RESUMEN
OBJECTIVES: To investigate the possible causes for false negative results in BacT/ALERT® 3D Signature System despite bacterial contamination of platelet units. BACKGROUND: The Northern Ireland Blood Transfusion Service (NIBTS) routinely extends platelet component shelf life to 7 days. Components are sampled and screened for bacterial contamination using an automated microbial detection system, the BacT/ALERT® 3D Signature System. We report on three platelet components with confirmed bacterial contamination, which represent false negative BacT/ALERT® results and near-miss serious adverse events. METHODS: NIBTS protocols for risk reduction of bacterial contamination of platelet components are described. The methodology for bacterial detection using BacT/ALERT® is outlined. Laboratory tests, relevant patient details and relevant follow-up information are analysed. RESULTS: In all three cases, Staphylococcus aureus was isolated from the platelet residue and confirmed on terminal sub-culture using BacT/ALERT® . In two cases, S. aureus with similar genetic makeup was isolated from the donors. CONCLUSION: Risk reduction measures for bacterial contamination of platelet components are not always effective. Automated bacterial culture detection does not eliminate the risk of bacterial contamination. Visual inspection of platelet components prior to release, issue and administration remains an important last line of defence.
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Plaquetas/microbiología , Seguridad de la Sangre , Contaminación de Medicamentos , Staphylococcus aureus/aislamiento & purificación , Reacciones Falso Positivas , Humanos , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
Previous studies suggest that while lung angiotensin converting enzyme (ACE) activity is reduced during chronic hypoxia, inhibitors of ACE attenuate hypoxic pulmonary hypertension. In an attempt to explain this paradox we investigated the possibility that whole lung ACE activity may not reflect local pulmonary vascular ACE expression. The experimental approach combined in vivo hemodynamic studies in control and chronically hypoxic rats, measurement of whole lung ACE activity, and evaluation of local pulmonary vascular ACE expression by in situ hybridization and immunohistochemistry. Total lung ACE activity was reduced to 50% of control activity by 5 d of hypoxia and remained low for the duration of the study. Immunohistochemistry showed a marked reduction of ACE staining in alveolar capillary endothelium. However, an increase in ACE staining was observed in the walls of small newly muscularized pulmonary arteries at the level of alveolar ducts and walls. In situ hybridization studies showed increased signal for ACE mRNA in the same vessels. Inhibition of ACE by captopril during chronic hypoxia attenuated pulmonary hypertension and markedly reduced distal muscularization of small pulmonary arteries. In addition, we demonstrated marked longitudinal variation in ACE expression along the normal pulmonary vasculature with the highest levels found in small muscular arteries associated with terminal and respiratory bronchioles. We conclude that local ACE expression is increased in the walls of small pulmonary arteries during the development of hypoxic pulmonary hypertension, despite a generalized reduction in alveolar capillary ACE expression, and we speculate that local arteriolar ACE may play a role in the vascular remodeling associated with pulmonary hypertension.
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Hipertensión Pulmonar/enzimología , Hipoxia/complicaciones , Peptidil-Dipeptidasa A/biosíntesis , Arteria Pulmonar/enzimología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Inmunohistoquímica , Hibridación in Situ , Riñón/enzimología , Masculino , Peptidil-Dipeptidasa A/genética , ARN Mensajero/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
Mechanisms that regulate endothelial nitric oxide synthase (eNOS) expression in normal and hypoxic pulmonary circulation are poorly understood. Lung eNOS expression is increased after chronic hypoxic pulmonary hypertension in rats, but whether this increase is due to altered hemodynamics or to hypoxia is unknown. Therefore, to determine the effect of blood flow changes on eNOS expression in the normal pulmonary circulation, and to determine whether the increase in eNOS expression after chronic hypoxia is caused by hemodynamic changes or low oxygen tension, we compared eNOS expression in the left and right lungs of normoxic and chronically hypoxic rats with surgical stenosis of the left pulmonary artery (LPA). LPA stenosis in normoxic rats reduced blood flow to the left lung from 9.8+/-0.9 to 0.8+/-0.4 ml/100 mg/min (sham surgery controls vs. LPA stenosis, P < 0.05), but there was not a significant increase in right lung blood flow. When compared with the right lung, eNOS protein and mRNA content in the left lung was decreased by 32+/-7 and 54+/-13%, respectively (P < 0.05), and right lung eNOS protein content was unchanged. After 3 wk of hypoxia, LPA stenosis reduced blood flow to the left lung from 5.8+/-0.6 to 1.5+/-0.4 ml/100 mg/min, and increased blood flow to the right lung from 5.8+/-0.5 to 10.0+/-1.4 ml/ 100 mg/min (sham surgery controls vs. LPA stenosis, P < 0.05). Despite reduced flow and pressure to the left lung and increased flow and pressure to the right lung, left and right lung eNOS protein and mRNA contents were not different. There were also no differences in lung eNOS protein levels when compared with chronically hypoxic sham surgery controls (P > 0.05). We conclude that reduction of pulmonary blood flow decreases eNOS mRNA and protein expression in normoxic adult rat lungs, and that hypoxia increases eNOS expression independently of changes in hemodynamics. These findings demonstrate that hemodynamic forces maintain eNOS content in the normoxic pulmonary circulation of the adult rat, and suggest that chronic hypoxia increases eNOS expression independently of changes in hemodynamics.
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Endotelio Vascular/enzimología , Hipoxia/enzimología , Pulmón/enzimología , Óxido Nítrico Sintasa/biosíntesis , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Endotelio Vascular/patología , Hemodinámica , Hipoxia/patología , Hipoxia/fisiopatología , Pulmón/patología , Pulmón/fisiopatología , Masculino , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Tamaño de los Órganos , Arteria Pulmonar/enzimología , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , ARN Mensajero , Ratas , Ratas Sprague-DawleyRESUMEN
Acute hypoxic vasoconstriction and development of hypoxic pulmonary hypertension (PHTN) are unique properties of the pulmonary circulation. The pulmonary endothelium produces vasoactive factors, including nitric oxide (NO), that modify these phenomena. We tested the hypothesis that NO produced by endothelial nitric oxide synthase (eNOS) modulates pulmonary vascular responses to hypoxia using mice with targeted disruption of the eNOS gene (eNOS-/-). Marked PHTN was found in eNOS-/- mice raised in mild hypoxia when compared with either controls or eNOS-/- mice raised in conditions simulating sea level. We found an approximate twofold increase in partially and fully muscularized distal pulmonary arteries in eNOS-/- mice compared with controls. Consistent with vasoconstriction being the primary mechanism of PHTN, however, acute inhalation of 25 ppm NO resulted in normalization of RV pressure in eNOS-/- mice. In addition to studies of eNOS-/- mice, the dose-effect of eNOS was tested using heterozygous eNOS+/- mice. Although the lungs of eNOS+/- mice had 50% of normal eNOS protein, the response to hypoxia was indistinguishable from that of eNOS-/- mice. We conclude that eNOS-derived NO is an important modulator of the pulmonary vascular response to chronic hypoxia and that more than 50% of eNOS expression is required to maintain normal pulmonary vascular tone.
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Hipertensión Pulmonar/genética , Óxido Nítrico Sintasa/genética , Circulación Pulmonar/genética , Administración por Inhalación , Animales , Análisis de los Gases de la Sangre , Relación Dosis-Respuesta a Droga , Hematócrito , Heterocigoto , Homocigoto , Hipertensión Pulmonar/fisiopatología , Hipertrofia Ventricular Derecha/genética , Hipoxia/fisiopatología , Pulmón/patología , Ratones , Ratones Noqueados , Óxido Nítrico/farmacología , ARN Mensajero/genética , Vasoconstricción/efectos de los fármacos , Vasoconstricción/genética , Presión Ventricular/genéticaRESUMEN
This prospective study evaluated the ability of serial biplane rest and exercise radionuclide angiography to predict the status of individual coronary bypass grafts in 20 patients 2 to 6 months after surgery. The preoperative coronary angiogram was used to assign vessels to 10 regions of distribution on the radionuclide angiogram. Predictions of graft adequacy for individual vessels were based on a detailed assessment of rest and exercise wall motion in their regions of supply. Of 59 grafts, 38 were judged adequate (patent with less than 75% stenosis) and 21 inadequate by postoperative catheterization. Radionuclide prediction of graft status was possible for 32 of the 59 grafts, including 19 of 24 left anterior descending, 7 of 19 circumflex and 6 of 16 right coronary artery grafts. The status of the remaining 27 grafts could not be assessed because of normal wall motion in their region of supply both pre- and postoperatively (22 vessels) or because a region of supply was not represented on the biplane radionuclide angiogram (5 vessels). Of the 32 predictions made, 25 (78%) were correct, including 13 (93%) of 14 predictions of graft adequacy and 12 (67%) of 18 predictions of graft inadequacy. The single incorrect prediction of graft adequacy resulted from improved exercise wall motion in a region supplied by a graft judged as having a 75% anastomotic stenosis. Most incorrect predictions of graft inadequacy were due to new septal or other rest wall motion abnormalities postoperatively. The comparison of pre- and postoperative studies was essential to maintain the predictive ability of the test. Thus, a detailed analysis of regional wall motion by rest and exercise radionuclide angiography can be used to predict the status of individual coronary artery bypass grafts. Reliable predictions can be made for most successful anterior descending grafts, and may permit cardiac catheterization to be deferred in certain cases. However, the method is limited by the need to perform preoperative exercise studies, by the low number of right and circumflex coronary artery grafts that can be evaluated and by the poor specificity of predictions of graft failure.
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Puente de Arteria Coronaria , Vasos Coronarios/diagnóstico por imagen , Adulto , Angiografía , Oclusión de Injerto Vascular/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Esfuerzo Físico , Complicaciones Posoperatorias , Estudios Prospectivos , Cintigrafía , DescansoRESUMEN
To evaluate the effectiveness and cost of low osmolarity, nonionic contrast agents for cardiac angiography, 443 patients were randomized to receive either iopamidol or diatrizoate. All adverse events that occurred within 24 h of the procedure were recorded prospectively by study personnel and classified according to previously determined criteria. Major events were defined as life threatening or requiring a procedure to treat, or both. Costs of the catheterization procedure, pharmacy, hospital laboratory and treatment of adverse events were determined on the basis of actual resource use. A total of 20 patients (8.5%) had major and 143 (61%) had minor adverse events with diatrizoate use; 10 patients (4.8%) had major and 53 (25%) had minor adverse events with iopamidol (p = 0.12 for major events; p less than 0.001 for total events). Most adverse events were treated fairly easily and inexpensively. The median overall cost was $186 higher for patients after iopamidol use compared with diatrizoate (p less than 0.0001), but all costs except the cost of the contrast agent were not significantly different between the two groups. Thus, patients who received iopamidol for cardiac angiography had a significantly lower rate of adverse events than those who received diatrizoate, but this difference was achieved at a considerably high overall cost.
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Angiocardiografía/economía , Diatrizoato , Yopamidol , Cateterismo Cardíaco/economía , Análisis Costo-Beneficio , Costos y Análisis de Costo , Diatrizoato/efectos adversos , Femenino , Humanos , Yopamidol/efectos adversos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
One year survival and event-free survival rates were analyzed in 342 patients with acute myocardial infarction who were consecutively enrolled in a treatment protocol of early intravenous thrombolytic therapy followed by emergency coronary angioplasty. Ninety-four percent of the patients achieved successful reperfusion, including 4% with failed angioplasty whose perfusion was maintained by means of a reperfusion catheter before emergency bypass surgery. The procedural mortality rate was 1.2% and the total in-hospital mortality rate was 11%. Ninety-two percent of surviving nonsurgical patients who underwent repeat cardiac catheterization were discharged from the hospital with an open infarct-related artery. The related cumulative 1 year survival rate for all patients managed with this treatment strategy was 87%, and the cardiac event-free survival rate was 84%. The 1 year survival for hospital survivors was 98% and the infarct-free survival rate was 94%. Multivariable analysis identified the following factors as independent predictors of subsequent cardiovascular death: cardiogenic shock, greater age, lower ejection fraction, female gender and a closed infarct-related vessel on the initial coronary angiogram. Among patients with cardiogenic shock, despite a 42% in-hospital mortality rate, only 4% died during the first year after hospital discharge. Similarly, the in-hospital and 1 year postdischarge mortality rates were 19 and 4%, respectively, for patients with an initial ejection fraction less than 40, and 25 and 3%, respectively, for patients greater than 65 years. An aggressive treatment strategy including early thrombolytic therapy, emergency cardiac catheterization, coronary angioplasty and, when necessary, bypass surgery resulted in a high rate of infarct vessel patency.(ABSTRACT TRUNCATED AT 250 WORDS)
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Angioplastia de Balón , Infarto del Miocardio/mortalidad , Grado de Desobstrucción Vascular , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Puente de Arteria Coronaria , Urgencias Médicas , Femenino , Fibrinolíticos/uso terapéutico , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/terapia , Choque Cardiogénico/mortalidad , Volumen SistólicoRESUMEN
All patients admitted to a community hospital coronary care unit during an 18-month-period were studied to validate previously reported criteria for early hospital discharge after myocardial infarction. Factors present during the first four hospital days, which predict subsequent complications requiring urgent medical attention, were classified as either urgent or prognostic. Patients whose initial four days were marked by either no complications (81 patients) or prognostic complications (51 patients) are described. Only one patient in the group of 81 patients had a subsequent urgent complication. Four of 55 patients had late urgent complications. Persistent sinus tachycardia occurred during the first four days in all four of these 55 patients. Early hospital discharge would be feasible in the group with neither urgent nor prognostic complications. Further study of persistent sinus tachycardia is required to improve its predictive ability.
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Tiempo de Internación , Infarto del Miocardio , Arritmias Cardíacas/etiología , Estudios de Seguimiento , Hospitales Comunitarios , Humanos , Hipotensión/etiología , Infarto del Miocardio/complicaciones , North Carolina , Pronóstico , Taquicardia/etiologíaRESUMEN
OBJECTIVE: To determine whether local cardiac angiotensin converting enzyme (ACE) expression is upregulated during the development of hypoxia-induced right ventricular hypertrophy. METHODS: ACE activity was measured in membrane preparations from the right ventricle and left ventricle plus septum in normoxic rats and animals exposed to chronic hypoxia for 8 and 14 days. Local cardiac ACE expression was studied by immunohistochemistry using a monoclonal antibody to ACE (9B9). RESULTS: In the normal rat heart, ACE expression was confined to vascular endothelium, the valvular endocardium, and localized regions of parietal endocardium. We found that the development of pulmonary hypertension and right ventricular hypertrophy were associated with 2.6- and 3.4-fold increases in membrane-bound right ventricular ACE activity by 8 and 14 days of hypoxia, respectively. Right ventricular ACE activity was positively correlated with the degree of right ventricular hypertrophy (r = 0.83, P < 0.001). In contrast, left ventricular plus septal ACE activity was significantly reduced by approximately 40 and 60% by 8 and 14 days of hypoxia, respectively, compared to controls. In the right ventricle of chronically hypoxic rats, immunohistochemistry demonstrated increased ACE expression in areas of myocardial fibrosis. Interestingly, increased ACE expression was noted in the right ventricular epicardium in chronically hypoxic rats. In the free wall of the left ventricle there was a significant reduction in the number of myocardial capillaries which expressed ACE in chronically hypoxic rats. CONCLUSION: Chronic hypoxia has a differential effect on left and right ventricular ACE activity and that the sites of altered ACE expression are highly localized. We speculate that locally increased right ventricular ACE activity and expression may play a role in the pathogenesis of right ventricular hypertrophy secondary to hypoxic pulmonary hypertension.
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Hipertensión Pulmonar/enzimología , Hipertrofia Ventricular Derecha/enzimología , Hipoxia/enzimología , Miocardio/enzimología , Peptidil-Dipeptidasa A/metabolismo , Animales , Biomarcadores , Activación Enzimática , Ventrículos Cardíacos , Inmunohistoquímica , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
We examined the hemodynamic effects of pirmenol, a new antiarrhythmic drug, for the first time in man. Right and left heart pressures, Fick cardiac output, and radionuclide ejection fraction were measured before and during infusion of pirmenol in 10 patients with coronary artery disease who were undergoing routine diagnostic cardiac catheterization. Pirmenol was given as a 50-mg IV injection over 2 min followed by a constant infusion of 2.5 mg/min for up to 36 min. Plasma pirmenol levels were within or near the previously determined therapeutic range in all patients. There were no significant changes in systolic blood pressure or cardiac output. Diastolic blood pressure rose from a mean (+/- SD) 78 +/- 7 during the control period to 82 +/- 6 during the infusion, heart rate rose from 66 +/- 6 during the control period to 75 +/- 7 during infusion and ejection fraction fell from 60 +/- 8 during control to 55 +/- 12 during infusion. Although the left ventricular end-diastolic pressure rose from 6 +/- 2 during control to 8 +/- 3 during the infusion, the left ventricular stroke work index fell and the left ventricular work index per minute did not change. The fall in ejection fraction did not correlate with the control ejection fraction, plasma pirmenol levels, or the change in heart rate. The decline in ejection fraction and the failure of the left ventricular work index per minute to rise despite a small rise in left ventricular end-diastolic pressure may indicate a potential myocardial depressant effect of pirmenol.
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Antiarrítmicos/farmacología , Hemodinámica/efectos de los fármacos , Piperidinas/farmacología , Evaluación de Medicamentos , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana EdadRESUMEN
A placebo-controlled, double-blind, crossover study was conducted to determine the effects of nifedipine (60 to 90 mg per day) monotherapy and propranolol (240 mg per day) monotherapy on symptoms, angina threshold, and cardiac function in patients with chronic stable angina. Following a two-week placebo period, patients were randomly assigned to receive either nifedipine or propranolol for a five-week treatment period, after which they crossed over to the alternative regimen. All 21 patients were men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. New York Heart Association functional class improved in patients taking either nifedipine or propranolol, and nitroglycerin consumption decreased with both treatments compared with placebo. Nifedipine significantly delayed the onset of chest pain and 1 mm of ST-segment depression during bicycle exercise; increases with propranolol were smaller and not statistically significant. Nine patients had a preferential clinical response to nifedipine compared with six patients to propranolol; this was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvement in radionuclide ejection fraction at identical work loads. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14 percent (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output. Thus, nifedipine is more effective on several measurements than propranolol when administered as single drug therapy in stable angina and has the advantage of preserving cardiac output during exercise.
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Angina de Pecho/tratamiento farmacológico , Nifedipino/administración & dosificación , Propranolol/administración & dosificación , Adulto , Anciano , Angina de Pecho/fisiopatología , Ensayos Clínicos como Asunto , Método Doble Ciego , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Nifedipino/efectos adversos , Nifedipino/uso terapéutico , Propranolol/efectos adversos , Propranolol/uso terapéuticoRESUMEN
Recovery of global and regional systolic and global diastolic left ventricular (LV) function was examined after 60 seconds of coronary arterial occlusion in 9 men without myocardial infarction undergoing elective percutaneous transluminal coronary angioplasty. Hemodynamic and electrocardiographic recordings and a simultaneous digital subtraction LV angiogram in the 30 degree right anterior oblique view were performed before coronary occlusion, after 60 seconds of the first 2 occlusions and at 20, 40, 60 and 90 seconds of reperfusion. Diastolic pressure-volume relations paired the digital volumes to corresponding high-fidelity analog pressures. Similar and significant depression of global ejection fraction, percent radial shortening in the jeopardized region, maximal positive dP/dt and significant elevation of LV end-diastolic pressure and ST segments occurred with each 60-second coronary occlusion. All of these variables except LV end-diastolic pressure returned to control levels within 40 seconds of reperfusion. Significant elevation of the diastolic pressure-volume relation occurred with each coronary occlusion and progressively diminished to control values with 60 seconds of reperfusion. No statistically significant difference in any measurement occurred between the 2 occlusions and reperfusions at any point. This study shows that similar and significant depression and time course of recovery of global and regional systolic and global diastolic LV function accompanied each 60-second coronary occlusion with recovery of systolic function preceding recovery of diastolic function.
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Angina de Pecho/terapia , Angioplastia de Balón , Contracción Miocárdica , Angina de Pecho/fisiopatología , Circulación Coronaria , Vasos Coronarios/fisiología , Electrocardiografía , Humanos , Masculino , Persona de Mediana Edad , Volumen Sistólico , Factores de TiempoRESUMEN
A simple method for the assessment of regional left ventricular (LV) function using gated radionuclide angiography is described. The method divides the LV region of interest in the left anterior oblique view into quadrants using a count-weighted center point and a transparent overlay. The regional ejection fraction (EF) was determined at rest and during upright bicycle exercise for each of 3 quadrants identified as posterior, septal and apical. The study group consisted of 50 patients with chest pain. Nine of these patients had normal coronary arteries and 41 had significant coronary artery disease (CAD). Regional EF measurements were highly reproducible at rest and exercise in all regions. Regional EF values at rest were compared with the subjective assessment of wall motion on the contrast ventriculogram and were significantly lower in regions with abnormal wall motion. Regional EF increased with exercise in all patients with normal coronary arteries. In patients with CAD and normal regional wall motion at rest, the regional exercise response was significantly more sensitive (p = 0.004) than global exercise response and marginally more sensitive (p = 0.06) than the subjective assessment of exercise wall motion on visual radionuclide images in the diagnosis of CAD. These results suggest that the measurement of regional LV function may be useful in the noninvasive diagnosis of CAD.
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Gasto Cardíaco , Enfermedad Coronaria/diagnóstico por imagen , Corazón/diagnóstico por imagen , Volumen Sistólico , Adulto , Anciano , Enfermedad Coronaria/fisiopatología , Prueba de Esfuerzo , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Radiografía , CintigrafíaRESUMEN
Multigated equilibrium radionuclide angiography was used to quantitate global and regional ejection fraction (EF) in 26 awake dogs 10 minutes after distal and then proximal occlusion of the left anterior descending (LAD) or left circumflex (LC) coronary artery. Changes in global and regional EF were correlated with simultaneous measurements of the extent of acute left ventricular (LV) ischemia measured by radioisotope-labeled microspheres. The extent of ischemia, defined as the percentage of LV mass with greater than 25% reduction in blood flow from normal regional flow, was linearly related to the percent change in global EF after LAD (r = 0.84) and LC (r = 0.77) occlusions. The extent of ischemia also correlated with regional EF (r = 0.47 to 0.88 for LAD and r = 0.41 to 0.69 for LC occlusions). In 24 of 25 LAD occlusions and in all 20 LC occlusions that produced a measurable ischemic zone, the maximal percent change in regional EF exceeded the percent change in global EF. Two LAD occlusions and 2 LC occlusions reduced regional EF but not global EF. Thus, global and regional EF decreased in direct proportion to the extent of acute myocardial ischemia; regional ischemia produced greater changes in regional than in global EF.
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Gasto Cardíaco , Circulación Coronaria , Enfermedad Coronaria/fisiopatología , Volumen Sistólico , Animales , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/fisiopatología , Enfermedad Coronaria/diagnóstico por imagen , Perros , Ventrículos Cardíacos/fisiopatología , Hemodinámica , Contracción Miocárdica , CintigrafíaRESUMEN
The relation between bicycle exercise performance and determinants of central and peripheral cardiovascular function was assessed in 17 patients with class II to III heart failure and in 9 normal subjects. Proportional changes in oxygen consumption (VO2) from rest (R) to maximal exercise (Ex), or Mets, were used as an objective measure of the exercise capacity or functional reserve of the cardiovascular system. Left ventricular ejection fraction (EF) and proportional changes in end-diastolic volume, stroke volume, and cardiac output were determined from appropriate count data by equilibrium radionuclide angiography. Proportional changes in arteriovenous oxygen difference (A-VO2) were derived from the equation Ex/R A-VO2 = Ex/R VO2 divided by Ex/R CO, where CO = count output. Each subject exercised to an anaerobic endpoint. Maximal VO2 was significantly lower in patients than in normal subjects. Because Ex/R A-VO2 was comparable in normal subjects and patients, the lower exercise performance in patients resulted from a reduced count output response. The reduced CO response in patients resulted from failure of the ejection fraction to increase or from an attenuated heart rate response, or both. Exercise performance was variable in both groups. Multivariable analysis in the patient group identified changes in heart rate, count output, and A-VO2 with exercise as important predictors of Mets, but found no relation between Mets and changes in ejection fraction or stroke counts during exercise. Similarly, multiple regression analyses between Mets and determinants of cardiovascular function demonstrated significant correlations with Ex/R heart rate, Ex/R count output, and Ex/R A-VO2 in both groups. In patients, EF at rest ranged from 0.09 to 0.36, but it did not correlate with Mets, nor did changes in ejection fraction, stroke counts, or end-diastolic counts during exercise. The variable exercise performance among patients with severe left ventricular dysfunction was determined predominantly by a variable heart rate and A-VO2 response and not by rest or exercise indexes of left ventricular function.
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Insuficiencia Cardíaca/diagnóstico , Adulto , Anciano , Presión Sanguínea , Prueba de Esfuerzo , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Cintigrafía , Descanso , Volumen SistólicoRESUMEN
The effects of medium-dose (160 mg/day) and high-dose (480 mg/day) oral propranolol were compared in 22 patients who had typical angina pectoris and objective evidence of myocardial ischemia during exercise. Left ventricular (LV) ejection fraction (EF) and wall motion score (WMS) (an index of regional LV dysfunction) were assessed by radionuclide angiography both at rest and during exercise to the pretreatment maximum work load. Functional class improved in 11 of the 22 patients during medium-dose propranolol therapy. Medium-dose propranolol reduced mean resting heart rate from 71 to 55 beats/min, exercise heart rate from 122 to 93 beats/min, and exercise systolic blood pressure from 183 to 162 mm Hg (p less than 0.001 for each). The incidences of exercise-induced chest pain and S-T segment depression were reduced from 19 to 9 patients (p less than 0.001), and from 20 to 10 patients (p = 0.002), respectively. Medium-dose propranolol had no effect on mean EF or WMS at rest, but improved function in ischemic regions during exercise; WMS decreased (p = 0.001), and mean exercise EF increased from 0.51 to 0.56 (p = 0.025). Compared with the medium dose, high-dose propranolol improved functional class in 3 additional patients, and further reduced mean resting heart rate (from 55 to 52 beats/min, p = 0.001) and mean exercise heart rate (from 93 to 86 beats/min, p = 0.001). Exercise-induced chest pain and S-T segment depression were abolished in a further 7 and 6 patients, respectively. Exercise EF and WMS improved further in several patients, but the changes were not statistically significant for the group (p = 0.095 and 0.082, respectively). Thus, in patients with coronary artery disease and exercise-induced ischemia, propranolol reduced heart rate and blood pressure and the incidence of exercise-induced chest pain, electrocardiographic changes, and ischemic LV dysfunction. Although most of these effects were seen with medium-dose propranolol, higher doses provided additional relief of chest pain and S-T segment depression, and further improved global and regional LV function in several patients.
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Angina de Pecho/tratamiento farmacológico , Enfermedad Coronaria/tratamiento farmacológico , Propranolol/administración & dosificación , Vasos Coronarios/diagnóstico por imagen , Relación Dosis-Respuesta a Droga , Prueba de Esfuerzo , Corazón/fisiopatología , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Propranolol/sangre , Cintigrafía , Volumen Sistólico/efectos de los fármacosRESUMEN
To determine the physiologic mechanisms of the decline in aerobic work performance with age, a cross-sectional study was performed. Twenty-four sedentary male volunteers, aged 20 to 50 years, underwent right-sided cardiac catheterization, arterial cannulation, radionuclide angiography and expired gas analysis for detailed evaluation of central and peripheral cardiovascular function during submaximal and maximal exercise. Habitual physical activity level varied but was well matched across the age range. Over the 3-decade age range studied, there was no detectable change in cardiovascular function at rest. When peak exercise variables were examined, an age-related 25% decrease in O2 consumption was noted (r = -0.43, p = 0.04); this was associated with a 25% decrease in peak cardiac index (r = -0.54, p = 0.01) and a 20% decrease in peak heart rate (r = -0.63, p = 0.002). In addition, there was an age-related increase in calculated systemic and pulmonary vascular resistances and an increase in left ventricular ejection time. No age relation was seen for exercise stroke volume index, end-diastolic volume index, end-systolic volume index, pulmonary artery wedge pressure, ejection fraction or arteriovenous O2 difference. These results indicate that the age-related decline in aerobic work performance among men aged 20 to 50 years results primarily from a reduced exercise heart rate in older subjects rather than from a reduction in stroke volume or peripheral O2 utilization.
Asunto(s)
Envejecimiento , Fenómenos Fisiológicos Cardiovasculares , Metabolismo Energético , Adulto , Aerobiosis , Corazón/diagnóstico por imagen , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Esfuerzo Físico , Aptitud Física , CintigrafíaRESUMEN
The effects of nifedipine (60 to 90 mg/day) and propranolol (240 mg/day) on symptoms, angina threshold and cardiac function were compared in a placebo-controlled, double-blind, crossover study. Five-week treatment periods with nifedipine and propranolol were compared with 2 weeks of placebo treatment in 21 men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. Compared with placebo, New York Heart Association functional class improved in patients equally with nifedipine (p = 0.001) and propranolol (p = 0.006). Frequency of chest pain decreased with nifedipine (p = 0.001) and propranolol (p = 0.01), and nitroglycerin consumption similarly decreased with both treatments. Nifedipine significantly delayed the onset of chest pain (p = 0.01) and 1 mm of ST-segment depression (p = 0.002) during bicycle exercise; smaller increases with propranolol were not statistically significant. A preferential clinical response to nifedipine (9 patients) or propranolol (6 patients) was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvements in ejection fraction at identical workloads, from 0.48 +/- 0.11 to 0.58 +/- 0.12 (p less than 0.001) and 0.56 +/- 0.14 (p less than 0.001), respectively. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14% (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Angina de Pecho/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Nifedipino/uso terapéutico , Esfuerzo Físico , Propranolol/uso terapéutico , Adulto , Anciano , Angina de Pecho/fisiopatología , Presión Sanguínea/efectos de los fármacos , Dióxido de Carbono/análisis , Gasto Cardíaco/efectos de los fármacos , Ensayos Clínicos como Asunto , Método Doble Ciego , Pruebas de Función Cardíaca , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Nitroglicerina/uso terapéutico , Oxígeno/análisis , Placebos , RespiraciónRESUMEN
This study compared the noninvasive assessment of left ventricular function with radionuclide angiography with that obtained with ultrasonic sonomicrometry. Left ventricular ejection fraction and rate of ventricular ejection (dV/dt) were measured with both techniques over a wide range of ventricular function. Six dogs were prepared with epicardial crystals across the major and minor axes of the left ventricle, paired transmural wall thickness crystals and a left ventricular catheter. The animals were studied while awake after they had recovered from operation. Left ventricular volume was calculated from the ultrasonic sonomicrometric dimension measurements and the equation for a prolate ellipsoid; dV/dt was calculated from the stroke volume and ejection time. Radionuclide angiograms were performed using technetium-99m--labeled red blood cells and an Anger camera with a converging collimator interfaced to a computer programmed for multigated acquisition. A wide range of ventricular function was produced with sequential infusion of isoproterenol, propranolol, phenylephrine and sodium thiamylal. Ejection fraction and dV/dt were measured simultaneously during each intervention using the time-activity curves of the multigated radionuclide angiogram and ultrasonic sonomicrometric dimensions. Regression analyses demonstrated a close correlation between the simultaneous measurements of ejection fraction (r values ranged from 0.95 to 0.99) and dV/dt (r values ranged from 0.87 to 0.99). These data indicate that noninvasive multigated radionuclide angiography accurately assesses changes in ejection fraction and dV/dt over a wide range of ventricular function.
Asunto(s)
Ventrículos Cardíacos/diagnóstico por imagen , Sonicación , Ultrasonido , Animales , Perros , Ventrículos Cardíacos/cirugía , Cintigrafía , Análisis de Regresión , Factores de Tiempo , Función VentricularRESUMEN
The value of rest and exercise radionuclide angiography (RNA) for predicting specific events including death, recurrent acute myocardial infarction (AMI), coronary care unit readmission for unstable chest pain, and medically refractory angina after AMI was studied in 106 consecutive survivors of AMI. Analysis of the RNA variables using the Cox proportional hazards regression model yielded significant associations of the time to death with ejection fraction at rest and during exercise (X2 = 11.1 and 14.0, respectively). Both variables added significant prognostic information to the clinical assessment (X2 = 4.3 and 5.7, respectively). The change in ejection fraction from rest to exercise predicted the time to coronary artery bypass grafting for medically refractory angina before (X2 = 21.0) and after (X2 = 13.2) adjustment for the clinical descriptors, but did not predict death or other non-fatal events. Significant correlations were found between RNA variables and a variety of clinical descriptors previously reported to have prognostic significance. Clinical and RNA variables that are measures of left ventricular function were predictive of subsequent mortality, whereas those that reflect residual potentially ischemic myocardium were predictive of subsequent nonfatal ischemic events. Rest and exercise RNA after AMI provides significant prognostic information regarding specific events during follow-up independent of that provided by clinical assessment.