Sielaff T D, Kellum J M, Sugerman H J, Kuemmerle J F, Tatum J L
J Surg Res. 1987 Aug;43(2):118-27. doi: 10.1016/0022-4804(87)90153-3.
The effects of the serotonin receptor blocker, ketanserin, were studied in a porcine Pseudomonas adult respiratory distress syndrome model. Swine, weighing 14-30 kg, were anesthetized and ventilated with 0.5 FiO2 and 5 cm H2O positive end expiratory pressure. Three groups were studied: saline control (C, n = 9), continuous intravenous Pseudomonas aeruginosa, 5.0 X 10(8)CFU/kg/min (Ps, n = 8), and Pseudomonas and intravenous ketanserin, 0.2 mg/kg, given at 20 and 120 min after the onset of the Pseudomonas infusion (KET, n = 5). Pulmonary arterial (PAP) and systemic arterial (SAP) pressures, cardiac index (CI), thermal Cardio-Green extravascular lung water (EVLW), pulmonary albumin flux (slope index, SI), arterial blood gases, and whole blood serotonin levels were measured and pulmonary shunt and pulmonary (PVRI) and systemic (SVRI) vascular resistance indices were calculated. At 3 hr the Ps group demonstrated significant (P less than 0.05) increases in PAP (34 +/- 1 vs C 13 +/- 2 mm Hg), EVLW (14.4 +/- 2.2 vs C 4.3 +/- 1.2 ml/kg), SI (2.05 +/- 0.23 X 10(-3) vs C 0.38 +/- 0.09 X 10(-3) U/min), pulmonary shunt (67 +/- 15% vs C 9 +/- 3%), PVRI (1599 +/- 89 vs C 184 +/- 14 dyn X sec X cm-5/m2), and SVRI (4542 +/- 774 vs C 2087 +/- 129 dyn X sec X cm-5/m2) and decreases in CI (0.9 +/- 0.1 L/min/m2 vs C 2.8 +/- 0.2 L/min/m2), PaO2 (93 +/- 17 Torr vs C 203 +/- 15 Torr) and arterial blood serotonin concentration (23.5 +/- 13% decrease from basal). Treatment with ketanserin was associated with maintenance of PaO2 (KET 207 +/- 5 mm Hg vs C 203 +/- 15 mm Hg), pulmonary shunt (KET 8 +/- 3% vs C 9 +/- 3%), and CI (KET 2.3 +/- 0.1 L/min/m2 vs C 2.8 +/- 0.2 L/min/m2) at control levels and attenuated the Pseudomonas-induced increase in PVRI (873 +/- 37 vs Ps 1599 +/- 89 dyn X sec X cm-5/m2) and SVRI (2089 +/- 287 vs Ps 4542 +/- 774 dyn X sec X cm-5/m2), but did not alter the development of pulmonary edema. These data indicate that serotonin plays a role in the development of the V/Q mismatch and arterial hypoxemia observed in this model by a mechanism independent of changes in microvascular injury and permeability and was probably a result of reduced peripheral bronchiolar constriction.
在猪的成人呼吸窘迫综合征模型中研究了5-羟色胺受体阻滞剂酮色林的作用。体重14-30千克的猪被麻醉，并以0.5的吸入氧分数（FiO2）和5厘米水柱的呼气末正压通气。研究了三组：生理盐水对照组（C组，n = 9）、持续静脉输注铜绿假单胞菌，5.0×10⁸CFU/千克/分钟（Ps组，n = 8），以及在铜绿假单胞菌输注开始后20分钟和120分钟静脉注射酮色林0.2毫克/千克（KET组，n = 5）。测量肺动脉（PAP）和体动脉（SAP）压力、心脏指数（CI）、热Cardio-Green血管外肺水（EVLW）、肺白蛋白通量（斜率指数，SI）、动脉血气和全血5-羟色胺水平，并计算肺分流以及肺（PVRI）和体循环（SVRI）血管阻力指数。3小时时，Ps组显示PAP（34±1对比C组13±2毫米汞柱）、EVLW（14.4±2.2对比C组4.3±1.2毫升/千克）、SI（2.05±0.23×10⁻³对比C组0.38±0.09×10⁻³单位/分钟）、肺分流（67±15%对比C组9±3%）、PVRI（1599±89对比C组184±14达因×秒×厘米⁻⁵/平方米）和SVRI（4542±774对比C组2087±129达因×秒×厘米⁻⁵/平方米）显著（P<0.05）升高，而CI（0.9±0.1升/分钟/平方米对比C组2.8±0.2升/分钟/平方米）、动脉血氧分压（PaO2）（93±17托对比C组203±15托）和动脉血5-羟色胺浓度（较基础值降低23.5±13%）降低。酮色林治疗使PaO2（KET组207±5毫米汞柱对比C组203±15毫米汞柱）、肺分流（KET组8±3%对比C组9±3%）和CI（KET组2.3±0.1升/分钟/平方米对比C组2.8±0.2升/分钟/平方米）维持在对照水平，并减轻了铜绿假单胞菌诱导的PVRI（873±37对比Ps组1599±89达因×秒×厘米⁻⁵/平方米）和SVRI（2089±287对比Ps组4542±774达因×秒×厘米⁻⁵/平方米）升高，但未改变肺水肿的发展。这些数据表明，5-羟色胺通过一种独立于微血管损伤和通透性变化的机制，在该模型中观察到的通气/血流比值失调和动脉低氧血症的发展中起作用，并且可能是外周细支气管收缩减少的结果。
