Background

Endothelial dysfunction in the nitric oxide-cyclic guanosine monophosphate pathway is a potential contributor to perioperative myocardial ischemia. The nitric oxide precursor, l-arginine, and the cyclic guanosine monophosphate degradation blocker, sildenafil, have vasodilatory effects under high dosage.

Objective

This study examined the hemodynamic safety and effect profiles of the combined administration of l-arginine and sildenafil using an in-vivo pig model.

Methods

Hemodynamic safety including mean arterial pressure, central venous pressure, heart rate, coronary vascular resistance, and systemic vascular resistance, as well as effect profiles including cardiac output and left anterior descending blood flow were measured in ten female swine after administrations of l-arginine, sildenafil, as well as combined l-arginine and sildenafil. Measurements were compared using repeated-measures analysis of variance and linear mixed models.

Results

The combination of l-arginine and sildenafil produced a significant dose-dependent increase in left anterior descending flow and cardiac output. In contrast, mean arterial pressure, heart rate, central venous pressure, coronary vascular resistance, and systemic vascular resistance did not show any significant changes. No significant change in serum osmolality was observed after administrations of l-arginine.

Conclusions

The combined intravenous administration of sildenafil and l-arginine in a porcine animal model was safe, well tolerated, and had at least additive effects on left anterior descending artery blood flow. Simultaneous application of both drugs might have dose-sparing effects leading to desired coronary effects at lower and safer sildenafil and l-arginine plasma concentrations. Hyperosmolality was only a minor factor in l-arginine hemodynamic effects.

中文翻译：

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在猪动物模型中静脉给予西地那非和L-精氨酸的联合给药：血液动力学安全性和对冠状动脉血流的影响。

背景

一氧化氮-环鸟苷一磷酸途径中的内皮功能障碍是围手术期心肌缺血的潜在原因。一氧化氮前体1-精氨酸和环状鸟苷单磷酸降解阻滞剂西地那非在高剂量下具有血管舒张作用。

目的

这项研究检查了使用猪体内模型联合使用l-精氨酸和西地那非的血液动力学安全性和疗效。

方法

在服用l-精氨酸后，对十只雌性猪进行了包括平均动脉压，中心静脉压，心率，冠状动脉血管阻力和全身血管阻力在内的血液动力学安全性测定，以及包括心输出量和左前降血流在内的各种影响曲线西地那非，以及1-精氨酸和西地那非的组合。使用重复测量方差分析和线性混合模型比较测量结果。

结果

1-精氨酸和西地那非的组合在左前降血流和心输出量上产生了明显的剂量依赖性增加。相反，平均动脉压，心率，中心静脉压，冠状动脉血管阻力和全身血管阻力没有显示任何明显变化。施用1-精氨酸后未观察到血清渗透压的显着变化。

结论

在猪动物模型中西地那非和1-精氨酸的静脉内联合给药是安全，耐受性良好的，并且至少对左前降支血流具有累加作用。两种药物的同时使用可能具有降低剂量的作用，从而在较低和较安全的西地那非和1-精氨酸血浆浓度下产生所需的冠状动脉作用。高渗透压只是1-精氨酸血流动力学作用的次要因素。