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A R Hall, N Burke, R K Dongworth, S B Kalkhoran, A Dyson, J M Vicencio, G W Dorn Ii, D M Yellon, D J Hausenloy
Mitochondria alter their shape by undergoing cycles of fusion and fission. Changes in mitochondrial morphology impact on the cellular response to stress, and their interactions with other organelles such as the sarcoplasmic reticulum (SR). Inhibiting mitochondrial fission can protect the heart against acute ischemia/reperfusion (I/R) injury. However, the role of the mitochondrial fusion proteins, Mfn1 and Mfn2, in the response of the adult heart to acute I/R injury is not clear, and is investigated in this study...
2016: Cell Death & Disease
R M Bell, H E Bøtker, R D Carr, S M Davidson, J M Downey, D P Dutka, G Heusch, B Ibanez, R Macallister, C Stoppe, M Ovize, A Redington, J M Walker, D M Yellon
In the 30 years since the original description of ischaemic preconditioning, understanding of the pathophysiology of ischaemia/reperfusion injury and concepts of cardioprotection have been revolutionised. In the same period of time, management of patients with coronary artery disease has also been transformed: coronary artery and valve surgery are now deemed routine with generally excellent outcomes, and the management of acute coronary syndromes has seen decade on decade reductions in cardiovascular mortality...
July 2016: Basic Research in Cardiology
B Cunniffe, V Sharma, M Cardinale, D Yellon
Remote ischaemic preconditioning is a non-invasive intervention with potential to protect a number of organs against ischaemia-reperfusion injury and possibly improve athletic performance. Little mechanistic evidence exists to support either limb choice or cuff inflation pressure that is most effective. This preliminary study aimed to establish the dose-response effect of different occlusion pressures on skeletal muscle oxygenation and blood flow in healthy males (n = 6). In a randomized controlled crossover study, cuff inflation pressures (140,160 and 180 mmHg) were used to induce limb ischaemia (× 3 cycles of 5-min) in upper (UL) and lower (LL) limbs on three separate occasions...
March 2, 2016: Clinical Physiology and Functional Imaging
Amber D Shaffer, Noel Jabbour, Mihaela Visoiu, Charles I Yang, Robert F Yellon
Acute Interventional Perioperative Pain Service consultants have routinely placed paravertebral nerve block (PVB) catheters for the continuous release of ropivacaine following stage I microtia reconstruction with costal cartilage graft at our institution since 2010. A retrospective chart review from July 2006 was performed to compare the length of hospital stay, median pain score (0-10 scale), and opioid use of patients receiving PVB with those of historical controls. Statistical analysis included t, Mann-Whitney U, and Fisher's exact tests...
May 2016: Otolaryngology—Head and Neck Surgery
Mojgan Ezzati, Alan Bainbridge, Kevin D Broad, Go Kawano, Aaron Oliver-Taylor, Eridan Rocha-Ferreira, Daniel Alonso-Alconada, Igor Fierens, Jamshid Rostami, K Jane Hassell, Ilias Tachtsidis, Pierre Gressens, Mariya Hristova, Kate Bennett, Sophie Lebon, Bobbi Fleiss, Derek Yellon, Derek J Hausenloy, Xavier Golay, Nicola J Robertson
Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention (n = 8); (ii) RIPostC - with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (n = 8)...
August 2016: Journal of Cerebral Blood Flow and Metabolism
A Malik, D I Bromage, Z He, L Candilio, A Hamarneh, S Taferner, S M Davidson, D M Yellon
No abstract text is available yet for this article.
October 20, 2015: Cardiovascular Drugs and Therapy
R M Bell, V Sivaraman, S P Kunuthur, M V Cohen, J M Downey, D M Yellon
No abstract text is available yet for this article.
2015: Cardiovascular Drugs and Therapy
Abigail E Dobyns, Ravi Goyal, Lauren Grisham Carpenter, Tom C Freeman, Lawrence D Longo, Steven M Yellon
As the critical gatekeeper for birth, prepartum remodeling of the cervix is associated with increased resident macrophages (Mφ), proinflammatory processes, and extracellular matrix degradation. This study tested the hypothesis that expression of genes unique to Mφs characterizes the prepartum from unremodeled nonpregnant cervix. Perfused cervix from prepartum day 21 postbreeding (D21) or nonpregnant (NP) rats, with or without Mφs, had RNA extracted and whole genome microarray analysis performed. By subtractive analyses, expression of 194 and 120 genes related to Mφs in the cervix from D21 rats were increased and decreased, respectively...
2015: PloS One
D A Healy, W A Khan, C S Wong, M Clarke Moloney, P A Grace, J C Coffey, C Dunne, S R Walsh, U Sadat, M E Gaunt, S Chen, S Tehrani, D J Hausenloy, D M Yellon, R S Kramer, R F Zimmerman, V V Lomivorotov, V A Shmyrev, D N Ponomarev, I A Rahman, J G Mascaro, R S Bonser, Y Jeon, D M Hong, R Wagner, M Thielmann, G Heusch, K Zacharowski, P Meybohm, B Bein, T Y Tang
BACKGROUND: A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. METHODS: Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists...
September 2014: International Journal of Cardiology
Jaime García-Prieto, Jose Manuel García-Ruiz, David Sanz-Rosa, Andrés Pun, Ana García-Alvarez, Sean M Davidson, Leticia Fernández-Friera, Mario Nuno-Ayala, Rodrigo Fernández-Jiménez, Juan A Bernal, José Luis Izquierdo-Garcia, Jesús Jimenez-Borreguero, Gonzalo Pizarro, Jesús Ruiz-Cabello, Carlos Macaya, Valentín Fuster, Derek M Yellon, Borja Ibanez
Selective stimulation of β3 adrenergic-receptor (β3AR) has been shown to reduce infarct size in a mouse model of myocardial ischemia/reperfusion. However, its functional long-term effect and the cardioprotective mechanisms at the level of cardiomyocytes have not been elucidated, and the impact of β3AR stimulation has not been evaluated in a more translational large animal model. This study aimed at evaluating pre-perfusion administration of BRL37344 both in small and large animal models of myocardial ischemia/reperfusion...
July 2014: Basic Research in Cardiology
A Myat, S R Redwood, B J Gersh, D M Yellon, M S Marber
No abstract text is available yet for this article.
October 2014: Heart: Official Journal of the British Cardiac Society
R K Dongworth, U A Mukherjee, A R Hall, R Astin, S-B Ong, Z Yao, A Dyson, G Szabadkai, S M Davidson, D M Yellon, D J Hausenloy
Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia-reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction...
2014: Cell Death & Disease
P S C Rees, S M Davidson, S E Harding, C McGregor, P M Elliot, D M Yellon, D J Hausenloy
No abstract text is available yet for this article.
June 2013: Cardiovascular Drugs and Therapy
Robert M Bell, Suma P Kunuthur, Cara Hendry, Damian Bruce-Hickman, Sean Davidson, Derek M Yellon
The mitochondrial permeability transition pore (mPTP) is widely accepted as an end-effector mechanism of conditioning protection against injurious ischaemia/reperfusion. However, death can be initiated in cells without pre-requisite mPTP opening, implicating alternate targets for ischaemia/reperfusion injury amelioration. Matrix metalloproteinases (MMP) are known to activate extrinsic apoptotic cascades and therefore we hypothesised that MMP activity represents an mPTP-independent target for augmented attenuation of ischaemia/reperfusion injury...
March 2013: Basic Research in Cardiology
Derek J Hausenloy, Abigail M Wynne, Mihaela M Mocanu, Derek M Yellon
AIMS: The diabetic heart is resistant to the myocardial infarct-limiting effects of ischemic preconditioning (IPC). This may be in part due to the downregulation of the phosphatidylinositol 3'-kinase-Akt pathway, an essential component of IPC protection. We hypothesized that treating the diabetic heart with the sulfonylurea, glimepiride, which has been reported to activate Akt, may lower the threshold required to protect the diabetic heart by IPC. METHODS: Goto-Kakizaki rats (a type II lean model of diabetes) received glimepiride (20 mg/kg per d, by oral gavage) or vehicle for (a) 3 months (chronic treatment) or (b) 24 hours (subacute treatment)...
May 2013: Journal of Cardiovascular Pharmacology and Therapeutics
Charles D Bluestone, J Douglas Swarts, Joseph M Furman, Robert F Yellon
We recently encountered a 15-year-old female with bilateral tympanostomy tubes who manifested persistent severe vertigo, at ground level, secondary to a unilateral middle-ear pressure of +200 mm H(2)O elicited by an obstructed tympanostomy tube in the presence of chronic nasal obstruction. We believe this is a previously unreported scenario in which closed-nose swallowing insufflated air into her middle ears, resulting in sustained positive middle-ear pressure in the ear with the obstructed tube. Swallowing, when the nose is obstructed, can result in abnormal negative or positive pressures in the middle ear, which has been termed the Toynbee phenomenon...
April 2012: Laryngoscope
D J Hausenloy, E K Iliodromitis, I Andreadou, A Papalois, G Gritsopoulos, M Anastasiou-Nana, D T Kremastinos, D M Yellon
BACKGROUND: The mechanism underlying remote ischemic conditioning (RIC) remains unclear. We investigated whether RIC protects the heart through the activation of the adenosine receptor and the PI3K-Akt pathway at the onset of myocardial reperfusion. METHODS AND RESULTS: Domestic pigs (27-35 kg) were subjected to in situ left anterior descending coronary artery ischemia (60 min) followed by reperfusion (180 min) and randomised to the following: (1) Control- No additional intervention; (2) Remote ischemic preconditioning (RIPC)- Four-5 min cycles of lower limb ischemia/reperfusion were administered prior to myocardial ischemia; (3) RIPC  +  Wort or 8-SPT: Wortmannin (Wort 20 μg/kg, a PI3K inhibitor) or 8-sulfophenyltheophylline (8-SPT 10 mg/kg, an adenosine receptor inhibitor) were administered intravenously 30 s before myocardial reperfusion to RIPC-treated animals; (4) Remote ischemic perconditioning (RIPerC)--Four-5 min cycles of lower limb ischemia/reperfusion were applied 1 min before myocardial reperfusion; (5) RIPerC  +  Wort or 8-SPT: Wort or 8-SPT were given 30 s before myocardial reperfusion to RIPerC-treated animals...
April 2012: Cardiovascular Drugs and Therapy
Derek J Hausenloy, E A Boston-Griffiths, D M Yellon
Ischaemic heart disease (IHD) is the leading cause of death and disability worldwide. The pathophysiological effects of IHD on the heart most often result from the detrimental effects of acute ischaemia-reperfusion injury (IRI) on the myocardium. Therefore, novel therapeutic targets for protecting the myocardium against acute IRI are required to reduce injury to the heart, preserve cardiac function and improve clinical outcomes in patients with IHD. In this regard, the mitochondrial permeability transition pore (mPTP) has emerged as a critical target for cardioprotection which is readily amenable to intervention at the time of myocardial reperfusion...
March 2012: British Journal of Pharmacology
Shiang Y Lim, Derek J Hausenloy, Sapna Arjun, Anthony N Price, Sean M Davidson, Mark F Lythgoe, Derek M Yellon
The pharmacological inhibition or genetic ablation of cyclophilin-D (CypD), a critical regulator of the mitochondrial permeability transition pore (mPTP), confers myocardial resistance to acute ischemia-reperfusion injury, but its role in post-myocardial infarction (MI) heart failure is unknown. The aim of this study was to determine whether mitochondrial CypD is also a therapeutic target for the treatment of post-MI heart failure. Wild-type (WT) and CypD(-/-) mice were subjected to either sham surgery or permanent ligation of the left main coronary artery to induce MI, and were assessed at either 2 or 28 days to determine the long-term effects of CypD ablation...
November 2011: Journal of Cellular and Molecular Medicine
R Goyal, S M Yellon, L D Longo, E Mata-Greenwood
OBJECTIVE: Placental insufficiency is a major factor associated with pregnancy complications such as miscarriages, intrauterine growth restriction and pre-eclampsia. Recent studies have identified the Brown Norway (BN) rat as a natural 'model' of placental insufficiency associated with decreased trophoblast remodeling of maternal uterine arteries. HYPOTHESIS: Genetic pathways involved in angiogenesis and immune cell regulation are dysregulated in the placenta of BN rats...
July 2010: Placenta
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