Characterization of age-related penile microvascular hemodynamic impairment using laser speckle contrast imaging: possible role of increased fibrogenesis.

Current technology for penile hemodynamic evaluations in small animals is invasive and has limitations. We evaluated a novel laser speckle contrast imaging (LSCI) technique to determine age-related changes in penile microvascular perfusion (PMP) and tested the role of cavernosal muscle (CC) fibrosis mediated by Wnt-TGF ß1 signaling pathways in a mouse model. Ten young (2-3 months) and old (24-28 months) wild-type C57BL6 male mice were subjected to PMP measured using a LSCI system. Penile blood flow (PBF, peak systolic velocity, PSV) was also measured using a color Doppler ultrasound for comparison. Measurements were made before and after injection of vasoactive drugs: prostaglandin E1 (PGE1) and acetylcholine (ACh). CC was processed for immunohistochemical studies for markers of endothelium and fibrosis. Protein levels were quantified by Western blot.PMP and PBF increased significantly from baseline after injection of vasoactive drugs. Peak PMP after PGE1 and ACh was higher in young mice (225.0 ± 12.0 and 211.3 ± 12.1 AU) compared to old (155.9 ± 7.1 and 162.6 ± 5.1 AU, respectively). PSV after PGE1 was higher in young than old mice (112.7 ± 8.5 vs. 78.2 ± 4.6 mm/sec). PSV after ACh was also higher in young (112.7 ± 5.6 mm/sec) than older mice (69.2 ± 7.1 mm/sec). PMP positively correlated with PSV (r = 0.867, P = 0.001). Immunostaining and Western blot showed increased protein expression of all fibrosis markers with aging. LSCI is a viable technique for evaluating penile hemodynamics. Increased cavernosal fibrosis may cause impaired penile hemodynamics and increased incidence of erectile dysfunction in older men.

The external anal sphincter operates at short sarcomere length in humans.

BACKGROUND: The length at which a muscle/sarcomere operates in vivo (operational length) and the length at which it generates maximal stress (optimal length) can be quite different. In a previous study, we found that the rabbit external anal sphincter (EAS) operates on the ascending limb of the length-tension curve, in other words at lengths shorter than its optimal length (short sarcomere length). In this study, we tested whether the human EAS muscle also operates at a short sarcomere length. METHODS: The length-tension relationship of the EAS muscle was studied in vivo in 10 healthy nullipara women. EAS muscle length was altered by anal distension using custom-designed probes of 5, 10, 15, and 20mm diameter. Probes were equipped with a sleeve sensor to measure anal canal pressure. The EAS muscle electromyograph (EMG) was recorded using wire electrodes. Ultrasound images of anal canal were obtained to measure EAS muscle thickness and anal canal diameter. EAS muscle stress was calculated from the anal canal pressure, inner radius, and thickness of the EAS muscle. KEY RESULTS: Rest and squeeze stress of the anal canal increased with the increase in probe size. Similarly, the change in anal canal stress, i.e. the difference between the rest and the squeeze, which represents the active contribution of EAS to the anal canal stress, increased with the increase in probe size. However, increase in probe size was not associated with an increase in the external anal sphincter EMG activity. CONCLUSIONS & INFERENCES: Increase in EAS muscle stress with the increase in probe size, in the presence of constant EMG (neural input), demonstrates that the human EAS muscle operates on the ascending limb of the length-tension curve or at low sarcomere lengths. We propose that surgically adjusting EAS sarcomere length may represent a novel strategy to treat fecal incontinence in humans.