Effect of amrinone during group B Streptococcus-induced pulmonary hypertension in piglets.
Intravenous infusion of group B Streptococcus (GBS) into neonatal animals produces pulmonary hypertension, ventilation/perfusion (VA/Q) mismatch, and an increase in serum levels of thromboxane B2 (TxB2) and tumor necrosis factor (TNF) alpha. The vasodilator amrinone (amr) is a cGMP-inhibited phosphodiesterase inhibitor and is reported to inhibit thromboxane A2 and TNF production. We hypothesized that infusion of amr would cause pulmonary vasodilation and reduce serum TxB2 and TNF levels in piglets with late phase GBS-induced pulmonary hypertension. The effect of amr on gas exchange was also determined. A continuous infusion of GBS was administered for 5 hr to 4 groups of anesthetized, mechanically ventilated neonatal piglets. An amr bolus of 8 mg/kg was given at 4 hr followed by a 1 hr continuous infusion of either 10 or 20 micrograms/kg/min of amr (amr 10 and amr 20, respectively). Control piglets received a bolus and 1 hr infusion of amr carrier. The infusion of amr, but not of carrier reversed late phase GBS-induced pulmonary hypertension. Piglets infused with amr 20 showed transient selective pulmonary vasodilation, based on a reduced ratio of pulmonary to systemic vascular resistance (PVR/SVR ratio) value at 30 min but not at 1 hr, compared to pre-amr treatment values. The PVR/SVR ratio values for amr 10 and control group did not change after treatment with either amr or carrier. Treatment with amr 10 or 20 did not decrease serum TxB2 or TNF levels or increase VA/Q mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)
Berger
J I
JI
Department of Pediatrics, RD-20, University of Washington School of Medicine, Seattle 98195.
Gibson
R L
RL
Clarke
W R
WR
Standaert
T A
TA
Redding
G J
GJ
Henderson
W R
WR
Truog
W E
WE
D000676:Amrinone / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology*; D011651:Pulmonary Artery / Q000503:physiopathology; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D013290:Streptococcal Infections / Q000150:complications*; D013292:Streptococcus agalactiae; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014655:Vascular Resistance / Q000187:drug effects; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects
D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D000676:Amrinone