The hpyertrohpy observed in the study that was called ‘the long awaited evidence’ is likely a pathologic smooth muscle hypetrophy. Not only no increase in size of the the penis, but also significative risks of structural changes of penile architecture and so potential ED.
No such significative structural changes with viagra et similars are observed (no smooth muscle hypertrophy/hyperplasia) because they don’t cause an high degree of smooth muscle pathologic changes.
Cytotoxicity of different intracavernous vasoactive drugs on cultured endothelial cells of human corpus cavernosum penis.
Schultheiss D, Pilatz A, Gabouev AI, Schlote N, Wefer J, Mertsching H, Sohn M, Jonas U, Stief CG.
bstract
OBJECTIVES:
To investigate the cytotoxic effect of prostaglandin E(1) (PGE(1)), a standard combination of papaverine/phentolamine, and a triple mixture of these agents on human cavernosal endothelial cells using a cell culture model. The endothelial layer of the corpus cavernosum plays an important role in signal transduction of penile erection and is directly exposed to vasoactive agents after intracavernous injection for erectile dysfunction.
METHODS:
Primary endothelial cells were obtained from the corpus cavernosum of 13 potent patients undergoing penile surgery. Cultured cells were exposed for 30 minutes to physiologic dilutions of 20 microg PGE(1), 30 mg papaverine/1 mg phentolamine, or the same dosages of the triple mixture of these agents, each dissolved in 5 to 50 mL sodium chloride. Lactate dehydrogenase release as a cytotoxicity marker was measured 6 hours after drug exposure, and the total cell metabolic activity was quantified after 48 hours with a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)-based assay. Additionally, the amount of viable cells was identified with a dual fluorescent staining procedure.
RESULTS:
The initial release of lactate dehydrogenase was elevated up to 3.2-fold in the concentrated papaverine/phentolamine and triple mixture group compared with PGE(1) and the control. After 48 hours, the papaverine-containing formulations led to a significant dose-dependent decrease in the viable cell count and metabolic activity of the cultures that was not noticed with PGE(1).
CONCLUSIONS:
These in vitro data strongly suggest an unfavorable effect of vasoactive agents containing papaverine on cavernosal endothelial cells. Before fibrotic changes of the smooth muscle stroma, the functionally important endothelium of the corpus cavernosum might suffer significantly from intracavernous injection therapy.
Therefore, papaverine should no longer be used for this indication.
Cytotoxicity of different intracavernous vasoactive drugs on cultured endothelial cells of human corpus cavernosum penis - PubMed
In vitro viability of human cavernosal endothelial and fibroblastic cells after exposure to papaverine/phentolamine and prostaglandin E1
OBJECTIVE
To investigate the influence of commercially available vasoactive drugs on human cavernosal endothelial and fibroblastic cells in vitro, as although corporal fibrosis is a well known side-effect of intracavernosal injection therapy for erectile dysfunction, the possible detrimental effect of these agents on the endothelium lining the cavernosal vascular spaces is uncertain.
MATERIALS AND METHODS
Cultured primary endothelial (13) and fibroblastic cells (12), obtained from potent patients undergoing penile surgery, were exposed to different physiological dilutions of prostaglandin E1 (PGE1), papaverine/phentolamine or the respective triple-mix of these agents for 30 min. Viable cells were counted and cell metabolic activity measured in these cultures 48 h after drug exposure.
RESULTS
There was a significant dose-dependent decrease in the viable cell count after exposure to papaverine-containing formulations, probably because of the low pH of this substance. This cytotoxic effect was more pronounced in endothelial than in fibroblastic cells, and was not apparent in the PGE1 groups. The relative increase in cell metabolic activity in cultures affected by a moderate cytotoxic effect indicated a regenerative process.
CONCLUSION
These comparative results in endothelial and fibroblastic cell cultures suggest that the endothelium rather than the interstitium of the corpus cavernosum is more sensitive to side-effects produced by intracavernosal injection therapy with papaverine. Thus, unfavourable consequences on the function of the endothelial layer might be as important as the risk of interstitial fibrosis. As these effects were not detected for PGE1 this drug should be preferred to papaverine in clinical practice.
http://onlineli brary.wiley.com … 5499.x/abstract
Long term and/or high doses intracevernous injections of prostaglandin is not without risks either:
"Sequential penile ultrasound monitoring of patients treated with chronic intracavernous prostaglandin e1
Abstract
Objectives
Clinical outcome studies of prostaglandin E1 (PGE1) have shown a markedly decreased rate of palpable fibrosis and plaque formation. In this prospective study we investigate the potential of this agent to produce subclinical fibrotic changes.
Methods
Real-time high-resolution ultrasound scanning of the corpora was performed using a 7.5 to 10 MHz linear array transducer in 80 men on initiation of treatment with self-administered PGE1 and at quarterly intervals during the course of follow-up (3 to 28 months). The dorsal portion of the penile shaft was scanned in the transverse and sagittal planes from base to glans for a side by side comparison of the cavernosal tissue, evaluating local abnormalities of tissue echogenicity.
Results
Palpable lesions were not detected in any men on quarterly follow-up examination. Thirteen (16.5%) men developed new echogenic foci not present on pretreatment scanning at the following locations: proximal corpus cavernosum, subcutaneous tissues, and corpus spongiosum. These changes were observed both as single and multiple lesions ranging in size from 1 to 10 mm. The presence of these findings was independent of the etiology of impotence, dose frequency, and duration of intracavernous therapy.
Conclusions
The significance of these subclinical changes is unknown but their low incidence should be recognized when considering long-term intracavernous therapy.
http://www.gold journal.net/art … 0127-7/abstract