Zucker Irving H, Hackley Johnnie F, Cornish Kurtis G, Hiser Bradley A, Anderson Nicholas R, Kieval Robert, Irwin Eric D, Serdar David J, Peuler Jacob D, Rossing Martin A
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA.
Hypertension. 2007 Nov;50(5):904-10. doi: 10.1161/HYPERTENSIONAHA.107.095216. Epub 2007 Sep 10.
Much of the current pharmacological therapy for chronic heart failure targets neurohormonal activation. In spite of recent advances in drug therapy, the mortality rate for chronic heart failure remains high. Activation of the carotid baroreceptor (BR) reduces sympathetic outflow and augments vagal tone. We investigated the effect of chronic activation of the carotid BR on hemodynamic and neurohormonal parameters and on mortality in dogs with chronic heart failure. Fifteen dogs were instrumented to record hemodynamics. Electrodes were applied around the carotid sinuses to allow for activation of the BR. After 2 weeks of pacing (250 bpm), electrical carotid BR activation was initiated in 7 dogs and continued for the remainder of the study. The start of BR activation was used as a time reference point for the remaining 8 control dogs that did not receive BR activation. Survival was significantly greater for dogs undergoing carotid BR activation compared with control dogs (68.1+/-7.4 versus 37.3+/-3.2 days, respectively; P<0.01), although arterial pressure, resting heart rate, and left ventricular pressure were not different over time in BR-activated versus control dogs. Plasma norepinephrine was lower in dogs receiving BR activation therapy 31 days after the start of BR activation (401.9+/-151.5 versus 1121.9+/-389.1 pg/mL in dogs not receiving activation therapy; P<0.05). Plasma angiotensin II increased less in dogs receiving activation therapy (plasma angiotensin II increased by 157.4+/-58.6 pg/mL in control dogs versus 10.1+/-14.0 pg/mL in dogs receiving activation therapy; P<0.02). We conclude that chronic activation of the carotid BR improves survival and suppresses neurohormonal activation in chronic heart failure.
目前，针对慢性心力衰竭的药物治疗大多以神经激素激活为靶点。尽管药物治疗最近取得了进展，但慢性心力衰竭的死亡率仍然很高。颈动脉压力感受器（BR）的激活可减少交感神经输出并增强迷走神经张力。我们研究了慢性激活颈动脉BR对慢性心力衰竭犬的血流动力学和神经激素参数以及死亡率的影响。15只犬被植入仪器以记录血流动力学。在颈动脉窦周围放置电极以激活BR。起搏2周（250次/分钟）后，7只犬开始进行颈动脉BR电激活，并在研究的剩余时间内持续进行。BR激活的开始被用作其余8只未接受BR激活的对照犬的时间参考点。与对照犬相比，接受颈动脉BR激活的犬的生存率显著更高（分别为68.1±7.4天和37.3±3.2天；P<0.01），尽管在BR激活组和对照组犬中，动脉压、静息心率和左心室压力随时间没有差异。在BR激活开始31天后，接受BR激活治疗的犬的血浆去甲肾上腺素较低（未接受激活治疗的犬为401.9±151.5 pg/mL，接受激活治疗的犬为1121.9±389.1 pg/mL；P<0.05）。接受激活治疗的犬的血浆血管紧张素II增加较少（对照犬的血浆血管紧张素II增加157.4±58.6 pg/mL，接受激活治疗的犬为10.1±14.0 pg/mL；P<0.02）。我们得出结论，慢性激活颈动脉BR可提高慢性心力衰竭犬的生存率并抑制神经激素激活。
