Inhibition of Sarcoplasmic Reticulum Calcium Release Reduces Myocardial Stunning

Effects of Dantrolene on Ischemia-Reperfusion Injury in Animal Models: A Review of Outcomes in Heart, Brain, Liver, and Kidney

“…2,14,21,24 Dantrolene (100 μmol/L), when given after perfusion, significantly increased reperfusion oxygen consumption up to 3 times that of controls. 21 Dantrolene (12.5-45 μmol/L) was also shown to have increased the percent recovery of left ventricular developed pressure, 71% versus controls 44%, 24 and reduced ectopic beats by 75%. 14 In vivo rabbit studies suggested that dantrolene (40 μmol/L) given after ischemia might have increased cardiac output versus controls; however, this was not statistically significant ( P = 0.09).…”

Protective effects of dantrolene against myocardial injury induced by isoproterenol in rats: biochemical and histological findings

“…Cytosolic Ca 2 + overload contributes to the development of cellular injury by multiple mechanisms [1 -3,20]. Mitchell et al [25] have shown that inhibition of SR Ca 2 + release reduces myocardial stunning and that dantrolene has a protective effect against ischemia-induced myocardial stunning. In addition, dantrolene has a coronary dilatory action [26,27].…”

Probing a putative dantrolene-binding site on the cardiac ryanodine receptor

“…The in vitro EGTA sensitivity of [ 3 H]dantrolene binding to RyR2, therefore, demonstrates that it is possible to conformationally modulate this isoform so as to allow dantrolene binding, but does not inform us with regard to a potential mechanism of in vivo regulation of this site. Of necessity, in vivo mechanisms would have to involve modulation of this site in the presence of increased myoplasmic Ca 2+ levels, rather than the decreased levels used herein, as the physiological studies that have demonstrated an effect of dantrolene on cardiac tissue have done so particularly during experimental pretreatment for physio- logical stresses associated with enhanced intracellular Ca 2+ release: hyperthyroid cardiomyopathy [32], heart failure [33], myocardial stunning and ischaemia [17,34,35], post-infarction contractility and responsiveness to isoprenaline (isoproterenol) [36], and endotoxin-or thermal injury-related suppression of myocardial function [20,21]. All of these are chronic physiological stressors, the effects of which on a dantrolene-RyR2 interaction may involve post-translational modification of the channel and/or result from gene expression of a channel-interacting protein(s).…”