Transactivation of epidermal growth factor receptor (EGFR) may contribute to specific protective responses (e.g. mediated by δ-opioid, bradykinin, or muscarinic receptors). No studies have assessed EGFR involvement in cardioprotection mediated by adenosine receptors (ARs), and the role of EGFR in ischemic preconditioning (IPC) is unclear. We tested EGFR, matrix metalloproteinase (MMP), and heparin-binding EGF (HB-EGF) dependencies of functional protection via A1AR agonism or IPC. Pretreatment of mouse hearts with 100 nM of A1AR agonist 2-chloro- N6-cyclopentyladenosine (CCPA) or IPC (3 × 1.5-min ischemia/2-min reperfusion) substantially improved recovery from 25-min ischemia, reducing left ventricular diastolic dysfunction up to 50% and nearly doubling pressure development and positive change in pressure over time (+dP/d t). Benefit with both CCPA and IPC was eliminated by inhibitors of EGFR tyrosine kinase (0.3 μM AG1478), MMP (0.3 μM GM6001), or HB-EGF ligand (0.3 ng/ml CRM197), none of which independently altered postischemic outcome. Phosphorylation of myocardial EGFR, Erk1/2, and Akt increased two- to threefold during A1AR agonism, with responses blocked by AG1478, GM6001, and CRM197. Studies in HL-1 myocytes confirm A1AR-dependent Erk1/2 phosphorylation is negated by AG1478 or GM6001, and reduced with CRM197 (as was Akt activation). These data collectively reveal that A1AR- and IPC-mediated functional protection is entirely EGFR and MMP dependent, potentially involving the HB-EGF ligand. Myocardial survival kinase activation (Erk1/2, Akt) by A1AR agonism is similarly MMP/HB-EGF/EGFR dependent. Thus MMP-mediated EGFR activation appears essential to cardiac protection and signaling via A1ARs and preconditioning.

BackgroundThe objective of this study is to analyse the effectiveness of the surgical torque limiter during operative use. The study also investigates the potential differences in torque between hand and drill-based screw insertion into locking plates using a standardised torque limiter.MethodsTorque for both hand and power screw insertion was measured through a load cell, registering 6.66 points per second. This was performed in a controlled environment using synthetic bone, a locking plate and locking screws to simulate plate fixation. Screws were inserted by hand and by drill with torque values measured.ResultsThe surgical torque limiter (1.5 Nm) was effective as the highest recorded reading in the study was 1.409 Nm. Comparatively, there is a statistically significant difference between screw insertion methods. Torque produced for manually driven screw insertion into locking plates was 1.289 Nm (95 % CI 1.269–1.308) with drill-powered screw insertion at 0.740 Nm (95 % CI 0.723–0.757).ConclusionsThe surgical torque limiter proved to be effective as per product specifications. Screws inserted under power produce significantly less torque when compared to manual insertion by hand. This is likely related to the mechanism of the torque limiter when being used at higher speeds for which it was designed. We conclude that screws may be inserted using power to the plate with the addition of a torque limiter. It is recommended that all screws inserted by drill be hand tightened to achieve adequate torque values.

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