Abstract 1002: Effect of Atrial Natriuretic Peptide on Myocardial Infarct Size and 30 Day Survival.
Acute coronary artery occlusion triggers the activation of molecular pathways (inflammatory, vasoactive, endocrine, reparative, etc.) that lead to myocardial ischemia and infarction. Atrial natriuretic peptide (ANP) is released from cardiomyocytes during ischemia and infarction, in response to atrial distension and volume overload, but the effect of ANP on these processes is unknown. We examined the effect of ANP on infarct size and survival in mice lacking the ANP gene (ANP-KO) and congenic wild-type (WT) mice. The left anterior descending artery was occluded by a blinded operator in isoflurane-anesthetized mice. The area of ischemia (area at risk, AAR) and infarct size (normalized to AAR) were assessed at 24 hours by another blinded observer using Evans blue perfusion and TTC staining, respectively. The AAR was indistinguishable between both groups of mice, but the infarct size was markedly reduced in ANP-KO vs. WT mice (62.6 ± 12.1% vs 100.8 ± 3.8%, p < 0.001). In control mice that underwent sham LAD occlusion the infarct size was 0%. Administration of ANP to ANP-KO mice via osmotic mini-pumps to achieve levels found in WT mice significantly increased infarct size when compared with mice lacking ANP (83.7 ± 10.2 % vs. 62.6 ± 12.1%, p < 0.05). Consistent with the decreased infarct size in ANP-KO mice, the median survival post-infarction was significantly better for ANP-KO (≥30 days) vs. WT mice (4 days, p < .02). At 24 hours after infarction both ANP-KO and WT mice showed significant increased neutrophil migration into the infarct zone (quantified by myeloperoxidase staining), but neutrophil migration was reduced in the non-infarct region in ANP-KO mice. At 30 days, collagen formation was comparable in the infarct region in both groups of mice, but collagen formation in the non-infarct region was increased in ANP-KO mice. Taken together these data suggest that in experimental myocardial infarction, ANP modulates the inflammatory response, increases infarct size and decreases 30 day survival.