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J Thorac Cardiovasc Surg 2008;136:1250-1256
© 2008 The American Association for Thoracic Surgery
Cardiopulmonary Support and Physiology |
a Department of Cardiovascular Surgery, Shizuoka Children's Hospital, Shizuoka, Japan
b Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
d Department of Laboratory Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
c Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
Received for publication September 30, 2007; revisions received March 28, 2008; accepted for publication May 9, 2008. * Address for reprints: Masashi Komeda, MD, PhD, Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. (Email: komelab{at}kuhp.kyoto-u.ac.jp).
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 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
50 µm) than the other groups (5.3 ± 2.6, 4.6 ± 2.8, 7.3 ± 2.5, and 18.9 ± 7.0 vessels/mm2, 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.
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