|Budget Amount *help
¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 1995 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1994 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Recently, number of severe opportunistic infections in aged, cancer-bearing or operated patients in hospital is increasing probubly due to excessive use of antibiotics. Among them, methicillin-resistant Staphylococcus aureus (MRSA) infection is sever and sometimes lethal. However, strategy for the medical treatmant of patients suffering from MRSA intoxication has not been established. Professor Noda and his colleagues, Chiba University School of Medicine, have isolated and purified two novel cytotoxins (HL-cytotoxin and HS-cytotoxin) of MRSA from patient hospitalized at an intensive care unit. We studied electrophysiological changes in cardiac tissue induced by the novel MRSA cytotoxins in mice and guinea pigs. Intravenous injection of the MRSA toxins produced marked ECG changes, such as prolongation of PR interval, widening in QRS complex, bradycardia and arrhythmias, in mice. Electrophysiological experiments using cnventional microelectrode techniques in isolated guinea-pig papillary muscles revealed that decreases in resting membrane potential and action potential duration and an indcrease in developed tensions (DT) were inuced by supefusion of the MRSA-toxins. The increase in DT was blocked by pre-treatment with alpha and beta adrenergic antagonists and was attenuated by repeated application of the toxins. These results imply the involvement of neural mechanism in cardiotoxicity of the MRSA toxins. We observed similar cardiotoxic effects with Pseudomonas toxin and MRSA toxin produced by molecular biological techniques (GST-HS-cytotoxin) in mice. Thus, MRSA toxin may produce lethal cardiotixicity through neural mechanisms. However, further studies are needed to clarify precise cellular mechanism (s) of the cardiotoxicity of MRSA toxins.