Novel approach with intratracheal administration of microgelatin hydrogel microspheres incorporating basic fibroblast growth factor for rescue of rats with monocrotaline-induced pulmonary hypertension

Objectives: 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 ofmGHMs/bFGF on ratswith 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 >= 50 mu m) 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.