Propofol對離體兔子心臟的直接作用

The Direct Cardiac Effect of Propofol on Intact Isolated Rabbit Heart

背景：Propofol在臨床使用日漸普及，但其低血壓作用仍是令人擔心的問題；近年來雖然已有多篇論文探討Propofol低血壓之機制，可能機制包括周邊阻力與心收縮力的抑制；但活體研究通常不易控制其他因子，如前負荷與血管阻力，甚至於可能受神經或賀爾蒙等影響致無法完全獨立探討；而離體模式則大部分以細胞為單位；目前已完整離體心臟模式Propofol濃度對心收縮力之影響之報告仍少。本研究以兔子的完整離體心臟模式（modified Langendorff Model），探討再不同濃度的Propofol灌注下對心臟收縮力及心率的直接作用。同時探討回復正常心率對心臟收縮力之影響。方法：第一階段（N=11）為利用兔子的離體心臟，藉由離體心臟冠狀動脈循環灌注不同濃度的Propofol（1, 5, 25, 50 mg/L）後，測量其左心室的壓力及收縮力（dp/dt單位時間內的壓力變化來表示）與心率。第二階段（N=7）除了給予不同濃度的Propofol灌注外，另外在完成不同濃度的Propofol灌注後，將兔子的心臟以心博控制器調整新率回基礎值，穩定後再紀錄左心室的壓力與收縮力，比較控制心率前後的差異。結果：左心室的壓力與收縮力與心率隨著給予Propofol的濃度增加而下降，尤其在給予高濃度（25和50 Mg/L）的情況下，達到顯著意義（P值小於0.05）。將兔子的心博速節律控制回基礎值後，發現左心室的壓力與收縮力並未跟著恢復。結論：Propofol隨著濃度的提高，心臟壓力及收縮力的抑制作用也會增強。另外，在給予Propofol高濃度下，也確實會降低心率。但，回復心率並無法回復心臟收縮力。

Background: The objective of the current study was to determine the direct effect of propofol on intact isolated rabbit heart using the modified Langendorff model. Methods: Eighteen rabbits were decerebrated under light ether anesthesia. Their hearts were then excised and prepared pursuant to the modified Langendorff model. Left ventricular pressure, left ventricular contractility (dp/ dt) and heart rate were recorded in the absence of propofol and in the presence of propofol of four different concentrations (1, 5, 25, 50 mg/L). In one group of hearts (N = 11) the heart rate was not paced. In another group of hearts (N = 7), the hearts were paced (during the control period and in propofol of each concentration) at a rate slightly higher than control rate and then allowed to revert to original state; pressure and contractility were measured and taken at both paced and unpaced rates. Results: In the unpaced group of hearts, a significant dose-dependent, negative effect on both left ventricular pressure and contractility was found at the two higher propofol concentrations (25 and 50 mg/L). A significant heart rate decrease was also revealed at these two concentrations. In the paced group, the left ventricular pressure and dp/dt also decreased significantly at higher propofol concentrations, and they did not return toward control values even though the heart was paced at the baseline unpaced rate. Conclusions: Propofol depressed left ventricular pressure and contractility and heart rate in a dose-dependent manner at higher concentrations. These negative cardiac effects were independent of changes in heart rate.