Why the study?
To observe the effect and mechanism of the alpha-adrenergic receptor inhibitor phentolamine in a rabbit model of acute pulmonary embolism combined with shock.
Does phentolamine improve hemodynamics and down-regulate alpha-adrenergic signaling in a rabbit model of acute pulmonary embolism combined with shock?
Does phentolamine improve hemodynamics and down-regulate alpha-adrenergic signaling in a rabbit model of acute pulmonary embolism combined with shock?
Phentolamine improves pulmonary and systemic circulation failure in a rabbit model of acute pulmonary embolism with shock by down-regulating alpha-adrenergic receptor signaling.
May improve hemodynamics in rabbit APE-shock models; leaves open human translation pending clinical trials.
Background To observe the effect and mechanism of alpha-adrenergic receptor inhibitor phentolamine (PTL) in a rabbit model of acute pulmonary embolism (APE) combined with shock. Methods Twenty-four New Zealand rabbits were randomly divided into sham operation group (S group, n = 8), model group (M group, n = 8) and PTL group ( n = 8), the model of APE combined with shock was established. Mean pulmonary arterial pressure (MPAP), peripheral mean arterial pressure (MAP) and pulmonary circulation time were evaluated. The expression levels of α 1 receptor, α 2 receptor and their downstream molecules in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions lung tissues were detected and compared, respectively. Results In M group, α receptor-related signaling pathways were significantly activated in both PE and non-PE areas as expressed by up-regulated α 1 , α 2 receptor and phospholipase C (PLC); the expression level of phosphorylated protein kinase A (p-PKA) was significantly down-regulated; myosin light chain kinase (MLCK) and α-smooth muscle actin (α-SMA) levels were up-regulated. PTL treatment significantly improved pulmonary as well as systemic circulation failure: decreased MPAP, restored blood flow in non-PE area, shortened pulmonary circulation time, increased MAP, and restored the circulation failure. PTL induced significantly down-regulated expression of α 1 receptor and its downstream molecule PLC in both PE and non-PE area, the expression level of α 2 receptor was also down-regulated, the expression level of p-PKA was significantly up-regulated. PTL treatment can inhibit both α 1 and α 2 receptor-related signaling pathways in whole lung tissues, and inhibit Ca 2+ signaling pathways. The expression level of MLCK and α-SMA were significantly down-regulated. Compared with PE area, the changes of expression levels of α receptor and its downstream molecules were more significant in the non-PE region. Conclusion In this model of APE combined with shock, the sympathetic nerve activity was enhanced in the whole lung, α 1 and α 2 receptor and their downstream signaling activation might mediate blood flow failure in the whole lung. PTL treatment can effectively restore pulmonary blood flow in non-PE area and improve pulmonary as well as systemic circulation failure possibly through down-regulating α 1 and α 2 receptor and their downstream signaling pathways.
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Wang et al. (2022) studied this question.
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