Effects of dipyridamole on myocardial glucose uptake in the newborn lamb.

Effects of dipyridamole on myocardial glucose uptake in the newborn lamb.
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双嘧达莫对新生羔羊心肌葡萄糖摄取的影响。

DOI:
10.1016/0022-4804(86)90094-6
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发表时间:
1986
期刊:
The Journal of surgical research
影响因子:
--
通讯作者:
MentzerJr,RM
MentzerJr,RM
中科院分区:
--
文献类型:
--
作者:
Mainwaring,RD;MentzerJr,RM

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碳水化合物是未成熟心肌的重要能量来源。由于双嘧达莫(DPY)已被报道促进成人心脏对葡萄糖的摄取,本研究旨在确定DPY是否能促进非缺血新生儿的葡萄糖摄取。在麻醉开胸羔羊(n=8)静脉注射DPY(0.2 mg/kg)前后,测定回旋冠脉血流量(CBF)、心肌腺嘌呤核苷酸含量以及主动脉和冠状静脉窦葡萄糖、乳酸和丙酮酸浓度。用高效液相色谱法测定腺嘌呤核苷酸含量。底物消耗量计算为CBF和主动脉-冠状静脉窦底物浓度差的乘积。冠脉血流量在未经治疗的动物中平均为114±6ml/min/100g,经潘生丁治疗后增加44%(P<0.01)。这与冠状动脉血管阻力降低32%有关(P<0.01)。在潘生丁治疗后,葡萄糖摄取量从9μ摩尔/分钟/100g增加到46mins/100g(P<0.01);乳酸摄取量下降了97%(P<0.01)。新生儿心脏有丙酮酸的净释放,从18增加到25μ摩尔/分钟/100g(P<0.05)。未治疗组大鼠心肌细胞三磷酸腺苷含量平均为4.08mole/g湿重,用药后增加11%至4.52μ(P<0.01)。该药对心肌组织中AMP、ADP水平无影响。这些数据表明,DPY是一种新生羔羊冠状动脉血管扩张剂,并增加葡萄糖摄取和心肌ATP含量。这些代谢效应为进一步研究缺氧和缺血期提供了理论基础。
Carbohydrates are an important source of energy for the immature myocardium. Since dipyridamole (DPY) has been reported to facilitate glucose uptake in the adult heart, the present study was designed to determine whether DPY could enhance glucose uptake in the nonischemic newborn. In anesthetized, open chest lambs (n= 8), circumflex coronary blood flow (CBF), myocardial adenine nucleotide content, and aortic and coronary sinus concentrations of glucose, lactate, and pyruvate were determined before and after a single dose of DPY (0.2 mg/kg, intravenously). Adenine nucleotides were measured by HPLC. The consumption of substrates was calculated as the product of CBF and the aortic-coronary sinus difference in substrate concentration. Coronary blood flow averaged 114 ± 6 ml/min/100 g in the untreated animals, and increased by 44% following treatment with dipyridamole (P< 0.01). This was associated with a 32% decrease in coronary vascular resistance (P< 0.01). Glucose uptake increased from 9 to 46 μmoles/min/100 g (P< 0.01) following dipyridamole treatment; lactate uptake decreased by 97% (P< 0.01). There was a net release of pyruvate from the neonatal hearts; this increased from 18 to 25 μmole/min/100 g (P< 0.05). Myocardial ATP content averaged 4.08 μmole/g wet wt in the untreated animals, and increased 11% to 4.52 following DPY (P< 0.01). The agent had no effect on the myocardial tissue levels of AMP or ADP. These data indicate that DPY is a coronary vasodilator in the newborn lamb and augments both glucose uptake and myocardial ATP content. These metabolic effects provide a rationale for further studies during periods of hypoxia and ischemia.
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