Neuromyogenic Properties of the Internal Anal Sphincter: Applications for the Treatment of Anal Fissures

Pharmacological therapy of anal fissures reduces maximum resting pressure (MRP), allowing healing by promoting anodermal vascular perfusion. In this thesis the clinical and manometric responses to diltiazem and botulinum toxin and the therapeutic potential of indoramin and salbutamol were investigated. A porcine internal anal sphincter model was developed to validate the responses to pharmacological agents. Of 33 patients with anal fissures with higher MRP than in 20 controls [110 (77-227) vs. 88 (46-175) cmH20 , P<0.05], the fissures healed in 19 (58%) after a two-month course of diltiazem, [110 (77-195) vs. 81 (53-147) cmH20, PO.OOOl]. Those with unhealed fissures [111 (77-227) vs. 92 (56-136) cmH20, PO.Ol] received another course. At four months in 18 (75%) of 20 the fissures healed; 12 [114 (88-195) vs. 113 (51-142) cmH20, P=0.07] that had healed initially and 6 [102 (77-227) vs. 109 (47-134) cmH20, P=0.50] of 8 after a second course. At six months the fissures healed in 13 (90%) of 15 patients [110 (77-144) vs. 125 (53-161) cmH20, P=0.63]. While 58% of fissures with high MRP healed with diltiazem, 42% did not despite reduction in MRP; a subgroup with normal MRP healed although MRP remained unchanged. A “no-needle” delivery, evaluated by injecting methylene blue in porcine anal sphincters allowed maximal instillation into the IAS at 60% to the horizontal axis, was employed to inject 25 Units botulinum toxin on either side of the fissure in 10 patients. At one week MRP [99 (71-185) vs. 81 (37-166) cmH20, PO.01] and pain scores [6 (3-8) vs. 4 (1-8), P<0.001] were reduced. At three months 5 (50%) fissures healed. Oral indoramin (20mg) reduced MRP at one hour in 10 volunteers [85 (46-136) vs. 63 (36-117) cmH20 , P<0.005] and 10 patients with anal fissures [131 (94-227) vs. 88 (57169) cmH20, P<0.0001] and the reduction was sustained for three hours. The results were similar with oral salbutamol (4mg) [94 (47-175) vs. 65 (44-101) cmH20, PO.01] and [144 (97-194) vs. 101 (78-181) cmH20, P<0.005]. Salbutamol caused tremors in 9