The oxygen supply-demand imbalance is the fundamental pathophysiology of myocardial infarction (MI). Reducing myocardial oxygen consumption (MVO 2 ) in acute MI (AMI) reduces infarct size. Since left ventricular (LV) mechanical work and heart rate are major determinants of MVO 2 , we hypothesized that the combination of LV mechanical unloading and chronotropic unloading during AMI can reduce infarct size via synergistic suppression of MVO 2 . In a dog model of ischemia-reperfusion, as we predicted, the combination of mechanical unloading by Impella and bradycardic agent, ivabradine (IVA), synergistically reduced MVO 2 . This was translated into the striking reduction of infarct size with Impella + IVA administered 60 min after the onset of ischemia compared to no treatment (control) and Impella groups (control 56.3 ± 6.5, Impella 39.9 ± 7.4 and Impella + IVA 23.7 ± 10.6%, p < 0.001). In conclusion, Impella + IVA during AMI reduced infarct size via marked suppression of MVO 2 . The mechano-chronotropic unloading may serve as a powerful therapeutic option for AMI.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Pharmaceutical Science
- Cardiology and Cardiovascular Medicine