ABSTRACT
The aim of the study was to evaluate a 1 M gadolinium-chelate (gadobutrol) for first-pass MR myocardial perfusion examinations in patients with suspected coronary artery disease (CAD). In phantom studies, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values of gadobutrol were compared with gadopentetate (Gd-DTPA). 25 consecutive patients with clinically suspected CAD were examined with dynamic rest/stress MR perfusion examinations using 0.05 mmol kg(-1) gadobutrol. Semi-quantitative evaluation of the myocardial perfusion was performed by calculating the myocardial perfusion reserve index (MPRI). Hypoperfused regions were correlated with data from X-ray coronary angiography. In phantom studies, SNR/CNR of gadobutrol-doped blood samples were consistently higher for all applied flip angles at concentrations < or =1.0 mmol L(-1) compared with Gd-DTPA. Assessment of 81 stress perfusion series with gadobutrol in 25 patients yielded a sensitivity of 82% and specificity of 91% for significant CAD. Combining the information from all perfusion series of one patient yielded a sensitivity of 89% and specificity of 94% on a per-vessel basis. Gadobutrol exhibited favourable signal properties in phantom studies. Rest/stress myocardial perfusion examinations using 1 M gadobutrol yielded high sensitivity and specificity in detection of malperfused areas (82% and 91%, respectively). This is comparable with recently published perfusion data using 0.5 M Gd-DTPA.
Subject(s)
Contrast Media , Coronary Artery Disease/diagnosis , Gadolinium DTPA , Magnetic Resonance Angiography , Organometallic Compounds , Adult , Aged , Aged, 80 and over , Coronary Angiography , Female , Humans , Magnetic Resonance Angiography/methods , Magnetic Resonance Angiography/standards , Male , Middle Aged , Sensitivity and SpecificityABSTRACT
In patients with acute myocardial infarction treated with thrombolytics, platelet activation as well as alterations of the hemostatic and fibrinolytic systems have been described favoring early infarct-related artery reocclusion. We investigated the effects of a newer thrombolytic regimen with half-dose double-bolus reteplase (2 x 5 IU, 20 patients) combined with abciximab versus full-dose reteplase (2 x 10 IU, 18 patients) on the fibrinolytic and the hemostatic system in patients with acute ST-segment elevation (in the electrocardiogram) myocardial infarction. The thrombolytic regimen with half-dose reteplase in combination with abciximab caused in vivo a lower systemic plasminemia and a lower paradoxical activation of the contact phase of the coagulation system (measured as activated factor XII); a lower paradoxical thrombin activation/generation; and a lesser extent of fibrinogen breakdown compared with the reteplase regimen. These results could be, at least in part, a possible explanation for the observed significantly lower rates of reinfarction until 7 days after enrollment and of recurrent ischemia in the combination group in the Global Use of Strategies to Open Occluded Coronary Arteries V (GUSTO V) trial.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Anticoagulants/therapeutic use , Fibrinolytic Agents/therapeutic use , Immunoglobulin Fab Fragments/therapeutic use , Myocardial Infarction/drug therapy , Recombinant Proteins/therapeutic use , Tissue Plasminogen Activator/therapeutic use , Abciximab , Aged , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Fibrinolytic Agents/administration & dosage , Humans , Male , Middle Aged , Platelet Aggregation/drug effects , Recombinant Proteins/administration & dosage , Tissue Plasminogen Activator/administration & dosageABSTRACT
PURPOSE: This study assesses the left ventricular function using a new multislice cine sequence and determines the diagnostic accuracy of stress-induced wall motion abnormalities in patients with coronary artery disease (CAD). MATERIALS AND METHODS: 15 patients (mean age 57.7 years) with angiographically proven CAD were examined on a 1.5 T whole body system (Magnetom Sonata, Siemens, Erlangen) at rest and during dipyridamole-induced (0.56 mg/kg body weight) stress. Left ventricular function was determined using a multislice (steady-state) sequence (TR 2.3 ms, TE 1.15 ms, slice thickness 10 mm, temporal resolution 77 ms) as well as a standard single-slice true FISP 2D sequence (TR 3.2 ms, TE 1.6 ms, slice thickness 5 mm, temporal resolution 45 ms) as reference. RESULTS: Both cine sequences provide high sensitivity and excellent correlation (r = 0.95) with angiographic findings for the detection of regional wall motion abnormalities. However, the measurement of functional parameters yielded significant differences. End-systolic left ventricular volumes (ESV) were systematically overestimated in the multislice images (mean 78 ml, + 5.8 %) compared with the reference single-slice images (mean 74 ml) (p < 0.05). This resulted in underestimation of the ejection fraction with multislice images (mean 40 %, - 11.3 %) compared with single-slice images (mean 46 %) (p < 0.05). CONCLUSION: The multislice sequence results in a substantial reduction of imaging time and breath-hold periods necessary to cover the left ventricle for functional assessment. The multislice sequence yields adequate images, especially for qualitative determination of wall motion abnormalities. Due to the reduced spatial and temporal resolution of the multi-slice sequence, however, some uncertainty concerning the functional parameters has to be taken into account.
Subject(s)
Coronary Disease/diagnosis , Exercise Test , Image Enhancement/methods , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging, Cine/methods , Ventricular Dysfunction, Left/diagnosis , Adult , Aged , Aged, 80 and over , Cardiac Volume/physiology , Coronary Angiography , Coronary Disease/physiopathology , Dipyridamole , Female , Heart Ventricles/physiopathology , Humans , Male , Mathematical Computing , Middle Aged , Myocardial Contraction/physiology , Prospective Studies , Reproducibility of Results , Stroke Volume/physiology , Vasodilator Agents , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left/physiologyABSTRACT
BACKGROUND: ACE inhibitors may have a cardioprotective effect by enhancing bradykinin levels during cardiopulmonary bypass (CPB). However, ACE inhibition could lead to unwelcome effects on the kallikrein contact phase during CPB (since reduction of kallikrein activity by aprotinin has been shown to be beneficial) and may alter the hemostasis. We examined the effects of ACE inhibitors on intraoperative myocardial damage, kallikrein contact phase and hemostasis in patients undergoing CPB. METHODS: 47 patients randomly received either 20 mg/d enalapril or placebo. Creatine kinase (CK and CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), thrombin-antithrombin III complex (TAT), fibrinogen and kallikrein-like activity were measured before surgery, during and immediately after CPB, at the end of surgery and 1, 3 and 5 days after surgery. RESULTS: No significant differences between enalapril- and placebo- treated patients concerning CK (318 +/- 38.6 U/l vs. 316 +/- 16.8 U/l), CK-MB, LDH, TnT (1.81 +/- 0.45 ng/ml vs. 1.52 +/- 0.34 ng/ml), TAT, fibrinogen and kallikrein-like-activity could be found during study period. CONCLUSIONS: Reduction of ischemic injury during CPB is not achieved with ACE inhibitors. However, treatment of patients with ACE inhibitors before and during CPB is fully feasible without side effects affecting the kallikrein contact phase or significant influence on hemostasis.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Coronary Artery Bypass , Enalapril/therapeutic use , Heart/drug effects , Hemostasis/drug effects , Intraoperative Complications/prevention & control , Kallikrein-Kinin System/drug effects , Myocardial Reperfusion Injury/prevention & control , Administration, Oral , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Coronary Disease/surgery , Double-Blind Method , Enalapril/pharmacology , Female , Fibrinogen/analysis , Humans , Male , Middle AgedABSTRACT
Thrombolytic drugs do not only stimulate the plasmin system but also induce thrombin activation additionally to the preexisting hypercoagulative state in patients with acute myocardial infarction. Testing the in vitro-derived hypothesis of a plasmin-mediated activation of the contact phase of the coagulation leading to the procoagulant effect, several thrombolytic regimen have been evaluated. Paradoxical thrombin activation (referred to as "thrombolytic paradox") was related to absence of fibrin specificity. Highly fibrin-specific drugs like tenecteplase did not cause additional thrombin activation, while non-fibrin-specific drugs like streptokinase caused a marked additional activation of the contact phase and of thrombin. It could be shown that the thrombolytic paradox was related to the extent of systemic plasmin activation confirming the hypothesis of a plasmin-mediated factor XII/kallikrein system activation as cause of the thrombolytic paradox.
Subject(s)
Thrombolytic Therapy/adverse effects , Fibrinolysin/drug effects , Fibrinolysin/metabolism , Fibrinolytic Agents/adverse effects , Fibrinolytic Agents/therapeutic use , Humans , Thrombin/drug effects , Thrombin/metabolismABSTRACT
PURPOSE: Increased T2 signal intensity (SI) can be regularly observed in myocardial infarction. However, there are controversial reports about the relationship of elevated T2 SI to myocardial viability and some authors propose that high T2 SI serves as a sign of irreversible myocardial injury. This study investigates increased T2 SI compared to myocardial function in patients with reperfused subacute myocardial infarction. Preserved function was used as criterion for viability. METHODS: Ten healthy volunteers and 17 patients with myocardial infarction and patent infarct related coronary artery were examined on a 1.5 T Magnetom Vision system (Siemens). For T2-weighted MR imaging a breath-hold STIR sequence with dark-blood preparation was used. Cine FLASH 2D imaging was applied to assess myocardial function. Signal-to-noise (S/N) in STIR T2 images was measured in normal and infarcted regions and subsequently identified by two independent observers. Based on a 20 segment model of the left ventricle findings were compared to regional myocardial function. RESULTS: Elevated STIR T2 SI was found in all 17 patients and observed in 27% (204/754) of segments. S/N of normal myocardium was 5.1 +/- 0.7 in volunteers and 4.9 +/- 0.8 in patients (P = NS). Infarcted myocardium presented with significantly increased S/N 12.8 +/- 1.9 (P < 0.0001). Significant transmural elevation of T2 SI was noted in 32% of segments with preserved systolic function. CONCLUSION: Increased STIR T2 SI can be observed transmurally in post-ischemic myocardial regions with preserved function. It therefore cannot be used as an exclusive marker for the non-viable region.
Subject(s)
Magnetic Resonance Angiography/methods , Magnetic Resonance Imaging/methods , Myocardial Infarction/diagnosis , Myocardium/pathology , Aged , Computers , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Time FactorsABSTRACT
Patients with acute coronary syndromes (ACS) frequently present with signs of disturbed fibrinolysis. The present study investigates the correlation of alterations in the fibrinolytic system and the amount of myocardial damage characterized by troponin release. In 85 patients with ACS markers of plasmin activation, plasminogen activator system and troponin T (TnT) were measured initially and after 48 h. Patients with TnT release (> or = 0.01 microg/l) at admission had higher TPA levels than those without release (10.2+/-0.7 ng/ml vs. 7.6+/-0.5 ng/ml; p <0.01). Additionally, patients with positive TnT had higher D-dimer levels initially (457+/-39 ng/ml vs. 316+/-22 ng/ml; p <0.01) and 48 h later (451+/-42 ng/ml vs. 275+/-37 ng/ml; p <0.01). The association of myocardial damage with a prothrombotic state and an enhanced fibrinolysis may explain the high prognostic value of troponin measurements in respect to future coronary events.
Subject(s)
Coronary Disease/blood , Fibrinolysis/physiology , Troponin T/metabolism , Acute Disease , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Case-Control Studies , Coronary Disease/diagnosis , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinolysin/metabolism , Humans , Male , Middle Aged , Myocardium/metabolism , Myocardium/pathology , Plasminogen/metabolism , Prognosis , Thrombophilia/blood , Thrombophilia/complications , Tissue Plasminogen Activator/blood , Troponin T/blood , Troponin T/physiologyABSTRACT
This study was undertaken to compare the effects of reteplase and alteplase regimens on hemostasis and fibrinolysis in acute myocardial infarction (AMI). Thrombolytic treatment in patients with AMI is hampered by paradoxical procoagulant effects that favor early reocclusion. In vivo data comparing this effect and the fibrin specificity of double-bolus reteplase and front-loaded alteplase regimens are not available. In a prospective, randomized study, 50 patients with AMI were either treated with double bolus (10 + 10 U) reteplase or with front-loaded alteplase (up to 100 mg) within 6 hours of symptom onset. Thirty apparently healthy persons served as controls. Molecular markers of coagulation and fibrinolysis were serially examined for up to 5 days. Paradoxical thrombin activation at 3 hours after initiation of therapy was comparable between reteplase and alteplase. Reteplase (65 +/- 5 U/L) and alteplase (72 +/- 8 U/L) caused significantly elevated kallikrein activity at 3 hours after adminstration (p <0.01 vs controls 30 +/- 1 U/L). Fibrin specificity was less for reteplase (p <0.05) with a decrease in fibrinogen at 3 hours to 122 +/- 27 mg/dl versus 224 +/- 28 mg/dl for alteplase (p <0.01 and p <0.05 vs controls). D-Dimer levels at 3 hours were higher (p <0.05) after reteplase (5,459 +/- 611 ng/ml) versus alteplase (3,445 +/- 679 ng/ml) (both p <0.01 vs controls 243 +/- 17 ng/ml). Plasmin generation (plasmin-antiplasmin complexes) was significantly (p <0.01) increased at 3 hours with both regimens to 27,079 +/- 3,964 microg/L (reteplase) and 19,522 +/- 2,381 microg/L (alteplase). The data from 3 hours after start of thrombolytic therapy proved less marked fibrin specificity of the reteplase regimen (in vivo) compared with front-loaded alteplase. Both regimens have a moderate procoagulant effect without differences in activation of the kallikrein system.
Subject(s)
Fibrin/drug effects , Fibrinolysin/metabolism , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Kallikreins/drug effects , Myocardial Infarction/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Adult , Aged , Aged, 80 and over , Antithrombin III/drug effects , Antithrombin III/metabolism , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Fibrin/metabolism , Fibrinolytic Agents/adverse effects , Hemostasis/drug effects , Humans , Kallikreins/metabolism , Male , Middle Aged , Myocardial Infarction/blood , Peptide Hydrolases/drug effects , Peptide Hydrolases/metabolism , Prospective Studies , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recurrence , Thrombin/metabolism , Tissue Plasminogen Activator/adverse effectsABSTRACT
PURPOSE: The aim of the study was to evaluate myocardial function and perfusion patterns using magnetic resonance imaging in normal subjects. MATERIALS AND METHODS: 22 healthy volunteers were examined. Cine-mode acquisitions along all three axes of the heart were generated and perfusion was measured on a mid-ventricular short-axis view. Myocardial wall thickening was scored and contrast enhancement during the first pass was analysed. RESULTS: For myocardial wall thickening increasing values from base (24-86%) to apex (63-106%) were found. Contrast enhancement patterns showed regional variability. In addition marked individual differences were detectable. CONCLUSION: Perfusion patterns should be interpreted only in combination with functional parameters. Standard values for perfusion measurements cover very large range as a result of the high individual variability.
Subject(s)
Heart/anatomy & histology , Heart/physiology , Magnetic Resonance Imaging/methods , Adult , Contrast Media , Female , Heart Function Tests , Humans , Male , Perfusion , Reference ValuesABSTRACT
RATIONALE AND OBJECTIVES: The purpose of this study was to develop and implement MR sequences for chemical shift-selective breath-hold cine imaging of the heart. Fibroadipose conversion of myocardium in cases suspected of right ventricular dysplasia should be revealed in fat- and water-selective MR images of high quality. METHODS: Frequency-selective saturation of one chemical shift component was applied in modified k-space-segmented, electrocardiography-gated sequences, allowing high-quality cine imaging of the human heart in a single breath-hold. Phantom studies and human examinations in eight normal subjects (aged 24-62 years) and in seven patients (aged 31-47 years) with suspected right ventricular dysplasia were performed. The patients showed suspicious findings, such as a dyskinetic and dilated right ventricle combined with ventricular arrhythmia, and underwent MR imaging after exclusion of other possible reasons (eg, coronary artery disease or pulmonary hypertension). RESULTS: High selectivity to the desired chemical shift component was confirmed by test measurements in a phantom containing water and lipids. In the human subjects, minor problems with magnetic field inhomogeneities appeared in the thoracic walls only. Four patients with suspected right ventricular dysplasia showed clearly abnormal signal behavior of the right myocardial wall in both fat- and water-selective cine images. Bright transmural structures were exhibited in fat-selective images, but the origin of the fat (epicardium or infiltrated myocardium) was often difficult to assess. CONCLUSIONS: Right ventricular areas with fibrosis and fatty degeneration often show normal signal intensity in standard T1-weighted images but can be differentiated from normal tissue by the new chemical shift-selective breath-hold cine techniques.
Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Magnetic Resonance Imaging, Cine , Adipose Tissue , Adult , Female , Humans , Male , Phantoms, Imaging , WaterABSTRACT
BACKGROUND: In acute coronary syndromes, marked alterations of coagulation and fibrinolysis have been observed, but no data are available concerning a possible relation to coronary stenosis morphology. METHODS: Thirty one patients with unstable angina pectoris were included. Culprit stenosis morphology judged from coronary angiography was graded using the modified ACC/AHA classification. Molecular and functional markers of hemostasis and fibrinolysis were determined from venous plasma samples obtained at admission. RESULTS: Patients with unstable angina pectoris had a moderate procoagulant state, especially a contact phase activation compared with age-matched controls (factor XII 93.9 +/- 5.6 vs 112.8 +/- 5.4%; P < 0.05; high molecular weight kininogen 55.3 +/- 5.4 vs 86.1 +/- 6.5%; P < 0.01). Thrombin-antithrombin (TAT) was not significantly elevated (7.6 +/- 1.9 vs 4.0 +/- 0.5 microg/l). Elevated plasminogen activator mass concentration (16.6 +/- 2.1 vs 5.4 +/- 0.6 ng/ml; P < 0.01) and plasminogen activator inhibitor (PAI) activity (9.9 +/- 3.0 vs 5.6 +/- 3.0 AU/ml; P < 0.05) indicated an alteration of the fibrinolysis. Complexity of coronary stenosis was positively correlated with tissue-type plasminogen activator (TPA) mass concentration (P < 0.01) and PAI activity (P < 0.05). No association was found to markers of a hypercoagulative state. CONCLUSION: These findings indicate a relation between alterations of the fibrinolytic system and coronary morphology, whereas the acute changes of coagulation occur independently of culprit stenosis complexity.
Subject(s)
Angina, Unstable/blood , Angina, Unstable/diagnostic imaging , Coronary Disease/diagnostic imaging , Factor XII/analysis , Kininogens/blood , Plasminogen Activator Inhibitor 1/blood , Adult , Aged , Angina, Unstable/physiopathology , Biomarkers/analysis , Coronary Angiography , Coronary Disease/blood , Coronary Disease/physiopathology , Female , Fibrinolysis/physiology , Humans , Logistic Models , Male , Middle Aged , Reference Values , Sensitivity and SpecificityABSTRACT
OBJECTIVE: Six patients who had undergone minimally invasive direct coronary artery bypass surgery were examined to evaluate an MR imaging protocol that provided information about cardiac function, bypass graft patency, and flow characteristics with a single examination. CONCLUSION: Preliminary results suggest that our imaging protocol allows accurate follow-up of patients after minimally invasive direct coronary artery bypass surgery. Bypass graft patency was correctly determined in all patients. In four patients, anastomoses were visualized by MR angiography, and flow measurements revealed a volume range of 28-84 ml/min (native and grafted internal mammary arteries) and a trend for the flow values of bypass grafts to be lower than those of native vessels. Interobserver reproducibility was good (r = .99; slope, .98).
Subject(s)
Internal Mammary-Coronary Artery Anastomosis , Magnetic Resonance Angiography , Contrast Media , Coronary Circulation , Gadolinium DTPA , Graft Occlusion, Vascular/diagnosis , Humans , Internal Mammary-Coronary Artery Anastomosis/methods , Male , Middle Aged , Minimally Invasive Surgical Procedures , Vascular PatencyABSTRACT
PURPOSE: To prove the accuracy of MR methods in the determination of left ventricular (LV) functional parameters and anatomy. MATERIALS AND METHODS: At 1.5 T, 20 healthy volunteers and 22 patients with aortic valvular disease (stenosis n = 15, regurgitation n = 7) were examined. Functional parameters like cardiac output, ejection fraction, end-diastolic volume, aortic flow maximum, and time interval from the R-wave to maximum flow were obtained using a velocity encoding 2D FLASH sequence (TR 24 ms, TE 5 ms, venc 250 cm/sec) and segmented breath-hold cine FLASH 2D technique (TR 100 ms, TE 4.8 ms, flip angle 25 degrees, temporal resolution 50 ms). Invasive measurements (Fick principle) served as gold standard, intra- and interobserver variability were determined. RESULTS: Differences of functional parameters between normal volunteers and patients were detectable at a high level of significance (p < 0.0001). For cardiac output a superior correlation with the gold standard was found using flow measurements (r = 0.66, p < 0.0007) compared to volumetric calculations from cine studies (r = 0.47, p < 0.02). Interobserver variability was 2.5 +/- 2.7%/4.5 +/- 6.9% (flow quantification/calculations from cine studies), intraobserver variability was 1.7 +/- 1.6%/3.3 +/- 2.2%. CONCLUSIONS: MRI is an appropriate tool for determining LV functional parameters and anatomy. Differences between normal volunteers and patients with aortic valvular disease can be detected reliably. Flow measurements turned out to be more accurate than calculations from cine images. Therefore, flow quantification techniques should be preferred for clinical use.
Subject(s)
Aortic Valve Insufficiency/diagnosis , Aortic Valve Stenosis/diagnosis , Hemodynamics/physiology , Magnetic Resonance Imaging, Cine , Ventricular Dysfunction, Left/diagnosis , Adult , Aortic Valve Insufficiency/physiopathology , Aortic Valve Stenosis/physiopathology , Cardiac Output/physiology , Diastole/physiology , Electrocardiography , Female , Humans , Male , Reference Values , Stroke Volume/physiology , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left/physiologyABSTRACT
Reinjection of 201Tl is used for improved detection of viable myocardium. Prospectively the effect of the redistribution time after injection for the quantification of the definitive perfusion defect size in multivessel coronary heart disease and severely impaired left ventricular function was examined. Thirty patients were included preoperatively before CABG. The study was performed with 80-90 MBq 201Tl-Cl and reinjection (40-50 MBq). Imaging was performed after an exercise test and 3 hours afterwards. Thereafter, the reinjection dose was given and repeated studies were performed 10 minutes, 2 hours, and 20 hours later. Defect sizes were compared with the 3-hour rest-study without reinjection. Imaging studies were repeated postoperatively. The defect size was expressed as % of left ventricular total myocardium. Perfusion defect sizes were as follows: post-stress study (27%), 3 hour rest-study (17%), post-reinjection-10 min (12%), 2 hours (9%), and 20 hours (7%). Compared with the 3 hour rest-study, the perfusion defect was reduced only in 7/30 patients in the study immediately after reinjection. In the delayed studies, defect sizes were markedly smaller (p < 0.05) both in studies 2 hours and 20 hours after reinjection. In 15/30 patients there was a marked reduction of 50% of defect sizes in the study 2 hours post-reinjection vs the 3 hour rest-study. The residual defects at 2 hours after reinjection were identical to the postoperative defect sizes (10%). Further prolongation of the redistribution time to 20 horus caused an additional small reduction in defect size only in two patients compared with the 2-hour post-reinjection images (n.s.). Using a marker as 201Tl with redistribution characteristics, the redistribution time after reinjection is of utmost importance to correctly identify the definitive size of the perfusion defect vs viable myocardium in patients with multivessel disease. A delay of 2 hours for redistribution after the reinjection most correctly corresponds to the postop defect size; a longer redistribution time did not provide additional advantages.
ABSTRACT
BACKGROUND: Thrombolytic therapy in patients with acute myocardial infarction (AMI) is hampered by procoagulant effects. In vitro studies have indicated that plasmin stimulation activates the kallikrein-contact-phase system, resulting in thrombin activation. This prospective comparative study was designed to examine the procoagulant effects of streptokinase or alteplase in AMI. METHODS AND RESULTS: Sixty-one patients with AMI received 1.5 million U of streptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control subjects were examined for comparison. Molecular markers of thrombin, plasmin activation, and coagulation activities were determined before therapy and serially for up to 10 days. Moderate thrombin (initial thrombin-antithrombin [TAT] complex 18+/-5 versus 4+/-0.3 microg/L, P<0.05) and kallikrein (up to 45+/-4 versus 30+/-1 U/L at 3 hours, P<0.01) activation occurs in patients with AMI. D-Dimers are increased (P<0.01), and plasmin is stimulated (P<0.01). Streptokinase and alteplase increase TAT to 50+/-17 and 51+/-18 microg/L at 3 hours and to 50+/-17 and 33+/-14 microg/L at 6 hours, respectively (P<0.01). Kallikrein activity is elevated (P<0. 01) to 76+/-5 and 71+/-7 U/L at 3 hours and 64+/-6 and 47+/-5 U/L by streptokinase and alteplase, respectively, at 6 hours. Reductions in fibrinogen and increases in D-dimers and plasmin-antiplasmin complexes are more marked (P<0.05 and 0.01) after streptokinase versus alteplase. Correlations were found among TAT, kallikrein activity, and plasmin activation (P<0.01). CONCLUSIONS: The data indicate a more marked procoagulant action of the streptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive procoagulant action in vivo.
Subject(s)
Fibrinolysin/analysis , Fibrinolytic Agents/administration & dosage , Kallikreins/analysis , Myocardial Infarction/drug therapy , Streptokinase/administration & dosage , Tissue Plasminogen Activator/administration & dosage , Acute Disease , Adult , Aged , Aged, 80 and over , Female , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Myocardial Infarction/blood , Streptokinase/therapeutic use , Tissue Plasminogen Activator/therapeutic useABSTRACT
The morphological correlate of acute coronary syndromes is a ruptured plaque with intraluminal thrombus formation. Furthermore, inflammation, coagulation, fibrinolysis, complement system, and corpuscular elements of the blood are activated. Certain markers as CRP, fibrinogen, plasminogen activator inhibitor or tissue-type plasminogen activator antigen are reported to have a prognostic impact to identify patients at risk. Morphological data provide evidence for the impact of inflammatory mechanisms for the rupture of an unstable plaque and an association of several infections with coronary syndromes was reported. To date it is not known to what extent the various patho-mechanisms influence the rupture of a plaque with the risk of consecutive formation of an occlusive thrombus. It can be assumed that a plaque rupture without critical occlusion of the vessel occurs frequently without symptoms, thus making the evaluation of causal relationships clinically difficult. Future studies should investigate the complex interactions of the different systems by determination of markers of activation in parallel during the acute phase of the disease. Furthermore, experiments should be designed to examine the relative impact of single factors for the pathophysiological process of plaque rupture in acute coronary syndromes including the meaning of infections agents.
Subject(s)
Coronary Artery Disease/pathology , Coronary Thrombosis/pathology , Systemic Inflammatory Response Syndrome/pathology , Coronary Vessels/pathology , Humans , Risk FactorsABSTRACT
OBJECTIVES: We sought to examine whether the disturbed fibrinolytic system in patients with an acute coronary syndrome is associated with a reduced endothelial fibrinolytic capacity. BACKGROUND: Intracoronary thrombus formation is a frequent finding in acute coronary syndromes. Systemic alterations of coagulation and fibrinolysis are known to occur, but possible disturbances of endothelial fibrinolytic function have not been investigated. METHODS: We compared 42 patients with an acute coronary syndrome (acute myocardial infarction in 11 and unstable angina pectoris in 31) with 25 patients with stable angina. Venous blood was sampled serially for determination of markers of the fibrinolytic system and of hypercoagulability from admission to day 10. An occlusion test to determine the maximal endothelial tissue-type plasminogen activator (t-PA) release was also performed. RESULTS: Both on day 0 and day 10, patients with an acute coronary syndrome had a marked elevation of t-PA mass concentration (mean value +/- SEM 14.4 +/- 1.6 [day 0], 18.9 +/- 2.5 ng/ml [day 10]) and of plasminogen activator inhibitor (PAI) (9.4 +/- 2.2 [day 0], 11.3 +/- 2.6 AU/liter [day 10], p < 0.05 vs. patients with stable angina). There was also a hypercoagulative state with elevated thrombin activity and increased D-dimers (p < 0.05 vs. patients with stable angina). Maximal endothelial t-PA release was initially reduced (p < 0.05 vs. patients with stable angina) to 2.3 +/- 0.9 ng/ml, but levels recovered during follow-up to 4.4 +/- 1.4 ng/ml (vs. 5.7 +/- 1.5 ng/ml in patients with stable angina). CONCLUSIONS: Despite the known prolonged systemic alteration of fibrinolysis in acute coronary syndromes, endothelial fibrinolytic capacity is reduced only during the acute phase and becomes normalized during follow-up, and thus is linked more to intravascular thrombus formation than to steady state levels of markers of the fibrinolytic system.
Subject(s)
Angina, Unstable/metabolism , Endothelium, Vascular/metabolism , Fibrinolysis , Myocardial Infarction/metabolism , Tissue Plasminogen Activator/metabolism , Antithrombin III/metabolism , Fibrinogen/metabolism , Humans , Peptide Hydrolases/metabolism , Plasminogen/metabolism , Prospective Studies , Time Factors , alpha-2-Antiplasmin/metabolismABSTRACT
OBJECTIVES: The purpose of the study was to evaluate the cardiopulmonary exercise capacity and ventilatory function in adults with atrial septal defect (ASD) preoperatively and 4 months and 10 years postoperatively. BACKGROUND: Only few data are available on cardiopulmonary exercise tolerance after ASD closure, but detailed knowledge might be helpful for indication for defect closure in certain patients. METHODS: The study was performed in adult patients (mean [+/-SD] age at operation 39.9 +/- 11.5 years; left-right shunt 9.6 +/- 5.6 liters/min; pulmonary/systemic flow ratio 2.8 +/- 1.2; mean pulmonary artery pressure 18.2 +/- 6.2 mm Hg). Cardiopulmonary exercise testing was performed with a bicycle ergometer. We determined peak oxygen uptake, anaerobic threshold, performance at anaerobic threshold and maximal performance in relation to these variables in a normal group. Ventilatory function at rest was expressed by vital capacity, maximal voluntary ventilation and forced expiratory volume in 1 s. RESULTS: Preoperatively, ventilatory function at rest was only moderately reduced to approximately 75% to 85%. Four months postoperatively we found no significant improvement, but 10 years postoperatively ventilatory function at rest was normalized. Preoperative cardiopulmonary exercise capacity was markedly reduced to 50% to 60%; early postoperatively it was only slightly higher, but late postoperatively exercise capacity significantly improved and was completely normalized. CONCLUSIONS: Although preoperative cardiopulmonary capacity in adult patients with nonrestrictive ASD was significantly decreased, some improvement was seen at 4 months postoperatively, with complete restitution to normal at 10 years after shunt closure.
Subject(s)
Exercise Tolerance/physiology , Heart Septal Defects, Atrial/physiopathology , Heart Septal Defects, Atrial/surgery , Adult , Cardiac Catheterization , Exercise Test , Female , Follow-Up Studies , Heart Septal Defects, Atrial/diagnosis , Humans , Male , Preoperative Care , Pulmonary Ventilation/physiology , Time FactorsABSTRACT
PURPOSE: With the advent of fast pulse sequences, MR imaging of myocardial function and perfusion in ischaemic heart disease has become possible. Prior studies examined either myocardial perfusion or systolic wall motion. We intended to establish an examination procedure to simultaneously investigate regional myocardial motility and perfusion in patients 7-14 days after myocardial infarction. METHODS: A Turbo-FLASH 2D sequence was optimised to maximise image contrast between normal and malperfused myocardium after Gd-injection using a calculation model basing on the Bloch equation. Calculated values for trigger delay TD, inversion time TI and flip angle alpha were confirmed in a Gd-phantom and healthy volunteers. Subsequently, myocardial motility was studied (cine FLASH 2D sequence) and in slice positions with reduced wall thickening first pass and post contrast studies after 2-10 minutes were performed using the optimised Turbo-FLASH sequence. RESULTS: First pass SI-differences of normal compared to malperfused myocardium vary in relation to TD, TI and alpha in a relevant degree. Reduced myocardial motility was found with a sensitivity of 81% and specificity of 96%. Pathological perfusion patterns were detectable in all of these patients. CONCLUSIONS: A combined examination of motility and perfusion is possible by means of MRI and information about the status of postinfarct myocardium can be obtained.