Pizzulli L, Hagendorff A, Zirbes M, Fehske W, Ewig S, Jung W, Lüderitz B
Department of Cardiology, University of Bonn, Germany.
Am Heart J. 1996 Feb;131(2):342-9. doi: 10.1016/s0002-8703(96)90364-6.
We investigated whether captopril is able to potentiate vasodilation and prevent tolerance to a 48-hour infusion of nitroglycerin (NTG). Twenty-six patients were randomly assigned to a 7-day regimen of captopril (50 mg/day) or placebo. The hemodynamic response to a 0.8 mg sublingual NTG dose was assessed by measuring mean arterial pressure (MAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), and cardiac output (CO), and calculating systemic (SVR) and pulmonary vascular resistances (PVR). The parameters were obtained serially at baseline and 1 to 10 minutes after the sublingual NTG application (day 1). Then intravenous NTG was started and maintained for 48 hours (1.5 micrograms/kg/min), and the hemodynamic study was repeated (day 3). There was no difference between the captopril and the placebo groups at day 1 (baseline values and response to sublingual NTG). After the 48-hour infusion, there was a complete loss of the NTG effects in the placebo group (day 1 vs day 3: PAP, 20 +/- 5 mm Hg vs 21 +/- 8 mm Hg; MAP, 86 +/- 11 mm Hg vs 90 +/- 9 mm Hg; SVR, 1295 +/- 330 mm Hg vs 1380 +/- 465 dyne.sec.cm-5) whereas there was still evidence of a persistent vasodilation in the captopril group (day 1 vs day 3: PAP, 19 +/- 4 mm Hg vs 13 +/- 4 mm Hg; MAP, 84 +/- 9 mm Hg vs 74 +/- 10 mm Hg; SVR, 1265 +/- 280 mm Hg vs 1140 +/- 425 dyne.sec.cm-5). The response to sublingual NTG on day 3 was markedly attenuated in the placebo group only. We conclude that captopril does not increase the vasodilatory response to nitroglycerin but is able to prevent developing nitrate tolerance in arterial and venous circulation.
我们研究了卡托普利是否能够增强血管舒张作用并预防对硝酸甘油（NTG）48小时输注产生耐受性。26例患者被随机分配至接受卡托普利（50毫克/天）或安慰剂治疗7天的方案。通过测量平均动脉压（MAP）、平均肺动脉压（PAP）、肺毛细血管楔压（PCWP）、右心房压（RAP）和心输出量（CO），并计算体循环（SVR）和肺血管阻力（PVR）来评估对0.8毫克舌下含服NTG剂量的血流动力学反应。这些参数在基线以及舌下含服NTG后1至10分钟（第1天）连续获取。然后开始静脉输注NTG并维持48小时（1.5微克/千克/分钟），并重复血流动力学研究（第3天）。在第1天（基线值和对舌下含服NTG的反应），卡托普利组和安慰剂组之间没有差异。48小时输注后，安慰剂组中NTG的作用完全消失（第1天与第3天比较：PAP，20±5毫米汞柱对21±8毫米汞柱；MAP，86±11毫米汞柱对90±9毫米汞柱；SVR，1295±330毫米汞柱对1380±465达因·秒·厘米⁻⁵），而卡托普利组仍有持续血管舒张的证据（第1天与第3天比较：PAP，19±4毫米汞柱对13±4毫米汞柱；MAP，84±9毫米汞柱对74±10毫米汞柱；SVR，1265±280毫米汞柱对1140±425达因·秒·厘米⁻⁵）。仅在安慰剂组中，第3天对舌下含服NTG的反应明显减弱。我们得出结论，卡托普利不会增加对硝酸甘油的血管舒张反应，但能够预防动脉和静脉循环中硝酸酯耐受性的产生。
