Umezawa S, Taniguchi K, Takeuchi J
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Jpn Heart J. 1988 Jan;29(1):19-33. doi: 10.1536/ihj.29.19.
To study the acute effects of ISDN, nifedipine, propranolol and placebo on cardiac function in patients with myocardial ischemia and to characterize their hemodynamic effects by PANOVA, we repetitively performed exercise radionuclide angiography (RNA) following random assignment of each drug in 20 patients with effort angina pectoris. We obtained exercise response curves of hemodynamic parameters determined by RNA. ANOVA was performed to analyze the sizes (average height) of those response curves, and PANOVA (principal component analysis, PCA, combined with ANOVA) to analyze differences in the profiles (patterns) of the curves. By conventional analysis of variance followed by a Scheffé type multiple comparison, end-diastolic volume after ISDN, which was significantly smaller than those after the other drugs at rest (p less than 0.01), was similar to those after nifedipine and propranolol during exercise (96.4 +/- 4.6 ml/m2 vs. 94.8 +/- 5.1 ml/m2 and 97.1 +/- 4.9 ml/m2, respectively). Systemic vascular resistance after nifedipine, which was also significantly lower than those after the other drugs at rest (p less than 0.05), was not different from that after placebo during exercise (16.9 +/- 1.1 units vs. 18.7 +/- 1.3 units). Thus, this analysis was considered insufficient to fully differentiate the characteristics of each drug. By PANOVA, the profiles of LVEF with these three antianginal drugs were similar, and significantly differentiated from that of placebo (p less than 0.05). This indicated that the antianginal effect could be represented by the profiles of the response curves of LVEF, using PANOVA. Evaluating the underlying hemodynamic mechanisms of these drugs by PANOVA, ISDN was significantly differentiated from nifedipine and propranolol by the profile of end-diastolic volume (p less than 0.05). The characteristics of nifedipine were clearly demonstrated by the size and profile of systemic vascular resistance, and those of propranolol were also differentiated by the size and profile of the double product and P-V index. Hence, it is concluded that with the aid of PANOVA, the changes in hemodynamic parameters during ischemia can be evaluated in a manner that is highly effective in differentiating the characteristics of the effects of antianginal drugs in patients with angina pectoris.
为研究硝酸异山梨酯(ISDN)、硝苯地平、普萘洛尔及安慰剂对心肌缺血患者心功能的急性影响,并通过主成分方差分析(PANOVA)来描述其血流动力学效应,我们对20例劳力性心绞痛患者随机给予每种药物后,重复进行运动放射性核素血管造影(RNA)。我们获得了由RNA测定的血流动力学参数的运动反应曲线。进行方差分析(ANOVA)以分析这些反应曲线的大小(平均高度),并进行主成分方差分析(PANOVA,即主成分分析(PCA)与方差分析相结合)以分析曲线轮廓(模式)的差异。通过常规方差分析及随后的谢费(Scheffé)型多重比较,ISDN后的舒张末期容积在静息时显著小于其他药物后的舒张末期容积(p<0.01),在运动时与硝苯地平和普萘洛尔后的舒张末期容积相似(分别为96.4±4.6ml/m² 、94.8±5.1ml/m²和97.1±4.9ml/m²)。硝苯地平后的全身血管阻力在静息时也显著低于其他药物后的全身血管阻力(p<0.05),在运动时与安慰剂后的全身血管阻力无差异(16.9±1.1单位 vs. 18.7±1.3单位)。因此,该分析被认为不足以充分区分每种药物的特性。通过PANOVA,这三种抗心绞痛药物的左室射血分数(LVEF)曲线轮廓相似,且与安慰剂的曲线轮廓有显著差异(p<0.05)。这表明使用PANOVA,抗心绞痛作用可以由LVEF反应曲线的轮廓来表示。通过PANOVA评估这些药物潜在的血流动力学机制,ISDN在舒张末期容积的曲线轮廓上与硝苯地平和普萘洛尔有显著差异(p<0.05)。硝苯地平的特性通过全身血管阻力的大小和曲线轮廓清晰地显示出来,普萘洛尔的特性也通过双乘积和P-V指数(pressure-volume index)的大小和曲线轮廓得以区分。因此得出结论,借助PANOVA,可以以一种非常有效的方式评估缺血期间血流动力学参数的变化,以区分心绞痛患者中抗心绞痛药物作用的特性。