The dose-response of canine focal gastric mucosal blood flow to misoprostol.
We studied the dose-response of focal gastric mucosal blood flow measured simultaneously by laser-Doppler flowmetry and hydrogen gas clearance in the canine chambered gastric segment to topical misoprostol (0.1, 1.0, 10, 100, and 1000 micrograms in 10 ml of 150 mM NaCl for two 15-min periods per dose). Simultaneously obtained mucosal blood flow values showed a highly significant linear correlation (r = 0.63, n = 20, p less than 0.01) in the basal but not misoprostol periods between the two techniques. Laser-Doppler flowmetry measured a dose-dependent increase in blood flow (Emax = 6.4 +/- 2.8 V at the 100-micrograms dose; equivalent to 92.8% increase above the basal mean blood flow value; ED50 = 1.0 micrograms). Peak increase in blood flow by laser-Doppler flowmetry after dosing was attained in 6.1 +/- 0.7 min and maintained for 1.9 +/- 0.3 min. In contrast, hydrogen gas clearance showed a gradual decline in blood flow after misoprostol administration throughout all experiments. The duration of each hydrogen gas clearance measurement was 13.1 +/- 0.1 min. In conclusion, misoprostol dose-dependently and transiently increases focal gastric mucosal blood flow. However, only laser-Doppler flowmetry is sensitive enough to detect it. Although it can measure steady-state blood flow, owing to the duration of one measurement, hydrogen gas clearance is incapable of detecting rapid flow changes.
Gana
T J
TJ
Dept. of Surgery, University of Alberta, Edmonton, Canada.
MacPherson
B R
BR
Koo
J
J
D000527:Alprostadil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D001783:Blood Flow Velocity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005740:Gases; D005753:Gastric Mucosa / Q000098:blood supply*; D006859:Hydrogen / Q000493:pharmacokinetics; D007834:Lasers; D008297:Male; D016595:Misoprostol
D000897:Anti-Ulcer Agents; D005740:Gases; D016595:Misoprostol; D006859:Hydrogen; D000527:Alprostadil