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新型强心剂DPI 201 - 106对犬总容量血管的影响。

Influence of the new inotropic agent DPI 201-106 on the total capacitance vasculature in dogs.

作者信息

Bell L, Rutlen D L

机构信息

Cardiology Section, Yale University School of Medicine, New Haven, Connecticut 06510.

出版信息

Circ Shock. 1990 Aug;31(4):377-85.

PMID:2397566
Abstract

Recent investigations have demonstrated that the piperazinyl-indole DPI 201-106 (DPI) acts to increase contractility independent of increases in cAMP or inhibition of Na+, K(+)-ATPase. Since associated changes in the capacitance vasculature would also be expected to influence ventricular performance, the influence of DPI on total intravascular volume (IV) was examined. In eight anesthetized dogs undergoing prior sinoaortic baroreceptor denervation and bilateral cervical vagotomy, blood from the venae cavae was drained to an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in IV could be recorded as reciprocal changes in reservoir volume. Racemic DPI at 50 micrograms/kg/min for 20 min was associated with a 65 +/- 7 ml (P less than 0.0001) decrease in total IV and a decrease in mean arterial pressure from 80 +/- 7 to 74 +/- 5 mmHg (P less than 0.0001). DPI administration was associated with a 67 +/- 9 ml (P less than 0.05) decrease in IV after beta adrenergic blockade and a 68 +/- 11 ml (P less than 0.05) decrease in IV after alpha and beta adrenergic blockade. Abdominal evisceration abolished the IV decrement due to DPI. Radionuclide imaging studies demonstrated that decreases in hepatic and splenic IV contributed to the decrease in splanchnic IV. Thus, DPI acts to decrease total IV. The IV decrement is due entirely to a decrease in splanchnic IV and is not mediated by baroreceptor stimulation or by adrenergic receptor stimulation. In the animal with an intact circulation, the total IV decrement would be expected to increase venous return and thereby act to maintain ventricular end diastolic pressure.

摘要

最近的研究表明,哌嗪基吲哚DPI 201-106(DPI)可独立于环磷酸腺苷(cAMP)增加或钠钾ATP酶抑制作用而增强收缩性。由于预计容量血管的相关变化也会影响心室功能,因此研究了DPI对血管内总容量(IV)的影响。在八只事先进行了窦主动脉压力感受器去神经支配和双侧颈迷走神经切断术的麻醉犬中,将腔静脉血引流至体外储液器,并以恒定速率回输至右心房,以便将IV的变化记录为储液器容量的相应变化。以50微克/千克/分钟的消旋DPI持续输注20分钟,可使血管内总容量减少65±7毫升(P<0.0001),平均动脉压从80±7毫米汞柱降至74±5毫米汞柱(P<0.0001)。给予DPI后,β肾上腺素能阻断后血管内总容量减少67±9毫升(P<0.05),α和β肾上腺素能阻断后血管内总容量减少68±11毫升(P<0.05)。腹部脏器摘除消除了DPI所致的血管内总容量减少。放射性核素成像研究表明,肝脏和脾脏血管内总容量的减少导致了内脏血管内总容量的减少。因此,DPI可使血管内总容量减少。血管内总容量的减少完全是由于内脏血管内总容量减少所致,并非由压力感受器刺激或肾上腺素能受体刺激介导。在循环完整的动物中,血管内总容量的减少预计会增加静脉回心血量,从而维持心室舒张末期压力。

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