Nitecki, Samy

Methods developed previously for studying the effect of cerebroventricular injection or ventriculocisternal perfusion of test substances are unsatisfactory because the test substance is not confined to the central compartment. Most likely the test substance enters the peripheral circulation via the arachnoid villi. The purpose of this paper is to describe a method for perfusing the cerebroventricular system of conscious dogs without passage of test substances to the peripheral circulation. With the method described, the mean (+/- SE) cerebroventricular pressure in conscious dogs was 7.4 +/- 0.8 cmH2O (n = 16), and the mean (+/- SE) production of cerebrospinal fluid (CSF) was 25 +/- 0.3 microliter/min (n = 16). Endogenously occurring migrating myoelectric complexes (MMCs) of the small intestine were recorded in dogs before catheters were implanted in the left and right lateral ventricles and the fourth ventricle and after catheter implantation during cerebroventricular perfusion with artificial CSF alone or with CSF containing sulfated (S-CCK-OP) or nonsulfated cholecystokinin octapeptide (NS-CCK-OP). Only cerebroventricular perfusion with S-CCK-OP (1.2 pmol.kg-1.min-1; n = 20) replaced spontaneously occurring MMCs with a fed-like pattern of myoelectric activity. The results suggest that replacement of the fasting pattern of myoelectric activity with a fed-like pattern in the fasted dog was mediated by CCK-A receptors located in one or more brain nuclei surrounding the third ventricle.

Background—Flufenamic acid, a fenamate, has been shown to alter markedly the membrane potential of small intestinal smooth muscle and increase intracellular calcium in single cells. Aims—To determine the effects of flufenamic acid on myoelectrical motor activity and gastrointestinal transit in the intact animal. Methods—Myoelectrical motor activity was recorded via seromuscular platinum electrodes sutured at regular intervals in the stomach and throughout the small intestine. Fasted and fed gastrointestinal transit was assessed using technetium-99m (99mTc) as the radioactive marker linked to 1 mm amberlite pellets or added to the meal. Results—Flufenamic acid (600 mg, intravenously) induced intense spike activity in the small intestine. The mean duration of irregular spike activity was 250 (7) minutes. Spike activity was more pronounced in the lower small intestine. Flufenamic acid also accelerated initial gastric emptying and markedly shortened transit time in the small intestine. In the fasted state the 50% transit time in the small intestine was 54 (8) minutes with infusion of flufenamic acid compared with 105 (10) minutes in the control group; in the fed state 99mTc first reached the colon at 220 (10) minutes compared with 270 (12) minutes in the control group. Conclusions—Flufenamic acid had marked effects on both myoelectrical motor complex activity and small intestinal transit in the dog. The observed effects suggest that flufenamic acid may be of potential use as a prokinetic agent.