Table 2 Pre-clinical data on effects of rhEPO and EPO analogs in models of myocardial I/R injury
From: Erythropoietin in the critically ill: do we ask the right questions?
Species | Model | Dose (IU·kg-1) | Protocol | Outcome | Histology | Apoptosis | Reference |
|---|---|---|---|---|---|---|---|
Rat | Coronary artery ligation | 8,000 | Immediately, or 3 weeks after artery ligation, once a week over 3 weeks | Decrease in LVDEP by 27 to 38%, improved contractility and relaxation, no difference in mortality | Early treatment: reduced infarct size (23 to 30%); late treatment: no difference, but increased capillary density (39 to 48%) | ND | [20] |
Mouse | Coronary artery ligation | 2,500 | 24 h and 30 minutes before, or immediately after ligation | nNOS-dependent reduction of ventricular arrhythmia | 50% reduction of infarct size | ND | [21] |
Swine | Coronary artery occlusion | 500 | 24 h and 90 minutes, or 90 minutes alone before ischemia | No cardioprotective effects | Infarct size not different | ND | [29] |
Dog | Coronary artery ligation | 1,000 | Immediately, 6 h, or 1 week after ischemia | Less ventricular fibrillation during reperfusion (0 versus 50%) | Reduced infarct size (8 versus 40%) | Less TUNEL cells (50%) | [30] |
Dog | Coronary artery ligation | 1,000 | Bolus immediately, 6 h, or 1 week after ischemia | Increase in LVEF (42 versus 49/56%), improved capillary density and myocardial blood flow (by 50%) | Reduced infarct size (10 versus18%) | ND | [31] |
Swine | Chronic myocardial ischemia | 300 | Endocardial injection 2 weeks after start of ischemia | LVEF 64 versus 55%; 2.2 versus 3.3 hypokinetic segments | Reduced ischemic surface (19 versus 41%), less fibrosis (8 versus 27%) | ND | [32] |
Swine | Coronary artery occlusion | Darbepoitein 30 μg·kg-1 | At time of reperfusion | Regional functional improvement | No reduction in infarct size, less fibrosis (7 versus 10%); increased capillary density (106 versus 89%) | ND | [33] |
Swine | Chronic myocardial ischemia | 300 | Endocardial injection 2 weeks after start of ischemia | LVEF 66 versus 55%; 2.2 versus 3.3 hypokinetic segments | Less fibrosis 8 versus 27% | TUNEL cells not detected | [34] |
Swine | Coronary artery occlusion | EPO analog 0.9/0.4 μg·kg-1 | At time of reperfusion, once weekly over 4 weeks | LVEF 39 versus 33%; improved wall motion score | Less fibrosis 7 versus 12%, 50% increase in peri-infarct capillary density, infarct size not different | ND | [35] |
Swine | Coronary artery ligation | 500 | 30 minutes and 24 h after ischemia | Fractional shortening 55 versus 36% at day 14; reduced oxidative stress and enhanced eNOS expression | 25% reduction of infarct size; enhanced angiogenesis | Less TUNEL cells (50%), less caspase-3 expression | [36] |
Swine | Coronary artery embolization | 200 | Every 2 days over 8 days | Cardiac function not different; increased VEGF and angiogenesis | Infarct size and fibrosis not different | ND | [37] |