Prevention by cromakalim of spontaneously occurring cardiac necroses in polymyopathic hamsters.
Previous studies on the heart necrotizing process at early stages of the hamster polymyopathy have led us to believe that this hereditary disease derives from a defective transmembrane ion flux resulting in myocardial Ca2+ over-load. On the other hand, certain K+ ATP channel openers were shown to prevent cytosolic Ca2+ accumulation in ischemic hearts. Therefore, we investigated the potential beneficial effect of chronic treatment with cromakalim (CR) on the development of necrotic changes in hamster myopathic hearts. Young cardiomyopathic (CM) hamsters were treated parenterally with CR over 4 consecutive weeks. The K+ ATP opener was dissolved in 5% DMSO and injected twice daily (s.c. and i.p. alternatively) at a dose level of 2.5 mg/kg per injection. Microscopic readings were carried out in staged serial paraffin sections of heart ventricles, the diaphragm, and tongue, will all tissues freshly taken at autopsy. In comparison with control untreated hearts, which exhibit numerous necrotic calcific foci, only minute myolytic lesions were found in 5 of 12 hamsters hearts receiving CR (p < 0.0001). Interestingly, the dystrophic process in the tongue was significantly less severe (p < 0.0004) in CR-treated animals. These observations provide evidence for the first time that in vivo sustained treatment with a K+ ATP opener exerts cardioprotection upon development of the hamster hereditary cardiomyopathy.
Jasmin
G
G
Département de Pathologie, Université de Montréal, Québec, Canada.
Proschek
L
L
D000818:Animals; D001578:Benzopyrans / Q000627:therapeutic use*; D009202:Cardiomyopathies / Q000517:prevention & control*; D003402:Creatine Kinase / Q000097:blood; D006224:Cricetinae; D019806:Cromakalim; D005260:Female; D008297:Male; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D010276:Parasympatholytics / Q000627:therapeutic use*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000627:therapeutic use*
D001578:Benzopyrans; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D003402:Creatine Kinase