Force-frequency relations in the failing rabbit heart and responses to adrenergic stimulation.
Force-frequency relations in the failing rabbit heart and responses to adrenergic stimulation.
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DOI：
10.1016/s1071-9164(97)90006-3
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发表时间：
1997-03-01
影响因子：
6
通讯作者：
Ross, J Jr
中科院分区：
文献类型：
--
作者：
Ryu, K H;Tanaka, N;Ross, J Jr
背景：最近的实验证明了β-肾上腺素能调节力-频率关系(FFR)在正常心脏和衰竭心脏中的重要性。在完整的兔心中，FFR的降支出现频率很高，因此建立了一种新的心房起搏诱导的心力衰竭模型。方法和结果：仪器化兔快速心房起搏平均19.5天，出现严重的左心室扩张，心输出量减少(超声心动图)，心肌收缩和舒张率降低(左心室dp/dt，导管尖端测压计)，并伴随着β-肾上腺素能受体密度和腺苷环化酶活性的降低。在心力衰竭之前，使用窦房结抑制剂(Zatebradine)将清醒动物的心率从280+/-30(SD)减慢至约225次/分钟，然后通过心房起搏从250次/分钟逐步增加心率至450次/分钟；心率对左心室dp/dtmax(FFR)的反应显示上升反应(增加收缩能力)，下行肢体的收缩速度大于375次/分钟，注射多巴酚丁胺扩大了FFR的上行肢体(斜率增加)并减弱了下行肢体。在心力衰竭时，基础FFR严重压低，下降肢超过350次/分钟；多巴酚丁胺使FFR上移，上升肢斜率无变化，而多巴酚丁胺则阻止FFR下降。在心率和心输出量之间的关系上也观察到类似的反应。结论：利用快速心房起搏建立了一种新的清醒兔心力衰竭模型，并应用于力-频率效应的研究。在心力衰竭时，多巴酚丁胺对FFR上升肢的正常β-肾上腺素能放大缺失，但在心率较高时，显著的FFR下降肢被多巴酚丁胺阻止。观察到的β-肾上腺素能受体系统成分的减少可能是导致β-肾上腺素能FFR扩增受损的原因，但对降支及其被多巴酚丁胺纠正的机制(S)尚未建立。FFR的这些反应可能会对衰竭的心脏对运动和压力的反应能力产生重要影响。
BACKGROUND: Recent experiments have documented the importance of beta-adrenergic regulation of the force-frequency relation (FFR) in the normal and failing heart. As in isolated human cardiac muscle, a descending limb of the FFR occurs at high frequencies in the intact rabbit heart, and therefore a new model of atrial pacing-induced heart failure was developed in the rabbit. Responses of the FFR to beta-adrenergic stimulation were then assessed in the conscious state before and after the induction of heart failure.METHODS AND RESULTS: Rapid atrial pacing for an average of 19.5 days in instrumented rabbits produced severe left ventricular dilation with reduced cardiac output (echocardiography) and depressed myocardial contractility and relaxation rate (left ventricular dP/dt, catheter-tip micromanometer), associated with reductions in beta-adrenergic receptor density and adenylyl cyclase activity. Before heart failure, heart rate was slowed in the conscious animal from 280 +/- 30 (SD) to about 225 beats/min using a sinus node inhibitor (zatebradine), and heart rate was then increased in steps by atrial pacing from 250 to 450 beats/min; the heart rate-versus-left ventricular dP/dtmax (FFR) response showed an ascending response (increasing contractility), with a descending limb at rates greater than 375 beats/min, and dobutamine infusion amplified the ascending limb of the FFR (increased slope) and attenuated the descending limb. In heart failure the basal FFR was severely depressed with a descending limb over 350 beats/min; dobutamine shifted the FFR upward somewhat without change in the slope of the ascending limb, whereas dobutamine prevented the descending limb of the FFR. Similar responses were observed in the relations between heart rate and cardiac output.CONCLUSIONS: A new model of heart failure in the conscious rabbit was developed using rapid atrial pacing and applied to study force-frequency effects. In heart failure, normal beta-adrenergic amplification of the ascending limb of the FFR by dobutamine was absent, but a marked descending limb of the FFR at higher heart rates was prevented by dobutamine. Observed reductions in components of the beta-adrenergic receptor system likely were responsible for impaired beta-adrenergic FFR amplification, but the mechanism(s) for the descending limb and its correction by dobutamine are not yet established. These responses of the FFR may influence importantly the ability of the failing heart to respond to exercise and stress.