Cardioprotective action of sodium gamma-hydroxybutyrate against isoproterenol induced myocardial damage.
In this study, the effects of graded doses of isoproterenol (IP) on the heart were examined in untreated gerbils and in gerbils anaesthetized with gamma-hydroxybutyrate (GHB), an endogenous metabolite with energy sparing properties. We were interested in the cardioprotective potential of GHB. IP was administered intraperitoneally in doses of 0.1, 0.3. 2.5 and 10.0 mg/kg to different groups of gerbils. Half the gerbils in each treatment group received 500 mg/kg of GHB 30 min before IP, and 250 mg/kg at three subsequent 2-hour intervals. The remaining gerbils in each treatment group received saline at these time points. The animals were sacrificed after 8 hours. The accumulation of neutral fat droplets in the sarcoplasm was the most consistent effect of IP. The highest dose also produced some scattered myofibre death. The accumulation of fat in the cells could be estimated semi-quantitatively using a histochemical reaction for succinic dehydrogenase, and the volume of fat could be measured more accurately by electron microscopic morphometry. These measurements showed that IP produced a three to five-fold increase in sarcoplasmic fat volume. GHB either abolished or significantly reduced the accumulation of fat and it also completely prevented the myofibre death caused by the highest doses of IP. This cardioprotective effect of GHB was independent of its hypothermic action. Based on this experience, ultrastructural morphometry of sarcoplasmic fat appears to be a promising method for evaluating cardioprotective measures.
Kolin
A
A
Department of Pathology, Sunnybrook Health Science Centre, University of Toronto, Canada.
Brezina
A
A
Mamelak
M
M
Pandula
E
E
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005849:Gerbillinae; D007545:Isoproterenol / Q000633:toxicity; D008055:Lipids / Q000032:analysis; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000648:ultrastructure; D009206:Myocardium / Q000737:chemistry / Q000648:ultrastructure; D012978:Sodium Oxybate / Q000627:therapeutic use*
D008055:Lipids; D012978:Sodium Oxybate; D007545:Isoproterenol