RESUMEN
Cholesterol embolism, a serious but infrequent complication of renal artery stenting, may be avoided by minimizing contact between the guide catheter and the atherosclerotic aorta. In this report, we illustrate the "no-touch" technique for stenting renal arteries. By placing a second 0.035-inch J-wire within the guide catheter during cannulation of the renal artery to prevent the tip of the guide from rubbing the aortic wall, we minimize the contact between the guide catheter and atherosclerotic plaques and reduce the potential for intimal disruption and cholesterol embolization.
Asunto(s)
Arteriosclerosis/terapia , Cateterismo Periférico/métodos , Arteria Renal , Stents , Embolia por Colesterol/prevención & control , HumanosRESUMEN
Growth factors have been implicated in the pathogenesis of restenosis (myointimal hyperplasia after coronary interventions). In this study, we examined the expression of insulin-like growth factor-I (IGF-1), IGF-1 receptor, and transforming growth factor-beta (TGF-beta) in atherosclerotic and normal rabbit iliac arteries following overstretch balloon angioplasty of the iliac arteries to create a vascular lesion. Animals were sacrificed at 0, 3, 7, 15 and 42 days post angioplasty. The iliac arteries were processed for immunocytochemical localization of IGF-1, IGF-1 receptor and TGF-beta using colloidal gold and the data were quantitatively analyzed. IGF-1, IGF-1 receptor and TGF-beta immunoreactivity were all significantly increased in atherosclerotic arteries compared to control at all of the time points examined. Following balloon angioplasty, the levels of IGF-1 and IGF-1 receptor increased significantly in both control and even further in hypercholesterolemic vessels. In control vessels, the IGF-1 levels returned to preintervention levels, while in atherosclerotic vessels, the levels of IGF-1 and IGF-1 receptor remained elevated. In addition, TGF-beta levels in control vessels showed an initial rise in the first week following injury but then returned to baseline levels. In contrast, atherosclerotic vessels demonstrated a sustained expression of TGF-beta. Thus, IGF-1 and TGF-beta expression is different in normal vs. atherosclerotic vessels following vascular injury. The intensity of expression of IGF-1 and its receptor, which is not reduced at 42 days compared to 15 days following injury, support a role for IGF-1 in smooth muscle cell proliferation and migration. The sustained increase in TGF-beta could facilitate extracellular matrix (ECM) accumulation. Local vascular therapy that is directed towards modulating the effects of IGF-1 and TGF-beta could reduce restenosis.
Asunto(s)
Angioplastia de Balón , Arteriosclerosis/metabolismo , Arteriosclerosis/terapia , Arteria Ilíaca/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Receptor IGF Tipo 1/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Angioplastia de Balón/métodos , Animales , Arteria Ilíaca/patología , Arteria Ilíaca/ultraestructura , ConejosRESUMEN
This pilot study evaluates the effects of quinapril, an angiotensin-converting enzyme inhibitor with high tissue-binding affinity, on microvascular endothelial function in patients with mild (<40% narrowing) coronary artery disease and epicardial endothelial dysfunction. Patients randomized to quinapril had a trend suggesting an increase in endothelium-dependent coronary blood flow response.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Circulación Coronaria/efectos de los fármacos , Enfermedad Coronaria/fisiopatología , Endotelio Vascular/fisiopatología , Isoquinolinas/farmacología , Tetrahidroisoquinolinas , Acetilcolina/farmacología , Adenosina/farmacología , Adulto , Anciano , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Enfermedad Coronaria/tratamiento farmacológico , Femenino , Humanos , Masculino , Microcirculación/fisiopatología , Persona de Mediana Edad , Nitroglicerina/farmacología , Proyectos Piloto , Quinapril , Vasodilatadores/farmacologíaRESUMEN
The molecular and cellular processes that induce rapid atherosclerotic plaque progression in patients with unstable angina and initiate restenosis following coronary interventional procedures are uncertain. We examined primary (de novo) and restenotic lesions retrieved at the time of directional coronary atherectomy for expression of insulin-like-growth factor-I (IGF-I). IGF-I receptor, and five IGF binding proteins (IGFBPs), IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-5 in smooth muscle cells (SMCs) using colloidal gold immunocytochemistry. IGF-1, its receptor and binding proteins were not detected in SMCs of normal coronary arteries. IGF-I localized primarily in synthetic smooth muscle cells (sSMCs) in both de novo and restenotic plaques. IGF-I receptor localized on sSMCs and their processes and colocalized with IGF-I. Although morphometric analysis of IGF-I and IGF-I receptor immunoreactivity in sSMCs of de novo and restenotic lesions showed comparable levels of IGF-I (3.2 +/- 1.0 and 2.9 +/- 0.9, respectively). IGF-I receptor was significantly higher in de novo lesions as compared to restenotic lesions (10.7 +/- 2.5 and 4.2 +/- 1.3, P < 0.05, respectively). IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-5 localized in the cytoplasm of sSMCs and in the extracellular matrix. Quantitative reverse transcription polymerase chain reaction (QRT-PCR) performed on de novo atherectomy specimens identified mRNA for IGF-I, IGF-I receptor, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5 levels and detected mRNA for IGFBP-3. The expression of IGF-I, IGF-I receptor, and IGFBPs in atherectomy plaques suggests that the development of coronary obstructive lesions may be a result of changes in the IGF system.
Asunto(s)
Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Receptor IGF Tipo 1/metabolismo , Aterectomía Coronaria , Enfermedad de la Arteria Coronaria/metabolismo , Vasos Coronarios/química , Vasos Coronarios/metabolismo , Electroforesis en Gel de Agar , Regulación de la Expresión Génica/genética , Oro Coloide/inmunología , Humanos , Microscopía Inmunoelectrónica , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , ARN Mensajero/metabolismoRESUMEN
The presence of angiographic evidence of thrombus is generally thought to be a contraindication to coronary stent placement. This report describes four patients in whom angiographic thrombus was lysed using the Dispatch infusion catheter prior to coronary stenting. Urokinase was infused via the Dispatch catheter with resolution of angiographic evidence of thrombus in all cases. No complications were encountered using this technique, and all patients had excellent angiographic results after stenting. We conclude that lysis of intracoronary thrombus using the Dispatch infusion catheter is feasible and appears safe in this small study. Further trials are needed to determine if this technique reduces the acute stent thrombosis rate compared to other techniques for stent deployment in the presence of angiographic evidence of thrombus.
Asunto(s)
Trombosis Coronaria/terapia , Stents , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Angioplastia Coronaria con Balón , Angiografía Coronaria , Trombosis Coronaria/diagnóstico por imagen , Heparina/administración & dosificación , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Proyectos Piloto , PremedicaciónRESUMEN
BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized. METHODS AND RESULTS: Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n = 54) and quinapril (n = 51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5 +/- 3.0% [mean +/- SEM] versus -0.1 +/- 2.8% at 10(-6) mol/L and 12.1 +/- 3.0% versus -0.8 +/- 2.9% at 10(-4) mol/L, quinapril versus placebo, respectively; overall P = .002). CONCLUSIONS: TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/fisiopatología , Endotelio Vascular/fisiopatología , Isoquinolinas/uso terapéutico , Tetrahidroisoquinolinas , Sistema Vasomotor/fisiopatología , Acetilcolina , Enfermedad Coronaria/diagnóstico por imagen , Método Doble Ciego , Endotelio Vascular/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Quinapril , Radiografía , Sistema Vasomotor/efectos de los fármacosRESUMEN
BACKGROUND: Coronary endothelium plays a key role in the regulation of coronary tone, platelet adhesion, and aggregation, which are important factors in triggering acute cardiovascular events. However, its role in modulating the effects of circadian variations on coronary tone is not known. METHODS AND RESULTS: Responses of 72 nonstenotic coronary segments to acetylcholine and nitroglycerin were measured in 12 patients with chronic stable angina at 6 AM and 1 PM. After baseline angiography, three infusions of acetylcholine (10(-6), 10(-5), and 10(-4) mol/L) were administered selectively into the left coronary artery, followed by nitroglycerin. Diameters (in millimeters) of proximal, middle, and distal segments were measured by quantitative techniques. Forty-seven segments showed a constrictor response to acetylcholine (group 1, dysfunctional endothelium), and 25 other segments showed a dilator response (group 2, normally functioning endothelium). In group 1, the constrictor response to acetylcholine was significantly greater in the morning than in the afternoon (23 +/- 3% and 10 +/- 1%, mean +/- SEM, respectively; P < .001), and the dilator response to nitroglycerin was also significantly greater in the morning than in the afternoon (19 +/- 2% and 11 +/- 2%; P < .01). In group 2, the dilator response to acetylcholine did not differ significantly between the morning and afternoon (22 +/- 3% and 17 +/- 2%, respectively; P = NS), and the dilator response to nitroglycerin was also similar at both times of the day (30 +/- 3% and 28 +/- 4%, respectively; P = NS). CONCLUSIONS: Coronary segments with dysfunctional endothelium exhibit an early morning exaggeration in vasomotor activity, whereas segments with normally functioning endothelium do not show circadian variations. This suggests a potential protective role for the endothelium in modulating variations in coronary tone that may contribute to increased incidence of cardiovascular events in the early morning hours.
Asunto(s)
Angina de Pecho/fisiopatología , Ritmo Circadiano/fisiología , Vasos Coronarios/fisiopatología , Endotelio Vascular/fisiología , Acetilcolina , Anciano , Angina de Pecho/diagnóstico por imagen , Cateterismo Cardíaco , Angiografía Coronaria , Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Nitroglicerina , Vasoconstrictores , VasodilatadoresAsunto(s)
Angina de Pecho/fisiopatología , Endotelio Vascular/fisiopatología , Óxido Nítrico , Acetilcolina , Anciano , Angina de Pecho/diagnóstico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/fisiología , Nitroglicerina , Valor Predictivo de las PruebasRESUMEN
In this study, we demonstrate, for the first time, the localization of insulin-like growth factor I (IGF-I) in de novo and restenotic human coronary atherectomy plaques by using immunocytochemical techniques. Smooth muscle cells (SMCs) exhibiting the synthetic phenotype contained a statistically significant higher concentration of IGF-I than SMCs of the contractile phenotype or SMCs from normal coronary arteries. In addition, we provide data to suggest that the long-acting somatostatin analogues octreotide and angiopeptin inhibit IGF-I- and basic fibroblast growth factor (b-FGF)- induced human coronary artery SMC proliferation. Platelet-derived growth factor (PDGF)-stimulated cultures were minimally affected by the addition of octreotide but were significantly inhibited by angiopeptin. All three growth factors stimulated SMC migration in a dose-dependent manner. The somatostatin analogues tested had no effect on growth factor-stimulated SMC migration. Our data suggest that by reducing SMC proliferation, somatostatin analogues may have clinical usefulness in reducing the high incidence of restenosis observed after percutaneous transluminal coronary artery interventions.
Asunto(s)
Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/análisis , Músculo Liso Vascular/efectos de los fármacos , Octreótido/farmacología , Oligopéptidos/farmacología , Somatostatina/análogos & derivados , Adulto , Angioplastia Coronaria con Balón , División Celular/efectos de los fármacos , Constricción Patológica/tratamiento farmacológico , Vasos Coronarios/química , Vasos Coronarios/citología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Humanos , Músculo Liso Vascular/química , Músculo Liso Vascular/citología , Péptidos Cíclicos , Factor de Crecimiento Derivado de Plaquetas/farmacología , Recurrencia , Somatostatina/farmacologíaRESUMEN
BACKGROUND: In patients with angiographically detectable atherosclerosis or in those with risk factors for coronary artery disease, intracoronary acetylcholine causes coronary constriction instead of endothelium-derived relaxing factor-mediated dilation. Therefore, it has been hypothesized that diffuse endothelial dysfunction precedes development of coronary atherosclerosis. We tested this hypothesis in a systematic investigation of the effects of ascending doses of acetylcholine on the diameters of nonstenotic segments of the left coronary artery in patients with advanced atherosclerosis and coronary risk factors. METHODS AND RESULTS: Effects of intracoronary infusion of acetylcholine (10(-6) to 10(-4) mol/L) on diameters of proximal, middle, and distal nonstenotic segments of the left coronary artery were studied in 28 consecutive patients with chronic stable angina, positive exercise tests, and angiographic evidence of obstructive atherosclerosis (> or = 50% reduction in lumen diameter in at least one vessel). Two patterns of response to the maximal acetylcholine dose (10(-4) mol/L) were observed. In 21 patients (group 1), only constriction was observed in all left anterior descending and circumflex artery segments studied (16 +/- 3%, 19 +/- 4%, and 23 +/- 4%, respectively; P < .01 compared with control). In 7 other patients (group 2), both constriction and dilation were observed in adjacent segments of the same vessel; maximal acetylcholine dose caused constriction in 14 left anterior descending artery segments from a control diameter of 1.94 +/- 0.19 to 1.33 +/- 0.26 mm (37% reduction, P < .01) and dilation in 16 other segments from 1.63 +/- 0.22 to 1.93 +/- 0.21 mm (25% increase, P < .01). In the circumflex artery, this dose caused constriction in 16 segments from a control diameter of 1.88 +/- 0.14 to 1.33 +/- 0.17 mm (31% reduction, P < .01) and dilation in 12 segments from 1.37 +/- 0.12 to 1.71 +/- 0.09 mm (34% increase, P < .01). CONCLUSIONS: In 25% of patients studied with advanced angiographic coronary atherosclerosis and coronary risk factors, coronary segments with acetylcholine-inducible dilatation are present. In these patients, the endothelium is not diffusely dysfunctional as currently believed but rather shows marked segmental heterogeneity in the response to acetylcholine reflecting degrees of endothelial dysfunction.
Asunto(s)
Acetilcolina/farmacología , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/fisiología , Acetilcolina/administración & dosificación , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/epidemiología , Vasos Coronarios/fisiopatología , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Femenino , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
A 30-year-old woman with tetralogy of Fallot and cavopulmonary anastomosis (Glenn shunt) presented with a large pulmonary arteriovenous fistula in the right lower lobe. This report describes the successful management following two successive therapeutic balloon embolizations.
Asunto(s)
Fístula Arteriovenosa/terapia , Cateterismo , Embolización Terapéutica , Complicaciones Posoperatorias/terapia , Arteria Pulmonar , Venas Pulmonares , Tetralogía de Fallot/cirugía , Adulto , Anastomosis Quirúrgica , Fístula Arteriovenosa/etiología , Femenino , Humanos , Arteria Pulmonar/cirugía , Factores de Tiempo , Vena Cava Superior/cirugíaRESUMEN
Radionuclide ventriculography and contrast ventriculography were performed in two comparable projections on 50 patients with suspected coronary artery disease. The efficacy of conventional cine display and Fourier image analysis of the radionuclide ventriculogram was compared using contrast ventriculography as the gold standard. Of seven different combinations of Fourier images, the combination of left anterior oblique amplitude and phase and left posterior oblique amplitude and phase provided the highest sensitivity (87%), specificity (83%), accuracy (86%), and kappa coefficient (0.64). To increase statistical power, segment data were collapsed to global data in which a heart was considered normal if all segments were normal and abnormal if one or more segments were abnormal. Fourier images had higher sensitivity (Fourier 87%, cine 47%); lower specificity (Fourier 83%, cine 92%), higher accuracy (Fourier 86%, cine 58%), and higher kappa coefficient (Fourier 0.64, cine 0.25), and these differences were statistically significant (p less than 0.01).
Asunto(s)
Enfermedad Coronaria/diagnóstico por imagen , Análisis de Fourier , Imagen de Acumulación Sanguínea de Compuerta , Películas Cinematográficas , Contracción Miocárdica/fisiología , Función Ventricular Izquierda/fisiología , Enfermedad Coronaria/fisiopatología , Presentación de Datos , Femenino , Humanos , MasculinoRESUMEN
Since thromboxane A2 (TXA2) release may relate to the extension of myocardial injury following coronary ligation, the authors examined the effects of pretreatment with a selective TXA2 synthetase inhibitor U-63,557A, or a TXA2 receptor antagonist SQ-29,548, on myocardial infarct size forty-eight hours following left coronary ligation in rats. Myocardial infarct size (as percent of left ventricle, LV) was decreased from 44 +/- 3% in saline-treated control animals to 34 +/- 4% (P less than 0.05) in U-63,557A-treated animals and to 32 +/- 4% (P less than 0.05) in SQ-29,548 treated animals (U-63,557A-treated vs SQ-29,548-treated, P = NS). LV creatine kinase (CK) was 5.08 +/- 0.42 IU/mg protein in noninfarcted untreated rats and 1.79 +/- 0.21 IU/mg protein in saline-treated infarcted rats. LV CK was 2.86 +/- 0.40 IU/mg protein in U-63,557A-treated rats and 3.11 +/- 0.51 IU/mg protein in SQ-29,548-treated infarcted rats (both P less than 0.05 compared with saline-treated rats). The beneficial effects of U-63,557A and of SQ-29,548 were not accompanied by reduction in indices of myocardial oxygen demand (heart rate and arterial pressure). However, neutrophil accumulation in the infarcted myocardium was markedly decreased by U-63,557A and SQ-29,548 pretreatment. Myocardial myeloperoxidase activity, a specific marker of neutrophil infiltration, was also decreased (P less than 0.02) in U-63,557A- and SQ-29,548-treated animals (0.09 +/- 0.03 and 0.07 +/- 0.02 units/100 mg, respectively) compared with saline-treated infarcted rats (0.19 +/- 0.04 units/100 mg). In vitro incubation of U-63,557A and SQ-29,548 caused a significant and similar reduction in f-MLP-induced neutrophil chemotaxis, and U-63,557A increased prostacyclin formation in whole blood. These data suggest that reduction in the extent of myocardial injury by TXA2 synthetase or receptor inhibitors may, in part, relate to a decrease in neutrophil accumulation in the infarcted tissue. In spite of differences in mechanisms of action of U-63,557A and SQ-29,548, both agents exert a similar protective effect on the extent of myocardial injury following coronary ligation. Reduction in neutrophil accumulation in the infarcted zone, as well as in f-MLP-directed chemotaxis in vitro, suggests that TXA2 inhibition may modulate neutrophil migration.
Asunto(s)
Infarto del Miocardio/patología , Miocardio/patología , Neutrófilos/patología , Tromboxano A2/antagonistas & inhibidores , Tromboxano-A Sintasa/antagonistas & inhibidores , Animales , Benzofuranos/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes , Quimiotaxis de Leucocito/efectos de los fármacos , Creatina Quinasa/metabolismo , Epoprostenol/sangre , Epoprostenol/metabolismo , Ácidos Grasos Insaturados , Hidrazinas/farmacología , Masculino , Infarto del Miocardio/sangre , Infarto del Miocardio/enzimología , Miocardio/enzimología , Neutrófilos/efectos de los fármacos , Neutrófilos/fisiología , Peroxidasa/metabolismo , Agregación Plaquetaria/efectos de los fármacos , Ratas , Ratas Endogámicas , Tromboxano B2/sangre , Tromboxano B2/metabolismoRESUMEN
It has been suggested that omega-3 polyunsaturated fatty acids (PUFAs) may alter the course of coronary artery disease by influencing platelet and neutrophil function, arachidonic acid metabolism, and circulating lipid concentrations. To examine this hypothesis, placebo or omega-3 PUFAs as Max-EPA (equivalent to 3.2 g of eicosapentaenoic acid and 2.2 g of docosahexaenoic acid daily) was administered to eight patients with stable coronary artery disease and positive exercise stress test results in a randomized, double-blind, crossover fashion over a 12-week period. With Max-EPA administration, platelet aggregation threshold to epinephrine was increased in only two patients, but neutrophil aggregation and chemotaxic functions decreased consistently (both p less than or equal to 0.01 compared with preceding placebo phase) in all eight. Serum and platelet-rich plasma thromboxane B2 concentrations decreased 40 percent and 28 percent, respectively (both p less than or equal to 0.05). Neutrophil leukotriene B4 formation decreased 23 percent (p less than or equal to 0.01) and synthesis of leukotriene B5 became apparent in all subjects. Serum triglyceride concentrations fell 52 percent (p less than or equal to 0.05) without significant change in total cholesterol, high-density lipoprotein-cholesterol, or low-density lipoprotein-cholesterol concentrations. Systolic blood pressure and the double product (heart rate X systolic blood pressure) were lower (p less than or equal to 0.05) at the end of the Max-EPA phase than in the preceding placebo phase. Heart rate, systolic blood pressure, and the double product were also lower (p less than or equal to 0.05) at three as well as at six minutes of an exercise stress test, indicating a significant reduction in myocardial oxygen demand. Despite these alterations in platelet and neutrophil function, arachidonic acid metabolism, serum triglyceride concentrations, and myocardial oxygen demand, there were no significant changes in subjective parameters of coronary artery disease during the Max-EPA phase (angina frequency 3.7 versus 2.8 episodes per week, nitroglycerin consumption 3.0 versus 1.9 tablets per week, both p = NS). Similarly, exercise times to ST-segment depression (6.5 versus 4.1 minutes) and to onset of angina (5.4 versus 5.0 minutes) were not altered by administration of Max-EPA. Thus, short-term dietary supplementation with omega-3 PUFAs to patients with stable coronary artery disease does not appear to alter subjective or objective parameters of myocardial ischemia.
Asunto(s)
Enfermedad Coronaria/dietoterapia , Grasas Insaturadas en la Dieta/uso terapéutico , Ácidos Docosahexaenoicos , Ácido Eicosapentaenoico , Ácidos Grasos Insaturados/uso terapéutico , Anciano , Quimiotaxis de Leucocito , Ensayos Clínicos como Asunto , Enfermedad Coronaria/sangre , Método Doble Ciego , Combinación de Medicamentos , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/fisiología , Esfuerzo Físico , Pruebas de Función Plaquetaria , Distribución AleatoriaRESUMEN
Dichloroacetate (DCA), which activates pyruvate dehydrogenase, has the potential to enhance carbohydrate and lactate utilization in animals, but data from patients with coronary artery disease are lacking. Accordingly, 9 patients (ages 49 to 72 years) with angina and coronary artery disease undergoing catheterization were studied. Systemic and coronary hemodynamic and metabolic measurements were made before and during DCA administration (mean dose 35 mg/kg, intravenously). DCA increased left ventricular (LV) stroke volume from 77 +/- 7 to 87 +/- 7 ml and decreased systemic vascular resistance from 1,573 +/- 199 to 1,319 +/- 180 dynes.s.cm-5 (both, p less than 0.01). There were no significant changes in heart rate, mean aortic pressure, LV end-diastolic pressure, LV dP/dt max, coronary sinus flow, coronary resistance or myocardial oxygen consumption, but myocardial efficiency index (LV work/myocardial oxygen consumption) improved from 24 to 32% (p less than 0.05). Myocardial lactate consumption was maintained (21 +/- 8 vs 19 +/- 11 X 10(-3) mEq/min, p is not significant at p less than or equal to 0.05 level) at a lower arterial lactate concentration (0.72 +/- 0.09 to 0.47 +/- 0.08 mEq/liter, p less than 0.05). DCA appears to stimulate myocardial lactate utilization at a lower arterial concentration, cause peripheral vasodilation, augment stroke volume and enhance myocardial efficiency in patients with coronary artery disease.
Asunto(s)
Acetatos/uso terapéutico , Enfermedad Coronaria/tratamiento farmacológico , Ácido Dicloroacético/uso terapéutico , Corazón/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Anciano , Cateterismo Cardíaco , Enfermedad Coronaria/metabolismo , Ácido Dicloroacético/farmacología , Femenino , Humanos , Lactatos/sangre , Masculino , Persona de Mediana EdadRESUMEN
We examined the effects of a new selective thromboxane A2 (TXA2) synthetase inhibitor, U-63,557A, on myocardial infarct size 48 hours following left coronary ligation in rats. With a single 8 mg/kg dose of U-63,557A (furegrelate) administered prior to coronary ligation, platelet aggregation and serum TXA2 formation declined significantly (p less than 0.02) for up to 48 hours. Myocardial infarct size, as measured by planimetry of serial left ventricular sections, was decreased from 44 +/- 3% (saline-treated control rats) to 34 +/- 4% (p less than 0.05). Left ventricular creatine kinase (CK) following coronary ligation was also preserved in U-63,557A vs saline-treated control animals (p less than 0.05). These beneficial effects of U-63,557A were not accompanied by reduction in the indices of myocardial oxygen demand (heart rate and arterial pressure). Furthermore, neutrophil accumulation in the infarcted myocardium was significantly decreased by U-63,557A (26 +/- 6 vs 96 +/- 3/high-power field [p less than 0.01]). These data suggest that administration of a single dose of selective TXA2 synthetase inhibitor prior to coronary ligation modulates platelet function for up to 48 hours and reduces the extent of myocardial injury, which may, in part, relate to decrease in neutrophil accumulation.
Asunto(s)
Infarto del Miocardio/patología , Miocardio/patología , Neutrófilos/fisiología , Espectinomicina/análogos & derivados , Tromboxano-A Sintasa/antagonistas & inhibidores , Animales , Creatina Quinasa/análisis , Hemodinámica/efectos de los fármacos , Recuento de Leucocitos , Masculino , Infarto del Miocardio/sangre , Agregación Plaquetaria , Ratas , Espectinomicina/farmacología , Tromboxano A2/sangreRESUMEN
The accumulated evidence indicates that myocardial ischemia is a complex process involving dysfunction of various cellular elements as well as coronary narrowing. A homeostatic imbalance of endogenously produced vasoactive compounds, released locally as a result of intricate platelet, neutrophil, and endothelial cell-cell interactions, participates in the eventual outcome of tissue ischemia. This imbalance is frequently caused by the formation of an intracoronary platelet thrombus. Therapeutic strategy aimed to modulate intrinsic eicosanoid biosynthesis and neutrophil platelet function may reduce ischemia and benefit patients with ischemic heart disease.