TY - JOUR
T1 - Pulmonary Responses to Selective Phosphodiesterase-5 and Phosphodiesterase-3 Inhibitors
AU - Matot, Idit
AU - Gozal, Yaacov
N1 - Funding Information:
This work was supported by grants from the Joint Research Fund of the Hebrew University and Hadassah Medical Organization, and the Chief Scientist, Israel Ministry of Health, Grant 4300.
PY - 2004/2
Y1 - 2004/2
N2 - 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 A2 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: These data show that zaprinast and milrinone exert a direct in vivo vasodilator effect on the PV bed at low (zaprinast) and elevated (zaprinast and milrinone) PV tone; however, at elevated PV tone, the pulmonary vasodilator effect was greater with zaprinast then with milrinone. This suggests that phosphodiesterase-5 inhibitors may potentially offer a therapeutic alternative in the management of acute pulmonary hypertension.
AB - 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 A2 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: These data show that zaprinast and milrinone exert a direct in vivo vasodilator effect on the PV bed at low (zaprinast) and elevated (zaprinast and milrinone) PV tone; however, at elevated PV tone, the pulmonary vasodilator effect was greater with zaprinast then with milrinone. This suggests that phosphodiesterase-5 inhibitors may potentially offer a therapeutic alternative in the management of acute pulmonary hypertension.
KW - Milrinone
KW - Phosphodiesterase inhibitor
KW - Pulmonary hypertension
KW - Thromboxane A
KW - Vasodilation
KW - Zaprinast
UR - http://www.scopus.com/inward/record.url?scp=1242284323&partnerID=8YFLogxK
U2 - 10.1378/chest.125.2.644
DO - 10.1378/chest.125.2.644
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C2 - 14769749
AN - SCOPUS:1242284323
SN - 0012-3692
VL - 125
SP - 644
EP - 651
JO - Chest
JF - Chest
IS - 2
ER -
