Granulocyte colony-stimulating factor attenuates early ventricular expansion after experimental myocardial infarction

OBJECTIVE: In the early phase after transmural myocardial infarction (MI), the infarcted myocardium undergoes replacement by scar tissue, which is essential for preserving the structural integrity of the infarcted tissue. Transforming growth factor (TGF)-beta1, which is known as a fibrotic cytokine, plays a pivotal role in the reparative fibrosis after MI. It is reported that granulocyte colony-stimulating factor (G-CSF) can accelerate wound healing. The aim of our study was to investigate the effect of G-CSF on early ventricular expansion after MI. METHODS: MI was induced by ligation of the left coronary artery in male Wistar rats. G-CSF (20 microg/kg/day, MI-GCSF) or saline (MI-saline) was injected subcutaneously 3 h after MI and every 24 h thereafter for 7 days. Hemodynamic and echocardiographic studies were performed at 14 days. Expression of TGF-beta1 and procollagen type I and type III mRNA in both the infarcted and noninfarcted areas was studied by quantitative RT-PCR at 1, 3, 7, and 14 days after MI. Histological studies were performed at 7 days. RESULTS: MI-GCSF had higher LV max dP/dt, lower LV end-diastolic pressure, and smaller LV end-diastolic and end-systolic dimensions compared to MI-saline. Infarct size was not different between MI-GCSF and MI-saline. Expression of TGF-beta1 mRNA in the infarcted area at 3 days was significantly higher in MI-GCSF than in MI-saline. Expression of procollagen type I and type III mRNA in the infarcted area at 3 days was higher in MI-GCSF compared to MI-saline, and the peak mRNA levels were earlier in MI-GCSF. In the noninfarcted area, there was no difference in TGF-beta1 mRNA expression between MI-GCSF and MI-saline. Histologically, collagen accumulation in the infarcted area at 7 days was more prominent in MI-GCSF than in MI-saline. CONCLUSION: G-CSF treatment improves early post-infarct ventricular expansion through promotion of reparative collagen synthesis in the infarcted area, suggesting some beneficial effect of G-CSF on the infarct healing process.     

Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction

OBJECTIVES: We sought to determine the influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) induction on post-myocardial infarction (MI) remodeling, especially in relation to the inflammatory response and myocardial fibrosis. BACKGROUND: Granulocyte-macrophage colony-stimulating factor modifies wound healing by promoting monocytopoiesis and infiltration of monocytes and macrophages into injured tissue; however, the effect of GM-CSF induction on the infarct healing process and myocardial fibrosis is unclear. METHODS: A model of MI was produced in Wistar rats by ligation of the left coronary artery. The MI animals were randomized to receive GM-CSF inducer (romurtide 200 microg/kg/day for 7 consecutive days) (MI/Ro) or saline (MI/C). RESULTS: Echocardiographic and hemodynamic studies on day 14 revealed increased left ventricular (LV) end-diastolic dimension, decreased fractional shortening, elevated LV end-diastolic pressure, and decreased LV maximum rate of isovolumic pressure development in MI/Ro compared with MI/C. Immunoblotting showed that expression of transforming growth factor (TGF)-beta1 in the infarcted site on day 3 after MI was decreased in MI/Ro compared with MI/C. In the infarcted site, TGF-beta1, collagen type I and type III messenger ribonucleic acid (mRNA) expression on day 3, and collagen content on day 7 were reduced in MI/Ro compared with MI/C, in association with marked infarct expansion. In MI/Ro, monocyte chemoattractant protein-1 mRNA level and the degree of infiltration of monocyte-derived macrophages (ED-1-positive)were greater in the infarcted site on day 7 than those in MI/C. CONCLUSIONS: The GM-CSF induction by romurtide facilitated infarct expansion in association with the promotion of monocyte recruitment and inappropriate collagen synthesis in the infarcted region during the early phase of MI.     

Relation between left ventricular dysfunction and ventricular arrhythmias after myocardial infarction

Ventricular arrhythmias occurring in the coronary care unit are not good predictors of ventricular arrhythmias or death during follow-up. However, arrhythmias detected by 24-hour electrocardiographic recordings at the time of hospital discharge are predictive of mortality over the subsequent 2 years. At discharge, only about 20% of patients have significant ventricular arrhythmias, defined as frequent or repetitive ventricular premature depolarizations. Using programmed ventricular stimulation, which can detect significant ventricular arrhythmias in patients with very little ectopy in 24-hour electrocardiographic recordings, 20% of patients have ventricular tachycardia 2 to 6 weeks after acute myocardial infarction (AMI). Both diastolic left ventricular (LV) dysfunction in the coronary care unit (i.e., rales or pulmonary congestion) and systolic LV dysfunction (i.e., LV ejection fraction) during hospitalization for AMI are potent predictors of mortality. Two large prospective studies examining the relations between LV dysfunction, ventricular arrhythmias and mortality concluded that mechanical dysfunction and ventricular arrhythmias are independently related to mortality. This finding provides a rationale for treating patients with frequent or repetitive ventricular arrhythmias detected near the time of hospital discharge after AMI. However, no study has yet examined whether reducing ventricular arrhythmias with antiarrhythmic drugs after AMI also reduces mortality. Lacking an answer to this question and given the frequency of adverse effects with antiarrhythmic drugs, most physicians are conservative in the treatment of patients with ventricular arrhythmias after AMI.     

Reversible left ventricular dysfunction simulating a myocardial infarction after pericardiectomy

A 39 year old man with postoperative constrictive pericarditis after pericardiectomy developed major left ventricular systolic dysfunction with an anterior wall infarct pattern on ECG but no regional wall motion abnormalities by echocardiography or serum enzymatic evidence of a myocardial infarction. The left ventricular dysfunction resolved over two weeks with supportive treatment. It is postulated that this patient's transient left ventricular dysfunction and ECG changes were caused by myocardial inflammation and oedema induced by operative trauma during pericardiectomy.     

Successful surgical repair of left ventricular rupture after acute myocardial infarction

A 61-year-old man with impending myocardial infarction was admitted and treated by percutaneous transluminal coronary recanalization (PTCR) therapy using Urokinase. Patient's symptoms subsided and his general condition maintained stable until the fifth hospital day, when he developed the signs of cardiac rupture. He was operated upon immediately, and the left ventricular rupture was confirmed and repaired successfully. Patient recovered from the surgery well. This report describes the rare successful surgical case of cardiac rupture secondary to acute myocardial infarction in Japan.     

Epidemiology of heart failure and left ventricular dysfunction after acute myocardial infarction

The development of heart failure and/or left ventricular systolic dysfunction has long been regarded as an ominous complication, significantly increasing the morbidity and short- and long-term mortality of survivors of acute myocardial infarction. Although the incidence of heart failure after myocardial infarction has fallen over the last few decades, it remains common, complicating up to 45% of infarcts. Moreover, up to 60% of myocardial infarcts will result in left ventricular systolic dysfunction, depending on the exact definition used. Those at greatest risk of developing heart failure are the elderly, females, and those with prior myocardial infarction. Advances in the management of acute myocardial infarction have led to reduced in-hospital mortality (even when complicated by heart failure), but longerterm mortality remains high in these patients.     

Early natural history of regional left ventricular dysfunction after experimental myocardial infarction

Existing studies provide conflicting information concerning the natural history of regional dysfunction after subacute myocardial infarction. The purpose of this study was to use quantitative computer-assisted two-dimensional echocardiography to define the natural history of abnormal wall motion in a subacute canine infarct model within individual short-axis echocardiographic planes, and in the entire ventricle as well. Serial short-axis echocardiograms were obtained from 10 closed-chest dogs before occlusion and at 0.5, 6, 24, 48, and 72 hours after ligation of the circumflex (six dogs) or left anterior descending (four dogs) coronary artery. The circumferential extent of abnormal wall motion was quantified by two different computer-assisted methods: the first, a derived correlation method, examined wall motion throughout the systolic contraction sequence; the second method examined the fractional radial change in endocardial ray length from end-diastole to end-systole. The study shows that for individual planes there is a slight but not statistically significant increase in the circumferential extent of abnormal wall motion from 0.5 to 72 hours after coronary artery occlusion; however, when the total extent of left ventricular asynergy was used to define a global functional infarct size, we observed a small (3.6% to 5.4%) but significant increase in the circumferential extent of abnormal wall motion.     

Early left ventricular dysfunction in acute myocardial infarct. Evaluation using imaging methods

A patient admitted in a Coronary Care Unit with an acute anterior myocardial infarction, is presented. He had initially normal left ventricular function and, on the 11th day he had, suddenly, an acute pulmonary edema. The reason for this episode was detected through imaging techniques--echocardiography and isotopic studies, and consisted on infarct expansion with early evolution for apical aneurysm. Contrast angiography confirmed the presence of a huge aneurysm and two vessels disease. Tallium Scintigraphy showed reversible ischemia beyond necrotic areas. The patient was submitted to aneurysmectomy and received three aorto-coronary bypass. He is now doing well, in class I, NYHA. The discussion emphasizes the actual role of imaging techniques in the diagnosis of infarct expansion and early functional aneurysm. We discuss the prognostic of infarct expansion and the importance of perfusion studies on defining areas of myocardium in jeopardy, enabling a better surgical approach.     

Comprehensive adrenergic blockade post myocardial infarction left ventricular dysfunction

Practice guidelines recommend that post myocardial infarction (MI) patients should be started and continued indefinitely on oral beta-blocker therapy unless absolutely contraindicated or not tolerated. Patients with post-MI left ventricular dysfunction (LVD) are at particularly high risk for recurrent cardiovascular events, heart failure, sudden death, and mortality and have been shown to derive substantial benefit from certain beta-blockers. Nevertheless, many of these patients are not prescribed beta-blockers, and some patients are treated with agents whose long-term use has not been shown to be effective. This article discusses the clinical trial evidence supporting the use of beta-blockers in patients post MI with LVD, provides the rationale for choosing specific beta-blockers, and presents practical approaches to implement this evidence-based therapy in the acute and chronic post-MI period.     

Nipradilol can prevent left ventricular systolic and diastolic dysfunction after myocardial infarction in rats.

The purpose of this study was to examine the effects of nipradilol on the cardiac function and mRNA expression in Wistar rats with a myocardial infarction (MI) that was created by ligation of the anterior descending coronary. Ten mg x kg(-1) x day(-1) of nipradilol were administrated to the rats in random order, and hemodynamic and Doppler-echocardiographic findings and myocardial mRNA expression were analyzed at 4 weeks after MI. Although left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) were increased in the MI rats, nipradilol significantly reduced the degree of the increase in both parameters. MI also significantly increased the weight of the left and right ventricles, and increased the left ventricular end-diastolic dimension (LVDd), effects that were attenuated by nipradilol. The MI rats showed decreased fractional shortening as systolic dysfunction and decreased E wave deceleration rate as diastolic dysfunction, and nipradilol significantly prevented these. Nipradilol significantly suppressed the increase in the non-infarcted myocardial mRNA expression of atrial natriuretic peptide, brain natriuretic peptide and collagen I and III. In conclusions, nipradilol prevents the cardiac remodeling that is accompanied by systolic and diastolic dysfunction, and inhibits abnormal myocardial gene expression after MI.     

Current concepts for the neurohormonal management of left ventricular dysfunction after myocardial infarction

The importance of addressing neurohormonal activation in patients after a myocardial infarction is now well-appreciated. Inhibition of the renin-angiotensin-aldosterone axis and the sympathetic nervous system can result in improved cardiac function and survival. As we learn more about other systems, we should be able to realize further benefits. In particular, the roles of endothelin, matrix metalloproteinases, and cytokines in remodeling are being investigated, with the potential to result in better outcomes for patients.