Nodari S, Metra M, Gei P, Danesi R, Furloni R, Cuminetti S, Dei Cas L
Cattedra di Cardiologia, Università degli Studi, Brescia.
Cardiologia. 1991 Jun;36(6):451-60.
The aim of this study was to assess the minimum time interval necessary to avoid the development of tolerance during nitroglycerin patch application. We studied 24 patients, aged 23 to 73 years, with ischemic or idiopathic dilated cardiomyopathy (LV EF less than 0.40) and stable clinical conditions during 30 days before the study. All patients had significant reduction of systemic and pulmonary arterial pressure after sublingual nitroglycerin. After the hemodynamic assessment of the response to the first dose of the nitroglycerin patch, the patients were randomized to 1 of 3 chronic treatment groups: continuous patch application (Group A), intermittent application with 4 hours intervals (Group B), intermittent application with 6 hours intervals (Group C). All patients were studied by right heart Swan-Ganz catheterization; the hemodynamic response to a 10 mg multilayer matrix nitroglycerin patch was assessed before and every hour, in the next 4 hours, after both the first application of the patch and after 1 month of therapy; after chronic intermittent therapy, hemodynamic parameters were also measured 24 hours after drug withdrawal. Hemodynamic parameters were significantly changed after the first nitroglycerin patch application: particularly, mean systemic arterial (MAP), right atrial (RAP) and pulmonary wedge pressures (PWP) declined from 96 +/- 10, 8.9 +/- 1.8 and 20.1 +/- 5 to 81 +/- 6, 4.7 +/- 1.5 and 12.2 +/- 3 mmHg (-15.6, -47.2 and -59.3%, respectively); systemic vascular resistance (SVR) and heart rate (HR) were reduced from 1645 +/- 121 to 1288 +/- 89 dyne.s.cm-5 and from 85 +/- 7 to 81 +/- 7 b/min; lastly, cardiac index (CI), stroke volume (SVI) and stroke work index (SWI) increased from 2.3 +/- 0.3, 28.2 +/- 5 and 28.7 +/- 9 to 2.7 +/- 0.3 l/min/m2, 33.3 +/- 5 ml/min/m2 and 31.5 +/- 8 g.m/m2 (+17.4, 18.1 and 9.7%). After 1 month of either continuous or intermittent patch application with 4 hours intervals, hemodynamic parameters returned to control values with no significant change after patch application. In contrast, after intermittent patch application with 6 hours intervals, a persistent hemodynamic response to nitroglycerin patches was still present.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究的目的是评估在应用硝酸甘油贴片期间避免耐受性产生所需的最短时间间隔。我们研究了24例年龄在23至73岁之间、患有缺血性或特发性扩张型心肌病（左室射血分数小于0.40）且在研究前30天临床状况稳定的患者。所有患者舌下含服硝酸甘油后，体循环和肺动脉压均有显著降低。在对第一剂硝酸甘油贴片的反应进行血流动力学评估后，患者被随机分为3个慢性治疗组中的1组：持续贴片应用（A组）、间隔4小时间歇性应用（B组）、间隔6小时间歇性应用（C组）。所有患者均通过右心Swan - Ganz导管插入术进行研究；在首次应用贴片后和治疗1个月后，于接下来的4小时内每小时评估对10 mg多层基质硝酸甘油贴片的血流动力学反应；在慢性间歇治疗后，停药24小时后也测量血流动力学参数。首次应用硝酸甘油贴片后血流动力学参数有显著变化：特别是，平均体循环动脉压（MAP）、右心房压（RAP）和肺楔压（PWP）分别从96±10、8.9±1.8和20.1±5降至81±6、4.7±1.5和12.2±3 mmHg（分别下降-15.6%、-47.2%和-59.3%）；体循环血管阻力（SVR）和心率（HR）分别从1645±121降至1288±89 dyn·s·cm⁻⁵和从85±7降至81±7次/分钟；最后，心脏指数（CI）、每搏量（SVI）和每搏功指数（SWI）分别从2.3±0.3、28.2±5和28.7±9增至2.7±0.3 l/min/m²、33.3±5 ml/min/m²和31.5±8 g·m/m²（分别增加+17.4%、18.1%和9.7%）。在持续或间隔4小时间歇性贴片应用1个月后，血流动力学参数恢复至对照值，贴片应用后无显著变化。相比之下，在间隔6小时间歇性贴片应用后，对硝酸甘油贴片仍存在持续的血流动力学反应。（摘要截断于400字）
