【摘要】：目的研究強心苷類正性肌力代表藥去乙酰毛花苷與非強心苷類正性肌力代表藥米力農的心血管動力學作用特點,分析其長期使用死亡率差別的可能機制。方法 1大鼠在體壓力-容積環(huán)分析:經左側頸外靜脈緩慢推注去乙酰毛花苷0.17 mg·kg~(-1)或米力農0.78 mg·kg~(-1),Miller導管記錄大鼠壓力-容積環(huán)變化及動脈壓。2大鼠離體心臟左心室收縮壓測定:實驗按正常灌流液→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。3大鼠心肌細胞鈣釋放測定:測定去乙酰毛花苷或米力農各10μmol·L~(-1)加藥前后鈣釋放。結果 1在體實驗表明:去乙酰毛花苷顯著增加大鼠動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;延長動脈收縮壓回復50%的時間;縮短主動脈瓣關閉時間(P0.05)。米力農顯著降低大鼠動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、射血分數(shù)、輸出量、心率、心室收縮末期壓與舒張彈性;縮短心室內壓及動脈收縮壓回復50%的時間(P0.05)。2兩者均能濃度依賴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,而米力農增加心率(P0.05)。3兩者均能增加大鼠心肌細胞鈣釋放幅值,米力農還能縮短鈣回吸收時間(P0.05)。結論去乙酰毛花苷具有正性肌力作用,而對外周阻力無明顯影響。米力農發(fā)揮正性肌力作用,但有明顯的擴張血管作用,且明顯增加心率;這些作用可能是米力農長期使用導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)藥大學藥學院國家科技部規(guī)范化中藥藥理實驗室;南京軍區(qū)總醫(yī)院干部病房呼吸科;南京中醫(yī)藥大學第一附屬醫(yī)院(江蘇省中醫(yī)院)心臟內科;泰州中國醫(yī)藥城中醫(yī)藥研究院;
【基金】：2014年度江蘇省高校自然科學研究重大項目(14KJA360002) 江蘇省自然科學基金(BK20151355);江蘇省自然科學基金(BK20131262) 泰州中國醫(yī)藥城第四批次高層次創(chuàng)新人才“113人才計劃”(2016024)~~
【分類號】：R965
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本文編號：2436266