Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism

Figures

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  Fig. 1.. Study design. Animals were anesthetized and instrumented before baseline evaluation. Pulmonary emboli were administered until doubling of pulmonary pressure from baseline. Animals were randomized to either levosimendan, milrinone, or dobutamine. For all inodilators, four logarithmically increasing doses were administered for 30 min each.

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  Fig. 2.. Cardiopulmonary effects of levosimendan, milrinone, and dobutamine in acute pulmonary embolism. Effects of inodilators are shown as absolute changes from PE time point. Different effects were noted on pulmonary pressure (a), despite each drug decreased calculated pulmonary vascular resistance (b), and increased cardiac output (c). Note the U-shaped curve of pulmonary to systemic resistance (d). Values are mean ± SD. n = 6 for each mean. Each p-value describes the overall test-for-trend. *p < 0.05, **p < 0.01, *** < 0.001 vs. PE. PE: pulmonary embolism.

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  Fig. 3.. Effects of inodilators on right ventricular function. Effects of inodilators are shown as absolute changes from PE time point. Levosimendan and milrinone consistently decreased end-systolic pressure (a) and increased ejection fraction (b) with no effects on pressure–volume area relative to end-diastolic volume, i.e. total mechanical work (d). On the contrary, dobutamine increased the end-systolic pressure and increased mechanical work as surrogate for oxygen consumption. All increased RV ventriculo–arterial coupling (c). Values are mean ± SD. n = 6 for each mean. Each p-value describes the overall test-for-trend. *p < 0.05, **p < 0.01, *** < 0.001 vs. PE. PE: pulmonary embolism.

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  Fig. 4.. Right ventricular pressure–volume loops. Representative right ventricular pressure–volume loops from baseline and after acute pulmonary embolism (top). Note the difference in shape where the normal right ventricle at baseline has a more triangular shape with pressure decrease during systolic ejection contrary to the end-systolic notch present after pulmonary embolism reflecting increased afterload. Levosimendan and milrinone cause left- and downward shift in pressure–volume loops, whereas dobutamine causes leftwards shift and increased pressure. For simplicity of the figure, only two doses are shown.