高血壓藥物在血壓波型特定諧頻的影響

Abstract

根據衛生署統計，高血壓性疾病及其有關的慢性病皆名列國人十大死因之中。對於血壓有效的控制可降低25%的心肌梗塞發生機率、40%的腦中風發生機率及50%的心衰竭發生機率。因此對於高血壓預防與治療始終是個重要的課題。正確的量測血壓是控制血壓的必要條件，一般常用在手臂或手腕上非侵入的量測方式代替較準確侵入式的動脈量測。但在一些高血壓藥的臨床實驗中也發現，量測週邊血壓會因量測造成誤判而用藥過量。本研究由徑向共振理論出發，以頻譜分析方式來分析脈波，探討年齡、不同藥理機制高血壓藥物在血壓波型特定諧頻的影響。 在對不同年齡受測者脈壓波形的頻譜分析中，我們定義Cn = An / A0，An為第n諧波大小，A0為脈壓波的平均值。分析結果A0與C1隨著年齡而增加， C3與C4隨著年齡增加而遞減。此諧波指標提供一個類似動脈反射波增強係數的評估指標，隨著年齡的改變而改變。對於老年高血壓或高血壓疾病的評估提供一個新的指標。在不同藥理機制高血壓藥物的研究中，我們利用自我比較的方式評估高血壓藥物對於同一隻老鼠血壓波形諧頻比例的影響。三種高血壓藥物皆能使大白鼠血壓下降，但對於能放鬆周邊血管的captopril與losartan同時還有C4上升的效應，而使心臟輸出減少的atenolol則無此效應，這些結果與這些高血壓藥物在人體的反應相同。此實驗確立可以正常血壓大白鼠作為評估高血壓藥物的動物模型，且證實C4與高血壓關聯。在中藥方天麻鉤藤飲(TGY)的研究裡，同時也採用自發性高血壓鼠(SHR)及atenolol來當作對照組。從實驗結果可發現TGY能降低正常血壓鼠的血壓、心率，同時降低血壓波型的各個諧波，其效用類似atenolol，而且有濃度反應。對於SHR則在降壓的同時也升高C2至C4，這也說明中藥方的優點，在解除症狀的同時也能修補有缺陷的器官系統。最後，在加強補肺中藥的新配方實驗中可發現，血壓在餵藥後有顯著的下降。而舒張壓下降的比例較收縮壓多，以及C4顯著的增加，證實當初的推論，以中醫補肺的方式來降低舒張壓，在改善整體循環(增加諧頻比例)後，能有效的降低血壓。 本研究提出一套可用於評估高血壓藥物的方式與指標，以及可應用在高血壓治療的中藥方，在未來還需有更多的臨床試驗來證實其效用。

According to the report of the Department of Health, hypertension and its complications have long been the main causes of mortality in our society. Antihypertensive therapy has been associated with reductions in myocardial infarction for 25 percent, stroke incidence for 40 percent and heart failure for 50 percent. therefore the prevention and treatment of hypertension is always an important issue. The accurate measurement of blood pressure (BP) is the sine qua non for successful management. The radial or brachial pressure is commonly used as a noninvasive index to measure BP instead of central aortic pressure. However, in some clinic trial of vasodilator treatments, the BP measured on the peripheral radial artery often overestimates that measured on the central artery. This study which is based on the resonance theory evaluates the aging and antihypertensive drugs effect on pressure pulse waveform by harmonic analysis. In the study of the age-related changes in specific harmonic indices of pressure pulse waveform, we defined the harmonic proportions (Cn) as the ratio of the amplitude of the n-th harmonic (An) to the mean value of the pressure pulse (A0). A0 and C1 increased but C3 and C4 decreased with ageing. These results suggest these harmonic indices could be similar to AI which corresponds to the pressure pulse waveform affected from ageing. The harmonic indices could be clinically useful in non-invasive cardio risk assessing for the elderly patients. In the study of the effects of antihypertensive drugs, we used a self-comparison method and harmonic analysis to compare the BP wave before and after the injection of antihypertensive in normotensive Wistar Kyoto (WKY) rats. BP decreased significantly after the injection of each of these drugs. Atenolol significantly reduced all the harmonic proportions of the pulse wave, while captopril and losartan significantly increased C4. These findings are the same as those reported for human subjects and confirm that the animal model and harmonic analysis of the pressure pulse is a useful method to study the efficacy of antihypertensive drugs. In the study of the effects of the Chinese herbal formula Tian Ma Gou Teng Yin (TGY), the respective effects of atenolol and TGY in WKY and spontaneously hypertensive rats (SHR) were studied for comparison. TGY which was similar to atenolol decreased the BP, heart rate and all of the Cn values in WKY. In contrast, TGY decreased the BP and increased C2, C3 and C4 at the same time in SHR. These results show that the Chinese herb formula can improve the circulation in weak organs. At last in the study of the new formula, BP was decreased significantly after feeding new formula. The diastolic blood pressure decreased more then that of the systolic blood pressure and C4 was increased significantly. These results prove the hypothesis that to lower blood pressure by enhancing the lung meridians in traditional Chinese medicine. In this study we present a procedure and indices to evaluate the effect of antihypertensive drugs and new Chinese herb formula for hypertension treatment. In the future, more clinic test would be done for proving the curative effect of the new formula.