RESUMO
Delayed recovery of contractile function after myocardial ischemia may be due to prolonged recovery of high-energy phosphates, persistent acidosis, increased inorganic phosphate, and/or calcium loading. To examine these potential mechanisms, metabolic parameters measured by 31P nuclear magnetic resonance spectroscopy, and spontaneous diastolic myofilament motion caused by sarcoplasmic reticulum-myofilament calcium cycling indexed by the scattered light intensity fluctuations (SLIF) it produces in laser beam reflected from the heart, were studied in isolated atrioventricularly blocked rat hearts (n = 10) after 65 min of ischemia at 30 degrees C. All metabolic parameters recovered to their full extent 5 min after reperfusion. Developed pressure evidenced a small recovery but then fell abruptly. This was accompanied by an increase in end diastolic pressure to 37 +/- 5 mm Hg and a fourfold increase in SLIF, to 252 +/- 58% of baseline. In another series of hearts initial reperfusion with calcium of 0.08 mM prevented the SLIF rise and resulted in improved developed pressure (74 +/- 3% vs. 39 +/- 13% of control), and lower cell calcium (5.9 +/- 3 vs. 10.3 +/- 1.4 mumol/g dry wt). Thus, during reperfusion, delayed contractile recovery is not associated with delayed recovery of pH, inorganic phosphate, or high-energy phosphates and can be attributed, in part, to an adverse effect of calcium loading which can be indexed by increased SLIF occurring at that time.
Assuntos
Cálcio/metabolismo , Reperfusão Miocárdica , Miocárdio/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Doença das Coronárias/metabolismo , Diástole , Espectroscopia de Ressonância Magnética , Masculino , Contração Miocárdica , Fosfocreatina/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Isometric performance at 29degreesC was measured in left ventricular trabeculae carneae from young adult (6-mo) and aged (25-mo) rats (n equals 18 in each group). Active tension and maximal rate of tension development did not differ with age, but contraction duration was 255plus or minus6 ms in the young adult and 283plus or minus6 ms in the aged group (P less than0.001). Although catecholamine content per gram heart weight was less in the aged myocardium, additional experiments showed that neither 1 times 10-6 M propranolol nor pretreatment with 6-hydroxydopamine eliminated the age difference in contraction duration. To determine if this age difference resulted from a prolonged active state, electromechanical dissociation and the overshoot of contraction duration during recovery from hypoxia were measured. During paired stimulation greater mechanical refractoriness was found in aged muscles (P less than0.01), but intracellular action potential recordings showed no age difference in the electrical refractory period. On recovery from hypoxia, contraction duration overshoot was 117plus or minus 4percent of control in the young and 138plus or minus 4percent of control in the aged muscles (P less than0.01). The greater electromechanical dissociation and greater overshoot in contraction duration following hypoxia in aged myocardium suggests that prolonged contraction duration in aged myocardium results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content.
Assuntos
Envelhecimento , Coração/fisiologia , Potenciais de Ação , Animais , Catecolaminas/análise , Estimulação Elétrica , Coração/efeitos dos fármacos , Coração/fisiopatologia , Hidroxidopaminas/farmacologia , Hipóxia/fisiopatologia , Masculino , Miocárdio/análise , Propranolol/farmacologia , Ratos , Período Refratário Eletrofisiológico , Estresse Mecânico , Fatores de TempoRESUMO
Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin-oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin-oxygen affinity, a 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment-length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin-oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia.
Assuntos
Compostos de Anilina/administração & dosagem , Antidrepanocíticos/administração & dosagem , Hemoglobinas/metabolismo , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/prevenção & controle , Oxigênio/metabolismo , Fosfocreatina/metabolismo , Propionatos/administração & dosagem , Animais , Cães , Isquemia Miocárdica/fisiopatologia , Consumo de OxigênioRESUMO
Cardiovascular aging is associated with decreased endothelial vasoreactivity and prolonged diastolic relaxation. As diminished NO signaling contributes to age-associated endothelial dysfunction, we tested the hypothesis that impaired NO signaling or bioactivity also contributes to slowed ventricular relaxation with age. Accordingly, we measured myocardial NO synthase (NOS) enzyme activity, protein abundance, and cGMP production in old (22 to 25 months) and young adult (4 to 7 months) male Wistar rats. Both NOS3 protein abundance and calcium-dependent NOS activity were elevated in old compared with young adult hearts (7.2+/-1.1 versus 4.2+/-0.6 pmol/mg protein, respectively, P=0.03). However, NOS activity and protein abundance were similar in isolated myocytes, indicating that endothelial NOS likely explains the age difference. Cardiac effluent cGMP (enzyme immunoassay) was 4.8-fold higher (1794+/-373 fmol/min per mg heart tissue) in older versus younger hearts (P=0.003). To assess NO pathway responsiveness, we administered the NOS substrate l-arginine (100 micrometer) to isolated perfused rat hearts. Baseline isovolumic relaxation (tau) was prolonged in old (42.9+/-2.5 ms, n=16) versus young hearts (36.0+/-1.9 ms, n=11, P=0.03). l-Arginine decreased tau (P<0.001) and left ventricular end-diastolic pressure in both old and young hearts. Supporting an NO/cGMP-mediating mechanism, the NO donor sodium nitroprusside reduced tau (maximal effect, -14+/-2%, n=5, P<0.001), and this lusitropic effect was attenuated by the soluble guanylyl cyclase inhibitor 1H:-[1,2,4]oxadiazolo-[4,3,-a]quinoxalin-1-one (n=7, P<0.001). Thus, the NO-cGMP pathway is upregulated in the endothelial cells of aged hearts. l-Arginine, the NOS precursor, enhances ventricular relaxation in old and young hearts, indicating that the NOS pathway may be exploited to modulate diastolic function in aged myocardium.
Assuntos
Envelhecimento/fisiologia , GMP Cíclico/metabolismo , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Animais , Arginina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Coração/efeitos dos fármacos , Coração/fisiologia , Técnicas In Vitro , Masculino , Contração Miocárdica/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III , Nitroprussiato/farmacologia , Oxidiazóis/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais , Regulação para CimaRESUMO
The appearance of 13C label in glutamate has been used to quantify cellular tricarboxylic acid (TCA) cycle activity using 13C-NMR spectroscopy. Glutamate is linked to the TCA cycle by the amino-transferase reactions, however the consequences of alterations in amino-transferase activity on glutamate labelling kinetics, at a constant total tricarboxylic acid cycle activity, have not been investigated. Aspartate amino-transferase activity in [2-13C]acetate-perfused beating rat hearts was found to be similar to total TCA cycle flux in the presence of normal perfusion conditions and was reduced by more than 50% with the subsequent administration of amino-oxyacetic acid (AOA). AOA did not reduce contractile or kinetic measures of total TCA cycle flux, but did slow the 13C labelling of glutamate, in accord with current mathematical predictions. The impact of similar reductions in amino-transferase activity on estimates of total TCA cycle flux derived from several previously reported methods was also evaluated. Because total TCA cycle and the amino-transferase activities both affect the kinetics of 13C-glutamate labelling and because the amino-transferase activities are often unknown under physiologic conditions and can be reduced under pathologic conditions, the calculation of total TCA cycle flux from 13C-NMR data in the future is probably best accomplished either with a sufficiently sophisticated mathematical model that assesses amino-transferase activity or with an empiric model that is relatively insensitive to variations in amino-transferase activity.
Assuntos
Aspartato Aminotransferases/metabolismo , Ciclo do Ácido Cítrico , Ácido Glutâmico/metabolismo , Miocárdio/enzimologia , Ácido Amino-Oxiacético/farmacologia , Animais , Isótopos de Carbono , Glucose/metabolismo , Cinética , Espectroscopia de Ressonância Magnética , Masculino , Matemática , Modelos Biológicos , Ratos , Ratos WistarRESUMO
BACKGROUND: The benefit of intravenous thrombolytic therapy in elderly patients with myocardial infarction is uncertain. There are no randomized trials of thrombolytic efficacy or observational studies of clinical effectiveness that focus specifically on the elderly. METHODS AND RESULTS: To determine whether thrombolytic therapy for elderly patients is associated with a survival advantage in a large observational database, we conducted a retrospective cohort study of 7864 Medicare fee-for-service patients aged 65 to 86 years with the primary discharge diagnosis of acute myocardial infarction who were admitted with clinical and ECG indications for thrombolytic therapy and no absolute contraindications. The study included all US acute care nongovernment hospitals without on-site angioplasty capability. Using proportional-hazards methods, we found that in a comprehensive multivariate model, there was a significant interaction (P<0.001) between age and the effect of thrombolytic therapy on 30-day mortality rates. For patients 65 to 75 years old, thrombolytic therapy was associated with a survival benefit, consistent with randomized trials. Among patients aged 76 to 86 years, thrombolytic therapy was associated with a survival disadvantage, with a 30-day mortality hazard ratio of 1.38 (95% CI 1. 12 to 1.71, P=0.003). For these patients, there was no benefit from thrombolytic therapy in any clinical subgroup. CONCLUSIONS: In nationwide clinical practice, thrombolytic therapy for patients >75 years old is unlikely to confer survival benefit and may have a significant survival disadvantage. Reperfusion research that is focused on elderly patients is urgently needed.
Assuntos
Infarto do Miocárdio/terapia , Terapia Trombolítica , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Estudos de Coortes , Feminino , Humanos , Injeções Intravenosas , Masculino , Infarto do Miocárdio/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Silent myocardial ischemia as detected on Holter electrocardiographic (ECG) monitoring is present in greater than 50% of patients with unstable angina despite intensive medical therapy. The presence and the extent of silent ischemia have been correlated with an increased risk of early (1 month) unfavorable outcome including myocardial infarction and need for coronary revascularization for persistent symptoms. Seventy patients with unstable angina who had undergone continuous ECG monitoring for silent ischemia were followed up for 2 years; 37 patients (Group I) had Holter ECG evidence of silent ischemia at bed rest in the coronary care unit during medical treatment with nitrates, beta-receptor blockers and calcium channel antagonists; the other 33 patients (Group II) had no ischemic ST segment changes (symptomatic or silent) on Holter monitoring. Over a 2 year follow-up period, myocardial infarction occurred in 10 patients in Group I (in 2 it was fatal) compared with one nonfatal infarction in Group II (p less than 0.01 by Kaplan-Meier analysis); revascularization with either coronary bypass surgery or angioplasty for symptomatic ischemia was performed in 11 Group I and 5 Group II patients (p less than 0.05). Multivariate Cox's hazard analysis demonstrated that the presence of silent ischemia was the best predictor of 2 year outcome. Therefore, persistent silent myocardial ischemia despite medical therapy in patients with unstable angina carries adverse prognostic implications that persist over a 2 year period.
Assuntos
Angina Pectoris/fisiopatologia , Angina Instável/fisiopatologia , Doença das Coronárias/complicações , Infarto do Miocárdio/etiologia , Doença das Coronárias/fisiopatologia , Eletrocardiografia , Seguimentos , Humanos , Monitorização Fisiológica , Infarto do Miocárdio/mortalidade , Prognóstico , RiscoRESUMO
A randomized prospective clinical trial compared combined treatment with intraaortic balloon pumping and intravenous nitroglycerin for 4 to 5 days with routine clinical management in 20 patients with extensive myocardium at risk for infarction as evidenced by a thallium defect score of 7.0 units or greater. No significant differences in mortality or clinical outcome were observed between the 10 patients receiving the combined treatment and the 10 receiving routine management. In 14 patients two-dimensional echocardiograms obtained 6 to 24 hours after the onset of symptoms and at follow-up 6 to 16 days later (after completion of combined intraaortic balloon pumping plus nitroglycerin therapy) were analyzed to determine whether infarct segment or noninfarct segment lengths were affected by therapy. Among these 14 patients, 5 (3 receiving the combined therapy and 2 receiving routine management) demonstrated an increase in infarct segment length of greater than 1.0 cm. Mean infarct segment length increased 0.30 +/- 0.44 cm in patients receiving the combined therapy and 0.29 +/- 0.36 cm in patients on routine management (p = NS). In contrast, noninfarct segment length increased greater than 1.0 cm (mean increase 1.20 +/- 0.39) in five of seven patients on routine management but in none of 7 patients receiving intraaortic balloon pumping plus nitroglycerin therapy (mean decrease 0.22 +/- 0.20 cm) (p less than 0.05). No significant differences were noted in left ventricular ejection fraction, as measured by gated blood pool scintigraphy, or thallium perfusion defect score in a comparison of day 1 (pretreatment) with day 4 thallium or day 7 to 14 gated blood pool scintigrams. Thus, in patients with extensive myocardium at risk, it is unlikely that a reduction in mortality or a significant improvement in myocardial perfusion or ventricular function can be obtained by early intervention with intraaortic balloon pumping in combination with nitroglycerin. Although this combined therapy failed to prevent infarct segment lengthening (infarct expansion), the combined afterload-lowering effects of intraaortic balloon pumping and nitroglycerin did appear to prevent dilation or remodeling of noninfarcted segments during the first 2 weeks after acute myocardial infarction.
Assuntos
Circulação Assistida , Balão Intra-Aórtico , Infarto do Miocárdio/terapia , Nitroglicerina/administração & dosagem , Adulto , Circulação Assistida/efeitos adversos , Cateterismo Cardíaco , Ensaios Clínicos como Assunto , Terapia Combinada , Creatina Quinase/sangue , Ecocardiografia , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hemodinâmica , Humanos , Infusões Parenterais , Balão Intra-Aórtico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Nitroglicerina/efeitos adversos , Pré-Medicação , Estudos Prospectivos , Cintilografia , Distribuição Aleatória , Volume SistólicoRESUMO
Reports of acute ischemic events after withdrawal of calcium antagonist therapy in outpatients and during bypass surgery in patients with prior angina at rest prompted the examination of the effect of nifedipine withdrawal in 81 patients who had completed a prospective, double-blind randomized trial of nifedipine versus placebo for rest angina. Thirty-nine patients underwent bypass surgery for uncontrolled angina or left main coronary artery disease. No significant difference between patients withdrawn from nifedipine or placebo was seen in the incidence of perioperative myocardial infarction, hypotension requiring intraaortic balloon counterpulsation, vasopressor or vasodilator requirements or incidence of significant arrhythmias. An additional 42 patients had completed 2 years on a protocol consisting of nitrates and propranolol in addition to nifedipine or placebo. During a mean of 66 hours of continuous monitoring after withdrawal of nifedipine or placebo, heart rate and blood pressure were unchanged. A worsening of previously present angina at rest occurred in five patients who had continued to experience rest angina before drug withdrawal, four of whom were withdrawn from nifedipine. No patient with class I to III angina experienced new onset of rest angina during drug withdrawal. No patient experienced myocardial infarction. There was no significant difference between patients withdrawn from nifedipine or placebo in the duration or frequency of ischemic ST changes on continuous electrocardiographic monitoring, or in duration or positive results of serial exercise treadmill testing. Thus, no early adverse effects of acute nifedipine withdrawal were found in patients with prior rest angina at the time of bypass surgery or in stable patients receiving long-term medical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Angina Pectoris/fisiopatologia , Angina Instável/fisiopatologia , Ponte de Artéria Coronária , Nifedipino/efeitos adversos , Síndrome de Abstinência a Substâncias/fisiopatologia , Angina Instável/induzido quimicamente , Angina Instável/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Ensaios Clínicos como Assunto , Método Duplo-Cego , Eletrocardiografia , Teste de Esforço , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêuticoRESUMO
OBJECTIVES: We tested the hypothesis that acute intravenous verapamil acutely enhances aerobic exercise performance in healthy older individuals in association with a combined reduction of ventricular systolic and arterial vascular stiffnesses. BACKGROUND: Age-related vascular stiffening coupled with systolic ventricular stiffening may limit cardiovascular reserve and, thus, exercise performance in aged individuals. METHODS: Nineteen healthy volunteers with mean age 70 +/- 10 years underwent maximal-effort upright ergometry tests on two separate days after receiving either 0.15 mg/kg i.v. verapamil or 0.5 N saline in a double-blind, randomized, crossover study. RESULTS: Baseline vascular stiffness, indexed by arterial pulse-wave velocity (Doppler) and augmentation index (carotid tonometry) declined with verapamil (-5.9 +/- 2.1% and -31.7 +/- 12.8%, respectively, both p < 0.05). Preload-adjusted maximal ventricular power, a surrogate for ventricular end-systolic stiffness, also declined by -9.5 +/- 3.6%. Peripheral resistance and peak filling rate were unchanged. With verapamil, exercise duration prior to the anaerobic threshold (AT) increased by nearly 50% (260 +/- 129 to 387 +/- 176 s) with a corresponding 13.4 +/- 4.7% rise in oxygen consumption (VO2) at that time (both p < 0.01). Total exercise duration prolonged by +6 +/- 2.7% (p < 0.05) with no change in maximal VO2. Baseline cardiodepression from verapamil reversed by peak exercise with net increases in stroke volume and cardiac output (p < 0.05). CONCLUSIONS: Acute intravenous verapamil reduces ventriculovascular stiffening and improves aerobic exercise performance in healthy aged individuals. This highlights a role for heart-arterial coupling in modulating exertional capacity in the elderly, suggesting a potentially therapeutic target for aged individuals with exertional limitations.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Teste de Esforço/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos , Verapamil/farmacologia , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Método Duplo-Cego , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
To evaluate functional recovery in 20 consecutive patients with acute myocardial infarction who received recombinant tissue-type plasminogen activator, serial two-dimensional echocardiograms were performed before and immediately after tissue plasminogen activator administration and at 1 and 10 days postinfarction. Tissue plasminogen activator was administered intravenously (17 patients) or by intracoronary infusion (3 patients) after angiographic confirmation of total occlusion. Reperfusion, documented by angiography, occurred in 13 of the 20 patients. The mean time from onset of chest pain to thrombolysis was 5.1 +/- 1.1 hours. Echocardiograms were evaluated for regional function with a visual semiquantitative scoring system by two independent observers who had no knowledge of patient identity, temporal sequence, therapy or effect of therapy. There was no immediate or 24 hour improvement in wall motion. At day 10 compared with pretreatment, 28 of 33 reperfused infarct zone segments versus 6 of 20 nonreperfused infarct segments demonstrated improved wall motion (p = 0.01). This improvement did not relate to time from onset of chest pain to successful thrombolysis. Of reperfused infarct zone segments in the distribution of coronary artery balloon dilation, 19 of 23 segments exhibited improvement versus 7 of 17 (reperfused, no angioplasty) and 6 of 20 (nonreperfused, no angioplasty) segments (p = 0.001). Infarct zone segments reperfused at the time of ongoing chest pain demonstrated functional recovery compared with segments reperfused in the absence of chest pain (18 of 23 versus 10 of 20, respectively; p = 0.05). Thus, in this uncontrolled series, there was echocardiographically detectable improvement in function of reperfused infarct segments 10 days after coronary thrombolysis with recombinant tissue plasminogen activator.
Assuntos
Angioplastia com Balão , Doença das Coronárias/tratamento farmacológico , Contração Miocárdica/efeitos dos fármacos , Ativadores de Plasminogênio/uso terapêutico , Adulto , Idoso , Arteriopatias Oclusivas/tratamento farmacológico , Arteriopatias Oclusivas/fisiopatologia , Arteriopatias Oclusivas/terapia , Angiografia Coronária , Doença das Coronárias/fisiopatologia , Doença das Coronárias/terapia , Ecocardiografia , Feminino , Fibrinólise , Humanos , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica , Recidiva , Fatores de TempoRESUMO
Unstable angina is a common ischemic syndrome that is characterized by chest pain occurring at rest often with transient ischemic electrocardiographic changes. Although most patients with unstable angina experience relief of pain with intensive medical therapy while in the coronary care unit, they subsequently have a high incidence of unfavorable cardiac events usually occurring within several months. Continuous electrocardiographic monitoring for ischemia has demonstrated a relatively high incidence of ischemic episodes both in patients with stable and unstable angina pectoris. The prognostic importance of such findings has been previously uncertain. The prognostic significance of silent myocardial ischemia in patients with unstable angina receiving intensive medical therapy has been addressed in a study of hospitalized patients in a coronary care unit. All patients were treated with nitrates, nifedipine, and propranolol. Continuous two-channel electrocardiographic monitoring was performed during the first two days of medical therapy. The electrocardiographic recordings were interpreted blindly for frequency and duration of ischemic changes, and these episodes were determined to be either symptomatic or silent. The prevalence of silent ischemic episodes, their prognostic significance, their contribution to the total ischemic burden, and the effects of different medical regimens on these variables are discussed.
Assuntos
Doença das Coronárias/diagnóstico , Eletrocardiografia , Monitorização Fisiológica , Antagonistas Adrenérgicos beta/uso terapêutico , Angina Instável/complicações , Ponte de Artéria Coronária , Doença das Coronárias/terapia , Quimioterapia Combinada , Humanos , Nifedipino/uso terapêutico , Nitratos/uso terapêutico , Prognóstico , Propranolol/uso terapêuticoRESUMO
Unstable angina pectoris is a high-risk ischemic syndrome with complex, interacting pathophysiologic mechanisms that include coronary atherosclerosis, coronary vasoconstriction, and thrombosis. The roles of various medical strategies, including nitrates, beta blockers, calcium antagonists, and antiplatelet, anticoagulant, and thrombolytic agents, are discussed in conjunction with revascularization procedures such as coronary angioplasty and bypass surgery.
Assuntos
Angina Pectoris/tratamento farmacológico , Angina Instável/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Angina Instável/cirurgia , Angioplastia com Balão , Anticoagulantes/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ensaios Clínicos como Assunto , Ponte de Artéria Coronária , Método Duplo-Cego , Humanos , Propranolol/uso terapêutico , Distribuição Aleatória , RiscoRESUMO
The ability of a strongly positive stress test to predict left main coronary artery disease in people with suspected coronary artery disease but with minimal or no angina was investigated in 40 such patients. Nine had a history of myocardial infarction but no angina. Thirty-one had mild angina or a history of mild angina. The stress electrocardiograms were analyzed according to criteria known to be associated with left main coronary artery disease in moderately or severely symptomatic patients; (1) early S-T segment changes (stage I or II of exercise), (2) 2 mm or more S-T segment depression, (3) downsloping S-T segments, (4) associated exercise-induced hypotension, (5) prolonged S-T segment changes after the test (greater than or equal to 8 minutes) and (6) anterior and inferior S-T segment depression. The prevalence of left main coronary artery disease was 35 percent and that of any severe coronary artery disease 75 percent. The criterion of anterior and inferior electrocardiographic changes with exercise was most predictive of left main coronary artery disease (P less than 0.01 by chi 2). Exercise electrocardiography is useful in the prediction of left main or other severe coronary artery disease even when performed in patients who have minimal angina or in those who are asymptomatic after myocardial infarction.
Assuntos
Doença das Coronárias/diagnóstico , Teste de Esforço , Adulto , Idoso , Angina Pectoris/etiologia , Cateterismo Cardíaco , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnósticoRESUMO
Unstable angina pectoris may be manifested as new-onset angina, a change in the anginal pattern, pain at rest with associated electrocardiographic (ECG) changes, or postinfarction angina. Of these, pain at rest with ischemic ECG changes is known to be associated with the poorest prognosis. The pathogenesis of unstable angina pectoris involves a combination of a fixed atherosclerotic obstruction and a dynamic component related to coronary vasoconstriction, thrombus formation, or both. Long-acting nitrates, inhibitors of platelet aggregation, beta blockers, and calcium antagonists are among the agents that have been shown to be effective in the medical management of unstable angina. A study now in progress is evaluating the routine use of thrombolytic therapy for this indication. Although alleviation of symptoms and prevention of death and myocardial infarction are important therapeutic goals, the overall efficacy of a particular medical therapy can best be assessed by objective evaluation of its ability to control ischemia, using such techniques as exercise scintigraphy and ambulatory ECG monitoring. Cardiac catheterization and revascularization are indicated for patients with unstable angina who continue to experience symptoms or who show evidence of silent ischemia despite medical therapy. A study is under way to determine the advisability of routine revascularization of such patients. Revascularization will provide symptomatic relief in most patients with unstable angina and may prolong survival and improve left ventricular function in certain subsets.
Assuntos
Angina Instável/terapia , Angina Instável/tratamento farmacológico , Angina Instável/fisiopatologia , Angina Instável/cirurgia , Humanos , Revascularização Miocárdica , Resultado do TratamentoRESUMO
The acute effects of nifedipine withdrawal were studied in 81 patients with angina at rest who had completed a prospective, double-blind, randomized trial of nifedipine versus placebo. Thirty-nine of the 81 patients (group 1) were withdrawn from nifedipine or placebo at the time of coronary artery bypass surgery for uncontrolled angina or left main coronary artery disease. When the patients withdrawn from nifedipine were compared with those withdrawn from placebo, no significant differences were seen in the incidence of hypotension, myocardial infarction, significant arrhythmias or vasopressor or vasodilator requirements during the perioperative period. Forty-two patients (group 2) completed 2 years on a protocol consisting of nitrates and propranolol, in addition to nifedipine or placebo. These patients were hospitalized for a controlled withdrawal of the study drug (nifedipine or placebo), and no significant difference was noted in either exercise performance on serial treadmill testing or the number or duration of episodes of ischemic ST-segment changes during continuous electrocardiographic monitoring. Eight patients continued to experience occasional episodes of angina at rest. Angina at rest recurred during the withdrawal period in 5 of these 8 patients. Four of these 5 patients were withdrawn from nifedipine. Of the 34 stable patients in group 2 who were not experiencing angina at rest before withdrawal, none had angina at rest during the withdrawal study period. Thus, there were no early untoward effects of acute nifedipine withdrawal either in patients undergoing coronary bypass surgery or in stable patients on long-term medical therapy. However, patients with persistent symptoms of angina at rest may experience early recurrent ischemia upon withdrawal from nifedipine.
Assuntos
Angina Pectoris/tratamento farmacológico , Angina Instável/tratamento farmacológico , Doença das Coronárias/induzido quimicamente , Hipotensão/induzido quimicamente , Nifedipino/efeitos adversos , Síndrome de Abstinência a Substâncias , Ponte de Artéria Coronária , Método Duplo-Cego , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esforço Físico , Estudos Prospectivos , Distribuição Aleatória , DescansoRESUMO
The effect of lidocaine on His-Purkinje conduction in dogs with ischemic damage to the His bundle was compared with the effect of lidocaine in normal dogs. The anterior septal artery was ligated in 14 dogs, and 30 minutes later atrial pacing was performed to increase residual ischemic damage. Four to 6 days later, His bundle recordings were obtained during sinus rhythm and atrial pacing before and after the administration of lidocaine in a dose of 2 mg/kg and a total dose of 4 mg/kg. His bundle recordings were also obtained in nine control animals beofre and after the administration of lidocaine. Lidocaine significantly increased the H-V time in the animals with ischemic damage during sinus rhythm and at all packing rates. It also resulted in advanced His-Purkinje conduction defects including His bundle block and right bundle branch block in these animals. In contrast, the effect of lidocaine in the normal animals was negligible. It is concluded that lidocaine significantly depresses His-Purkinje conduction in the setting of preexisting ischemic damage. These results suggest that lidocaine may be used as a diagnostic tool to unmask latent His-Purkinje conduction defects due to ischemia.
Assuntos
Fascículo Atrioventricular/efeitos dos fármacos , Doença das Coronárias/fisiopatologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Lidocaína/farmacologia , Ramos Subendocárdicos/efeitos dos fármacos , Animais , Fascículo Atrioventricular/fisiopatologia , Estimulação Cardíaca Artificial , Cães , Eletrocardiografia , Injeções Intravenosas , Lidocaína/administração & dosagem , Ramos Subendocárdicos/fisiopatologiaRESUMO
Coronary disease causes the majority of perioperative complications after peripheral vascular surgery. Twenty-four patients with stable coronary disease undergoing peripheral revascularization were studied using continuous electrocardiographic monitoring to determine the incidence of perioperative asymptomatic myocardial ischemia and its relation to postoperative clinical ischemic events. Patients were monitored preoperatively (17 +/- 1 hours), intraoperatively and postoperatively (29 +/- 2 hours) using 4-channel calibrated amplitude-modulated units. Fifteen patients (63%) had early postoperative silent ischemia; 3 also had preoperative silent ischemia and 5 intraoperative transient ischemia. Patients with and without silent ischemia had similar clinical characteristics, perioperative antianginal medications and postoperative episodes of hemodynamic instability. However, 8 of 15 patients (53%) with silent ischemia had postoperative clinical ischemic events (2 had myocardial infarction, 2 had new congestive heart failure and 4 had new rest angina), versus only 1 of 9 patients (11%) without silent ischemia who had angina (p less than 0.05). Early postoperative silent myocardial ischemia occurs frequently after vascular surgery and is associated with postoperative clinical ischemic events.
Assuntos
Doença das Coronárias/epidemiologia , Complicações Intraoperatórias , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Vasculares , Idoso , Doença das Coronárias/etiologia , Eletrocardiografia Ambulatorial , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Prognóstico , Método Simples-CegoRESUMO
Estrogen therapy is associated with a 50% reduction in the clinical manifestations of coronary artery disease in postmenopausal women. Attenuation of coronary vasomotor dysfunction may contribute to estrogen's cardioprotective effects. We hypothesized that conjugated estrogens, which contain several vasoactive estrogenic compounds, may favorably influence the vasomotor response to acetylcholine in men. Twenty men, 56 +/- 5 years of age, referred for clinically indicated coronary angiography, participated in this study. Acetylcholine-induced changes in coronary flow were measured by quantitative coronary angiography and intracoronary Doppler ultrasonography before and 15 minutes after intravenous administration of conjugated estrogens (0.625 mg) in 12 men and placebo in 8 men. Initial acetylcholine infusion resulted in no significant increase in coronary blood flow. However, 15 minutes after estrogen administration repeat acetylcholine infusion caused a mean 32% increase in coronary blood flow from 41 +/- 5 to 54 +/- 8 ml/min (p = 0.02). Acetylcholine-induced change in flow after estrogen was significantly different from that before estrogen (p = 0.03). Placebo administration did not affect acetylcholine-induced changes in coronary flow. Thus, intravenous conjugated estrogens favorably modulate acetylcholine-induced changes in coronary hemodynamics in men. This suggests that novel nonfeminizing estrogenic compounds may have anti-ischemic effects in men.
Assuntos
Acetilcolina , Angiografia Coronária/métodos , Circulação Coronária/efeitos dos fármacos , Estrogênios/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Estrogênios/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Cardiac volumes by equilibrium gated cardiac blood pool scans and heart rate were measured in the supine and sitting positions in 64 male volunteer subjects (age 25-80 yrs) who had been rigorously screened to exclude cardiovascular disease. After the upright position was assumed, the average cardiac output of all subjects was unchanged but heart rate increased and stroke volume decreased due to a decrease in end diastolic volume. Neither the supine or sitting cardiac output nor the average postural change in cardiac output, cardiac volumes or heart rate was age-related. While the average cardiac output among the subjects was unaltered with a change in posture, in some individuals it increased slightly while in others it decreased. The postural change in cardiac output among the individuals correlated by linear regression analysis with a change in heart rate only in younger subjects and with a change in stroke volume in all age groups, but the slope of this relationship was greater in older than in younger subjects. The postural change in stroke volume was strongly correlated with a change in end diastolic volume and this relationship did not vary with age. Thus, although the average postural change in cardiac output among healthy subjects is not age-related, a given change in cardiac output with posture in an older individual depends more on a change in stroke volume and less on a heart rate change than in a younger one. This result, like the response to vigorous upright exercise previously demonstrated to occur with aging, indicates a greater reliance in the elderly on the Frank-Starling mechanism than on heart rate for a given change in cardiac output in response to perturbations from the basal supine state.