Effects of pyruvate fortified cardiopulmonary resuscitation on myocardial injury after cardiac arrest




Ray, George
Batliwala, Shehzad
Nguyen, Anh
Estrada, Juan
Olivencia-Yurvati, Albert H.
Mallet, Robert T.


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Effects of pyruvate fortified cardiopulmonary resuscitation on myocardial injury after cardiac arrest BACKGROUND: Cardiac arrest kills 400,000 Americans annually. Over 90% of victims outside the hospital and 76% of those inside the hospital succumb to the destructive effects of cardiac arrest on the vital organs. To save the victims, forceful precordial chest compressions and trans-thoracic countershocks are applied, but the use of metabolic substrates as adjuvant treatments for cardiac arrest has not been tested clinically. Pyruvate, a natural intermediary metabolite, energy substrate and antioxidant, has been found to be cardioprotective during ischemia. Pyruvate accomplishes this cardioprotection through several mechanisms including enhancement of myocardial energy reserves and antioxidant defenses, and reduction of reactive oxygen species. Pyruvate-fortified cardioplegic solution administered during cardiopulmonary bypass hastened recovery of cardiac function and shortened hospitalization in patients undergoing coronary revascularization. Despite these discoveries, pyruvate’s effects on myocardial structural damage and inflammation after cardiopulmonary resuscitation and defibrillatory countershocks treated cardiac arrest have not been reported. This study tested the hypothesis that intravenous pyruvate administration minimizes left ventricular structural damage and inflammation that result from myocardial ischemia-reperfusion, precordial chest compressions, and trans-thoracic countershocks. METHODS: Isoflurane-anesthetized Yorkshire swine, 25-40 kg of both genders were studied. The heart was arrested by rapid pacing. After 6 minutes of arrest, precordial compressions were applied at a rate of 100/min for 4 minutes while sodium pyruvate or NaCl control was infused iv to a concentration of 4 mM. Transthoracic countershocks (200-300 J) were administered until spontaneous cardiac rhythm was restored, and infusions maintained until 60 min recovery. The pigs were recovered for 72 hours, and then transmural biopsies of left ventricular free wall were collected, formalin-fixed and paraffin-embedded. Non-arrested sham experiments also were performed and compared with pyruvate- and NaCl-treated cardiac arrest-resuscitation. Sections were cut, stained with hematoxylin and eosin, and 20 random high power (100x) fields were examined and scored by an investigator blinded to the protocol. Structural endpoints included extracellular expansion, neutrophil invasion and hypercontracted tissue. RESULTS: Sections of left ventricular myocardium are currently being analyzed from the 6 sham, 6 cardiac arrest, and 6 pyruvate treated cardiac arrest experiments for neutrophil infiltration, edema, hypercontraction and other evidence of structural damage. CONCLUSIONS: Evidence of decreased neutrophil count, extracellular volume and cardiomyocyte hypercontraction in pyruvate-treated vs. control myocardium 72 h after cardiac arrest will be taken as evidence supporting the hypothesis. Such outcomes would argue for the acute use of pyruvate based interventions during initial treatment to promote post-cardiac arrest myocardial structural integrity.