Lerman B B, Engelstein E D, Burkhoff D
Department of Medicine, Division of Cardiology, The New York Hospital-Cornell University Medical Center, New York, NY, USA.
Circulation. 2001 Jul 24;104(4):486-90. doi: 10.1161/hc2901.091397.
Augmented preload increases myocardial excitability by shortening action potential duration (APD). The mechanism governing this phenomenon is unknown. Because myocardial stretch increases intracellular cAMP, we hypothesized that load-dependent changes in myocardial excitability are mediated by beta-adrenergic stimulation of a cAMP-sensitive K(+) current.
The effects of propranolol on load-induced changes in electrical excitability were studied in 7 isolated ejecting canine hearts. LV monophasic APD at 50% and 90% repolarization (MAPD(50) and MAPD(90)) and refractoriness were determined at low (9+/-3 mL) and high (39+/-4 mL) load before and after beta-adrenergic blockade. During control, the MAPD(50) decreased from 193+/-26 to 184+/-26 ms with increased load, as did the MAPD(90) (238+/-28 to 233+/-28 ms), P</=0.04. Similar changes were observed in ventricular refractoriness. Treatment with propranolol completely abolished these load-induced effects. Myocardial catecholamine depletion with reserpine in 2 hearts also abolished changes in MAPD and excitability in response to increased preload.
Increases in ventricular load mediate a decrease in ventricular APD and refractoriness through activation of the beta-adrenergic receptor. An increase in a cAMP-mediated K(+) current, possibly the slowly activating delayed rectifier I(Ks), may account in part for this form of mechanoelectrical coupling.
增加前负荷可通过缩短动作电位时程（APD）来提高心肌兴奋性。但支配这一现象的机制尚不清楚。由于心肌牵张可增加细胞内cAMP，我们推测心肌兴奋性的负荷依赖性变化是由β-肾上腺素能刺激cAMP敏感的钾电流介导的。
在7个离体搏动的犬心脏中研究了普萘洛尔对负荷诱导的电兴奋性变化的影响。在β-肾上腺素能阻断前后，分别在低负荷（9±3 mL）和高负荷（39±4 mL）状态下测定左心室50%和90%复极化时的单相APD（MAPD50和MAPD90）以及不应期。在对照期间，随着负荷增加，MAPD50从193±26 ms降至184±26 ms，MAPD90也有类似变化（从238±28 ms降至233±28 ms），P≤0.04。心室不应期也观察到类似变化。普萘洛尔治疗完全消除了这些负荷诱导的效应。在2个心脏中用利血平使心肌儿茶酚胺耗竭也消除了因前负荷增加而导致的MAPD和兴奋性变化。
心室负荷增加通过激活β-肾上腺素能受体介导心室APD和不应期缩短。cAMP介导的钾电流增加，可能是缓慢激活的延迟整流钾电流（IKs），可能部分解释了这种形式的机械电耦合。
