ALTERATIONS IN COLONIC SMOOTH-MUSCLE FUNCTION IN CATS WITH IDIOPATHICMEGACOLON

Objective-To determine whether colonic smooth muscle dysfunction is in volved in the pathogenesis of idiopathic megacolon in cats. Design-In vitro smooth muscle mechanical measurements. Animals-Colon from health y cars and cars with idiopathic megacolon. Procedure-Colonic smooth mu scle strips were suspended in physiologic buffer solution, attached to isometric force transducers, and contracted with acetylcholine (ACh; 10(-9) to 10(-4)M), substance P (SP; 10(-10) to 10(-6)M), cholecystoki nin (CCK; 10(-11) to 10(-6)M), potassium chloride (KCl; 10 to 80 mM), or electrical field stimulation (EFS; 25 V, 1 to 30 Hz, 0-5-millisecon d duration). Isometric stress responses were compared with those obtai ned from healthy controls. Colonic smooth muscle strips were also eval uated histologically for neuronal and smooth muscle cell morphology. R esults-Passive isometric stress was not altered, but the active isomet ric stress responses of megacolon smooth muscle to ACh, SP, CCK, KCl, and EFS were significantly (P < 0.05) diminished, compared with health y controls. Differences were observed in longitudinal and circular smo oth muscle from proximal and distal portions of the colon. Histologic evaluation revealed few abnormalities of smooth muscle cells or of mye nteric or submucosal plexus neurons. The contractile response of megac olon smooth muscle to EFS, and the inhibition of this response by tetr odotoxin, suggest that myenteric and submucosal plexus neurons in mega colon smooth muscle are functional. Conclusions-Idiopathic megacolon i s a generalized dysfunction of colonic smooth muscle in cats. The dimi nished isometric stress responses to receptor occupancy (ACh, SP, and CCK) and membrane depolarization (KCl) further suggest that the disord er involves disturbance in the activation of smooth muscle myofilament s.