Primary pulmonary hypertension (PPH) had been considered a uniformly fatal disease.

Primary pulmonary hypertension (PPH) had been considered a uniformly fatal disease. In the past several years, there have been several published reports forward new therapies for the treatment of PPH that appear to improve quality of life and survival. Data upon four such treatments regarding their efficacy and recommendations for their use will be reviewed.

ANTICOAGULANT THERAPY

In 1973 the World Health Organization held an international symposium upon PPH where the pathology of the disease was reviewed and characterized from three histologic subtypes.[1] single in kind of those sub-types, recurrent pulmonary thromboembolism, was derived from the observation that more [i]or[/i] less patients who die of PPH have in succession postmortem evidence of recanalized thrombotic lesions in their pulmonary arteriolar bed. Although it is no longer believed that returning microembolism is a cause of pulmonary hypertension, there is substantial evidence to recommend that thrombosis occurs in the pulmonary arteriolar utensils as an integral part of the pathophysiology of PPH Several large pathology series in succession PPH have documented the widespread neighborhood of these "classical thrombotic lesions" characterized as intravascular fibrous webs representing recanalized organized thrombi, either alone or in conjunction with plexogenic lesions.[2] The greatest in quantity common histologic abnormality, however, in patients with PPH is eccentric intimal fibrosis manifest as a crescentlike fibrous intimal cushion that causes luminal narrowing, which likely has as its origin vascular thrombosis and organization.

Biochemical studies also support the character of thrombosis in PPH. Structural changes in the pulmonary vascular endothelium have been associated with increased concentrations of factor VIII as well as abnormalities in the erection of circulating von Willebrand factor polymers[3] and increased concentrations of plasma fibrinopeptide A have been noted in the majority of patients with PPH indicating procoagulant activity.[4]

The clinical efficacy of anticoagulants as therapy of PPH however, has been difficult to assay A retrospective review of patients with PPH followed above a 15-year period suggested that those who received warfarin anticoagulant therapy had improved survival compared to those who did not.[5] More freshly the impact of warfarin therapy was investigated in patients with PPH who failed to rejoin to high doses of calcium blockers[6] A significant improvement in survival occurr in those patients who received anticoagulants, with a survival of 91 62 and 47 percent after 1 2 and 3 years compared to 52 31 and 31 percent respectively, in patients who were not receiving anticoagulants.

The effectiveness of warfarin anticoagulation in patients with PPH has not at any time been tested in a randomized prospective long-term trial. However, based upon available histologic, biochemical, and clinical data, it is reasonable to approve warfarin anticoagulant therapy to patients with PPH either alone or in combination with other treatment measures. It is our practice to use low-dose warfarin, as has been make acceptableed for prophylaxis of venous thromboembolism, controlling the INR to 15 to 25 times control

There remain important questions regarding the use of anticoagulant therapy in these patients. The choice for recommending low-dose warfarin is to minimize the risk of bleeding while still offering protection against thrombosis. What even of anticoagulation is most appropriate has not at any time been tested. In addition, whether there exists an ideal anticoagulant is also unknown. There are several reasons to believe that heparin, given its inhibitory events on smooth muscle cell proliferation, might be a more suitable anticoagulant in these patients.

CALCIUM CHANNEL BLOCKERS

Early reports forward the hemodynamic response to intravenous acetylcholine l to the belief that vasoconstriction of the pulmonary vascular bed is a major pathophysiologic mechanism in PPH The clinical rejoinder to a variety of vasodilators has been in like manner inconsistent, however, that is remains unclear as to what part vasoconstriction may be playing in any given patient. Calcium channel blocker have been the in the greatest degree widely tested class of put drugs intos in patients with PPH and appear to about a more consistent reduction in pulmonary artery influence and pulmonary vascular resistance than other vasodilators. lately we reported our experience in 64 patients with PPH who were evaluated with high doses of calcium channel blocker and followed for more than 5 years.[6] Twenty-six percent of the patients had large reductions in pulmonary artery constraining force and pulmonary vascular resistance which, on the subject of serial catheterization were maintained up to 5 years. More importantly, the quality of life was restored with improved functional class in these patients, and their survival was markedly improved (94 percent at 5 years) compared to nonresponders and historic have the direction of subjects (36 percent). This reflection showed for the first time that high doses of calcium blocker can improve quality of life and survival in a subset of patients with PPH

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