Evaluation of protective effects of lidoflazine and mioflazine in cardiac ischemia

Abstract

The protective effects of lidoflazine and mioflazine against normothermic ischemia were evaluated in isolated rabbit hearts used in the working mode. Pretreatment with 0.125 mgl liter of these drugs improved recovery of cardiodynamic function during postischemic reperfusion. Functional recovery was preceded by less severe impairment of sarcolemmal structure and Ca2+ distribution at the end of the ischemic period, allowing the normalization of other substructures and the prevention of cellular Ca2+ overload during postischemic reperfusion. When cardiac output and semi-quantitative histology are taken as parameters, the protective effects of mioflazine were greater than that of lidoflazine.

Effects of lidoflazine and mioflazine against potassium and veratrine induced shape changes in isolated rat cardiac myocytes

“…The latter process, however, is not mediated by blockade of slow calcium channels (4,9). Furthermore, histochemical observations in the present and earlier studies (2,4,11,15) show the preservation of sarcolemma-bound calcium suggesting that lidoflazine and mioflazine exert their protective effect at the level of the sarcolemma, in the sense that the structural integrity of the membrane is preserved with retention of the membranes' capacity to bind calcium. Thus, ion fluxes causing cellular calcium overload could be prevented.…”

“…Such a picture is typical of cellular calcium overloading during an ischemic insult in whole hearts as well as in anoxic isolated myocytes (2,4,5,11,15). Observations on calcium shifts in anoxic cardiac myocytes by Borgers and Piper (5) suggest that disappearance of sarcolemma-bound calcium may represent the first ultrastructural sign of irreversible cellular damage.…”

“…The mechanisms of cardiac protection by lidoflazine and mioflazine are not completely understood. Protection has been shown not to be due to energy-sparing mechanisms because of lower cardiac work (15). The pharmacological effects of both drugs are related to inhibition of adenosine transport (19,(22)(23)(24) and to inhibition of excessive calcium-entry in cardiac cells.…”

Cytochemical evidence of NADH-oxidase activity in the isolated working rabbit heart subjected to normothermic global ischaemia

“…Two hearts did not recover at all and only in 3 hearts a minimal degree of recovery was seen. An account of the haemodynamic recovery has been previously described (Liu et al, 1986).…”