Abstract | OBJECTIVE: To compare the direct pulmonary vasodilating activity and specificity of phosphodiesterase-5 ( zaprinast) and phosphodiesterase-3 ( milrinone) inhibitors on the pulmonary vascular (PV) bed of the spontaneously breathing cat with an intact chest. DESIGN: Prospective, randomized animal study. SETTING: Laboratory of university hospital. SUBJECTS: Experiments were performed in vivo in intact-chest, spontaneously breathing cats with controlled pulmonary blood flow and constant left atrial pressure. INTERVENTIONS: The responses to intralobar injections of zaprinast and milrinone were investigated at low PV tone. PV tone was then increased by intralobar arterial infusion of a thromboxane A(2) mimic, U46619. Animals received intralobar bolus injections of zaprinast or milrinone, followed by continuous IV infusion of the drug, which was administered in incremental doses titrated to produce a 20% reduction in mean systemic arterial pressure. MEASUREMENTS AND MAIN RESULTS: At low PV tone, zaprinast, but not milrinone, decreased lobar arterial pressure (LoAP). At elevated PV tone, both drugs caused dose-dependent decreases in LoAP; however, milrinone caused significantly less pulmonary vasodilation. Dose-related decreases in mean systemic arterial pressure were observed with milrinone, but not with zaprinast. When the continuous IV infusion was titrated to produce a 20% reduction in mean systemic arterial pressure, the decreases in lobar arterial pressure with zaprinast infusion were significantly greater than those produced by milrinone. CONCLUSIONS:
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Authors | Idit Matot, Yaacov Gozal |
Journal | Chest
(Chest)
Vol. 125
Issue 2
Pg. 644-51
(Feb 2004)
ISSN: 0012-3692 [Print] United States |
PMID | 14769749
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Purinones
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
- Phosphoric Diester Hydrolases
- 3',5'-Cyclic-AMP Phosphodiesterases
- Cyclic Nucleotide Phosphodiesterases, Type 3
- 3',5'-Cyclic-GMP Phosphodiesterases
- Cyclic Nucleotide Phosphodiesterases, Type 5
- zaprinast
- Milrinone
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Topics |
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
- 3',5'-Cyclic-AMP Phosphodiesterases
(pharmacology)
- 3',5'-Cyclic-GMP Phosphodiesterases
- Analysis of Variance
- Animals
- Cats
- Cyclic Nucleotide Phosphodiesterases, Type 3
- Cyclic Nucleotide Phosphodiesterases, Type 5
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Female
- Hypertension, Pulmonary
(drug therapy)
- Infusions, Intravenous
- Injections, Intralesional
- Male
- Milrinone
(pharmacology)
- Phosphoric Diester Hydrolases
(pharmacology)
- Probability
- Pulmonary Circulation
(drug effects, physiology)
- Purinones
(pharmacology)
- Random Allocation
- Risk Factors
- Sensitivity and Specificity
- Vascular Resistance
(drug effects)
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