A clinically relevant model of heart failure: effects of ticlopidine.

A clinically relevant model of heart failure has been developed in chronically instrumented mini-pigs by injecting Sephadex beads into the left main or circumflex coronary arteries under fluoroscopic control. In six control animals, left atrial pressure (LAP) increased from 10 +/- 2 to 19 +/- 2 mmHg (p less than 0.01) and remained elevated for 3 days. Heart rate increased by 26 beats X min-1 (p less than 0.05) and diastolic pressure fell after 24 h but recovered over the next 48 h. In six animals treated with ticlopidine (50 mg X kg-1 p.o.) for four days prior to embolisation, the acute haemodynamic changes were less in the first day but similar to control after 3 days. Infarct size was approximately 20% of the left ventricle in control animals and 9.5% in the treated group (p less than 0.01). ADP-induced platelet activity was reduced in the treated animals suggesting that coronary occlusion followed both physical occlusion by the beads and later development of platelet thrombi.