Introduction Remote ischaemic preconditioning (RIPC) has emerged as a non-invasive, low-cost therapeutic intervention for reducing peri-operative myocardial injury (PMI) in patients undergoing coronary artery bypass graft (CABG) and/or valve surgery. However, some studies have been neutral, suggesting that the standard single limb RIPC stimulus may be ineffective under certain conditions. We investigated the effect of increasing the strength of the RIPC stimulus in patients undergoing elective cardiac bypass surgery. Methods and results 180 consecutive patients undergoing elective CABG and/or valve surgery were randomised to receive either RIPC (2–5 min cycles of simultaneous upper arm and thigh cuff inflation and deflation, N=90) or control (uninflated cuffs placed on the upper arm and thigh for 20 min, N=90). Patients randomised to RIPC had less PMI (26% reduction in 72 h area-under-the-curve high-sensitivity Troponin T; p=0.003), reduced incidence of post-operative atrial fibrillation (AF, 11% RIPC vs 24% control; p=0.031), decreased the incidence of acute kidney injury (AKI, 7% RIPC vs 17% control; p=0.036), and shortened the stay on the intensive care unit (ICU, 2 days RIPC vs 3 days control; p=0.043). Interestingly, we found that in those patients who received IV GTN during surgery sustained less PMI, and RIPC was ineffective. Conclusions Multi-limb RIPC induced by simultaneous upper arm and leg cuff inflation reduced PMI, decreased the incidence of post-operative AF, reduced the incidence of AKI and shortened the ITU stay, in patients undergoing CABG and/or valve surgery.

Introduction Remote ischaemic preconditioning (RIPC) using brief cycles of upper or lower limb ischaemia and reperfusion has been reported to protect the heart against ischaemia-reperfusion injury (IRI). Previous studies suggest that the diabetic heart is more resistant to the cardioprotective effects of myocardial ischaemic preconditioning. Whether the diabetic heart is amenable to RIPC is unknown and is investigated in this study. Methods Non-diabetic and diabetic patients undergoing elective coronary artery bypass graft (CABG) surgery were randomised to receive three different treatment protocols after the induction of anaesthesia: (1) Control—no RIPC; (2) RIPC1 comprising 3-five min cycles of upper arm cuff inflation/deflation; or (3) RIPC2 comprising 2-five min cycles of simultaneous upper and lower limb cuff inflations/deflations (total 4). A section of the right atrial appendage was harvested, from which atrial trabeculae were isolated and subjected to 90 min simulated ischaemia and 120 min simulated reperfusion, at the end of which the recovery of baseline contractile function was determined. Results Atrial trabeculae harvested from diabetic (N=13 patients) and non-diabetic control patients (N=20 patients) were demonstrated to recover 24.5%±2.4% and 29.3%±1.3% of baseline contractile function, respectively. Prior treatment of patients with RIPC1 increased the recovery of function in both non-diabetic (50.4%±1.9%; p<0.05) and diabetic (41.6%±1.9%; p<0.05) patients. Interestingly, the stronger RIPC2 stimulus resulted in a greater recovery of function in both non-diabetic (59.3%±1.9%; p<0.05) and diabetic (50.7%±2.1%; p<0.05) patients. As a positive control direct hypoxic preconditioning (HPC) of atrial trabeculae also improved the recovery of function (56.4%±1.8% with HPC vs 27.5%±1.7% in control; N=10 patients; p<0.05). The administration of the MEK-Erk1/2 inhibitors U0126 and PD98059 at the onset of reperfusion abrogated the protective effect in both non-diabetic (30.9%±0.8% U0126 and 31.3%±0.8% PD98059; p>0.05) and diabetic (28.6%±0.9% U0126 and 30.0%±1.2% PD98059; p>0.05) atrial trabeculae. Conclusion We demonstrate for the first time that in vivo RIPC can protect ex vivo atrial trabeculae against simulated IRI. Both non-diabetic and diabetic atrial trabeculae were amenable to RIPC protection. Increasing the intensity of the RIPC stimulus resulted in greater functional recovery. The pro-survival kinase MEK-Erk1/2 appears to contribute to RIPC protection in human atria trabeculae.

Background Surgery is the treatment of choice for early stage non-small cell lung cancer (NSCLC). However, curative intent is commonly not achieved due to inaccurate clinical staging and disease recurrence. Aim We aimed to determine the incidence of futile thoracotomies (FT) in patients with NSCLC following surgery with curative intent. In addition, we wished to identify prognostic factors that predicted FT. Methods In this analytical retrospective cohort study, thoracotomy cases between October 2003 and September 2008 at a single institution were identified. Confirmed cases of primary NSCLC only were included. A thoracotomy was deemed futile if any one of the following criteria were met: pathologically confirmed N2, N3, or M1 disease, an exploratory thoracotomy, or a thoracotomy in a patient who developed recurrent disease or died within 1 year of surgery. When a PET scan was performed, the SUVmax of the primary tumour was reported by a radiologist blinded to the clinical information. Case notes and hospital systems were interrogated for evidence of recurrence and survival. Statistical analysis was performed with STATA version 10 for Windows. Results We identified 171 consecutive patients with NSCLC who underwent lung resection with curative intent. 105 (61%) were male and mean age at the time of surgery was 66 years. 134 (78%) had lobectomy, 8 bi-lobectomy, 19 pneumonectomy and 10 sub-lobar resection (segmentectomy or wedge resection). Overall 46 (27%) underwent FT. Nine patients (5.2%) had clinically unsuspected N2 disease at pathological staging. An SUVmax of the primary tumour greater than 8 was associated with an increased risk of FT (RR 2.35 (p=0.03)) (Abstract P222 Table 1). The presence of lymphovascular invasion was also associated with a increased risk of FT (RR 1.71 (p=0.04)). Those with a primary tumour greater than or equal to 3 cm in size had a RR of 1.91 (p=0.02) of FT. Conclusions Between 2003 and 2008, 27% of patients at our cardiothoracic centre for lung cancer underwent a futile thoracotomy. High SUVmax, the presence of lymphovascular invasion and tumour size ≥3 cm are predictors of FT. Future, prospective studies employing adjuvant chemotherapy in these patient groups are warranted.

Background: Remote ischaemic preconditioning (RIPC) induced by brief ischaemia and reperfusion of the arm reduces myocardial injury in coronary artery bypass (CABG) surgery patients receiving predominantly cross-clamp fibrillation for myocardial protection. However, coldblood cardioplegia is the more commonly used method world wide.Objective: To assess whether RIPC is cardioprotective in CABG patients receiving cold-blood cardioplegia.Design: Single-centre, single-blinded, randomised controlled trial.Setting: Tertiary referral hospital in London.Patients: Adults patients (18-80 years) undergoing elective CABG surgery with or without concomitant aortic valve surgery with cold-blood cardioplegia. Patients with diabetes, renal failure (serum creatinine > 130 mmol/l), hepatic or pulmonary disease, unstable angina or myocardial infarction within the past 4 weeks were excluded.Interventions: Patients were randomised to receive either RIPC (n = 23) or control (n = 22) after anaesthesia. RIPC comprised three 5 min cycles of right forearm ischaemia, induced by inflating a blood pressure cuff on the upper arm to 200 mm Hg, with an intervening 5 min reperfusion. The control group had a deflated cuff placed on the upper arm for 30 min.Main outcome measures: Serum troponin T was measured preoperatively and at 6, 12, 24, 48 and 72 h after surgery and the area under the curve (AUC at 72 h) calculated.Results: RIPC reduced absolute serum troponin T release by 42.4% (mean (SD) AUC at 72 h: 31.53 (24.04) mu g/l. 72 h in controls vs 18.16 (6.67) mg/l. 72 h in RIPC; 95% Cl 2.4 to 24.3; p = 0.019).Conclusions: Remote ischaemic preconditioning induced by brief ischaemia and reperfusion of the arm reduces myocardial injury in CABG surgery patients undergoing cold-blood cardioplegia, making this non-invasive cardioprotective technique widely applicable clinically.

Introduction Experimental animal studies suggest that acute treatment with “statins” reduces myocardial infarct size. However, this cardioprotective effect is lost with chronic statin therapy but can be recaptured with an acute high dose of statin therapy given before infarction. We hypothesised that pretreatment with high-dose atorvastatin confers additional cardioprotection in patients undergoing elective cardiac surgery, when compared with standard statin therapy. Methods Patients undergoing elective cardiac surgery were randomly assigned to the following treatment groups: (1) control: patients received their usual statin therapy before cardiac surgery; (2) patients were given high-dose atorvastatin (160 mg) 12 h before cardiac surgery in place of their usual statin therapy. During cardiac surgery, right atrial appendages were harvested from which atrial trabeculae were dissected. The isolated atrial trabeculae were then suspended in an organ bath and subjected to 90 minutes hypoxia followed by 120 minutes rexoygenation in order to simulate ischaemia–reperfusion injury. At the end of the reoxygenation period, the recovery of baseline contractile function was determined. A group of atrial trabeculae harvested from control patients taking their usual statin therapy was subjected to a standard hypoxic preconditioning protocol comprising 3 minutes hypoxia followed by 7 minutes reoxygenation before the index hypoxic episode. Results Atrial trabeculae harvested from control patients taking standard statin therapy (N = 15 patients) were shown to recover 35.2 ± 1.1% of baseline contractile function. Interestingly, there was a significant improvement in the recovery of baseline contractile function in atrial trabeculae taken from patients (N = 10 patients) pretreated with the high dose of oral atorvastatin (54.0 ± 1.5% with atorvastatin vs 35.2 ± 1.1% in control; p Conclusions Pretreatment with high-dose oral atorvastatin improves recovery of function from hypoxia–reoxygenation injury over and above that obtained by standard statin therapy in patients undergoing elective cardiac surgery.