Therapeutic concepts for hypoxic pulmonary vasoconstriction involving ion regulation and the smooth muscle contractile apparatus.
Hypoxic pulmonary vasoconstriction (HPV) and pulmonary hypertension present a common and formidable clinical problem for practicing intensivists, thoracic, transplant, and trauma surgeons. The Redox Theory for the mechanisms of HPV has provided researchers with a new understanding of the etiology behind HPV that has opened the door to many new avenues of therapy for the disease. Potassium channels have been proposed to be the main mediator contributing to HPV, and treatment concepts that attempt to manipulate the function and number of those channels have been explored. Additionally, attempts to transfer genes that express the formation of specific potassium channels directly into pulmonary hypertensive lungs have proven to be very promising. Finally, 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. The purposes of this review are to: (1) briefly discuss some of the basic mechanisms that undergird HPV, including the Redox Theory for the mechanisms of HPV; (2) address current research involving treatments concepts related to ion channels; (3) report on research involving gene therapy to combat pulmonary hypertension; and (4) examine potential therapeutic avenues associated with inhibition of rho kinase.
Morrell
Eric D
ED
Sections of General and Cardiothoracic Surgery, Department of Surgery, Indiana University Medical Center, Indianapolis, IN 46202, USA.
Tsai
Ben M
BM
Crisostomo
Paul R
PR
Wang
Meijing
M
Markel
Troy A
TA
Lillemoe
Keith D
KD
Meldrum
Daniel R
DR
D006801:Humans; D000860:Hypoxia / Q000503:physiopathology* / Q000628:therapy*; D007473:Ion Channels / Q000378:metabolism*; D008168:Lung / Q000503:physiopathology*; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*
D007473:Ion Channels