RESUMO
As worded, the question "Should silent ischemia be treated?" needs to be examined carefully, assuming that silent ischemia is even the correct topic of the question. The way the question is phrased influences the answer. The more the question's permutations are examined, the clearer it becomes that the problem is one of definition. Our conceptualization of the ischemic process is still incomplete, and the question of whether to treat silent ischemia remains. Ultimately, the decision will depend on demonstrable benefit for prognosis. Every acute ischemic syndrome is indicative of poor prognosis, independent of other factors associated with adverse outcome and of the method of measurement. The true determinant of the need to treat is the total ischemic pattern, and how silent ischemia and angina fit within that context is not yet known.
Assuntos
Doença das Coronárias/terapia , Ensaios Clínicos como Assunto , Doença das Coronárias/diagnóstico , Doença das Coronárias/fisiopatologia , Eletrocardiografia Ambulatorial , Teste de Esforço , Humanos , Nifedipino/uso terapêutico , Nitroglicerina/uso terapêuticoRESUMO
Exercise treadmill tests and ambulatory monitoring were used in a double-blind, placebo-controlled, double-dummy crossover comparison of nifedipine (10 mg, 3 times daily) and transdermal nitroglycerin (15 mg). All patients (n = 20) had chronic stable angina with symptomatic and silent events. All patients had 3 episodes of angina/week and 3 episodes of ischemia/24 hr. The protocol was made up of 2 weeks of placebo followed by 2 weeks of active drug, then crossed over for 2 weeks of placebo followed by the other active drug. At the end of each 2-week period, patients had ambulatory monitoring and exercise treadmill testing. All ambulatory monitoring reports were read blind and entered into an independent data base. The results were the following: on transdermal nitroglycerin, the duration of ischemia decreased by 57% from 140 min/24 hr to 60 min/24 hr (p = 0.0054). The exercise time increased by 5.5% from 4.8 to 5.0 minutes (p = 0.16). With nifedipine, the duration of ischemia decreased by 22% from 175 min/24 hr to 137 min/24 hr (p = 0.16). The exercise tolerance time increased by 13% from 4.5 to 5.0 minutes (p = 0.0264). Nifedipine increased exercise time without altering total ischemic time, while transdermal nitroglycerin decreased total ischemic time without increasing exercise time. Thus, changes in exercise time do not necessarily predict changes in total ischemic time.
Assuntos
Angina Pectoris/fisiopatologia , Teste de Esforço , Administração Cutânea , Angina Pectoris/tratamento farmacológico , Circulação Coronária/efeitos dos fármacos , Eletrocardiografia Ambulatorial , Humanos , Pessoa de Meia-Idade , Nifedipino/administração & dosagem , Nifedipino/uso terapêutico , Nitroglicerina/administração & dosagem , Nitroglicerina/uso terapêuticoRESUMO
Investigations into the mechanisms and characteristics of ischemic heart disease have increasingly documented evidence of myocardial ischemia in the absence of symptoms. Recent work using objective criteria of ischemic episodes confirmed that angina pectoris or its equivalents need not accompany myocardial ischemia and noted that these episodes appear to be quite common. The impact on prognosis awaits further study, but preliminary data suggest an adverse prognosis for patients with recurrent spontaneous silent vasoconstrictive ischemia. Furthermore, treatment of silent ischemic episodes with nitrates may be associated with reduced ischemia. Preliminary trials show reduction of the number, duration, and magnitude of silent ischemic episodes by transdermal nitroglycerin given to patients receiving beta-blockers. Therapy of acute ischemic syndromes should be designed to eliminate ischemia completely, not merely ameliorate pain.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Alprazolam/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Nitroglicerina/uso terapêutico , Administração Cutânea , Angina Pectoris/tratamento farmacológico , Angina Pectoris/etiologia , Método Duplo-Cego , Quimioterapia Combinada , Eletrocardiografia , Teste de Esforço , Humanos , Nitroglicerina/administração & dosagem , Prognóstico , Estresse Fisiológico/complicações , Estresse Fisiológico/tratamento farmacológicoRESUMO
Studies of the mechanisms and characteristics of ischemic heart disease have increasingly documented evidence of myocardial ischemia in the absence of symptoms. Recent work using objective criteria of ischemic events has confirmed that angina pectoris or its equivalents need not accompany true myocardial ischemia, and this appears to be quite common. The impact of these findings on prognosis awaits further study, but preliminary data suggest an improved prognosis for persons in whom coronary artery disease remains asymptomatic compared with symptomatic patients. Further, reduction of silent ischemic events with nitrate therapy may be associated with a more benign subsequent course. Preliminary trials show a reduction of the number, duration and magnitude of silent ischemic events by transdermal nitroglycerin. Ongoing technical innovations in monitoring systems should allow more complete characterization of this syndrome and lead to definition of medical therapy for it.
Assuntos
Doença das Coronárias/tratamento farmacológico , Nitroglicerina/administração & dosagem , Administração Tópica , Angina Pectoris/tratamento farmacológico , Angina Pectoris/fisiopatologia , Doença das Coronárias/diagnóstico , Doença das Coronárias/fisiopatologia , Eletrocardiografia , Humanos , Nitratos/uso terapêutico , Nitroglicerina/uso terapêutico , Prognóstico , Fatores de Tempo , Vasodilatadores/uso terapêuticoRESUMO
Using agarose gel electrophoresis MB-creatine kinase (MB-CK) activity was examined in the serum of 120 patients with acute alcohol intoxication admitted to a detoxification ward. Total CK activity was increased in 67 percent of patients and MB-CK activity was increased in 8.3 percent. Alcoholic patients also were studied by Sephadex chromatography and, in seven cases, MB-CK was greater than three standard deviations from the normal. Thus, this study demonstrates that acute alcohol intoxication is associated with increased MB-CK activity. These findings raise the possibility that excessive alcohol ingestion may lead to acute myocardial injury.
Assuntos
Alcoolismo/enzimologia , Cardiomiopatia Alcoólica/enzimologia , Creatina Quinase/sangue , Adulto , Idoso , Feminino , Humanos , Isoenzimas , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
alpha-1 acid glycoproteins become elevated in the patient's serum within a few hours after an acute myocardial infarction. Previous reports have suggested a correlation between the magnitude of this elevation and infarct size as estimated by enzyme markers. Correlation has also been observed between the mortality following infarction and appearance of elevated alpha-1 acid glycoproteins. We now report that these glycoproteins are detectable in normal myocardium using immunohistochemical techniques. Diminished amounts are observed in necrotic tissue in acute myocardial infarcts. Ultrastructural localization by immunoelectron microscopy using sections of normal myocardium established the presence of alpha-1 acid glycoproteins primarily at the cell surface in the region of the sarcolemma. The observations suggest that myocardium may directly contribute to the elevation of serum alpha-1 acid glycoproteins after an infarct, and the assessment of these components may serve as an additional serum marker.
Assuntos
Miocárdio/análise , Orosomucoide/análise , Animais , Histocitoquímica , Humanos , Técnicas Imunoenzimáticas , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/patologia , Miocárdio/ultraestrutura , Necrose , CoelhosRESUMO
Intermittent vasospasm and/or platelet aggregation may play an important role in producing transient coronary artery obstruction leading to an unstable ischemic syndrome. To determine whether intravenous infusion of prostaglandin E1 (PGE1) a known coronary vasodilator and inhibitor of platelet aggregation, produces salutary effects in unstable angina, we evaluated its effects in 19 patients with an unstable acute ischemic syndrome. PGE1 produced a significant decrease in the number of episodes of rest angina (p less than 0.001) and eliminated the need for intravenous nitroglycerin and morphine in 10 patients. These salutary clinical effects were associated with a significant (p less than 0.05) reduction in mean arterial pressure, mean pulmonary artery pressure, mean pulmonary capillary wedge pressure, and the double product, without a reduction in the endocardial perfusion gradient (aortic diastolic blood pressure--mean pulmonary capillary wedge pressure). Adverse effects were generally minor and easily controlled. Thus PGE1 infusion may be of value in the treatment of acute unstable ischemic syndromes.
Assuntos
Angina Pectoris/tratamento farmacológico , Angina Instável/tratamento farmacológico , Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Prostaglandinas E/uso terapêutico , Idoso , Alprostadil , Angina Instável/diagnóstico por imagem , Angina Instável/fisiopatologia , Tempo de Sangramento , Pressão Sanguínea/efeitos dos fármacos , Feminino , Coração/diagnóstico por imagem , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Prostaglandinas E/efeitos adversos , Artéria Pulmonar/fisiopatologia , Pressão Propulsora Pulmonar/efeitos dos fármacos , Cintilografia , Volume Sistólico/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacosAssuntos
Ponte Cardiopulmonar , Circulação Coronária , Monitoramento de Radiação/instrumentação , Adenosina/farmacologia , Animais , Velocidade do Fluxo Sanguíneo , Ponte Cardiopulmonar/métodos , Vasos Coronários/efeitos dos fármacos , Cães , Desenho de Equipamento , Feminino , Parada Cardíaca Induzida , Hiperemia/fisiopatologia , Masculino , Microcirculação/fisiologia , Vasodilatação/efeitos dos fármacos , Radioisótopos de XenônioRESUMO
We utilized immunoperoxidase methods to study the distribution of CK-B and CK-M in normal, ischemic and necrotic myocardium. Human myocardium was obtained from autopsy (n = 10) and surgery (n = 16). Cardiac tissue from 22 dogs with experimental myocardial infarction induced by closed-chest coronary balloon occlusion and four dogs with myocardial ischemia without necrosis induced by a 50% reduction in left main coronary artery blood flow for 3 h were studied. Duration of occlusion was 45 min (n = 2), 3 h (n = 8), 5 to 6 h (n = 7), 15 to 24 h (n = 5). Highly purified anti-CK-B and M were prepared in our laboratory and obtained commercially. In all cases, control experiments were performed. Microscopically normal human and dog myocardium uniformly stained for CK-B and CK-M. Necrotic myocardium from patients with acute infarcts (10 to 24 h old) showed markedly reduced immunostaining. In dogs with 3 to 24 h occlusion immunostaining was significantly reduced for both CK-B and CK-M in regions confirmed to be necrotic by triphenyl tetrazolium chloride (TTC) and H & E staining. Myocardial necrosis was confirmed in the 3-h infarcts by electron microscopy (EM). In the four dogs with a 50% reduction in left main flow for 3 h, ischemia was demonstrated by glycogen loss in periodic acid-Schiff stained-sections; but there was no evidence of necrosis by EM or TTC, and there was no loss of immunostaining evident for CK-B and CK-M. Thus, using immunoperoxidase techniques, CK-B and CK-M were visualized in normal and ischemic myocardium, with decreased staining in necrotic tissue. These findings indicate that cell death is necessary for the demonstration of CK-M and CK-B loss from the myocardium by this technique.
Assuntos
Doença das Coronárias/enzimologia , Creatina Quinase/análise , Miocárdio/enzimologia , Animais , Cães , Histocitoquímica , Humanos , Técnicas Imunoenzimáticas , Miocárdio/patologia , NecroseAssuntos
Débito Cardíaco , Eletrocardiografia , Teste de Esforço , Infarto do Miocárdio/fisiopatologia , Volume Sistólico , Adulto , Idoso , Creatina Quinase/sangue , Feminino , Coração/fisiopatologia , Humanos , Isoenzimas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Miocárdio/patologiaRESUMO
A new radioimmunoassay for alpha 1-acid glycoprotein (AGP) for monitoring the therapy of cancer patients was evaluated. Plasma levels of this glycoprotein were measured in 49 normal healthy volunteers, 71 patients with illnesses other than cancer, 190 patients with solid tumors, and 58 patients with hematologic neoplasms. Plasma levels of AGP were elevated in 89% of the solid tumor patients and 87% of the patients with hematologic neoplasms who had newly diagnosed, locally recurrent, or metastatic cancer. Only 18% of patients with illnesses other than cancer and normal renal function had elevations of plasma AGP. Serial measurements of AGP may be useful for monitoring therapy in several tumor types, including small-cell lung cancer, colon cancer, lymphoma, and non-small-cell lung cancer.
Assuntos
Leucemia/sangue , Linfoma/sangue , Orosomucoide/análise , Estudos de Avaliação como Assunto , Neoplasias Gastrointestinais/sangue , Humanos , Leucemia/patologia , Neoplasias Pulmonares/sangue , Linfoma/patologia , RadioimunoensaioRESUMO
Elevation of levels of the myocardial-specific isoenzyme of creatine kinase (CK-MB) in the immediate postoperative period in patients undergoing coronary artery bypass grafting is usually associated with myocardial necrosis. However, mean isoenzyme elevations of 18 +/- 2 IU/L (standard error of the mean) were recently observed in 6 patients in the absence of electrocardiographic or scintigraphic (technetium 99m stannous pyrophosphate) evidence of perioperative myocardial infarction. To test the hypothesis that surgical trauma of the atrium and aorta during cannulation for cardiopulmonary bypass might contribute to elevated CK-MB levels, biopsy of the right atrial appendage and aorta of 7 patients was done at operation, the tissue samples were assayed for total creatine kinase (CK) activity using the Rosalki technique, and for CK-MB using column chromatography. The results indicate that the human atrium is a rich source of CK, with the proportion of CK-MB similar to that present in the ventricle (20%). In addition, technical considerations inherent in the performance of coronary bypass surgery may result in release of CK-MB, causing elevated serum enzyme levels in the post-coronary artery bypass patient in the absence of myocardial infarction.
Assuntos
Ponte de Artéria Coronária , Creatina Quinase/sangue , Aorta/enzimologia , Átrios do Coração/enzimologia , Humanos , IsoenzimasRESUMO
The initial PCW, Killip-Scheidt classification, presence of third heart sound, and mortality were compared in 90 patients presenting with acute transmural myocardial infarction. Clinical and hemodynamic assessment was performed within 12 hours (time to clinical classification = 4.7 +/- 2.7 hours (mean +/- SD), time to hemodynamic assessment = 5.8 +/- 2.4) of the sentinel event. A poor correlation was observed between early Killip-Scheidt clinical classification and early hemodynamic state when measured as percent correct classification (66%) or as a Kappa statistic (36% for the total population, 9% for nonsurvivors). Increased initial LVFP (greater than 18 mm Hg) was associated with increased mortality (p less than 0.01) and early clinical classification was not. Addition of third heart sound information did not alter this observation.
Assuntos
Hemodinâmica , Infarto do Miocárdio/diagnóstico , Idoso , Ruídos Cardíacos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Exame Físico , Pressão Propulsora Pulmonar , Volume SistólicoRESUMO
Large doses of morphine sulfate have been reported to cause myocardial lactate production and reduction in coronary blood flow in animals. Similar effects with clinical doses in man would significantly alter the management of cardiac patients. Eleven adult patients with significant coronary arterial disease and normal left ventricular ejection fraction were studied before and 30 minutes after infusion of morphine (0.25 mg/kg IV). Evaluation of myocardial metabolism showed an increase in coronary sinus oxygen content (p less than 0.001) and a reduction in myocardial oxygen consumption. Myocardial lactate extraction was not altered. No change in coronary sinus blood flow was seen. It is concluded that infusion of morphine sulfate, 0.25 mg/kg IV, does not produce global myocardial ischemia in patients with coronary artery disease and normal ventricular function.
Assuntos
Doença das Coronárias/fisiopatologia , Coração/efeitos dos fármacos , Morfina/farmacologia , Idoso , Gasometria , Circulação Coronária/efeitos dos fármacos , Feminino , Humanos , Lactatos/metabolismo , Ácido Láctico , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Consumo de Oxigênio/efeitos dos fármacosRESUMO
The early release patterns of MB-creatine kinase (CK-MB) in myocardial ischemia and infarction are largely unknown. We utilized a sensitive column chromatographic assay of CK-MB activity (precision = 1.1 IU/liter) and sequential CK-MB samples were obtained during the first 6 hours of illness to define the early time course of enzyme release. The average CK-MB in 39 normal subjects was 2.4 +/- 0.93 (mean +/- standard deviation (SD)). Twenty-two patients with ischemic chest pain, in whom myocardial infarction did not develop, were characterized by normal CK-MB's (2.4 +/- 1.0). Of 39 patients in whom transmural myocardial infarction developed, 28 (72 percent) were found to have abnormal CK-MB either initially or over a 20-minute sampling period. In contrast, 100 percent of the patients considered to have sustained a nontransmural myocardial infarction had abnormal initial CK-MBs and subsequently demonstrated significant increases in CK-MB from 28 +/- 19 initially to 41 +/- 30 IU/liter (P less than 0.01, N = 16) over the 20-minute sampling period. Thus, CK-MB appears earlier in plasma following nontransmural myocardial infarction than transmural myocardial infarction, probably reflecting perfusion to ischemic myocardium.
Assuntos
Creatina Quinase/sangue , Infarto do Miocárdio/diagnóstico , Cromatografia por Troca Iônica , Humanos , Isoenzimas , Dor , Fatores de TempoRESUMO
Myocardial beta-adrenoceptor binding was investigated, with (-)3H dihydroalprenolol as radioligand, in microsomes derived from anterior (ALV) and inferior (ILV) myocardial wall sections of the canine left ventricle. Characterisation of specific binding sites revealed a hierarchy of myocardial beta-adrenoceptor binding with greater binding occurring to the anterior than the inferior wall of the left ventricle, under identical experimental conditions. Equilibrium analysis by Scatchard plots suggested a significant (P less than 0.01) difference in the number of receptors (Bmax ALV = 70 fmol . mg-1 protein vs Bmax ILV = 37 fmol . mg-1 protein) with no alteration in the binding affinity of the receptors (KDALV = 10.1 nmol . litre-1 vs KDILV = 6.7 nmol . litre-1). Such differences in the extent of binding of beta-adrenoreceptors in cardiac muscle may be of physiological and pathological significance and may account for the heterogeneity of regional autonomic responses in the heart.
Assuntos
Alprenolol/análogos & derivados , Di-Hidroalprenolol/metabolismo , Miocárdio/metabolismo , Receptores Adrenérgicos beta/metabolismo , Receptores Adrenérgicos/metabolismo , Antagonistas Adrenérgicos beta/metabolismo , Animais , Sítios de Ligação , Cães , Ventrículos do Coração/metabolismo , Cinética , Masculino , Microssomos/metabolismo , EstereoisomerismoRESUMO
We describe a rapid, sensitive radioimmunoassay for enzymatically inactive creatine kinase B protein (CK-Bi) in plasma. 125I-CK-Bi of high specific activity and good stability was prepared by oxidant-based iodination. A 12 minute first antibody incubation was used. Bound and free antigen were separated by a second antibody system. Large excesses of purified CK-MM from human skeletal muscle did not react in the assay. Cross reactivity to CK-MB purified from the plasma of patients with acute myocardial infarction was negligible. The 95th percentile of plasma CK-Bi in 150 adults was 145 microgram equivalents/ml. Within-assay and between-assay precision ranged from 5% to 9% and 6% to 10%, respectively. Evidence is presented indicating that the assay measures inactive creatine kinase B protein, a protein not measured by current assay systems dependent on biological activity.