肺高压2012xiong.ppt

* * * * * * * * * * * * * What is the optimal treatment strategy? For patients with a negative acute vasodilatory test, it is helpful to start with an assessment of our patients’ risk profiles. This slide is an algorithm of treatment options based on assessment of a patient’s risk status. Thus, CCBs must NOT be used without initially demonstrating that pts have a true acute vasoreactivity to a short-acting vasodilator in the cath lab (adenosine, NO, IV epo) And the response is not a subtle one. Pts with a reasonable chance of having a clinical response to CCBs go a long way toward normalizing their hemodynamics with acute testing– it is not just a small decrement in mPA pressure or 5% drop in PVR. Three major categories of therapy are now approved for treatment of PAH. These therapies target endothelial cell dysregulation and smooth muscle cell tone and proliferation. Three major pathways are involved: The endothelin pathway The nitric oxide pathway, including PDE5 inhibitors that enhance NO-mediated vasodilation. The prostacyclin pathway The earliest clinical trials demonstrating benefit of intervention in PAH studied the effect of prostacyclin. Prostacyclin derivatives are now available as well. Prostacyclin therapy restores beneficial cAMP-mediated effects altered by impaired prostaglandin I2 synthesis: Vascular smooth muscle cell relaxation, antiproliferation, antiinflammation, and antiplatelet effects. Prostacyclin and prostacyclin analogues are available in intravenous (IV), subcutaneous (SC), and inhaled formulations. These drug delivery systems are complex. IV epoprostenol and treprostinil require a chronic indwelling central venous catheter, usually a tunneled catheter exiting the left upper or right upper chest wall. Potential complications: infection (blood stream, tunnel, or exit site infection), thrombosis, accidental removal, device malfunction. SQ trepostinil Treprostinil, a prostacyclin analogue, has a longer half-life (approximately 4.5