| Research Abstract |
Ischemia of the heart produces damage on the heart by a decrease in blood (oxygen) supply and/or an increase in oxygen demand of the myocardium. Reperfusion damage, however, occurs when blood supply increases after ischemia. We postulate that it is toxic substances, i. e., ischemic poisons, that inflict damage to the cell during ischemia/reperfusion. The ischemic poisons include oxygen radicals, lysophospholipids and acylcarnitines.
The present study was designed to answer to the following two questions. First, do the ischemic poisons inflict an ischemia-like damage to the myocardium and do anti-ischemic drugs attenuate the myocardial damage induced by ischemic poisons? Second, are nitric oxide involved in the production of myocardial damage induced by ischemic poisons?
We confirmed that H_2O_2, lysophosphatidylcholine (LPC) and palmitoylcarnitine (PALCAR) produced the ischemia-like damage to the myocardium, and some anti-ischemic substances including dilazep, K-7259 and d-propranolol attenuated the myocardial damage induced by ischemic poisons.
We then measured NO_2 and NO_3 in the perfusate in the isolated, perfused rat heart in the hope that dilazep and K-7259 will change the concentrations of NO_2 and NO_3 in the perfusate. However, both dilazep and K-7259 did not modify the concentrations of NO_2 and NO_3 in the perfusate. We also examined whether N^G-L-arginine (L-NAME) attenuates the myocardial damage induced by PALCAR.L-NAME attenuated the PALCAR-induced myocardial damage, but the effect of L-NAME was not reversed by L-arginine. Therefore, we conclude that nitric oxide may not mainly contribute to ischemia/reperfusion damage in the heart.
|
