradigm-specific increases of neural cell adhesion molecule sialylation state in hippocampal immunoprecipitates obtained at 24 h after task acquisition and 4 h following intraventricular infusion of the labelled sialic acid precursor — N-acetyl-D-mannosamine. Oxotremorine alone did not influence neural cell adhesion molecule sialylation state. These observations provide further evidence of a regulatory role for neural cell adhesion molecule sialylation state in information storage processes.Abbreviations NCAM neural cell adhesion molecule - RSA relative specific activity - SDS-PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis - TCA trichloroacetic acid - TFP trifluoperazine