Serotonin receptor blockade improves cardiac output and hypoxia in porcine ARDS.
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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects*; D004195:Disease Models, Animal; D006633:Histamine Antagonists / Q000627:therapeutic use; D000860:Hypoxia / Q000188:drug therapy*; D007650:Ketanserin / Q000627:therapeutic use; D011549:Pseudomonas; D011985:Receptors, Serotonin / Q000187:drug effects*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D012701:Serotonin / Q000097:blood; D012702:Serotonin Antagonists / Q000627:therapeutic use; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D006633:Histamine Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin