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Polyol pathway‐mediated changes in cardiac muscle contractile properties: studies in streptozotocin‐diabetic and galactose‐fed rats
Author(s) -
Cotter MA,
Cameron NE,
Robertson S
Publication year - 1992
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.1992.sp003649
Subject(s) - medicine , endocrinology , papillary muscle , streptozotocin , contraction (grammar) , chronotropic , isoprenaline , polyol pathway , chemistry , diabetes mellitus , diabetic cardiomyopathy , heart rate , cardiomyopathy , aldose reductase , stimulation , heart failure , blood pressure
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.