Effect of stellate block on vasomotor factor, vascular endothelial nitricoxide synthase and pulmonary arterial pressure in rabbits with hypoxic pulmonary artery hypertension*

Abstract

Background At present, inhalation of nitrogen monoxidum (NO) or other angiotenic is widely used to cure hypoxic pulmonary artery hypertension. In addition, recent researches demonstrate that postganglionic fiber of stellate ganglion can regulate contents of blood vessel endothelium-calcitonin gene-related peptide (BVE-CGRP) and nitricoxide synthase (NOS) in lung tissue. Therefore, stellate ganglion which is blocked with the local anesthetic may cause therapeutic effects on hypoxic pulmonary artery hypertension. Objective To observe the effects of stellate block on calcitonin gene-related peptide (CGRP) of vasodilation factors, prostacyclin, endothelin-1 of vasoconstriction factors, thromboxan, blood vessel endothelium-nitricoxide synthase (BVE-NOS) and mean arterial pressure of lung tissue in rabbits with hypoxic pulmonary artery hypertension. Design Randomly controlled animal study. Setting Neurological Institute of Taihe Hospital Affiliated to Yunyang Medical College. Materials A total of 24 adult Japanese rabbits of both genders and weighing 2.3–2.6 kg were provided by Animal Experimental Center of Hubei Academy of Medical Science. SP kit was provided by Beijing Zhongshan Biotechnology Co., Ltd.; moreover, kits of endothelin-1, CGRP, prostacyclin and thromboxan were provided by Radioimmunity Institute, Scientific and Technological Developing Center, General Hospital of Chinese PLA, and color image analytical system (Leica-Q500IW) was made in Germany. Methods The experiment was carried out in the Neurological Institute of Taihe Hospital affiliated to Yunyang Medical College from February to December 2002. ▪ Rabbits were performed with aseptic manipulation to exposure left stellate ganglion and then it was put in epidural catheter for 1 week. In addition, one end of epidural catheter was fixed near by stellate ganglion and the other end was fixed through dorsal neck. All rabbits were randomly divided into 4 groups, including normal control group, stellate block group, hypoxia group and hypoxia + stellate block group, with 6 in each group. Rabbits in the normal control group were perfused with saline through epidural catheter with 0.5 mL once for three times per day and 3 successive days in total; in addition, rabbits in the stellate block group were perfused with 2.5 g/L bupivacaine through epidural catheter with 0.5 mL once for three times per day and 3 successive days in total. Rabbits in the hypoxia group were used to establish hypoxic pulmonary artery hypertension models. That was to say, the experimental rabbits were put in hypoxic box (containing sodalime and calcium chloride to absorb CO2 and water) and given various flows of oxygen and nitrogen through the two lateral wells simultaneously. And then, oxygen was monitored with oxygen-concentration monitoring device to control the concentration in (10±2)% for 8 hours per day and 2 successive weeks in total. Rabbits in the hypoxia + stellate block group were used to establish hypoxia models as the same as those in the hypoxia group. Two weeks later, 2.5 g/L bupivacaine was pushed into epidural catheter with 0.5 mL once for three times per day and 3 successive days in total. Breast was directly opened to measure mean pulmonary artery pressure. ▪ 6 mL blood was collected through pulmonary arterial duct to measure levels of plasma CGRP, prostacyclin, endothelin-1 and thromboxane with radio-immunity technique; meanwhile, immunohistochemical staining was used to observe the changes of BVE-NOS content of the experimental rabbits in all groups. Main outcome measures Changes of CGRP, prostacyclin, endothelin-1 and thromboxane and BVE-NOS. Results A total of 24 experimental rabbits were involved in the final analysis. ▪ As compared with those in the normal control group, hypoxic pulmonary artery hypertension of the experimental rabbits was higher in the hypoxia group and hypoxia + stellate block group after hypoxia [(3.84±0.30), (3.16±0.45), (2.60±0.27) kPa, P < 0.05, 0.01]; CGRP was lower [(68.20±8.78), (108.24±14.35), (130.25±22.70) ng/L, P < 0.05, 0.01]; prostacyclin was lower [(94.45±10.68), (98.77±12.31), (155.27±20.67) ng/L, P < 0.01]; endothelin-1 was higher [(184.74±29.66), (115.27±13.62), (98.20±11.52), ng/L, P < 0.05, 0.01]; thromboxan was higher [(226.27±30.46), (207.67±27.32), (124.25±16.89) ng/L, P < 0.01]. As compared with that in hypoxia group, hypoxic pulmonary artery hypertension was decreased in hypoxia + stellate block group (P < 0.05), CGRP was increased ( P < 0.01), and endothelin-1 was decreased remarkably ( P < 0.05). ▪ Level of BVE-NOS of the experimental rabbits was higher in stellate block group, hypoxia group and hypoxia + stellate block group than that in the normal control group [(0.25±0.06), (0.27±0.07), (0.46±0.12), (0.14±0.03), P < 0.05], and NOS level was higher in the hypoxia + stellate block group than that in hypoxia group ( P < 0.05). Conclusion Mean arterial pressure is decreased in rabbits with hypoxic pulmonary artery hypertension after stellate block and level of endothelin-1 is also decreased; however, levels of CGRP and NOS are increased respectively.