UTHR--a detailed description of the problem they are trying to treat:
<<What is primary pulmonary hypertension?
Primary pulmonary hypertension is a disease that affects the pulmonary vascular bed and results in sustained pulmonary hypertension for which there is no apparent cause. The incidence of PPH ranges from 1-2 cases per 1 million people in the general population, but it is increased in patients with portal hypertension and HIV infection, and with the use of appetite suppressants. Six percent of the 186 cases of PPH described in the National Institutes of Health registry were familial. The pathogenesis of PPH has several components, including vasoconstriction, intimal proliferation, and thrombosis in situ. Pulmonary vascular endothelial function is believed to be impaired.
The most common presenting symptom is dyspnea, which eventually occurs in nearly every patient as the disease progresses. PPH is a diagnosis of exclusion, so other secondary forms of pulmonary hypertension must be ruled out. Important diagnostic studies when PPH is suspected include the electrocardiogram, chest x-ray, echocardiogram, ventilation perfusion scan, and pulmonary function tests. At times more extensive testing, including pulmonary angiography and a high resolution chest computed tomogram are indicated. A cardiac catheterization is necessary to confirm the diagnosis, establish its severity, and test the patients response to vasodilators.
How is primary pulmonary hypertension treated?
Anticoagulants
Thrombosis in situ is believed to be integral to the pathogenesis of PPH. Anticoagulant therapy has been investigated in patients with PPH and is associated with improved survival. Although the effectiveness of warfarin anticoagulation in patients with PPH has never been tested in a randomized, prospective, long-term trial, based on the known pathogenesis of PPH and the available data, we recommend the use of low-dose warfarin with an international normalized ratio of 1.5 to 2.5 times control as therapy for PPH.
Calcium Channel Blockers
Vasoconstriction is important in the pathogenesis of PPH. Although many drugs have been used for vasodilation in the setting of PPH, calcium channel blockers have been the most widely tested class of drugs for this purpose, and they appear to produce a more consistent reduction in pulmonary artery pressure and pulmonary vascular resistance that other vasodilators. Approximately 25% of patients with PPH will respond to calcium channel blockers.
Prostacyclin
Prostacyclin is a metabolite of arachidonic acid that is produced primarily in the vascular endothelium. Its major pharmacologic actions include potent vasodilatation of the pulmonary and systemic arterial and venous beds and inhibition of platelet aggregation. Prostacyclin is administered through a permanent intravenous catheter and delivered by an ambulatory infusion system. The delivery system is complex and requires patients to learn the techniques of sterile preparation, operation of the pump, and care of the intravenous catheter.
Others
Diuretics are frequently required to reduce excessive edema in patients with right heart failure. they are particularly useful when hepatic congestion, ascites, and edema are present. Digoxin can increase cardiac output and reduce circulating neurohormones. Patients with hypoxemia, either at rest or with exercise, should receive supplemental oxygen. Because of increased cardiovascular stress, pregnancy is generally poorly tolerated by patients with PPH.
Heart and Lung Transplantation
Bilateral lung transplantation and single-lung transplantation have been performed successfully in patients with PPH. The immediate reduction in pulmonary artery pressure and pulmonary vascular resistance is associated with an improvement in right ventricular function. Bilateral lung transplantation is preferred at most centers, because there is greater pulmonary vascular reserve if the patient sustains rejection or infection. Single lung transplantation may be preferred in some situations because the operation is technically less challenging and the waiting time is shorter. As with any type of organ transplantation, the major long-term morbidity and mortality are related to the high incidence of rejection and opportunistic infections. In addition, lung transplantation carries a high risk of the development of bronchiolitis obliterates. In the era of prostacyclin, lung transplantation should be considered a treatment of last resort for PPH.>>
Source: rush.edu
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