Novel approach with intratracheal administration of microgelatin hydrogel microspheres incorporating basic fibroblast growth factor for rescue of rats with monocrotaline-induced pulmonary hypertension.
OBJECTIVE
Pulmonary hypertension is a life-threatening disease, and alternative strategies are essential for patients with critical pulmonary hypertension. We developed a new procedure using microgelatin hydrogel microspheres incorporating basic fibroblast growth factor (mGHMs/bFGF) for intratracheal administration and evaluated the effect of a single intratracheal administration of mGHMs/bFGF on rats with monocrotaline-induced pulmonary hypertension.


METHODS
Monocrotaline was injected into 54 rats simultaneously with intratracheal administration of plain mGHMs (vehicle group), bFGF in solution form (free-bFGF group), mGHMs/bFGF (mGHMs/bFGF group), and plain saline with subcutaneous injection of saline instead of monocrotaline (control group, n = 18). Three weeks after the administration, 48 rats (n = 12 from each group) were subjected to hemodynamic and histologic evaluations. Survival was assessed in 6 rats of each group 10 weeks after the intratracheal administration.


RESULTS
The mGHMs/bFGF group showed significantly lower right ventricular/left ventricular pressure ratios at 3 weeks than the vehicle and free-bFGF groups (0.35 +/- 0.04, 0.54 +/- 0.11, 0.58 +/- 0.21, and 0.36 +/- 0.05 for the control, vehicle, free-bFGF, and mGHMs/bFGF groups, respectively; P < .01). Histologically, the mGHMs/bFGF group had a significantly higher number of vessels (diameter > or = 50 microm) than the other groups (5.3 +/- 2.6, 4.6 +/- 2.8, 7.3 +/- 2.5, and 18.9 +/- 7.0 vessels/mm(2), respectively; P < .01). Ten weeks after the intratracheal administration, 6 (100.0%) rats had survived in the control group, and 1 (16.7%) survived in the vehicle, 0 (0%) in the free-bFGF, and 5 (83.3%) in the mGHMs/bFGF groups (n = 6 each).


CONCLUSIONS
A single intratracheal administration of mGHMs/bFGF increased the number of vessels in the lung and ameliorated survival and hemodynamics in rats with monocrotaline-induced pulmonary hypertension.
Hirose
Keiichi
K
Department of Cardiovascular Surgery, Shizuoka Children's Hospital, Shizuoka, Japan.
Marui
Akira
A
Arai
Yoshio
Y
Kushibiki
Toshihiro
T
Kimura
Yu
Y
Sakaguchi
Hisashi
H
Yuang
Huang
H
Chandra
B I R Shyamal
BI
Ikeda
Tadashi
T
Amano
Shigeru
S
Tabata
Yasuhiko
Y
Komeda
Masashi
M
D000818:Animals; D001784:Blood Gas Analysis; D001835:Body Weight; D018450:Disease Progression; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005780:Gelatin / Q000008:administration & dosage*; D006439:Hemodynamics; D020100:Hydrogels / Q000008:administration & dosage*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D008168:Lung / Q000378:metabolism; D008297:Male; D008863:Microspheres; D016686:Monocrotaline; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea
D020100:Hydrogels; D016222:Fibroblast Growth Factor 2; D016686:Monocrotaline; D005780:Gelatin