Brain Natriuretic Peptide Reverses the Effects of Myocardial Stunning in Rabbit Myocardium

We tested the hypothesis that brain natriuretic peptide (BNP) would decrease the effects of myocardial stunning in rabbit hearts. We also examined the mechanisms responsible for these effects. In two groups of anesthetized open-chest rabbits, myocardial stunning was produced by 2 15-min occlusions of the left anterior descending artery separated by 15 min of reperfusion. The treatment group had BNP (10^–3 mol/l) topically applied to the stunned area. Hemodynamic and functional parameters were measured. Coronary flow and O₂ extraction were used to determine myocardial O₂ consumption. In separate animals, we measured the function of isolated control and simulated ischemia (95% N₂/5% CO₂, 15 min)-reperfusion ventricular myocytes with BNP or C-type natriuretic peptide (10^–8–10^–7 mol/l) followed by KT5823 (10^–6 mol/l, cyclic GMP protein kinase inhibitor). In the in vivo control group, baseline delay to contraction was 47 ± 4 ms and after stunning it increased to 71 ± 10 ms. In the treatment group, baseline delay to contraction was 40 ± 7 ms, and after stunning and BNP it did not significantly increase (43 ± 6 ms). Neither stunning nor BNP administration affected regional O₂ consumption. In control myocytes, BNP (10^–7 mol/l) decreased the percent shortening from 6.7 ± 0.4 to 4.5 ± 0.2%; after KT5823 administration, the percent shortening increased to 5.4 ± 0.5%. In ischemia-reperfusion myocytes, BNP (10^–7 mol/l) decreased the percent shortening less from 5.0 ± 0.5 to 3.8 ± 0.2%; KT5823 administration did not increase the percent shortening (3.8 ± 0.2%). BNP similarly and significantly increased cyclic GMP levels in control and stunned myocytes. The data illustrated that BNP administration reversed the effects of stunning and its mechanism may be independent of the cyclic GMP protein kinase.