Gastric fundus relaxation and emetic sequences induced by apomorphine and intragastric lipid infusion in healthy humans

Abstract

OBJECTIVES: Experimental animal studies have suggested that gastric relaxation precedes emesis, whether induced by peripheral or central stimuli. We aimed to quantify the gastric relaxatory and symptomatic responses to a standardized emetic inductor. METHODS: In healthy volunteers, we measured the gastric and symptomatic response to two different proemetic stimuli: a peripheral stimulus (intragastric infusion at 5 ml/min of 50% fat emulsion in water) and a central stimulus (s.c. apomorphine at 0.01 mg/kg). Proximal gastric tone was continuously recorded by an electronic barostat. Symptoms were simultaneously quantified by a graded questionnaire. RESULTS: Lipid-induced gastric relaxation occurred in 17/17 subjects and was followed by nausea in 12/17. The total amount of intragastric fat required to trigger gastric relaxation was 139 ± 34 ml and to induce nausea, 258 ± 32 ml. Gastric relaxation after subcutaneous apomorphine occurred in 13/14, and nausea/emesis, in the same 13/14. As expected, timing of events after stimulation was much shorter in response to the central than to the peripheral stimulus. Thus, gastric relaxation began 4.0 ± 0.6 min after subcutaneous apomorphine and 28 ± 7 min after the onset of lipid infusion ( p < 0.05); likewise, the symptomatic response to central stimulation with apomorphine was 8.5 ± 1.8 min versus 52 ± 6 min for lipid infusion, p < 0.05. However, the magnitude of gastric relaxation was quite similar for both stimuli (apomorphine: 208 ± 35 ml; intragastric lipid: 235 ± 23 ml). No correlation was observed between the symptomatic response and the magnitude of the gastric relaxation, whether elicited by intragastric infusion of lipids or by subcutaneous apomorphine. Specifically, when symptomatic and gastric motor responses were compared in each of the 14 subjects who received both stimuli, no significant correlation between individual responses was detected. CONCLUSIONS: Gastric relaxation invariably precedes nausea and emesis and is of the same magnitude whether induced by apomorphine (central stimulus) or intragastric lipid infusion (peripheral stimulus). Nevertheless, in some instances and depending on the nature of the stimulus, fundic relaxation is a physiological event unassociated with nausea.