Introduction:
Extracorporeal membrane oxygenation (ECMO) supports hemodynamics in cardiogenic shock (CS) at the expense of left ventricular (LV) overload. LV assist device (LVAD) also supports hemodynamics, whereas LVAD unloads LV. Therefore, the combination of ECMO and LVAD would augment hemodynamic support and unload LV. We hypothesized that the combination therapy in acute myocardial infarct (AMI) in CS could synergistically improve hemodynamics and unload LV, which, in turn, reduces infarct size.
Methods:
In protocol 1, we ligated coronary arteries and created AMI with CS in 5 mongrel dogs (15.1±0.3 kg). We transvascularly introduced Impella CP into LV. We kept the ECMO flow constant at 1.8L/min. We compared hemodynamics and the LV pressure-volume area (PVA, an index of LV oxygen consumption) under 3 conditions; Control, ECMO, and ECMO+Impella (ECPELLA) in each dog. In protocol 2 (n=15), we ligated coronary arteries for 180 min and then reperfused. We activated Impella CP and/or ECMO from 60 min after the coronary ligation to the end of the experiment. We allocated dogs into 3 groups, no support (Control), ECMO, and ECPELLA and compared infarct size at 180 min after reperfusion among 3 groups.
Results:
In protocol 1, both ECMO and ECPELLA increased arterial pressure compared to Control (Control: 63±9, ECMO: 88±10 and ECPELLA: 97±18 mmHg, p < 0.05), and resolved the CS status. ECPELLA strikingly reduced PVA by 83% relative to Control (1500±326, 2038±357 and 258±182 mmHg*ml, p<0.001). In protocol 2, ECPELLA markedly reduced the infarct size (15±8%) compared to Control (53±7%, p<0.05) and ECMO (39±10%, p<0.05).
Conclusions:
ECPELLA before reperfusion markedly improved hemodynamics, reduced PVA, and limited infarct size in a dog model of MI with CS. ECPELLA could prevent ECMO-induced LV overload and synergistically exert powerful anti-infarct effects in AMI with CS.
444. Immune Activation and Transgene Stability Following AAV9 Gene Transfer to an Acute Myocardial Infarct Mouse Model
