Abstract
BackgroundReperfusion after resuscitation from cardiac arrest (CA) is an event that increases reactive oxygen species production leading to oxidative stress. More specifically, myocardial oxidative stress may play a role in the severity of post-CA myocardial dysfunction. This study investigated the relationship between myocardial oxidative stress and post-CA myocardial injury and dysfunction in a rat model of CA and cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced in 26 rats and was untreated for 6 min. CPR, including mechanical chest compression, ventilation, and epinephrine, was then initiated and continued for additional 6 min prior to defibrillations. Resuscitated animals were sacrificed at two h (n = 9), 4 h (n = 6) and 72 h (n = 8) following resuscitation, and plasma collected for assessment of: high sensitivity cardiac troponin T (hs-cTnT), as marker of myocardial injury; isoprostanes (IsoP), as marker of lipid peroxidation; and 8-hydroxyguanosine (8-OHG), as marker of DNA oxidative damage. Hearts were also harvested for measurement of tissue IsoP and 8-OHG. Myocardial function was assessed by echocardiography at the corresponding time points. Additional 8 rats were not subjected to CA and served as baseline controls.ResultsCompared to baseline, left ventricular ejection fraction (LVEF) was reduced at 2 and 4 h following resuscitation (p < 0.01), while it was similar at 72 h. Inversely, plasma hs-cTnT increased, compared to baseline, at 2 and 4 h post-CA (p < 0.01), and then recovered at 72 h. Similarly, plasma and myocardial tissue IsoP and 8-OHG levels increased at 2 and 4 h post-resuscitation (p < 0.01 vs. baseline), while returned to baseline 72 h later. Myocardial IsoP were directly related to hs-cTnT levels (r = 0.760, p < 0.01) and inversely related to LVEF (r = -0.770, p < 0.01). Myocardial 8-OHG were also directly related to hs-cTnT levels (r = 0.409, p < 0.05) and inversely related to LVEF (r = -0.548, p < 0.01).ConclusionsThe present study provides evidence that lipid peroxidation and DNA oxidative damage in myocardial tissue are closely related to myocardial injury and LV dysfunction during the initial hours following CA.
Highlights
Reperfusion after resuscitation from cardiac arrest (CA) is an event that increases reactive oxygen species production leading to oxidative stress
Due to the complexity and interplay of events occurring during cardiac arrest and after return of spontaneous circulation (ROSC), mechanisms involved in post-resuscitation myocardial dysfunction are not completely understood, and new injury pathways have been described [3]
Eight control rats were not subjected to cardiac arrest and served as baseline, while the other 26 underwent cardiac arrest and cardiopulmonary resuscitation (CPR)
Summary
Reperfusion after resuscitation from cardiac arrest (CA) is an event that increases reactive oxygen species production leading to oxidative stress. Ischemia-reperfusion (I/R) is a process characterized by reactive oxygen species (ROS) generation, which starts during ischemia and is further exacerbated by defibrillation attempts and subsequently by return of oxygenated blood to the tissues after ROSC [4,5,6] This increase in ROS production leads to oxidation of cell macromolecules, such as lipids, proteins, and possibly DNA, in a process overall named oxidative stress [7,8]. The oxidative stress events are recognized to participate in processes leading to acute inflammatory response, cell damage, mitochondrial dysfunction, decrease in nitric oxide (NO) availability, and cell apoptosis and death [4,5,6,7,9,10,11,12] In the heart, these events may impair the normal function of cardiomyocytes, contributing to the severity of post-cardiac arrest myocardial dysfunction [4]
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