Purpose: Pharmacologic treatments are gaining widespread acceptance as first-line therapy for anal fissure. However, existing treatments have limited clinical usefulness because of side effects and incomplete healing rates.
Methods: Fresh human surgical resection specimens containing internal anal sphincter and rectal circular muscle were collected. Strips of smooth muscle were cut from each muscle group and mounted in a superfusion organ bath. The effects of increasing concentrations of phosphodiesterase inhibitors were evaluated.
Results: All phosphodiesterase inhibitors tested caused a dose-dependent reduction in the tone of the internal anal sphincter, with potencies as follows: vinpocentine (phosphodiesterase-1 inhibitor; 50 percent maximum inhibition concentration = 0.87 +/- 0.10 microM), erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (phosphodiesterase-2 inhibitor; 32 +/- 4.8 microM), trequinsin (phosphodiesterase-3 inhibitor; 0.28 +/- 0.041 microM), rolipram (phosphodiesterase-4 inhibitor; 63 +/- 9 microM), zaprinast (phosphodiesterase-1,5,6,9,11 inhibitor; 3 +/- 0.69 microM), and dipyridamole (phosphodiesterase-5,6,8,10,11 inhibitor; 5.5 +/- 2 microM). Although all inhibitors were also effective on rectal circular muscle strips, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride, trequinsin, and rolipram were at least an order of magnitude more potent in this tissue than in the internal anal sphincter.
Conclusions: There are several functionally important phosphodiesterases in the internal anal sphincter and rectal circular muscle. Both adenosine 3', 5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate appear to be important in the myogenic tone of the internal anal sphincter, and this study provides further evidence of the sphincteric specialization of this tissue. Phosphodiesterase inhibitors might represent a new therapy for the treatment of anal fissure.