Association Between Inflammatory Mediators and Pulmonary Blood Flow in a Rabbit Model of Acute Pulmonary Embolism Combined With Shock

Abstract

Background The pro-inflammatory cytokines were detected in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) tissues to explore the role of inflammation responses and their relationship with the pulmonary blood flow in a rabbit model of acute pulmonary embolism combined with shock. Methods and Results Nineteen rabbits were randomly divided into sham operation group (S group, n = 8) and massive PE (MPE group, n = 11). The MPE model was established by injecting the autologous blood clots into the main pulmonary artery of rabbit. Pulmonary angiography showed that the pulmonary circulation time was significantly prolonged in the MPE group, and pulmonary blood flow was attenuated at 120 min post PE. Hematoxylin–eosin (HE) staining revealed enhanced inflammatory cell infiltration around the pulmonary vessels in PE and non-PE tissues, and obvious edema on the perivascular region. Meanwhile, the expressions of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg-1) in pulmonary vascular and alveolar tissues were significantly upregulated and the iNOS/Arg-1 ratio was significantly higher in the MPE group than in the S group. Moreover, the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were also significantly increased in PE and non-PE tissues, and interleukin-6 (IL-6) level was significantly increased in non-PE tissues in the MPE group as compared to the S group. Thromboxane A2 (TXA 2 ) and alpha smooth muscle actin (α-SMA) levels were significantly higher in both PE and non-PE tissues in the MPE group than in the S group. Conclusion Activation of inflammation mediators in PE and non-PE tissues might be one of the crucial factors responsible for pulmonary vasculature constriction and pulmonary blood flow attenuation in this MPE model.

Effects and related mechanism of alpha-adrenergic receptor inhibitor phentolamine in a rabbit model of acute pulmonary embolism combined with shock

“…The pulmonary circulation time was measured as previously described, by calculating the time taken for the contrast medium to reach from the initiation site of the pulmonary artery trunk to the left atrium through the pulmonary artery trunk and branches, pulmonary capillary, and pulmonary vein. The pulmonary circulation time was calculated for all of the survived rabbits at 120 min after the moment of successfully modeling, which was designed as the study end [ 6 ].…”

“…All rabbits were fasted food and water for the preoperative experiments, and were anesthetized with the 3% sodium pentobarbital anesthesia (20 mg/kg) through the ear vein. After the anesthetization, the rabbit was fixed on the operating table with the supine position and connected to the cardiogram monitor (LEAD-7000, Sichuan Jinjiang Electronic Technology Co. China) [4][5][6].…”

“…The Seldinger puncturing method was used to puncture the femoral artery and the femoral vein, which 5F sheath tubes (Radio focus TERUMO) were placed, respectively. Under X perspective, the 4F Cordis sheath was inserted into to the main trunk of the pulmonary artery for real-time monitor of pulmonary artery for real-time monitor of mean pulmonary arterial pressure (MPAP) [4][5][6]. Mean arterial pressure (MAP) was detected by femoral artery sheath.…”

“…APE model was established and autologous blood clots were prepared according to the methods described in our previous studies [4][5][6]. Briefly, a plastic tube with an inner diameter of 4 mm and length of 20 cm was used to collect 5 mL of autologous venous blood via the femoral vein sheath.…”

“…It is known that APE induced by obstruction of a small percentage of pulmonary vascular trees can cause marked reduction of whole pulmonary blood flow [3], which suggests that non-embolized lung tissues are also involved in mediating the failure of pulmonary blood flow in APE. Our previous study showed that hyperactivation of sympathetic nerve and the sharp decline of pulmonary blood flow in the non-embolized lung tissue served as important factors contributing to hemodynamic collapse of pulmonary circulation and systemic circulation in rabbit APE model combined with shock [4][5][6]. It is well known that tyrosine hydroxylase (TH) catalyzes the synthesis of norepinephrine (NE); the latter can regulate pulmonary vessels tone via stimulating α receptor on the vascular smooth muscle cells.…”