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1.
Cardiovasc Drugs Ther ; 37(4): 807-813, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748147

RESUMO

PURPOSE: Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a series of meta-analyses linking digoxin treatment and mortality have contributed to a narrower application of this medication for the management of heart failure (HF) and atrial fibrillation (AF). Given the conflicting data from the earlier RCTs and more recent meta-analyses, there is a growing polarization among providers for and against the use of digoxin in managing these conditions. METHODS: To help close this divide, we provide a perspective on the literature with special attention to the quality of both older and more recent studies on this subject. RESULTS: The data from the highest quality studies we have, RCTs, suggest that digoxin use in patients with HF and/or AF is associated with improvement in several areas of outcomes including functional capacity, symptom management, reduced hospitalizations, fewer deaths due to HF, and treatment of refractory chronic heart failure with rEF, and may even have overall mortality benefit when serum digoxin concentrations are within therapeutic range. These effects are more pronounced in patients with EF < 25% and NYHA Class II-IV and at highest risk for hospitalization. CONCLUSION: As the risk of confounding factors was minimized by the study design, the likelihood that positive outcomes were identified with digoxin use increased. Clinicians and researchers need further adequately designed and powered RCTs exploring the connection between digoxin therapy and mortality, hospitalizations, and symptom management.


Assuntos
Fibrilação Atrial , Digitalis , Insuficiência Cardíaca , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Digoxina/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico
2.
Cardiovasc Drugs Ther ; 36(3): 525-532, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34245446

RESUMO

Dipyridamole is an old anti-platelet and coronary vasodilator agent that inhibits platelet phosphodiesterase and increases interstitial adenosine levels. Its use in coronary artery disease (CAD) has fallen out of practice in the modern era with the advent of new anti-platelet agents, and most modern guidelines on the management of CAD either neglect to comment on its utility or outright recommend against it. The majority of the studies used in these guidelines are outdated and took place in an era when high doses of aspirin were used and statins were not widely utilized. There is growing evidence in rat models of dipyridamole's synergy with statins through adenosine modulation resulting in significant myocardial protection against ischemia-reperfusion injury and limitation of infract size. The data in human studies are limited but show a similar potential synergy between dipyridamole and statins. It would thus be prudent to reconsider the recommendations against the use of dipyridamole in CAD and to re-evaluate its possible role and potential benefits through well-designed randomized trials combining it with statins, low-dose aspirin, and/or other anti-platelet agents.


Assuntos
Dipiridamol , Inibidores de Hidroximetilglutaril-CoA Redutases , Adenosina , Animais , Aspirina , Dipiridamol/farmacologia , Dipiridamol/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Ratos , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico
3.
BMC Cardiovasc Disord ; 19(1): 13, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630413

RESUMO

BACKGROUND: In the standard ECG display, limb leads are presented in a non-anatomical sequence: I, II, III, aVR, aVL, aVF. The Cabrera system is a display format which instead presents the limb leads in a cranial/left-to-caudal/right sequence, i.e. in an anatomically sequential order. Lead aVR is replaced in the Cabrera display by its inverted version, -aVR, which is presented in its logical place between lead I and lead II. MAIN TEXT: In this debate article possible implications of using the Cabrera display, instead of the standard, non-contiguous lead display, are presented, focusing on its use in patients with possible acute coronary syndrome. The importance of appreciating reciprocal limb-lead ECG changes and the diagnostic and prognostic value of including aVR or lead -aVR in ECG interpretation in acute coronary syndrome is covered. Illustrative cases and ECGs are presented with both the standard and contiguous limb lead display for each ECG. A contiguous lead display is useful when diagnosing acute coronary syndrome in at least 3 ways: 1) when contiguous leads are present adjacent to each other, identification of ST elevation in two contiguous leads is simple; 2) a contiguous lead display facilitates understanding of lead relationships as well as reciprocal changes; 3) it makes the common neglect of lead aVR unlikely. CONLUSIONS: It is logical to display the limb leads in their sequential anatomical order and it may have advantages both in diagnostics and ECG learning.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Apresentação de Dados , Eletrocardiografia/instrumentação , Potenciais de Ação , Síndrome Coronariana Aguda/fisiopatologia , Desenho de Equipamento , Frequência Cardíaca , Humanos , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador
4.
Ir J Med Sci ; 187(2): 369-377, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28936580

RESUMO

BACKGROUND: Data from randomized trials evaluating the efficacy of on- versus off-pump coronary artery bypass grafting remain inconclusive, particularly in high-risk populations. AIMS: The aim of this study is to compare the outcomes associated with on- versus off-pump coronary artery bypass grafting among high-risk patients. METHODS: We performed a meta-analysis of randomized control trials comparing on- versus off-pump coronary artery bypass grafting, focusing on high-risk populations. Studies focusing on "high-risk" features: European System of Cardiac Operative Risk Evaluation (EuroSCORE) ≥ 5, age > 70 years, preexisting renal insufficiency, history of stroke(s), and the presence of left ventricular dysfunction were included. MEDLINE, Scopus, and Embase were searched for all publications between January 1, 2000 and August 1, 2016, using the following terms: on-pump, off-pump, coronary artery bypass, high-risk, left ventricular dysfunction, elderly, aged, and renal insufficiency. Endpoints included cardiovascular and all-cause mortality, non-fatal myocardial infarction, stroke, need for revascularization, renal failure, and length of hospital stay. RESULTS: Nine studies incorporating 11,374 patients with a mean age of 70 years were selected. There was no statistical difference in cardiovascular mortality, all-cause mortality, non-fatal myocardial infarction, and renal failure between the two groups. There was a decrease in further revascularization at 1 year with on-pump (OR 0.67 (0.50-0.89)). However, there was an increase in length of hospital stay by 2.24 days (p = 0.03) among the on-pump group with no difference in stroke (OR 1.34 (1.00-1.80)). CONCLUSIONS: On-pump is associated with a decreased risk of additional revascularization by 1 year. However, this appears to be a cost of longer hospitalization.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Ponte de Artéria Coronária/métodos , Idoso , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
5.
Am J Cardiol ; 113(2): 270-4, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24176061

RESUMO

Inversion of the T waves (T-) in electrocardiographic leads with ST-segment elevation after the initiation of reperfusion therapy is considered a sign of reperfusion. However, the significance of T- on presentation before the initiation of reperfusion therapy is unclear. The aim of this study was to assess whether T- on presentation predicts patency of the infarct-related artery in patients with acute ST-segment elevation myocardial infarctions (STEMIs) who undergo primary percutaneous interventions. The medical records, electrocardiograms, and angiographic findings of 209 consecutive patients who underwent emergent coronary angiography as part of primary percutaneous coronary intervention protocol activation for STEMI were reviewed. A total of 179 patients (86%) had positive T waves (T+), 16 (8%) had biphasic T waves (T+/-), and 14 (7%) had T-. Patency of the infarct-related artery (Thrombolysis In Myocardial Infarction [TIMI] flow grades 2 and 3) was seen in 64.3% of the patients in the T- group compared with only 31.2% in the T+/- group and 19.0% in the T+ group (p <0.001). Among patients with anterior STEMI, patency of the infarct-related artery was seen in all 7 patients in the T- group, compared with 50% of the 4 patients in the T+/- group and 10.1% of the 79 patients in the T+ group (p <0.001). There were no significant differences in TIMI flow grade among the groups in patients with nonanterior STEMIs (p = 0.985). In conclusion, T- in the leads with maximal ST-segment elevation on the presenting electrocardiogram was associated with higher prevalence of patency of the infarct-related artery before intervention (64.3%), especially in patients with anterior STEMIs (100%).


Assuntos
Circulação Coronária/fisiologia , Eletrocardiografia , Infarto do Miocárdio/fisiopatologia , Recuperação de Função Fisiológica , Idoso , Angiografia Coronária , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea , Prognóstico , Estudos Retrospectivos
6.
Am J Physiol Heart Circ Physiol ; 299(1): H153-64, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20435846

RESUMO

The purpose of the present study was to assess whether resolvin E1 (RvE1), an anti-inflammatory mediator derived from eicosapentaenoic acid, would limit myocardial infarct size in the rat. The H9c2 cell line was used to assess whether RvE1 has direct protective effects on cardiomyocytes. In in vivo experiments, Male Sprague-Dawley rats underwent 30 min of ischemia/4 h of reperfusion. Before reperfusion, rats received intravenous RvE1 (0, 0.03, 0.1, or 0.3mg/kg). In in vitro experiments, H9c2 cells were incubated with RvE1 (0, 1, 10, 100, or 1000 nM). Cells were subjected to 18 h of incubation under normoxic conditions, 16 h of hypoxia, or 16 h of hypoxia and 2 h of reoxygenation. In vivo, RvE1 dose dependently reduced infarct size (30.7 +/- 1.7% of the area at risk in the control group and 29.1 +/- 1.6%, 14.7 +/- 1.3%, and 9.0 +/- 0.6% in the 0.03, 0.1, and 0.3 mg/kg groups, respectively, P < 0.001). In vitro, RvE1 increased viability and decreased apoptosis in a dose-dependent fashion in cells exposed to hypoxia or hypoxia/reoxygenation. A maximal effect was achieved at a concentration of 100 nM. RvE1 augmented phosphoinositide 3-kinase activity, attenuated caspase-3 activity, and augmented calcium-dependent nitric oxide synthase activity in cells exposed to hypoxia or hypoxia/reoxygenation. RvE1 increased Akt, ERK1/2, and endothelial nitric oxide synthase phosphorylation and attenuated the levels of activated caspase-3 and phosphorylated p38 levels. AG-1478, an EGF receptor tyrosine kinase inhibitor, blocked the protective effect of RvE1 both in vivo and in vitro and attenuated the RvE1-induced increase in Akt and ERK1/2 phosphorylation. In conclusion, RvE1, an anti-inflammatory mediator derived from eicosapentaenoic acid, has a direct protective effect on cardiomyocytes against ischemia-reperfusion injury and limits infarct size when administered intravenously before reperfusion.


Assuntos
Anti-Inflamatórios/farmacologia , Ácido Eicosapentaenoico/análogos & derivados , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Caspase 3/metabolismo , Hipóxia Celular , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/farmacologia , Receptores ErbB/metabolismo , Injeções Intravenosas , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismo
7.
Heart ; 92(11): 1577-82, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16740918

RESUMO

OBJECTIVE: To determine whether ischaemia grade (GI) on the presenting ECG and duration of symptoms can identify subgroups of patients who would derive more benefit than the general population of patients with ST segment elevation acute myocardium infarction (STEMI) from primary percutaneous coronary intervention (pPCI) over thrombolytic treatment (TT) in reducing mortality or reinfarction. METHODS: 1319 DANAMI-2 (Danish trial in Acute Myocardial Infarction-2) patients were classified as having grade 2 ischaemia (GI2; ST segment elevation without terminal QRS distortion) or grade 3 ischaemia (GI3; ST segment elevation with terminal QRS distortion in > or = 2 adjacent leads), and were divided into early and late groups split by the median time (3 h) from symptom onset to treatment. Outcomes were 30-day mortality and reinfarction. RESULTS: Mortality was significantly higher for GI3 than for GI2 (9.7% v 4.8%, p < 0.001) and doubled for patients presenting late (GI2: 6.0% v 3.3%, p = 0.01; GI3: 12.5% v 4.7%, p = 0.05). Overall mortality did not differ significantly between pPCI and TT; however, a 5.5% absolute mortality reduction was seen in GI3 treated early with pPCI (1.4% v 6.9%, p = 0.10). Reinfarction rate was particularly high among GI3 patients presenting late and treated with TT (12.2%). pPCI in such patients significantly reduced the rate of reinfarction (0%, p < 0.001). Logistic regression analysis showed that age (odds ratio (OR) 1.09, 95% confidence interval (CI) 1.06 to 1.12, p < 0.001), prior angina (OR 2.56, 95% CI 1.44 to 4.54, p = 0.001), heart rate (OR 1.03, 95% CI 1.01 to 1.04, p = 0.001) and GI3 (OR 1.91, 95% CI 1.06 to 3.44, p = 0.031) were independently associated with mortality, whereas the sum of ST segment elevation was not. CONCLUSIONS: GI3 is an independent predictor of mortality among patients with STEMI. Mortality increased significantly with symptom duration in both GI2 and GI3. pPCI may be especially beneficial for patients with GI3 presenting early, whereas patients with GI3 presenting late and treated with TT are at particular risk of reinfarction.


Assuntos
Angioplastia Coronária com Balão/mortalidade , Infarto do Miocárdio/terapia , Isquemia Miocárdica/diagnóstico , Terapia Trombolítica/mortalidade , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Isquemia Miocárdica/mortalidade , Prevenção Secundária , Fatores de Tempo , Resultado do Tratamento
9.
Physiol Meas ; 25(4): 957-65, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15382834

RESUMO

Compared to other non-invasive methods, the conventional 12-lead electrocardiogram (ECG) has low sensitivity and specificity for identifying coronary artery disease (CAD). We compared the newly developed high-frequency QRS electrocardiogram (HFQRS ECG, 150-250 Hz) with adenosine sestamibi myocardial perfusion study (MPI)-the most sensitive non-invasive study in cardiology practice. Using advanced 12-lead computer-based ECG software recently developed at NASA, criteria for a positive 12-lead HFQRS-ECG test for obstructive CAD were developed using 300 signal-averaged beats from patients undergoing elective coronary angiograms for evaluation of chest pain. These criteria, which rely strictly upon the presence or the absence of morphologic 'reduced amplitude zones' (RAZs) and not upon the 'root mean squared' (RMS) voltage amplitudes of the HFQRS complexes, were then applied prospectively to 18 patients undergoing MPI. Active CAD was considered present when reversible ischemic defects were present on MPI. Of the 18 patients, 9 had reversible defects on MPI (positive scan), whereas the other 9 had no reversible perfusion defects (negative scan). Patients with a positive nuclear study went on to coronary angiography confirming CAD, except in one patient who had nonobstructive coronary disease (<50% stenosis). Eight of the 18 subjects therefore had active CAD, whereas 10 were judged not to have active CAD. The 12-lead HFQRS-ECG result was consistent with nuclear scan results in 14 of 18 patients. The HFQRS-ECG and nuclear results differed in: (1) one patient who had a low score positive MPI, negative HFQRS-ECG and normal coronary angiogram; (2) one patient who had a small reversible anterior wall perfusion defect, 60% LAD lesion on angiogram but a negative HF-QRS result; and (3) two individuals who had positive HFQRS-ECG results in the face of negative nuclear scans but who did not undergo angiography. 12-lead HFQRS ECG had excellent sensitivity (87.5% based on 7/8 true positives correctly identified) and specificity (no worse than 80%, >8/10 true negatives correctly identified) for identifying CAD. 12-lead HFQRS ECG is an easily performed, inexpensive and potentially widely available technique that utilizes the same leads and electrodes as the conventional 12-lead ECG. It had accuracy comparable to MPI in this study. Resting 12-lead HFQRS ECG appears to be a very promising non-invasive technique for identifying CAD and may represent a viable alternative to many of the more expensive and time-consuming techniques presently utilized for non-invasively identifying CAD.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Eletrocardiografia/métodos , Processamento de Sinais Assistido por Computador , Idoso , Angiografia , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Software
11.
Clin Cardiol ; 26(12): 588-90, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14677814

RESUMO

This paper reports on two cases of large volume pericardiocentesis followed by transient severe acute left ventricular (LV) systolic failure in the absence of any prior history of LV dysfunction. Acute LV volume overload due to interventricular volume mismatch is believed by most authors to be the cause for this phenomenon. Another plausible physiopathologic explanation is the acute increase in "wall stress" (Laplace's law) due to acute distention of the cardiac chambers secondary to a sudden increase in venous return at high filling pressures, combined with a "vacuum" effect of the evacuated pericardial space.


Assuntos
Insuficiência Cardíaca/etiologia , Derrame Pericárdico/cirurgia , Pericardiocentese/efeitos adversos , Disfunção Ventricular Esquerda/etiologia , Adulto , Angiografia Coronária , Dispneia/etiologia , Ecocardiografia , Eletrocardiografia , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Humanos , Pessoa de Meia-Idade , Derrame Pericárdico/complicações , Pericardiocentese/métodos , Choque Cardiogênico/etiologia , Volume Sistólico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda
12.
Postgrad Med J ; 79(935): 490-504, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-13679544

RESUMO

The electrocardiogram is considered an essential part of the diagnosis and initial evaluation of patients with chest pain. This review summarises the information that can be obtained from the admission electrocardiogram in patients with ST elevation acute myocardial infarction, with emphasis on: (1) prediction of infarct size, (2) estimation of prognosis, and (3) the correlations between various electrocardiographic patterns and the localisation of the infarct and the underlying coronary anatomy.


Assuntos
Eletrocardiografia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/fisiopatologia , Necrose , Prognóstico , Fatores de Risco
13.
Cardiovasc Drugs Ther ; 15(2): 119-23, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11669404

RESUMO

BACKGROUND: In vitro studies showed that low-frequency ultrasound (US) causes blood clot dissolution. This effect is augmented with thrombolytics, microbubbles and microparticles. However, in animal models of transcutaneous delivery, US alone is not effective, probably due to attenuation of US energy by overlying skin. When combined with thrombolytics or microbubbles, transcutaneous US is highly effective. PURPOSE: To assess the synergistic effect of low-intensity low-frequency US and saline, hydroxyethyl starch (HAES) (a non-gas filled microparticle containing solution), streptokinase (STK), and their combination on blood clot disruption. METHODS: Human blood clots from 4 healthy donors, 2-4 hours old, were immersed for 0, 15, or 30 min in 37 degrees C in 10 ml of the above-mentioned solutions, and then were randomized to 10 sec of 20 kHz US or no US. The % difference in weight was calculated. RESULTS: Immersion for 30 min without US resulted in 13.8 +/- 1.2% clot lysis in saline, and 22.0 +/- 1.3%, 21.7 +/- 2.1%, and 23.2 +/- 1.9% in STK, HAES, and STK + HAES, respectively (p = 0.002). US augmented clot lysis in all groups and at all time points. With low-intensity US, HAES was not better than saline. However, the combination of HAES + STK with US resulted in larger clot disruption at 15 sec incubation time (46.7 +/- 3.2%) than with saline (29.6 +/- 2.1%), HAES (29.6 +/- 2.5%), and STK (32.8 +/- 3.6%) (p < 0.001). CONCLUSION: low-frequency, low-intensity US combined with HAES and STK resulted in greater clot disruption at short incubation times. This combination may assist in achieving faster reperfusion in in vivo models.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Sangue/diagnóstico por imagem , Fibrinolíticos/farmacologia , Derivados de Hidroxietil Amido/farmacologia , Estreptoquinase/farmacologia , Interações Medicamentosas , Humanos , Ultrassonografia
14.
Am J Cardiol ; 88(8): 842-7, 2001 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11676944

RESUMO

We investigated the impact of primary angioplasty compared with thrombolysis in 894 patients with ST elevation acute myocardial infarction and electrocardiographic grades II and III ischemia on enrollment. Patients were divided into 2 groups based on the enrollment electrocardiogram-grade III: (1) absence of an S wave below the isoelectric baseline in leads that usually have a terminal S configuration (leads V(1) to V(3)), or (2) ST J-point amplitude > or =50% of the R-wave amplitude in all other leads. To be included in the grade III group, grade III criteria in > or =2 adjacent leads were required. Patients with ST elevation but without grade III criteria were classified as having grade II. In-hospital mortality was 3.2% and 6.8% in the grade II (n = 616) and grade III (n = 278) groups, respectively (p = 0.016). In the grade II group, in-hospital mortality was similar in the thrombolysis and angioplasty subgroups (3.2% and 3.3%, p = 0.941). In patients with grade III, in-hospital mortality was 6.4% and 7.3%, respectively (p = 0.762). The odds ratio for the grade III group for death with thrombolysis was 2.06 (95% confidence intervals [CI] 0.82 to 5.19; p = 0.125); the odds ratio for primary angioplasty was 2.30 (95% CI 0.93 to 5.66; p = 0.07). In the thrombolysis group, reinfarction occurred in 3.3% and 6.5% of the grade II and grade III subgroups (p = 0.137). In the angioplasty group, reinfarction occurred in 1.3% and 4.4%, respectively (p = 0.239). Grade III ischemia on admission was associated with higher in-hospital and 30-day mortality and a higher rate of reinfarction. There was no difference in mortality between primary angioplasty and thrombolysis in the grade II and grade III ischemia patients.


Assuntos
Angioplastia Coronária com Balão , Eletrocardiografia , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/terapia , Isquemia Miocárdica/terapia , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
15.
J Thromb Thrombolysis ; 11(3): 223-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11577261

RESUMO

BACKGROUND: Glycoprotein IIb/IIIa antagonists and heparin are increasingly used for treatment of acute coronary syndromes. There is no data on the effect of these drugs on clot dissolution when combined with low frequency high-intensity ultrasonic energy. We examined a possible additive effect of low frequency high-intensity ultrasound with an antithrombotic, an antiplatelet and a fibrinolytic agent alone or in combinations for in vitro blood clot dissolution. METHODS: Human blood clots were incubated for 10', 15' and 30' in normal saline containing commonly used concentrations of heparin, tirofiban, t-PA and Optison (echocardiographic contrast agent) alone and in combinations. Clots were then randomly exposed to low frequency high-intensity ultrasound (27[emsp3 ]kHz) for 5 minutes. The percent difference in clot weight and the incremental effect of ultrasound energy were calculated. RESULTS: The most significant additive effect of ultrasound energy was detected with the combination of tirofiban and heparin (39+/-2% augmentation after 10' of incubation, p<0.0001). The greatest magnitude of percent clot weight reduction was observed with ultrasound energy combined with either t-PA alone (72+/-1% after 30' incubation, p=0.0016) or with the combination of t-PA, tirofiban, heparin and Optison (68+/-4% after 30' incubation, p=0.015). CONCLUSIONS: Application of low frequency high-intensity ultrasound has an additive effect to antiplatelet, antithrombotic and fibrinolytic drugs, specifically with the combination of tirofiban and heparin or with t-PA; this effect is observed after a short incubation period.


Assuntos
Coagulação Sanguínea , Fibrinolíticos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Terapia por Ultrassom/métodos , Ultrassonografia de Intervenção/métodos , Coagulação Sanguínea/efeitos dos fármacos , Terapia Combinada , Combinação de Medicamentos , Humanos , Técnicas In Vitro
16.
J Thromb Thrombolysis ; 11(3): 229-34, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11577262

RESUMO

BACKGROUND: Recently it has been demonstrated that transcutaneous delivery of ultrasound combined with tissue plasminogen activator (tPA) is more effective than tPA alone in recanalizing acutely thrombosed canine coronary arteries. In the present study, we investigated the incidence of partial (> or =50%) and complete (> or =70%) ST-segment elevation resolution in the precordial leads of dogs with experimental acute myocardial infarction that were treated with tissue plasminogen activator (tPA) alone or in combination with noninvasive transcutaneous delivery of high-intensity low frequency (27[emsp3 ]kHz) ultrasound. METHODS: Thrombotic coronary occlusions were induced in the midportion of left anterior descending (LAD) coronary artery by electrical injury in 24 dogs. All dogs were given intravenous heparin and tPA. Dogs were randomized to tPA alone (n=12) or combined tPA and adjunctive transcutaneous ultrasound (US) delivery (n=12). Electrocardiograms were recorded at 1) baseline, 2) after coronary occlusion just before initiation of therapy, 3) when coronary angiography showed recanalization of the coronary artery (or at 90 minutes after initiation of therapy if reperfusion did not occur before then) and 4) 90 minutes later. ST amplitude was measured in all 6 precordial leads. RESULTS: ST-segment amplitude at baseline was comparable between the tPA and the US group. Before initiation of therapy, sum of ST-segment elevation tended to be higher in the US group. At reperfusion and 90 minutes thereafter, sum of ST-segment amplitude tended to be smaller for the US group than in the tPA group (p<0.001 for the time effect; p=0.118 for the time x group interaction). Up to 90 minutes after initiation of therapy >/=50% resolution of the sum of precordial ST elevation was detected in 7 out of 11 dogs (63.6%) in the tPA group versus 10 out of 11 dogs (90.9%) in the US group. Ninety minutes thereafter, 3 out of 7 dogs in the tPA group (42.9%) versus 9 of 11 dogs in the US group (81.8%) had >/=50% resolution of the sum of precordial ST elevation. CONCLUSIONS: The combination of tPA with noninvasive transcutaneous delivery of low frequency high-intensity ultrasound resulted in greater resolution of ST-segment elevation when reperfusion occurs and 90 minutes thereafter, as well as a higher rate of epicardial coronary artery reperfusion.


Assuntos
Infarto do Miocárdio/terapia , Terapia Trombolítica/métodos , Terapia por Ultrassom/métodos , Ultrassonografia de Intervenção/métodos , Animais , Terapia Combinada , Modelos Animais de Doenças , Cães , Eletrocardiografia , Infarto do Miocárdio/fisiopatologia , Reperfusão Miocárdica/métodos , Terapia Trombolítica/normas , Ativador de Plasminogênio Tecidual/administração & dosagem , Ultrassonografia de Intervenção/normas
17.
Thromb Res ; 103(4): 337-44, 2001 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-11562343

RESUMO

OBJECTIVE: Ultrasound is emerging as a promising modality for recanalization of acutely thrombosed blood vessels, especially when associated with fibrinolytics. We assessed the efficacy of ultrasound combined with saline, heparin, eptifibatide, aspirin, and streptokinase in disruption of fresh as well as aged human blood clots, using an in vitro model. METHODS: Blood clots from five donors, 2-4 or 48 hours old, were cut into 250-400 mg slices and immersed for 1, 15, or 30 min in 10 ml saline containing either heparin, eptifibatide, aspirin, streptokinase, or saline alone. Clots were then randomized to 10 s of 20 kHz ultrasound or immersion alone. After treatment, the percentage difference in weight was calculated. RESULTS: Immersion of fresh clots without ultrasound in eptifibatide and heparin resulted in significantly more clot lysis than immersion in saline, aspirin, and streptokinase. Immersion of aged thrombi without ultrasound in heparin, eptifibatide, and aspirin had no additive effect over immersion in saline. Ultrasound enhanced clot disruption in all five solutions, in each immersion time and both in fresh and aged clots. Heparin and aspirin had no additive effect, compared with saline, on ultrasound disruption of both fresh and aged clots, whereas eptifibatide was less effective than saline. In contrast, streptokinase greatly enhanced disruption of both fresh (P=.004) and aged (P<.001) thrombi by ultrasound. The combinations of ultrasound with saline, heparin, eptifibatide, and aspirin were less effective on aged than fresh thrombi, whereas the combination of ultrasound with streptokinase was equally effective on fresh and aged thrombi. CONCLUSIONS: Using a simple in vitro model, we found that the combination of streptokinase and low-frequency ultrasound had a synergistic effect on disruption of both fresh and aged blood clots. Further studies are needed to assess the role of heparin and antiplatelet agents in augmenting clot disruption by ultrasound in in vivo models of acute and subacute thrombosis.


Assuntos
Fibrinólise/efeitos dos fármacos , Fibrinólise/efeitos da radiação , Fibrinolíticos/farmacologia , Ultrassom , Aspirina/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/efeitos da radiação , Terapia Combinada , Eptifibatida , Heparina/farmacologia , Humanos , Cinética , Peptídeos/farmacologia , Estreptoquinase/farmacologia
18.
J Am Soc Echocardiogr ; 14(7): 668-75, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11447411

RESUMO

We assessed the utility of milrinone to predict recovery of function after surgical myocardial revascularization in patients with severe baseline left ventricular systolic dysfunction caused by coronary artery disease (CAD). Prediction of viable myocardial segments that will regain function after revascularization may help in the selection of patients who will benefit from coronary artery bypass graft surgery (CABG) as well as aid in the choice of target sites for coronary revascularization. We investigated 20 consecutive patients with CAD and left ventricular ejection fraction < or = 40% who had evidence of myocardial viability by either thallium scan or dobutamine viability test and were candidates for elective CABG. Left ventricular regional wall motion and global ejection fraction were assessed by transesophageal echocardiography in the operating room. Measurements were done before and 10 minutes after milrinone infusion, and immediately after CABG. Left ventricular wall motion score was derived by means of a 12-segment model. Functional improvement for each segment was defined as a wall motion change > 1. Baseline ejection fraction was 27% +/- 5% (mean +/- SD). Ejection fraction increased to 35% +/- 5% after milrinone infusion (P < .0001) and to 36% +/- 6% after CABG (P < .0001). Post-CABG ejection fraction was significantly correlated with postmilrinone ejection fraction (r = 0.65, P < .0001). Milrinone infusion resulted in augmentation of contraction in 98 of the 209 abnormal segments (wall motion score > or = 2); 91 (92.9%) of these improved after CABG. One hundred nine of the 111 segments that showed no improvement with milrinone did not improve after revascularization (98.2%). Seventy-three segments were akinetic or dyskinetic at baseline; 46 (63.0%) of these improved with milrinone. Improvement in regional wall motion after revascularization was detected in 84.8% of the segments that improved with milrinone versus only 3.7% of the segments that did not improve with milrinone. In patients with ischemic cardiomyopathy, improvement in left ventricular function (segmental wall motion and global ejection fraction) during milrinone infusion is highly predictive of improvement after CABG.


Assuntos
Ponte de Artéria Coronária , Ecocardiografia Transesofagiana , Milrinona , Disfunção Ventricular Esquerda/cirurgia , 3',5'-AMP Cíclico Fosfodiesterases , Idoso , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3 , Dobutamina , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Contração Miocárdica/efeitos dos fármacos , Revascularização Miocárdica , Seleção de Pacientes , Inibidores de Fosfodiesterase/farmacologia , Projetos Piloto , Valor Preditivo dos Testes , Ventriculografia com Radionuclídeos , Recuperação de Função Fisiológica , Volume Sistólico/efeitos dos fármacos , Radioisótopos de Tálio , Disfunção Ventricular Esquerda/complicações , Função Ventricular Esquerda/efeitos dos fármacos
20.
Am Heart J ; 141(6): 915-24, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11376304

RESUMO

BACKGROUND: The grade of ischemia, as detected by the relation between the QRS complex and ST segment on the admission electrocardiogram, is associated with larger infarct size and increased mortality rates in acute myocardial infarction. METHODS: We assessed the correlation between left ventricular function and the admission electrocardiogram in 151 patients with first anterior acute myocardial infarction who received thrombolytic therapy and underwent cardiac catheterization at 90 minutes and before hospital discharge. The number of leads with ST elevation, sum of ST elevation, maximal Selvester score, and the presence of severe (grade 3) ischemia were determined in each electrocardiogram. Left ventricular ejection fraction, the number of chords with wall motion abnormalities, and the severity of dysfunction (SD/chord) were determined. RESULTS: At 90 minutes, the 39 ischemia grade 3 patients had lower ejection fraction than the 112 grade 2 patients. Both at 90 minutes and at hospital discharge, the grade 3 group had more chords with wall motion abnormalities and more severe regional dysfunction (SD/chord). However, the number of leads with ST elevation, sum of ST elevation, and maximal Selvester score had no correlation with ejection fraction at 90 minutes and only mild correlation with the extent of dysfunction (number of chords) at 90 minutes. There was no correlation between either the number of leads with ST elevation or the sum of ST elevation and the severity of regional dysfunction. CONCLUSIONS: The number of leads with ST elevation, sum of ST elevation, and maximal Selvester score had only mild correlation with the extent of myocardial dysfunction but not with the severity of dysfunction. Grade 3 ischemia is predictive of more extensive myocardial involvement and greater severity of regional dysfunction.


Assuntos
Eletrocardiografia/normas , Infarto do Miocárdio/diagnóstico , Disfunção Ventricular Esquerda/diagnóstico , Idoso , Angiografia Coronária , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Terapia Trombolítica , Disfunção Ventricular Esquerda/fisiopatologia
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