Burchell S A, Spinale F G, Crawford F A, Tanaka R, Zile M R
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425.
J Thorac Cardiovasc Surg. 1992 Oct;104(4):1006-12.
Chronic supraventricular (or ventricular) tachycardia causes a dilated cardiomyopathy. Effective treatment requires ablation of the tachycardia using antiarrhythmic agents, cryoablation, electroablation, or surgical interruption/excision. However, the underlying pathophysiologic mechanisms responsible for the development of supraventricular tachycardia-induced cardiomyopathy have not been fully identified. We hypothesized that chronic supraventricular tachycardia is associated with significant changes in the beta-adrenergic system that may have implications for the pathophysiology and treatment of supraventricular tachycardia-induced cardiomyopathy. Accordingly, we examined the relationship between left ventricular function, plasma norepinephrine level, beta-receptor number and affinity, and response to a beta-agonist (isoproterenol) infusion in eight control pigs and eight pigs subjected to supraventricular pacing-induced tachycardia (240 beats/min for 3 weeks). Left ventricular function was measured using simultaneous echocardiography and catheterization. Left ventricular end-diastolic dimension and pressure increased in pigs with supraventricular tachycardia (5.1 +/- 0.4 cm and 27 +/- 2 mm Hg) versus control pigs (3.8 +/- 0.3 cm and 8 +/- 2 mm Hg), p < 0.05. Left ventricular fractional shortening decreased in supraventricular tachycardia (10 +/- 1%) versus control pigs (34 +/- 1%), p < 0.05. In addition, in the pigs with supraventricular tachycardia the fractional shortening versus left ventricular end-systolic stress relationship fell below the control relationship. Plasma norepinephrine level (measured by high-performance liquid chromatography) increased in pigs with supraventricular tachycardia (3592 +/- 1606 pg/ml plasma) versus control pigs (323 +/- 74 pg/ml plasma), p < 0.05. beta-Receptor number and affinity (measured by [3H]dihydroalprenolol binding) did not change in supraventricular tachycardia (98.6 +/- 11.5 fmol/mg protein and 7.2 +/- 1.1 nmol) versus control pigs (99.1 +/- 9.4 fmol/mg protein and 6.8 +/- 0.5 nmol). The response to isoproterenol infusion (10 micrograms/kg) in supraventricular tachycardia was blunted: the absolute increase in left ventricular peak (+)dP/dt was reduced in supraventricular tachycardia (833 +/- 233 mm Hg/sec) versus control pigs (2180 +/- 139 mm Hg/sec), p < 0.05. Chronic supraventricular tachycardia caused a decreased contractile state, increased plasma norepinephrine level, and caused no change in beta-receptor number or affinity; however, the response to beta-agonist infusion was blunted. These results suggest that chronic supraventricular tachycardia is associated with uncoupling of the beta-receptor from subsequent intracellular components of the beta-adrenergic system. Therefore medical management of chronic supraventricular tachycardia-induced cardiomyopathy before and immediately after definitive ablation may require use of pharmacologic agents whose actions do not depend on an intact beta-adrenergic pathway.
慢性室上性（或室性）心动过速可导致扩张型心肌病。有效的治疗需要使用抗心律失常药物、冷冻消融、电消融或手术阻断/切除来消除心动过速。然而，导致室上性心动过速性心肌病发生的潜在病理生理机制尚未完全明确。我们推测慢性室上性心动过速与β-肾上腺素能系统的显著变化有关，这可能对室上性心动过速性心肌病的病理生理和治疗具有重要意义。因此，我们研究了8只对照猪和8只接受室上性起搏诱导的心动过速（240次/分钟，持续3周）的猪的左心室功能、血浆去甲肾上腺素水平、β受体数量和亲和力以及对β-激动剂（异丙肾上腺素）输注的反应之间的关系。使用超声心动图和导管插入术同时测量左心室功能。与对照猪（3.8±0.3cm和8±2mmHg）相比，室上性心动过速猪的左心室舒张末期内径和压力增加（5.1±0.4cm和27±2mmHg），p<0.05。与对照猪（34±1%）相比，室上性心动过速时左心室缩短分数降低（10±1%），p<0.05。此外，在室上性心动过速的猪中，缩短分数与左心室收缩末期应力的关系低于对照关系。与对照猪（323±74pg/ml血浆）相比，室上性心动过速猪的血浆去甲肾上腺素水平（通过高效液相色谱法测量）升高（3592±1606pg/ml血浆），p<0.05。室上性心动过速时β受体数量和亲和力（通过[3H]二氢阿普洛尔结合测量）与对照猪（99.1±9.4fmol/mg蛋白和6.8±0.5nmol）相比没有变化（98.6±11.5fmol/mg蛋白和7.2±1.1nmol）。室上性心动过速时对异丙肾上腺素输注（10μg/kg）的反应减弱：与对照猪（2180±139mmHg/秒）相比，室上性心动过速时左心室峰值（+）dP/dt的绝对增加减少（833±233mmHg/秒），p<0.05。慢性室上性心动过速导致收缩状态降低、血浆去甲肾上腺素水平升高，且β受体数量或亲和力无变化；然而，对β-激动剂输注的反应减弱。这些结果表明，慢性室上性心动过速与β受体与其后的β-肾上腺素能系统细胞内成分解偶联有关。因此，在明确消融前后对慢性室上性心动过速性心肌病进行药物治疗可能需要使用其作用不依赖完整β-肾上腺素能途径的药物。
