Pharmacologic protection of perfused rat heart against global ischemia.

Using a Langendorff rat heart model, studies were performed on the effects of three drugs in protecting the heart against global ischemia. The drugs used were: (a) MR-256, a prostaglandin oligomeric derivative, which is a calcium chelating agent and at the same time, is an inhibitor of phospholipase A2 activity, (b) chlorpromazine which is not a calcium chelator, but is a calmodulin antagonist and is an inhibitor of phospholipase A2 activity, and (c) BAPTA/AM, a calcium chelating agent, but which is not an inhibitor of phospholipase A2 activity. The perfused heart was exposed to 15 minutes of global ischemia. In control experiments (no drug), the ventricular pressure recovered to 26.4 +/- 6.7% (n = 22) of the original level. With pretreatment of (a) MR-256 (b) chlorpromazine, and (c) BAPTA/AM, maximum recoveries were 0.5 +/- 6.7% (n = 5), 88.7 +/- 8.5% (n = 5), 45.3 +/- 26.6% (n = 5), respectively. MR-256 and chlorpromazine were found to react with free radicals. The modes of action of these three different types of drugs are discussed.