A STUDY ON DILAZEP .2. DILAZEP ATTENUATES LYSOPHOSPHATIDYLCHOLINE-INDUCED MECHANICAL AND METABOLIC DERANGEMENTS IN THE ISOLATED, WORKING RAT-HEART

The effects of dilazep, d-propranolol and lidocaine on the mechanical and metabolic changes induced by lysophosphatidylcholine (LPC) were st udied in isolated, perfused working rat heart. After a stabilization p eriod, the heart was perfused for 5 min with LPC (10 mu M) alone, LPC plus dilazep (5, 10 or 20 mu M), LPC plus d-propranolol (30 or 50 mu M ) or LPC plus lidocaine (30 or 100 mu M) and then perfused with normal Krebs-Henseleit bicarbonate (KHB) buffer for a further 20 min. Perfus ion with LPC for 5 min followed by KHB for 20 min irreversibly decreas ed cardiac mechanical function, decreased the tissue levels of adenosi ne triphosphate and creatine phosphate significantly, and increased th e tissue levels of lactate and free fatty acids including arachidonic acid. Dilazep or d-propranolol significantly attenuated the mechanical and metabolic changes induced by LPC, but lidocaine did not. These re sults indicate that the exogenous LPC causes ischemia-like changes, su ggesting that LPC is one of the important factors in producing ischemi a-reperfusion derangements in terms of mechanical and metabolic functi ons, and that both dilazep and d-propranolol can prevent the LPC-induc ed myocardial damage.