[The myocardium protective effects of erythropoietin (EPO) in a rat model of asphyxia-induced cardiac arrest/cardiopulmonary resuscitation (CPR)].

OBJECTIVE: To examine the effects of EPO administration on the integrity of myocardium in a rat model of asphyxia-induced cardiac arrest/CPR.

METHODS: 24 male Sprague-Dawley (SD) rats were randomly divided into three groups (8 each) to receive (1) cardiac arrest (induced by tracheal catheter clamping for 8 minutes)/CPR (by chest compressions and mechanical ventilation 8 minutes after cardiac arrest), (2) cardiac arrest/CPR +EPO (5 kU/kg, i.v, 3 minutes after restoration of spontaneous circulation (ROSC), and (3) no-treatment (control). The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal positive/negative filling pressure change versus time (±dp/dt max) in the animals were recorded 30, 60, 90, and 120 minutes after ROSC. Blood and heart tissue samples were collected 120 minutes after ROSC for the examination of serum troponin I (cTnI) level, myocardium pathological change (by light/electronic microscopy), and myocardium apoptosis [by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) staining].

RESULTS: The LVSP, +dp/dt max and - dp/dt max absolute value in CPR group and EPO group were significantly lower than those of baseline at 30, 60, 90, 120 minutes after ROCS. In comparison with the control group, the LVSP( mm Hg, 1 mm Hg = 0.133 kPa: 119.52±12.68, 134.32±15.78 vs. 165.82±7.05), +dp/dt max (mm Hg/sec: 4457.14±826.22, 6019.85±1192.19 vs. 10325.93±773.09), and - dp/dt max ( mm Hg/sec: - 3956.04±952.37, - 4957.22±838.60 vs. - 8421.33±886.65) were significant lower (all P < 0.01) in the CPR and EPO group 30 minutes after ROSC, and such tendency remained till 120 minutes after ROSC: (LVSP: 124.62±8.07, 145.61±16.70 vs. 162.34±7.63; +dp/dt max: 4977.67±350.40, 7471.62±998.32 vs. 9999.39±727.96; - dp/dt max: - 4145.51±729.77, - 5895.64±787.30 vs. - 8089.75±981.52). Compared to the CPR group, the value of LVSP, + dp/dt max and - dp/dt max at all time points were significantly higher in EPO group (all P < 0.05). The LVEDP value was significantly higher ( P < 0.01) in both CPR and EPO group in comparison with the control (mm Hg/sec: 22.94±3.94, 11.18±2.58 vs. 2.89±0.70) 120 minutes after ROSC, and it was significantly lower in EPO group in comparison with CPR group ( P < 0.05). Light/electronic microscopy revealed myocardial necrosis, inflammatory cell infiltration, myocardial cell membrane integrity loss, mitochondrial swelling, and increased number of apoptotic cardiomyocyte (314.1±30.7 vs. 165.2±45.9 as in control) in CPR group samples. In contrast, the cardiomyocyte morphologic damages were significantly fewer in EPO group, so is the numbers of apoptotic cardiomyocyte (242.1±20.0 vs. 314.1±30.7, P < 0.05). In comparison with the control, the serum cTnI 120 minutes after ROSC was significantly higher (all P < 0.01) in CPR and EPO group (μg/L: 20.70±5.96,16.98±3.81 vs. 2.60±0.86), but no such difference was found between these two groups.

CONCLUSION: EPO can attenuate the post resuscitation myocardial injury probably through its mitochondrial protective, anti-apoptotic effect.