CONTRIBUTION OF ANTIPLATELET ACTIVITY TO THE EFFECTS OF 5-HT2 RECEPTOR ANTAGONISTS ON REPERFUSION-INDUCED ARRHYTHMIAS IN ANESTHETIZED RATS

The effects of certain 5-HT receptor antagonists were examined on ischaemia-induced and reperfusion-induced arrhythmias, on ex vivo platelet aggregation and on isolated cardiac muscle. Methiothepin (1 mg kg-1) reduced the total number of ischaemia-induced ventricular premature beats whereas ICI 170,809 (1 mg kg-1) reduced reperfusion-induced mortality to 10% compared with 70% in controls. ICI 169,369 did not significantly alter either ischaemia- or reperfusion-induced arrhythmias. High concentrations of both ICI 169,369 and ICI 170,809 caused reductions in the maximum driving frequency of isolated cardiac muscle but methiothepin had no significant effect. Administration of ketanserin, ritanserin, methiothepin or ICI 170,809, but not ICI 169,369, abolished the ability of 5-HT to enhance platelet aggregation. The results of these experiments suggest that the ability of 5-HT2 receptor antagonists to reduce reperfusion-induced arrhythmias may be related to their antiplatelet activity.