Dantrolene sodium in vitro inhibited the ATP-dependent efflux of calcium from human Fed cells, the Ca++-ATPase activity of red blood cell membrane fragments (RBCMF) and passive calcium binding to RBCMF. These effects were obtained With concentrations of dantrolene sodium between 2.5 and 20 uM. However the passive influx of Ca++ was measured at 37 degrees C in cells pretreated to abolish Ca++ pumping and was not influenced by dantrolene sodium. From these results, it was concluded that dantrolene sodium inhibits an active Ca++ extrusion across the red cell membrane by inhibiting Ca++-ATPase activity which is intimately involved with the Ca++ transport mechanism in the red cell membrane.
Calcium/metabolism* ; Dantrolene/pharmacology* ; Erythrocyte Membrane/drug effects* ; Erythrocyte Membrane/metabolism ; Human ; Ion Channels/drug effects* ; Ion Channels/metabolism

OBJECTIVETo study the mechanism of Ca(2+) on the apoptosis induced by hyperthermia in neonate rat hippocampal neurons to provide the applicative evidence of dantrolene for preventing brain injuries.

METHODSDantrolene, Ca(2+) specific blocking agent, was used in the hyperthermia-induced apoptosis of primary hippocampal neurons in vitro to observe its effect on the apoptosis, fluorescent intensity, and dynamic change of Ca(2+) by flowcytometry and laser confocal microscopy.

RESULTSThe rate of apoptosis was decreased significantly after hyperthermia treatment by dantrolene sodium. The intracellular Ca(2+) fluorescent intensity in 42 degrees C treatment group (107.35 +/- 6.0) was significantly lower than that in control group (159.12 +/- 33.8). The concentration of Ca(2+) began to decrease 20 approximately 25 s after adding dantrolene sodium, and reached the lowest level about 50 s later, and then kept lower than the basal level.

CONCLUSIONDantrolene sodium has an important protective effect on hippocampal neurons apoptosis induced by hyperthermia and may have some applicative value of preventing heat-induced brain injury.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Calcium ; metabolism ; Calcium Channel Blockers ; pharmacology ; Cells, Cultured ; Dantrolene ; pharmacology ; Female ; Hippocampus ; cytology ; drug effects ; Male ; Neurons ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Temperature

We had a 52-year-old male presented for a surgery for old fracture of the 7th cervical vertebra. Generalized muscle rigidity and high fever with tachycardia was revealed 25 minutes after succinylcholine and enflurane administration. Then the body temperature was risen from 37.8 degrees C to 40.5 degrees C within 20 minutes and the arterial blood gas analysis showed a severe respiratory and metabolic acidosis. Under the suspicion of malignant hyperthermia, all anesthetics were discontinued, refrigerated intravenous solutions were started, and gastric lavage with cold saline was initiated together with packing the body with ice. Oral dantrolene 125mg, the only drug we could obtain, was administered through Levins tube after lavage. Serial serum CPK level were 4414 IU/L on third day and 74 IU/L on seventh day postoperatively. The postoperative course was uneventful and the patient could be walked after fifth day postoperatively and discharged without any sequelae.
Acidosis ; Anesthesia ; Anesthesia, General* ; Anesthetics ; Blood Gas Analysis ; Body Temperature ; Dantrolene ; Enflurane ; Fever ; Gastric Lavage ; Humans ; Ice ; Male ; Malignant Hyperthermia ; Middle Aged ; Muscle Rigidity ; Pharmacology ; Spine ; Succinylcholine ; Tachycardia ; Therapeutic Irrigation