Clinico-morphologic results of laser myocardial revascularization in ischemic heart disease]

Transmyocardial laser revascularization was applied in 58 patients with ischemic heart disease. The objective criterion of the method efficiency was an increase in myocardium perfusion due to newly formed blood vessels under influence of laser irradiation. The laser treatment has improved cardiac function and general condition of the patients. The surgery did not exert considerable influence on the contractile capacity of the myocardium in the patients treated.     

氟烷和七氟醚对缺血再灌注心肌功能和氧自由基的影响

目的：研究１５肺泡最小浓度（ＭＡＣ）的氟烷和七氟醚对缺血再灌注心肌功能和氧自由基的影响。方法：应用离体大鼠心脏Ｌａｎｇｅｎｄｏｒｆ逆行灌注模型研究１５ＭＡＣ的氟烷、七氟醚对心肌缺血前后心功能的影响,测定缺血前、缺血１０ｍｉｎ、复灌３０ｍｉｎ３个不同时间的心肌超氧化物歧化酶（ＳＯＤ）活性和丙二醛（ＭＤＡ）含量。结果：七氟醚不同程度地抑制心肌收缩功能。缺血１０ｍｉｎ时,七氟醚组ＳＯＤ酶活性明显下降,ＭＤＡ含量显著升高。缺血２５ｍｉｎ复灌３０ｍｉｎ后,二药均能促进心肌功能和ＳＯＤ酶活性恢复,抑制ＭＤＡ生成,其中七氟醚的作用较为明显。结论：二药对缺血再灌注心肌具有一定的保护作用,七氟醚优于氟烷。     

Role of the changes in the sarcoplasmic reticulum in disorders of myocardial function]

Acute focal ischemia of the myocardium, acute hemodynamic overloading of the heart, coarctation of the aorta, and fibrillation of the heart were simulated on rabbits. The animals were studied for the contractile function of the myocardium, and potential work capacity of the heart was calculated according to a special formula. The rebbits were sacrificed at the acute period of the development of a pathological process, and the contractile myocardium was investigated by electron microscope. The studies of the bioelectric activity of the heart revealed periodically appearing disorders of the cardiac rhythm. The electron-microscopy investigation showed, apart from changes in the ultrastructure of cells of the contractile myocardium reflecting their hyperfunction, marked dilatation of small canals of the sarcoplasmic reticulum, right to the formation of cisterns containing sequesters of cells. It is established that the changes referred to above in the sarcotubular system were associated with potassium dysbalance. The conclusion was drawn that the above said changes in the sarcoplasmic reticulum was a stereotype reaction of the alterative heart at the level of ultrastructures developing according to the principle of a vicious circle.     

Mitochondrial complexes I, II, III, IV, and V in myocardial ischemia and autolysis

Ischemic myocardium was produced by occluding the left circumflex coronary artery in anesthetized dogs. Autolyzed myocardium was produced by incubating transmural samples of canine left ventricle at 37 degrees C. Tissue pH was recorded continuously in each model using a microcombination pH electrode impaled into the midmyocardium. The activities of the five mitochondrial inner membrane enzyme complexes of electron transport and coupled oxidative phosphorylation were assayed as a function of time of ischemia or autolysis. While the activities of complex II (succinate-CoQ reductase) and IV (cytochrome c oxidase) were completely stable, that of complex I (NADH-CoQ reductase) decreased markedly, but largely only after 20 min of ischemia or autolysis. At 20 min and beyond, the decrease in the activity of complex I paralleled closely the decrease in whole mitochondrial oxygen uptake with NAD-linked substrates in both models. The activity of complex III (CoQH2-c reductase) decreased at a more gradual rate during ischemia or autolysis, and its rate of decrease paralleled that of succinate-supported oxygen uptake. The activity of complex V (oligomycin-sensitive ATPase) decreased most rapidly (by 40% in only 5 min of autolysis) but nearly leveled off beyond 20 min in the two models. A strikingly similar pattern of differential enzyme lability was observed in isolated control mitochondria incubated at lowered pH values. The results demonstrate 1) differential enzyme lability within the mitochondrial inner membrane, 2) a connection between severity of acidosis and the degree of enzyme activity loss, and 3) the usefulness of simple tissue autolysis as an analogue of in situ myocardial ischemia.     

粉防己碱对心肌顿抑损伤的保护作用

用兔冠脉前降支结扎缺血再灌模型,观察粉防己碱（Ｔｅｔ）对心肌顿抑损伤的保护作用并分析其作用机理。结果示：①顿抑心肌收缩舒张功能明显降低,心电图ＳＴ段抬高,血清ＬＤＨ水平升高,左室湿重增大,Ｔｅｔ可减轻缺血及再灌后心肌功能的损害,降低血清ＬＤＨ水平与心肌湿重;②顿抑组血清ＮＯ水平略升高,Ｔｅｔ组血清ＮＯ无明显变化;③顿抑组心肌Ｎａ＾＋－ｋ＾＋－ＡＴＰ酶及Ｃａ＾２＋－ＡＴＰ酶活力均明显下降,Ｔｅｔ组Ｔ     

Heart resistance to oxidative stress in rats of different genetic strains

In August rats reperfusion after regional myocardial ischemiain situ or intracoronary administration of hydrogen peroxide less significantly suppressed contractile activity of the heart compared to Wistar rats. Activities of catalase and superoxide dismutase in the myocardium during reperfusion remained unchanged in August rats. In Wistar rats a profound inhibition of cardiac function was accompanied by a decrease in enzyme activity. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 250–253, September, 2004     

Mechanism of action of nonachlazine on the blood supply and activity of the heart

Nonachlazine (10 mg/kg, intravenously) has a biphasic effect on cardiac activity. A short phase of weakening of cardiac activity is followed by a marked increase in the cardiac output and contractile function of the myocardium. The increase in the blood supply and activity of the heart coincides in time with the accumulation of noradrenalin in the myocardium and an increase in phosphorylasea. β-Adrenoblockers prevent the development of these effects. It is postulated that the effectiveness of nonachlazine in ischemic heart disease is connected with its ability to activate adrenergic mechanisms of glycogenolysis control, leading to switching of metabolism in the myocardium to the anaerobic pathway of energy liberation.     

Local myocardial function following coronary occlusion in cats. Effect on non-ischaemic regions

The mechanical function and perfusion in ischaemic and non-ischaemic myocardium after coronary occlusion was studied in 10 cats using pressure-length loop analysis and radiolabelled microspheres. Measurements in three regions--ischaemic, adjacent normal and remote normal myocardium--all showed different responses to coronary occlusion. In the ischaemic region loop area, segment shortening and tissue flow were markedly reduced. In the adjacent normal region, both loop area and segment shortening as well as flow increased. In the remote normal region, neither loop area, segment shortening nor flow showed consistent changes. End-diastolic segment length increased in all regions, most in the ischaemic region and least in the remote region. The increased end-diastolic segment length in all regions after coronary occlusion indicates activation of the Frank-Starling mechanism as an attempt to maintain stroke volume. However, the end-diastolic segment length did not increase uniformly for all normal myocardium: it depended on the proximity to the ischaemic region. Increased contractile function in the adjacent normal myocardium due to non-uniform distribution of the Frank-Starling effect is the most likely mechanism behind the left ventricle's ability to partially compensate for loss of contractile mass during acute regional ischaemia in anaesthetized cats.     

氟烷和七氟醚对缺血心肌功能和代谢及Ca2+-ATP酶活性的影响

目的: 研究氟烷、七氟醚(1.5MAC)对缺血心肌的影响。方法: 应用离体大鼠心脏Langendorff逆行灌注模型研究氟烷、七氟醚对心肌缺血前心率(HR)、左室舒张末期压力(LVEDP)、左室发展压(LVDP)、左室压力升高速率(+dp/dt)、左室压力下降速率(-dp/dt)和冠脉流量(CF)的影响,测定缺血前、缺血10min、缺血25min3个不同时间的心肌ATP含量、Ca²⁺-ATP酶活性,同时记录缺血间期左室内压的变化情况。结果: 七氟醚显著增加正常离体心脏的CF,氟烷、七氟醚均不同程度地抑制心肌收缩功能和Ca²⁺-ATP酶活性,能够增加正常心肌的能量贮备。缺血10min时,二药能够减缓心肌ATP含量及Ca²⁺-ATP酶活性的下降,氟烷的作用比较明显。缺血间期,氟烷明显推迟缺血性挛缩的起始时间,降低挛缩幅度。结论: 氟烷的抗缺血损伤作用优于七氟醚,延缓缺血期心肌ATP含量及Ca²⁺-ATP酶活性的下降可能是氟烷抗缺血损伤作用的重要机制之一。     

Gene Expression for the Renin System in the Myocardium of Hypertensive ISIAH Rats

The concentration of mRNA for angiotensin-converting enzyme (ACE) and angiotensin type 1A receptor (AT1A) in the myocardium of hypertensive ISIAH rats and normotensive WAG rats was measured by real-time PCR. Gene expression of the angiotensin type 1A receptor in the myocardium of 4-month-old ISIAH rats was lower than in WAG rats. The content of mRNA for angiotensin-converting enzyme in the myocardium of adult ISIAH rats was elevated by 80%. Therefore, the development of myocardial hypertrophy anticipates the increase in enzyme expression in the myocardium. Water deprivation (17 h) was accompanied by a decrease in the concentration of mRNA for angiotensin-converting enzyme in the myocardium of ISIAH rats, which did not differ from that in normotensive animals. Our results suggest that the decrease in cardiac preload and increase in plasma renin activity during dehydration reduce requirements for hyperactivity of the local cardiac renin—angiotensin system.     

丝瓜络对小鼠心肌缺血性损伤的预防效应

目的：探讨中药丝瓜络（RLF）对小鼠心肌缺血性损伤的防治作用。 方法： 预先给予昆明小鼠166.7，333.3，666.7 g/L的丝瓜络煎剂0.01 mL/g灌胃，每日2次，1周后腹腔注射垂体后叶素30 U/kg诱发急性心肌缺血，观察心电图变化，检测血清乳酸脱氢酶（LDH）、心肌组织中丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性的改变。 结果： 各种剂量RLF均能降低垂体后叶素所引起的小鼠心电图中T波增高幅度及抑制心率减慢；并显著降低心肌缺血后造成的血清LDH以及心肌组织内MDA含量的增高，增加心肌组织中SOD活性。 结论： RLF对急性缺血心肌有明显的保护作用，其作用机制可能与抑制心肌脂质过氧化，增强其抗氧化能力有关。     

Human myocardial and skeletal muscle enzyme activities: creatine kinase and its isozyme MB as related to citrate synthase and muscle fibre types

Activities of myocardial and skeletal muscle total creatine kinase (CK) and its isozyme MB were related to the oxidative capacity [measured as the citrate synthase (CS) activity] and to the contractile characteristics (estimated as the percentage of type I muscle fibres). Skeletal muscle biopsies were obtained both from physically trained and untrained men and myocardial biopsies from patients subjected to open-heart surgery performed because of mitral or aortic valve disease. Enzyme activities were determined on freeze-dried muscle specimens. The CK-MB activity was about twice as high in trained skeletal muscle as in untrained ones reaching the myocardial level. The total CK activity was about three times higher in skeletal muscle than in myocardium; the myocardium, however, had CS activity 3-4 times larger than that of skeletal muscle. A close correlation was demonstrated between activities of CK-MB on one hand and CS (r = 0.76) or percentage type I fibres (r = 0.83) on the other hand suggesting a connection between CK-MB activity and the oxidative capacity of the cell. This was in contrast to total CK where different regressions were obtained when comparing the myocardium and the skeletal muscle of trained or untrained men. In conclusion, CK-MB activity in trained skeletal muscle in athletes were similar to that in myocardium. CK-MB was related to the oxidative capacity and formation of cellular energy in skeletal and heart muscle.     

Structural correlates of regional myocardial dysfunction in patients with critical coronary artery stenosis: Chronic hibernation?

The morphological changes in the myocardium of hypocontractile segments, especially the possible structural counterparts underlying chronic ischemia, are not well documented. Light and electron microscopy was performed on myocardium derived from the anterior wall of the left ventricle of 98 patients during coronary artery bypass grafting. Wall motion data were collected from the region corresponding to the biopsied zone. The changes seen in a substantial part of the cardiomyocytes corresponded to “dedifferentiation” rathern than degeneration characteristics. The affected cardiomyocytes showed a partial to complete loss of sarcomers, sarcoplasmic reticulum, and T-tubules and presented abundant plaques of glycogen, strands of rough endoplasmic reticulum, lots of minimitochondria, and a tortous nucleus. The volume of the cells was similar to that of normal cells. The number of the affected cells was consistently higher in endocardial parts than in epicardial ones. The cell changes occurred in the myocardium of patients both with andn without a previous Q-wave infarction. There was a significant relation between anterior wall motion abnormalities and the incidence of affected cells in the endocardium, but not in the epicardium. A significant relatiosnhip was found in noninfarcted patients between the presence of affected cells and the amount of connective tissue. Furthermore, in these patietns the number of affected cells depended on the degree of stenosis. It is proposed that segments in which these structural changes prevail will not recover immediately after revascularization but that they might how a delayed recovery of function, because structural remodeling requires time in order to regain sufficient contractile material.     

Ultrastructural observations on mitosis in myocardial cells of the rat embryo

Cardiac tissue from rat embryos at 10, 11, 12, 13, 14, 15, days of gestation and newborn rats were processed and studied under the electron microscope. A unique observation in the developing myocardium is detection of the simulataneous occurrence of mitosis and synthesis of muscle-specific contractile proteins (actin and myosin filaments) in the same cells. Mitotic cells containing sites of myofilaments are discernible throughout the gestational period covered in this investigation, including the myocardium of new born. Unlike skeletal muscle, in the myocardium of rat embryos the onset of fibrillogenesis is not correlated with cessation of mitotic activity.     

Oxidative metabolism and myocardial function in rats with different sensitivities to oxygen deficiency in hypoxia

In exposure to mild hypoxia, the electron-transport function of the myocardial respiratory chain in the NAD-cytochrome b area is limited in a different manner in animals highly resistant (HR) and those poorly resistant (PR) to hypoxia. In PR animals this process develops very rapidly, leads to diminution of the oxidative capacity of the respiratory chain and of ATP production, and, as a consequence, to suppression of the energy-dependent contractile function of the myocardium. In HR animals this process is less manifest and develops very slowly, which confirms the lesser role of NAD-dependent oxidation of substrates in the metabolism of the myocardium of these animals. The ability of the HR animals to maintain in mild hypoxia a higher ATP level than that in PR animals suggests that ATP synthesis in them occurs through oxidation of endogenous substrates which enter the respiratory chain by bypassing the NAD-dependent area. Compounds of the group of quinones, which facilitate removal of the block of the electron-transport function of the respiratory chain on the level of the first enzyme complex, normalize processes of ATP production and myocardial contractility and may be used as antihypoxic agents.     

Heart resistance to oxidative stress in rats of different genetic strains

In August rats reperfusion after regional myocardial ischemia in situ or intracoronary administration of hydrogen peroxide less significantly suppressed contractile activity of the heart compared to Wistar rats. Activities of catalase and superoxide dismutase in the myocardium during reperfusion remained unchanged in August rats. In Wistar rats a profound inhibition of cardiac function was accompanied by a decrease in enzyme activity.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 9, pp. 250–253, September, 2004     

The effects of tetrandrine on the contractile function and microvascular permeability in the stunned myocardium of rats

The effects of tetrandrine (Tet) on the contractile function and microvascular permeability in stunned rat myocardium in vivo were studied. Stunned myocardium was induced by 15 (MS(15) group) or 20 (MS(20) group) min of myocardial ischemia plus 60 min of reperfusion. The following was shown. (1) FITC-BSA concentration was 166.0 +/- 7. 9 microg/g myocardium in the control group. The concentrations in ischemic myocardium increased by 35.4 and 45.6% in MS(15) and MS(20) groups respectively (p<0.05). (2) Administration of Tet (64.2 and 96. 3 micromol/kg, I.P.) 20 min before ischemia not only ameliorated the contractile function, but also reduced the FITC-BSA concentrations in ischemic myocardium. At 60 min after reperfusion, the contractile function parameters in Tet-treated groups were significantly superior to those in corresponding stunning groups. FITC-BSA concentrations in Tet-treated groups were lower than those in stunning groups. Then, there was already no significant difference in FITC-BSA concentrations between Tet-treated groups and the control group. The FITC-BSA concentrations at the end of experiments were correlated negatively with dp/dt(max) (r = -0.83, p<0.01). (3) Tet inhibited KCl-induced calcium influx in isolated cardiomyocytes. The results suggest that Tet given before ischemia may be involved in the reduction of microvascular permeability in stunned myocardium, which might be associated with its calcium channel blocking effect.     

Genetically determined differences in the resistance to myocardial infarction in Wistar and August rats

In intact August rats, the cardiac contractile function at rest was by 76% higher than in Wistar rats, while their hearts, both intact and after acute myocardial infarction, were more resistant to isometric load than the hearts of Wistar rats. Postinfarction mortality in August rats was 18% vs. 70% in Wistar rats. Adrenoreactivity of the myocardium in August rats was decreased compared to that in Wistar rats. These peculiarities can determine high resistance of August rats to myocardial infarction.     

Changes in Passive But Not Active Mechanical Properties Predict Recovery of Function of Stunned Myocardium

The time course of alterations in active and passive mechanical properties of stunned myocardium during ischemia and throughout reperfusion has not been thoroughly quantified. This investigation tested the hypothesis that the amount of injury as well as the rate and extent of recovery of contractile function in postischemic, reperfused myocardium are directly correlated to changes in regional active and passive elastance and viscosity. A modified viscoelastic Voigt model was employed to quantify myocardial mechanical properties. Left ventricular pressure and segment length (in both ischemic and normal regions) were fit to the model consisting of an active elastic spring in parallel with a viscous damper and a passive elastic spring. The mechanical properties of myocardium from dogs which recovered (50%) baseline regional contractile function as determined by percent segment shortening (n=7) were compared to those from dogs that did not recover function (n=7). Both groups displayed decreased active elastance in the ischemic region during coronary artery occlusion, and this decrease was maintained in the nonrecovery group. Increases in viscosity of ischemic myocardium were observed in both groups during coronary occlusion but returned to control only in the recovery group. The nonrecovery group demonstrated increased passive elastance in the ischemic region during coronary occlusion and throughout the reperfusion period whereas the recovery group remained unchanged. We conclude that functional recovery of stunned myocardium is directly related to alterations in mechanical properties caused by ischemia and that changes in passive elastance during occlusion may predict the ability of ischemic myocardium to recover contractile function. © 1999 Biomedical Engineering Society. PAC99: 8719Rr, 8719Uv, 8710+e     

Ghrelin reduces rat myocardial calcification induced by nicotine and vitamin D3 in vivo

Ghrelin, a newly discovered bioactive peptide, initially was identified as a strong stimulant for the release of growth hormone (GH) and that has improved cardiac function in patients suffering from end-stage chronic heart failure. Increasing evidence has demonstrated that ghrelin may have myocardial protective effects. However, the role of ghrelin in the pathogenesis of cardiovascular diseases remains unclear. In this study, an in vivo model of rat myocardial calcification induced by vitamin D3 and nicotine was used to study the possible mechanism in the regulatory action of ghrelin on the calcified myocardium. Calcification increased total Ca2+ content and 45Ca2+ deposition in the myocardium and alkaline phosphatase (ALP) activation in the plasma. Compared with the control group, ghrelin mRNA expression was up-regulated and the myocardium calcium content was significantly increased in vitamin D3 and nicotine-treated rats. Rats were subcutaneously injected with 1 or 10 nmol/kg ghrelin. Rats treated with both low- and high-dose ghrelin decreased total Ca2+ content and 45Ca2+ deposition in cardiac muscle and inhibited ALP activation in the myocardium and plasma, in a concentration-dependent manner. In addition, osteopontin (OPN) mRNA expression significantly decreased and that of endothelin (ET-1) significantly increased with myocardial calcification. Ghrelin treatment increased OPN expression at the mRNA level and reduced ET-1 mRNA expression in a dose-dependent manner. These results indicate that exogenous administration with ghrelin attenuates myocardial calcification induced by nicotine and vitamin D3, and that the possible mechanism is via the ghrelin-induced increase in the OPN mRNA levels and decrease in the ET-1 mRNA expression in the myocardium.