卡维地洛、西拉普利及其合用防治大鼠急性心肌梗死左室重塑的作用

目的:评价卡维地洛、西拉普利及其合用防治大鼠急性心肌梗死(AMI)左室重塑(LVRM)的作用。方法:AMI术后24h存活的100只雌性SD大鼠随机分成:①AMI对照(n=25)、②AMI+卡维地洛(1mg·kg^-1·d^-1, n=25)、③AMI+西拉普利(1mg·kg^-1·d^-1, n=25)及④AMI+合用(n=25)4组;另设假手术组(n=17).直接灌胃给药。4周后行血流动力学测定和病理学分析。去除梗死面积<35%或>55%者, 最终在以上各组分别有(13, 12, 12, 14)和13只大鼠。结果:AMI各组间梗死面积差异均无显著性(45.2%-46.7%, 均P>0.05).AMI对照组的左室舒张末压(LVEDP)、容积(LVV)、重量(LVW)和室间隔厚度(STh)均显著大于假手术组(均P<0.01), 左室内压最大上升和下降速率(±dp/dt)及其校正值(±dp/dt/LVSP)均显著低于假手术组(P<0.05, P<0.01).卡维地洛、西拉普利及合用组的LVEDP、LVV均显著低于AMI对照组(P<0.01), STh均显著薄于AMI对照组(P<0.01), LVW均显著轻于AMI对照组(P<0.05, P<0.01), ±dp/dt显著高于AMI对照组(P<0.05, P<0.01), 且LVEDP和STh在合用组显著低于两单用药组(P<0.05, P<0.01), 余指标在3个用药组间差异均无显著性(均P>0.05).结论:卡维地洛、西拉普利及其合用均能有效防治大鼠AMI左室重塑并改善血流动力学和左室功能,且以合用更佳。     

氟伐他汀对大鼠心肌梗死后左室功能、肌球蛋白重链基因表达及胶原重建的影响

目的：观察羟甲基戊二酰辅酶A还原酶抑制剂氟伐他汀对大鼠急性心肌梗死(AMI)后左室功能、肌球蛋白重链（α、β MHC）基因转录mRNA表达及胶原重建的影响。 方法： 雌性SD大鼠AMI术后6 h随机分为：①AMI对照组；②氟伐他汀组；③假手术组。 直接灌胃给药8周后行高频多普勒超声、血流动力学、左室心肌α、β MHC的mRNA、非梗死区胶原容积分数(CVF)及Ⅰ/Ⅲ胶原的免疫组化测定。 结果： AMI组E峰、E峰减速度、E/A、左室舒张末压(LVEDP)、β MHC mRNA、非梗死区CVF及Ⅰ/Ⅲ胶原比值明显高于假手术组，左室短轴速短率（FS）、射血分数（EF）、平均动脉压（MAP）和α MHC mRNA 显著低于假手术组。氟伐他汀组的E峰、E峰减速度、E/A、LVEDP、β MHC mRNA、非梗死区CVF及I/Ⅲ胶原比值明显低于AMI组，FS、EF、MAP和α MHC mRNA显著高于AMI组。 结论： 氟伐他汀对心梗后左室功能、肌球蛋白链基因mRNA表达及胶原重建可产生有益的影响。     

Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction

Background

We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model.

Methods

Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h.

Results

In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05).

Conclusion

MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model.     

The effects of cycle racing on pulmonary diffusion capacity and left ventricular systolic function

The purpose of this study was to examine the effects of a 20 km cycle race (TT) on left ventricular (LV) systolic and pulmonary function in 12 endurance cyclists. Spirometry, single-breath diffusion capacity (DLCO) with partitioning of membrane (DM) and capillary blood volume (Vc) components and 2-D echocardiograms were performed before and after the TT. During the TT mean oxygen consumption was 3.79 +/- 0.5 L x min(-1) (83 +/- 5.5% of VO2max) and mean blood lactate was 8.4 +/- 2.4 mM. Following the TT, spirometry values were unchanged, however, DLCO and DM were significantly (P<0.05) reduced. LV systolic function was increased (P<0.05) immediately after exercise, while end-diastolic area was decreased (P<0.05) at all points during recovery. The reduction in DM was correlated with LV systolic function following the TT. This relationship suggests a cardiovascular contribution to pulmonary diffusion impairment following exercise.     

Endurance rather than sprint running training increases left ventricular wall thickness in female athletes

Competitive athletics is often associated with moderate left ventricular (LV) hypertrophy. The aim of this study was to shed more light on the extent and type of cardiac hypertrophic response to different athletic conditioning in females. Standard two-dimensional M-mode and Doppler echocardiography was performed at rest in Caucasian female sprinters (n = 10) and long-distance runners (n = 10) of similar age (range 16–34 years), training experience (5–18 years) and competitive level, and in age-matched healthy female sedentary controls (n = 10). No differences in echocardiographic parameters were detected between female sprinters and sedentary controls (p > 0.05). Interventricular septum and LV wall (p < 0.05) were thicker, and LV mass was greater (p < 0.01) in long-distance runners as compared with sprinters or sedentary controls. Absolute LV diameter was not increased in long-distance runners (p > 0.05), though relative LV diameter was higher in long-distance runners as compared to sprinters (p < 0.05). As compared with controls, relative wall thickness (the sum of LV wall thickness and interventricular septum thickness divided by LV diameter) was higher (p = 0.004) in long-distance runners. Neither systolic nor diastolic LV parameters were different among the groups (p > 0.05). In conclusion, sprint running training has not been found to induce alterations in cardiac morphology or function at rest in female athletes. Cardiac mass in female long-distance runners is higher mainly due to myocardial wall thickening, while integral myocardial function at rest is not affected as a consequence of either this hypertrophy or sprint training.     

Preload maintenance and the left ventricular response to prolonged exercise in men

This study examined whether left ventricular function was reduced during 3 h of semi-recumbent ergometer cycling at 70% of maximal oxygen uptake while preload to the heart was maintained via saline infusion. Indices of left ventricular systolic function (end-systolic blood pressure-volume relationship, SBP/ESV) and diastolic filling (ratio of early to late peak filling velocities into the left ventricle, E:A) were calculated during recovery and compared with baseline resting data. During exercise in seven healthy, trained male subjects, an arterial catheter allowed continuous assessment of arterial pressure, stroke volume (SV), cardiac output ( ) and an index of contractility (dP/dt(max)). A venous catheter assessed that central venous pressure (CVP) was maintained throughout rest, exercise and 10 min into recovery. Both systolic blood pressure and heart rate (HR) increased with the onset of exercise (from 132 +/- 5 to 185 +/- 19 mmHg and from 66 +/- 9 to 135 +/- 23 beats min(-1); increases from rest to the end of the first 5 min of exercise in SBP and HR, respectively) but systolic blood pressure did not change from 30 to 180 min of exercise ( approximately 150 mmHg), while heart rate only increased by 8 +/- 9 beats min(-1) (means +/- s.d.; P > 0.05). The attenuated increase in HR compared with other studies suggests that the maintained CVP ( approximately 5 mmHg) helped to prevent cardiovascular drift in this protocol. Stroke volume, and dP/dt(max) were all increased with the onset of exercise (from 85 +/- 8 to 120 +/- 18 ml, from 5.4 +/- 1.3 to 16.5 +/- 3.3 l min(-1) and from 14.4 +/- 4 to 28 +/- 8 mmHg s(-1); values from rest to the end of the first 5 min of exercise for SV, and dP/dt(max), respectively) and were maintained during exercise. There was no difference in the SBP/ESV ratio from pre- to postexercise. Conversely, E:A was reduced from 2.0 +/- 0.4 to 1.6 +/- 0.5 postexercise (P < 0.05), returning to normal values at 24 h postexercise. This change in diastolic filling could not be fully explained (r(2) = 0.39) by an increased heart rate and, with CVP unchanged, it is likely to represent some depression of intrinsic relaxation properties of left ventricular myocytes. Three hours of semi-supine cycling resulted in no evidence of a depression in left ventricular systolic function, while left ventricular diastolic function declined postexercise.     

Left ventricular pressure-volume relationships during normal growth and development in the adult rat--studies in 8- and 50-week-old male Wistar rats

AIMS: Left ventricular (LV) pressure-volume relations provide relatively load-independent indexes of systolic and diastolic LV function, but few data are available on pressure-volume relations during growth and development in the normal adult heart. Furthermore, to quantify intrinsic ventricular function the indexes should be normalized for heart weight. However, in many studies the indexes are reported in absolute terms, or body weight-correction is used as a surrogate for heart weight-correction. METHODS: We determined pressure-volume relations in young (8-week-old, n = 13) and middle-aged (50-week-old, n = 19) male Wistar rats in relation to their heart and body weights. The animals were anaesthetized and a 2F pressure-conductance catheter was introduced into the LV to measure pressure-volume relations. RESULTS: Heart and body weights were significantly higher in the 50-week-old rats, whereas the heart-to-body weight ratio was significantly lower (2.74 +/- 0.32 vs. 4.41 +/- 0.37 mg g(-1), P < 0.001). Intrinsic systolic function, quantified by the slopes of the end-systolic pressure-volume relation (E(ES)), the dP/dt(MAX) vs. end-diastolic volume relation (S-dP), and the preload recruitable stroke work relation (PRSW), normalized for heart weight, was slightly decreased in the 50-week-old rats (S-dP: -6%, P < 0.004; PRSW: -3%, P < 0.06). Heart weight-corrected diastolic indexes were not significant different. The absolute indexes qualitatively showed the same results, but body-weight corrected pressure-volume indexes showed improved systolic function and significantly depressed diastolic function. CONCLUSIONS: Intrinsic systolic function slightly decreases from the juvenile to the middle-aged period in normal male Wistar rats. Furthermore, correction of pressure-volume indexes for body weight is not an adequate surrogate for heart weight-correction in these animals.     

Diastolic function in healthy humans: non-invasive assessment and the impact of acute and chronic exercise

Left ventricular (LV) diastolic function is important because the enhanced systolic function that underpins high levels of cardio-respiratory fitness has to be matched by changes in LV filling, and LV diastolic dysfunction plays a key early role in the development and progression of a myriad of cardiovascular diseases. This review serves to detail knowledge in relation to: (1) the definition of diastole and the mechanical processes that occur during the diastolic period, (2) the quantitative assessment of diastolic function, predominantly focusing on non-invasive echocardiographic imaging modes such as tissue Doppler imaging and deformation analysis, (3) the impact of acute aerobic exercise on diastolic function, from the augmentation of function necessary to meet the demand for an increased cardiac output at exercise onset, to current concerns related to the impact of prolonged or ultra-endurance activity on diastolic function during recovery, (4) the adaptation in diastolic function observed with chronic aerobic exercise training in athletes and sedentary individuals who undergo training programmes, and (5) directions for future research.     

基质金属蛋白酶及其组织型抑制剂活性及表达失衡与高血压性左心室重塑的关系

目的： 探讨慢性压力负荷增高时，大鼠左心室（LV）基质金属蛋白酶（MMPs）/组织型基质金属蛋白酶抑制剂（TIMPs）失衡与LV重塑的关系。方法：40只6周龄雄性卒中易感性自发性高血压大鼠（SHR-SPs）作为研究对象，10只同周龄雄性Wistar-Kyoto（WKY）大鼠作为对照。6个月后，以Millar压力容积导管评价2组大鼠的在体LV血流动力学，并对2组大鼠的心脏进行组织病理学、明胶酶谱和免疫印迹法分析。结果：反映LV收缩与舒张功能的血流动力学参数在2组间有显著差异（P＜0.05）；SHR-SPs心脏胶原容积分数、血管周胶原面积/管腔面积、心肌横断面积、心室壁动脉中膜面积/管腔面积均增高（P＜0.05）；心肌MMP-2活性、蛋白含量及TIMP-1蛋白含量在SHR-SPs中明显增高（P＜0.05）。结论：慢性压力超负荷能够导致心脏细胞外基质代谢失调及MMPs/TIMPs系统失衡，继而产生心室腔扩张、LV收缩与舒张功能障碍。     

Transmural distribution of left ventricular glucose uptake in spontaneously hypertensive rats during rest and exercise

The transmural distribution of glucose uptake was studied in the left ventricle of 6-month-old male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) during rest and swimming (20 min) using the 2-deoxyglucose method. The baseline mean arterial pressure was 128 +/- 8 (n = 8) in the WKY and 188 +/- 22 mmHg (n = 8) in the SHR (P less than 0.001). This pressure remained constant in the resting groups, whereas the product of mean arterial pressure and heart rate was initially 45 x 10(3) +/- 3 x 10(3) and 63 x 10(3) +/- 4 x 10(3) mmHg beats min-1 in the swimming WKY and SHR and increased by 34-48 x 10(3) mmHg beats min-1 during the swimming period. Total glucose uptake was 3.9 +/- 1.2 mumol min-1 g-1 protein in the resting WKY rats and 1.4 +/- 0.4 mumol min-1 g-1 protein (P less than 0.001) in the swimming ones, the corresponding values for the resting and swimming SHR being 4.8 +/- 1.4 mumol min-1 g-1 protein and 3.2 +/- 1.2 mumol min-1 g-1 protein (P less than 0.01). Glucose uptake was 30% greater in the subendocardium (ENDO) of the resting WKY than in the subepicardium (EPI) (P less than 0.01), but this gradient disappeared during swimming. Glucose uptake in the resting SHR was greatest in the middle layer of the ventricular wall, with no difference between ENDO and EPI, whereas during swimming the glucose uptake was distributed evenly across the left ventricular wall. The blood lactate/pyruvate ratio increased only transitorily during the first minutes in the swimming SHR, while their plasma free fatty acid concentration was 1.2-1.3 mM initially and decreased by 32% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

缬沙坦对阿霉素心肌病大鼠的心脏保护作用及机制研究

目的： 探讨AT1受体阻滞剂缬沙坦对阿霉素心肌病(ADR-DCM)大鼠的心脏保护作用及其机制。方法: 雄性Wistar大鼠分3组：(1)阿霉素心肌病组(ADR-DCM，n=25)，阿霉素 2.5 mg/kg，尾静脉注射，每周1次，连续10周；(2)阿霉素心肌病+缬沙坦治疗组(ARB，n=10)， 缬沙坦 30 mg/kg，每天1次，灌胃治疗；(3)正常对照组(CON，n=10)。12周时进行超声和血流动力学检测，氯胺T法检测羟脯氨酸及胶原含量， Western印迹分析检测MMP-2、MMP-9及TIMP-1的表达，明胶酶谱法检测MMPs活性。结果: ARB组死亡率明显低于ADR-DCM组(20% vs 40%，P<0.01)。ADR-DCM组大鼠左室内径大于CON组，心功能明显低于CON组， ARB组左室内径增加程度及心功能各项指标变化低于ADR-DCM组。ADR-DCM组心肌羟脯氨酸及胶原含量高于CON组， ARB组显著低于ADR-DCM组(P<0.01)。ADR-DCM组左室心肌MMP-2、MMP-9蛋白表达及MMPs明胶酶活性明显高于CON组 (P<0.01)，ARB组MMP-2、MMP-9表达及活性明显低于ADR-DCM组(P<0.01)，而TIMP-1的表达在3组间均无显著差异(P>0.05)。结论: 缬沙坦部分通过抑制MMPs表达及活性逆转ADR-DCM左室重构，改善心功能。     

Serum profiles of C-C chemokines in acute myocardial infarction: possible implication in postinfarction left ventricular remodeling.

C-C chemokines are essential factors in the recruitment and activation of leukocytes from the circulation into inflamed tissue and may play a role in ischemia-induced myocardial injury and left ventricular remodeling after acute myocardial infarction (AMI). We investigated the kinetics of three major C-C chemokines, macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and regulated on activation normally T cell expressed and secreted (RANTES), in the sera of AMI patients and correlated the findings with the severity of the disease. Serum levels of C-C chemokines were determined in 35 AMI patients by ELISA assays serially during the first week of hospitalization and 1 month after hospital admission. Patients (n = 18) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 17) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, and 15 age-matched and sex-matched volunteers were used as healthy controls. A sustained increase in serum C-C chemokines was observed in both AMI groups during the 7-day hospitalization period. Peaks of these inflammatory factors were significantly higher in group B than in group A (MCP-1, 295 +/- 11 vs. 203 +/- 9 pg/ml, p < 0.01; MIP-1 alpha, 30 +/- 1 vs. 24 +/- 2 pg/ml, p < 0.05; RANTES, 32 +/- 2 vs. 16 +/- 1 ng/ml, p < 0.01) and healthy controls (MCP-1, 125 +/- 7 pg/ml, p < 0.001; MIP-1 alpha, 14 +/- 1 pg/ml, p < 0.001; RANTES, 12 +/- 1 ng/ml, p < 0.001). In group B, significant correlations were found between the peak of MCP-1 and the peak of C-reactive protein levels (r = 0.55, p < 0.02) as well as wedge pressure (r = 0.40, p < 0.05). In the same group, the peak of MIP-1 alpha levels was also significantly correlated with the peak of serum creatine kinase-myocardial band (MB) (r = 0.51, p < 0.04) and left ventricular ejection fraction (LVEF) (r = -0.45, p < 0.05). After 1 month, AMI patients (n = 14) with severe left ventricular dysfunction (LVEF < or = 35%) exhibited significantly higher levels of C-C chemokines (all p < 0.05) than the other AMI patients (n = 21) (LVEF > 35%). A significant correlation was found between MIP-1 alpha levels and left ventricular end-diastolic diameter (r = 0.47, p < 0.03) in this patient population. In conclusion, we have detected a significant elevation of major C-C chemokines during the course of AMI, with the highest levels in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. The elevation of these chemotactic inflammatory factors may actively contribute to the pathophysiology of the disease and the subsequent left ventricular remodeling.     

Effect of aerobic training on diabetic nephropathy in a rat model of type 2 diabetes mellitus

The effect of aerobic exercise intervention on the renal functional and ultrastructural changes associated with diabetes mellitus were studied in the obese Zucker rat, a rat model of type 2 diabetes. The obese Zucker rats began training at 18 wk of age (n=8) and were compared to obese sedentary controls (n=12) and lean sedentary nondiseased littermates (n=10). Body weight, kidney weight, serum creatinine, urine creatinine, creatinine clearance, urine IgG, urine IgG/creatinine ratio, urine total protein, urine albumin, urine albumin/creatinine ratio, glycated hemoglobin, serum fructosamine, fasting serum glucose, serum insulin, serum total cholesterol, serum triglycerides, blood pressure, and morphometric analyses of cortical glomeruli by light microscopy and electron microscopy were performed to evaluate renal function, structure, and metabolic control. The exercise training consisted of treadmill running, 5 da/wk for 1 hr/da. Exercise intervention lowered the body weight (p <0.05), reduced the percentage of glycated hemoglobin (p <0.05), and diminished the urine albumin concentration (p <0.05), compared to the obese sedentary controls. Exercise intervention did not significantly affect morphometric indices of renal ultrastructure. This study shows that aerobic exercise intervention significantly improved metabolic control and reduced albuminuria in a rat model of type 2 diabetes.     

Device based left ventricular shape change: validation of conductance technology in shape changed hearts

We have reported that device based left ventricular (LV) shape change, accomplished by Myosplint, improved LV systolic function by three-dimensional echocardiography (3-D echo). However, evaluation of this device using the pressure-volume relationship is still important. This study was conducted to validate the use of conductance technology for this evaluation in shape-changed hearts. An ex vivo study using excised ovine hearts (n = 11) and an in vivo study using a canine pacing-induced heart failure model (n = 11) were performed. Three Myosplints were implanted. Before and after the shape changes, volumes measured by a conductance catheter were compared with volumes measured by the amount of saline in the ex vivo study or by 3-D echo in the in vivo study. The conductance volumes were linearly correlated with the saline volumes (r2 = 0.961+/-0.046; p < 0.0001) in the ex vivo study and with 3-D echo volumes (r2 = 0.757+/-0.220; p < 0.0001) in the in vivo study. The conductance volumes were linearly correlated with LV volumes even in the shape-changed hearts. This technology can be used to evaluate pressure-volume loops in the shape-changed hearts as long as the conductance volume is calibrated by a reliable method.     

Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction

Adult bone marrow (BM) contains Sca-1+/Lin-/CD45- very small embryonic-like stem cells (VSELs) that express markers of several lineages, including cardiac markers, and differentiate into cardiomyocytes in vitro. We examined whether BM-derived VSELs promote myocardial repair after a reperfused myocardial infarction (MI). Mice underwent a 30-minute coronary occlusion followed by reperfusion and received intramyocardial injection of vehicle (n= 11), 1 x 10(5) Sca-1+/Lin-/CD45+ enhanced green fluorescent protein (EGFP)-labeled hematopoietic stem cells (n= 13 [cell control group]), or 1 x 10(4) Sca-1+/Lin-/CD45- EGFP-labeled cells (n= 14 [VSEL-treated group]) at 48 hours after MI. At 35 days after MI, VSEL-treated mice exhibited improved global and regional left ventricular (LV) systolic function (echocardiography) and attenuated myocyte hypertrophy in surviving tissue (histology and echocardiography) compared with vehicle-treated controls. In contrast, transplantation of Sca-1+/Lin-/CD45+ cells failed to confer any functional or structural benefits. Scattered EGFP+ myocytes and capillaries were present in the infarct region in VSEL-treated mice, but their numbers were very small. These results indicate that transplantation of a relatively small number of CD45- VSELs is sufficient to improve LV function and alleviate myocyte hypertrophy after MI, supporting the potential therapeutic utility of these cells for cardiac repair. Disclosure of potential conflicts of interest is found at the end of this article.     

Endurance training accelerates exhaustive exercise-induced mitochondrial DNA deletion and apoptosis of left ventricle myocardium in rats

Even though exhaustive exercise-induced oxidative stress increases the risk of tissue damage, regular endurance training is widely assumed to improve cardiac function and protects against heart disease. We tested the hypothesis that an endurance training program prevents exhaustive exercise-induced increases in cardiac dysfunction and apoptosis in left ventricle (LV). Thirty-two male Sprague-Dawley rats were randomly divided into four groups: sedentary control (C), trained (T), exhaustively exercised (E), and trained plus exhaustively exercised (TE). Rats in T and TE groups ran on a motorized treadmill for 12 weeks. Rats in groups E and TE performed an exhaustive running test on a treadmill. The main effects of training were indicated by increased running time to exhaustion (80 ± 5 and 151 ± 13 min for groups E and TE, respectively, P = 0.0001), myocardial hypertrophy (0.38% and 0.47% for untrained and trained rats, respectively, P = 0.0002), decreased LV ejection fraction (88% and 71% for untrained and trained rats, respectively, P < 0.0001), accelerated mitochondrial DNA 4834-bp large deletion (mtDNA⁴⁸³⁴ deletion), and up-regulated protein levels of heat shock protein-70, cytochrome C, cleaved capsase-3, and cleaved PARP in LV following a bout of exhaustive exercise. Contrary to our hypothesis, these results suggest that endurance training induced significant impairment of regional systolic and diastolic LV myocardial function and ejection fraction in rats. Our findings show that endurance training accelerates exhaustive exercise-induced mtDNA⁴⁸³⁴ deletion and apoptosis in the LV.     

Vagal reflex actions of atrial natriuretic peptide survive physiological but not pathological cardiac hypertrophy in rat

Atrial natriuretic peptide (ANP) enhances cardiac vagal baroreflexes in normotensive animals. In spontaneously hypertensive rats (SHRs) this effect of ANP was absent. The reflex actions of ANP were preserved if hypertrophy was completely prevented in SHRs. However even a small amount of cardiac hypertrophy, with no hypertension, in SHRs was accompanied by a loss of the reflex bradycardic actions of ANP. In the present study, we investigated whether pathophysiological cardiac hypertrophy, induced by one-kidney, one-clip renovascular hypertension (1K-1C; n = 6), or physiological cardiac hypertrophy induced by chronic spontaneous, wheel-running exercise training (n = 7), similarly prevented vagal reflex actions of ANP. Cardiac baroreceptor-activated bradycardia was measured during rapid ramp increases ( approximately 5 s) in blood pressure after bolus doses of methoxamine or vehicle in conscious, chronically instrumented rats during infusions of ANP (50 pmol kg(-1) min(-1)). Compared with uninephrectomised control rats (n = 10), rats with 1K-1C had cardiac hypertrophy (approximately 55% increase in left ventricle:body weight (LV:BW) ratio; P < 0.05) and blunted vagal baroreflex gain (-0.93 +/- 0.18 versus-0.50 +/- 0.13 beats min(-1) mmHg(-1); P < 0.05). ANP did not augment baroreflex function in 1K-1C. Compared with their sedentary controls (n = 7), exercise-trained rats with cardiac hypertrophy ( approximately 20% increase LV:BW ratio; P < 0.05) also had blunted ramp baroreflex bradycardia (-1.28 +/- 0.23 versus-0.57 +/- 0.09 beats min(-1) mmHg(-1); P < 0.05). In contrast, ANP more than doubled baroreflex bradycardia in exercise-trained rats (P < 0.05). The aetiology of cardiac hypertrophy therefore influenced whether ANP retained its vagal baroreflex enhancing properties.     

Quantification of left ventricular wall dysfunction by M-mode echocardiographic mapping in heart failure following acute myocardial infarction

Echocardiographic mapping was performed in 44 patients on arrival in hospital and day 2 following acute myocardial infarction (AMI). To evaluate left ventricular (LV) function the per cent deviation of the mean systolic wall velocity (PD-V) from the normal was measured from 16 LV segments. Adequate data were obtained from 89% of the segments. The number of hypokinetic segments was somewhat higher in anterior than inferior AMI, reaching significance (p less than 0.05) on day 2. Dyskinetic segments were also more common in patients with anterior infarction (p less than 0.001), who also had significantly higher enzyme maxima than patients with inferior AMI (p less than 0.01). Enzyme maxima correlated well with the sum of PD-V from all hypokinetic segments on day 1 (r = 0.79, p less than 0.01). Compensatory hyperkinesia was more common in inferior than anterior AMI (p less than 0.001). Global LV function, estimated by subtracting the number of hyper- from hypokinetic segments (score sigma S:Adj), was significantly related to heart failure (Killip classification) (p less than 0.01) and the respiratory rate (r = 0.71, p less than 0.01) in the acute phase as well as to heart failure during the first post AMI month (New York Heart Association classification).     

Preservation of renal structure and function in the rat remnant kidney model of chronic renal failure by enalapril treatment

The remnant kidney model of chronic renal failure was established in rats subject to subtotal (1 7/8) nephrectomy and the evolution of renal injury studied over a period of 6 wk. One wk after subtotal nephrectomy, rats had a mean conscious systolic blood pressure of 158 +/- 5 mm Hg and serum creatinine of 128 +/- 9 mumol/l. Both systolic blood pressure and serum creatinine rose over the next 5 wk in concert with progressive glomerulosclerosis and proteinuria. Enalapril, an angiotensin converting enzyme inhibitor, was administered (5 mg/kg/day) to rats (n = 11) from 1 wk after subtotal nephrectomy. Enalapril lowered systolic blood pressure over the treatment period. Systolic blood pressure was 122 +/- 5 mm Hg compared with 176 +/- 7 mm Hg in untreated rats (p less than 0.001) at 6 wk. Serum creatinine 6 wk after subtotal nephrectomy was 110 +/- 9 mumol/l with enalapril treatment, compared with 159 +/- 21 mumol/l (p less than 0.025) in control animals. Enalapril treated rats had lower urinary protein excretion than controls (15 +/- 3 mg/24 hr vs 85 +/- 22 mg/24 hr, p less than 0.0001) at 6 weeks. Glomerulosclerosis, assessed by blinded histological score, was also reduced in the enalapril treated group (1.79 +/- 0.08 vs 2.36 +/- 0.16, p less than 0.01). Enalapril treatment was associated with a reduction in filtration fraction (51Cr-EDTA/125I-hippurate clearance). At 6 wk, filtration fraction was 0.30 +/- 0.03 in enalapril treated and 0.48 +/- 0.03 in control rats (p less than 0.001). Enalapril treatment in the subtotal nephrectomy model of renal failure preserved renal structure and function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between tyrosine hydroxylase polymorphisms and left ventricular structure in young normotensive men

Tyrosine hydroxylase (TH) is a rate-limiting enzyme for catecholamine biosynthesis. Increased sympathetic activity is associated with an increased left ventricular (LV) mass. However, the influence of TH gene polymorphisms on LV structure and function has yet to be investigated. Here, we analyse the association of Val-81-Met and tetranucleotide TCAT repeat TH polymorphisms with LV structure and function (assessed by echocardiography) in 108 normotensive men aged < or = 35 years (mean age: 25+/-4 years) with body mass index (BMI) < or = 30 kg/m2 (mean BMI: 23+/-3 kg/m2). The distribution of genotypes was VV homozygotes (n=42), VM heterozygotes (n=49) and MM homozygotes (n=17). The Val-81-Met polymorphism showed significant linkage disequilibrium with the TCAT polymorphism (P<0.0001). No differences were seen between the subgroups with respect to age, BMI and blood pressure. Compared with the VV and VM genotypes, subjects with the MM genotype showed significantly (all P<0.05) increased LV cavity diameter (VV: 52.8+/-3.9 mm, VM: 52.9+/-3.6 mm, MM: 56.1+/-3.2 mm), global LV mass (VV: 159+/-31 g, VM: 165+/-36 g, MM: 187+/-30 g) and LV mass index (VV: 81+/-14 g/m2, VM: 84+/-17 g/m2, MM: 93+/-12 g/m2). No differences were seen between the subgroups in parameters of LV function. In addition, plasma epinephrine and norepinephrine levels were comparable in the three subgroups. The results suggest an important association between the MM genotype of Val-81-Met TH gene polymorphism and increased LV cavity dimension and mass in a young normotensive male population, indicating an important role for genetic determination of the sympathetic system in LV growth.