Physiopathology and Severity of Postresuscitation Myocardial Dysfunction: Effects of Sodium-Hydrogen Exchanger Isoform-1 (NHE-1) Inhibitors and Erythropoietin

  • R. J. Gazmuri
  • I. M. Ayoub
  • J. Radhakrishnan
Conference paper


The working heart is a highly metabolic organ that under normal resting conditions extracts nearly 70% of the oxygen supplied by the coronary circulation [1, 2], representing close to 10% of the total body oxygen consumption. However, the heart has minimal capability for extracting additional oxygen, and increases in metabolic demands can only be met by autoregulatory increases in coronary blood flow through vasodilation of the coronary circuit [3]. Consequently, a severe energy imbalance develops when cardiac arrest occurs and coronary blood flow ceases. The severe energy imbalance continues during the ensuing resuscitation effort when current closed-chest resuscitation techniques are used because of the very limited capability for generating systemic and coronary blood flow [4]. The magnitude of energy imbalance is contingent upon the metabolic requirements and is particularly severe in the presence of ventricular fibrillation (VF), when oxygen requirements are comparable with or exceed those of the normally beating heart [5, 6]. A lesser energy deficit is expected during cardiac arrest with a quiescent or minimally active heart (i.e. asystole or pulseless electrical activity precipitated by asphyxia or exsanguination). Moreover, with reperfusion during resuscitation, multiple pathogenic mechanisms — collectively known as reperfusion injury — are activated and further contribute to myocardial injury. Primary contributors to reperfusion injury are mitochondrial calcium (Ca2+) overload [7, 8] and generation of reactive oxygen species (ROS) [9]. Limited oxygen supply and concomitant reperfusion injury compromise the mitochondrial capability for regenerating adenosine triphosphatase (ATP) through oxidative phosphorylation. Limited amounts of ATP, however, are generated at the substrate level from anaerobic glycolysis and breakdown of creatine phosphate. Taking these processes together, the myocardium develops a marked lactic acid increase, rapid creatine phosphate depletion and relatively slow ATP depletion during cardiac arrest and resuscitation [10]. Accordingly, the resuscitation effort typically proceeds — and occasionally succeeds — in the presence of ischaemia and in the midst of reperfusion injury.


Ventricular Fibrillation Coronary Blood Flow Chest Compression Spontaneous Circulation Coronary Perfusion Pressure 
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© Springer-Verlag Italia 2011

Authors and Affiliations

  • R. J. Gazmuri
  • I. M. Ayoub
  • J. Radhakrishnan

There are no affiliations available

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