Effects of isoproterenol on myocardial lipid metabolism in rat hearts perfused with and without exogenous substrates

Effects of isoproterenol on myocardial lipid metabolism were studied in perfused rat hearts by the Langendorff apparatus without recirculation. Fatty acids in phospholipid, free fatty acid and partial glyceride fractions did not alter during the initial 30-min perfusion. However, fatty acids in triglyceride fraction decreased along with the perfusion. Isoproterenol enhanced the decrease in triglyceride fatty acid in the presence of glucose, but not in the absence of glucose. When hearts were perfused for 30 min with exogenous myristirate in the presence of glucose, triglyceride fatty acid did not decrease in the control perfusion, and incorporation of myristiric acid into triglyceride fraction increased in the presence of isoproterenol. When hearts were perfused with myristirate in the absence of glucose, fatty acid in triglyceride fraction slightly decreased during the control 30-min perfusion, and marked bradycardia or ventricular arrest occurred within 10 min after the start of perfusion with solution containing isoproterenol. Triglyceride content 10 min after perfusion was not different from the control value. Mechanical performance of hearts with myristirate and isoproterenol improved when the amount of glucose in the perfusing solution was increased. The findings indicate that glucose may play an important role in the mechanical performance of the heart perfused with a solution containing isoproterenol.     

野生山葡萄多酚对异丙肾上腺素诱发的小鼠心肌缺血的保护作用

目的评价野生山葡萄多酚(PVAS)对异丙肾上腺素诱发的小鼠心肌缺血的保护作用。方法采用皮下注射异丙肾上腺素(ISO)建立小鼠急性心肌缺血模型,观察不同剂量PVAS对模型小鼠ECGⅡ导联异常ST段,心肌含水量(MWC),心肌指数(M I)及血清磷酸肌酸激酶(CK)和乳酸脱氢酶(LDH)的影响。结果400 mg/kg PVAS可显著改善ISO诱发小鼠异常ECGⅡ导联ST段抬高,抑制MWC、M I的升高并降低血清CK、LDH水平(P<0.05)。结论PVAS对小鼠急性心肌缺血损伤具有保护作用。     

Cyclic adenosine monophosphate modulation of contractility via slow Ca2+ channels in chick heart

The catecholamines exert a positive inotropic effect associated with elevated tissue cyclic AMP levels and possibly with increase in the number of membrane slow cationic channels available for voltage activation. In the present study, catecholamines (isoproterenol, dopamine and dobutamine) were tested for their ability to affect the maximum upstroke velocity (+ V_max) of the slow action potentials, the first derivative ($\text{d}\text{T}\text{d}\text{t}$) of developed tension accompanying the slow responses, and the tissue cyclic AMP levels in the ventricular myocardium of isolated perfused chick hearts. To study the slow channels exclusively, the fast Na⁺ channels were voltage inactivated by elevated (25 mm) K⁺. In this condition of functional removal of the fast channels, the heart could not be excited by intense electrical stimulation. It was found that these catecholamines induced slow action potentials accompanied by contractions. Elevation of the concentration of these agents produced increases in + V_max, $\text{d}\text{T}\text{d}\text{t}$, and cyclic AMP in a dose-dependent fashion; a close correlation was obtained between the cyclic AMP level, + V_max and $\text{d}\text{T}\text{d}\text{t}$. These results support the hypothesis that the increases in + V_max of the slow action potentials and in contraction are explained by increase in the number of available slow channels mediated by intracellular cyclic AMP levels, and the resulting increase in the Ca²⁺ influx.     

Cardioprotective effects of cerebrolysin on the lesion severity and inflammatory factors in a rat model of isoproterenol-induced myocardial injury

BackgroundMyocardial injury (MI) is an important heart condition and a major cause of morbidity and mortality worldwide. The current study was designed to investigate the cardioprotective effects of cerebrolysin (CLY) on the lesion severity and inflammatory factors in male rats using isoproterenol (ISO)-induced MI model.MethodsMI in rats was induced by injecting ISO (100 mg/kg) subcutaneously (sc) on the first 2 days. Then, CLY (5 ml/kg) was injected intraperitoneally (ip) post-treatment for 7 days. On the 3rd day, creatine phosphokinase (CK-MB) and cardiac troponin I (cTnI) levels in serum and, on the 10th day, the TNF-α and IL6 levels in serum and heart tissue were measured by enzyme-linked immunosorbent assay (ELISA). Finally, the heart of each rat was dissected out and stained for histopathological examination.ResultsOn the 3rd day, the serum CK-MB and cTnI levels in the ISO and CLY + ISO groups were significantly increased compared with that in the control and CLY + Sal groups. One week after the induction of MI, ISO administration showed a significant increase in the serum level of TNF-α in the ISO group compared with that in the control and CLY + Sal groups. Also, our findings showed only a moderate reduction in inflammatory cell infiltration and extent of edema following CLY treatment in the CLY + ISO group. Also, CLY induced vascular proliferation in the heart tissue.ConclusionsWe conclude that the severity of pathological changes induced by ISO in MI (e.g. inflammation and edema) can be limited by CLY treatment.     

Tacrolimus ameliorates functional disturbances and oxidative stress in isoproterenol-induced myocardial infarction

Background

The inflammatory responses play a major role in the pathogenesis of acute myocardial infarction (MI). Early inhibition of inflammation may improve post MI cardiac function. The aim of this study was to investigate the effects of tacrolimus on cardiac function, hemodynamic parameters as well as histopathologic and electrocardiographic changes in isoproterenol-induced myocardial infarction.

Methods

Male Wistar rats were randomly divided into six groups of control, isoproterenol alone, tacrolimus alone, and isoproterenol plus tacrolimus (0.5, 1 and 2 mg/kg). Isoproterenol (100 mg/kg) was injected subcutaneously for two consecutive days to induce myocardial infarction, and simultaneously tacrolimus was administered orally twice a day for three days.

Results and conclusions

Administration of isoproterenol resulted in myocardial edema and necrosis as well as a marked reduction in the left ventricular systolic pressure (LVSP), left ventricular contractility (LVdP/dt_max) and relaxation (LVdP/dt_min) along with a severe elevation in left ventricular end-diastolic pressure (LVEDP). Isoproterenol also elevated the ST-segment and suppressed the R-amplitude and R-R interval on ECG. It was found that all doses of tacrolimus could amend the ECG pattern and ameliorated the isoproterenol induced disturbances in cardiac function. Acute and short term treatment with tacrolimus at dose of 2 mg/kg significantly (P < 0.001) improved LVdP/dt_max from 2712 ± 82 in myocardial infarcted rats to 4592 ± 149 mmHg/sec. Similarly, tacrolimus lowered LVEDP from 17.6 ± 0.68 in MI group to the value of 5.6 ± 0.22 mmHg (P < 0.001). Furthermore, tacrolimus was found to reduce malondialdehyde concentration in serum and myocardium by 50-70% (P < 0.001).The results of this study showed that acute treatment with tacrolimus, coincided with the occurrence of myocardial infarction, strongly protected the myocardium against the isoproterenol-induced myocardial infarction; where this might be due to the anti-inflammatory properties of tacrolimus.     

异丙肾上腺素致大鼠心肌损伤肥大时骨架蛋白的变化及意义

目的复制异丙肾上腺素(isoproteronol,Iso)致大鼠心肌损伤及肥大模型,观察细胞骨架蛋白微管蛋白(tubulin)、结蛋白(desmin)变化特点,探讨心肌支持蛋白在心肌肥厚过程中的关系和变化规律,为抑制心室肥厚的发生和发展提供实验依据。方法①将雄性Wistar大白鼠随机分成对照组和损伤肥大组(Iso组)。Iso组皮下多点注射中等剂量Iso,建立大鼠损伤、代偿性肥厚模型。②光镜观察心肌组织的病理变化。③RT-PCR法检测tubulin、desminmRAN表达。④免疫组化法检测tubulin、desmin蛋白表达。结果光镜下Iso组心肌组织有明显的损伤肥大及纤维化,tubulinmRNA(0.9252±0.3765)和desminmRNA(1.2453±0.5326)表达与对照组(0.6846±0.2372)和(0.7142±0.1416)比较明显升高,差异有统计学意义(t=2.3258,P<0.05;t=4.0972,P<0.01)。Iso组tubulin(0.75±0.32)和desmin(0.85±0.29)蛋白表达与对照组(0.56±0.25)和(0.64±0.31)比较,差异也有统计学意义(t=2.5627,P<0.05;t=2.7544,P<0.01)。结论Iso致大鼠心肌损伤肥大时,tubulin、desmin无论在蛋白水平,还是在基因水平都增加,提示异丙基肾上腺素对大鼠心肌tubulin、desmin蛋白水平和基因水平的影响是平行、一致的。     

滁菊总黄酮对异丙肾上腺素致大鼠急性心肌缺血的影响

目的 观察滁菊总黄酮对异丙肾上腺素（ISO）致急性心肌缺血模型大鼠的保护作用。方法 将大鼠皮下注射ISO复制大急性心肌缺血模型,观察滁菊总黄酮对模型大鼠心电,血清肌酸激酶（CK）、乳酸脱氢酶（LDH）、心肌组织超氧物歧化酶（SOD）、过氧化氢酶（CAT）和丙二醛（MDA）含量的影响。结果 滁菊总黄酮能够抑制急性心肌缺血模型大鼠心电图J点抬高,降低血清CK、LDH活性,升高心肌组织SOD、CAT活性,降低MDA含量。结论 滁菊总黄酮对ISO致心肌缺血模型大鼠有保护作用。     

儿茶酚胺对大鼠血管内皮功能的影响

目的探讨儿茶酚胺对大鼠血管内皮分泌功能的影响。方法利用大鼠异丙肾上腺素（ISP）心肌损伤模型,采用放免的方法测定血中内皮素（ET-1）,前列腺素代谢产物6-酮前列腺素F1α（6-keto-PG1α）和血栓素B2（TXB2）的含量。结果试验组ISP导致血浆中ET-1明显增高;6-keto-PG1α含量明显降低而TXB2的含量明显增高。结论异丙肾上腺素损伤血管内皮分泌功能,从而可能影响血管的舒缩功能、血小板的凝血与止血的平衡状态,进一步导致心肌损伤及其他脏器的损伤。     

Scanning electron microscopy of nasal arterioles effected by vasoactive agents

Summary Morphological changes in nasal blood vessels induced by - and -adrenergic and cholinergic agonists were studied under a scanning electron microscope after removal of extracellular connective tissue and the basal lamina. Arterioles were constricted and dilatated following topical application of -adrenergic and cholinergic agonists. Distinctive morphological changes were observed on their smooth muscle cells. Smooth muscle cells of constricted arterioles had a rugged surface with numerous fine invaginations. However, in dilatated arterioles the cells had a smooth surface and intercellular spaces were clearly revealed. No remarkable changes were produced in smooth muscle cells by the -adrenergic agonist. It is concluded that nasal arterioles are sensitive to -adrenergic and cholinergic stimulation but not to -adrenergic stimulation.