N-Methyl-D-aspartate receptor blockade by dizocilpine prevents stress-induced sudden death in cardiomyopathic hamsters.
We previously demonstrated that repeated cold-immobilization stress exposure had lethal effects in cardiomyopathic Syrian hamsters. To clarify the mechanisms of the sudden death, we investigated the effects of N-methyl-D-aspartate (NMDA) receptor blockade by dizocilpine on the sudden death of cardiomyopathic hamsters. Repeated exposure (5 days) to cold-immobilization stress induced a lethal effect in the cardiomyopathic hamsters in agreement with our previous results. Dizocilpine (0.1-10 mg/kg, i.p.), administered just prior to the stress, for 5 consecutive days markedly prevented the lethal effects of the stress. It was further demonstrated that treatment drug significantly reduced the observed increase in organ weights. These results suggest that NMDA receptors have an important role in stress-induced sudden death in cardiomyopathic hamsters and provide the first evidence for the potential therapeutic value of NMDA antagonists against cardiac sudden death.
Matsuoka
Nobuya
N
Basic Research Group, Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Tsukuba, Ibaraki, Japan. nobuya_matsuoka@po.fujisawa.co.jp
Kodama
Hiroshi
H
Arakawa
Hiroyuki
H
Yamaguchi
Isamu
I
D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003080:Cold Temperature / Q000009:adverse effects; D006224:Cricetinae; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012149:Restraint, Physical / Q000009:adverse effects; D013312:Stress, Physiological / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015996:Survival Rate; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate