【摘要】：目的研究強(qiáng)心苷類(lèi)正性肌力代表藥去乙酰毛花苷與非強(qiáng)心苷類(lèi)正性肌力代表藥米力農(nóng)的心血管動(dòng)力學(xué)作用特點(diǎn),分析其長(zhǎng)期使用死亡率差別的可能機(jī)制。方法 1大鼠在體壓力-容積環(huán)分析:經(jīng)左側(cè)頸外靜脈緩慢推注去乙酰毛花苷0.17 mg·kg~(-1)或米力農(nóng)0.78 mg·kg~(-1),Miller導(dǎo)管記錄大鼠壓力-容積環(huán)變化及動(dòng)脈壓。2大鼠離體心臟左心室收縮壓測(cè)定:實(shí)驗(yàn)按正常灌流液→0.01→0.1→1μmol·L~(-1)濃度梯度灌流去乙酰毛花苷,或正常灌流液→0.1→1→10μmol·L~(-1)灌流米力農(nóng)。3大鼠心肌細(xì)胞鈣釋放測(cè)定:測(cè)定去乙酰毛花苷或米力農(nóng)各10μmol·L~(-1)加藥前后鈣釋放。結(jié)果 1在體實(shí)驗(yàn)表明:去乙酰毛花苷顯著增加大鼠動(dòng)脈壓與心室收縮末期壓、心輸出量、搏出功、心室收縮末期壓最大上升速率和心室收縮彈性;降低舒張彈性及心室收縮末期容積;延長(zhǎng)動(dòng)脈收縮壓回復(fù)50%的時(shí)間;縮短主動(dòng)脈瓣關(guān)閉時(shí)間(P0.05)。米力農(nóng)顯著降低大鼠動(dòng)脈壓與室收縮末期壓、降低心室收縮及舒張末期容積、搏出功;增加每搏輸出量、射血分?jǐn)?shù)、輸出量、心率、心室收縮末期壓與舒張彈性;縮短心室內(nèi)壓及動(dòng)脈收縮壓回復(fù)50%的時(shí)間(P0.05)。2兩者均能濃度依賴(lài)性地增加離體大鼠心臟收縮的發(fā)展力及收縮壓最大上升速率,但去乙酰毛花苷減慢心率,而米力農(nóng)增加心率(P0.05)。3兩者均能增加大鼠心肌細(xì)胞鈣釋放幅值,米力農(nóng)還能縮短鈣回吸收時(shí)間(P0.05)。結(jié)論去乙酰毛花苷具有正性肌力作用,而對(duì)外周阻力無(wú)明顯影響。米力農(nóng)發(fā)揮正性肌力作用,但有明顯的擴(kuò)張血管作用,且明顯增加心率;這些作用可能是米力農(nóng)長(zhǎng)期使用導(dǎo)致死亡率增加的原因。
[Abstract]:Aim to study the cardiovascular dynamic characteristics of deacetythrin, a positive inositive agent of cardiac glycosides, and milrinone, a non-cardiosides positive inotropic drug, and to analyze the possible mechanism of the difference in mortality between long-term use of amrinone. Methods 1in vivo pressure-volume loop analysis: deacetylinoside 0.17 mg kg~ (- 1) or milrinone 0.78 mg kg~ (- 1) was slowly injected into the left external jugular vein. The changes of pressure-volume ring and arterial pressure were recorded by Miller catheter. 2 the systolic pressure of left ventricle in isolated rat heart was measured by perfusion of deacetythrin at the concentration of 0. 01 to 0. 1 渭 mol 路L ~ (- 1) in normal perfusate. [WT5 "HZ] [WT5" BZ] [WT5BZ] Results 1Deacetyloside significantly increased arterial pressure, ventricular end systolic pressure, cardiac output, pulsatile work, maximal rise rate of ventricular end systolic pressure and ventricular systolic elasticity in rats. Reduce diastolic elasticity and ventricular end systolic volume; prolong arterial systolic pressure recovery time by 50%; shorten aortic valve closure time (P0.05). Milrinone significantly decreased arterial pressure and end-systolic pressure, reduced ventricular systolic and diastolic volumes, and increased stroke output, ejection fraction, output, heart rate, ventricular end-systolic pressure and diastolic elasticity, as well as ventricular systolic and diastolic volume, and increased stroke output, ejection fraction, output, heart rate, ventricular end-systolic pressure and diastolic elasticity. (2) both of them could increase the contractility of isolated rat heart in a concentration-dependent manner and the maximal increase rate of systolic blood pressure, but deacetyloside slowed down the heart rate, but deacetyloside decreased the heart rate in a concentration-dependent manner. While milrinone increased the heart rate (P0.05). 3 both of them could increase the amplitude of calcium release from rat cardiac myocytes, and milrinone could shorten the calcium absorption time (P0.05). Conclusion Deacetyloside has positive inotropic effect, but has no obvious effect on peripheral resistance. Milrinone plays a positive inotropic role, but has a significant vasodilating effect and significantly increases heart rate, which may be the cause of the increase in mortality caused by long-term use of milrinone.
【作者單位】： 南京中醫(yī)藥大學(xué)藥學(xué)院國(guó)家科技部規(guī)范化中藥藥理實(shí)驗(yàn)室;南京軍區(qū)總醫(yī)院干部病房呼吸科;南京中醫(yī)藥大學(xué)第一附屬醫(yī)院(江蘇省中醫(yī)院)心臟內(nèi)科;泰州中國(guó)醫(yī)藥城中醫(yī)藥研究院;
【基金】：2014年度江蘇省高校自然科學(xué)研究重大項(xiàng)目(14KJA360002) 江蘇省自然科學(xué)基金(BK20151355);江蘇省自然科學(xué)基金(BK20131262) 泰州中國(guó)醫(yī)藥城第四批次高層次創(chuàng)新人才“113人才計(jì)劃”(2016024)~~
【分類(lèi)號(hào)】：R965
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本文編號(hào)：2436266