Early Stage Of Acute Myocardial Infarction Research Articles

Automated Assessment of Myocardial Viability After Acute Myocardial Infarction by Global Longitudinal Peak Strain on Low-Dose Dobutamine Stress Echocardiography

Low-dose dobutamine stress echocardiography (DSE) assesses myocardial viability at the early stage of acute myocardial infarction (AMI), but its assessment is subjective and variable. Automated function image (AFI) determines global longitudinal peak strain (GLPS) based on tissue tracking technique. The ability of GLPS obtained by AFI during dobutamine stress to assess myocardial viability after AMI was investigated. Low-dose DSE at day 3 in 23 consecutive patients with AMI was performed using Vivid 7 (GE Healthcare). Segmental longitudinal peak strain with AFI and obtained GLPS was analyzed. Wall motion score index (WMSI) by echocardiography 1 month later was determined. In 18 patients, left ventriculography was also performed at 3.2±1.5 months later to obtain left ventricular ejection fraction (LVEF) and regional wall motion (RWM, SD/chord). GLPS was improved during dobutamine infusion at 10 µg · kg(-1) · min(-1) (-12.9 ± 3.5% to -15.2 ± 3.6%, P=0.0004). GLPS during dobutamine stress showed good correlations with follow-up WMSI (R=0.47, P=0.02), with peak CK-MB (R = 0.52, P=0.01), with RWM (R = -0.48, P=0.04), and with LVEF (R = -0.54, P=0.02), whereas GLPS at baseline showed no correlations with them. Averaged segmental peak strain at baseline and during stress were correlated with follow-up WMSI (R = 0.50 and 0.43, respectively), but not with LVEF. GLPS during dobutamine stress determined by AFI is a promising, objective index to assess myocardial viability on the early stage of AMI.

Abstract 5016: Circulating MicroRNA: A Novel Potential Biomarker for Early Detection of Acute Myocardial Infarction

Background: MicroRNA (miRNA), a class of 19~25-nucletide noncoding RNA, is present in the plasma or serum of humans and other animals, and has been increasingly reported to be the potential biomarkers for several diseases including cancers and liver injury. The objective of this study is to determine the potential of cardiac-specific miRNAs to serve as early-detectable biomarkers in the plasma for acute myocardial infarction (AMI). Methods and Results: With miRNA microarray analysis, we observed the expression profile of miRNAs from the plasma of 5 healthy people. In the plasma, several miRNAs including miR-451 and miR-16 were presented with relative high levels, and the muscle-specific miRNAs, miR-1 and miR-133a were detected with low abundance. However, miR-499 and miR-208, specifically expressed in heart, were undetectable in the plasma. The above results with 6 miRNAs were additionally confirmed by real-time PCR analysis. Interestingly, the levels of miR-1, miR-133a, miR-499, and miR-208, but not miR-451 and miR-16 were significantly increased in the plasma from the rats with coronary artery ligation for 3 hours, compared to those from sham-operated controls (n=6 in both groups). Among them, the elevation of miR-208 was most remarkable. The level of miR-208 in plasma was then examined at various time points (0, 1, 3, 6, 12, 24 hours after coronary artery occlusion). Real-time PCR analysis showed that the amount of miR-208 in plasma became detectable at as early as 1 hour, peaked at 3~6 hours, and declined after 12 hours. Next, the levels of these 6 miRNAs in plasma from 18 patients with AMI, 12 patients with non-AMI CHD and 15 patients with non-CHD were evaluated. The levels of miR-1, miR-133a, miR-499 and miR-208 were substantially higher in AMI group than those in the two other groups. Additionally, the plasma levels of these 4 miRNAs from 5 of 18 AMI patients were decreased during the follow-up investigation. Conclusions: Our results that the levels of miR-1, miR-133a, miR-499 and miR-208 increase in plasma from both AMI rats and patients reveal for the first time that they may serve as potential biomarkers for AMI diagnosis. Importantly, miR-208, increased rapidly at the early stage of AMI, may improve the accuracy in early diagnosis of myocardial damage.

Early Ghrelin Treatment after Myocardial Infarction Prevents an Increase in Cardiac Sympathetic Tone and Reduces Mortality

Acute myocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (CSNA), which ultimately exacerbates chronic cardiac dysfunction. Ghrelin (Ghr), a GH-releasing peptide, is an effective treatment for improving cardiac function in chronic heart failure. Ghr also suppresses renal sympathetic nerve activity (SNA) and, therefore, may have important therapeutic benefits in the early stages of acute MI: by reducing CSNA. In this study we hypothesized that early Ghr administration may prevent an increase in CSNA in the acute phase after MI. CSNA was continuously recorded in urethane-anaesthetized rats before and for 5 h after acute MI (or sham). MI was induced by ligation of the left anterior descending coronary artery. Rats received an injection of either saline or Ghr (150 microg/kg, sc) 1 min, or 2 h, after the infarct. CSNA remained stable during the 5-h recording duration in sham rats. MI induced a maximal 110% increase in SNA, which was prevented in rats that received Ghr 1 min after infarct. When Ghr was injected 2 h after MI (SNA had increased by approximately 85%), SNA decreased to pre-MI activity. Importantly, early Ghr administration significantly reduced the high mortality rate associated with MI (61% mortality in untreated MI rats cf. approximately 23% in Ghr-treated MI rats). These results show that early Ghr treatment prevents the increase in CSNA after MI, which may contribute to the improved chances of survival. Whether these early beneficial effects of Ghr also have long-term benefits for improving cardiac function is an area that requires further investigation.

Elevation of matrix metalloproteinases and interleukin‐6 in the culprit coronary artery of myocardial infarction

Interleukin-6 (IL-6) and metalloproteinases (MMPs) are involved in the instability of vulnerable plaque associated with the induction of acute myocardial infarction (AMI). We examined the regional changes of cytokines, MMPs and adhesion molecules in patients with AMI to elucidate how these factors are involved in the onset of AMI. One hundred and twenty-two patients with AMI were included. Blood was aspirated from the culprit coronary artery with a thrombectomy catheter, and was also sampled from peripheral veins during the coronary intervention. Control samples were obtained from the peripheral blood of age-matched patients. The serum levels of IL-6 (P < 0.05), tumour necrosis factor-alpha (P < 0.005), MMP-1 (P < 0.001), MMP-13 (P < 0.001), soluble intercellular adhesion molecule-1 (P < 0.005), and soluble vascular cellular adhesion molecule-1 (P < 0.05) in peripheral blood were significantly higher in the AMI group than in the controls. Aspirated serum contained significantly higher levels of IL-6 (P < 0.001), MMP-1 (P < 0.001), and MMP-13 (P < 0.05) compared to the peripheral blood of AMI. Serum IL-6 levels were significantly higher in the aspirated than in the peripheral blood in the patients hospitalized within 6 h and 6-12 h, but were similar in the aspirated and peripheral blood of the patients hospitalized 12-24 h after the onset of AMI. There were no differences between the aspirated serum and peripheral blood in the levels of interleukin-1beta and MMP-2. The levels of MMP-1, MMP-13 and IL-6 were higher in the culprit coronary artery than in the peripheral blood. These factors appear to be involved in the early stage of AMI.

Very Early Stage Detection of Acute Myocardial Infarction by Harmonic Ultrasonic Integrated Backscatter

To study the very early diagnosis of acute myocardial infarction (AMI) by harmonic imaging ultrasonic integrated backscatter (IBS). Thirty normal persons, 68 cases with AMI, of whom 28 cases were at the very early stage of acute myocardial infarction (in 2 h), and 40 cases with acute myocardial infarction (in 2 to 12 h) were examined by IBS and the cyclic variation of integrated backscatter (CVIB) with HP-5500 ultrasonic system in different segment (the segment of myocardial infarction and no myocardial infarction). In the segment of AMI of the very early stage (in 2 h) the IBS (dB) is much higher than that of the segment of no AMI (18.7 versus 8.3), p < 0.001, the CVIB (dB) are lower (6.1 versus 7.6), p < 0.001. But at that time there are no obvious changes in ECG. In the other 40 cases with AMI in 2 to 12 h, IBS in the segment of AMI is obviously higher than the normal person and no infarction segment in the same heart (21.3:8.3, 20.2:8.5) p < 0.05, but CVIB (dB) is obviously lower than the normal person and no infarction segment in the same heart (5.8:7.6, 5.9:9.4) p < 0.05 the changes of the ultrasonic is coincidence with ECG. IBS (dB) are very obvious just as in ECG. The result demonstrates that ultrasonic tissue characterization with harmonic imaging integrated backscatter can be used for diagnosis in the very early stage of AMI, and can judge the segment range of AMI and function of the whole heart. (E-mail: wuxiaoqing48@hotmail.com)

RNA interference targeting SHP‐1 attenuates myocardial infarction in rats

The Src homology domain 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1) plays a key role in apoptosis and decreases phosphorylation of Akt. Apoptosis of cardiomyocytes is thought to contribute to the increased area of acute myocardial infarction (AMI), and Akt activation exerts a powerful cardioprotective effect after ischemia. Thus, a therapeutic strategy designed to inhibit expression of SHP-1 would be beneficial in AMI. Here we report that siRNA targeting SHP-1 reduced infarct size in a rat model of AMI. Upon injection into the ischemic left ventricular wall, the vector-based siRNA significantly suppressed the increase in the SHP-1 mRNA and the SHP-1 protein levels. The siRNA vector also significantly reduced the SHP-1 that bound to Fas-R. The SHP-1 siRNA vector increased phospho-Akt and reduced DNA fragmentation and caspase activity compared with the scramble siRNA vector. Finally, the area of myocardial infarction was significantly smaller with the SHP-1 siRNA vector than with the scramble siRNA vector at 2 days after LCA ligation. In conclusion, SHP-1 in the heart increased from the early stage of AMI, and this increase was thought to contribute to the increased area of myocardial infarction. Suppression of SHP-1 with the SHP-1 siRNA vector markedly reduced the infarct size in AMI.

Detection of cardiomyocyte apoptosis in forensic autopsy cases.

The purpose of the present study was to determine reliable parameters for the detection of apoptotic cells for use as a diagnostic marker during the early stage of acute myocardial infarction (AMI) in forensic autopsy cases. Myocardial tissues taken from forensic autopsy cases were examined by immunohistochemical and molecular-biological methods using the terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labelling (TUNEL) and the DNA laddering methods. In cases of AMI with a time period between 2 h from onset to death and 20 h post-mortem time, the nuclei of cardiomyocytes were stained positive with the TUNEL method and DNA fragmentation of myocardial cells was detected by agarose gel electrophoresis. Similar findings were obtained in cases of carbon monoxide (CO) intoxication. However, no apoptotic cells were found in other cases such as methamphetamine (MAP) intoxication, tetrodotoxin intoxication, alcohol intoxication, asphyxia, head injury, heart injury or myocarditis. These findings suggested that it would be possible to apply TUNEL-positive cells as a diagnostic marker during the early stages of AMI.

Increased plasma adrenomedullin in acute myocardial infarction

Adrenomedullin has a potent vasodilating effect comparable to that of calcitonin gene-related peptide. To investigate the pathophysiologic role of endogenous adrenomedullin, we determined sequentially the plasma adrenomedullin level in 15 consecutive patients with acute myocardial infarction (AMI). Plasma adrenomedullin was higher immediately after the onset of AMI and decreased gradually; plasma levels during the 3-week period after the AMI were higher than plasma levels in 15 healthy control subjects ( p < 0.001), with higher levels in patients with congestive heart failure than in patients without congestive heart failure throughout the period of the study ( p < 0.05). Plasma adrenomedullin was positively correlated with pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and heart rate in the early stage of AMI. These findings suggest that the elevation of plasma adrenomedullin is related to the retention of body fluid volume, the enhancement of sympathetic activity, and/or the elevation of pressure in pulmonary vascular beds. Adrenomedullin may act against excessive vasoconstrictors increased in AMI.

Beyond Coronary Thrombolysis

Coronary heart disease, the leading cause of death in the United States, is responsible for 500 000 deaths annually. Furthermore, 5 to 6 million individuals in this country suffer from symptomatic coronary disease, with the potential to sustain an acute myocardial infarction (AMI). Pump failure is the most common cause of death following AMI and is determined by the extent of myocardial necrosis. Therefore, methods to limit infarct size have been vigorously sought. The pathogenesis of AMI in general and the contributory role of intracoronary thrombosis in particular have been debated for decades. However, the work of DeWood et al,¹performing coronary angiography during the early stages of AMI, has established an occlusive thrombus as the primary event in transmural myocardial infarction. Having recognized this important fact, attention quickly turned to interventional therapies designed to remove intracoronary thrombus, thereby restoring myocardial blood flow.^2,3Early investigations utilizing clot lysing

Clinical significance of early myocardial 99mTc-pyrophosphate uptake in patients with acute myocardial infarction

Early 99mTc-pyrophosphate (PYP) scintigrams of 29 patients receiving coronary thrombolysis induced by urokinase, 3.9 ± 1.2 hours after the onset of acute myocardial infarction (AMI), were evaluated. Intravenous 99mTc-PYP scintigraphy was performed 2.8 to 8.0 hours after the onset of AMI. All 19 patients with positive findings on early scintigrams had good recanalization, compared to only 3 of the 10 patients with negative findings. The seven patients with unsuccessful recanalization after coronary thrombolysis had total occlusion or subtotal occlusion with delayed washout of contrast material, and three of them had collaterals. The sensitivity, specificity, and predictive accuracy of positive results of early scintigraphy in predicting the presence of early reperfusion were 73%, 100%, and 90%, respectively. Patients with positive early scintigrams showed increasing regional ejection fraction and decreasing thallium defect scores from the acute stage to the chronic stage. These findings indicate that early 99mTc-PYP scintigraphy is a sensitive noninvasive technique for detecting early recanalization in infarcted vessels. The collateral flow or antegrade flow with delay is not enough to cause 99mTc-PYP uptake in a very early stage of AMI.

Thromboxane A 2 in acute myocardial infarction

We evaluated the presence of thromboxane B 2, the stable metabolite of thromboxane A 2, early in the course of acute myocardial infarction (AMI) in both animal and patient studies. In an open-chest model, the left anterior descending artery (LAD) was isolated and the great cardiac vein was cannulated in nine dogs. Following occlusion of the LAD, there was an increase in thromboxane B 2 concentration from 0.77 ± 0.093 to 1.79 ± 0.46 pmol/ml ( p < 0.05) and 1.96 ± 0.48 pmol/ml ( p < 0.05) at 1 and 5 minutes, respectively, following coronary occlusion. At 30 and 60 minutes after occlusion there was no significant increase compared to the baseline. In 17 patients with AMI the mean thromboxane B 2 concentration was 0.96 ± 0.13 pmol/ml at 4.88 ± 0.40 hours after the onset of chest pain. In 12 patients with sequential samples before and after restoration of patency of the occluded vessel, the initial concentration was 0.71 ± 0.058 pmol/ml. At 5 minutes after restoration of patency thromboxane B 2 concentration was 1.1 ± 0.17 pmol/ml ( p = 0.05). One hour later a return to baseline was noted (0.82 ± 0.75 pmol/ml). Two patients with the highest thromboxane B 2 concentrations (2.0 and 2.6 pmol/ml) were unable to have successful recanalization. We conclude that generation of thromboxane A 2 occurs during the early stages of AMI and may be an important pathophysiologic phenomenon in AMI.

Collateral function in early acute myocardial infarction

The role of the collateral circulation < 6 hours after the onset of acute myocardial infarction (MI) was evaluated in 34 consecutive patients without previous MI. There were 19 patients with and 15 without collaterals. The group was subdivided into those with nonjeopardized collaterals (group A, 14 patients) and those with jeopardized collaterals (group B, 5 patients), and the group without collaterals into those with partially obstructed coronary arteries (group C, 5 patients) and those with totally obstructed coronary arteries (group D, 10 patients). These groups had similar sites of coronary stenoses and MI. Eleven of 14 collaterals in group A were poor, but MI mass measured by peak creatine kinase (CK) was smaller in group A than in group B (p < 0.01) or group D (p < 0.01), and cardiac function was significantly better in group A than in group D (cardiac index, p < 0.05; stroke index, p < 0.01; ejection fraction, p < 0.01; regional wall motion, p < 0.01). Group C was not statistically different from group A in myocardial function and CK. Group B was similar to group D in MI mass and cardiac function (cardiac index, stroke index, ejection fraction and regional wall motion). Thus, patients with nonjeopardized collaterals and those with partially obstructed coronary arteries had less myocardial damage and better cardiac function than did those with jeopardized collaterals and those with totally obstructed coronary arteries. A nonjeopardized collateral circulation may play a role in limiting MI mass and preserving myocardial function in the early stages of acute MI.

Cardiac function and peripheral circulatory adjustments in patients with acute myocardial infarction. Observations during the early stage of AMI.

Since little is known concerning the effect of different types of cardiac dysfunction on the peripheral circulation in acute myocardial infarction, cardiac and peripheral circulatory hemodynamics were measured simultaneously and sequentially in the Coronary Care Unit in 40 patients with acute myocardial infarction (AMI) using a Swan-Ganz catheter and venous occlusion plethysmography. Patients were classified by clinical assessment (Killip) and into four hemodynamic subsets (HS) according to pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) measures obtained by invasive central hemodynamic monitoring (Forrester): uncomplicated AMI, HS-I (PCWP less than or equal to 18 mmHg, CI greater than 2.2 L/min/m2) 15; pulmonary congestion, HS-II (PCWP greater than 18 mmHg, CI greater than 2.2 L/min/m2) 15; peripheral hypoperfusion, HS-III (PCWP less than or equal to 18 mmHg, CI less than or equal to 2.2 L/min/m2) 4; cardiogenic shock, HS-IV (PCWP greater than 18 mmHg, CI less than or equal to 2.2 L/min/m2) 6. Measurements taken within 48 hours after the onset of AMI showed significantly lower calf blood flow (p less than 0.05) and calf venous capacitance (p less than 0.01) and higher calf vascular resistance (p less than 0.05) in all AMI classifications compared to 10 normal subjects. In uncomplicated AMI group (Killip I and HS-I) calf blood flow and venous capacitance were significantly reduced while calf vascular resistance remained unchanged from normal. In AMI complicated by pulmonary congestion (Killip II and HS-II), in addition to reduced calf venous capacitance, calf blood flow was further significantly reduced (p less than 0.05) due, in part, to a rise in calf vascular resistance (p less than 0.05). In AMI complicated by severe heart failure and shock (Killip III, VI and HS-IV), mean changes in the periphery were not statistically different from those seen in patients with pulmonary congestion alone. In patients with AMI complicated by poor peripheral perfusion (HS-III), the peripheral changes did not show significant differences from those seen in uncomplicated AMI (HS-I). Significant correlations were found between calf blood flow and PCWP (r = -0.37, p less than 0.05) and CVP (r = -0.31, p less than 0.05); calf vascular resistance and PCWP (r = +0.36, p less than 0.05) and systemic vascular resistance (r = +0.43, p less than 0.01). Sequential daily peripheral hemodynamic changes in 14 H-I patients not requiring specific therapy showed that calf blood flow took 5 days, calf vascular resistance 3 days and calf venous capacitance 7 days to return to within normal levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasma level of norepinephrine and cyclic nucleotides following acute myocardial infarction.

The plasma concentrations of norepinephrine (NE), adenosine cyclic 3', 5'-monophosphate (cyclic AMP), and guanosine cyclic 3', 5'-monophosphate (cyclic GMP) were measured serially for 2 weeks after the onset of symptoms in 17 patients with acute myocardial infarction (AMI). The mean concentrations of NE in patients without complications were significantly elevated during the first 2 days following AMI. There was a significant correlation between the maximum concentration of plasma NE and of plasma CK. The mean concentrations of plasma cyclic AMP and cyclic GMP in patients without complications were significantly elevated on the first day and for 8 days respectively following AMI. The concentration of plasma cyclic AMP on admission in patients with complications was significantly higher than that in those without complications. There were significant correlations between the maximum concentration of plasma cyclic AMP and those of plasma CK, GOT, and LDH. Significant but weak correlations between the concentration of plasma NE and those of cyclic AMP and cyclic GMP were found. The results of the present study suggest an enhanced sympathetic nervous system activity at an early stage of AMI, a prolonged enhancement of parasympathetic nervous system activity in the course of AMI, and the potential value of plasma cyclic AMP concentrations as a useful index to estimate the seriousness and size of AMI.