Impact of hypoxia, simulated ischemia and reperfusion in HL-1 cells on the expression of FKBP12/FKBP12.6 and intracellular calcium dynamics.

AIMS: To establish a cardiac cell culture model for simulated ischemia and reperfusion and in this model investigate the impact of simulated ischemia and reperfusion on expression of the calcium handling proteins FKBP12 and FKBP12.6, and intracellular calcium dynamics. METHODS: HL-1 cell cultures were exposed to normoxia (as control), hypoxia, simulated ischemia (HEDA) or HEDA+reactive oxygen species (ROS) for up to 24 h and after HEDA, with or without ROS, followed or not by simulated reperfusion (REPH) for 6 h. Viability was analyzed with a trypan blue exclusion method. Cell lysates were analyzed with real-time PCR and Western blot (WB) for FKBP12 and FKBP12.6. Intracellular Ca(2+)measurements were performed using dual-wavelength ratio imaging in fura-2 loaded cells. RESULTS: A time-dependent drop in viability was shown after HEDA (P<0.001). Viability was not further influenced by addition of ROS or REPH. The general patterns of FKBP12 and FKBP12.6 mRNA expression showed upregulation after hypoxia, downregulation after ischemia and normalization after reperfusion, which was partially attenuated if ROS was added during HEDA. The protein contents were unaffected after hypoxia, tended to increase after ischemia and, for FKBP12.6, a further increase after reperfusion was shown. Hypoxia or HEDA, with or without REPH, resulted in a decreased amplitude of the Ca(2+) peak in response to caffeine. In addition, cells subjected to HEDA for 3 h or HEDA for 3 h followed by 6 h of REPH displayed irregular Ca(2+) oscillations with a decreased frequency. CONCLUSION: A threshold for cell survival with respect to duration of ischemia was established in our cell line model. Furthermore, we could demonstrate disturbances of calcium handling in the sarcoplasmic reticulum as well as alterations in the expressions of the calcium handling proteins FKBP12 and FKBP12.6, why this model may be suitable for further studies on ischemia and reperfusion with respect to calcium handling of the sarcoplasmic reticulum.

From European to national guidelines on heart disease.

BACKGROUND/AIMS: Guidelines from the European Society of Cardiology are important tools for defining and establishing current standards of care for various heart diseases. The aim of the present paper is to describe the process of how these international guidelines may be transformed and implemented at a national level in Sweden. METHODS/RESULTS: The structure and process behind the national guidelines for heart diseases in Sweden and their relationship to the underlying European guidelines are described and differences between the national and European levels highlighted. We also give examples of how the scientific values of health care measures are weighted against health economic perspectives and integrated in a prioritization process. Compared to the European guidelines, the Swedish national guidelines have a broader economic perspective and aim to ensure that health care is cost effective and provided to all Swedish citizens on equal terms. DISCUSSION: When certain health care measures are implemented, the national process can result in other priorities than could be expected from the European guidelines alone. On the other hand, a forceful implementation may be facilitated by the societal context in which these national guidelines are produced.

Cost and health outcome of primary percutaneous coronary intervention versus thrombolysis in acute ST-segment elevation myocardial infarction-Results of the Swedish Early Decision reperfusion Study (SWEDES) trial.

BACKGROUND: In ST-elevation myocardial infarction, primary percutaneous coronary intervention (PCI) has a superior clinical outcome, but it may increase costs in comparison to thrombolysis. The aim of the study was to compare costs, clinical outcome, and quality-adjusted survival between primary PCI and thrombolysis. METHODS: Patients with ST-elevation myocardial infarction were randomized to primary PCI with adjunctive enoxaparin and abciximab (n = 101), or to enoxaparin followed by reteplase (n = 104). Data on the use of health care resources, work loss, and health-related quality of life were collected during a 1-year period. Cost-effectiveness was determined by comparing costs and quality-adjusted survival. The joint distribution of incremental costs and quality-adjusted survival was analyzed using a nonparametric bootstrap approach. RESULTS: Clinical outcome did not differ significantly between the groups. Compared with the group treated with thrombolysis, the cost of interventions was higher in the PCI-treated group ($4,602 vs $3,807; P = .047), as well as the cost of drugs ($1,309 vs $1,202; P = .001), whereas the cost of hospitalization was lower ($7,344 vs $9,278; P = .025). The cost of investigations, outpatient care, and loss of production did not differ significantly between the 2 treatment arms. Total cost and quality-adjusted survival were $25,315 and 0.759 vs $27,819 and 0.728 (both not significant) for the primary PCI and thrombolysis groups, respectively. Based on the 1-year follow-up, bootstrap analysis revealed that in 80%, 88%, and 89% of the replications, the cost per health outcome gained for PCI will be <$0, $50,000, and $100,000 respectively. CONCLUSION: In a 1-year perspective, there was a tendency toward lower costs and better health outcome after primary PCI, resulting in costs for PCI in comparison to thrombolysis that will be below the conventional threshold for cost-effectiveness in 88% of bootstrap replications.

Myocardial release of FKBP12 and increased production of FKBP12.6 in ischemia and reperfusion experimental models.

BACKGROUND: Coronary artery occlusion and reperfusion may trigger reversible and irreversible ischemic and reperfusion injury. The primary aim of this study was to evaluate protein release into the myocardium in a porcine model during ischemia and reperfusion to search for clarifying models for reperfusion injury and secondarily to investigate release and production of the immunophilins FKBP12/12.6 in this model and in cell cultures. METHODS: In a porcine model local myocardial ischemia was induced during 45min followed by 120min of reperfusion. Microdialysis samples from ischemic and non-ischemic areas were analyzed with surface-enhanced laser desorption ionization (SELDI) mass spectrometry (MS) and Western blotting (WB). Myocardial biopsies from areas at risk and control areas were analyzed with reverse transcription polymerase chain reaction (RT-PCR). Myocardial cell cultures from mice (HL-1 cells) were exposed to hypoxia and then analyzed with WB and RT-PCR. RESULTS: FK binding protein12 (FKBP12), ubiquitin and myoglobin were identified as being released during ischemia and reperfusion in microdialysates. RT-PCR analysis on the biopsies after ischemia revealed a non-significant increase in mRNA expression of FKBP12 and a significant increase in mRNA expression of FKBP12.6. Lysates from HL-1 cells exposed to hypoxia demonstrated increase of FKBP12 and a significant increase in mRNA expression of FKBP12.6. CONCLUSION: In a myocardial ischemic-reperfusion porcine model as well as in hypoxic HL-1 cells, release of FKBP12 and increased production of FKBP12.6 was demonstrated. The findings indicate important mechanisms related to these immunophilins in the reaction to ischemia/hypoxia and reperfusion in the heart.

Distorted T-vector loop and increased heart rate are associated with ventricular fibrillation in a porcine ischemia-reperfusion model.

BACKGROUND: The ventricular repolarization (VR) response to short-lasting coronary occlusion has been characterized by 3-dimensional vectorcardiography during angioplasty in humans; the T-vector loop becomes distorted (increased T(avplan)) and more circular (decreased T(eigenvalue)), but these changes have not been related to ventricular arrhythmias. PURPOSE: The VR response was therefore explored in a porcine ischemia-reperfusion model and compared in pigs with (n = 16) vs without (n = 17) ventricular fibrillation (VF). METHODS: Different aspects of VR were evaluated at baseline, at maximum ischemia, before reperfusion and at the subsequent ST maximum, after 1 hour of reperfusion, and before VF. Three aspects of the VR response were assessed: the ST-segment, the T-vector angles, and the T-vector loop morphology. RESULTS: All parameters changed significantly from baseline during ischemia and/or reperfusion. The early changes were similar to those previously observed in humans during angioplasty. The VF episodes were preceded by a significantly exaggerated T-loop distortion (increased T(avplan)) and increased heart rate. CONCLUSION: Aggravated T-loop distortion might, in this porcine ischemia-reperfusion model, reflect aspects of VR relevant to arrhythmogenesis.

The impact of general usage of stents on short- and long-term health care costs following percutaneous coronary intervention.

BACKGROUND: The general usage of stents during percutaneous coronary intervention (PCI) reduces the need for subsequent repeated revascularizations when compared with balloon dilatation. The aim was to evaluate the impact of stenting on short- and long-term in-hospital care costs after PCI. METHOD AND RESULTS: Patients who underwent PCI from July 1992 to June 1993 (group A, n = 166; 4.2% stents) and from July 1996 to June 1997 (group B, n = 233; 61.4% stents) were included. The clinical outcome and all in-hospital care costs during 2.5 years following the procedures were analyzed. During the study period the number of deaths and acute myocardial infarctions was similar in the groups, but repeated revascularization occurred more often in group A than in group B (53.6 vs. 39.5%; p = 0.007). The initial procedural cost per patient was higher in group B than in group A (EUR 7,653 +/- 5,071 vs. EUR 6,048 +/- 3,242; p = 0.002), but after 2.5 years the costs were similar in the 2 groups (not significant). CONCLUSION: General usage of stents increases immediate health care cost compared with balloon dilatation, but despite reduction in subsequent revascularization, there is no reduction in long-term in-hospital costs.

Temporal changes in TIMI myocardial perfusion grade in relation to epicardial flow, ST-resolution and left ventricular function after primary percutaneous coronary intervention.

BACKGROUND: Myocardial perfusion at the end of reperfusion therapy assessed angiographically with thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG) has been associated with recovery of left ventricular (LV) function and survival. The aim of this analysis was to study the evolution of TMPG within the first week following primary percutaneous coronary intervention (PCI) and its association with ECG-derived ST-segment resolution (STRES) and recovery of LV function. METHODS: A total of 76 patients with acute myocardial infarction were pretreated with enoxaparine and abciximab and subjected to primary PCI within a prospective study and evaluated with TMPG assessed on coronary angiography at the end of the procedure and after 5-7 days. STRES was evaluated at 120 min post inclusion and global LV function was assessed by echocardiography after 30 days. RESULTS: Reperfusion (TIMI flow 2-3) was reached in all patients. Forty one percent had 'open myocardium' (i.e. TMPG 2 or 3) after PCI, a number that increased to 61% after 5-7 days (P=0.003). STRES >50% was reached in 73% of the patients and there was a good correlation between TMPG and STRES. Furthermore, those who improved from 'closed' to 'open myocardium' had higher STRES (and similar to those with 'open myocardium' already post-PCI) than those who had 'closed myocardium' at both occasions (80 vs. 52%, P=0.012). CONCLUSION: A significant increase was found in the number of patients with 'open myocardium' within the first week post-primary PCI and STRES seems to predict this improvement.

Patients expectations and fulfilment of expectations before and after treatment for suspected coronary artery disease assessed with a newly developed questionnaire in combination with established health-related quality of life questionnaires.

BACKGROUND: Clinical decision-making is often based on evidence of outcome after a specific treatment. Healthcare providers and patients may, however, have different perceptions and expectations of what to achieve from a certain healthcare measure. AIMS: To evaluate patients' expectations, perceptions and health related quality of life (HRQoL) before a care process including coronary angiography for suspected coronary artery disease and to evaluate the fulfilment of these expectations in relation to established patient reported outcome measures (PROMs) 6 months later. Furthermore, an aim was to try to define meaningful patient reported experience measures (PREMs) in this population. METHODS: 544 patients planned for coronary angiography completed a newly developed questionnaire to assess expectations and perceptions of treatment, the expectation questionnaire (ExpQ) and two established HRQoL questionnaires together with the established generic Short-Form 36 (SF36) and the disease specific Seattle Angina Questionnaire (SAQ). RESULTS: Patients had before the intervention, in general, high expectations of improvement after investigation and treatment and there was a positive attitude towards life style changes, medication and participation in decision-making regarding their own treatment. Only, 56.4% of the patients, however, reported fulfilment of treatment expectations. Fulfilment of treatment expectations correlated strongly with improvement in HRQoL after the care process. CONCLUSIONS: To measure patients ´ expectations and fulfilments of these may offer simple and meaningful outcomes to evaluate a healthcare process from a patient ´s perspective. To approach patients' expectations may also strengthen patient involvement in the care process with the possibilities of both higher patient satisfaction and medical results of the treatment.

Comparison of very early treatment with either fibrinolysis or percutaneous coronary intervention facilitated with abciximab with respect to ST recovery and infarct-related artery epicardial flow in patients with acute ST-segment elevation myocardial infarction: the Swedish Early Decision (SWEDES) reperfusion trial.

BACKGROUND: Results from a number of studies indicate that primary percutaneous coronary intervention (PCI) is superior to fibrinolysis for treatment of acute ST-elevation myocardial infarction. Modern adjunctive antithrombotic treatment with systematic use of low-molecular-weight heparins, fibrin-specific thrombolysis, and glycoprotein IIb/IIIa receptor inhibitors may improve the outcome compared with what was achieved in previous studies. METHODS: Patients with ST-elevation myocardial infarction were randomized to receive enoxaparin followed by reteplase (group A; n = 104) or enoxaparin followed by abciximab and transfer to invasive center for optional PCI (group B; n = 101). Primary end points were ST-segment resolution 120 minutes and TIMI flow at coronary angiography 5 to 7 days after randomization. RESULTS: Forty-two percent of the patients started therapy in the prehospital phase. Time from symptom to treatment was 114 minutes in group A and 202 minutes in group B. Baseline characteristics were similar in the 2 groups. Sixty-four percent in group A and 68% in group B had ST resolution of > 50% at 120 minutes (not significant). At control angiography, 54% in the fibrinolytic group and 71% in the invasive group had TIMI 3 flow (P = .04). At 30 days, the composite of death, stroke, or reinfarction occurred in 8% in the fibrinolytic group compared with 3% in the invasive group (not significant). CONCLUSIONS: Despite much shorter time delay to start of fibrinolysis than PCI, this did not result in signs of superior myocardial reperfusion. Epicardial flow in the infarct-related artery was better after invasive therapy, and there was a trend toward better clinical outcome after this treatment compared with after fibrinolysis.

Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial.

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population). The primary reason for not completing treatment was > or =1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm(3), respectively; P=0.16 to 0.72). CONCLUSIONS: Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae.

Early versus periprocedural administration of abciximab for primary angioplasty: a pooled analysis of 6 studies.

BACKGROUND: The 2004 ACC/AHA guidelines on ST-elevation myocardial infarction state that it is reasonable to start treatment with abciximab as early as possible before primary percutaneous coronary intervention (PCI). We investigated the potential benefit of early use of abciximab by pooling data from all the available studies. METHODS: Six prospective studies were identified that had allocated 260 patients to receive early abciximab (either prehospital or soon after the patient arrived in hospital) and 342 to receive late abciximab (at the time of PCI). RESULTS: TIMI flow grade 2 or 3 was present in 42% of the early group compared with 29% in the late group (P = .001). After PCI, 59% of patients in the early group showed ST-resolution >or = 70%, compared with 41% in the late group (P = .003). The composite clinical outcomes death, new myocardial infarction, or repeat target vessel revascularization at 30 days occurred in 7.3% of the early group compared with 9.7% in the late group (odds ratio 0.73, 95% CI 0.41-1.32) and death alone occurred in 2.7% versus 4.7%, respectively (odds ratio 0.56, 95% CI 0.23-1.39). CONCLUSIONS: Early administration of abciximab improves epicardial patency (TIMI flow) before PCI and results in better myocardial tissue perfusion (ST-resolution) after the procedure. The promising effects on clinical outcomes need to be tested in larger studies.

Cardioprotection of the enkephalin analog Eribis peptide 94 in a rat model of ischemia and reperfusion is highly dependent on dosing regimen and timing of administration.

Eribis Peptide 94 (EP94) is an enkephalin analog with cardioprotective properties in ischemia and reperfusion. The aim of the present study was to define the optimal timing and dosing of the administration of EP94 during ischemia and reperfusion in a rat model. 172 anesthetized and mechanically ventilated male Sprague-Dawley rats were randomly assigned to different administration protocols of EP94 and subjected to 30 or 40 min of coronary artery occlusion followed by 2h of reperfusion. EP94 was administered intravenously at different doses and time intervals. Area at risk (AAR) and infarct size (IS) were determined by staining with Evans Blue (EB) and Triphenyl tetrazolium chloride (TTC), respectively. EP94 reduced IS/AAR when administered as a double bolus (0.5 µg/kg per dose), whereas single (1 µg/kg) or triple boluses (0.5 µg/kg per dose) did not confer any protection. Reduction of IS/AAR was of highest magnitude if EP94 was administered 5 and 0 min before the 30 min ischemic period (47% reduction, P<0.05), with declining cardioprotective effect with later administration during ischemia. When EP94 was administered after 15 and 20 min of a 40-min ischemic period, reduction of IS/AAR was of the same magnitude as when given after 5 and 10 min of a 30-min ischemic period. It is concluded that EP94 confers cardioprotection after double bolus administration. The effects are highly dependent on the timing of administration in relation to ischemia and reperfusion. Time of reperfusion from drug administration seems to be more critical than the total duration of ischemia.

Myocardial damage, coagulation activity and the response to thrombin inhibition in unstable coronary artery disease.

Unstable coronary artery disease is in most cases associated with plaque rupture, activation of the coagulation system and subsequent intracoronary thrombus formation which may cause myocardial cell damage. The aim of the present analysis was to assess the relation between troponin T, markers of coagulation activity, i.e. prothrombin fragment 1+2, thrombin-antithrombin complex, soluble fibrin and D-dimer, and ischemic events, i.e. death, myocardial (re-)infarction or refractory angina. 320 patients with unstable coronary artery disease were randomized to 72 hours infusion with inogatran, a low molecular weight direct thrombin inhibitor, or unfractionated heparin. Patients with elevated troponin levels had higher levels of prothrombin fragment 1+2, soluble fibrin and D-dimer before, during, and at 24 hours after cessation of anticoagulant treatment. These troponin-positive patients tended to have worse short-term clinical outcome, without relation to markers of coagulation activity. Troponin-negative patients with unchanged or early increased thrombin generation during treatment had a cluster of ischemic events within 24 hours after cessation of the study drug. The 30-day ischemic event rate was 19 % in troponin-negative patients with unchanged or early increased prothrombin fragment 1+2, and 5.7 % in patients with decreased prothrombin fragment 1+2, p=0.006, and similarly 15 % in troponin-negative patients with unchanged or early increased thrombin-antithrombin complex and 4.5 % in patients with decreased thrombin-antithrombin complex, p=0.02. In conclusion, in unstable coronary artery disease a troponin elevation indicates higher risk and higher coagulation activity. However, among the troponin negative patients, with a lower risk and lower coagulation activity, a part of the patients seem to be non-responders to treatment with a thrombin inhibitor expressed as unchanged or raised coagulation activity and a raised risk of ischemic events early after cessation of treatment.

One-year outcome after percutaneous coronary intervention for stable and unstable angina pectoris with or without application of general usage of stents in unselected European patient groups.

The outcome after percutaneous coronary intervention (PCI) of all patients treated for stable and unstable angina pectoris from July 1992 to June 1993 (group A [n = 590], of whom 3.7% received stents) was compared with the outcome in patients treated from July 1996 to June 1997 (group B [n = 768], of whom 64.7% received stents). All patients were followed up for at least 1 year. PCI was performed due to unstable angina in 34.1% and 33.5% of patients in groups A and B, respectively. More patients in group B than in group A had systemic hypertension, previous coronary artery bypass grafting, and PCI. Within 1 year, 42.2% of patients in group A versus 27.2% in group B (p <0.001) either died, had a nonfatal acute myocardial infarction (AMI), or underwent a new revascularization procedure. The difference between the groups persisted after correction for differences in baseline characteristics. No difference was seen in the subgroup that had previously undergone PCI. Mortality (2.0% vs 1.4%, p = NS) and the composite of death plus AMI (6.6% vs 6.1%, p = NS) was similar in groups A and B. The diagnoses of unstable angina and systemic hypertension at the time of the procedure were also predictors of adverse outcome. Thus, in a cohort of patients treated after the general acceptance of stenting, the composite of death, AMI, and/or revascularization procedures was significantly less than that in the cohort treated before this increase in stenting. However, this did not result in a reduced frequency of death or AMI.

The influence of direct and antithrombin-dependent thrombin inhibitors on the procoagulant and anticoagulant effects of thrombin.

INTRODUCTION: Clinical trials evaluating direct thrombin inhibitors in unstable coronary artery disease (CAD) have been disappointing. The hypothesis tested in the present study was that these agents may inhibit the anticoagulant effect of thrombin to a further extent than the procoagulant effect of thrombin. MATERIALS AND METHODS: We studied both reversible and irreversible thrombin inhibitors and compared the effects of each inhibitor on activated protein C (APC) generation vs. the effect on fibrinopeptide A (FPA) generation. A mixture of protein C, thrombin inhibitor, fibrinogen, fibrin polymerisation blocker and thrombin was incubated with thrombomodulin (TM)-expressing human saphenous vein endothelial cells (HSVECs). The inhibitors investigated were melagatran, inogatran, hirudin, hirugen, D-Phe-D-Pro-D-arginyl chloromethyl ketone (PPACK), and antithrombin (AT) alone or in combination with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). RESULTS: All agents, except hirugen, inhibited APC and FPA generation in a dose-dependent manner. FPA inhibition/APC inhibition ratios, based on IC50 for inogatran, melagatran, hirudin, PPACK, AT, AT-UFH and AT-LMWH were 1.73, 0.85, 0.55, 2.1, 0.5, 0.65 and 3.1 respectively. CONCLUSIONS: All agents, except hirugen, inhibited APC and FPA generation approximately to a similar extent. Thus, it can be inferred that the poor efficacy of thrombin inhibitors in recent clinical trials in patients with unstable CAD is unlikely to be a consequence of their effects on the protein C system.

Melagatran attenuates fibrin and platelet deposition in a porcine coronary artery over-stretch injury model.

Melagatran is the active form of the oral direct thrombin inhibitor, ximelagatran. The purpose of this study was to compare the effects of different doses of melagatran with heparin or placebo on platelet deposition and relative fibrin content after coronary angioplasty in pigs. After 125I-labelled fibrinogen and autologous 111Indium-labelled platelets had been infused a balloon injury was performed in the left anterior descending and the right coronary arteries. Pigs were randomized to receive either heparin 200 IU/kg bolus plus 20 IU/kg per h infusion (n = 7); melagatran 1 mg/kg bolus plus 0.33 mg/kg per h infusion (n = 7); melagatran bolus 0.5 mg/kg plus 0.17 mg/kg per h infusion (n = 7); melagatran 0.15 mg/kg bolus plus 0.05 mg/kg per h infusion (n = 6) or saline (n = 4). Seventy-five minutes after the angioplasty, the pigs were euthanized and the injured vessel segments were measured in a gamma counter. Compared with placebo, platelet deposition and relative fibrin content were reduced after both heparin and melagatran, in the latter case with a dose-response relationship. Melagatran reduced platelet deposition and relative thrombus size in a dose-dependent manner when compared with placebo after coronary angioplasty in pigs. No statistically significant difference between melagatran and heparin was found.

Endocardial electromechanical mapping in a porcine acute infarct and reperfusion model evaluating the extent of myocardial ischemia.

OBJECTIVE: Catheter-based, left ventricular, electromechanical mapping (EMM) has evolved as a diagnostic tool to characterize ischemic and injured myocardium. In the acute setting, diagnostic criteria for ischemic or infarcted myocardium are not well defined. In the present study, the capacity of separating myocardium with evolving necrosis from viable myocardium was investigated. METHODS AND RESULTS: Pigs were subjected to balloon occlusion of the left anterior descending coronary artery for 45 minutes. Using the NOGATM cardiac mapping system, EMM was performed at the baseline and after two hours of reperfusion. EMMs were evaluated regarding unipolar voltage (UPV), bipolar voltage (BPV) and local linear shortening (LLS). The pigs were sacrificed four hours after reperfusion and morphological estimation of infarct size and localization was performed. Baseline UPV activity was significantly lower in the anterior, lateral and posterior basal segments as compared to the septal and posterior midventricular segments. After reperfusion, UPV, but not BPV, was significantly decreased in the apical, midventricular septal and basal segments. LLS demonstrated significant impairment of mobility in the septal midventricular segment. The thresholds for separating electromechanical activity at baseline from after infarction differed between the myocardial regions. The ability of EMM to correctly detect infarcted myocardium showed a sensitivity and specificity in the order of 50 85%, as compared to the morphological standard. CONCLUSION: In a porcine acute infarct and reperfusion model, electromechanical activity thresholds, for infarct detection, could be established, but there was significant intersegmental threshold variability at baseline and after infarction. Accordingly, applying general thresholds demonstrated a poor correlation between infarct extension evaluated by EMM and morphology.

Characteristics and outcome of patients with ST-elevation infarction in relation to whether they received thrombolysis or underwent acute coronary angiography: are we selecting the right patients for coronary angiography?

BACKGROUND: During the last decade, there has been an on-going debate with regard to whether percutaneous coronary intervention (PCI) or thrombolysis should be preferred in patients with ST-elevation acute myocardial infarction (AMI). Some studies clearly advocate PCI, while others do not. HYPOTHESIS: The study aimed to describe the characteristics and to evaluate outcome of patients with suspected ST-elevation or left bundle-branch block infarction in relation to whether they received thrombolysis or had an acute coronary angiography aiming at angioplasty. METHODS: The study included all patients admitted to Sahlgrenska University Hospital in Göteborg, Sweden, with suspected acute myocardial infarction who, during 1995-1999, had ST-elevation or left bundle-branch block on admission electrocardiogram (ECG) requiring either thrombolysis or acute coronary angiography. A retrospective evaluation with a follow-up of 1 year after the intervention was made. RESULTS: In all, 413 patients had thrombolytic treatment and 400 had acute coronary angiography. The patients who received thrombolysis were older (mean age 70.3 vs. 64.1 years). Mortality during 1 year of follow-up was 20.9% in the thrombolysis group and 16.6% in the angiography group (p = 0.12). Among patients in whom acute coronary angiography was performed, only 85% underwent acute percutaneous coronary intervention (PCI). There was a mortality of 12.1 vs. 41.7% among those who did not undergo acute PCI. Development of reinfarction, stroke, and requirement of rehospitalization was similar regardless of type of initial intervention. The thrombolysis group more frequently required new coronary angiography (36.9 vs. 20.6%; p<0.0001) and new PCI (17.8 vs. 11.9%; p = 0.01). Despite this, after 1 year symptoms of angina pectoris were observed in 27% of patients in the thrombolysis group and in only 14% of those in the angiography group (p = 0.0002). CONCLUSION: In a Swedish university hospital with a high volume of coronary angioplasty procedures, we found no significant difference in mortality between patients who had thrombolysis and those who underwent acute coronary angiography. However, requirement of revascularization and symptoms of angina pectoris 1 year later was considerably less frequent in those who had undergone acute coronary angiography. However, distribution of baseline characteristics was skewed and efforts should be focused on the selection of patients for the different reperfusion strategies.