Burkhard von Heyden

Intracavernous Pharmacotherapy for Impotence: Selection of Appropriate Agent and Dose

We performed a retrospective analysis of 101 impotent patients using intracavernous self-injections as primary therapy for vasculogenic impotence. A total of 70 patients used an average of 5.58 micrograms prostaglandin E1 (95% confidence interval 4.83 to 6.34 micrograms) as a single agent, and 31 injected 0.40 ml. (95% confidence interval 0.342 to 0.457 ml.) of a combination of papaverine (12 mg./ml.), phentolamine (1 mg./ml.) and prostaglandin E1 (9 micrograms/ml.). We describe the procedure to establish the dosage for home use and discuss the implications of the low dosages relative to previous reports.

Can a venous patch graft be a substitute for the tunica albuginea of the penis

We describe our experience with plaque excision and placement of a venous patch graft. Sprague Dawley rats (n = 20) underwent excision of a wedge of tunica albuginea with the defect covered by a segment of detubularized femoral vein, endothelial side towards the cavernous tissue. Erectile function, as determined by the rise in intracavernous pressure with cavernous nerve stimulation (mean 54.0 +/- 4.2 cm. H2O), was equal to that in a group of 10 intact age-matched controls (mean 46.9 +/- 3.37 cm. H2O). Penile cross-sections stained with Harts elastic fiber stain or Trichrome stain revealed only minimal fibrosis in the region of the patch. In 3 dogs, a wedge of tunica was removed, and the defect was covered with a segment of detubularized deep dorsal vein. When sacrificed at 3 months, all animals had retained their erectile function with histologic evidence of minimal fibrosis. On the basis of histologic and functional data, the venous patch appears to be a reasonable alternative substance to those in common use.

A Prostaglandin E1 Dose-Response Study in Man

Because prostaglandin E1 causes erection by smooth muscle relaxation in a receptor-dependent manner, one would expect increasing dosages to cause a progressively greater response and that, at receptor saturation, further increases would not be beneficial. To test this hypothesis a single-blind, placebo-controlled study of increasing dosages of prostaglandin E1 injected intracavernously was done. In 16 men with vasculogenic impotence erections were monitored by the RigiScan device in real time for 2 hours after injection, and rigidity, tumescence and duration of erection were measured. Summary parameters to characterize erection with each dosage were developed: maximal rigidity, maximal rigidity sustained for 30 minutes and duration of greater than 60% rigidity. The dose-response curve was similar for all 3 parameters. The initial response to escalating doses of prostaglandin E1 from 2.5 to 20 micrograms. demonstrated a steep dose-dependent increase; at greater than 20 micrograms. a plateau was reached, indicating a nonlinear response. More than 80% of the patients attained the maximal response at doses of 20 micrograms. or less and less than 20% benefited from a further increase. Based on these results, the effects of prostaglandin E1 appear to be receptor-dependent and prostaglandin E1 monotherapy for impotence could be limited to 20 micrograms. or less, since larger amounts offer little additional benefit.

Neurotransmitters in the human urethral sphincter in the absence of voiding dysfunction

Abstract The purpose of this study was to elucidate the neuroregulation of sphincteric relaxation by investigating the density of nerves containing acetylcholine, noradrenaline, neuropeptide Y (NPY), galanin, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) in the urethral sphincter in patients without a voiding disorder. The complete urethral sphincter (from the bladder neck to beyond the striated external sphincter) was excised from four male and four female adult cadavers and one male and one female fetus. In transverse paraffin or cryostat sections, the above transmitters were identified by histochemical methods. The striated sphincter was densely innervated by cholinergic nerves. Adrenergic nerves next to striated fibers were rare, but were present in all patients. NPY was seen rarely along striated fibers. In the smooth sphincteric component, noradrenaline-, acetylcholine-, NPY- and galanin-reactive nerves were observed frequently. Only functional studies can clarify the clinical implications of these results. Judging from NPYs scarcity in the striated sphincter no efferent function is anticipated. In the smooth component the frequent appearance of NPY, galanin and noradrenaline suggests a regulatory role for these transmitters.

The Latissimus Dorsi Muscle for Detrusor Assistance: Functional Recovery after Nerve Division and Repair

The treatment of choice for bladder atonia is clean intermittent catheterization. To eliminate the catheter-related morbidity and increase the quality of life for patients with an atonic bladder, the restoration of bladder contractility would be desirable. Based on our hypothesis that skeletal muscle might augment bladder contractility, we designed the present study to examine the ability of the latissimus dorsi muscle in situ to empty a bladder-like reservoir and to regenerate after division and repair of the supplying motor nerve. In 4 dogs, the left latissimus dorsi muscle was dissected, mobilized and wrapped around a bladder substitute (100-ml. silicone reservoir). Stimulation of the thoracodorsal nerve resulted in the evacuation of 63.8 +/- 6.2% of the reservoirs volume and a maximum pressure of 109.5 +/- 18.6 cm. H2O. Four months later, the thoracodorsal nerve supplying motor control to the muscle was transected and microsurgically reanastomosed. Using transcutaneous stimulation, we recorded the pressure generation and resulting evacuation at regular intervals for 8 months (that is, 12 months after the initial surgery). At the end of this period, the pressure was 79.3 +/- 12.1 cm. H2O (72.4% of the initial value), expelling 48.3 +/- 6.7% of total volume. This long-term study demonstrates: (1) the ability of the transposed latissimus dorsi muscle to evacuate a bladder-like reservoir; and (2) the regenerative potential of muscle and nerve after nerve transsection and repair. Use of skeletal muscle, which can be readily stimulated, may serve to facilitate bladder emptying and provide a treatment alternative to intermittent catheterization in the future.

Urethral Relaxation After Electrostimulation in the Guinea Pig is Independent of Nitric Oxide

PURPOSE To investigate whether the relaxation of the striated urethral sphincter in guinea pigs is mediated by nitric oxide. MATERIALS AND METHODS After sacrifice, urethral rings were cut between the bladder neck and the penile crura and mounted in an in vitro bath. Maximal isometric tension obtained at 1, 3, 10 and 25 Hz electrical stimulation (Tmax) for 5 to 30 sec was measured. RESULTS Tmax at 25 Hz was not changed by pretreatment with 10(-4)M nitroprusside or 10(-4)M NG-nitro-L-arginine. In urethral tissue precontracted with 10(-4)M noradrenaline, a significant relaxation of 16-25% was found at 10 Hz. This relaxation could not be prevented by pretreatment with 10(-4)M NG-nitro-L-arginine and was not enhanced by the presence of 10(-3)M L-arginine. CONCLUSION Noradrenaline-precontracted urethral rings of male guinea pigs exhibit a maximal relaxation at 10 Hz, which does not depend on nitric oxide.

In vitro electrostimulation-induced urethral relaxation in the guinea pig is blocked by prazosin

The purpose of this study was to characterize the electrostimulation‐induced relaxation in guinea pig urethral rings. From sacrificed male guinea pigs, urethral rings were cut between the bladder neck and the penile crura and mounted in an in vitro bath. The drop in baseline tension in response to electrical stimulation (rectangular pulses of 0.8‐msec pulse duration, a frequency of 3, 5, 10, and 20 Hz, and 75‐mA current) was measured in the presence of various pharmacologic agents. In urethral tissue precontracted with 10−5 norepinephrine, a significant relaxation of 34.8% was found at 10 Hz. This relaxation was not affected by the addition of neuropeptide Y (NPY, 10−8–10−6 M), 10−6 M atropine, 10−5 M α‐β‐methylene‐adenosine,5′‐triphosphate (α‐β‐methylene‐ATP, a purinergic antagonist), and tolazoline (α2 antagonist, 10−8–10−4 M). However, with the α−1 antagonist prazosin (5 × 10−8–5 × 10−7 M), no relaxation occurred. The tissue response was of neurogenic origin as it was blocked by 10−7 M tetrodotoxin. Norepinephrine‐precontracted urethral rings of male guinea pigs exhibit a relaxation response at 10 Hz that is α1‐adrenergic, non‐cholinergic, non‐purinergic, and independent of NPY. Neurourol. Urodynam. 18:33–39, 1999.