Experimental therapies for hypoxia-induced pulmonary hypertension during acute lung injury.
Hypoxic pulmonary vasoconstriction (HPV) and pulmonary hypertension present a common and formidable clinical problem for practicing thoracic, transplant, and trauma surgeons. The recent discovery of efficacious drugs that are selective for the pulmonary vasculature has brought about the potential for very powerful therapeutic agents. Inhaled nitric oxide (NO) therapy has already found broad clinical utility, yet its use is limited by potential toxicities. Rho kinase (ROK) has been discovered to play a very central role in the formation of hypoxia induced pulmonary hypertension, and the advent of very specific ROK inhibitors has shown positive clinical results. Finally, phosphodiesterase-5 inhibitors have been found to selectively vasodilate the pulmonary vasculature in the midst of HPV. The purposes of this review are to: 1) discuss the advantages and disadvantages of inhaled preparations of NO; 2) address experimental alternatives to inhaled preparations of NO to treat HPV; 3) explore potential therapeutic avenues associated with inhibition of Rho-kinase; and, 4) examine the use of phosphodiesterase-5 (PDE-5) inhibitors and combination therapy in the treatment of HPV.
Section of Cardiothoracic Surgery, Department of Surgery, Indiana University Medical Center, Indianapolis, Indiana.
Eric D
ED
Morrell
Ben M
BM
Tsai
Paul R
PR
Crisostomo
Zane T
ZT
Hammoud
Daniel R
DR
Meldrum
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology* / Q000628:therapy*; D000860:Hypoxia / Q000150:complications*; D011652:Pulmonary Circulation; D012128:Respiratory Distress Syndrome / Q000150:complications*; D014661:Vasoconstriction / Q000502:physiology*; D014665:Vasodilator Agents / Q000627:therapeutic use
D014665:Vasodilator Agents