不全心における交感神経系の反応—家兎大動脈弁閉鎖不全症モデルによる経時的検討

Role of adrenergic-neural regulation in failing heart due to aortic regurgitation in rabbits

　【目的】心不全の病態生理における交感神経調節の役割を明らかにする。【方法】日本白色種家兎25羽にて大動脈弁閉鎖不全（AR）を作成した。17羽を3群に分け，AR作成後1日（1日群），1週後（1週群），4週後（4週群）に心筋交感神経β受容体（BAR）およびノルエピネフリン（MNE）を測定した。残る8羽にて血中ノルエピネフリン（PNE）を経時的に測定した。ARのない家兎6羽を対照に用いた。【結果】左室自由壁の重量は1週群および4週群で増加した。壁厚は4週群でのみ増加した。BARは1日群で低下し，その低下は1週群でも持続した。MNEは1週群で低下した。4週群ではこれらの変化は改善した。PNEはAR作成後1日で増加したが，以後作成前の値に回復した。【結論】AR作成後1日では交感神経系の緊張亢進により左室の収縮能を維持しようとしている。1週後に生じる交感神経系の異常は4週後に回復し，ARに対する左室の代償過程と関連していると思われた。

The purpose of this study was to determine the characteristics of the role of adrenergic-neural regu-lation in the pathophysiology of heart failure, produced by aortic regurgitation (AR), especially in relation to the compensatory process. AR was pro-duced by perforation of the aortic valves in 25 rabbits. Another 6 normal rabbits served as con-trols. Myocardial beta-adrenoceptors and catechola-mines were measured in 17 rabbits with AR after various periods : 1 day (n=5), 1 week (n=6), and 4 weeks after production of AR (n=6). Serial blood samples were taken without anesthesia through a catheter placed in the jugular vein for determination of the serum catecholamine level in 8 rabbits with AR. Left ventricular free wall weight increased 1 week and 4 weeks after AR. Wall thickness didn't increase until 4 weeks had passed. Maximal binding sites of myocardial beta-adrenoceptors were reduced from 67. 8±16. 7 fmol/mg. protein in the controls to 37. 6 ±9. 21 day after AR (p＜0. 01). Down regulation persisted for 1 week (37. 3±5. 5). This change was reversed in the 4-week group (55. 5 ± 13. 9). Myo-cardial norepinephrine content was preserved at 1 day, but depleted at 1 week after AR. In the 4-week group it was restored. Serum norepinephrine level increased 1 day after AR. However, it returned toward the normal range thereafter. These data suggest that 1) 1 day after AR, left ventricular contractile performance was supported by augmented adrenergic drive, which could have led to down regulation in beta-adrenoceptors and depletion in catecholamine stores 1 week after AR. 2) Altera-tions in adrenergic-neural regulation were reversed 4 weeks after AR in association with developed hypertrophy. This phenomenon may be related to the compensatory process for AR. Thus, adrenergic-neural regulation has a central role in the patho-physiology of heart failure.