Takazo Minamino

Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction.

BackgroundWe investigated myocardial perfusion dynamics after thrombolysis and its clinical implications. Methods and ResultsWe studied 39 patients with acute anterior myocardial infarction (AMI). Myocardial contrast echocardiography (MCE) was performed before and immediately after successful reflow with intracoronary injection of sonicated loxaglate. The average segmental score by twodimensional echocardiography (graded 0, normal, to 3, akinetic/dyskinetic) and global ejection fraction (left ventricular ejection fraction, LVEF%) by left ventriculography were measured at 1 day and at 4 weeks after reflow. Hypokinesis in the infarct region was assessed by the centerline method and expressed in terms of standard deviations (regional wall motion [RWM:SD/chord) of normal. Immediately after reflow, 30 of 39 patients (group A) showed significant contrast enhancement within the risk area. The other nine patients (23%, group B), however, showed the residual contrast defect in the risk area (myocardial no reflow). There were no significant differences in the elapsed time, angiographic collateral grade, and degree of residual stenosis between group A and group B. Before reflow, both groups exhibited similar levels of global and regional left ventricular function. Improvement in global (LVEF, average segmental score) and regional left ventricular function was greater in group A than in group B (average segmental score, 0.44±0.41 versus 0.97±0.36, p < 0.01; LVEF, 56.4± 13.4 versus 42.7±8.9, p < 0.0S; RWM, −1.87±0.85 versus −3.18±0.52, p < O.O05). ConclusionsMCE demonstrates that angiographically successful reflow cannot be used as an indicator of successful myocardial reperfusion in AMI patients. The residual contrast defect in the risk area demonstrated immediately after reflow is a predictor of poor functional recovery of the postischemic myocardium.

Myocardial Perfusion Patterns Related to Thrombolysis in Myocardial Infarction Perfusion Grades After Coronary Angioplasty in Patients With Acute Anterior Wall Myocardial Infarction

BACKGROUND Epicardial coronary flow is occasionally reduced even after coronary intervention despite the absence of vessel obstruction in patients with acute myocardial infarction. Our aim was to clarify the cause and outcomes of radiocontrast slow filling in patients with reperfused acute anterior myocardial infarction by assessing microvascular damage with the use of myocardial contrast echocardiography (MCE) and functional outcomes. METHODS AND RESULTS We carefully reviewed the cineangiograms of 86 patients who achieved coronary revascularization within 12 hours of the onset and underwent MCE before and soon after recanalization with the intracoronary injection of sonicated microbubbles. Antegrade coronary flow after recanalization was graded by two observers based on Thrombolysis in Myocardial Infarction (TIMI) trial flow grades. Left ventricular ejection fraction was measured on the day of infarction and 1 month later. TIMI grade 2 was observed in 18 patients (21%), and the other 68 patients manifested TIMI grade 3 after recanalization. All patients with TIMI 2 showed substantial MCE no reflow, whereas only 11 patients (16%) with TIMI 3 showed MCE no reflow. Functional improvement was worse in patients with TIMI 2 than in those with TIMI 3 (TIMI 2, 38 +/- 8% versus 40 +/- 8%, P = NS [acute versus late]; TIMI 3, 44 +/- 13% versus 55 +/- 13%, P < .001). Among patients with TIMI 3, significant functional improvement was observed only in patients with MCE reflow (MCE reflow, 46 +/- 13% versus 57 +/- 12%, P < .001; MCE no reflow, 35 +/- 11% versus 45 +/- 12%, P = NS). CONCLUSIONS Despite no obstructive lesion of the vessel, TIMI 2 is caused by advanced microvascular damage and is a highly specific, although not sensitive, predictor of poor functional outcomes in patients with acute myocardial infarction. TIMI 3 does not necessarily indicate myocardial salvage, and detection of MCE no reflow in these patients is particularly useful for the prediction of functional outcome.

Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction

OBJECTIVES We assessed whether the intravenous administration of nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts beneficial effect on microvascular function and functional and clinical outcomes in patients with acute myocardial infarction (AMI). BACKGROUND Experimental studies documented that ATP-sensitive K+ channel opener exerts cardioprotection after prolonged ischemia. METHODS We randomly divided 81 patients with a first anterior AMI into two groups, nicorandil (n = 40) and control groups (n = 41). All patients received successful coronary angioplasty within 12 h after the symptom onset and underwent myocardial contrast echcardiography (MCE) with the intracoronary injection of sonicated microbubbles. In the nicorandil group, we injected 4 mg of nicorandil followed by the infusion at 6 mg/h for 24 h and by oral nicorandil (15 mg/day). RESULTS The improvement in regional left ventricular function, wall motion score and regional wall motion was significantly better in the nicorandil group then in the control group. Intractable congestive heart failure, malignant ventricular arrhythmia and pericardial effusion were more frequently found in the control group than in the nicorandil group (15% vs. 37%, 5% vs. 20% and 8% vs. 37%, p < 0.05, respectively). The frequency of sizable MCE no reflow phenomenon was significantly lower in the nicorandil group than in the control group (15% vs. 33%, p < 0.05). CONCLUSIONS Intravenous nicorandil in conjunction with coronary angioplasty is associated with better functional and clinical outcomes compared to angioplasty alone in patients with an anterior AMI. Myocardial contrast echocardiography findings imply that an improvement in microvascular function with nicorandil may be attributable to this better outcome.

The role of intracoronary thrombus in unstable angina: angiographic assessment and thrombolytic therapy during ongoing anginal attacks.

Intracoronary thrombus is regarded as a potentially important factor in the etiology of unstable angina, but the incidence of intracoronary thrombus in unstable angina has not been clearly defined. To determine the occurrence of intracoronary thrombus during ongoing angina pectoris, coronary angiography was performed during spontaneous ischemic attacks in 37 patients with prolonged rest angina. All patients exhibited significant (greater than 50%) stenoses of at least one major coronary artery. Of the 37 patients, 21 (57%) had intracoronary thrombus in major coronary arteries, whereas 14 (38%) had fixed narrowings without evidence of intracoronary thrombus and two exhibited coronary spasm. ST segment elevation was observed in 16 of 21 patients with thrombus and in all of the patients with coronary spasm, but all the patients with organic stable obstruction showed ST segment depression. Twenty of the 21 patients with thrombus improved after thrombolytic therapy with intracoronary injection of urokinase; obstructed arteries were reopened, or narrowings were attenuated, with relief of ischemic symptoms. In patients with fixed obstructions, the rate-pressure product during active symptoms was significantly higher than during an asymptomatic period, indicating that a transient increase in myocardial oxygen demand may contribute to the ischemic attack in these patients. A high incidence (71%) of recurrent symptoms was observed in patients with intracoronary thrombus even after successful thrombolysis, in contrast to a much lower incidence (36%) in those without intracoronary thrombus. Myocardial infarction within 4 weeks after catheterization was observed more frequently in patients with intracoronary thrombus (24%) than in those without thrombus (7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Dobutamine Stress Echocardiography Predicts Reversible Dysfunction and Quantitates the Extent of Irreversibly Damaged Myocardium After Reperfusion of Anterior Myocardial Infarction

OBJECTIVES This study was designed to evaluate dobutamine stress echocardiography in identifying reversible dysfunction and assessing the extent of irreversibly damaged myocardium early in acute myocardial infarction. BACKGROUND Several experimental and clinical studies have suggested that dobutamine enhances contractile function of stunned or hibernating, or both, myocardium. It is important for clinical strategy to predict the magnitude of improvement in myocardial function early in acute myocardial infarction. METHODS We studied 21 patients with a reperfused first anterior myocardial infarction. Two-dimensional echocardiography was performed before and during dobutamine infusion (10 micrograms/kg body weight per min) at a mean of 3 days after the infarction. Follow-up echocardiography was performed at a mean of 25 days later. To assess segmental wall motion, we divided the left ventricle into 17 segments and assigned a wall motion abnormality score: 3 = dyskinesia or akinesia; 0 = normal. Improvement in wall motion was indicated by a decrease of at least one grade in segmental score. For quantitative assessment, the ratio of endocardial length showing dyskinesia or akinesia to a left ventricular endocardial length (akinetic length ratio) was determined in the apical long-axis view at each stage. RESULTS Sensitivity and specificity of dobutamine infusion in detecting improvement in wall motion at follow-up echocardiography were 83% (55 of 66 segments) and 86% (43 of 50 segments), respectively. Excellent correlation was found (r = 0.93, p < 0.001; absolute difference [mean +/- SD] 0.03 +/- 0.05) between the akinetic length ratios measured during dobutamine infusion and in the late convalescent stage. CONCLUSIONS In the early stage of acute myocardial infarction, low dose dobutamine stress echocardiography provides a useful method for predicting reversible dysfunction with excellent sensitivity and specificity and can also be used to quantitate the extent of irreversibly damaged myocardium.

Effect of angina pectoris on myocardial protection in patients with reperfused anterior wall myocardial infarction: retrospective clinical evidence of "preconditioning".

OBJECTIVES We examined whether angina pectoris occurring shortly before the onset of acute myocardial infarction can actually preserve postischemic left ventricular function in humans. BACKGROUND Experimental studies indicate that brief, transient episodes of ischemia render the heart very resistant to infarction from a subsequent sustained ischemic insult, an effect termed ischemic preconditioning. However, no clinical data are available concerning the implications of angina pectoris shortly before the onset of infarction in humans. METHODS We studied 84 patients with an acute anterior myocardial infarction. All patients had total occlusion of the proximal or medial portion of the left anterior descending coronary artery and achieved reflow within 6 h of onset. Patients were classified into three groups on the basis of duration of antecedent angina pectoris: group 1 = no angina (37 patients); group 2 = new angina pectoris occurring < or = 7 days of onset of infarction (22 patients); group 3 = angina pectoris beginning > 7 days before onset of infarction (25 patients). All patients underwent left ventriculography on the day of, and 28 days after, onset of infarction to determine ejection fraction and regional wall motion in the territory of the left anterior descending coronary artery by the centerline method. RESULTS Angiographic collateral flow grade was higher in group 3 than in groups 1 and 2 ([mean +/- SD] group 1 = 0.08 +/- 0.7, group 2 = 0.7 +/- 0.7, group 3 = 1.5 +/- 0.8). Although there were no differences in baseline ejection fraction and regional wall motion among the three groups, the degree of improvement was significantly greater in groups 2 and 3 than in group 1 (late minus baseline ejection fraction: group 1 = 0 +/- 8%, group 2 = 7 +/- 10% group 3 = 6 +/- 10% [p < 0.05 group 1 vs. groups 2 and 3]; late minus baseline regional wall motion: group 1 = 0.2 +/- 0.4, group 2 = 0.6 +/- 0.5, group 3 = 0.5 +/- 0.6 SD/chord [p < 0.05, group 1 vs. group 2]). When the study was limited to those patients with no or poor collateral flow (31 in group 1, 19 in group 2, 10 in group 3), only group 2 patients had a significant improvement in wall motion. Angina pectoris within 24 h before onset of infarction was more frequent in group 2 (82%) than group 3 (28%, p < 0.05). CONCLUSIONS Episodes of angina pectoris occurring shortly before the onset of infarction may preserve myocardial contractile function in reperfused myocardial infarction despite less support from collateral flow channels, although these are suggestive results in a limited number of patients.

Time course of functional improvement in stunned myocardium in risk area in patients with reperfused anterior infarction.

BackgroundThe beneficial effect of coronary reflow on myocardial salvage may be assessed more accurately than in previous studies if the size of risk area is taken into account, particularly because the size of risk area varies significantly among patients. In this study, the risk area was determined with myocardial contrast echocardiography to investigate the time course of functional recovery of postischemic myocardium within the risk area in patients with reperfused anterior myocardial infarction. Methods and ResultsThe study population consisted of 21 patients with anterior myocardial infarction who achieved coronary reflow within 6 hours of onset by means of thrombolysis or coronary angioplasty. Myocardial contrast echocardiography was performed with the injection of hand-agitated Haemaccel (5 ml) into the right and left coronary arteries before coronary reflow, and the risk area was defined as the area of contrast perfusion defect in the apical long-axis view. The ratio of the endocardial length of abnormal contraction (dyskinesis/akinesis) segment to that of contrast defect segment (AS/CD) was determined at days 1, 2, 3, 7, 14, and 28 of reflow. Before reflow, the length of contrast defect correlated well with the segment length of dyskinesis/akinesis. The values for AS/CD in patients with successful reperfusion significantly and progressively decreased until day 14; 1.00±0.02 at day 1, 0.93±0.11 at day 2 (p<0.05 versus day 1), 0.84±0.16 at day 3 (p<0.05 versus day 2), 0.80±0.13 at day 7 (p<0.01 versus day 2), 0.73±0.10 at day 14, and 0.72±0.10 at day 28. Greater improvement in function was obtained in patients reperfused within 4 hours than in those reperfused at 24 hours (AS/CD at day 28, 0.64±0.12 versus 0.75±0.09, p<0.05). ConclusionThus, a significant amount of myocardium, an average of 28%o in segment length of the risk area, is salvaged in patients with reperfused anterior myocardial infarction. Major functional improvement seems to be achieved within 14 days of reflow.

Ultrasonic Tissue Characterization Predicts Myocardial Viability in Early Stage of Reperfused Acute Myocardial Infarction

BACKGROUND The aim of the present study was to characterize temporal changes in cyclic variation of ultrasonic integrated backscatter (IBS), which reflects intrinsic contractile performance, in patients with reperfused acute myocardial infarction (AMI) and to elucidate the clinical value of tissue characterization in predicting myocardial viability. METHODS AND RESULTS We recorded short-axis IBS images before and 3, 7, and 21 days after reperfusion in 26 patients with AMI and obtained the cyclic variation of IBS in the normal and infarct zones. When cyclic variation showed synchrony and asynchrony, we expressed its magnitude as positive and negative values, respectively, called the phase-corrected magnitude. We also measured average wall motion score (dyskinesis, 4; normal, 0) of the infarct segments. The phase-corrected magnitude was lower in the infarct zone than in the normal zone before reperfusion (0.3+/-2.5 versus 5.2+/-1.7 dB, P<.05). At day 3, the phase-corrected magnitude increased by 2.1+/-2.6 dB despite no improvement in wall motion. Improvement in wall motion was observed only at day 21. The patients with the phase-corrected magnitude of > or =2.0 dB at day 3 showed significantly lower wall motion score at day 21 than did the other patients (1.7+/-0.6 versus 2.4+/-0.5, P<.01). CONCLUSIONS In patients with AMI, cyclic variation of IBS is blunted during ischemia but recovers much faster after reperfusion than the improvement in wall motion. The greater phase-corrected magnitude at day 3 may be a predictor of better functional improvement.

Concentrations and molecular forms of human brain natriuretic peptide in plasma

Using a highly sensitive radioimmunoassay (RIA) system for human brain natriuretic peptide (BNP), immunoreactive (ir-) human BNP was found to be present in plasma, in addition to heart and brain tissue. Plasma concentrations of ir-BNP were 0.17-0.74 fmol/ml (mean: 0.35 fmol/ml) in normal young men, being about 1/17 of the plasma concentration of human atrial natriuretic peptide (ANP). In patients with heart disease, plasma concentration of ir-BNP increased about 100-fold (5.00-177.37 fmol/ml), being nearly comparable to that of ir-ANP, even though ANP concentration also increased about 7-fold. Two molecular forms of ir-BNP in plasma were identified as BNP-32 and gamma-BNP (pro-BNP), which are also found in cardiac atrium. In normal human plasma, gamma-BNP is the predominant molecular form, while the main form in cardiac atrium is BNP-32. These results suggest that biosynthesis and secretion of BNP are augmented in heart disease and that human BNP has a unique processing and metabolic system distinct from that of ANP.

Roles of NO and Ca2+-activated K+ channels in coronary vasodilation induced by 17beta-estradiol in ischemic heart failure.

Estrogen induces the generation of nitric oxide (NO) and produces coronary vasodilation by opening the Ca2+‐activated K+ (KCa) channels. The hypothesis that 17β‐estradiol produces NO and activates KCa channels during coronary hypoperfusion was investigated. In open‐chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. 17β‐Estradiol was infused into the bypass tube for 20 min after coronary blood flow was reduced by partial occlusion of the bypass tube. 17β‐Estradiol increased the difference in NO concentrations between the coronary venous and arterial blood as well as coronary blood flow. The lactate extraction ratio and pH of coronary venous blood were both also increased by 17β‐estradiol, indicating a reduction in myocardial anaerobic metabolism. Whereas the increase in the coronary arteriovenous difference in NO concentration was completely attenuated by NG‐nitro‐L‐arginine methyl ester (L‐NAME, an inhibitor of NO synthase), the increase in coronary blood flow induced by 17β‐estradiol was only partially attenuated by L‐NAME. The combination of L‐NAME and iberiotoxin (a blocker of high‐conductance KCa channels) completely abolished the coronary vasodilatory effect of 17β‐estradiol. The data indicate that during coronary hypoperfusion in canine hearts, 17β‐estradiol increases coronary blood flow and improves metabolic dysfunction by increasing NO release and opening KCa channels.—Node, K., Kitakaze, M., Kosaka, H., Minamino, T., Sato, H., Kuzuya, T., Hori, M. Roles of NO and Ca2+‐activated K+ channels in coronary vasodilation induced by 17β‐estradiol in ischemic heart failure. FASEB J. 11, 793–799 (1997)