PULMONARY-HYPERTENSION IN A MURINE MODEL OF THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME

Rapidly accumulating evidence suggests that a proportion of patients w ith acquired immunodeficiency syndrome (AIDS) develop hypertensive pul monary vascular disease reminiscent of primary pulmonary hypertension. As an initial step to explore the link between AIDS and hypertensive pulmonary vascular disease, the present study determined whether pulmo nary hypertension is present in a well-characterized murine model of r etrovirus-induced immunodeficiency. In agreement with previous reports , mice infected with the LP-BM5 murine leukemia virus developed polycl onal B and T cell activation followed by progressive and severe B and T cell immunodeficiency. At 12 wk postinfection, when persistent immun odeficiency was established, mice were anesthetized, and right ventric ular systolic pressure was determined in open-chest, mechanically vent ilated animals. Mean right ventricular systolic pressure was 14.7 +/- 1.3 mm Hg in control animals and was increased significantly to 22.5 /- 3.2 mm Hg in virus-infected mice. Right ventricular hypertrophy was also present in infected mice as evidenced by a 27% increase in the r atio of right to left ventricular weights; there were no group-depende nt differences in the left ventricular to total-body weight ratio. Mor phometric evaluation indicated that medial thickness in muscularized p ulmonary arteries, expressed as a percentage of the external diameter, was 9.6 +/- 0.4% in control lungs and increased to 14.4 +/- 0.5% in l ungs from infected animals. Qualitative histopathologic analysis sugge sted increased perivascular collagen deposition in lungs from infected animals relative to control animals. Unlike AIDS patients with pulmon ary hypertension, infected mice did not exhibit plexiform lesions or i ntimal fibrosis of the pulmonary arteries. Neither hematocrits nor art erial PO2 values differed between control and infected mice, indicatin g that chronic hypoxia did not contribute to the pulmonary hypertensiv e response to the virus. Compared with controls, lungs from infected m ice contained fourfold more lymphocytes, consisting primarily of CD4() T cells and B cells. Nearly 35% of the CD4(+) T cells were activated in virus-infected mice, whereas only 15% of this lymphocyte populatio n was activated in control mice. These findings suggest that a murine model of AIDS exhibits pulmonary hypertension that cannot be attribute d to chronic hypoxia and that is associated with substantial increases in the pulmonary immune cell population. This murine model maybe usef ul for delineating pathogenic mechanisms underlying pulmonary hyperten sion in the setting of AIDS.