Abstract 12984: Heterogeneous Transmural Distribution of Small Conductance Calcium Activated K Currents in Failing Human Ventricles
INTRODUCTION: Apamin-sensitive K current (IKAS) conducted by small-conductance calcium-activated K channels is heterogeneously upregulated in failing rabbit ventricle. It remains unknown if there is heterogeneous upregulation in IKAS in the transmural surface of failing human ventricles.
METHODS: We studied 5 native hearts of transplant recipients (47.8 ± 15.9 years old, 2 male). Left ventricular (LV) ejection fraction was 25 ± 7%. An LV free wall wedge preparation was Langendorff perfused in 37°C Tyrode with 15-20µM blebbistatin and stained with di-4 ANEPPS for optical mapping at baseline and after adding 100nM apamin to the perfusate.
RESULTS: With endocardial pacing cycle length (PCL) of 1000ms, APD80 were 360 ± 46ms at baseline and 446 ± 61ms (p=0.01) after apamin. APD80 uniformly increased from the epicardium to the endocardium in 1 wedge. In the remaining 4 wedges, there is highly heterogeneous transmural distribution of the APD80 at baseline. Apamin administration aggravated the heterogeneous distribution of APD80 by prolonging APD80 to different degrees over the transmural surface. The figure shows a typical preparation with ΔAPD80 on average 43 ± 19ms (site B), but prolongation in the M cell island averaged 73 ± 11ms (site A). Across all patients, APD80 is prolonged 24% ± 12% relative to baseline at 1000ms PCL and 18% ± 9% at 500ms PCL. The average prolongation in the epicardial layer, mid-myocardium, M cell island and endocardial layer were, respectively, 100 ± 83ms, 88 ± 43ms, 132 ± 41ms and 76 ± 30ms. The correlation coefficients between baseline APD80 and apamin APD80 in each of the 5 patients were, respectively, 0.50, 0.65, 0.82, 0.72 and 0.86 (p<0.001 for all).
CONCLUSION: Failing human ventricles exhibit heterogeneous transmural IKAS upregulation. There is more APD prolongation in M cell islands than in other parts of the mid-myocardium.
- © 2012 by American Heart Association, Inc.