Dakak N, Makhoul N, Flugelman M Y, Merdler A, Shehadeh H, Schneeweiss A, Halon D A, Lewis B S
Department of Cardiology, Lady Davis Carmel Hospital, Haifa, Israel.
Am J Cardiol. 1990 Sep 1;66(5):608-13. doi: 10.1016/0002-9149(90)90489-n.
The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.
通过对12例接受硝酸甘油治疗的患者（第1组）和9例接受硝酸甘油并同时接受卡托普利治疗（60±29毫克/天）的患者（第2组）的耐受程度进行量化，研究了血管紧张素转换酶抑制在预防或最小化重度充血性心力衰竭（CHF）患者对静脉注射硝酸甘油的耐受性方面的可能作用。在峰值效应时，硝酸甘油在两组中产生了几乎相同的血流动力学变化，右心房和肺动脉楔压、收缩压以及全身和肺血管阻力均显著降低。心脏指数增加。计算每个血流动力学参数的硝酸盐耐受程度，即药物达到的峰值效应损失的百分比。在24小时时，第1组中关于右心房压力所获得的益处损失了98±80%，第2组中损失了61±74%（第1组与第2组相比，差异不显著）。对于肺动脉楔压，效应损失了51±31%（第1组）和85±53%（第2组）（差异不显著），对于心脏指数，损失了53±58%（第1组）和54±44%（第2组）（差异不显著）。在收缩压以及全身和肺血管阻力方面，耐受性也几乎相同。因此，卡托普利的给药并未改变CHF患者对高剂量静脉注射硝酸甘油的耐受程度，这表明在临床剂量下，涉及肾素 - 血管紧张素系统的反调节神经体液机制在其发展过程中似乎并不重要。
