Nicotinamide Riboside Delivery Generates NAD+ Reserves to Protect Vascular Cells Against Oxidative Damage

The ability of vascular cells to withstand oxidative insults is critical to vascular health. NAD+, which drives poly (ADP-ribose) polymerase (PARP) and sirtuin (SIRT) reactions, can be compromised and strategies for overcoming this limitation in the vasculature do not exist. This study determines if nicotinamide riboside (NR) delivery can augment NAD+ stores and fuel resistance to oxidative stress. I established that oxidative-stress insult on vascular cells decreased NAD+ levels, accompanied by a striking increase in nuclear PAR-chain accumulation. PARP inhibition abolished PAR-chain formation and preserved NAD+ levels, establishing PARP in NAD+ consumption in this model. NR delivery protected against cell-shrinkage and cell death and promoted DNA repair efficiency. PARP inhibition mimicked NR’s beneficial effects on cell-shrinkage and viability but at the cost of DNA repair efficiency. Interestingly, the beneficial effects of NR on viability and DNA repair were abrogated upon SIRT1 knock-down (KD). SIRT6 KD was similarly implicated in NR-mediated DNA repair. Furthermore, NR delivery protected against oxidative-stress-induced senescence. This protection was partially lost by SIRT1 KD. NR delivery protects vascular cells from H2O2–induced cell death, cytoskeletal collapse and senescence and promotes DNA repair efficiency. This NAD+ fueling strategy may offer new opportunities for resisting oxidative-stress insults in the aging vasculature

Cardiac failure following inadvertent administration of high-dose epinephrine subcutaneously

Our aim is to report the consequences of epinephrine toxicity leading to cardiac failure in a child and the successful management with dopamine and milrinone. A previously healthy 13-year-old girl undergoing a left tympanomastoidectomy was inadvertently administered 10 mL of 1:1000 epinephrine subcutaneously (0.175 mg/kg) on the left post auricular region in lieu of lidocaine. She developed sudden supraventricular tachycardia, hypertension and flash pulmonary edema. She was initially treated with propofol, nitrogycerin and increased peak end-expiratory pressure. Within 4 h, she remained tachycardic, but was hypotensive with an increased central venous pressure. Electrocardiogram and echocardiogram investigations showed ST changes indicative of myocardial ischemia and globally reduced function, respectively. Dopamine infusion was administered, together with milrinone, resulting in a gradual improvement of cardiac function within 3 days. She was transitioned to enalapril and discharged home. This case highlights the clinical features of high dose epinephrine toxicity secondary to iatrogenic subcutaneous overdose followed by hypotension and pulmonary edema as a possible late effect of epinephrine and the successful management of secondary cardiac failure with administration of dopamine, milrinone and enalapril. © 2012 - IOS Press and the authors

Effects of glycol-split low molecular weight heparin on placental, endothelial, and anti-inflammatory pathways relevant to preeclampsia

The authors thank the donors, the Research Centre for Women’s and Infants’ Health BioBank program, the Lunenfeld-Tanenbaum Research Institute and the MSH/University Health Network Department of Obstetrics & Gynaecology for the human specimens used in this study.Peer reviewedPublisher PD