Effects of Nifedipine on Systemic and
Pulmonary Vascular Impedance in Subjects
Undergoing Cardiac Catheterization
Toshitaka NODA1), Toshio YAGINUMA2),*, Michael F. O’ROURKE3),4),
and Saichi HOSODA5)
下面是google翻譯
硝苯地平對接受心導管插入術的受試者全身和肺血管阻抗的影響 Toshitaka NODA1), Toshio YAGINUMA2),*, Michael F. O'ROURKE3),4), and Saichi HOSODA5) 硝苯地平 10 mg，舌下含服於診斷後的 12 名患者心導管術，導致全身阻力降低，阻抗改變以及升主動脈和左心室壓力波輪廓的改變。儘管每搏量和心輸出量增加，但硝苯地平顯著降低了升主動脈和左心室收縮壓，並且與平均壓力和波反射指數的類似降低有關。在同一患者中，肺血管阻力或阻抗沒有顯著變化，也不在肺動脈或右心室壓力脈搏輪廓中。對於全身循環，與硝酸甘油和硝普鈉一樣，波反射的減少似乎是藥物作用的一個重要因素，並且在治療心絞痛、全身性高血壓和左心室衰竭時它對心臟負荷有有益作用。因此，觀察到的硝苯地平作用歸因於全身動脈和小動脈的血管擴張。（高血壓研究 2006；29：505–513）因此，觀察到的硝苯地平作用歸因於全身動脈和小動脈的血管擴張。（高血壓研究 2006；29：505–513）因此，觀察到的硝苯地平作用歸因於全身動脈和小動脈的血管擴張。（高血壓研究 2006；29：505–513）
簡介 硝苯地平和其他二氫吡啶類鈣通道阻滯劑 (CCB) 廣泛用於治療高血壓、缺血性心髒病和保留左心室收縮功能的心力衰竭 (1–6)。硝苯地平還用於治療主動脈瓣關閉不全 (7) 和肺動脈高壓 (8)。這些藥物可有效降低動脈壓、緩解心肌缺血以及改善收縮和舒張左心室功能 (3, 4, 9)。它們的有益作用歸因於外周小動脈擴張，這會導致平均動脈壓和左心室後負荷降低 (5, 9)。然而，關於硝苯地平對體循環或肺循環中的搏動現象影響的研究很少。雖然硝苯地平已被證明可以降低早期波反射和中心主動脈收縮壓 (10)，但有限的血管阻抗研究並未顯示該藥物對升主動脈阻抗的頻率依賴性成分具有一致的影響 (11, 12)。儘管硝苯地平用於治療肺動脈高壓 (8)，但沒有關於硝苯地平對肺血管阻抗影響的數據。本研究的目的是研究硝苯地平對因已知或疑似缺血性心髒病而接受心導管術的人類受試者的動脈搏動血流動力學以及全身和肺血管阻抗的影響。血管阻抗的有限研究並未顯示藥物對升主動脈阻抗的頻率依賴性成分的一致影響 (11, 12)。儘管硝苯地平用於治療肺動脈高壓 (8)，但沒有關於硝苯地平對肺血管阻抗影響的數據。本研究的目的是研究硝苯地平對因已知或疑似缺血性心髒病而接受心導管術的人類受試者的動脈搏動血流動力學以及全身和肺血管阻抗的影響。血管阻抗的有限研究並未顯示藥物對升主動脈阻抗的頻率依賴性成分的一致影響 (11, 12)。儘管硝苯地平用於治療肺動脈高壓 (8)，但沒有關於硝苯地平對肺血管阻抗影響的數據。本研究的目的是研究硝苯地平對因已知或疑似缺血性心髒病而接受心導管術的人類受試者的動脈搏動血流動力學以及全身和肺血管阻抗的影響。
結果
12例患者的臨床特徵見表1，對照條件下的基本血流動力學數據見表2。所有患者均為男性，平均年齡55.4±6.3歲（年齡範圍43-63歲）。在左心室和右心室以及主動脈和肺動脈中同時記錄的壓力和流量的代表性描記圖如圖 2 所示，分別為硝苯地平給藥前後的情況。所有患者服用硝苯地平前後血流動力學參數的平均值見表 3。服用硝苯地平可使心率從每分鐘 70 次增加到 84 次，每搏輸出量增加，因此，心輸出量增加更大 (31%)。服用硝苯地平可顯著降低全身而非肺血管阻力（分別從 1,664 到 1,126 dyn s cm-5 [p<0.001] 和 241 到 182 dyn s cm-5 [NS]）。硝苯地平的其他肺血流動力學數據或肺血管阻抗沒有顯著變化，但全身血管阻抗有非常明顯的變化（圖 3）。硝苯地平增加的心輸出量與平均壓力從 102 mmHg 降低到 90 mmHg 相關，表明外周系統阻力降低。與此同時，收縮壓下降了 25 mmHg (p<0.0001)，但舒張壓僅下降了 9 mmHg (p<0.02)。收縮壓的大幅下降與晚期收縮峰振幅的降低有關，並且主要由其引起（圖 1）。2). 測量的主動脈收縮壓波增強被確定為第一個收縮壓肩和壓力峰值之間的壓差 (14, 15)。這從 22 mmHg 下降到 10 mmHg (p<0.0001)。儘管每搏輸出量增加了 8%，但脈壓實際上下降了 30% (p<0.0001)。儘管流量波動增加，但壓力波動的這種減少表明波反射減少或動脈僵硬度降低。壓力波形狀的變化，以及第一次肩部收縮後增強的減少，表明外周波反射減少 (12–14)。阻抗模量從 47 到 29 dyn s cm-5 (p < 0.01) 減少了 43%（從 193 到 110 dyn s cm-5 [p<0.0001]）；這是模量圍繞其特徵值波動的量度。特性阻抗從 103 下降 22% 至 80 dyn s cm−5 ，但這種變化沒有達到統計學意義的水平。特徵阻抗的任何降低都可能是由於動脈壓降低導致近端主動脈的擴張性被動下降。給予硝苯地平後，左心室外部做功的穩定成分沒有顯著增加，心輸出量的增加被平均壓力的下降所抵消。阻抗模量的降低抵消了每搏輸出量和脈動流量的增加，因此外部做功的脈動分量沒有變化，脈動與總外部做功的比率也沒有變化。在肺循環中，服用硝苯地平後平均壓力沒有變化（前後均為 15 mmHg），特徵阻抗也沒有變化（前後分別為 37 和 33 dyn s cm−5）。硝苯地平給藥不影響左心室或右心室的舒張末期壓力，並且不改變波反射的時間，如阻抗相位的零交叉所衡量的那樣（圖 4）。對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量 特性阻抗也沒有（前後分別為 37 和 33 dyn s cm−5）。硝苯地平給藥不影響左心室或右心室的舒張末期壓力，並且不改變波反射的時間，如阻抗相位的零交叉所衡量的那樣（圖 4）。對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量 特性阻抗也沒有（前後分別為 37 和 33 dyn s cm−5）。硝苯地平給藥不影響左心室或右心室的舒張末期壓力，並且不改變波反射的時間，如阻抗相位的零交叉所衡量的那樣（圖 4）。對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量 對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量 對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量
討論 據我們所知，本文是第一個同時確定在人類受試者中使用口服有效血管擴張劑之前和之後呈現給左心室和右心室的脈動水力負荷的文章。輸入阻抗由三部分組成：阻力（平均壓力÷平均流量）、近端動脈硬度（升主動脈或主肺動脈特徵阻抗）和反射率（壓力增加或阻抗波動）(10)。結果很有趣，因為它們對肺阻抗和右心室搏動負荷沒有顯著影響，但對左心室搏動負荷有相當大的影響。觀察到的對全身循環的影響主要歸因於硝苯地平引起的外周阻力降低和波反射減少。升主動脈阻抗被廣泛接受為左心室負荷的表達 (15-26)，而肺血管阻抗被廣泛接受為右心室負荷的表達 (27-29)。已在患有胸痛綜合徵但沒有明確心血管疾病的患者、高血壓患者、心肌病患者以及本文所述的冠狀動脈粥樣硬化患者中進行了研究（表 4）。在過去的血管擴張劑作用研究中，大部分注意力都集中在阻抗模量的零頻率分量——外周阻力上。在 70 年代末和 80 年代初，注意力開始轉移到由潛在疾病或藥物治療引起的特徵阻抗和主動脈硬度的變化 (16-20)。此處描述的全身阻力和肺阻力值與之前報導的相似；主動脈和肺特徵阻抗的值也在之前報告的範圍內（表4）。在這項研究中，我們發現硝苯地平外周系統阻力降低，與心輸出量增加和全身動脈壓下降有關。然而，我們已經表明，這些效應的發生不會改變肺部特徵阻抗，也不會顯著降低全身特徵阻抗。我們已經指出，收縮壓和脈壓的顯著下降，以及主動脈和左心室波輪廓形狀的變化，不能僅用平均壓力和特徵阻抗的變化來解釋。然而，收縮壓和脈壓的降低以及波形的變化可以很容易地解釋為從外周血管末端返回的反射波振幅降低，從而導致外周血管舒張 (10, 16, 24)。這方面的證據是阻抗模量波動的減少，以及在脈衝的一次諧波頻率下升主動脈阻抗模量的顯著下降。硝酸甘油 (23, 24) 和硝普鈉 (18–21) 也出現了類似的變化，這歸因於壓力波反射的減少。這些對波反射的影響在硝普鈉 (21, 22) 的情況下歸因於小動脈擴張，而在硝酸甘油的情況下，阻力小動脈上游的小導管動脈的口徑和順應性發生變化 (10, 23, 24)。在這項研究中，升主動脈阻抗的變化與升主動脈壓力增加的顯著減少有關。這種增加的下降（12 毫米汞柱）與平均全身壓力下降（12 毫米汞柱）的幅度相似，並且在很大程度上解釋了脈壓顯著下降（16 毫米汞柱）。主動脈收縮壓的降低是由壓力增加的減少和平均壓力的下降引起的。兩者都歸因於外周血管擴張，以不同的方式起作用——第一種情況是通過減少波反射，第二種情況是通過減少外周阻力。因此，硝苯地平的有益治療效果主要歸因於外周阻力和波反射的降低。在成熟的成年人中，高主動脈脈搏波速度以及腹主動脈區域的結構變化 (10, 26, 30) 導致波反射不適當地提前返回心臟，並增加收縮晚期心室射血產生的壓力. 這種增壓包括左心室後負荷的重要組成部分 (10, 13, 14, 31)。它的減少，例如通過硝普鈉給藥，導致左心室負荷減少和左心室功能改善，特別是在左心室衰竭患者運動期間（32）。通過這種機制降低收縮壓也部分解釋了這種藥物對高血壓和心絞痛患者的益處 (10, 31)。此處描述的硝苯地平的作用與之前描述的硝普鈉 (18、19、21、22) 和硝酸甘油 (23、24) 的作用相似，儘管與硝酸甘油不同，硝苯地平和硝普鈉均持續降低外周阻力 (18、19、21) ). 然而，有人強調，當測量外周動脈的壓力時，硝酸甘油和硝普鈉的有益作用可能被低估 (8, 10, 33, 34)。不能通過傳統的上肢動脈峰值（收縮壓）和最低（舒張壓）壓力測量來正確解釋或評估早期波反射的不良影響及其減少的有益影響；然而，它們可以通過對肱動脈或橈動脈壓力波輪廓的解釋進行評估 (10, 33, 34)。同樣的原則很可能也適用於硝苯地平。然而，尚未進行任何研究來確定硝苯地平對中央動脈和外周動脈之間壓力波輪廓差異的影響。此處顯示的全身動脈血流動力學結果與 Ting 等人的報告一致。（12），但與 Chang 等人報導的不一致。(11) 在高血壓受試者組中。張等。(11) 發現硝苯地平降低了全身血管阻力，並降低了左心室的穩定成分，但無法證明對升主動脈阻抗的頻率依賴成分有任何影響。他們確實顯示硝苯地平的收縮壓比舒張壓有更大的降低，以及阻抗的一次諧波分量幅度的降低和脈壓的降低，但後兩種效應在統計學上並不顯著。作者只研究了 7 名患者，並且可能在接近造影血管造影時間時獲取了對照數據，當時造影劑的血管舒張作用仍然很明顯。該研究中心輸出量沒有增加的事實引發了一個問題，即藥物是否在採集數據時發揮藥理作用，即舌下給藥後 10-30 分鐘。婷等。(12) 使用了更高劑量的硝苯地平，並且與我們一樣，顯示出波反射測量值和全身血管阻力的降低。婷等。還顯示主動脈特徵阻抗降低。此處提供的數據與 Ting 等人的數據一致。(12) 並支持這樣的概念，即硝苯地平是治療高血壓或其他動脈系統硬化和波反射增加左心室負荷的病症（包括老年人的心力衰竭和冠心病）的合乎邏輯的治療劑（ 24、31、34-36）。然而，對於短效硝苯地平的使用，如本文所用，應注意一件事——即血管阻力降低可能導致冠狀動脈竊血和/或心動過速，從而加重心肌缺血 (10)。單純收縮期高血壓的理想抗高血壓藥物 (37) 和理想的抗心絞痛藥物 (10) 可能是一種與硝酸甘油類似的藥物，降低波反射和主動脈收縮壓，同時保持外周阻力和平均動脈壓 (10, 24, 33–35, 37, 38)。長效硝苯地平在療效和副作用方面與血管緊張素轉化酶抑製劑相當 (39)，並且不會像本研究中使用的短效製劑那樣誘發交感神經刺激和心動過速。
Nifedipine 10 mg, administered sublingually to 12 patients following diagnostic cardiac catheterization,
caused reduction in systemic resistance, and change of impedance together with alteration in contour of
the ascending aortic and left ventricular pressure waves. The substantial reduction in ascending aortic and
left ventricular systolic pressure with nifedipine occurred despite an increase in stroke volume and cardiac
output, and was associated with similar reductions in mean pressure and indices of wave reflection. In the
same patients, there were no significant changes in pulmonary vascular resistance or impedance, nor in pulmonary artery or right ventricular pressure pulse contour. For the systemic circulation, as with nitroglycerin
and nitroprusside, reduction in wave reflection appears to be an important factor in the drug’s action and
for its beneficial effects on cardiac load in the treatment of angina pectoris, systemic hypertension and left
ventricular failure. Thus the observed effects of nifedipine were attributed to vasodilatation of the systemic
arteries and arterioles. (Hypertens Res 2006; 29: 505–513)
Introduction
Nifedipine and other dihydropyridine calcium channel blockers (CCBs) are widely used in the treatment of hypertension,
ischemic heart disease and cardiac failure with preserved left
ventricular systolic function (1–6). Nifedipine is also used in
the treatment of aortic valve incompetence (7) and pulmonary
hypertension (8). These drugs are effective in lowering arterial pressure, relieving myocardial ischemia, and improving
both systolic and diastolic left ventricular function (3, 4, 9).
Their beneficial effects have been attributed to peripheral
arteriolar dilation, which results in decreases in mean arterial
pressure and left ventricular afterload (5, 9). However, therehave been few studies on the effects of nifedipine on pulsatile
phenomena, either in the systemic or pulmonary circulations.
While nifedipine has been shown to reduce early wave reflection and central aortic systolic pressure (10), the limited studies of vascular impedance have not shown a consistent effect
of the drug on the frequency-dependent components of
ascending aortic impedance (11, 12). And despite the drug’s
use in pulmonary hypertension (8), no data are available on
the effects of nifedipine on pulmonary vascular impedance.
The purpose of this study was to investigate the effects of
nifedipine on pulsatile arterial hemodynamics and systemic
and pulmonary vascular impedance in human subjects undergoing cardiac catheterization for known or suspected
ischemic heart disease.
Results
The clinical characteristics of the twelve patients are given in
Table 1, and the basic hemodynamic data under control conditions are given in Table 2. All patients were male with an
average age of 55.4±6.3 years (age range 43–63 years).
Representative tracings of pressure and flow recorded
simultaneously in the left and right ventricles, and in the aorta
and pulmonary arteries are shown in Fig. 2, before and after
administration of nifedipine. The averaged values of hemodynamic parameters in all patients before and after nifedipine
administration are given in Table 3.
Nifedipine administration led to an increase in heart rate
from 70 to 84 beats per min (bpm), as well as an increase in
stroke volume and, consequently, an even greater (31%)
increase in cardiac output. Nifedipine administration resulted
in a significant reduction in systemic but not pulmonary vascular resistance (from 1,664 to 1,126 dyn s cm−5
[p<0.001],
and 241 to 182 dyn s cm−5
[NS], respectively). There was no
significant change in other pulmonary hemodynamic data or
in pulmonary vascular impedance with nifedipine, but there was a very clear change in the systemic vascular impedance
(Fig. 3).
The increase in cardiac output with nifedipine was associated with a decrease in mean pressure from 102 to 90 mmHg,
signifying a decrease in peripheral systemic resistance.
Accompanying this, there was a fall of 25 mmHg (p<0.0001)
in systolic pressure but only 9 mmHg (p<0.02) in diastolic
pressure. The substantial fall in systolic pressure was associated with and largely caused by a reduction in the amplitude
of the late systolic peak (Fig. 2). Measured aortic systolic
pressure wave augmentation was determined as the pressure
difference between the first systolic shoulder and the pressure
peak (14, 15). This fell from 22 to 10 mmHg (p<0.0001).
Despite the 8% increase in stroke volume, the pulse pressure
actually decreased by 30% (p<0.0001). Such a decrease in
pressure fluctuation despite an increase in flow fluctuation
suggests either a decrease in wave reflection or a decrease in
arterial stiffness. The change in shape of the pressure wave,
with a reduction in augmentation after the first systolic shoulder, suggests a reduction in the peripheral wave reflection
(12–14). This was supported by the 43% reduction (from 193
to 110 dyn s cm−5
[p<0.0001]) of the modulus of impedancefrom 47 to 29 dyn s cm−5
(p<0.01); this is a measure of the
fluctuation of modulus around its characteristic value. Characteristic impedance fell by 22% from 103 to 80 dyn s cm−5
,
but this change did not reach the level of statistical significance. Any decrease in characteristic impedance could have
been due to a passive fall in the distensibility of the proximalaorta with the reduction in arterial pressure.
The steady component of external left ventricular work did
not increase significantly after nifedipine administration, the
increase in cardiac output being offset by a fall in mean pressure. The decrease in impedance modulus more than offset
the increase in stroke volume and pulsatile flow, such that the
pulsatile component of external work did not change, and neither did the ratio of pulsatile to total external work.
In the pulmonary circulation, mean pressure did not change
after administration of nifedipine (15 mmHg both before and
after), and neither did characteristic impedance (37 and 33
dyn s cm−5
before and after). Nifedipine administration did
not affect end-diastolic pressure of the left or right ventricle,
and did not alter the timing of wave reflection, as gauged by
the zero crossing of the impedance phase (Fig. 4). For the
ascending aorta, this frequency was 3.3±0.6 Hz before, and
3.4±0.6 Hz (NS) after nifedipine administration; for the pulmonary artery, this frequency was 2.5±0.8 Hz before, and
2.8±1.2 Hz (NS) after nifedipine. This frequency corresponded to the minimal value of the impedance modulus, but
could be measured more accurately
Discussion
To our knowledge, this paper is the first to simultaneously
determine the pulsatile hydraulic load presented to the left
and right ventricle, before and after use of an orally effective
vasodilator agent in human subjects. Input impedance is composed of three components: resistance (mean pressure ÷ mean
flow), stiffness of proximal arteries (ascending aortic or main
pulmonary artery characteristic impedance) and reflectance
(augmented pressure or impedance fluctuation) (10). The
results are intriguing in that they show no significant effect on
pulmonary impedance and right ventricular pulsatile load, but
considerable effect on left ventricular pulsatile load. The
observed effects on the systemic circulation were largely
attributed to the decreased peripheral resistance and
decreased wave reflection induced by nifedipine.
Ascending aortic impedance is widely accepted as an
expression of left ventricular load (15–26), and pulmonary
vascular impedance as an expression of right ventricular load
(27–29). Studies have been undertaken in patients with chest
pain syndromes but without definite cardiovascular disease,
in patients with hypertension, in patients with cardiomyopathy, and in patients such as those described here, with coronary atherosclerosis (Table 4). In past studies of vasodilator
action, most attention has been directed to the zero frequency
component of impedance modulus—the peripheral resistance. In the late 1970s and early 1980s, the attention began to
shift to the changes in characteristic impedance and aortic
stiffness resulting from the underlying disease or from drug
therapy (16–20). The values of the systemic and pulmonary
resistance described here are similar to those reported earlier;
the values of aortic and pulmonary characteristic impedance
are also in the range of those reported before (Table 4).
In this study we have shown a decrease in peripheral systemic resistance with nifedipine, in association with an
increase in cardiac output and fall in systemic arterial pressure. We have shown, however, that these effects occur without any change in pulmonary characteristic impedance and no
significant reduction in systemic characteristic impedance.
We have pointed out that the marked falls in systolic pressure
and pulse pressure, and the change in shape of the aortic and
left ventricular wave contours, cannot be explained solely by
the change in mean pressure and characteristic impedance.
However, the decrease in systolic and pulse pressure and the
change in waveform can readily be explained on the basis of
the decrease in the amplitude of the reflected wave returning
from peripheral vascular terminations and consequently on
peripheral vasodilation (10, 16, 24). The evidence for this is
the reduction in fluctuation of the impedance modulus, and
the substantial fall in the ascending aortic impedance modulus
at the frequency of the first harmonic of the pulse. Similar
changes have been noted with nitroglycerin (23, 24) and with
nitroprusside (18–21), and have been attributed to a reduction
in pressure wave reflection. These effects on wave reflection
have been attributed to arteriolar dilation in the case of nitroprusside (21, 22), and in the case of nitroglycerin, to a change
in the caliber and compliance of the small conduit arteries
immediately upstream from the resistive arterioles (10, 23,
24).
In this study, the change in ascending aortic impedance was
associated with a marked reduction in pressure augmentation
in the ascending aorta. This fall in augmentation (of 12
mmHg) was of similar magnitude to the degree of fall in mean
systemic pressure (12 mmHg) and largely explains the
marked reduction in pulse pressure (of 16 mmHg). The reduction of aortic systolic pressure was caused both by a reduction
in pressure augmentation and a fall in mean pressure. Both are
attributable to peripheral vasodilation, acting in different
ways—in the first case through a decrease in wave reflection,
and in the second through a decrease in peripheral resistance.
The beneficial therapeutic effects of nifedipine can thus be
largely attributed to reductions in the peripheral resistance
and wave reflection. In mature adults, high aortic pulse wave
velocity, together with structural changes in the region of the
abdominal aorta (10, 26, 30) result in wave reflection returning inappropriately early to the heart, and boosting the pressure generated by ventricular ejection in late systole. This
pressure boost comprises a substantial component of the left
ventricular afterload (10, 13, 14, 31). Its reduction, such as by
nitroprusside administration, leads to a reduction in left ventricular load and an improvement in left ventricular function,
especially during exercise in patients with left ventricular failure (32). The decrease in systolic pressure by this mechanism
also partially explains the benefit of this drug in patients with
hypertension and angina pectoris (10, 31).
The effects of nifedipine described here are similar to those
previously described for nitroprusside (18, 19, 21, 22) and for
nitroglycerin (23, 24), although unlike nitroglycerin, both
nifedipine and nitroprusside consistently decrease peripheral
resistance (18, 19, 21). It has been stressed, however, that the
beneficial effects of nitroglycerin and of nitroprusside may be
underestimated when pressure is measured in a peripheral
artery (8, 10, 33, 34). The ill effects of early wave reflection,
and the beneficial effects of its reduction cannot be properly
interpreted or assessed from conventional measurement of the
peak (systolic) and lowest (diastolic) pressure in an upper
limb artery; they can, however, be assessed from interpretation of the brachial or radial artery pressure wave contour (10,
33, 34). It is quite likely that the same principles also apply to
nifedipine. However, no study has yet been conducted to
determine the effects of nifedipine on the differences in pressure wave contour between the central and peripheral arteries.
The results presented here for systemic arterial hemodynamics are in line with the report by Ting et al. (12), but at
variance with those reported by Chang et al. (11) in groups of
hypertensive subjects. Chang et al. (11) found a reduction in
systemic vascular resistance, and in the steady component of
left ventricular work with nifedipine, but were unable to demonstrate any effect on the frequency-dependent components
of ascending aortic impedance. They did show a greaterreduction in systolic than in diastolic pressure with nifedipine, as well as a reduction in amplitude of the first harmonic component of impedance, and a reduction of pulse
pressure, but the latter two effects were not statistically significant. The authors studied just seven patients and may have
taken control data close to the time of contrast angiography,
when the vasodilating effect of the contrast agent was still in
evidence. The fact that cardiac output did not increase in that
study raises a question as to whether the drug was exerting a
pharmacological effect at the time data were taken, i.e., 10–30
min after sublingual administration. Ting et al. (12) used a
higher dose of nifedipine and showed, as did we, reductions
in the measures of wave reflection and in the systemic vascular resistance. Ting et al. also showed a reduction in aortic
characteristic impedance.
The data presented here are concordant with those of Ting
et al. (12) and support the concept that nifedipine is a logical
therapeutic agent for management of hypertension or of other
conditions (including cardiac failure and coronary disease in
older persons) in which the arterial system is stiffened and
wave reflection adds to the left ventricular load (24, 31, 34–
36). However, one caveat should be made in regard to the use
of short-acting nifedipine, such as used here—namely, the
decrease in vascular resistance may cause coronary steal and/
or tachycardia, which could worsen myocardial ischemia
(10). The ideal antihypertensive agent in isolated systolic
hypertension (37), and the ideal anti-anginal agent (10) may
be one which, like nitroglycerin, reduces wave reflection and
aortic systolic pressure while maintaining peripheral resistance and mean arterial pressure (10, 24, 33–35, 37, 38).
Long-acting nifedipine is comparable to an angiotensin converting enzyme inhibitor in efficacy and side effect profile
(39), and does not induce sympathetic stimulation and tachycardia as can the short-acting preparations used in this study.
沒有留言:
張貼留言