Myocardial viability: impact on left ventricular dilatation after acute myocardial infarction

Objective: To evaluate whether the presence of viable myocardium, detected by low dose dobutamine echocardiography, limits the likelihood of left ventricular dilatation in patients with acute myocardial infarction.     

Does left ventricular dyssynchrony immediately after acute myocardial infarction result in left ventricular dilatation?

BACKGROUND: Reverse remodeling of the left ventricle (LV) is one of the advantageous mechanisms of cardiac resynchronization therapy (CRT). Substantial LV dyssynchrony seems mandatory for echocardiographic response to CRT. Conversely, LV dyssynchrony early after acute myocardial infarction may result in LV dilatation during follow-up. OBJECTIVE: The purpose of this study was to evaluate the relation between LV dyssynchrony early after acute myocardial infarction and the occurrence of long-term LV dilatation. METHODS: A total of 124 consecutive patients presenting with acute myocardial infarction who underwent primary percutaneous coronary intervention were included. Within 48 hours of intervention, two-dimensional echocardiography was performed to assess LV volumes, LV ejection fraction (LVEF), and wall motion score index (WMSI). LV dyssynchrony was quantified using color-coded tissue Doppler imaging (TDI). At 6-month follow-up, LV volumes and LVEF were reassessed. RESULTS: Patients with substantial LV dyssynchrony (> or =65 ms) at baseline (18%) had comparable baseline characteristics to patients without substantial LV dyssynchrony (82%), except for a higher prevalence of multivessel coronary artery disease (P = .019), higher WMSI (P = .042), and higher peak levels of creatine phosphokinase (P = .021). During 6 months of follow-up, 91% of the patients with substantial LV dyssynchrony at baseline developed LV remodeling, compared with 2% in the patients without substantial LV dyssynchrony. LV dyssynchrony at baseline was strongly related to the extent of long-term LV dilatation at 6 months of follow-up. CONCLUSION: Most patients with substantial LV dyssynchrony immediately after acute myocardial infarction develop LV dilatation during 6 months of follow-up.     

The prevention of postinfarction left ventricular dilatation by captopril]

Thirty patients admitted to the ICCU with a first myocardial infarction (MI) of any localization, with left ventricular dysfunction revealed by echo-Doppler ejection fraction (EF) < 40%, where randomly divided in three groups of ten: GROUP 1 who was treated with captopril 25 mg orally between the 5th and 7th day post MI, and sustained until the end of the study. GROUP 2 received nifedipine, 10 mg capsules t.i.d. also started between days 5 and 7 post MI. GROUP 3 as a control group was treated conventionally, according to the ICCU routine. The treatment was maintained during 12 months. All patients had a second echo-Doppler at the 5th day post MI to confirm the EF criteria. Also left ventricular end-systolic and end-diastolic diameters were measured. At the 5th day post MI and before the drug administration, a low level treadmill stress test was performed in all patients. Subsequently a maximal stress test (Bruce protocol) was done at the first month and at 6 and 12 months of the study. The results showed a significant increase EF in patients of GROUP 1 from an average basal value of 38 +/- 2 to 54 +/- 5 at six months (p < 0.01) and to 60 +/- 3 at 12 months (p < 0.005). The increments observed in patients of GROUP 2 and 3 were more modest; only the 12 month value in GROUP 3, from a basal figure of 41 +/- 3 to 50 +/- 4, had a p < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heart rate variability and left ventricular dilatation early after myocardial infarction.

To assess clinically whether alterations of autonomic tone precede left ventricular dilatation, heart rate variability and early left ventricular dilatation after a first myocardial infarction were assessed. Low-frequency power (LF), high-frequency power (HF), and total power (TP) were obtained by ambulatory electrocardiogram on day 1 in 53 patients with a first acute myocardial infarction. Left ventricular end-diastolic volume determined by echocardiography was obtained on day 1 and day 14. Stepwise linear regression analysis was used to assess the associations of early left ventricular dilatation with heart rate variability adjusted for clinical variables. Higher LF and TP were significantly associated with early left ventricular dilatation after adjustment for age, sex, site of myocardial infarction, acute revasucularization, peak creatine kinase level, history of hypertension, and use of angiotensin-converting enzyme inhibitors and beta-blockers. Higher LF and TP preceded early left ventricular dilatation after myocardial infarction.     

Effects of captopril treatment on left ventricular remodeling and function after anterior myocardial infarction: comparison with digitalis.

The effects of captopril and digoxin treatment on left ventricular remodeling and function after anterior myocardial infarction were evaluated in a randomized unblinded trial. Fifty-two patients with a first transmural anterior myocardial infarction and a radionuclide left ventricular ejection fraction less than 40% were randomly assigned to treatment with captopril (Group A) or digoxin (Group B). The two groups had similar baseline hemodynamic, coronary angiographic, echocardiographic and radionuclide angiographic variables. Among the 40 patients (20 in each group) who were followed up for 1 year, echocardiographic end-diastolic and end-systolic volumes were unmodified in Group A and global wall motion index was improved (p less than 0.01); in Group B, end-diastolic and end-systolic volumes increased (p less than 0.001 for both) and global wall motion index was unchanged. Rest radionuclide ejection fraction increased significantly in both groups (p less than 0.001, Group A; p less than 0.005, Group B). A comparison of the changes in the considered variables between the two groups after 1 year of treatment showed a difference in end-diastolic (p less than 0.005) end-systolic volumes (p less than 0.001) and global wall motion index (p less than 0.005) without differences in radionuclide ejection fraction, which improved to a similar degree in both groups. The results of this study suggest that captopril therapy, started 7 to 10 days after symptom onset in patients with anterior myocardial infarction and an ejection fraction less than 40%, improves both left ventricular remodeling and function and prevents left ventricular enlargement and in these patients performs better than digitalis.     

Serial changes in left ventricular relaxation and chamber stiffness after large myocardial infarction in rats

To determine the time course of changes in left ventricular diastolic properties after a large myocardial infarction, we serially measured left ventricular relaxation, chamber stiffness, and the ratio of left ventricular cavity to wall volume (V/VW) after coronary artery ligation in rats. Left ventricular relaxation was measured during the occlusion and then both relaxation and chamber stiffness were measured at 3 hr, 24 hr, and 3, 5, and more than 22 days after infarction. Left ventricular pressures and left ventricular dP/dt were recorded with micromanometer-tipped catheters. Left ventricular relaxation was measured by computer digitization of the left ventricular pressure tracings and averaged over 100 to 150 cardiac cycles. Five chamber stiffness constants were calculated from pressure-volume curves that were obtained ex vivo. We found ventricular relaxation prolonged for the first hour after coronary occlusion; relaxation was maximally prolonged at 10 to 15 min after onset of occlusion. After 1 hr relaxation returned to normal. However, by 5 days ventricular relaxation was again prolonged. Left ventricular stiffness constants were increased at 3 and 24 hr, resulting in a shift of the left ventricular pressure-volume relation to the left. At 3 days after coronary artery ligation, all stiffness constants and the pressure-volume relation returned to normal. At more than 22 days the pressure-volume relation was shifted to the right and the stiffness constant for low filling pressures was decreased. V/VW was significantly decreased from 0.603 +/- 0.021 at 3 and 24 hr to 0.379 +/- 0.024 and 0.362 +/- 0.032, respectively. V/VW was significantly increased at more than 22 days (0.921 +/- 0.094).(ABSTRACT TRUNCATED AT 250 WORDS)     

Early and late effects of captopril treatment after large myocardial infarction in rats

The early (after 21 days) and late (after 4 months) effects of continuous treatment with captopril on left ventricular performance, weight and volumes were studied in rats with myocardial infarction. Early effects were examined in rats subjected to coronary ligation and randomized to either immediate treatment with captopril (2 g/liter drinking water) starting 2 h after surgery or no treatment. After 21 days, the treated group showed reductions in mean arterial, left ventricular systolic and left ventricular end-diastolic pressures compared with untreated rats. Right and left ventricular weight and left ventricular volumes were decreased and the ejection fraction index was increased by captopril treatment. To study the late effects of captopril, a second group of rats was randomized to immediate captopril treatment (starting 2 h after surgery), delayed captopril treatment (starting 21 days after surgery) or no treatment. When studied after 4 months of treatment, rats started on captopril treatment 2 h after infarction showed no differences compared with rats started on treatment 21 days after infarction. Treatment with captopril for 4 months produced changes that were similar to those in rats treated for 21 days. Captopril treatment improved hemodynamic function after myocardial infarction in rats examined after either 21 days or 4 months of treatment. The extent of the benefit was similar in the two treatment periods. Initiation of captopril therapy immediately after infarction did not appear to produce a greater effect than treatment started at 21 days after infarction in rats studied after the drug had been administered for 4 months.     

卡托普利联合美托洛尔对急性心肌梗死晚期左心室重构的影响

目的探讨急性心肌梗死(AMI)后应用卡托普利联合美托洛尔治疗与单用卡托普利治疗对晚期左心室重构的影响。方法将121例AMI患者随机分成治疗组(卡托普利联合美托洛尔)63例和对照组(卡托普利)58例,采用彩色多普勒心动超声仪分别于发病后早期(<24 h)、3、6个月末连续随访并测量、计算左心室形态、构型等多项指标。结果进行治疗组早期到6个月末前后比较,左心室形态均呈逐渐扩大,6个月末最大,对照组扩大程度更明显。对照组与治疗组同期对应比较,左心室形态逐渐扩大,6个月末最明显,且差异有显著性意义。同时左心室射血分数同组和两组间对应比较,均有明显改善(P<0.05,P<0.01)。结论AMI后应用卡托普利联合美托洛尔对晚期左心室重构的抑制作用明显优于单用卡托普利。     

芪苈强心胶囊对大鼠心肌梗死后心肌重构及心功能的影响

目的 探讨芪苈强心胶囊对心肌梗死后大鼠心肌重构及心功能的影响.方法 结扎大鼠左前降支,建立AMI模型,存活者随机分为梗死对照组（MI组）和芪苈强心胶囊治疗组（MI-D组）,另设假手术组（Sham组）.MI-D组术后4周每天予芪苈强心胶囊生药4 g/kg（生理盐水溶为1.5 ml溶液）治疗,MI组和Sham组仅以等体积生理盐水灌胃,4周后对相关指标进行检测.结果 术后4周大鼠心脏超声及血流动力学均显示左室功能减低;基质金属蛋白酶2,9活性升高;α-MHC/β-MHC mRNA的比值下降.经芪苈强心胶囊治疗后左室功能有明显改善;基质金属蛋白酶2,9活性降低,α-MHC/β-MHC mRNA的比值升高.结论 芪苈强心胶囊治疗AMI可以改善心肌重构和心功能.芪苈强心胶囊治疗有效改善心功能的作用机制至少部分与其抑制心肌重构有关.     

Effects of captopril on left ventricular systolic and diastolic function after acute myocardial infarction.

The left ventricle progressively dilates in some patients after acute myocardial infarction (AMI). Both systolic and diastolic left ventricular (LV) dysfunction can be of significance in the development of heart failure. Captopril has been shown to prevent dilatation, but the effect on LV diastolic function is unknown. In a placebo-controlled double-blind parallel study, 58 AMI patients with heart failure or low ejection fraction, or both, were consecutively randomized at day 7 to either placebo or captopril (25 mg twice daily). No differences were present between the groups at baseline. Fifty-three patients completed the 6-month study period. Both LV diastolic and systolic volume indexes increased significantly in the placebo group (17 and 14%, respectively); in the captopril group there was no change in LV diastolic volume index, but a 13% reduction in LV systolic volume index. Ejection fraction increased significantly in the captopril group. The peak flow velocities of the early and atrial filling phases were measured, and the ratio between the velocities was calculated. A significant reduction was observed during the study period in early peak flow velocity (65 to 52 cm/s) and in the ratio between early and atrial peak flow velocity (1.3 to 0.8) in the placebo group (p less than 0.05), but no significant changes occurred in the captopril group. No correlation was found between dilatation of the left ventricle and reduction in early peak flow velocity or the ratio between early and atrial peak flow velocity. In conclusion, captopril prevented LV dilatation, improved ejection fraction and prevented LV diastolic dysfunction in AMI patients with early signs of LV systolic dysfunction.     

Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction

BACKGROUND: Transforming growth factor (TGF)-beta is a locally generated cytokine involved in healing processes and tissue fibrosis, all relevant for cardiac remodeling and the development of heart failure after myocardial infarction (MI). However, data regarding the function of TGF-beta after ischemic injury are inconclusive. METHODS AND RESULTS: We tested the effect of TGF-beta inhibition by application of a blocking antibody in mice with MI. Starting 1 week before or 5 days after coronary artery ligation mice were treated with intraperitoneal injections of an anti-TGF-beta (5 mg/kg bodyweight 1D11, Genzyme) or control antibody. Mortality over 8 weeks was significantly higher in the groups treated with the anti-TGF-beta antibody. Both, pre or post MI treatments were associated with increased left ventricular dilatation after MI as determined by serial echocardiography. In anti-TGF-beta treated mice collagen production decreased and matrix-metalloproteinase expression increased. However, the expression of TGF pro-inflammatory cytokine TNF-alpha was not altered by the treatment. Anti-TGF-beta treatment before or after coronary artery ligation increases mortality and worsens left ventricular remodeling in mice with non-reperfused MI. The detrimental effects of TGF-beta inhibition may be mediated by alterations in extracellular matrix remodeling.     

Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction

The effect of preexistent coronary collateral perfusion on the prevention of left ventricular aneurysm formation was examined in 47 patients undergoing an intracoronary thrombolysis within 6 hours after the onset of a first acute anterior myocardial infarction. Left ventricular aneurysm formation and wall motion were analyzed with cineventriculography. A left ventricular aneurysm was determined as well-defined demarcation of the infarcted segment from normally contracting myocardium. In 25 patients with successful thrombolysis (group A), a left ventricular aneurysm was observed in one patient (4%) during the chronic stage of infarction. In 10 patients who had a significant collateral circulation to the infarct-related coronary artery and unsuccessful reperfusion (group B), the left ventricular aneurysm was observed in only one patient (10%). In the remaining 12 patients with unsuccessful recanalization in the absence of a significant collateral perfusion (group C), there was a higher incidence (seven of 12, 58%) of left ventricular aneurysm formation than in groups A and B (p less than 0.05). In group A, both the global ejection fraction and regional wall motion in the infarct areas improved significantly (p less than 0.05) between the acute and chronic stages of infarction. By contrast, in groups B and C, these indexes on the ventricular function did not change significantly during the convalescent period. Thus, although the collateral perfusion existing at the onset of acute myocardial infarction may not improve ventricular function, it exerts a beneficial effect on the prevention of left ventricular aneurysm formation.     

Survival after myocardial infarction in rats: captopril versus losartan

Objectives. This study sought to compare the effects of angiotension-converting enzyme inhibition versus angiotensin II receptor blockade on survival in rats with myocardial infarction.Background. The effects of speciifc nonpeptide angiotensin receptor blocking agents on survival after myocardial infarction are unknown.Methods. Rats with a moderate to large myocardial infarction were treated with captpril (2 g/liter drinking water, n= 87) or losartan (2 g/liter drinking water, n= 96). Therapy was initiated immediately after coronary artery ligation and continued for 1 years.Results. Uncensored median survival in captopril-treated rats that survived at least 48 h was 201.5 days versus 236.0 days for losartan-treated rats (p = 0.066). Median survival censored for rats with lung infections was 201.5 days in captopril-treated rats versus 243.0 days for losartan-treated rats (p = 0.028). Conscious hemodynamic measurements and remodeling data obtained at 1 year in the surviving rats (n = 5 for captopril; n = 9 for losartan) revealed no differences in heart weight, left ventricular pressure, dP/dt, cardiac index, time constant of relaxation or any variable of left ventricular remodeling. The only differences (mean ± SD) were an increase in heart rate (293 ± 19 vs. 260 ± 15 beats/min, p < 0.05) and a decrease in peak developed pressure (153 ± 21 vs. 180 ± 16 mm Hg, p < 0.05) in the losartan-treated rats.Conclusions. We conclude that in this experimental model of heatr failure, there was no difference between survival after angiotensin II receptor blockade with losartan and with angiotensin-converting enzyme inhibition with captopril.     

Hemodynamic comparison of primary venous or arteriolar dilatation and the subsequent effect of furosemide in left ventricular failure after acute myocardial infarction

The hemodynamic effect of venous dilatation (intravenous isosorbide dinitrate [ISDN]) and arteriolar dilatation (intravenous hydralazine), both as firstline treatment and then combined with intravenous furosemide, were evaluated in a randomized, between-group comparison in 20 men with severe acute left-sided cardiac failure after myocardial infarction (MI). Both ISDN (50 to 200 micrograms/kg/hour) (Group 1) and hydralazine (0.15 mg/kg) (Group 2) reduced systemic arterial pressure (p less than 0.05) and vascular resistance (p less than 0.05). Pulmonary artery occluded pressure was reduced (p less than 0.01) only by ISDN, whereas heart rate (p less than 0.01), cardiac output (p less than 0.01) and stroke volume (p less than 0.05) were increased only after hydralazine. After ISDN, furosemide (1 mg/kg) decreased left-sided cardiac filling pressure by 1 mm Hg (p greater than 0.05), whereas after hydralazine, furosemide in a similar dose reduced pulmonary artery occluded pressure by 5 mm Hg (p less than 0.01). In both groups of patients, furosemide transiently increased systemic arterial pressure (p less than 0.05). Cardiac output was reduced (p less than 0.05) and systemic vascular resistance increased (p less than 0.05) in Group 1 patients after furosemide. Similar changes in both variables in Group 2 patients did not attain statistical significance. In conclusion, ISDN-induced venous dilatation is preferable to primary arteriolar dilatation by hydralazine as first-line treatment in acute left-sided cardiac failure. However, hydralazine and furosemide in combination were equally effective in reducing pulmonary artery occluded pressure and increasing cardiac output. The influences of each regimen on prognosis await further investigation.     

心肌梗死后心房结构重构的实验研究

心房颤动（房颤）是心肌梗死病程中较为常见的并发症，文献报道其发生率为7％～20％。越来越多的证据表明心房缝隙连接通道的改变在房性心律失常的发生中起重要作用，有研究发现缝隙连接蛋白40（connexin 40，Cx40）敲除小鼠的房性心动过速的易患性增加，提示心房Cx40的改变可能有助于房性心律失常的发生。本研究的目的是观察慢性心肌梗死后心房结构的改变，尤其是Cx40的空间分布和基因表达的变化，以阐明房颤发生的可能基质。     

心肌梗死后左室重构发病机制进展

急性心肌梗死(AMI)是威胁人类健康的重大疾病,心肌梗死(MI)后30 min,部分心肌细胞即发生不可逆的坏死,因此,MI有效救治的时间窗极为短暂,许多患者不能够得到及时有效的治疗,使得MI后心力衰竭(HF)的发生率仍然居高不下。最新调查研究表明,MI后1年HF的发生率约为14.2%。因MI后HF再次入院的患者,1年死亡率高达为45.5%。MI后HF的主要原因是部分心肌细胞坏死,左室重构,心脏扩张,继而引发HF。目前,MI后左室重构的机制尚未完全阐明。本文介绍了AMI后左室重构的发病机制主要进展。     

Effects of left ventricular shape and captopril therapy on exercise capacity after anterior wall acute myocardial infarction

The importance of left ventricular (LV) shape in determining exercise capacity was assessed in 40 male patients with LV dysfunction after anterior acute myocardial infarction (AMI). Because captopril therapy is known to improve exercise capacity in this patient population, the potential interaction between LV shape and captopril therapy was also evaluated. Patients underwent cardiac catheterization 2 to 4 weeks after AMI followed by randomization to receive placebo or captopril. LV shape was defined from biplane ventriculography by a sphericity index (volume observed/volume of sphere using long axis as diameter). Quarterly clinical assessments and maximal exercise testing were performed. A cumulative heart failure score, specific activity scale and average exercise time for the year were calculated. A greater shape distortion (increasing sphericity index) was associated with increased LV volumes, decreased ejection fraction and a larger abnormally contracting segment. Sphericity index was the only independent predictor of average exercise duration in the placebo group. Placebo-treated patients in the tercile with the most spherical ventricles had not only the lowest exercise capacity (p less than 0.01), but also accumulated the highest heart failure (p less than 0.05) and specific activity scale (p less than 0.05) scores. Captopril-treated patients with the same baseline distortion of LV shape did not manifest these shape-dependent objective and subjective measures of reduced functional capacity.     

Cellular basis of chronic ventricular remodeling after myocardial infarction in rats.

To determine whether the hypertrophic response of the surviving myocardium after infarction leads to normalization of ventricular hemodynamics and wall stress, the left coronary artery was ligated in rats. One month later, the rats were killed. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium bordering and remote from the scar was documented by increases in myocyte cell volume per nucleus of 43% and 25%, respectively. These cellular enlargements resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), myocyte hypertrophy was 81% and 32% in the regions adjacent to and distant from the scar, respectively. A 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased ninefold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Chamber dilation was the consequence of the combination of gross anatomic and cellular changes consisting, in the presence of small infarcts, of a 6% and a 19% increase in transverse midchamber diameter and in average myocyte length per nucleus, respectively. In the presence of large infarcts, transverse and longitudinal chamber diameters expanded by 27% and 11%, respectively, myocyte length per nucleus expanded by 26%, and the mural number of myocytes decreased by 10%. In conclusion, decompensated eccentric ventricular hypertrophy develops chronically after infarction, and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistance of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure.     

Beneficial effects of adrenomedullin on left ventricular remodeling after myocardial infarction in rats

OBJECTIVE: We previously reported that plasma adrenomedullin (AM) levels increase in patients with acute myocardial infarction (MI) and AM inhibits growth of rat cardiac myocytes and fibroblasts. The aim of this study was to examine the effects of long-term administration of AM on left ventricular (LV) remodeling, hemodynamic and hormonal parameters in a rat model of MI. METHODS: Rats with MI induced by left coronary ligation were intravenously infused with 1.0 microg/h of recombinant human AM or saline by osmotic mini-pump. After infusion for 4 weeks, hemodynamic and hormonal studies were performed, and the myocyte size and collagen volume in non-infarct LV area were quantified morphometrically. RESULTS: When compared with the MI rats infused with saline, continuous infusion of AM reduced the heart weight/body weight (4.4+/-0.2 vs. 3.6+/-0.1 g/kg, P<0.01), myocyte size (922+/-23 vs. 868+/-10 microm(2), P<0.05) and collagen volume fraction of non-infarct LV area (7.6+/-0.8 vs. 4.8+/-0.5%, P<0.05), without affecting the infarct size. The AM infusion had no significant effect on the arterial pressure, but decreased the LV end-diastolic pressure (8.8+/-1.8 vs. 4.4+/-0.5 mmHg, P<0.05) in the MI rats. The plasma level of endogenous rat AM in the MI rats infused with human AM was reduced by 27% (P<0.05), with a slight reduction of plasma atrial natriuretic peptide, compared with the control. CONCLUSIONS: Continuous administration of AM had beneficial effects on LV remodeling and hemodynamics in MI rats, suggesting the possibility that this peptide could be a useful therapeutic tool for acute MI.