SUMMARY1. We have examined the effect of bradykinin on impulse traffic in sympathetic afferent fibres from the heart, great vessels and pleura, and have attempted to identify cardiac nociceptors that on the basis of their functional characteristics might have a role in the initiation of cardiac pain.2. In anaesthetized cats, we recorded afferent impulses from 'single-fibre' slips of the left 2nd-5th thoracic rami communicantes and associated chain, and selected fibres arising from endings in the heart, great vessels, pericardium and pleura. We applied bradykinin solution (0 1-1.0 jug/ml.) locally to the site of the ending; we also injected bradykinin (0 3-1 0 ,ug/kg) into the left atrium.3. Afferent endings excited by bradykinin (158 of 191 tested) were of two types. The larger group (140) were primarily mechanoreceptors with Ad or C fibres (mean conduction velocity, 7-5 + 0-6 m/sec). They were very sensitive to light touch. Those located in the heart, great vessels or overlying pleura had a cardiac rhythm of discharge and were stimulated by an increase in blood pressure or cardiac volume.4. Bradykinin increased mechanoreceptor firing from 0 7 + 0.1 to 5 0 + 0 3 (mean + S.E. of mean) impulses/sec. Some endings appeared to be stimulated directly by bradykinin, others sensitized by it so that they responded more vigorously to the pulsatile mechanical stimulation associated with the cardiac cycle.5. The smaller group of eighteen endings, of which ten were in the left ventricle, were primarily chemosensitive. Most had C fibres, a few had A6 fibres (mean conduction velocity, 2-3 + 0-7 m/sec). They were insensitive to light touch. With one exception they never fired with a cardiac rhythm, and even large increases in aortic or left ventricular pressure had little effect on impulse frequency. 6. Chemosensitive endings were stimulated by bradykinin, impulse activity increasing from 0.6 + 0-2 to 15-6 + 1-3 impulses/sec and remaining above the control level for 1-3 min. The evoked discharge, which was either continuous or occurred in irregular bursts, was not secondary to mechanical changes in the heart and great vessels.

Bradykinin applied to the epicardium stimulates cardiac sympathetic afferents and evokes a reflex increase in arterial blood pressure. In anesthetized cats we examined the potentiation of these effects by prostaglandin E1 (PGE1) applied to the ventricular epicardium. We recorded cardiac afferent impulses from the second to the fifth left thoracic sympathetic rami. PGE1 (0.1 microgram/ml) alone had little effect on blood pressure, but it significantly increased the pressor response to bradykinin, and it reduced or abolished tachyphylaxis to repeated applications of bradykinin. Both mechanosensitive and chemosensitive sympathetic cardiac afferents were stimulated by bradykinin. Indomethacin (intravenous) caused a small reduction in the afferent response to bradykinin. Epicardial application of PGE1 significantly increased the response (magnitude and duration) of chemosensitive endings to bradykinin but not that of mechanosensitive endings; however, PGE1 abolished the tachyphylaxis of both chemosensitive and mechanosensitive endings to repeated applications of bradykinin. Because both bradykinin and prostaglandins are released in the ischemic myocardium, their interactive effect on cardiac sympathetic afferents could play a part in the sensory and reflex responses to myocardial ischemia.

Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.

One hundred and thirty-seven consecutive outpatients with non-ulcer dyspepsia (NUD) and erosive prepyloric changes (EPC) were randomly allocated to double-blind treatment with 400-micrograms misoprostol tablets twice daily or placebo for 4 weeks. Misoprostol had a significant worsening effect on epigastric pain, nausea, meteorism, lower abdominal pain, and diarrhoea, as compared with placebo. The fact that symptoms in patients with NUD and EPC were exacerbated by an antisecretory dose of misoprostol indicates that the symptoms are largely unrelated to gastric acid.