DOES DIGOXIN (DIG) ACTIVATE SODIUM-CALCIUM (NA-CA) EXCHANGE IN INTACT IMMATURE MAMMALIAN MYOCARDIUM? † 190

Although Na-Ca exchange has been clearly demonstrated in isolated immature cardiomyocytes, the degree to which DIG can stimulate Na-Ca exchange has not been studied in the intact, beating immature mammalian heart. We studied 37 paced, isovolumically contracting, constant pressure-perfused 3-week old New Zealand white rabbit modified Langendorff heart preparations at 37° C: 1) DIG dose-response curves under varying perfusate [Ca]; 2) response to DIGvs. low potassium (1 mM KCl) perfusate (which stimulates Na-Ca exchange) in 1.3 mM perfusate [Ca]; 3) resPonse to DIG vs. low K, in 0.2 uM nifedipine and 1.3 mM [Ca]. Results are expressed as% of baseline (mean± SE). DIG exerted inotropic and lusitropic effects only at 1 uM, but the degree increased with decreasing [Ca] in dose-dependent fashion. Low K consistently enhanced contractility and relaxation. During nifedipine Ca channel blockade, contractility and relaxation decreased markedly, recovered somewhat with 1 uM DIG, and were enhanced further with low K, with greater recovery of contractility than relaxation. As changes in contractile state are most directly related to Ca fluxes, our results show that Na-Ca exchange can be stimulated in the intact heart to enhance Ca entry and efflux markedly, corresponding to improved inotropy and lusitropy. DIG can stimulate Na-Ca exchange only to a limited degree, except under conditions of low [Ca]; under physiologic conditions of 1.0 mM [Ca], DIG has no significant inotropic actions. Interpretation of prior results with DIG should take into account the[Ca] used in the preparation. TableTable Table

Table 1

Table 2

Table 3