Magnetic Resonance Imaging Assessment of Regional Cerebral Blood Flow after Asphyxial Cardiac Arrest in Immature Rats

Manole, Mioara D.; Foley, Lesley M.; Hitchens, T. Kevin; Kochanek, Patrick M.; Hickey, Robert W.; Bayır, Hülya; Alexander, Henry; Ho, Chien; Clark, Robert S. B.

doi:10.1038/jcbfm.2008.112

Cited by 68 publications

(86 citation statements)

References 40 publications

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“…1,4 We previously showed that pretreatment of dV1-1 before ACA can enhance perfusion 24 hours after ischemia, resulting in improved neuronal survival in the hippocampal CA1 and cortex regions in our rat model of ACA.…”

Section: Introductionmentioning

confidence: 99%

“…3 Inhibition of PKCd (via specific inhibitor of PKCd, dV1-1) can cause a revival of CBF 24 hours after ischemia to counteract hypoperfusion or low CBF found to be suppressed after cardiac arrest from 38% to 65%. 1,4 We previously showed that pretreatment of dV1-1 before ACA can enhance perfusion 24 hours after ischemia, resulting in improved neuronal survival in the hippocampal CA1 and cortex regions in our rat model of ACA. 1 Here, we sought out to define the specific mechanism(s) of how inhibition of PKCd can alleviate these pathologies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protein Kinase C Delta Modulates Endothelial Nitric Oxide Synthase after Cardiac Arrest

Lin

Gresia

Stradecki

et al. 2014

J Cereb Blood Flow Metab

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We previously showed that inhibition of protein kinase C delta (PKCd) improves brain perfusion 24 hours after asphyxial cardiac arrest (ACA) and confers neuroprotection in the cortex and CA1 region of the hippocampus 7 days after arrest. Therefore, in this study, we investigate the mechanism of action of PKCd-mediated hypoperfusion after ACA in the rat by using the two-photon laser scanning microscopy (TPLSM) to observe cortical cerebral blood flow (CBF) and laser Doppler flowmetry (LDF) detecting regional CBF in the presence/absence of dV1-1 (specific PKCd inhibitor), nitric oxide synthase (NOS) substrate (L-arginine, L-arg) and inhibitor (N o -Nitro-L-arginine, NLA), and nitric oxide (NO) donor (sodium nitroprusside, SNP). There was an increase in regional LDF and local (TPLSM) CBF in the presence of dV1-1 þ L-arg, but only an increase in regional CBF under dV1-1 þ SNP treatments. Systemic blood nitrite levels were measured 15 minutes and 24 hours after ACA. Nitrite levels were enhanced by pretreatment with dV1-1 30 minutes before ACA possibly attributable to enhanced endothelial NOS protein levels. Our results suggest that PKCd can modulate NO machinery in cerebral vasculature. Protein kinase C delta can depress endothelial NOS blunting CBF resulting in hypoperfusion, but can be reversed with dV1-1 improving brain perfusion, thus providing subsequent neuroprotection after ACA. Keywords: asphyxial cardiac arrest; middle cerebral artery occlusion; neuroprotection; palmitic acid methyl ester; stearic acid methyl ester INTRODUCTIONWe previously showed that inhibition of protein kinase C delta (PKCd) via dV1-1 can increase perfusion 24 hours after asphyxial cardiac arrest (ACA). Global cerebral ischemia (via ACA) causes derangement of cerebral blood flow (CBF) responsible for neuronal cell death in the CA1 region of the hippocampus as well as the cortex.1 Owing to the overall decrease in CBF after ischemia, neuronal cell death 1 can occur in major regions of the brain responsible for learning, memory, and cognitive function.2 It is thought that during global ischemia, PKCd (a novel PKC) levels are elevated causing PKCd to translocate to the nucleus (activation) resulting in cellular damage. In the normal brain, PKCd levels are nominal whereas global ischemia can cause activation/translocation of PKCd.3 Inhibition of PKCd (via specific inhibitor of PKCd, dV1-1) can cause a revival of CBF 24 hours after ischemia to counteract hypoperfusion or low CBF found to be suppressed after cardiac arrest from 38% to 65%. 1,4 We previously showed that pretreatment of dV1-1 before ACA can enhance perfusion 24 hours after ischemia, resulting in improved neuronal survival in the hippocampal CA1 and cortex regions in our rat model of ACA.1 Here, we sought out to define the specific mechanism(s) of how inhibition of PKCd can alleviate these pathologies. The possible endothelium and endothelial-mediated nitric oxide synthase (eNOS) involvement as a target for PKCd relating to general circulation was first reported by Monti et al.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protein Kinase C Delta Modulates Endothelial Nitric Oxide Synthase after Cardiac Arrest

Lin

Gresia

Stradecki

et al. 2014

J Cereb Blood Flow Metab

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“…CPR research depends mostly on the use of animal models that are designed to simulate CA in humans. 19 -21 The animal models that have been used in studies are swine, rodents, 22,23 canines, 24,25 primates, 26 rabbits, sheep 27 and cats. 28 Among others, asphyxial arrest in animals such as rhesus monkeys, rabbits and sheep were extensively studied in the 1960s by Dawes and colleagues.…”

Section: Discussionmentioning

confidence: 99%

Asphyxial cardiac arrest, resuscitation and neurological outcome in a Landrace/Large-White swine model

et al. 2011

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The vast majority of laboratory studies on animals have focused on ventricular fibrillation (VF) and not on cardiac arrest (CA) resulting from asphyxia. The aim of this study was to develop a clinically relevant animal model in Landrace/Large-White swine of asphyxial CA resuscitated using the European Resuscitation Council guidelines. Survival and 24 h neurological outcome in terms of functional deficit were also evaluated. Asphyxial arrest was induced by clamping the endotracheal tube (ETT) in 10 Landrace/Large-White piglets. After 4 min of untreated arrest, resuscitation was initiated by unclamping the ETT, 100% oxygen mechanical ventilation, 2 min chest compressions and epinephrine administration. Advanced Life Support algorithm was followed. In case of restoration of spontaneous circulation, the animals were supported for one hour and then observed for 23 h. Coronary perfusion pressure was significantly higher in surviving animals (P , 0.001) during cardiopulmonary resuscitation. End-tidal CO 2 was significantly higher in the animals that survived than in non-surviving animals (P ¼ 0.001). All of the animals were severely neurologically impaired 24 h after CA. This refined model of asphyxia CA is easily reproducible and may be used for pharmacological studies in CA.

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“…Several therapies have shown promise in this model, e.g., mild hypothermia, glucose and insulin, and neurotensin [223,[226][227][228][229]. There also are pediatric analogs [230][231][232][233], which use post-natal Day 17 rats. Promising results have been obtained with hypothermia and minocycline [231,233].…”

Section: Rat Aca Modelsmentioning

confidence: 99%

Brain Resuscitation in the Drowning Victim

Warner

Knape

2006

Handbook on Drowning

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. This manuscript is dedicated to the memory of Peter Safar, M.D. Peter Safar combined genius, incredible purpose, elegance, and humanism to move the collective fields of acute medicine to a new level. His work in resuscitation medicine, critical care, anesthesiology, emergency medicine, and disaster medicine saved countless lives. As a mentor he taught us a great deal. Peter left us with an important message-in both clinical care and research: namely, to always ask, "what is your intervention or research doing for the patient?" Whether physician or scientist, it is a critical message never to forget.Portions of this manuscript are being reproduced in the Handbook of Drowning. Bierens JJ (ed.). Springer, 2nd Edition. NIH Public Access AbstractDrowning is a leading cause of accidental death. Survivors may sustain severe neurologic morbidity. There is negligible research specific to brain injury in drowning making current clinical management non-specific to this disorder. This review represents an evidence-based consensus effort to provide recommendations for management and investigation of the drowning victim. Epidemiology, brain-oriented prehospital and intensive care, therapeutic hypothermia, neuroimaging/monitoring, biomarkers, and neuroresuscitative pharmacology are addressed. When cardiac arrest is present, chest compressions with rescue breathing are recommended due to the asphyxial insult. In the comatose patient with restoration of spontaneous circulation, hypoxemia and hyperoxemia should be avoided, hyperthermia treated, and induced hypothermia (32-34 °C) considered. Arterial hypotension/hypertension should be recognized and treated. Prevent hypoglycemia and treat hyperglycemia. Treat clinical seizures and consider treating nonconvulsive status epilepticus. Serial neurologic examinations should be provided. Brain imaging and serial biomarker measurement may aid prognostication. Continuous electroencephalography and N20 somatosensory evoked potential monitoring may be considered. Serial biomarker measurement (e.g., neuron specific enolase) may aid prognostication. There is insufficient evidence to recommend use of any specific brain-oriented neuroresuscitative pharmacologic therapy other than that required to restore and maintain normal physiology. Following initial stabilization, victims should be transferred to centers with expertise in age-specific postresuscitation neurocritical care. Care should be documented, reviewed, and quality improvement assessment performed. Preclinical research should focus on models of asphyxial cardiac arrest. Clinical research should focus on improved cardiopulmonary resuscitation, re-oxygenation/ reperfusion strategies, therapeutic hypothermia, neuroprotection, neurorehabilitation, and consideration of drowning in advances made in treatment of other central nervous system disorders.

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Magnetic Resonance Imaging Assessment of Regional Cerebral Blood Flow after Asphyxial Cardiac Arrest in Immature Rats

Cited by 68 publications

References 40 publications

Protein Kinase C Delta Modulates Endothelial Nitric Oxide Synthase after Cardiac Arrest

Protein Kinase C Delta Modulates Endothelial Nitric Oxide Synthase after Cardiac Arrest

Asphyxial cardiac arrest, resuscitation and neurological outcome in a Landrace/Large-White swine model

Brain Resuscitation in the Drowning Victim

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