Anti-inflammatory effects of exercise training in the early period after myocardial infarction

The aim of this investigation was to determine the effect of exercise training on the levels of plasma cytokines and acute phase reactants in the early post acute myocardial infarction (AMI) period. Sixty patients were enrolled into this three-week cardiac rehabilitation study. The mean time from AMI was 7.08 +/- 1.60 days, and the patient mean age was 60 +/- 10 years. Subjects were randomly assigned to one of the two groups: the control group treated with standard measures, and the group with additional regular moderate-intensity exercise training. Physical activity was based on the ergospirometry test results. Apart from clinical follow-up and routine laboratory analysis we determined the levels of plasma cytokines: tumor necrosis factor (TNF-alpha), soluble TNF-alpha receptor 1 (TNF-alphaSR1), interleukin (IL)-8, IL-10, and acute phase reactants: high sensitivity C-reactive protein (hsCRP) and fibrinogen. The obtained results confirmed the hypothesis that the early post AMI period is an inflammatory state the intensity of which gradually decreases with standard treatment during the first month after AMI, while including patients into early exercise training improves their inflammatory profile by decreasing the level of acute phase reactant and TNF-alphaSR1.     

Thrombolytic therapy for acute myocardial infarction

A retrospective analysis of 4,094 deliveries among Navajo Indian women was carried out to determine the prevalence of gestational diabetes mellitus and diabetes antedating pregnancy. Three data sources--a local prenatal registry, a delivery room log, and hospital discharge records--were evaluated for their usefulness as surveillance systems for gestational diabetes. In all, 177 cases of gestational diabetes and 13 cases of preexisting diabetes were identified, giving a prevalence of maternal diabetes in pregnancy of 4.6%. When women with preexisting diabetes or documented gestational diabetes during a previous pregnancy were excluded, the prevalence of gestational diabetes during the study period was 3.4%. Although each data source used separately failed to identify 20% to 40% of diabetic pregnancies, more than 97% of cases were identified using a combination of the prenatal registry and the delivery log.     

Atorvastatin therapy during the peri-infarct period attenuates left ventricular dysfunction and remodeling after myocardial infarction

Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI). Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14) received oral atorvastatin (10 mg/kg/d) daily for 3 wk before and 4 wk after MI, while group I (n = 12) received equivalent doses of vehicle. Infarct size (Masson''s trichrome-stained sections) was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF) and fractional area change (FAC) were higher while LV end-diastolic volume (LVEDV) and LV end-systolic and end-diastolic diameters (LVESD and LVEDD) were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dt_max, end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) and lower LV end-diastolic pressure (LVEDP). Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis.     

Gender differences in cardiac function during early remodeling after acute myocardial infarction in mice

There are conflicting data about gender differences in cardiac function after myocardial infarction (MI), including cardiac rupture and mortality. Using a mouse model of MI, we recently found that the cardiac rupture rate during the first week after MI was significantly lower in females than in males, suggesting that females have attenuated structural remodeling. Thus in this study, we attempted to determine whether: a) females have attenuated remodeling and faster healing during the early phase post-MI, and b) females have better cardiac function and outcome during the chronic phase compared to males. MI was induced in 12-week-old male and female C57BL/6J mice. Signs of early remodeling, including cardiac rupture, infarct expansion, inflammatory response, and collagen deposition, were studied during the first 2 weeks post-MI. Left ventricular remodeling and function were followed for 12 weeks post-MI. We found that males had a higher rate of cardiac rupture, occurring mainly at 3 to 5 days of MI and associated with a higher infarct expansion index. Neutrophil infiltration at the infarct border was more pronounced in males than females during the first days of MI, which were also characterized by increased MMP activity. However, the number of infiltrating macrophages was significantly higher in females at day 4. During the chronic phase post-MI, males had significantly poorer LV function, more prominent dilatation and significant myocyte hypertrophy compared to females. In conclusion, males have delayed myocardial healing, resulting in cardiac rupture, and the survivors have poorer cardiac function and pronounced maladaptive remodeling, whereas females show a better outcome during the development of HF.     

Use of beta-blocker therapy in older patients after acute myocardial infarction in Ontario.

BACKGROUND: Despite its proven efficacy, beta-blocker therapy remains underused in elderly patients after myocardial infarction (MI). The objectives of this study were to identify undertreated groups of seniors and to determine whether older and frailer patients are being selectively dispensed low-dose beta-blocker therapy. METHODS: From a comprehensive hospital discharge database, all people aged 66 years or more in Ontario who survived an acute MI between April 1993 and March 1995 were identified and classified into those who did not receive beta-blocker therapy and those dispensed low, standard or high doses of this agent. Logistic regression models were used to study the effect of age, sex, comorbidity, potential contraindications to beta-blocker therapy and residence in a long-term-care facility on the odds of not being dispensed a beta-blocker. Among beta-blocker users, the odds of being dispensed low relative to standard or high doses of this agent were evaluated. RESULTS: Of the 15,542 patients, 7549 (48.6%) were not dispensed a beta-blocker. Patients 85 years of age or more were at greater risk of not receiving beta-blocker therapy (adjusted odds ratio [OR] 2.8, 95% confidence interval [CI] 2.5-3.2) than were those 66 to 74 years. Having a Charlson comorbidity index of 3 or greater was associated with an increased risk of not receiving beta-blocker therapy (adjusted OR 1.5, 95% CI 1.3-1.8) compared with having lower comorbidity scores. Patients who resided in a long-term-care facility were at increased risk of not being prescribed beta-blocker therapy (adjusted OR 2.6, 95% CI 2.0-3.4). Among the 5453 patients with no identifiable contraindication to beta-blocker therapy, women were significantly less likely than men to receive this agent (p = 0.005). Of the 6074 patients who received beta-blockers, 2248 (37.0%) were dispensed low-dose therapy. Patients aged 85 years or more had an increased risk of being dispensed low-dose therapy (adjusted OR 1.6, 95% CI 1.3-2.0) compared with those aged 66 to 74 years. Compared with those who had the lowest comorbidity scores, patients with the highest comorbidity scores were more likely to be dispensed low-dose beta-blocker therapy (adjusted OR 1.3, 95% CI 1.0-1.8). INTERPRETATION: Almost half of Ontario patients aged 66 or more who survived an MI, particularly those who were older or frailer, did not receive beta-blocker therapy. Among those dispensed beta-blocker therapy, older and frailer patients were more frequently dispensed low-dose therapy.     

Left ventricular catecholamines during acute myocardial infarction in the dog

To determine whether changes in left ventricular catecholamine content occur during the first 30 to 90 min of acute myocardial infarction, myocardial catecholamine (radioenzymatic assay) over the interval was studied in the dog. In nine pentobarbital-anesthetized opened-chest dogs without coronary ligation, myocardial catecholamine at 2.5 h after pentobarbital (i) consisted mainly of norepinephrine (87% total catecholamine), (ii) showed a base to apex gradient in norepinephrine (1.44 +/- 0.10 vs. 1.03 +/- 0.10 micrograms/g, p less than 0.05) and dopamine (0.20 +/- 0.03 vs. 0.12 +/- 0.02 micrograms/g, p less than 0.05) but not epinephrine (0.017 vs. 0.016 micrograms/g), and (iii) showed no difference in norepinephrine, dopamine, or epinephrine across basal, mid, and apical left ventricular transverse planes spanning the vascular territories of the two coronary arteries. In 18 pentobarbital-anesthetized dogs with coronary ligation, (i) norepinephrine, measured in 14 regions across the mid left ventricle after 90 min ischemia in four dogs, was less in the ischemic center of the occluded bed than normal myocardium (1.01 +/- 0.04 vs. 1.29 +/- 0.04 micrograms/g, p less than 0.05), and (ii) norepinephrine was unchanged in normal myocardium of 14 dogs at 30, 60, 90 min, and 48 h but decreased in ischemic myocardium by 31% at 60 min (0.89 +/- 0.10 vs. 1.29 +/- 0.08 micrograms/g, p less than 0.025) and 79% at 48 h (0.27 +/- 0.04 vs. 1.26 +/- 0.08 micrograms/g, p less than 0.001). Thus, norepinephrine depletion from ischemic but not normal myocardium is detectable by 60 min during acute myocardial infarction.     

Policy for early discharge after acute myocardial infarction.

Simple criteria were used to select a low-risk group of patients after acute myocardial infarction. The criteria depended on the presence or absence of diabetes, pulmonary oedema, serious rhythm disorders, and recurrent cardiac pain. Patients in the low-risk category with a suitable home environment were discharged from hospital after five to seven days (mean 6.2 days); they constituted 47% of the 267 hospital survivors over 18 months. Mortality in the selected patients was 2.4% at six weeks and 7% at one year. Most complications preventing early discharge were identified on the first day. Provisional selection for a short hospital stay was made after two days, and 76% of those judged suitable at 48 hours remained free of complications. Early selection of a low-risk category is justifiable and of practical value, though subsequent events will delay discharge for some patients. All patients who died in hospital or within two weeks after infarction had developed overt complications by the end of the fourth day. The results suggest that a policy of hospital discharge after four days would be justifiable for a low-risk group selected by the present criteria.     

Platelet aggregation, lipids and excretion of catecholamines after acute physical exercise in patients with myocardial infarction

The effect of acute physical exercise and a four-month conditioning program on cardiovascular risk factors was investigated in patients with myocardial infarction. The bicycle exercise testing caused a moderate rise in urinary epinephrine, serum cholesterol and HDL cholesterol levels. The changes in platelet aggregation and urinary catecholamines were markedly greater in the group with exercise induced ischaemic changes. Under the effect of the conditioning program a significant improvement in the performance capacity and circulatory response could be observed. The direction of changes in platelet aggregation and in the lipid parameters were favourable too.     

Trial of early nifedipine in acute myocardial infarction: the Trent study.

Over 30 months 9292 consecutive patients admitted to nine coronary care units with suspected myocardial infarction were considered for admission to a randomised double blind study comparing the effect on mortality of nifedipine 10 mg four times a day with that of placebo. Among the 4801 patients excluded from the study the overall one month fatality rate was 18.2% and the one month fatality rate in those with definite myocardial infarction 26.8%. A total of 4491 patients fulfilled the entry criteria and were randomly allocated to nifedipine or placebo immediately after assessment in the coronary care unit. Roughly 64% of patients in both treatment groups sustained an acute myocardial infarction. The overall one month fatality rates were 6.3% in the placebo treated group and 6.7% in the nifedipine treated group. Most of the deaths occurred in patients with an in hospital diagnosis of myocardial infarction, and their one month fatality rates were 9.3% for the placebo group and 10.2% for the nifedipine group. These differences were not statistically significant. Subgroup analysis also did not suggest any particular group of patients with suspected acute myocardial infarction who might benefit from early nifedipine treatment in the dose studied.     

急性心肌梗死患者肠道优势菌群分析

目的探讨急性心肌梗死患者肠道优势菌群的改变及其与疾病严重程度的关系。方法共筛选急性心肌梗死患者71名及正常健康体检者33名,急性心肌梗死患者根据是否心衰分为急性心肌梗死组36名和急性心肌梗死伴泵衰竭组35名,所有入选者收集大便及血清标本,分别采用qPCR及化学发光仪测定肠道优势菌群改变和血清脑钠肽前体及肌钙蛋白水平。结果急性心肌梗死患者肠道优势菌群显著改变,肠道肠杆菌以及肠球菌细菌数量较对照组显著增加,均与脑钠肽前体、肌钙蛋白、Killip分级显著正相关,而双歧杆菌、乳酸杆菌等细菌数量显著降低,与脑钠肽前体、肌钙蛋白、Killip分级显著负相关。结论急性心肌梗死患者呈现典型的肠道菌群紊乱,且与患者疾病严重程度相关。     

Increased release of beta thromboglobulin during acute myocardial infarction

Beta thromboglobulin (betaTG) is a platelet-specific protein released during platelet aggregation. To classify the role of platelet aggregation in acute myocardial infarction (AMI), betaTG levels were measured by means of a specific and highly sensitive radioimmunoassay in patients admitted to the Coronary Care Unit for the evaluation of acute chest pain. These levels were compared to creatine phosphokinase (CPK) values and the percentage of myocardial fraction (MB), as well as electrocardiographic criteria for AMI. Beta thromboglobulin was considered elevated when it was greater than 132 micro/1. The CPK and MB fraction were considered to indicate AMI if there was an increase of MB fraction greater than 5% of the total CPK and a progressive increase of the total CPK and MB fraction during the course of the disease. Ten patients were compared to 28 control subjects. Seven patients had electrocardiographic evidence of AMI in addition to CPK and MB criteria. Six of these patients also had elevated betaTG values, whereas one did not. This patient was admitted late during his clinical course, as evidenced by the CPK-MB curve. Of the three patients without clinical evidence of AMI, two had normal betaTG levels, whereas the third patient had one normal betaTG level and one mildly elevated level. This study implicates the role of platelet aggregation in AMI and suggests its potential usefulness as a diagnostic aid in evaluating acute chest pain.     

Course of patients discharged early after myocardial infarction.

Two hundred and seventy-one (76%) out of 358 survivors of infarction were discharged by the eighth hospital day, and 251 (93%) of them survived to six weeks after discharge. Six of the 20 patients who died between discharge and six weeks did so after readmission and 14 died as outpatients. All these patients who died at home had transmural infarction and four had diabetes. In inpatients successful resuscitation occurred mainly within the first 48 hours, with only three successful long-term results from all the patients who suffered arrest later. This suggests that more prolonged inpatient care would not have reduced the late mortality. These figures justify continuing with an early discharge policy for most patients, but coronary care should probably be more prolonged for patients with diabetes.     

Plasma intermedin levels in patients with acute myocardial infarction

It has been shown that adrenomedullin (ADM) may function as a cardiovascular-regulatory peptide in humans. Intermedin (IMD) is a newly discovered peptide related to ADM and has a greater range of biological effects on the cardiovascular in animal experiments. The purpose of the study was to investigate the pathophysiological role of IMD in patients with acute myocardial infarction (AMI). The present study included twenty patients with acute ST-segment elevation myocardial infarction (STEMI), thirty-three with stable coronary heart disease (SCHD), and eighteen healthy controls. Plasma levels of IMD, malonaldehyde (MDA), and superoxide dismutase (SOD) and cardiac biomarkers were determined at one, two, four and seven days following AMI. Plasma IMD levels were significantly increased on day 1 in AMI patients when compared with SCHD subjects (P = 0.014), and reached a peak of 181.88 ± 9.47 pg/ml at 96 h. Plasma IMD concentrations were correlated with MDA and SOD. Furthermore, patients with severe lesions in their coronary arteries tended to have higher plasma IMD levels (P < 0.05) in AMI patients. A significant increase in plasma IMD following AMI may be associated with oxidative stress, and could be used as a marker to reflect the severity of the coronary stenosis.     

The effect of bone marrow-derived cells on diastolic function and exercise capacity in patients after acute myocardial infarction

The purpose of this study is to establish a murine embryonic stem cell (mESC) line for isolation of functional ventricular cardiomyocytes (VCMs) and then to characterize the derived VCMs. By crossing the myosin light chain 2v (Mlc2v)-Cre mouse line with the reporter strain Rosa26-yellow fluorescent protein (YFP), we generated mESC lines from these double transgenic mice, in which Cre-mediated removal of a stop sequence results in the expression of YFP under the control of the ubiquitously active Rosa26 promoter specifically in the VCM. After induction of differentiation via embryoid body (EB) formation, contracting YFP⁺ cells were detected within EBs and isolated by fluorescence-activated cell sorting. N-cadherin, the cadherin expressed in cardiomyocytes, and the major cardiac connexin (Cx) isoform, Cx43, were detected in the respective adherens and gap junctions in these VCMs. Using current clamp recordings we demonstrated that mESC-derived VCMs exhibited action potential characteristics comparable to those of neonatal mouse VCMs. Real-time intracellular calcium [Ca²⁺]_i imaging showed rhythmic intracellular calcium transients in these VCMs. The amplitude and frequency of calcium transients were increased by isoproterenol stimulation, suggesting the existence of functional β-adrenergic signaling. Moreover, [Ca²⁺]_i oscillations responded to increasing frequencies of external electrical stimulation, indicating that VCMs have functional excitation-contraction coupling, a key factor for the ultimate cardiac contractile performance. The present study makes possible the production of homogeneous and functional VCMs for basic research as well as for cardiac repair and regeneration.