A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial?.

AIMS: Clinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1-7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy. METHODS AND RESULTS: A multi-centre phase II randomized, double-blind, and placebo-controlled trial. One hundred patients with anterior AMI and significant regional wall motion abnormality were randomized to receive either intracoronary infusion of BMC or placebo (1:1) within 24 h of successful primary percutaneous intervention (PPCI). The primary endpoint was the change in left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging. At 1 year, although LVEF increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: -0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0-0.20; P = 0.048). Major adverse events were rare in both treatment groups. CONCLUSION: The early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT00765453 and EudraCT 2007-002144-16.

Effects of continuous positive airway pressure treatment on coronary vasoreactivity measured by (82)Rb cardiac PET/CT in obstructive sleep apnea patients.

PURPOSE: Obstructive sleep apnea syndrome (OSA) increases the risk of cardiovascular disease. We aimed at evaluating the effect of continuous positive airway pressure (CPAP) treatment on coronary endothelium-dependent vasoreactivity in OSA patients by quantifying myocardial blood flow (MBF) response to cold pressure testing (CPT). METHODS: In the morning after polysomnography (PSG), all participants underwent a dynamic (82)Rb cardiac positron emitting tomography/computed tomography (PET/CT) scan at rest, during CPT and adenosine stress. PSG and PET/CT were repeated at least 6 weeks after initiating CPAP treatment. OSA patients were compared to controls and according to response to CPAP. Patients' characteristics and PSG parameters were used to determine predictors of CPT-MBF. RESULTS: Thirty-two untreated OSA patients (age 58 ± 13 years, 27 men) and 9 controls (age 62 ± 5 years, 4 men) were enrolled. At baseline, compared to controls (apnea-hypopnea index (AHI) = 5.3 ± 2.6/h), untreated OSA patients (AHI = 48.6 ± 19.7/h) tend to have a lower CPT-MBF (1.1 ± 0.2 mL/min/g vs. 1.3 ± 0.4 mL/min/g, p = 0.09). After initiating CPAP, CPT-MBF was not different between well-treated patients (AHI <10/h) and controls (1.3 ± 0.3 mL/min/g vs. 1.3 ± 0.4 mL/min/g, p = 0.83), but it was lower for insufficiently treated patients (AHI ≥10/h) (0.9 ± 0.2 mL/min/g vs. 1.3 ± 0.4 mL/min/g, p = 0.0045). CPT-MBF was also higher in well-treated than in insufficiently treated patients (1.3 ± 0.3 mL/min/g vs. 0.9 ± 0.2 mL/min/g, p = 0.001). Mean nocturnal oxygen saturation (β = -0.55, p = 0.02) and BMI (β = -0.58, p = 0.02) were independent predictors of CPT-MBF in OSA patients. CONCLUSIONS: Coronary endothelial vasoreactivity is impaired in insufficiently treated OSA patients compared to well-treated patients and controls, confirming the need for CPAP optimization.

FemHab: The effects of bed rest and hypoxia on oxidative stress in healthy women.

Independently, both inactivity and hypoxia augment oxidative stress. This study, part of the FemHab project, investigated the combined effects of bed rest-induced unloading and hypoxic exposure on oxidative stress and antioxidant status. Healthy, eumenorrheic women were randomly assigned to the following three 10-day experimental interventions: normoxic bed rest (NBR;n= 11; PiO2 = 133 mmHg), normobaric hypoxic bed rest (HBR;n= 12; PiO2 = 90 mmHg), and ambulatory hypoxic confinement (HAMB;n= 8: PiO2 = 90 mmHg). Plasma samples, obtained before (Pre), during (D2, D6), immediately after (Post) and 24 h after (Post+1) each intervention, were analyzed for oxidative stress markers [advanced oxidation protein products (AOPP), malondialdehyde (MDA), and nitrotyrosine], antioxidant status [superoxide dismutase (SOD), catalase, ferric-reducing antioxidant power (FRAP), glutathione peroxidase (GPX), and uric acid (UA)], NO metabolism end-products (NOx), and nitrites. Compared with baseline, AOPP increased in NBR and HBR on D2 (+14%; +12%;P< 0.05), D6 (+19%; +15%;P< 0.05), and Post (+22%; +21%;P< 0.05), respectively. MDA increased at Post+1 in NBR (+116%;P< 0.01) and D2 in HBR (+114%;P< 0.01) and HAMB (+95%;P< 0.05). Nitrotyrosine decreased (-45%;P< 0.05) and nitrites increased (+46%;P< 0.05) at Post+1 in HAMB only. Whereas SOD was higher at D6 (+82%) and Post+1 (+67%) in HAMB only, the catalase activity increased on D6 (128%) and Post (146%) in HBR and HAMB, respectively (P< 0.05). GPX was only reduced on D6 (-20%;P< 0.01) and Post (-18%;P< 0.05) in HBR. No differences were observed in FRAP and NOx. UA was higher at Post in HBR compared with HAMB (P< 0.05). These data indicate that exposure to combined inactivity and hypoxia impairs prooxidant/antioxidant balance in healthy women. Moreover, habitual activity levels, as opposed to inactivity, seem to blunt hypoxia-related oxidative stress via antioxidant system upregulation.