The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor

Brain-dead donors are the major source of lungs for transplantation. Brain death is characterized by two hemodynamic phases. Initially, massive sympathetic discharge results in a hypertensive crisis. This is followed by neurogenic hypotension. Up-regulation of pro-inflammatory mediators occurs in all organs and lung injury develops; this can adversely affect graft function post-transplantation. The mechanisms of the systemic and lung inflammation are unknown. We hypothesized that the hemodynamic changes are responsible for these inflammatory phenomena. Brain death was induced by intra-cranial balloon inflation in rats. This resulted in hypertensive crisis, followed by hypotension. There was a significant increase in blood neutrophil CD11b/CD18 expression and pro-inflammatory cytokine levels in serum and bronchoalveolar lavage, compared with control animals. Rupture of the capillary-alveolar membrane was demonstrated by electron microscopy. Elimination of the hypertensive response by α-adrenergic antagonist pre-treatment prevented inflammatory lung injury, reduced the systemic inflammatory markers and preserved capillary-alveolar membrane integrity. Correction of the neurogenic hypotension with noradrenaline ameliorated the systemic inflammatory response and improved oxygenation. We conclude that the sympathetic discharge triggers systemic and lung inflammation, which can be further enhanced by neurogenic hypotension. Management of the brain-dead donor with early anti-inflammatory treatment and vasoconstrictors is warranted.     

Transportation of a client with muscular dystrophy on commercial air: a unique setting for a rehabilitation nurse.

This experience was very well suited to rehabilitation nursing, demanding specialized knowledge and care. Our talents can be used in unique situations. We can make a difference in the lives of persons who have altered functional abilities to promote optional function--no matter what the location.     

Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval.

BACKGROUND: The QT interval on the ECG is prolonged by more than 50 marketed drugs, an effect that has been associated with syncope and/or sudden cardiac death due to an arrhythmia. Because changes in heart rate also change the QT interval, it has become standard practice to use a correction formula, such as the Bazett formula, to normalize the QT interval to a heart rate of 60 bpm, that is, the rate-corrected QT or QTc. Numerous other formulas have been devised to make this correction, including the Fridericia, Hodges, and Framingham formulas. OBJECTIVES: The purpose of this study was to investigate how the Bazett formula and three other formulas influence assessment of the QT-prolonging effect of the potassium channel-blocking drug ibutilide. METHODS: Using a standardized physical activity protocol, the QT interval was assessed over a broad range of heart rates before and after an infusion of ibutilide (4.75 microg/kg) that produced a stable 15- to 20-ms QT prolongation in consenting normal subjects (9 men and 9 women). The QT interval was measured digitally over a range of heart rates from 60 to 120 bpm, and then four correction formulas (Bazett, Fridericia, Framingham, or Hodges) were applied. The uncorrected change in QT interval due to ibutilide was compared with the change using each of the formulas by repeated measures analysis of variance. RESULTS: At heart rates from 60 to 120 bpm, the Bazett and Fridericia correction formulas overestimated the change in QT in both men and women (P <.001). However, the Framingham and Hodges formulas did not alter the accuracy of the assessment of QT interval change. CONCLUSION: Rate correction of QT intervals using the standard Bazett and Fridericia formulas can introduce significant errors in the assessment of drug effects on the QT interval. This has implications for the clinical assessment of drug effects and for the safety assessment of new drugs under development.     

The utility of bipolar electrocautery in hereditary hemorrhagic telangiectasia

OBJECTIVE: The surgical treatment of epistaxis associated with hereditary hemorrhagic telangiectasia (HHT) is varied. Laser therapy is often inadequate for larger complex lesions. This study sought to determine if bipolar cautery can be effectively and safely used in treating HHT-associated epistaxis. STUDY DESIGN AND SETTING: Records from all patients with HHT treated surgically over 8 years were reviewed retrospectively. Outcomes or complications were noted in the clinic on follow-up evaluation. RESULTS: Twenty-seven patients with HHT who underwent surgical treatment of epistaxis were evaluated; 18 were treated with bipolar cautery. Forty-two separate bipolar treatments were performed. No new septal perforations or synechiae were noted. Twenty-two of 42 treatments were coupled with ancillary laser treatments. The bipolar was also used as the sole technique in 20 procedures. CONCLUSION: Bipolar electrocautery is a safe and effective tool for the intraoperative control of HHT-related epistaxis. SIGNIFICANCE: Bipolar electrocautery may be used as an adjunct to laser techniques or as a stand-alone technique. EBM RATING: C-4.     

APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.