Relation between white blood cell counts and myocardial reperfusion in patients with recanalized anterior acute myocardial infarction.

BACKGROUND: The clinical significance of the white blood cell (WBC) count on admission in relation to the duration of ischemia in acute myocardial infarction (AMI) remains unclear. METHODS AND RESULTS: The relationship of the WBC count on admission to myocardial reperfusion was examined in 135 patients with recanalization of an anterior AMI within 6 h of symptom onset. Patients were classified according to the WBC count on admission: Group L (n=75), WBC count <12,000 cells/mm(3) and group H (n=60), WBC count >or=12,000 cells/mm(3). Peak creatine kinase (CK) was higher and impaired myocardial reperfusion, defined as a myocardial blush grade of 0/1, was more frequent in group H than in group L. Among the patients in group H, those with early (3 h) recanalization; however, peak CK and the incidence of impaired myocardial reperfusion were similar in these subgroups of patients. Multivariate analysis showed that WBC count >or=12,000 cells/mm(3) on admission was an independent predictor of impaired myocardial reperfusion in patients with early recanalization (odds ratio 7.9, p=0.04), but not in those with late recanalization. CONCLUSIONS: A higher WBC count may be associated with progression of myocardial damage after recanalization in patients with early recanalization of an anterior AMI.     

Relationship between collateral blood flow and microvascular perfusion after reperfused acute myocardial infarction

During acute occlusion of an epicardial vessel collaterals preserve the microvascular perfusion and limit the extent of myocardial damage. Pressure-derived collateral flow index (CFIp) assessed by intracoronary pressure measurement allow us to quantify collateral vessel development. The angiographic myocardial blush (MB) scores, based on the contrast dye density and washout in the infarcted myocardium, provide important information about microvascular perfusion after acute myocardial infarction (AMI). In this study we assessed the microvascular perfusion with MB and studied the relation between CFIp in patients with AMI who treated with thrombolytic therapy and TIMI grade III flow restored in the infarct related artery (IRA). Forty-one patients with AMI who were treated with thrombolytic therapy and underwent stent implantation (mean of 3 days after AMI) to the IRA were included in this study. After angiography, CFIp was calculated as the ratio of simultaneously measured coronary wedge pressure--central venous pressure (Pv) to mean aortic pressure--Pv. Myocardial blush was graded densitometrically based on visual assessment of the relative contrast opacification of the myocardial territory subtended by the infarct vessel. There was a statistically significant correlation between CFIp and post-stent myocardial blush grades (P < 0.01, r = 0.70). There was a significant difference in mean CFIp among myocardial blush grades implying that higher CFIp is associated with better MB (0.39 +/- 0.11 in grade 3, 0.32 +/- 0.10 in grade 2, 0.24 +/- 0.09 in grade 1, and 0.16 +/- 0.08 in grade 0, P < 0.01). Well developed collaterals can limit microvascular damage by preserving microvascular perfusion. A higher pressure-derived collateral flow index is associated with better tissue level perfusion as evidenced by the higher myocardial blush score.     

Changes in the flow properties of white blood cells after acute myocardial infarction

Because they can obstruct blood vessels and release noxious substances, white blood cells may contribute to the development of tissue ischaemia. The flow properties of white cells were tested after myocardial infarction, by measuring the filtration rates of cell suspensions through 8 microns pore filters. Compared with mononuclear cells from age matched controls, mononuclear cells from patients with infarction showed impaired filterability within the first day after the onset of pain; this condition persisted for at least two days and by day 10 it was improved. On day 1, granulocyte filterability and the proportion showing morphological evidence of activation were nearly normal. By day 3 the flow resistance and activation had increased, but the changes seen depended on the age of the patient. The filterability and activation of granulocytes from patients aged less than 60 were significantly increased from day 1, whereas there were no changes in granulocytes from patients aged greater than 60 years. Suspensions of unfractionated white cells showed changes intermediate between the mononuclear cells and granulocytes. A group of five patients who presented with chest pain but who were subsequently found not to have had an infarction showed no evidence of abnormal filterability or activation. The changes in filterability probably reflect white cell activation, which may have an adverse effect on the perfusion of the ischaemic myocardium.     

C-反应蛋白和白细胞计数与急性心肌梗死患者住院期间死亡的关系

目的探讨急性心肌梗死(AMI)患者入院后C-反应蛋白(CRP)和白细胞(WBC)计数水平与住院期间死亡的关系。方法以1998年1月到2010年10月期间在苏州大学附属第二医院住院的843例AMI的患者为研究对象,收集患者的人口统计学、生活方式、病史、入院后血压、实验室检查结果等相关资料,采用Logistic回归和Kaplan-Meier生存曲线分析CRP和WBC水平与患者住院期间死亡的关联关系。结果在Logistic回归分析中,经多因素调整后,随着CRP和WBC水平的升高,AMI患者发生死亡的危险性呈逐渐升高的趋势(均为P<0.05)。以CRP和WBC最低分位为参比,最高分位的患者发生死亡的OR值(95%CI)分别是1.82(0.92³.59)和4.49(2.143.59)和4.49(2.14⁹.42)。Kaplan-Meier生存曲线分析结果显示,CRP和WBC正常组的生存率显著高于CRP和WBC异常组(均为P<0.05)。结论 CRP和WBC水平升高与AMI患者住院期间死亡的危险性相关联。     

Changes in the flow properties of white blood cells after acute myocardial infarction.

Because they can obstruct blood vessels and release noxious substances, white blood cells may contribute to the development of tissue ischaemia. The flow properties of white cells were tested after myocardial infarction, by measuring the filtration rates of cell suspensions through 8 microns pore filters. Compared with mononuclear cells from age matched controls, mononuclear cells from patients with infarction showed impaired filterability within the first day after the onset of pain; this condition persisted for at least two days and by day 10 it was improved. On day 1, granulocyte filterability and the proportion showing morphological evidence of activation were nearly normal. By day 3 the flow resistance and activation had increased, but the changes seen depended on the age of the patient. The filterability and activation of granulocytes from patients aged less than 60 were significantly increased from day 1, whereas there were no changes in granulocytes from patients aged greater than 60 years. Suspensions of unfractionated white cells showed changes intermediate between the mononuclear cells and granulocytes. A group of five patients who presented with chest pain but who were subsequently found not to have had an infarction showed no evidence of abnormal filterability or activation. The changes in filterability probably reflect white cell activation, which may have an adverse effect on the perfusion of the ischaemic myocardium.     

A randomized trial of late reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction-6 Study Group.

BACKGROUND. Experimental and observational clinical studies of acute coronary occlusion have suggested that late reperfusion prevents infarct expansion and facilitates myocardial healing. The purpose of this trial was to assess whether infarct vessel patency could be achieved in late-entry patients and what benefit, if any, can be demonstrated. METHODS AND RESULTS. In a double-blind fashion, 197 patients with 6 to 24 hours of symptoms and ECG ST elevation were randomly assigned to tissue-type plasminogen activator (100 mg over 2 hours) or placebo. Coronary angiography within 24 hours was used to determine infarct vessel patency status. Patients with infarct-related occluded arteries were then eligible for a second randomization to either angioplasty (34 patients) or no angioplasty (37 patients). Ventricular function and cavity size were reassessed at 1 month by gated blood pool scintigraphy and at 6 months by repeat cardiac catheterization. The primary end point, infarct vessel patency, was 65% for plasminogen activator patients compared with 27% in the placebo group (p less than 0.0001). There were no differences between these groups in ejection fraction or infarct zone regional wall motion at 1 or 6 months. At 6 months, infarct vessel patency was 59% in both groups. In the placebo group, there was a significant increase in end-diastolic volume from acute phase of 127 ml to 159 ml at 6-month follow-up (p = 0.006) but no increase in cavity size for the plasminogen activator group patients. Coronary angioplasty was associated with an initial 81% recanalization success and improved ventricular function at 1 month, but by late follow-up no advantage could be demonstrated for this procedure, and there was a 38% spontaneous recanalization rate in the patients assigned to no angioplasty. CONCLUSIONS. The study demonstrates that it is possible to achieve infarct vessel recanalization in the majority of late-entry patients with either thrombolytic therapy or angioplasty. Thrombolytic intervention had a favorable effect on prevention of cavity dilatation and left ventricular remodeling, but there are no late benefits on systolic function after thrombolysis or coronary angioplasty. The conclusions concerning overall potential benefit of applying late reperfusion therapy will require data from large-scale trials designed to assess mortality reduction.     

Association between white blood cell count, epicardial blood flow, myocardial perfusion, and clinical outcomes in the setting of acute myocardial infarction: a thrombolysis in myocardial infarction 10 substudy

BACKGROUND: Elevation of the white blood cell (WBC) count during acute myocardial infarction (AMI) is associated with adverse outcomes. We examined the relationship between the WBC count and angiographic findings to gain insight into this relationship. Results and Methods-We evaluated data from 975 patients in the Thrombolysis In Myocardial Infarction (TIMI) 10A and 10B trials. Patients with a closed artery at 60 and 90 minutes had higher a WBC count than patients with an open artery (P:=0.02). Likewise, the presence of angiographically apparent thrombus was associated with a higher WBC count (11.5+/-5.2x10(9)/L, n=290, versus 10.7+/-3. 5x10(9)/L, n=648; P=0.008). In addition, a higher WBC count was associated with poorer TIMI myocardial perfusion grades (4-way P=0.04). Mortality rates were higher in patients with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 4.9% for WBC count 5 to 10x10(9)/L, 3.8% for WBC count 10 to 15x10(9)/L, 10.4% for WBC count >15x10(9)/L; P=0.03). The development of new congestive heart failure or shock was also associated with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 5.2% for WBC count 5 to 10x10(9)/L, 6.1% for WBC count 10 to 15x10(9)/L, 17.1% for WBC count >15x10(9)/L; P<0.001), an observation that remained significant in a multivariable model that adjusted for potential confounding variables (odds ratio 1.21, P=0.002). CONCLUSIONS: Elevation in WBC count was associated with reduced epicardial blood flow and myocardial perfusion, thromboresistance (arteries open later and have a greater thrombus burden), and a higher incidence of new congestive heart failure and death. These observations provide a potential explanation for the higher mortality rate observed among AMI patients with elevated WBC counts and helps explain the growing body of literature that links inflammation and cardiovascular disease.     

Relationship between corrected TIMI frame counts at three weeks and late survival after myocardial infarction

OBJECTIVES: To evaluate the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC) as a predictor of late survival after myocardial infarction. BACKGROUND: Thrombolysis in Myocardial Infarction flow grades predict late survival after myocardial infarction. The CTFC provides a more reproducible measurement of infarct-related artery blood flow than the TIMI flow grade, and has been linked to 30-day outcomes, but it has not yet been established how the CTFC correlates with late survival. METHODS: Of 1,001 patients with acute myocardial infarction presenting within 4 h of symptom onset, 882 underwent angiography at approximately three weeks. Infarct artery flow was assessed, blinded to clinical outcomes, according to the CTFC and TIMI flow grade. Late cardiac mortality and survival were determined in 97.5% of patients. RESULTS: The mean CTFC was 40 +/- 29 in 644 patent infarct arteries (median, 34 [interquartile range, 24 to 47]). The CTFC, assessed as a continuous univariate variable, was found to be a predictor of five-year survival, as was the TIMI flow grade (both p < 0.001). On multivariate analysis, factors associated with five-year survival included the ejection fraction or end-systolic volume index (both p < 0.001); exercise duration (p = 0.005), age (p = 0.008), diabetes (p = 0.02) and CTFC (p = 0.02) or TIMI flow (p = 0.02). The same factors, except for the CTFC and TIMI flow grade, were predictors of 10-year survival. CONCLUSIONS: The CTFC three weeks after myocardial infarction was an independent predictor of five-year survival, but not 10-year survival. Although the CTFC provided additional prognostic information within TIMI flow grades, its superiority was not demonstrated.     

Comparison of white blood cell counts in acute myocardial infarction patients with significant versus insignificant coronary artery disease

The response of high-density lipoprotein cholesterol to hypolipidemic monotherapy with diet, statins, fibrates, or nicotinic acid was investigated prospectively in 801 patients with dyslipidemia. We hypothesized that the behavior of high-density lipoprotein cholesterol after treatment would depend on its baseline levels and the therapy used.     

急性心肌梗死的心肌再灌注血流与脑钠肽的关系

目的探讨急性心肌梗死(AMI)心肌血流再灌注水平与血浆脑钠肽(BNP)水平的关系及其临床意义。方法对67名AMI成功行急诊介入治疗(PCI)的患者分别进行TIMI心肌灌注分级(TMPG)、心肌灌注显影分级(MBG)和校正的TIMI血流帧数计数(CTFC),采用荧光免疫抗原抗体结合方法测定发病24h即刻血浆脑钠肽(BNP)水平并评价其相互关系。结果TMPG方法评定的心肌灌注水平中,TMPG0/1级组12例,TMPG2级组29例,TMPG3级组26例,其对应血浆BNP平均水平分别为(1026±1119)ng/L,(346±192)ng/L和(219±95)ng/L。各组间血浆BNP水平差异有统计学意义(P=0·001)。其中TMPG0/1级组血浆BNP水平分别高于TMPG2级组和TMPG3级组(P<0·01,P<0·001);TMPG2级组高于TMPG3级组(P<0·01)。MBG方法评定的心肌灌注水平中,MBG0/1级组22例,MBG2级组25例,MGG3级组20例,其对应血浆BNP平均水平分别为(735±886)ng/L,(343±137)ng/L和(148±65)ng/L。各组间血浆BNP水平差异有统计学意义(P<0·001)。其中MBG0/1级组血浆BNP水平分别高于MBG2级组和MBG3级组(P<0·05,P<0·001);MBG2级组高于MBG3级组(P<0·001)。CTFC方法评定的冠脉血流中CTFC>40帧组20例,CTFC≤40帧组47例,血浆BNP平均水平分别为(453±265)ng/L和(397±650)ng/L,CTFC>40帧组血浆BNP水平高于CTFC≤40帧组(P=0·0036)。结论AMI患者心肌血流再灌注水平与血浆BNP水平负相关,再灌注水平越低组血浆BNP水平越高。心肌缺血损伤是BNP释放的重要刺激因素。     

Reduction in incidence of inducible ventricular tachycardia after myocardial infarction by treatment with streptokinase during infarct evolution

The aim of this study was to determine whether intravenous streptokinase administered with or without oral aspirin to patients with evolving myocardial infarction reduces the inducibility of ventricular tachycardia at electrophysiologic study and thus the risk of sudden death in infarct survivors. Of 159 patients randomized at Westmead Hospital to the multicenter Second International Study of Infarct Survival (ISIS-2) after streptokinase and aspirin in acute myocardial infarction, 87 underwent electrophysiologic testing 6 to 28 days after infarction to determine their risk of subsequent ventricular arrhythmias (streptokinase 20 patients; aspirin 25 patients; streptokinase and aspirin 21 patients; both placebos 21 patients). Patients who underwent electrophysiologic testing had similar clinical characteristics to those of patients who did not. The stimulation protocol comprised up to and including four extrastimuli applied to the right ventricular apex at twice diastolic threshold. An abnormal result was defined as ventricular tachycardia with a cycle length greater than or equal to 230 ms lasting greater than or equal to 10 s. Ventricular tachycardia was inducible at electrophysiologic study in 8 patients who received placebo streptokinase, but in no patient who received active streptokinase (8 of 46 versus 0 of 41; p = 0.005, Fischer's exact test). Ventricular tachycardia was inducible in 4 patients who received aspirin therapy and 4 who did not (4 of 41 versus 4 of 46; p = NS). During a mean follow-up period of 39 +/- 9 months, there were no spontaneous episodes of ventricular tachycardia, ventricular fibrillation or witnessed sudden death in the streptokinase-treated group compared with three such events in the placebo-treated group (p = 0.13). When compared with placebo therapy, intravenous streptokinase substantially reduced the incidence of inducible ventricular tachycardia in infarct survivors. No similar benefit was attributable to aspirin therapy.     

Megadose heparin and streptokinase produce similar TIMI 3 flow at discharge in patients of acute myocardial infarction presenting between 7-12 hours

The present study was undertaken to assess the impact of megadose heparin bolus on angiographic patency of infarct-related artery in patients of acute myocardial infarction presenting between 7-12 hours and to compare it with streptokinase. Forty-seven patients (27 males, mean age 58.1 +/- 9.6 years) of acute myocardial infarction between 7-12 hours of onset of chest pain were randomised to receive either megadose heparin bolus (300 IU/kg body weight, group 1, n = 24; or streptokinase 1.5 million units over one hour, group 2, n = 23). Parameters noted were: relief of pain at 90 minutes, 50 percent or more resolution of ST segment at 90 minutes, TIMI grade flow and left ventricular ejection fraction at discharge. Mean age (59.0 +/- 12.9 years in group 1; 57.2 +/- 8.1 years in group 2), mean time to drug (7.5 +/- 1.3 hours in group 1; 7.8 +/- 1.6 hours in group 2), site of anterior wall infarction (12 in group 1, 10 in group 2), relief of pain at 90 minutes (15 in group 1, 14 in group 2) and more than 50 percent resolution of ST segment elevation at 90 minutes (12 patients in each group) were similar. On coronary angiography performed in 42 patients (21 in each group) at a mean interval of 7.2 +/- 1.3 days after acute myocardial infarction, TIMI grade 3 flow was seen in 7 (33.3%) patients in each group and TIMI grade 2/3 flow was also similar in both the groups (p = NS). No major bleed occurred in either group. We conclude that heparin given as a megadose bolus produces similar TIMI 3 flow in infarct-related artery as compared to streptokinase in acute myocardial infarction patients presenting between 7-12 hours.     

Relation of admission white blood cell count to left ventricular remodeling after anterior wall acute myocardial infarction

We investigated whether a high white blood cell (WBC) count on admission for acute myocardial infarction (AMI) may be associated with a higher risk of subsequent left ventricular (LV) remodeling. We included 107 patients with anterior AMI. Echocardiographic studies were performed at hospital discharge, at 3 months, and at 1 year after AMI. LV remodeling (>20% increase in end-diastolic volume) was observed in 27% of patients. WBC counts during hospitalization were higher in patients who subsequently underwent LV remodeling (p = 0.003 for WBC count on admission). The increase in end-diastolic volume from baseline to 1 year was greater for patients in the higher tertile of WBC count on admission (p = 0.04). When adjusting for baseline clinical and echocardiographic characteristics by multivariate analysis, WBC count on admission was independently associated with LV remodeling (odds ratio 1.23, 95% confidence interval 1.04 to 1.45, p = 0.018). In conclusion, a high WBC count on admission for AMI is an independent predictor of LV remodeling, even when predischarge echocardiographic variables are taken into account.     

Recovery rates of regional sympathetic reinnervation and myocardial blood flow after acute myocardial infarction

BACKGROUND: The implication of an arrhythmogenic role for infarction-induced disruption of regional myocardial sympathetic nerve activity has led to a search for noninvasive methods to study regional sympathetic nerve activity in patients after infarction. METHODS AND RESULTS: By using positron emission tomography, we measured the time course of myocardial hypoperfusion with [13N]-ammonia retention and sympathetic innervation with [18F]-6-fluorodopamine within the infarct zone in 10 patients at 2 weeks, 3 months, and 6 months after a first-onset Q-wave myocardial infarction. The time course for reestablishment of global cardiac autonomic function was also determined by measuring the power spectrum of heart rate variability with an autoregressive technique. The average infarct defect size as determined by the fractional uptake of [13N]-ammonia was 17.22% +/- 5.95% of the left ventricular myocardium. The fractional uptake of [18F]-fluorodopamine in the infarct zone was similar, at 15.83% +/- 4.45% (not significant). There was a significant increase (14% to 15%; P <.05) in myocardial blood flow and [18F]-fluorodopamine uptake to the infarct zone between 2 weeks and 3 months, with no further change between 3 months and 6 months. However, the average rate of loss (t1/ 2 hour) of [18F]- fluorodopamine continued to decrease between 2 weeks and 6 months. This paralleled a continuing fall in the low-frequency to high-frequency autospectral power ratio throughout the 6 months after infarction. CONCLUSIONS: This study demonstrates a modest increase in myocardial blood flow and evidence for sympathetic reinnervation to the infarct zone between 2 weeks and 3 months after acute myocardial infarction. Despite a flow-dependent effect on the uptake of [18F]-fluorodopamine by 3 months, there is a suggestion that restoration of sympathetic activity within the infarct zone continues between 3 months and 6 months after acute myocardial infarction.     

Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis in Myocardial Infarction, Phase II, pilot and clinical trial

In the Thrombolysis in Myocardial Infarction, Phase II pilot and clinical trial, 908 patients [326 (35.9%) in the pilot study and 582 (64.0%) in the randomized study] were treated with 150 mg recombinant tissue-type plasminogen (rt-PA) activator in combination with heparin and aspirin, and 3,016 patients [64 (2.1%) in the pilot study and 2,952 (97.9%) in the randomized study] were treated with 100 mg rt-PA in combination with heparin and aspirin. Adverse neurological events occurred in 23 patients treated with 150 mg rt-PA (2.5%) [nine cerebral infarctions (1.0%), 12 intracerebral hemorrhages (1.3%), and two subdural hematomas (0.2%)] and in 33 patients treated with 100 mg rt-PA (1.1%) [20 cerebral infarctions (0.7%), 11 intracerebral hemorrhages (0.4%), and two subdural hematomas (0.1%)]. The difference in adverse neurological events observed comparing the two rt-PA regimens was primarily due to a higher frequency of intracerebral bleeding among patients treated with 150 mg rt-PA (1.3% versus 0.4%, p less than 0.01). Patients with recent (within 6 months) histories of stroke were not eligible for the study, and patients with any history of cerebrovascular disease were declared ineligible early in the study. The small number of patients (89, or 2.3%) with any history of neurological disease, intermittent cerebral ischemic attacks, or stroke who were enrolled before the stricter eligibility criteria were imposed or on the basis of incomplete baseline information experienced an increased frequency of intracerebral hemorrhage compared with patients without such histories (3.4% versus 0.5%). Mortality at 6 weeks after presentation among 23 patients who had intracerebral hemorrhage was 47.8%. Intracerebral hemorrhage is a severe but infrequent complication of rt-PA therapy for acute myocardial infarction. The combined frequency of intracerebral hemorrhage, subdural hematoma, and cerebral infarction after treatment with 100 mg rt-PA is comparable to that observed in other trials with thrombolytic agents in acute myocardial infarction.     

Oxidative stress in young subjects with acute myocardial infarction: evaluation at the initial stage and after 12 months

In 105 subjects (97 men and 8 women) aged <46 years (mean age 39.6 +/- 5.5 years), with recent acute myocardial infarction (T1), thiobarbituric acid reactive substances and total antioxidant status were determined; NO production was evaluated by measuring the nitrite and nitrate (NOx) concentration. The patients with acute myocardial infarction were subdivided according to the main risk factors, number of risk factors, and extent of coronary lesions. The evaluation was repeated after 12 months (T2). In these subjects, thiobarbituric acid reactive substances and NOx were significantly increased and total antioxidant status was significantly decreased at T1. In single risk factor, only NO metabolites were significantly lower in acute myocardial infarction subjects who smoke than in subjects who do not. Subdividing the subjects according to the number of risk factors and number of stenosed coronary vessels, there were no significant differences between the subgroups. At T2, thiobarbituric acid reactive substances and NOx were decreased and total antioxidant status was increased, but all parameters were still altered.