Reperfusion Therapy For Myocardial Infarction Research Articles

Effect of inflammatory factor-induced cyclo-oxygenase expression on the development of reperfusion-related no-reflow phenomenon in acute myocardial infarction.

No reflow after reperfusion therapy for myocardial infarction is a strong predictor of clinical outcome. Increased levels of inflammatory factors, including C-reactive protein (CRP), in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) may affect myocardial perfusion. However, why the no-reflow phenomenon increases in inflammation stress after PCI is not clear. The aim of the present study was to determine the effects and molecular mechanisms underlying the effects of CRP on the expression of cyclo-oxygenase (COX) on the development of the no-reflow phenomenon. There was a significant increase in plasma levels of CRP and interleukin (IL)-6 in no-reflow patients, suggesting that inflammatory factors play an important role in the development of the no-reflow phenomenon. The mechanisms involved were further evaluated after reperfusion in a rat model mimicking the no-reflow phenomenon. Compared with normal reflow rats, there were significant increases in both COX-1 and COX-2 in cardiac tissue from no-reflow rats. The COX inhibitor indomethacin (5 mg/kg, i.p.) significantly reduced the no-reflow area. In another series of experiments, human coronary artery endothelial cells (HCAEC) were treated with CRP at clinically relevant concentrations (5-25 μg/mL). C-Reactive protein significantly increased COX-1 and COX-2 levels in a time- and concentration-dependent manner. In addition, extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) were activated in CRP (5, 10, 25 μg/mL)-treated HCAEC cultures. Furthermore, the ERK inhibitor pd98059 (30 μmol/L) and the JNK inhibitor sp600125 (10 μmol/L) blocked CRP-induced COX-1 and COX-2 expression for 12 h. Together, the findings of the present study suggest that CRP can promote the development of the no-reflow phenomenon by increasing COX-1 and COX-2 expression, which is regulated, in part, via ERK and JNK activity.

Diferencias de género en el tratamiento de los síndromes coronarios agudos: Los resultados de la Epi-Cardio Registro

Gender Differences in the Treatment of Acute Coronary Syndromes: Results of the Epi-Cardio Registry Background Controversial evidence has been reported regarding gender bias in the management of patients with acute coronary syndromes; thus, it is relevant to have data related to this topic in our country. Objective The aim of this study was to assess gender differences in the management of acute coronary syndromes in cardiovascular care units participating in the Epi-Cardio registry. Methods We included 8997 records of patients with diagnosis of acute coronary syndromes. Propensity score adjusted analyses and sensitivity analysis were performed. Results In patients with non ST-segment elevation acute coronary syndromes, women were independently associated with lower in-hospital indication of coronary angiography (OR 0.73, 95% CI 0.65 to 0.82), and lower use of IIb/IIIa inhibitors than men. After adjusted analyses, there were no significant differences between men and women in the use of reperfusion therapy for myocardial infarction or in in-hospital mortality. At discharge, women were significantly less likely than men to receive prescriptions for beta-blockers and statins, and more likely to receive prescriptions for benzodiazepines. Conclusions These findings suggest gender bias in the treatment of patients with acute coronary syndromes, evidenced by selection of a more conservative strategy and lower prescription of drugs recommended for secondary prevention in women. Differences between genders in the approach of acute coronary syndromes should be studied more deeply, as the underutilization of evidence-based therapies could have an impact on women clinical outcomes.

Gender Differences in the Treatment of Acute Coronary Syndromes: Results From the Epi-Cardio Registry

mtsAc, 1 , hernan dov Al mtsAc,1 Results In patients with non ST-segment elevation acute coronary syndromes, women were independently associated with lower in-hospital indication of coronary angiography (OR 0.73, 95% CI 0.65 to 0.82), and lower use of IIb/IIIa inhibitors than men. After adjusted analyses, there were no significant differences between men and women in the use of reperfusion therapy for myocardial infarction or in in-hospital mortality. At discharge, women were significantly less likely than men to receive prescriptions for beta-blockers and statins, and more likely to receive prescriptions for benzodiaz- epines. Conclusions These findings suggest gender bias in the treatment of patients with acute coronary syndromes, evidenced by selection of a more conservative strategy and lower pre- scription of drugs recommended for secondary prevention in women. Differences be- tween genders in the approach of acute coronary syndromes should be studied more deeply, as the underutilization of evidence-based therapies could have an impact on women's clinical outcomes.

Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury

We have previously identified exosomes as the paracrine factor secreted by mesenchymal stem cells. Recently, we found that the key features of reperfusion injury, namely loss of ATP/NADH, increased oxidative stress and cell death were underpinned by proteomic deficiencies in ischemic/reperfused myocardium, and could be ameliorated by proteins in exosomes. To test this hypothesis in vivo, mice (C57Bl6/J) underwent 30min ischemia, followed by reperfusion (I/R injury). Purified exosomes or saline was administered 5min before reperfusion. Exosomes reduced infarct size by 45% compared to saline treatment. Langendorff experiments revealed that intact but not lysed exosomes enhanced viability of the ischemic/reperfused myocardium. Exosome treated animals exhibited significant preservation of left ventricular geometry and contractile performance during 28days follow-up. Within an hour after reperfusion, exosome treatment increased levels of ATP and NADH, decreased oxidative stress, increased phosphorylated-Akt and phosphorylated-GSK-3β, and reduced phosphorylated-c-JNK in ischemic/reperfused hearts. Subsequently, both local and systemic inflammation were significantly reduced 24h after reperfusion. In conclusion, our study shows that intact exosomes restore bioenergetics, reduce oxidative stress and activate pro-survival signaling, thereby enhancing cardiac function and geometry after myocardial I/R injury. Hence, mesenchymal stem cell-derived exosomes are a potential adjuvant to reperfusion therapy for myocardial infarction.

Left bundle branch block without concordant ST changes is rarely associated with acute coronary occlusion

BackgroundThe Sgarbossa score has been used to identify acute myocardial infarction on ECG in the presence of LBBB but has relied on elevated CK-MB for validation rather than angiographic evidence of vessel occlusion. MethodsWe determined (a) the presence or absence of Sgarbossa criteria with concordant (S-con) or discordant (S-dis) ST changes, (b) the presence of acute coronary occlusion or likely recent occlusion on angiography and (c) the biochemical evidence of myocardial infarction (Troponin T >0.10μg/L, Troponin I >1.0μg/L) in patients field-triaged with suspected AMI and LBBB. ResultsBetween April 2004 and March 2009, 102 patients had field ECGs transmitted by paramedics for triage — 8 with S-con, 26 with S-dis and 68 with LBBB alone. Acute coronary occlusion was present in 8/8 with S-con but none of the S-dis or LBBB alone patients, and in all 8 S-con patients reperfusion resulted in resolution of S-con changes. Likely culprit lesions with TIMI 3 flow were found in 3 S-dis patients but stenting did not result in resolution of S-dis. LBBB did not resolve in any patient. Troponin was elevated in 26 patients — 11 with occlusion or likely culprit lesions, 15 with non-ischaemic causes. ConclusionsIn the absence of S-con, LBBB is not associated with acute coronary occlusion and should not be used as criteria for reperfusion therapy in myocardial infarction.

ORAL PRESENTATION

ORAL PRESENTATION

Three life years gained after reperfusion therapy in acute myocardial infarction: 25−30 years after a randomized controlled trial

Reperfusion therapy in acute myocardial infarction reduces infarct size and increases hospital survival. We investigated whether the benefit of reperfusion therapy for myocardial infarction was sustained long-term and assessed the gain in life expectancy by reperfusion therapy. We analysed the outcome of 533 patients (mean age 56 years, 82% men), who were randomized to either reperfusion therapy or conventional therapy during 1980-1985. Median follow up was 27 years (25-30 years). At follow up, 59 patients (22%) of the 269 patients allocated to reperfusion treatment and only 39 patients (15%) of the 264 conventionally treated patients were still alive (p = 0.02). The cumulative 10-, 15-, 20-, and 25-year survival rates were 69, 48, 37, and 24% after reperfusion therapy and 59, 38, 27, and 18% in the control group, respectively (p < 0.001). Life expectancy of the reperfusion group was 15.6 years vs. 12.5 years in the conventionally treated group (p < 0.02). Myocardial reinfarction and subsequent coronary interventions were more frequent after reperfusion therapy, particularly during the first year. In multivariable analysis, reperfusion therapy was an important independent predictor of lower mortality at long-term follow up. Other independent predictors of mortality were age, impaired left ventricular function, multivessel disease, infarct size, and inability to perform an exercise test at the time of discharge. These data confirm that the benefits of early reperfusion therapy for acute myocardial infarction are sustained throughout the lifetime of the patients. More than 3 life years were gained by reperfusion therapy.

No-Reflow Phenomenon: Maintaining Vascular Integrity

The no-reflow phenomenon relates to the inability to reperfuse regions of the myocardium after ischemia, despite removal of the large epicardial coronary artery occlusion. The mechanism involves microvascular obstruction. In experimental studies, using markers for flow (thioflavin S, carbon black, microspheres), perfusion defects associated with no-reflow demonstrated ultrastructural evidence of localized endothelial swelling and blebs that appeared to obstruct flow. In humans no-reflow is more complicated due to the microemboli of atherosclerotic debris and thrombi generated by percutaneous coronary intervention. The no-reflow zone expands during the first few hours of reperfusion suggesting an element of reperfusion injury. In animal models, extensive no-reflow was associated with worse infarct expansion. The phenomenon of no-reflow following reperfusion therapy for myocardial infarction in humans has been demonstrated by magnetic resonance imaging, echo contrast agents, thallium, technecium-99m-labeled albumin microspheres, Thrombolysis In Myocardial Infarction (TIMI) scores, and myocardial blush grade. Patients exhibiting no-reflow following reperfusion therapy for myocardial infarction have greater left ventricular dilation and remodeling, more congestive heart failure, shock, and reduced survival. Certain vasodilators (adenosine, nitroprusside, nicorandil, and calcium blockers) are used acutely in the catheterization laboratory and appear to improve no-reflow, but systematic studies on therapy for no-reflow are needed. There is now clinical evidence that no-reflow is a strong predictor of long-term mortality that is independent of and beyond that provided by infarct size. Identifying and treating no-reflow may have important benefits including enhancing delivery of nutrients and cells required for healing and reducing infarct expansion and ventricular remodeling, which ultimately may reduce congestive heart failure and mortality.

Early Short-Term Vagal Nerve Stimulation Attenuates Cardiac Remodeling After Reperfused Myocardial Infarction

Background Vagal nerve stimulation (VS) has been suggested to be an effective adjunct to reperfusion therapy in myocardial infarction (MI). However, the effect of VS on left ventricular (LV) remodeling after reperfused MI has not been examined. Methods and Results We investigated the effects of early, brief VS on acute inflammatory reactions (study 1) and chronic LV remodeling (study 2) in a rabbit model of reperfused MI. In study 1, rabbits were subjected to 60-minute coronary artery occlusion followed by reperfusion alone (MI, n = 8) or treated with 24-hour VS (MI-VS, n = 8). At 24 hours after ischemia-reperfusion, MI-VS rabbits showed significantly decreased myocardial infiltration of neutrophils and reduced myocardial expressions of tumor necrosis factor-α and matrix metalloproteinase-8 and -9, compared with MI rabbits. Myocardial expression of interleukin-6 was not affected by VS. In study 2, rabbits were subjected to coronary occlusion and reperfusion alone (n = 16) or treated with VS for 3 days (n = 14). At 8 weeks after ischemia-reperfusion, MI-VS rabbits showed significantly improved LV dysfunction and dilatation, and significantly reduced infarct size, infarct wall thinning, and LV weight compared with MI rabbits. Conclusion Early, short-term VS attenuates LV remodeling after reperfused MI, which may be associated with suppression of acute inflammatory reactions.

Single Dose GLP-1-Tf Ameliorates Myocardial Ischemia/Reperfusion Injury

Glucagon-like peptide-1 (GLP-1) has insulinomimetic, insulinotropic, and antiapoptotic properties that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI); however, GLP-1 has a short plasma half-life. Fusion of GLP-1 to human transferrin (GLP-1-Tf) significantly prolongs drug half-life. We tested the ability of single dose GLP-1-Tf to limit myocardial ischemia (30 min)/reperfusion (180 min) injury in rabbits. Nineteen animals were untreated controls. The pre-ischemic group (n=10) was given 10mg/kg of GLP-1-Tf 12 h before ischemia. Immediately after reperfusion, the post-ischemic group (n=10) received GLP-1-Tf (10 mg/kg) and the Tf group (n=4) received transferrin alone. Infarct size as a percentage of the area at risk was 59.1% ± 1.3%, 45.7% ± 1.9%, 44.1% ± 3.3%, 59.7% ± 2.0% in the control group, pre-ischemic group, post-ischemic group, and Tf group, respectively (P<0.05 for both GLP-1-Tf treatments group versus control). GLP-1-Tf reduced the apoptotic index from 4.67% ± 0.40% in the control group to 3.15% ± 0.46% in the pre-ischemic group and to 2.66% ± 0.40% in the post-ischemic group (P<0.05 for both GLP-1-Tf treatments versus control). The size of the wall motion abnormality and ejection fraction was significantly improved in the post-ischemic group relative to the control group. Serum GLP-1 levels were 239.8 ± 25.7 μg/mL in the post-ischemic group, 27.9 ± 5.8 μg/mL in the pre-ischemic group, and undetectable in the control group. GLP-1-Tf limits myocardial reperfusion injury whether given prior to the onset of ischemia or given at reperfusion. GLP-1-Tf may also limit myocardial stunning at high serum levels of the drug.

Regional Heterogeneity of Myocardial Reperfusion Injury: Effect of Mild Hypothermia

Mild hypothermia confers a myocardial protective effect that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI). The effect of temperature on the extent and distribution of myocardial reperfusion injury in a collateral deficient ovine model was studied. Topical cooling maintained left atrial temperature at 39.5 degrees C (n = 8), 38.5 degrees C (n = 5), 37.5 degrees C (n = 6), 36.5 degrees C (n = 6), or 35.5 degrees C (n = 5) in sheep prior to 1 hour of coronary occlusion to produce an anteroapical myocardial risk area (AR) followed by 3 hours of reperfusion. A dual staining and planimetry technique was used to assess infarct size as a percentage of the AR in 3 myocardial short axis slices that included the entire AR (slice 1= most apical; slice 3= most basal). The subendocardial, midmyocardial, and subepicardial extent in short axis of the infarct was also assessed in each slice. Microspheres assessed transmural blood flow. At 39.5 degrees C there was a long-axis gradient in myocardial injury that was most severe at the apex and lessened toward the base. The midmyocardial region was most susceptible to injury at all long axis levels. Temperature reduction (as little as 1 degrees C) was associated with improved salvage that was most pronounced in the apical subendocardium and least in the basilar midmyocardium. Reperfusion at 39.5 degrees C resulted in severe transmural microvascular injury (no-reflow) that was completely obviated at temperatures below 38.5 degrees C. Myocardial reperfusion injury varies over the long and short LV axes. Mild hypothermia preferentially improves myocardial salvage at the LV apex. Small temperature changes can dramatically affect microvascular integrity.

Total absence of ST-segment resolution after failed thrombolysis is correlated with unfavorable short- and long-term outcomes despite successful rescue angioplasty

Introduction ST-segment resolution (STR) is a well-established and simple tool for assessing the efficacy of reperfusion therapy in myocardial infarction. An incomplete (<50%) STR is a recognized marker of failed thrombolysis and a suitable recruitment criterion for rescue angioplasty. Objective We sought to determine the predictive value of the total absence of STR after thrombolysis in rescue angioplasty (percutaneous coronary intervention [PCI]). Methods Eighty-one consecutive patients who underwent a rescue angioplasty for failed thrombolysis in our institution from 2001 to 2007 were included. Two groups of patients were defined according to their STR extent, 90 minutes after lysis: partial resolution group 1 (10%-50% STR) vs absence of resolution group 2 (<10% STR) and compared in terms of in-hospital and long-term outcomes. Results Patients of group 2 were more likely to experience hemodynamic deterioration (50% vs 24%; odds ratio [OR] = 3.17; P = .017), to have a Thrombolysis in Myocardial Infarction 0 flow on the culprit artery (62.3% vs 42%; OR = 2.24; P = .045), to have a multivessel disease (66.7% vs 40%; OR = 3; P = .018), and to die during index hospitalization (26.7% vs 6%; OR = 5.69; P = .013) despite statistically similar rates of PCI failure in both groups (10% vs 7%; P = .402) and similar post-PCI STR (72% ± 18.25% vs 75% ± 11.62%; P = .36). In multivariate analysis, total absence of STR proved to be an independent predictor of in-hospital mortality (HR = 7.02; P = .032; 95% confidence interval, 1.18-41.58). Long-term major adverse cardiac events occurred more frequently in group 2 (log rank, P = .004) and were (on the Cox regression model) independently predicted by total absence of STR (HR = 6.21; P = .023; 95% confidence interval, 1.28-29.1). Conclusions The STR assessment before rescue PCI proved to be a good and simple means to predict the short- and long-term prognosis in these patients.

Thrombolysis or primary angioplasty? Reperfusion therapy for myocardial infarction in the UK

Intravenous thrombolysis and percutaneous coronary intervention (PCI) are alternative treatment options for coronary reperfusion in acute myocardial infarction. Recent trials and meta-analyses have produced increasing evidence that primary coronary intervention...

Effect of Reperfusion on Left Ventricular Regional Remodeling Strains After Myocardial Infarction

Reperfusion therapy for myocardial infarction is currently the most effective means for limiting early and late mortality. We sought to elucidate how reperfusion influences remodeling strains in the infarct, borderzone, and remote myocardial regions. Understanding the effects of reperfusion on regional remodeling will help to evaluate and optimize emerging treatments for patients who do not achieve effective reperfusion after myocardial infarction. An ovine infarct model (n = 13) was used to assess the effect of 1 hour of ischemia followed by reperfusion on regional and global myocardial geometry, function, and perfusion using sonomicrometry, echocardiography, and microspheres. Thirteen additional animals were assessed chronically (8 weeks) with echocardiography and postmortem analysis after either reperfusion (n = 5) or untreated infarction (n = 8). During ischemia the area at risk thinned, stretched, and became dyskinetic. The normally perfused borderzone also stretched, and contraction decreased by 40% during ischemia. Reperfusion increased area at risk wall thickness and reduced area at risk stretching but did not restore contractile function. Borderzone stretching was reduced and contractile function improved by reperfusion. Contractile function of remote regions was also improved with reperfusion. Ventricular dilatation after ischemia was reversed within 180 minutes of reperfusion. Chronically, reperfusion significantly improved global remodeling when compared with nonreperfused controls. Reperfused animals had thicker infarcts and akinetic rather than dyskinetic apical segments. Reperfusion acutely increases area at risk wall thickness, reduces area at risk and borderzone stretching, and improves borderzone and remote function. Reperfusion increases mature scar thickness and improves chronic global remodeling. These beneficial effects of reperfusion result primarily from reduced infarct expansion (stretching).

α-Melanocyte Stimulating Hormone Fused to Transferrin: A Novel Adjunct to Reperfusion Therapy for Acute MI

Background: α-Melanocyte Stimulating Hormone (α-MSH) is an active fragment of adrenocorticotropic hormone (ACTH) and has been reported to have antiapoptotic properties that may make it a useful adjunct reperfusion therapy for myocardial infarction. However, the very short half-life (minutes) of α-MSH limits its therapeutic applicability. The fusion MSH to transferrin (MSH-Tf) extends its functional half-life to days. Hypothesis: Single dose administration of MSH-Tf at reperfusion reduces myocardial reperfusion injury.

Feasibility of the single‐bolus strategy for measuring the partition coefficient of Gd‐DTPA in patients with myocardial infarction: Independence of image delay time and maturity of scar

The partition coefficient of Gd-DTPA (lambda) is elevated in infarcted relative to normal myocardium. Although MRI following an infusion of Gd-DTPA allows for the quantification of lambda, infarct imaging is more routinely performed using a bolus. In this study we sought to determine how image delay time and time postinfarction influence the estimation of lambda by the bolus strategy. Both infusion and bolus imaging were performed twice in the same group of patients (N = 9): once at 3-4 weeks and again 6 months after reperfusion therapy for myocardial infarction (MI). Bolus estimates of lambda were compared with those calculated after 60 min infusion, and comparisons were repeated at 6 months. The lambda of infarcted myocardium was significantly greater than that of normal tissue, irrespective of either the technique used or the time postinfarction (P < 0.0001, for each). The concordance (Rc) between bolus and infusion estimates of lambda was >0.83 for all image delays >4 min postinjection, and Rc at 2 min (0.78 +/- 0.04) was significantly less than Rc determined for longer image delay times (P = 0.009). Rc did not change with time postinfarction (P = 0.604). Thus, the bolus strategy can be used to provide estimates of lambda that are stable from 1-6 months postinfarction and independent of image delay time.

Sustained Benefit 20 Years After Reperfusion Therapy in Acute Myocardial Infarction

The goal of this research was to clarify whether the benefit of reperfusion therapy for myocardial infarction was sustained long-term and to assess the gain in life expectancy by reperfusion therapy. Reperfusion therapy in acute myocardial infarction reduces infarct size and increases hospital survival. We analyzed the 20-year outcome of 533 patients (mean age 56 years; 82% men) who were randomized to either reperfusion therapy or conventional therapy during the years 1981 to 1985. Mean follow-up was 21 years (range 19 to 23 years). At follow-up, 101 patients (36%) of the 269 patients allocated to reperfusion treatment and only 71 patients (26%) of the 264 conventionally treated patients were alive (p = 0.02). The cumulative 10-, 15-, and 20-year survival rates were 69%, 48%, and 37% after reperfusion therapy and 59%, 38%, and 27% in the control group, respectively (p = 0.005). Life expectancy of the reperfusion group was 15.2 years versus 12.4 years in the conventionally treated group (p < 0.0001). Myocardial re-infarction and subsequent coronary interventions were more frequent after reperfusion therapy, particularly during the first year. In multivariable analysis, reperfusion therapy was an important independent predictor of lower mortality at long-term follow-up (hazard ratio 0.7; 95% confidence interval 0.6 to 0.8). Other independent predictors of mortality were age, impaired left ventricular function, multivessel disease, infarct size, and inability to perform an exercise test at the time of discharge. This is the first study demonstrating sustained (20-year) improved survival after reperfusion therapy. The gain in life expectancy was almost three years, representing about one-third of the life-years lost by myocardial infarction.

Microvascular alterations after temporary coronary artery occlusion: the no-reflow phenomenon.

In experimental models of temporary coronary artery occlusion, tissue perfusion at the microvascular level remains incomplete even after patency of the infarct-related epicardial coronary artery is established, and distinct perfusion defects develop within the risk zone. This no-reflow phenomenon can be regarded as a basic cardiac response to ischemia-reperfusion. Perfusion defects observed in the clinical realm after reperfusion therapy for myocardial infarction may substantially be related to this mechanism in addition to microembolization and activation of platelets, as suggested in several recent studies. A major determinant of the amount of no-reflow seems to be infarct size itself. Reperfusion-related expansion of no-reflow zones occurs within the first hours after the reopening of the coronary artery with a parallel reduction of regional myocardial flow, resulting in a potential therapeutic window. With various cardioprotective interventions, a close correlation between the size of the anatomic no-reflow and necrosis is a reproducible feature, which suggests a causal link between both entities of ischemic cardiac damage. Although vasodilating interventions failed to uncouple no-reflow zones from necrosis, the steps in the causal chain between microvascular and myocardial damage remain to be identified. On a long-term basis, tissue perfusion after ischemia-reperfusion remains markedly compromised for at least 4 weeks. Recent morphometric cardiac analyses suggested that the level of tissue perfusion after 4 weeks is a significant predictor of various indices of infarct healing, such as scar thickness, and infarct expansion index. As a consequence, improving tissue perfusion might concomitantly improve the healing process, which may provide the pathoanatomic basis for prognostic implications of no-reflow.

Early Definition of Treatment Outcomes After Reperfusion Therapy for Myocardial Infarction

Aims. Early definition of treatment outcomes, including coronary patency and infarct size, after reperfusion therapy for myocardial infarction (MI) is desirable to identify patients requiring further intervention. Methods and Results. Patients receiving reperfusion therapy for a first MI had continuous 12-lead ST segment monitoring to document reperfusion and ischaemia time. Infarct size was measured by 12-lead QRS score and radionuclide scintigraphy ( 201 Tl single-photon emission computed tomography, SPECT) at 1 week, and left ventricular function by echocardiography at 1 week and 1 month. Resolution of ST elevation accurately detected TIMI 2 or 3 reperfusion (predictive accuracy 93%) in 55 patients undergoing immediate angioplasty, but ST recovery was delayed (17±14 min) after angiographic reperfusion. A multivariate model, including risk region and ischaemia time, accurately predicted MI size ( R 2=0.80, P<0.00001) in these patients. The same model, prospectively applied on Day 1 to 154 patients receiving thrombolytic therapy, accurately predicted MI size, measured by QRS score ( R 2=0.88, P<0.0000001) and 201 Tl SPECT ( R 2=0.75, P<0.000001) at 1 week for individual patients. Regional myocardial wall motion at 1 month was directly correlated with MI size predicted by the model on Day 1 ( r=0.73, P<0.0001). Conclusions. Use of ST segment monitoring during reperfusion therapy facilitates early prediction of treatment outcomes, including coronary reperfusion, infarct size and ventricular function.

No-Reflow Phenomenon Persists Long-Term After Ischemia/Reperfusion in the Rat and Predicts Infarct Expansion

No-reflow after reperfusion therapy for myocardial infarction is a strong predictor of clinical outcome. But its fate on a long-term basis and potential significance for infarct healing are not yet known. Twenty-nine female Fisher rats were subjected to 60 minutes of coronary occlusion followed by reperfusion. At 4 weeks, 15 survivors were euthanized after measurement of regional myocardial blood flow (radioactive microspheres) and in vivo staining of perfused tissue (0.5 mL 50% Uniperse blue IV). Infarct size (34.3+/-3.4%), scar thickness (1.19+/-0.10 mm), and infarct expansion index (0.51+/-0.04) were assessed from histological sections (2 additional exclusions because of failed occlusion). Regional myocardial blood flow in the reperfused infarct was reduced significantly compared with noninfarcted tissue (1.98+/-0.47 versus 4.55+/-0.86 mL x min(-1) x g(-1), P<0.003, apical slice, and 1.77+/-0.44 versus 5.34+/-0.38 mL x min(-1) x g(-1), P<0.0001, second slice), accompanied by a striking reduction of perfused capillaries within the infarct (n=23+/-4 versus 163+/-8 in the noninfarcted tissue, P<0.0001, microscopically assessed as capillaries containing blue particles per high-power field). Macroscopically, no-reflow areas were visible in 9 of 13 hearts. The number of perfused capillaries within the infarct correlated significantly with infarct expansion index (r=-0.76, P<0.003), infarct thickness (r=0.60, P<0.03), and the ratio of infarct to septum thickness (r=0.74, P<0.004). The no-reflow phenomenon persists for 1 month after reperfusion and predicts worse scar thinning and infarct expansion. Thus, one might shift the "open-artery" hypothesis downstream to an "open-microvessel" hypothesis, relating infarct healing, infarct expansion, and outcome to the completeness of microvascular reperfusion above and beyond epicardial artery patency.