Limiting sarcolemmal Na<sup>+</sup>entry during resuscitation from ventricular fibrillation prevents excess mitochondrial Ca<sup>2+</sup>accumulation and attenuates myocardial injury

Wang, Sufen; Radhakrishnan, Jeejabai; Ayoub, Iyad M.; Kolarova, Julieta D; Taglieri, Domenico M.; Gazmuri, Raúl J.

doi:10.1152/japplphysiol.01167.2006

Cited by 41 publications

(55 citation statements)

References 62 publications

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“…Its effect on myocardial carbon dioxide concentration is not clear. Be that as it may, elegant studies of cardiac arrest induced by ventricular fibrillation revealed improvement in cardiac function during fibrillation [25] and significant attenuation of postresuscitation ventricular arrhythmias including prevention of recurrent episodes of ventricular fibrillation with cariporide and other NHE1 inhibitors in both pig and rat models (table 1) [26,27,28,29,30,31,32]. …”

Section: Cardiac Arrestmentioning

confidence: 99%

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

Wu¹,

Kraut²

2014

Am J Nephrol

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Background: Metabolic acidosis is associated with impaired cellular function. This has been attributed to the accompanying reduction in intracellular and interstitial pH of the myocardium. Recent studies suggest that activation of the cellular Na⁺-H⁺ exchanger NHE1 might contribute to myocardial dysfunction. This review examines the experimental evidence which supports the role of NHE1 in the genesis of acidosis-induced cellular dysfunction, the benefits of its inhibition, and the type of acidosis that might benefit from therapy. Summary: Information was obtained by searching MEDLINE for articles published between 1969 and 2013 using the terms: NHE1, metabolic acidosis, lactic acidosis, ischemia-reperfusion, shock, resuscitation, high anion gap acidosis, and non-gap acidosis. Each article was also reviewed for additional suitable references. Nineteen manuscripts published between 2002 and 2013 assessed the impact of inhibition of NHE1 on cellular function. They revealed that NHE1 is activated with metabolic acidosis associated with hypoxia, hypoperfusion, hemorrhagic shock, and sepsis. This was associated with a rise in cellular sodium and calcium and cardiac dysfunction including reduced contractility and a predisposition to cardiac arrhythmias. Inhibition of NHE1 with specific inhibitors improved cardiac function, reduced blood and tissue levels of proinflammatory cytokines, and decreased mortality. Key Message: These results suggest that use of inhibitors of NHE1 might be worthwhile in the treatment of some types of acute metabolic acidosis, specifically the lactic acidosis associated with hypoxia, hemorrhagic shock, and cardiac arrest. Its potential role in the treatment of other forms of acute metabolic acidosis remains to be determined.

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Section: Cardiac Arrestmentioning

confidence: 99%

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

Wu¹,

Kraut²

2014

Am J Nephrol

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“…It was previously reported that NHE-1 inhibitors attenuate myocardial reperfusion injury by limiting sodium-induced cytosolic and mitochondrial calcium overload, and thereby help preserve left ventricular distensibility during chest compression and attenuate post-resuscitation myocardial dysfunction 12 . In this study, the NHE-1 inhibitor cariporide (1 mg/kg), which had been extensively investigated in the past, was compared with the newer compound AVE4454B (1 mg/kg) and vehicle control in three groups of 10 rats each, all subjected to 10 min of untreated VF followed by 8 min of chest compression before delivering electrical shocks.…”

Section: Representative Resultsmentioning

confidence: 99%

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

Lamoureux

Radhakrishnan

Gazmuri

2015

JoVE

Self Cite

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Citation: Lamoureux, L., Radhakrishnan, J., Gazmuri, R.J. A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique. J. Vis. Exp. (98), e52413, doi:10.3791/52413 (2015). AbstractA rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic components of cardiopulmonary resuscitation in humans is herein described. The model was developed in 1988 and has been used in approximately 70 peer-reviewed publications examining a myriad of resuscitation aspects including its physiology and pathophysiology, determinants of resuscitability, pharmacologic interventions, and even the effects of cell therapies. The model featured in this presentation includes: (1) vascular catheterization to measure aortic and right atrial pressures, to measure cardiac output by thermodilution, and to electrically induce ventricular fibrillation; and (2) tracheal intubation for positive pressure ventilation with oxygen enriched gas and assessment of the endtidal CO 2 . A typical sequence of intervention entails: (1) electrical induction of ventricular fibrillation, (2) chest compression using a mechanical piston device concomitantly with positive pressure ventilation delivering oxygen-enriched gas, (3) electrical shocks to terminate ventricular fibrillation and reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic and metabolic function, and (5) assessment of survival and recovery of organ function. A robust inventory of measurements is available that includes -but is not limited to -hemodynamic, metabolic, and tissue measurements. The model has been highly effective in developing new resuscitation concepts and examining novel therapeutic interventions before their testing in larger and translationally more relevant animal models of cardiac arrest and resuscitation. Video LinkThe video component of this article can be found at

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“…29 Sodium-hydrogen exchanger inhibitors Animals/rat-heart model Decrease in peri-arrest arrhythmias, amelioration of ischaemic contracture, improvement of myocardial performance post-ROSC. 37,38 Humans, RCT Cariporide decreased MI rates but increased cerebrovascular events and short term mortality after CABG 39,40 Erythropoietin Animals Increase in coronary and mean aortic perfusion pressure and reduction of adrenaline dose during CPR. Improvement of cardiac performance and short-term survival after CA.…”

Section: ␤-Blockersmentioning

confidence: 99%

Emerging pharmaceutical therapies in cardiopulmonary resuscitation and post-resuscitation syndrome

Charalampopoulos

Νικολάου

2011

Resuscitation

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Limiting sarcolemmal Na⁺entry during resuscitation from ventricular fibrillation prevents excess mitochondrial Ca²⁺accumulation and attenuates myocardial injury

Cited by 41 publications

References 62 publications

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

Emerging pharmaceutical therapies in cardiopulmonary resuscitation and post-resuscitation syndrome

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Limiting sarcolemmal Na+entry during resuscitation from ventricular fibrillation prevents excess mitochondrial Ca2+accumulation and attenuates myocardial injury

Cited by 41 publications

References 62 publications

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

Emerging pharmaceutical therapies in cardiopulmonary resuscitation and post-resuscitation syndrome

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Product

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Limiting sarcolemmal Na⁺entry during resuscitation from ventricular fibrillation prevents excess mitochondrial Ca²⁺accumulation and attenuates myocardial injury