Effects of phosphodiesterase inhibitor-induced insulin resistance on glucose and lipid metabolism in rats

AIM:To investigate the effects of milrinone (a selective phosphdiesterase III inhibitor PDE₃) on insulin secretion, blood glucose, plasma free fatty acids (FFA) and dose-response relationship, and assess possible effects of milrinone on glucose metabolism and insulin sensitivity in conscious rats.METHODS:The catheterized nonstressed rats were administered by the varying doses of milrinone (1, 5, 25 μmol/kg) and were compared with controls. A hyperinsulinaemic- euglycaemic clamp was established in awake rats, and milrinone(25 μmol/kg) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 min during hyperinsulinaemic- euglycaemic clamp. Glucose turnover was decided by gas chromatograph mass spectrometer (GC-MS).RESULTS:After dosing, plasma FFA levels in 3 milrinone groups significantly increased compared with the controls and before dosing. The percentages of elevation of FFA by the different milrinone doses were very similar, 50%, 52%, 55% for 1, 5, 25 μmol/kg respectively at 2 min after dosing. Plasma insulin levels were significantly elevated in the 5 and 25 μmol/kg groups, and the effect of milrinone on glucose concentration was detectable only 25 μmol/kg group. During hyperinsulinaemic clamp, there were significant increase in plasma FFA (from 173.1±15.2 to 633.8±87.3 μEq/L) and hepatic glucose production (HGP), and a significant decrease in glucose infusion rates (GIR) (to about 21%).CONCLUSION:These data suggest that milrinone impaires the abilities of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization in peripheral tissue. Therefore, milrinone administration may induce an acute insulin resistancein vivo.     

PDE3与亮甲酚蓝在绵羊卵母细胞体外培养中的应用研究

[目的]探讨磷酸二酯酶3（PDE3）特异性抑制剂Milrinone与亮甲酚蓝染色液（BCB）相结合在绵羊卵母细胞体外培养中的应用。[方法]比较了BCB对绵羊卵母细胞的筛选与传统的形态分级之间的差异,以及对胚胎后期发育的影响;研究了Milrinone对绵羊卵母细胞的最佳抑制时间,并用于BCB-卵母细胞体外培养。[结果]A、B级卵母细胞中BCB＋卵母细胞的比例为64.42%,极显著高于C级卵母细胞的17.00%;BCB＋卵母细胞的成熟率（86.16%）、卵裂率（85.29%）、囊胚率（34.40%）分别极显著高于BCB-卵母细胞（50.94%、36.19%和6.73%）;6 h是Milrinone对绵羊卵母细胞的最佳抑制时间,该试验组体外培养效率显著高于其他组;Milrinone对BCB-卵母细胞抑制培养6 h,极显著提高了体外胚胎发育率。[结论]为提高绵羊卵母细胞体外培养效率提供了依据。     

磷酸二酯酶抑制剂对水牛卵母细胞体外成熟的影响

[目的]探讨磷酸二酯酶抑制剂米力农(milrinone)对水牛卵母细胞成熟的影响。[方法]水牛卵母细胞分成3组,分别在含0、50、100μmol/L的milrinone的成熟液中培养16 h后,每组的一半卵母细胞用来染色,检验核成熟情况;另一半卵母细胞再在不含milrinone的成熟液中培养12 h,挑选形态正常的卵母细胞受精后培养。[结果]添加50和100μmol/L milrinone的成熟液成熟的卵母细胞的生发泡破裂(GVBD)比率分别为25.9%和12.1%,显著低于对照组(76.9%);但另一半卵母细胞再培养、受精后试验组(50、100μmol/L mil-rinone)的分裂率(59.3%和61.2%)和囊胚率(35.9%和31.1%)与对照组(56.7%和28.8%)相比均无显著性差异(P0.05)。[结论]milrinone对水牛卵母细胞的成熟具有明显的抑制作用,成熟抑制解除后水牛卵母细胞仍可保持较高的发育潜能。     

Effects of 4 classes of cardiovascular drugs on ventricular function in dogs with mitral regurgitation

BACKGROUND: There have been few trials in which dogs with mitral regurgitation (MR) have been treated with various cardioactive drugs to determine effects on left ventricular (LV) function. HYPOTHESIS: Four classes of cardiovascular drugs may improve LV function in dogs with MR without increasing MR. ANIMALS: Nine mature dogs were included in the study. METHODS: MR was produced in 9 dogs. Five months later under butorphanol narcosis, parameters of LV function and left atrial dimension (LAD) were monitored by LV micromanometry and echocardiography/Doppler. Dogs were given (in random order) enalaprilat, nitroglycerine, ouabain, milrinone, and placebo. RESULTS: Nitroglycerin produced no significant change; milrinone and ouabain increased contractility; ouabain decreased heart rate; and there was evidence that enalaprilat and milrinone decreased LAD. Milrinone and ouabain decreased isovolumetric contraction time and therefore the time available for MR. There was no evidence that a positive inotrope increased MR despite increasing LV contractility and stroke volume. CONCLUSION AND CLINICAL IMPORTANCE: This study contradicts the hypotheses that (1) strengthening the left ventricle may increase MR and (2) treatment of MR (even before symptoms of heart failure develop) may decrease LAD. It is reasonable that strengthening the force of LV contraction should increase the driving pressure for MR; however, this effect did not appear to increase MR. Although some investigators believe that treating dogs with MR with afterload reducers and decreasing hindrance to ejection of blood from the LV to aorta may lengthen life by decreasing MR, there did not appear to be a reduction in MR, at least in response to the angiotensin-converting enzyme (ACE) inhibitor.     

PDE3与亮甲酚蓝在绵羊卵母细胞体外培养中的应用研究(英文)

[目的]探讨磷酸二酯酶3(PDE3)特异性抑制剂Milrinone与亮甲酚蓝染色液(BCB)相结合在绵羊卵母细胞体外培养中的应用。[方法]比较了BCB对绵羊卵母细胞的筛选与传统的形态分级之间的差异,以及对胚胎后期发育的影响;研究了Milrinone对绵羊卵母细胞的最佳抑制时间,并用于BCB-卵母细胞体外培养。[结果]A、B级卵母细胞中BCB+卵母细胞的比例为64.42%,极显著高于C级卵母细胞的17.00%; BCB+卵母细胞的成熟率(86.16%)、卵裂率(85.29%)、囊胚率(34.40%)分别极显著高于BCB-卵母细胞(50.94%、36.19%和6.73%);6 h是Milrinone对绵羊卵母细胞的最佳抑制时间,该试验组体外培养效率显著高于其他组;Milrinone对BCB-卵母细胞抑制培养6 h,极显著提高了体外胚胎发育率。[结论]为提高绵羊卵母细胞体外培养效率提供了依据。