Postoperative ST-segment elevation: was vasospasm caused by anaphylaxis or by its treatment with epinephrine?

BACKGROUND: Anaphylaxis must be recognized and treated promptly to avoid significant morbidity and mortality. In this clinical setting, electrocardiographic changes can be multifactorial. OBJECTIVE: To discuss vasospasm as a cause of myocardial ischemia and its possible triggering by anaphylaxis itself or by the administration of epinephrine. METHODS: We describe a patient with multiple previous allergies who received intravenous epinephrine to treat suspected anaphylaxis. She immediately developed crushing chest pain with ST-segment elevations in the inferior leads. Throughout the discussion, we address differential diagnoses, physiologic features, and treatment. RESULTS: Her symptoms and electrocardiographic changes were consistent with vasospasm, which resolved after treatment with sublingual nitroglycerin. However, the reaction was sufficient to cause an elevation in the troponin T level and, therefore, myocardial damage on the cellular level. CONCLUSIONS: Cardiovascular complications, including electrocardiographic changes, may be induced by anaphylactic mediators or by medications used for its treatment.     

GRK2 as a therapeutic target for heart failure

Introduction: G protein-coupled receptor (GPCR) kinase-2 (GRK2) is a regulator of GPCRs, in particular β-adrenergic receptors (ARs), and as demonstrated by decades of investigation, it has a pivotal role in the development and progression of cardiovascular disease, like heart failure (HF). Indeed elevated levels and activity of this kinase are able to promote the dysfunction of both cardiac and adrenal α- and β-ARs and to dysregulate other protective signaling pathway, such as sphingosine 1-phospate and insulin. Moreover, recent discoveries suggest that GRK2 can signal independently from GPCRs, in a ‘non-canonical’ manner, via interaction with non-GPCR molecule or via its mitochondrial localization.

Areas covered: Based on this premise, GRK2 inhibition or its genetic deletion has been tested in several disparate animal models of cardiovascular disease, showing to protect the heart from adverse remodeling and dysfunction.

Expert opinion: HF is one of the leading cause of death worldwide with enormous health care costs. For this reason, the identification of new therapeutic targets like GRK2 and strategies such as its inhibition represents a new hope in the fight against HF development and progression. Herein, we will update the readers about the ‘state-of-art’ of GRK2 inhibition as a potent therapeutic strategy in HF.     

Expression of the genes GAD67 and Distal-less-4 in the forebrain of Xenopus laevis confirms a common pattern in tetrapods

We investigated whether gamma-amino butyric acidergic (GABAergic) cell populations correlate positionally with specific Dlx-expressing histogenetic territories in an anamniote tetrapod, the frog Xenopus laevis. To that end, we cloned a fragment of Xenopus GAD67 gene (xGAD67, expressed in GABAergic neurons) and compared its expression with that of Distal-less-4 gene (xDll-4, ortholog of mouse Dlx2) in the forebrain at late larval and adult stages. In Xenopus, GABAergic neurons were densely concentrated in xDll-4-positive territories, such as the telencephalic subpallium, part of the hypothalamus, and ventral thalamus, where nearly all neurons expressed both genes. In contrast, the pallium of Xenopus generally contained dispersed neurons expressing xGAD67 or xDll-4, which may represent local circuit neurons. As in amniotes, these pallial interneurons may have been produced in the subpallium and migrated tangentially into the pallium during development. In Xenopus, the ventral division of the classic lateral pallium contained extremely few GABAergic cells and showed only low signal of the pallial gene Emx1, suggesting that it may represent the amphibian ventral pallium, homologous to that of amniotes. At caudal forebrain levels, a number of GABAergic neurons was observed in several areas (dorsal thalamus, pretectum), but no correlation to xDll-4 was observed there. The location of GABAergic neurons in the forebrain and their relation to the developmental regulatory genes Dll and Dlx were very similar in Xenopus and in amniotes. The close correlation in the expression of both genes in rostral forebrain regions supported the notion that Dll/Dlx are among the genes involved in the acquisition of the GABAergic phenotype.     

Enhanced uptake of ifosfamide into GH3 prolactinomas with hypercapnic hyperoxic gases monitored in vivo by (31)P MRS

Previously, ³¹P magnetic resonance spectroscopy (MRS) has been used to detect ifosfamide (IF) in vivo and to show that breathing carbogen (5% CO₂/95% O₂) enhances the uptake and increases the efficacy of IF in rat GH3 prolactinomas [Rodrigues LM, Maxwell RJ, McSheehy PMJ, Pinkerton CR, Robinson SP, Stubbs M, and Griffiths JR (1997). In vivo detection of ifosfamide by ³¹P MRS in rat tumours; increased uptake and cytotoxicity induced by carbogen breathing in GH3 prolactinomas. Br J Cancer 75, 62–68]. We now show that other hypercapnic and/or hyperoxic (5% CO₂ in air, 2.5% CO₂ in O₂) gas mixtures also increase the uptake of IF into tumors, measured by ³¹P MRS. All gases caused an increased uptake (C_max) of IF compared to air breathing, with carbogen inducing the largest increase (85% (P<.02) compared to 46% with 2.5% CO₂ in O₂ (P<.004) and 48% with 5% CO₂ in air (P<.004)). The T_max (time of maximum concentration in tumor posintravenous injection of IF) was significantly (P<.04) later in the cohort that breathed 5% CO₂ in air. The increased uptake of IF with carbogen breathing was selective to tumor tissue and there were no significant increases in any of the normal tissues studied, suggesting that any host tissue toxicity would be minimal. Carbogen breathing by patients causes breathlessness. There was no significant difference in IF uptake between breathing carbogen and 2.5% CO₂ in O₂ and, therefore, the ability of 2.5% CO₂ in O₂ to also increase IF uptake may be clinically useful as it causes less patient discomfort.     

Expression patterns of developmental regulatory genes show comparable divisions in the telencephalon of Xenopus and mouse: insights into the evolution of the forebrain

In this study, we review data on the existence of comparable divisions and subdivisions in the telencephalon of different groups of tetrapods based on expression of some developmental regulatory genes, having a particular focus in the comparison of the anuran amphibian Xenopus and the mouse. The available data on Xenopus, mouse, chick and turtle indicate that apparently all tetrapod groups possess the same molecularly distinct divisions and subdivisions in the telencephalon. This basic organization was likely present in the telencephalon of stem tetrapods. Each division/subdivision is characterized by expression of a unique combination of developmental regulatory genes, and appears to represent a self-regulated and topologically constant histogenetic brain compartment that gives rise to specific groups of cells. This interpretation has an important consequence for searching homologies, since a basic condition for cell groups in different vertebrates to be considered homologous is that they originate in the same compartment. However, evolution may allow individual cell groups derived from comparable (field homologous) subdivisions to be either similar or dissimilar across the vertebrate groups, giving rise to several possible scenarios of evolution, which include both the evolutionary conservation of similar (homologous) cells or the production of novel cell groups. Finally, available data in the lamprey, a jawless fish, suggest that not all telencephalic subdivisions were present at the origin of vertebrates, raising important questions about their evolution.     

Estimating respiratory system compliance during mechanical ventilation using artificial neural networks

In this study we evaluated whether a technology based on artificial neural networks (ANN) could estimate the static compliance (C(RS)) of the respiratory system, even in the absence of an end-inspiratory pause, during continuous mechanical ventilation. A porcine model of acute lung injury was used to provide recordings of different respiratory mechanics conditions. Each recording consisted of 10 or more consecutive breaths in volume-controlled mechanical ventilation, followed by a breath having an end-inspiratory pause used to calculate C(RS) according to the interrupter technique (IT). The volume-pressure loop of the breath immediately preceding the one with pause was given to the ANN for the training, together with the C(RS) separately calculated by the IT. The prospective phase consisted of giving only the loops to the trained ANN and comparing the results yielded by it to the compliance separately calculated by the investigators. Determination of measurement agreement between ANN and IT methods showed an error of -0.67 +/- 1.52 mL/cm H(2)O (bias +/- SD). We could conclude that ANN, during volume-controlled mechanical ventilation, can extract C(RS) without needing to stop inspiratory flow. IMPLICATIONS: We studied the application of artificial neural networks (ANN) to the estimation of respiratory compliance during mechanical ventilation. The study was performed on an animal model of acute lung injury, testing the performance of ANN in both healthy and diseased conditions of the lung.     

Nucleic acid testing (NAT) for HCV RNA in Italian transfusion centres: an external quality assessment.

BACKGROUND: We conducted an external quality assessment of the results obtained in Italian transfusion centre laboratories employing nucleic acid testing (NAT) for detection of HCV RNA in donated blood. STUDY DESIGN: Of 110 transfusions centres in Italy, 101 voluntarily participated. Each laboratory received seven separate shipments of samples for HCV RNA testing by NAT. Each shipment contained 8 plasma samples for a total of 23 negative and 33 positive samples with viral loads ranging from 25 to 1000 IU/mL. RESULTS: Of the 2080 HCV RNA-negative samples, 14 (0.7%) were reported as positive. The highest percent of false-negative results (6.9%) was found on samples from the first shipment with viral loads from 75 to 100 IU/mL. In subsequent shipments, the highest false-negative percentage ranged from 0.6% for samples with viral loads of 170-1000 IU/mL to 3.4% for samples with viral loads of 35-50 IU/mL. A false-negative rate of 4.9% occurred in samples in the sixth shipment with the lowest viral load (25IU/mL). Five (4.9%) centres were identified as having laboratories with low-performance. There were no significant differences among genotypes 1b, 2c and 3a with respect to percent of false-negative results reported. CONCLUSIONS: Overall, the accuracy of NAT observed in this study of Italian transfusion centre laboratories was excellent for all HCV genotypes tested, even for samples with low HCV RNA titres.