Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 1. Developing and established hypertrophy.

The effects of a large arteriovenous fistula on left and right ventricular hemodynamics and cardiac myocyte size were examined in adult rats at 1 week and 1 month after surgery. Cardiac output, left ventricular function, and right ventricular function were evaluated before obtaining isolated myocytes for cell size measurements. Average heart weight increased 35% at 1 week and 86% at 1 month in rats with fistulas. In general, myocyte hypertrophy was due to a proportional increase in length and width (length/width ratio remained constant). This change was more evident in the large hearts from rats with 1-month fistulas. At both the 1-week and 1-month intervals, the hypertrophic response of right ventricular myocytes was slightly greater than that observed in the left ventricle or interventricular septum. Left ventricular systolic pressure and dP/dtmax were significantly reduced at 1 week but returned to normal after 1 month of overloading. Left ventricular end-diastolic pressure was increased approximately fivefold and twofold at 1 week and 1 month, respectively. Right ventricular systolic pressure and dP/dtmax were increased at both intervals examined. We conclude that severe volume overloading from a large aortocaval fistula in the rat is characterized by 1) depressed left ventricular function at 1 week followed by a large compensatory hypertrophy and near normal function at 1 month, 2) right ventricular pressure overload, and 3) changes in myocyte shape that resemble normal physiological growth.     

Regional changes in myocyte size during the reversal of thyroid-induced cardiac hypertrophy

Regional changes in cardiac myocyte size resulting from thyroid treatment, and the subsequent reversal of hypertrophy following removal of the thyrotoxic stimulus, were examined. Isolated myocytes were prepared from weight-matched controls and rats treated with desiccated thyroid hormone for 10 weeks. Cells were collected from the right and left ventricles. Cell volume was determined with a Coulter Channelyzer system. Cell length was measured directly using a phase microscope. Myocyte cross-sectional area was calculated from cell volume/length. After 10 weeks thyroid treatment, cell volume was increased in all regions, especially the right ventricle and the epimyocardium of the left ventricle (P less than 0.01). Although cell length was increased in all regions (N.S.), most of the myocyte hypertrophy was due to an increase in cross-sectional area, especially in the right ventricle (P less than 0.01) and epimyocardium of the left ventricle (N.S.). By 2 weeks post-treatment, a substantial regression of myocyte hypertrophy had occurred. However, heart weight was still significantly larger than control (P less than 0.001), due to an incomplete regression of myocyte volume. This study indicates that thyroid hormones stimulate myocyte hypertrophy by increasing both cross-sectional area and cell length. The response is more pronounced in right ventricles than in left ventricles. Within the left ventricle, epimyocardial cells enlarge the most. At 2 weeks post-treatment, cardiac hypertrophy is still present and myocytes have not completely returned to a normal size.     

Regional changes in creatine kinase and myocyte size in hypertensive and nonhypertensive cardiac hypertrophy

Several intracellular enzymes have been shown to have altered total activity or isoenzyme composition in cardiac hypertrophy. This study tests the hypothesis that the accumulation of the fetal-type (BB + MB) creatine kinase (CK) isoenzymes in hypertrophied adult myocardium is related to an increase in blood pressure. Consideration was made for the location, size, and hemodynamic load of the myocytes. By using the two-kidney, one-clip (2K1C) rat model of renal hypertension with and without hydralazine treatment, CK (total and isoenzyme), lactate dehydrogenase, and citrate synthase activities and myocyte size were measured. An increased heart weight/body weight ratio occurred in both untreated 2K1C rats (4.15 +/- 0.09) and hydralazine-treated 2K1C rats (4.12 +/- 0.13) as compared with control rats (3.25 +/- 0.10). Blood pressure was high only in untreated 2K1C rats (196 +/- 9 mm Hg), as compared with hydralazine-treated 2K1C rats (142 +/- 6 mm Hg) and control rats (135 +/- 3 mm Hg). Myocytes were isolated from five ventricular regions: left ventricular epicardial and endocardial free wall, left and right halves of the interventricular septum, and right ventricular free wall. Regional differences in normal and hypertrophied myocardium were demonstrated for morphological and biochemical parameters, with the greatest changes occurring in left ventricular endocardium. The shift in CK isoenzyme expression toward accumulating more BB + MB was greater in "hypertensive hypertrophy" (untreated 2K1C rats) than in "nonhypertensive hypertrophy" (hydralazine-treated 2K1C rats). Calculations incorporating isolated myocyte volume showed that the cellular content of total CK remained the same during the hypertrophic process, accounting for a decrease in the tissue activity. Measurement of lactate dehydrogenase and citrate synthase activities suggests that hypertrophied myocardium has relatively higher glycolytic capacity and that this effect is exacerbated in the presence of high blood pressure. We conclude that increased blood pressure is more closely linked to the fetal CK isoenzyme shift than is hypertrophy alone.     

Change in cardiac myocyte size distribution in aortic-constricted neonatal rats

Summary Regional changes in cardiac myocyte size and population distribution were examined in Sprague Dawley rats receiving an abdominal aortic constriction at five days of age. At specific time intervals post-constriction, hearts were recovered from constricted animals and weight-matched controls and isolated myocytes were obtained from right and left ventricles using retrograde coronary perfusion with collagenase. Cell volume and cardiac myocyte population distribution curves were determined using a Coulter Channelyzer system. Cell length was measured directly using a Bioquant Image Analysis system. Myocyte cross-sectional area was calculated from cell volume/length. By three months of age, heart weight and heart weight-body weight ratio in constricted animals had increased by approximately 115% (p<0.001) in females and 85% (p<0.001) in males compared to controls. Between 15 and 90 days of age, the growth response, as indicated by increased cell volume, was approximately 4× greater in constricted females and 2.5× greater in constricted males compared to corresponding controls. This increase was manifested by a shift in the mean size of the myocyte population to the right and a substantial widening of the distribution. Most of the enlargement was due to increased cross-sectional area, with only a moderate contribution from increased cell length. Significant increases in size were seen in both left and riggt ventricles. By three months of age, a significant interaction was apparent between aortic constriction and sex. The capacity for hypertrophy was greater in the smaller myocytes in female rats of similar age compared to males. The final degree of hypertrophy was similar formale and female rats, possibly indicating a critical upper limit in cell size for cardiac myocytes.This work was supported by the Ontario Heart and Stroke Foundation (Postdoctoral Research Fellowship to Dr. Campbell and grant to Dr. Rakusan) and Grant RO1 HL30696 from the National Institutes of Health to Dr. Gerdes.     

Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: I. Regional hemodynamics and myocyte remodeling

A chronic pressure overload animal model was created in young guinea pigs by surgical constriction of the descending thoracic aorta. Hemodynamics, echocardiography and myocyte size characterization demonstrated compensated pressure overloaded left ventricular (LV) hypertrophy at 4 weeks (4 wk), and congestive left heart failure 6 months (6 mo) after aortic constriction. Compared to age-matched sham-surgery control groups, the cell length and length/width ratio of isolated LV myocytes were significantly increased at 6 mo but not at 4 wk. LV myocyte lengthening was statistically correlated to an increase in LV chamber dimension and diastolic wall stress at 6 mo. These data demonstrate that myocyte lengthening occurs in mechanical overload-induced congestive heart failure, contributes to LV chamber dilatation, and is associated with increased end-diastolic wall stress. Myocytes of the other three chambers remained morphometrically normal at 4 wk. Hypertrophy of left atrial (LA) and right ventricular and atrial myocytes was evident at 6 mo. Increases in both cell length and cross-sectional area contributed significantly to the hypertrophy in the three chambers. More than 85% of LV myocytes were binucleate and the binucleation remained unchanged in the sham-surgery group from the tested 4 wk to 6 mo time point. LV hypertrophy and failure showed no significant effects on the binucleation of LV myocytes. By contrast, over 96% of LA myocytes were mononucleate. The mononucleate percent of LA myocytes was not appreciably altered during either normal growth or hypertrophy induced by secondary hemodynamic overload due to LV failure.     

Developmental changes in cardiac myocyte calcium regulation

Developmental changes in the contributions of transsarcolemmal Ca2+ influx and Ca2+ release from intracellular storage sites to myocardial contraction were evaluated in isolated ventricular myocytes from neonatal (aged 1-7 days) and adult (aged 8-10 weeks) New Zealand White rabbits. Contractions ceased in one beat when extracellular Ca2+ was decreased from 1mM to micromolar levels using a rapid perfusion technique. On reperfusion with 1 mM Ca2+, recovery of control contraction amplitude occurred after significantly fewer beats in neonatal myocytes compared with adult myocytes, and after 1 minute compared with 5 minutes of reduced Ca2+. After 15 minutes of perfusion with either 1 or 10 microM ryanodine, contraction amplitude decreased in both age groups, but the decrease was significantly greater in adults than in neonates. These experiments indicate that isolated ventricular myocytes may be used in the study of developmental changes in intracellular Ca2+ regulation. Results suggest that cardiac contraction in neonates is relatively more dependent on transsarcolemmal Ca2+ influx. Furthermore, although Ca2+ release from intracellular storage sites is present in both neonates and adults, its role in cardiac contraction is more significant in adults.     

Regional myocyte size in two-kidney, one clip renal hypertension

Regional variations in the size and shape of isolated myocytes were studied using the two-kidney, one clip (2K1C) renal model of hypertension. Weanling male Sprague-Dawley rats (50 to 75 g) were anesthetized by ketamine (100 mg/kg) during renal artery clipping (0.2 mm internal diameter silver clip) and were then allowed to grow for 6 to 8 weeks, when the blood pressure had stabilized at 180 mmHg. Hearts were removed, weighed and then were perfused with a calcium-free Joklik medium containing collagenase. Isolated myocytes were collected from five regions and fixed in isoosmolar glutaraldehyde: right ventricular free wall (RVFW), right and left halves of the interventricular septum (RIVS, LIVS), and epicardial and endocardial halves of the left ventricular free wall (LEPI, LENDO). Myocyte volume was measured by Coulter Counter. Myocyte length was measured by sonic digitizer. Cross-sectional area was calculated from myocyte volume and length. Tailcuff systolic pressure and heart weight were significantly increased in 2K1C rats as compared to control. Body weights were not different. Cell volume was significantly increased in RIVS, LIVS, LEPI, and LENDO, but not in RVFW. Cell length was not significantly increased in any region. Thus, the 2K1C model showed a predominant left ventricular hypertrophy in which the right half of the septum acted in concert with the left ventricle. The shape of the hypertrophied myocytes, having an increase in volume due to an increase in cross-sectional area but not length, was most consistent with a pressure-induced form of cardiac hypertrophy.     

Multiple aortocaval fistulas associated with a ruptured abdominal aneurysm in a patient with Ehlers-Danlos syndrome.

Aortocaval fistula (ACF) is a rare complication of spontaneous abdominal aortic aneurysm (AAA) rupture, with an incidence of 2-4%. A unique case of ruptured AAA complicated by multiple aortovenous fistulas involving the inferior vena cava and left internal iliac vein is presented, and is the first published report of a patient with Ehlers-Danlos syndrome undergoing surgical treatment for an ACF.     

Regional myocyte size in compensated right ventricular hypertrophy in the ferret

The effect of pressure-induced right ventricular hypertrophy on regional myocyte size and shape and regional myocardial wet weight was studied by comparing 20 ferrets which underwent pulmonary artery banding at a weanling age to 19 non-operated siblings. Using isolated myocyte preparations from six myocardial regions in 10 banded and seven non-banded ferrets, a 60% increase in cell volume in the right ventricular outflow tract and the right ventricular free wall was shown to be due primarily to an increased cross-sectional area of individual myocytes. The right side of the interventricular septum exhibited an intermediate increase in cell volume, while the left side of the interventricular septum did not respond to the pulmonary artery banding procedure. These findings confirm that localized hemodynamic changes produce hypertrophy of individual myocytes in selected regions of the heart and that a pressure-induced model of hypertrophy involves an increased cross-sectional area of myocytes, with minimal change in cell length.     

Myocardial infarction in rats. Infarct size, myocyte hypertrophy, and capillary growth

To determine the compensatory reserve capacity of the ventricular myocardium following infarction, the left coronary artery in rats was ligated, and the animals were killed 40 days later. Infarcts affecting an average 23% of the left ventricle were characterized by a 27% hypertrophic growth of the remaining myocardium that produced a complete replacement of the necrotic tissue. In contrast, infarcts with an average 50% loss of mass resulted in 83% expansion of the spared myocardium that was inadequate for a complete restoration of ventricular tissue. Myocyte hypertrophy was 26% and 78% in small and large infarcts, respectively. Cellular hypertrophy in both cases involved significant increases in myocyte transverse area and myocyte length. After large infarcts, there was an 18% reduction in capillary surface and a 16% increase in the diffusion distance. Corresponding values for small infarcts were -10% and 9%. These alterations combined with the deficient reconstitution of myocardial mass following large infarcts resulted in 25%, 29%, and 30% deficits in the absolute amounts of capillary lumen, surface, and length per ventricle respectively. Even with small infarcts, a deficit was seen in capillary luminal surface (-16%), and length (-19%). In conclusion, we have demonstrated that cardiac hypertrophy following myocardial infarction is consistent with cellular shape changes characteristic of a combination of concentric and eccentric hypertrophic growth. However, cardiac muscle cells appear to be unable to compensate for the loss of mass induced by a 50% infarct. The inadequate adaptation of the capillary vasculature in the infarcted hearts suggests that the injured ventricle is more vulnerable to additional ischemic episodes.     

Characterization of cardiac myocyte and tissue beta-adrenergic signal transduction in rats with heart failure

OBJECTIVE: The cellular basis of alterations in beta-adrenergic signal transduction in rats with chronic heart failure (CHF) remains unclear. The aim of the present study was to examine this signal transduction system in isolated ventricular cardiomyocytes of rats with CHF. We focused on changes in the levels of stimulatory (Gs) and inhibitory G-proteins (Gi). METHODS: CHF was induced in male Wistar rats by coronary artery ligation (CAL). Hemodynamic and biochemical parameters were measured 8 weeks after CAL. Alterations in contractile function and Ca(2+) transients via beta-adrenergic receptor signaling of cardiomyocytes isolated from rats with CHF were characterized by simultaneous measurements of cell shortening and fura-2 fluorescence intensity. RESULTS: Coronary artery-ligated rats showed symptoms of CHF, such as decreased contractile function, increased left ventricular volume, decreased chamber stiffness, and about 40% infarct formation of the left ventricle, by 8 weeks after surgery. The contractile function and Ca(2+) dynamics of cardiomyocytes from the rats with CHF remained normal under basal conditions. Only cardiac cell length was increased. The responses of peak shortening, fura-2 fluorescence ratio amplitude, and cAMP content to beta-adrenoceptor stimulation were reduced in cardiomyocytes of the rats with CHF, whereas direct stimulation of adenylate cyclase did not affect the response of these variables. Cardiomyocyte Gsalpha protein was decreased, whereas no changes in Gialpha proteins were seen in these cells. Increases in tissue Gsalpha and Gialpha proteins in the scar zone were detected. The results on tissue levels of collagen and G-proteins in the viable left ventricle appeared to depend on the presence of nonmyocytes. CONCLUSIONS: The results suggest that impaired contractile function of cardiomyocytes is unlikely to account for global LV contractile dysfunction, and that down-regulation of beta-adrenoceptors occurs in cardiomyocytes per se. The difference in changes of G-protein between the cardiomyocyte and myocardial tissue suggests an appreciable contribution of nonmyocytes to myocardial G-protein levels.     

福辛普利对自发性高血压大鼠心室重塑时左室心肌细胞凋亡和Bcl_2及Bax基因表达的影响

目的 :研究福辛普利对自发性高血压大鼠 ( SHR)左室心肌细胞凋亡和 Bcl2 、Bax基因表达的影响。方法 :1使用左室重量指数作为大鼠左室重构的指标 ;2使用末端脱氧核苷酸转移酶标记技术和 DNA电泳技术 ,研究心肌细胞凋亡的发生情况 ;3使用核酸原位杂交技术研究左室心肌细胞 Bcl2 、Bax基因表达的变化。结果 :1福辛普利使 SHR左室重量指数显著降低 ,由 3 .3 1± 0 .17下降至 2 .5 6± 0 .2 5 ,P <0 .0 5 ;2福辛普利能显著减少左室心肌细胞凋亡的发生〔( 2 14± 2 8)下降至 ( 5 4± 11)个凋亡细胞 / 10 5细胞 ,P<0 .0 1〕;3福辛普利能显著增加细胞 Bcl2 基因的表达 ,同时减少 Bax的基因表达。福辛普利使切片的 Bcl2 与 Bax基因表达阳性面积百分数之比恢复正常 (均 P <0 .0 1)。结论 :血管紧张素转换酶抑制剂能有效地抑制心室重塑的发生以及此过程中的心肌细胞凋亡 ;福辛普利使心肌细胞 Bcl2 及 Bax基因表达阳性面积百分数之比恢复正常是其抗细胞凋亡作用的一个机制。     

DDFA方案对重症急性胰腺炎大鼠心肌细胞凋亡及Bax,Bcl-2表达的影响

目的:探讨DDFA方案对重症急性胰腺炎(SAP)大鼠心肌细胞凋亡及Bax、Bcl-2基因表达的影响.方法:SD大鼠45只随机分为假手术组、SAP组和DDFA治疗组(DDFA:地塞米松、低分子右旋糖酐、5-氟脲嘧啶、抑肽酶)大鼠SAP模型采用0.05牛磺胆酸钠逆行胆胰管注射法建立,建模后6,12,18h时测定血心肌肌钙蛋白Ⅰ(cTnⅠ,μg/L)和肌酸激酶同功酶(CK-MB,nkat/L),光镜观察心肌组织病理变化,TUNEL法测定心肌细胞凋亡指数(AI),SABC免疫组化染色法测定心肌Bax和Bcl-2基因表达.结果:SAP组血cTnⅠ(6h:2.14±0.09vs0.18±0.07;12h:3.30±0.25vs0.20±0.08;18h:3.74±0.42vs0.19±0.08),CK-MB(6h:7681±252vs3389±204;12h:11576±251vs2553±205;18h:12972±458vs3522±218)和心肌细胞凋亡指数(6h:5.73±0.84vs0.99±0.13;12h:8.79±0.68vs1.00±0.44;18h:14.09±1.22vs1.02±0.32)、Bax(6h:4.42±1.05vs1.03±0.13;12h:7.39±0.38vs1.08±0.13;18h:8.51±1.07vs1.02±0.12)和Bcl-2(12h:1.83±0.18vs1.11±0.11;18h:3.31±0.75vs1.02±0.12)表达较假手术组升高(P<0.01),光镜下见心肌组织损害明显;经DDFA治疗后,血cTnⅠ(6h:0.87±0.06;12h:1.73±0.12;18h:2.48±0.34)、CK-MB(6h:5858±232;12h:8275±257;18h:8975±430)和心肌细胞凋亡指数(6h:2.44±0.27;12h:5.93±0.39;18h:8.75±0.66)、Bax表达(6h:3.05±0.87;12h:6.46±0.36;18h:6.97±1.04)下降(P<0.05),而Bcl-2表达(6h:3.05±0.87;12h:4.86±0.46;18h:4.53±1.04)增强(P<0.05),光镜下见心肌组织损害减轻.心肌细胞凋亡与血CK-MB、cTnⅠ呈正相关(r=0.812,P<0.05;r=0.807,P<0.05).结论:心肌细胞凋亡、Bax和Bcl-2表达参与SAP发病机制,在SAP早期给予DDFA治疗对减轻心脏损害程度、改善预后是有益的.     

Acetate-induced changes in cardiac energy metabolism and hemodynamics in the rat

Summary The hemodynamic and metabolic effects of acetate were studied in rats in vivo and in the isolated perfused heart. Hemodynamic parameters, myocardial phosphagens, inorganic phosphate, and adenosine were measured in vivo. Acetate uptake, coronary flow, O₂ consumption, parameters of the cellular energy state, and hypoxanthine compounds and their washout were measured in heart perfusion experiments. Heart rate (HR), cardiac output, and the peak derivative of the left ventricular pressure rise (dP/dt_max) increased significantly during acetate infusion in vivo, but mean arterial pressure, systolic arterial pressure, and systemic vascular resistance decreased. Heart muscle ATP concentrations decreased after 7 min of acetate infusion. In vivo cardiac work load (HR·(peak left ventricular pressure)) showed a positive correlation with tissue adenosine concentration and a negative correlation with phosphorylation potential. Acetate uptake in the perfused hearts was about 2.5 mol/min per gram wet weight. Acctate perfusion increased O₂ consumption and coronary flow concomitantly with a decrease in tissue ATP concentration. Tissue AMP and perfusate effluent adenosine concentration and adenosine output increased significantly, perfusate adenosine showing a non-linear positive correlation with coronary flow. The results demonstrate that acetate induces considerable changes in hemodynamics and metabolism in the heart.     

Long-term effects of nitrendipine on hemodynamics and oxygen transport in patients with cor pulmonale

Recent studies have suggested that vasodilators may acutely improve pulmonary hemodynamics in patients with chronic obstructive pulmonary disease and cor pulmonale, but the effects of long-term therapy have not been assessed. We evaluated the hemodynamic and gas exchange effects of nitrendipine, a calcium channel blocker with a cardiovascular profile similar to nifedipine, acutely and after five days and six weeks of therapy in eight patients with stable COPD and cor pulmonale. After six weeks, nitrendipine significantly decreased both mean pulmonary artery pressure (40.4 +/- 10.3 to 31.2 +/- 6.6 mm Hg, p less than 0.01) and pulmonary vascular resistance (6.8 +/- 3.9 to 3.0 +/- 1.1 units, p less than 0.01), while cardiac index increased (2.4 +/- 0.8 to 3.6 +/- 1.0 L/min/m2, p less than 0.001). Despite a fall in arterial PO2 (53.1 +/- 18.7 to 45.5 +/- 11.3 mm Hg, p = NS), systemic oxygen transport increased by over 30 percent (843 +/- 284 to 1,111 +/- 373 ml/min, p less than 0.05). Systemic arterial pressure, pulmonary capillary wedge pressure, and heart rate were unchanged. Despite these hemodynamic changes, three patients died from complications of their underlying disease while receiving long-term therapy after eight, nine, and ten months. These preliminary findings suggest that long-term vasodilator therapy can result in persistent hemodynamic improvement in some patients with cor pulmonale secondary to COPD, although the impact of this form of therapy on survival remains to be clarified.     

Effects of gender difference on cardiac myocyte dysfunction in streptozotocin-induced diabetic rats

The main characteristics of type 1 diabetic cardiomyopathy include depressed contractility and altered electrophysiological properties in ventricular myocytes. The goal of the present study was to determine the potential influence of gender in the diabetes-induced pathogenesis of ventricular myocyte function. Diabetes in both male and female rats was induced by a single intravenous injection of streptozotocin (STZ). Diabetic rats exhibited hyperglycemia and reduced body weight gain in both male and female groups. Neither contractile profiles nor activity of three types of K+ channels of ventricular myocytes was significantly different between nondiabetic male and female rats. Ventricular myocytes isolated from diabetic rats exhibited significant depression in cell contraction and relaxation, which was associated with depression of intracellular Ca2+ ([Ca2+]i) transient. The degrees of contractile depression were comparable in ventricular myocytes obtained from both male and female diabetic rats. Similarly, diabetes depressed three types of outward K+ currents (Ito, Ik, and Iss) to the same extent in both gender myocytes. These data demonstrate that in this animal model of diabetes, gender difference in cardiac myocyte functions was eliminated.     

福辛普利对自发性高血压大鼠心室重塑时左室心肌细胞凋亡和Bcl2及BaX基因表达的影响

目的研究福辛普利对自发性高血压大鼠(SHR)左室心肌细胞凋亡和Bcl2、Bax基因表达的影响.方法①使用左室重量指数作为大鼠左室重构的指标;②使用末端脱氧核苷酸转移酶标记技术和DNA电泳技术,研究心肌细胞凋亡的发生情况;③使用核酸原位杂交技术研究左室心肌细胞Bcl2、Bax基因表达的变化.结果①福辛普利使SHR左室重量指数显著降低,由3.31±0.17下降至2.56±0.25,P＜0.05;②福辛普利能显著减少左室心肌细胞凋亡的发生[(214±28)下降至(54±11)个凋亡细胞/105细胞,P＜0.01];③福辛普利能显著增加细胞Bc12基因的表达,同时减少Bax的基因表达.福辛普利使切片的Bcl2与Bax基因表达阳性面积百分数之比恢复正常(均P＜0.01).结论血管紧张素转换酶抑制剂能有效地抑制心室重塑的发生以及此过程中的心肌细胞凋亡;福辛普利使心肌细胞Bcl2及Bax基因表达阳性面积百分数之比恢复正常是其抗细胞凋亡作用的一个机制.     

Nutritional supplementation with MyoVive repletes essential cardiac myocyte nutrients and reduces left ventricular size in patients with left ventricular dysfunction

Background Congestive heart failure depletes the myocardium of carnitine, coenzyme Q10 (CoQ10), and taurine—substances known to influence mitochondrial function and cell calcium. We hypothesized that feeding patients a nutritional supplement that contained carnitine, CoQ10, and taurine would result in higher myocardial levels of these nutrients and improve left ventricular function. Methods Forty-one patients who underwent aortocoronary artery bypass with an ejection fraction ≤40% at referral were randomly assigned to a double-blind trial of supplement or placebo. Radionuclide ventriculography was performed at randomization and before surgery. Surgical myocardial biopsies, adjusted for protein content, were analyzed for carnitine, CoQ10, and taurine levels. Results The groups were well matched. Minor exceptions were supplement group versus placebo group for digoxin use (7 vs 0, respectively; P = .009) and age (62 ± 11 years vs 69 ± 5 years, respectively; P = .04). There were significantly higher levels in the treated group compared with the placebo group for myocardial levels of CoQ10 (138.17 ± 39.87 nmol/g wet weight and 56.67 ± 23.08 nmol/g wet weight; P = .0006), taurine (13.12 ± 4.00 μmol/g wet weight and 7.91 ± 2.81 μmol/g wet weight; P = .003), and carnitine (1735.4 ± 798.5 nmol/g wet weight and 1237.6 ± 343.1 nmol/g wet weight; P = .06). The left ventricular end-diastolic volume fell by −7.5 ± 21.7 mL in the supplement group and increased by 10.0 ± 19.8 mL in the placebo group (P = .037). Conclusions Supplementation results in higher myocardial CoQ10, taurine, and carnitine levels and is associated with a reduction in left ventricular end-diastolic volume in patients with left ventricular dysfunction before revascularization. Because the risk of death for surgical revascularization is related to preoperative left ventricular end-diastolic volume, supplementation could improve outcomes. (Am Heart J 2002;143:1092-100.)