Polyol pathway-mediated changes in cardiac muscle contractile properties: studies in streptozotocin-diabetic and galactose-fed rats.
Contractile properties of left ventricular papillary muscles and atria from streptozotocin-diabetic and from non-diabetic rats fed a 40% galactose diet were measured in vitro. There was a characteristic slowing of twitch responses for both tissues and both treatments (P < 0.05). Time to peak contraction was prolonged by 18-33% and maximum rate of contraction was reduced by 10-17%. Relaxation was also affected, with a 13-37% increase in half-relaxation time and a 7-25% reduction in the maximum rate of relaxation. There were treatment differences between papillary muscles and left atrium, diabetes having a more marked effect on the former, whereas galactosaemia caused more pronounced changes in the latter. The resting beat rate of the right atrium was 22% reduced in diabetic and galactosaemic rats (P < 0.01). When maximally stimulated with isoprenaline, beat rate did not rise to the level of stimulated controls (P < 0.01). Papillary muscle speed-related contractile properties also showed a reduced response to isoprenaline in diabetic and galactosaemic groups compared to normal controls. The greatest deficit was found for maximum rate of relaxation where responsiveness was 41 and 34% less for diabetic and galactosaemic groups respectively (P < 0.01). Polyol pathway metabolites in diabetic ventricles were increased 8-fold. In galactosaemic rats galactitol accumulation led to a 530-fold increase in polyols. The data suggest that polyol pathway activity may be an important factor in the aetiology of contractile and chronotropic changes in diabetic and galactosaemic cardiomyopathy.
Cotter
M A
MA
Biomedical Sciences, Marischal College, University of Aberdeen.
Cameron
N E
NE
Robertson
S
S
D000818:Animals; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004032:Diet; D005690:Galactose / Q000008:administration & dosage* / Q000494:pharmacology; D005693:Galactosemias / Q000503:physiopathology; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000503:physiopathology; D011108:Polymers / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011108:Polymers; C024617:polyol; D007545:Isoproterenol; D005690:Galactose