POLYOL PATHWAY-MEDIATED CHANGES IN CARDIAC-MUSCLE CONTRACTILE PROPERTIES - STUDIES IN STREPTOZOTOCIN-DIABETIC AND GALACTOSE-FED RATS

POLYOL PATHWAY-MEDIATED CHANGES IN CARDIAC-MUSCLE CONTRACTILE PROPERTIES - STUDIES IN STREPTOZOTOCIN-DIABETIC AND GALACTOSE-FED RATS
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DOI:
10.1113/expphysiol.1992.sp003649
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发表时间:
1992-11-01
影响因子:
2.7
通讯作者:
ROBERTSON, S
ROBERTSON, S
中科院分区:
医学4区
文献类型:
--
作者:
COTTER, MA;CAMERON, NE;ROBERTSON, S

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在体外测量了链脲佐菌素糖尿病大鼠和喂食40%半乳糖饮食的非糖尿病大鼠的左心室乳头肌和心房的收缩特性。两种组织和两种治疗组的抽搐反应均具有特征性减慢(P < 0.05)。达到峰值收缩的时间延长了18- 33%,最大收缩率降低了10- 17%。松弛也受到影响,半松弛时间增加13- 37%,最大松弛速率降低7- 25%。乳头肌和左心房之间存在治疗差异,糖尿病对前者的影响更明显,而半乳糖血症导致后者的变化更明显。糖尿病和半乳糖血症大鼠右心房静息搏动频率降低22%(P < 0.01).异丙肾上腺素最大刺激时,心率未升至刺激对照组水平(P < 0.01)。与正常对照组相比,糖尿病和半乳糖血症组的乳头肌速度相关收缩特性也显示出对异丙肾上腺素的反应降低。糖尿病组和半乳糖血症组的最大舒张率最低,分别为41%和34%(P <0.01)。糖尿病心室中的多元醇途径代谢物增加了8倍。在半乳糖血症大鼠中,半乳糖醇的积累导致多元醇增加530倍。这些数据表明,多元醇途径的活动可能是糖尿病和半乳糖血症性心肌病的收缩和变时性变化的病因学的一个重要因素。
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 < 0.0 1). 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.