Platelet-activating Factor Induces Selective Pulmonary Arterial Hyperreactivity in Isolated Perfused Rabbit Lungs

Abstract

The role of vasoreactivity in PAF-induced pulmonary hypertension (PHT) was assessed in isolated, perfused rabbit lungs. We evaluated the steady-state pulmonary vascular response to five vasoconstrictors: PGF2 alpha, norepinephrine, angiotensin II, PAF, and KCl. Pulmonary arterial pressure and pulmonary vascular resistance (PVR) were significantly greater in lungs of rabbits treated with PAF for 28 days than in control rabbits in response to PGF2 alpha and norepinephrine. When resistance was partitioned by the vascular occlusion method, at baseline the vascular resistance was equally distributed between arterial and venous segments in both experimental groups. Arterial resistance accounted for approximately 76% of PVR during norepinephrine injection and 60% of PVR during PGF2 alpha injection in PAF-treated lungs. Whereas arterial resistance accounted for approximately 63% of PVR during norepinephrine injection and 52% of PVR during PGF2 alpha injection in control lungs, there was no significant difference in the response to angiotensin II, acute PAF, and KCl in lungs from chronic PAF-treated rabbits compared with responses in control rabbit lungs, though the pressor response to acute PAF tended to be blunted in PAF-treated lungs. Chronic PAF treatment results in enhanced pulmonary arterial reactivity to selected autacoids in isolated perfused lungs.

Implantable Left Ventricular Assist Devices

“…68 Tumor necrosis factor a can induce pulmonary hypertension, 69 and its effect may be mediated by platelet-activating factor, 70,71 a potent vasoconstrictor of the pulmonary circulation. 72,73 Thromboembolism Historically, thromboembolic events occurred in about 20 percent of patients receiving a left or right ventricular assist device. 33 In a more recent multicenter study, 74 the total thromboembolic event rate was 0.01 per patient-month of device use among 223 patients supported with a Heartmate left ventricular assist device over a total support time of 531 patient-months.…”

Upregulation of Postbacteremic TNF- α and IL-1 α Gene Expression by Alveolar Hypoxia/Reoxygenation in Perfused Rat Lungs

“…A carotid artery was cannulated with PE-50 tubing through which the animals were exsanguinated following anticoagulation with sodium heparin (500 U intravenously). The lungs were aseptically harvested via a sternotomy and cannulation of the main pulmonary artery by a PE-280 polyethylene catheter (17). Lung perfusion with preoxygenated perfusate (P O 2 Ͼ 100 mm Hg, see below ) was begun at an initial rate of ‫ف‬ 5 ml/min.…”

“…Perfusions were in the recirculating mode in a temperature-controlled (37.0 Ϯ 3 Њ C) humidified plexiglass cabinet by a peristaltic pump (Masterflex; Cole Parmer, Chicago, IL) from a venous reservoir through a bubble trap and into the pulmonary artery (17). Flow rates (18-20 ml/min) were confirmed in each experiment by timed collection of perfusates.…”

“…H 2 O. Perfusates were freshly prepared by adding 10 mM glucose, canine serum (5% vol/vol; endotoxin content, Ͻ 5 pg/ml) for bacterial opsonization (12,13,18); penicillin (100 U/L), and streptomycin (0.1 mg/ml). After adding low-endotoxin bovine serum albumin (4% wt/vol, lot #L588404; Intergen, Newark, NJ) to maintain oncotic pressure (17) and pharmacy-grade polymyxin B sulfate (Roerig Pfizer, New York, NY) in a final concentration of 25 ng/ml to neutralize albumin-associated endotoxin, perfusates were filtered (0.22 m). The endotoxin content of perfusates prior to circuit priming was Ͻ 0.2 ng/ml by the Limulus assay.…”

“…After sample collection and double occlusion measurements at t ϭ 180 min, time-dependent changes in each preparation were evaluated by the response of the pulmonary vasculature to the vasoconstrictor PGF 2␣ (Sigma). A positive response was taken to be a rise in mean Ppa of у 5 mm Hg over 1-3 min after a 300 g bolus infusion (17). In certain experiments, lungs were then airway-fixed with cacodylatebuffered glutaraldehyde for 30 min at a transpulmonary pressure of 20-22 cm H 2 O, followed by fixation in glutaraldehyde overnight at 5Њ C (4).…”