Abstract 1906: Inhibition of Neutrophils is Critical to the in Vivo Cardioprotection of Postconditioning
Postconditioning (PoC) reduces infarct size (IS), myocardial •O2 generation and PMN accumulation. We hypothesized that IS reduction by PoC is dependent on PMNs inhibition, and PoC inhibits PMN •O2 generation. Rats were randomized after 30 min left coronary artery (LCA) occlusion and 3 h reperfusion (R) to Control: occlusion-R (n =13); PoC: 3 x 10-s R and 10-s re-occlusion at R (n=13); PMN depletion: rabbit anti-rat PMN antiserum injected 8 hr before ischemia (n=9); PoC in PMN-depleted rats (n=9). In PMN •O2 studies, blood was sampled at 2 and 24 hr from the anterior interventricular vein (AIV) draining the area at risk (AAR) in dogs with 60 min LAD occlusion and 24 hr R ± PoC (3 cycles 30 second R - re-occlusion) and immediately analyzed for PMN-derived •O2 (chemiluminescence, CL). In rats, PMN antiserum reduced plasma PMNs by 84%. PMNs in AAR were less in PoC (21.2 ± 0.3%* of total cells), PMN-depleted (9.4.± 0.3%*) and PMN-depleted rats (5.4 ± 0.6 %*) vs Control (30.5 ± 1.2%). IS (necrosis/AAR) was reduced in both PoC (42.6 ± 2.1%*) and PMN-depleted (43.9 ± 3.0%*) vs Control (58.8 ± 0.9%). There was no further decrease in IS with PoC in PMN depleted rats (37.2 ± 2.9%, p=0.1). In AIV blood (left fig⇓), 55% of CL signal was SOD-inhibitable; this •O2 signal was derived from PMNs since it was comparable to inhibition of PMN NADPH oxidase (10μM DPI) or removal of PMNs (De-PMN). In AIV blood from Controls, PMN-derived •O2 increased at 2 and 24 hrs of R (right fig⇓). PoC reduced PMN-derived •O2.
Conclusions: PoC or PMN depletion reduces AAR PMN accumulation and IS, but PoC did not further reduce IS in PMN-depleted rats. PoC inhibits PMN •O2 generation. PoC may reduce IS by inhibiting PMN •O2 generation.*P<0.05 vs Control