Antigen-evoked mast cell degranulation in the isolated rat heart: No effect on subsequent ischemia-reperfusion induced damage

Abstract

In the present study, the possible role of mast cells in ischemia/reperfusion-induced myocardial injury was evaluated in the isolated 'mast cell depleted' rat heart. Hearts isolated from sensitized and non-sensitized rats were perfused according to Langendorff. After 30 min of normoxic perfusion, hearts were challenged with antigen, a procedure which is known to result in a massive mast cell degranulation in sensitized hearts. After another 20 min, both 'mast cell depleted' and control hearts were subjected to 30 min of ischemia followed by 30 min of reperfusion. The release of lactate dehydrogenase (LDH) was determined, to quantitate the extent of irreversible injury of cardiomyocytes. Histamine release was measured to establish mast cell degranulation. Coronary flow (CF) and left ventricular developed pressure (LVDP) were monitored to study the consequences of the procedures on hemodynamic recovery. It was found that both CF and LVDP significantly increased during the first min after antigen challenge. These changes were accompanied by an almost complete degranulation of cardiac mast cells. The increase in CF and LVDP values were rapidly followed by a decrease, reaching minimal values of 159 +/- 4% and 85 +/- 4% of those before administration of antigen, respectively, at 2-3 min after antigen challenge. No effect of antigen challenge on LDH release were found indicating that mast cell degranulation did not compromise myocyte integrity. During reperfusion following 30 min of ischemia both the increase in CF and LVDP in 'mast cell-depleted' hearts were not significantly different from those in control (non-sensitized) hearts. Similarly, at the end of the reperfusion-phase, CF and LVDP values in sensitized hearts were comparable to those in control hearts. Reperfusion results in increased LDH release, which at no point in time was significantly different between sensitized and non-sensitized hearts. In non-sensitized hearts histamine release during the reperfusion phase was not detectable. Therefore, the results indicate that in the isolated rat heart, mast cells are most likely not involved in acute ischemia/reperfusion-induced myocardial injury.

Cardiac function in hearts isolated from a rat model deficient in mast cells

“…Similarly, the role of mast cells in the acute tissue damage and cardiac dysfunction elicited by ischemia and ischemiareperfusion (I/R) injury has not been resolved. Several reports suggest that mast cell stabilizers such as disodium cromoglycate and lodoxamide tromethamine diminish acute I/R damage in both rat and rabbit hearts (19,27,37) possibly via inhibition of TNF-␣ release (11), whereas other investigators found that antigen-evoked "mast cell depletion" or lodoxamide tromethamine has no effect on I/R or hypoxia/reoxygenation injury in the rat heart (8,36). The possible role of mast cell-derived histamine in acute ischemia as well as ischemic preconditioning has been discussed; however, several investigators have concluded that mast cell-derived histamine is not involved (3,22,37).…”