MECHANISMS OF VENOUS LEAKAGE - A PROSPECTIVE CLINICOPATHOLOGICAL CORRELATION OF CORPOREAL FUNCTION AND STRUCTURE

Purpose: We investigated the pathophysiology of structurally based cor poreal veno-occlusive dysfunction. Materials and Methods: We prospecti vely evaluated 24 impotent patients (mean age plus or minus standard e rror 46 +/- 3 years) who had exposure to vascular risk factors and/or disorders inducing diffuse trabecular structure alterations and who un derwent penile prosthesis insertion. Preoperative indexes of veno-occl usive function (flow to maintain, venous outflow resistance and pressu re decay measurements using repeat dosing pharmacocavernosometry) were correlated with postoperative erectile tissue computer assisted color histomorphometry (percent trabecular smooth muscle to total erectile tissue area). To develop further study findings and correlate histomor phometric findings with molecular biological properties molecular biol ogical studies (ribonuclease protection analysis, reverse transcriptio n-polymerase chain reaction assay for expression of transforming growt h factor-beta 1 messenger [m] ribonucleic acid [RNA] and protein affin ity labeling techniques for specific transforming growth factor-beta r eceptors) were performed in representative patients with high (39 to 4 3%), intermediate (30 to 37%) and low (13 to 29%) trabecular smooth mu scle content (normal 42 to 50%). Results: Flow to maintain, venous out flow resistance and pressure decay values significantly correlated wit h trabecular smooth muscle cell content (r = -0.89, 0.82 and -0.85, re spectively). In the high, intermediate and low smooth muscle content s ubgroups now to maintain, venous outflow resistance and pressure decay values were 1 to 5, 9 to 30 and 50 to 120 mi. per minute, 17 to 84, 3 to 9 and 1 to 2 mm. Hg/ml. per minute, and 40 to 60, 48 to 80 and 110 to 120 mm. Hg decrease in 30 seconds from 150 mm. Hg, respectively. T here were no significant differences in patient age or prevalence of r isk factors among the 3 subgroups. Patients representative of all 3 su bgroups had transforming growth factor-beta 1 mRNA, auto-induction of transforming growth factor-beta 1 mRNA and induction and/or increased availability of all 3 types of transforming growth factor-beta recepto rs. Conclusions: The pathophysiology of structurally based corporeal v eno-occlusive dysfunction is related to elevated corporeal connective tissue content. Based on our data and those in the literature corporea l fibrosis is hypothesized to develop secondary to abnormalities in th e regulation of normal collagen synthesis and degradation, most likely associated with adverse influences of chronic ischemia.