RESUMEN
Coronary artery calcification (CAC) is associated with atherosclerotic complications. However, elevated CAC may not always imply a worse prognosis. Herein, we report the clinical evolution of long-term red wine (RW) drinkers in relation to CAC. We followed 200 healthy male habitual RW drinkers and compared them to 154 abstainers for a period of 5.5 years. The initial evaluation included coronary computed tomography angiography (CTA), clinical, demographics, and laboratory data. CAC was quantified by the Agatston score. The follow-up process was conducted by telephone calls and/or hospital record review. The composite end-point of total death, acute myocardial infarction (AMI), or coronary revascularization (or major adverse cardiac event - MACE) was assessed. The RW drinkers ingested 28.9±15 g of alcohol/day for 23.4±12.3 years. They had higher high-density lipoprotein and low-density lipoprotein, but lower C-reactive protein than abstainers. Age, total cholesterol, triglycerides, glucose, and liver enzymes were similar. History of diabetes was lower among drinkers, but other risk factors were similar. However, drinkers had higher CAC than abstainers; the mean value was 131.5±362 in drinkers vs 40.5±320 in abstainers (P<0.001). The median and interquartile range were 15 (0.0-131.5) in RW drinkers and 1 (0.0-40.5) in abstainers (P=0.003). During the follow-up, MACE was significantly lower in drinkers than in abstainers, despite their higher CAC. The difference was driven mainly by AMI (0 vs 6; P<0.03). Greater CAC values in this setting did not predict worse prognosis. A possible underlying mechanism is lesion calcification, which leads to plaque stabilization and less clinical events.
Asunto(s)
Consumo de Bebidas Alcohólicas , Enfermedad de la Arteria Coronaria/prevención & control , Calcificación Vascular/prevención & control , Vino , Anciano , Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calcificación Vascular/diagnóstico por imagenRESUMEN
The relationship between lipid serum levels and coronary atherosclerotic plaque fat content was studied in 51 necropsy patients. Serum lipids were measured by standard techniques, during life, in the absence of lipid-lowering drugs. Intima, intimal fat and media areas were measured using a computerized system in cryosections of the odd segments of the right, anterior descending and circumflex coronary arteries stained with Sudan-IV. Mean intimal and lipid areas were 5.74 +/- 1.98 and 1.22 +/- 0.55 mm2 (22.12 +/- 8.48%) in 26 cases with high cholesterol (>or=200 mg/dL) and 4.98 +/- 1.94 and 1.16 +/- 0.66 mm2 (22.75 +/- 9.06%) in 25 cases with normal cholesterol (<200 mg/dL; P > 0.05). Patients with high levels of low-density lipoprotein (>or=130 mg/dL, N = 15) had a higher intima/media area ratio than those with normal levels of low-density lipoprotein (<130 mg/dL, N = 13, P < 0.01). No significant difference in the morphometrical variables was found in groups with high or low serum levels of triglycerides (>or=200 mg/dL, N = 13 vs <200 mg/dL, N = 36) or high-density lipoprotein (>or=35 mg/dL, N = 11 vs <35 mg/dL, N = 17). The association between the morphological measurements and serum levels of cholesterol, its fractions, and triglycerides was also tested and the correlation coefficients were low. Although high cholesterol is a risk factor, we show here that in patients with severe atherosclerosis blood cholesterol and triglyceride levels seem to have little influence on coronary lipid content, indicating that other factors may contribute to arterial lipid deposition and plaque formation.
Asunto(s)
Aterosclerosis/sangre , Aterosclerosis/patología , Vasos Coronarios/patología , Lípidos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Vasos Coronarios/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
The authors pay homage to the three founders of the Brazilian Journal of Medical and Biological Research Profs. Lewis Joel Greene, Sérgio Henrique Ferreira and Eduardo Moacyr Krieger for their vision and commitment to divulge the scientific production of developing countries.
Asunto(s)
Investigación Biomédica/historia , Publicaciones Periódicas como Asunto/historia , Brasil , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
Hyperhomocystinemia has been related to an increased risk of cardiovascular disease in several studies. The C677T polymorphism for the gene that encodes the methylenetetrahydrofolate reductase enzyme (MTHFR) and low plasma folate levels are common causes of hyperhomocystinemia. Due to differences in nutritional patterns and genetic background among different countries, we evaluated the role of hyperhomocystinemia as a coronary artery disease (CAD) risk factor in a Brazilian population. The relation between homocysteine (Hcy) and the extent of CAD, measured by an angiographic score, was determined. A total of 236 patients referred for coronary angiography for clinical reasons were included. CAD was found in 148 (62.7%) patients and 88 subjects had normal or near normal arteries. Patients with CAD had higher Hcy levels [mean (SD)] than those without disease (14 (6.8) vs 12.5 (4.0) microM; P = 0.04). Hyperhomocystinemia (Hcy >17.8 microM) prevalence was higher in the CAD group: 31.1 vs 12.2% (P = 0.01). After adjustment for major risk factors, we found an independent association between hyperhomocystinemia and CAD (OR = 2.48; 95% CI = 1.02-6.14). Patients with a more advanced coronary score had a higher frequency of hyperhomocystinemia and tended to have higher mean Hcy levels. An inverse relation between plasma folate and Hcy levels was found (r = -0.14; P = 0.04). Individuals with the MTHFR C677T polymorphism had a higher prevalence of hyperhomocystinemia than those without the mutated allele. We conclude that hyperhomocystinemia is independently associated with CAD, with a positive association between Hcy level and disease severity.
Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Homocisteína/sangre , Hiperhomocisteinemia/complicaciones , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/enzimología , Enfermedad de la Arteria Coronaria/genética , Estudios Transversales , Femenino , Humanos , Hiperhomocisteinemia/enzimología , Hiperhomocisteinemia/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Myocardial contrast echocardiography has been used for assessing myocardial perfusion. Some concerns regarding its safety still remain, mainly regarding the induction of microvascular alterations. We sought to determine the bioeffects of microbubbles and real-time myocardial contrast echocardiography (RTMCE) in a closed-chest canine model. Eighteen mongrel dogs were randomly assigned to two groups. Nine were submitted to continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) plus continuous imaging using power pulse inversion RTMCE for 180 min, associated with manually deflagrated high-mechanical index impulses. The control group consisted of 3 dogs submitted to continuous imaging using RTMCE without PESDA, 3 dogs received PESDA alone, and 3 dogs were sham-operated. Hemodynamics and cardiac rhythm were monitored continuously. Histological analysis was performed on cardiac and pulmonary tissues. No hemodynamic changes or cardiac arrhythmias were observed in any group. Normal left ventricular ejection fraction and myocardial perfusion were maintained throughout the protocol. Frequency of mild and focal microhemorrhage areas in myocardial and pulmonary tissue was similar in PESDA plus RTMCE and control groups. The percentages of positive microscopical fields in the myocardium were 0.4 and 0.7% (P = NS) in the PESDA plus RTMCE and control groups, respectively, and in the lungs they were 2.1 and 1.1%, respectively (P = NS). In this canine model, myocardial perfusion imaging obtained with PESDA and RTMCE was safe, with no alteration in cardiac rhythm or left ventricular function. Mild and focal myocardial and pulmonary microhemorrhages were observed in both groups, and may be attributed to surgical tissue manipulation.
Asunto(s)
Ecocardiografía/métodos , Glucosa , Microburbujas , Miocardio/ultraestructura , Albúmina Sérica , Animales , Perros , Infusiones Intravenosas , Albúmina Sérica Humana , Función Ventricular IzquierdaRESUMEN
Endomyocardial fibrosis has been treated surgically for many years. For complete removal of fibrosis from both ventricles by the classic technique, each atrioventricular (AV) valve was removed and replaced with a prosthesis. Relapse of endomyocardial fibrosis has not been observed after surgical correction. Reoperations have been carried out because of complications of valve prostheses. A new surgical technique for removal of ventricular fibrous tissue with preservation of the mitral and tricuspid valves was used in nine consecutive patients with endomyocardial fibrosis. Initial results show a reduction of pulmonary hypertension, mean right and left atrial pressures and end-diastolic pressures in both ventricles. Tricuspid annuloplasty was performed in seven patients and mitral annuloplasty in five. No valve prosthesis was used. There was no death and New York Heart Association functional class improved from class III or IV in the preoperative period to class I or II in the postoperative period. These data suggest that resection of endocardial fibrous tissue can be indicated early in the clinical course and performed with preservation of the AV valves.
Asunto(s)
Fibrosis Endomiocárdica/cirugía , Válvula Mitral/cirugía , Válvula Tricúspide/cirugía , Adulto , Fibrosis Endomiocárdica/mortalidad , Femenino , Estudios de Seguimiento , Prótesis Valvulares Cardíacas , Humanos , Hipertensión Pulmonar/prevención & control , Masculino , Persona de Mediana Edad , Reoperación , Volumen Sistólico/fisiologíaRESUMEN
OBJECTIVES: This study sought to characterize leukocyte and platelet activation and adhesion molecule expression after coronary angioplasty. BACKGROUND: Coronary angioplasty can be regarded as a clinical model of postischemic inflammation because this intervention leads to the release of inflammatory mediators as a result of plaque rupture and endothelial injury. METHODS: In 13 patients with stable angina (mean [ +/- SEM] age 56.0 +/- 2.4 years, range 44 to 79), blood samples were drawn from the aorta and coronary sinus immediately before and immediately and 15 min after coronary angioplasty. Subsequently, leukocyte and platelet functions were determined. Eleven control patients (57.5 +/- 2.3 years, range 52 to 78) underwent coronary arteriography. RESULTS: Coronary arteriography and angioplasty showed no difference in number of leukocytes between the coronary sinus and the aorta. However, 15 min after coronary angioplasty, there was an increase in neutrophil CD18 and CD11b, monocyte CD14 and platelet glycoprotein IIb/IIIa expression and a decrease in neutrophil L-selectin expression (189 +/- 25%, 163 +/- 27%, 158 +/- 35%, 141 +/- 22% and 31 +/- 10%, respectively, p < 0.01). In the control subjects, no change in adhesion molecule expression occurred. Superoxide production and aggregation in ex vivo-stimulated neutrophils collected from the coronary sinus 15 min after coronary angioplasty was significantly decreased compared with that after coronary arteriography (54 +/- 12% vs. 106 +/- 30% and 58 +/- 11% vs. 102 +/- 29%, respectively, p < 0.01). The reduced responses to phorbol ester stimulation may be explained by previous in vivo activation of neutrophils during coronary angioplasty. CONCLUSIONS: Coronary angioplasty increases neutrophil, monocyte and platelet adhesion molecule expression and induces a significant decrease in ex vivo-stimulated neutrophil superoxide generation and aggregation. These findings suggest that coronary angioplasty triggers cellular activation with an inflammatory response that could contribute to restenosis.
Asunto(s)
Angioplastia Coronaria con Balón , Moléculas de Adhesión Celular/metabolismo , Enfermedad Coronaria/terapia , Activación de Linfocitos , Activación Neutrófila , Activación Plaquetaria , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Superóxidos/metabolismo , Factores de TiempoRESUMEN
Although red wine (RW) reduces cardiovascular risk, the mechanisms underlying the effect have not been identified. Correction of endothelial dysfunction by RW flavonoids could be one mechanism. We measured brachial artery reactivity by high-resolution ultrasonography, plasma lipids, glucose, adhesion molecules (ICAM-1 and VCAM), and platelet function in 16 hypercholesterolemic individuals (8 men and 8 women; mean age 51.6 +/- 8.1 years) without other risk factors. Twenty-four normal subjects were used as controls for vascular reactivity. Subjects randomly received RW, 250 ml/day, or purple grape juice (GJ), 500 ml/day, for 14 days with an equal wash-out period. At baseline, all 16 subjects were hypercholesterolemic (mean LDL = 181.0 +/- 28.7 mg/dl) but HDL, triglycerides, glucose, adhesion molecules, and platelet function were within normal limits. Brachial artery flow-mediated dilation was significantly decreased compared to controls (9.0 +/- 7.1 vs 12.1 +/- 4.5%; P < 0.05) and increased with both GJ (10.1 +/- 7.1 before vs 16.9 +/- 6.7% after: P < 0.05) and RW (10.1 +/- 6.4 before vs 15.6 +/- 4.6% after; P < 0.05). RW, but not GJ, also significantly increased endothelium-independent vasodilation (17.0 +/- 8.6 before vs 23.0 +/- 12.0% after; P < 0.01). GJ reduced ICAM-1 but not VCAM and RW had no effect on either molecule. No significant alterations were observed in plasma lipids, glucose or platelet aggregability with RW or GJ. Both RW and GJ similarly improved flow-mediated dilation, but RW also enhanced endothelium-independent vasodilation in hypercholesterolemic patients despite the increased plasma cholesterol. Thus, we conclude that GJ may protect against coronary artery disease without the additional negative effects of alcohol despite the gender.
Asunto(s)
Bebidas , Endotelio Vascular/efectos de los fármacos , Hipercolesterolemia/sangre , Lípidos/sangre , Vitis , Vino , Estudios de Casos y Controles , Moléculas de Adhesión Celular/efectos de los fármacos , Femenino , Glucosa/análisis , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacosRESUMEN
To evaluate the impact of electroconvulsive therapy on arterial blood pressure, heart rate, heart rate variability, and the occurrence of ischemia or arrhythmias, 38 (18 men) depressive patients free from systemic diseases, 50 to 83 years old (mean: 64.7 +/- 8.6) underwent electroconvulsive therapy. All patients were studied with simultaneous 24-h ambulatory blood pressure and Holter monitoring, starting 18 h before and continuing for 3 h after electroconvulsive therapy. Blood pressure, heart rate, heart rate variability, arrhythmias, and ischemic episodes were recorded. Before each session of electroconvulsive therapy, blood pressure and heart rate were in the normal range; supraventricular ectopic beats occurred in all patients and ventricular ectopic beats in 27/38; 2 patients had non-sustained ventricular tachycardia. After shock, systolic, mean and diastolic blood pressure increased 29, 25, and 24% (P < 0.001), respectively, and returned to baseline values within 1 h. Maximum, mean and minimum heart rate increased 56, 52, and 49% (P < 0.001), respectively, followed by a significant decrease within 5 min; heart rate gradually increased again thereafter and remained elevated for 1 h. Analysis of heart rate variability showed increased sympathetic activity during shock with a decrease in both sympathetic and parasympathetic drive afterwards. No serious adverse effects occurred; electroconvulsive therapy did not trigger any malignant arrhythmias or ischemia. In middle-aged and elderly people free from systemic diseases, electroconvulsive therapy caused transitory increases in blood pressure and heart rate and a decrease in heart rate variability but these changes were not associated with serious adverse clinical events.
Asunto(s)
Presión Sanguínea/fisiología , Terapia Electroconvulsiva/métodos , Frecuencia Cardíaca/fisiología , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Monitoreo Ambulatorio de la Presión Arterial , Electrocardiografía Ambulatoria , Terapia Electroconvulsiva/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The frequency of complications of infective endocarditis and their influence on the outcome of the patients changed in the antibiotic era. Therefore, we evaluated the complications in a recent large series of patients with infective endocarditis. METHODS: We studied 300 episodes of endocarditis in 287 patients in a tertiary cardiology referral center. Predisposing cardiac conditions were valvular heart disease in 147 episodes, congenital heart disease in 37, other heart diseases in five, and prosthetic heart valves in 69. In 69 episodes, there was no previous heart disease. The infecting microorganisms were streptococci in 147 episodes, Staphylococcus aureus in 59, Staphylococcus epidermidis in 14, gram-negative bacteria in 16, other gram-positive bacteria in eight, and fungi in four. In 52 episodes, blood cultures were negative. Seventy-eight patients (26%) died. Complications were defined as any clinically unfavorable event occurring during treatment. RESULTS: A total of 386 complications occurred in 223 episodes (74%); one complication occurred in 128 episodes (57%), two in 57 (26%), three in 18 (8%), four in 13 (6%), five in three (1%), and six or more in three (1%). The complications were as follows: cardiac, 100 occurrences; neurological, 72; septic, 46; associated with medical treatment, 41; renal, 27; extracranial systemic arterial embolism, 16; septic pulmonary embolism, 26; complications related to surgical treatment, 11; acute prosthetic heart valve insufficiency, six; splenic infarction or abscess, three; cardiac rhythm disturbances, three; and other, 19. The distribution of the complications relative to outcome of the patients revealed that fatality exceeded survival rates for neurologic and septic complications. CONCLUSIONS: Complications may be common in patients with infective endocarditis. Cardiac complications were the most common ones, but fatality rates were higher for neurologic and septic complications. Hence, heart failure was replaced by neurologic and septic complications as the leading causes of death in patients with infective endocarditis.
Asunto(s)
Endocarditis/complicaciones , Adolescente , Adulto , Anciano , Niño , Preescolar , Endocarditis/microbiología , Endocarditis/mortalidad , Endocarditis Bacteriana/complicaciones , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Micosis/complicaciones , Análisis de SupervivenciaRESUMEN
The prominent role of redox processes in tissue injury and in vascular cell signaling suggest their involvement in the repair reaction to vessel injury, which is a key determinant of restenosis post-angioplasty. Experimental studies showed a protective effect of superoxide dismutase or antioxidants on vasospasm, neointimal thickening or remodeling after balloon injury. It was also shown that oxidized thiols induce chelatable metal-dependent amplification of the vascular repair reaction. Ongoing or completed clinical trials show a promising effect of the antioxidant probucol against restenosis. However, few studies addressed the molecular physiological mechanisms underlying the redox hypothesis of restenosis. We recently showed evidence for marked oxidative stress early after balloon injury, with superoxide production mediated primarily by non-endothelial NAD(P)H oxidase-type flavoenzyme(s). This effect was closely related to the degree of injury. There is evidence supporting a role for such early redox processes in apoptotic cell loss and NF-kappa B activation. We present new data on the time course of oxidative stress after balloon injury of intact rabbit iliac arteries. Our data show that despite substantial neointimal growth and lumen narrowing, superoxide production and glutathione levels are unaltered at day 14 and 28 after balloon injury. At day 7 after injury, the peak neointimal proliferation in this model, there was significant decrease of vascular superoxide dismutase activity, without clear evidence of spontaneous superoxide production. Thus, oxidative stress after injury is likely to be an early transient event, which parallels the inflammatory and proliferative phases of the vascular response. We propose that such early redox processes act as dose-dependent signal transducers of gene programs that affect the final repair.
Asunto(s)
Enfermedad Coronaria/metabolismo , Endotelio Vascular/metabolismo , Estrés Oxidativo , Transducción de Señal , Angioplastia Coronaria con Balón/efectos adversos , Animales , Antioxidantes/uso terapéutico , División Celular , Enfermedad Coronaria/patología , Enfermedad Coronaria/terapia , Endotelio Vascular/lesiones , Endotelio Vascular/patología , Humanos , Masculino , Oxidación-Reducción , Conejos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Túnica Íntima/lesiones , Túnica Íntima/metabolismo , Túnica Íntima/patologíaRESUMEN
OBJECTIVE: Our aim was to assess whether exposure to oxidized thiols--a known usual consequence of oxidant stress--has the potential to affect the vascular repair response to angioplasty-induced injury. In addition, we also assessed the role of redox active metals in disulfide effects. METHODS: In 82 rabbits submitted to overdistention of iliac arteries, the following variables were analyzed: neointimal thickening, immunoreactivity to Proliferating Cell Nuclear Antigen, and cellular and collagen densities. RESULTS: A single intraarterial challenge of oxidized glutathione (GSSG, 6.5 mumol/kg) during and immediately after injury triggered a marked increase of the vascular repair reaction, as follows: (A) at day 7 after injury, there was a 2.7-fold increase in proliferation (p < 0.001 vs. control); (B) at day 14, there was increase of intimal/medial area ratio to 1.35 +/- 0.14, vs. 0.56 +/- 0.08 in controls. Proliferating cells increased to 5.5 +/- 0.8 cells/mm2, vs. 2.2 +/- 0.5 in controls (p < 0.002 for both variables). Overall cellularity was enhanced 2.2-fold; (C) at day 28, there was ongoing vessel wall proliferation, contrarily to controls. All GSSG effects were completely prevented by co-infusion of reduced glutathione (GSH) and were mimicked by cystine (6.5 mumol/kg). The uninjured artery showed no response to disulfides. To assess the role of redox active metals in GSSG action, the effects of 1,10-phenanthroline or N-CBZ-Pro-Leu-Gly hydroxamic acid (HXA), metal chelators with metalloproteinase inhibitor properties, were evaluated. Both compounds totally blocked the GSSG-induced amplification of vascular responses. In rabbits not exposed to GSSG, HXA decreased neointimal thickening by 50% (p < 0.05). CONCLUSIONS: Exposure to excess disulfide levels early after vascular balloon injury markedly amplified the late cellular response through interaction with redox active metals. These pathways can potentially mediate noxious effects of oxidative stress in vessels.
Asunto(s)
Disulfuro de Glutatión/farmacología , Glutatión/farmacología , Arteria Ilíaca/lesiones , Compuestos de Sulfhidrilo/farmacología , Animales , Cateterismo , División Celular/efectos de los fármacos , Quelantes/farmacología , Colágeno/metabolismo , Inhibidores Enzimáticos/farmacología , Glutatión/sangre , Ácidos Hidroxámicos/farmacología , Arteria Ilíaca/efectos de los fármacos , Arteria Ilíaca/metabolismo , Arteria Ilíaca/patología , Inmunohistoquímica , Masculino , Metaloendopeptidasas/antagonistas & inhibidores , Oxidación-Reducción , Fenantrolinas/farmacología , Antígeno Nuclear de Célula en Proliferación/análisis , Conejos , Factores de Tiempo , Túnica Íntima/efectos de los fármacos , Túnica Íntima/patologíaRESUMEN
Vascular NAD(P)H oxidase activity contributes to oxidative stress. Thiol oxidants inhibit leukocyte NADPH oxidase. To assess the role of reactive thiols on vascular oxidase, rabbit iliac/carotid artery homogenates were incubated with distinct thiol reagents. NAD(P)H-driven enzyme activity, assessed by lucigenin (5 or 250 microM) luminescence, was nearly completely (> 97%) inhibited by the oxidant diamide (1mM) or the alkylator p-chloromercuryphenylsulfonate (pCMPS, 0.5mM). Analogous inhibition was also shown with EPR spectroscopy using DMPO as a spin trap. The oxidant dithionitrobenzoic acid (0.5mM) inhibited NADPH-driven signals by 92% but had no effect on NADH-driven signals. In contrast, the vicinal dithiol ligand phenylarsine oxide (PAO, 1 microM) induced minor nonsignificant inhibition of NADPH-driven activity, but significant stimulation of NADH-triggered signals. The alkylator N-ethyl maleimide (NEM, 0.5mM) or glutathione disulfide (GSSG, 3mM) had no effect with each substrate. Coincubation of N-acetylcysteine (NAC, 3mM) with diamide or pCMPS reversed their inhibitory effects by 30-60%, whereas NAC alone inhibited the oxidase by 52%. Incubation of intact arterial rings with the above reagents disclosed similar results, except that PAO became inhibitor and NAC stimulator of NADH-driven signals. Notably, the cell-impermeant reagent pCMPS was also inhibitory in whole rings, suggesting that reactive thiol(s) affecting oxidase activity are highly accessible. Since lack of oxidase inhibition by NEM or GSSG occurred despite significant cellular glutathione depletion, change in intracellular redox status is not sufficient to account for oxidase inhibition. Moreover, the observed differences between NADPH and NADH-driven oxidase activity point to complex or multiple enzyme forms.
Asunto(s)
Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/metabolismo , Glutatión/metabolismo , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , Reactivos de Sulfhidrilo/farmacología , Acridinas , Animales , Vasos Sanguíneos/enzimología , Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/metabolismo , Espectroscopía de Resonancia por Spin del Electrón , Arteria Ilíaca/efectos de los fármacos , Arteria Ilíaca/metabolismo , Técnicas In Vitro , Oxidación-Reducción , Estrés Oxidativo , ConejosRESUMEN
Available evidence for oxidative stress after angioplasty is indirect or ambiguous. We sought to characterize the pattern, time course, and possible sources of free radical generation early after arterial balloon injury. Ex vivo injury performed in arterial rings in buffer with lucigenin yielded a massive oxygen-dependent peak of luminescence that decayed exponentially and was proportional to the degree of injury. Signals for injured vs. control arteries were 207. 1 +/- 17.9 (n = 13) vs 4.1 +/- 0.7 (n = 22) cpm x 10(3)/mg/min (p <. 001). Data obtained with 0.25 mmol/l lucigenin were validated with 0. 005-0.05 mmol/l lucigenin or the novel superoxide-sensitive probe coelenterazine (5 micromol/l). Gentle removal of endothelium prior to injury scarcely affected the amount of luminescence. Lucigenin signals were amplified 5- to 20-fold by exogenous NAD(P)H, and were >85% inhibited by diphenyliodonium (DPI, a flavoenzyme inhibitor). Antagonists of several other potential free radical sources, including xanthine oxidase, nitric oxide synthase, and mitochondrial electron transport, were without effect. Overdistension of intact rabbit iliac arteries in vivo (n = 7) induced 72% fall in intracellular reduced glutathione and 68% increase in oxidized glutathione, so that GSH/GSSG ratio changed from 7.93 +/- 2.14 to 0. 81 +/- 0.16 (p <.005). There was also 28.7% loss of the glutathione pool. Further studies were performed with electron paramagnetic resonance spectroscopy. Rabbit aortas submitted to ex vivo overdistension in the presence of the spin trap DEPMPO (5-diethoxy-phosphoryl-5-methyl-1-pyrroline-N-oxide, 100 mmol/l, n = 5) showed formation of radical adduct spectra, abolished by DPI or superoxide dismutase. Computer simulation indicated a mixture of hydroxyl and carbon-centered radical adducts, likely due to decay of superoxide adduct. Electrical mobility shift assays for NF-kappaB activation were performed in nuclear protein extracts from intact or previously injured rabbit aortas. Balloon injury induced early NF-kappaB activation, which was decreased by DPI. In conclusion, our data show unambiguously that arterial injury induces an immediate profound vascular oxidative stress. Such redox imbalance is likely accounted for by activation of vessel wall NAD(P)H oxidoreductase(s), generating radical species potentially involved in tissue repair.
Asunto(s)
Cateterismo/efectos adversos , Endotelio Vascular/lesiones , Imidazoles , NADH NADPH Oxidorreductasas/metabolismo , NADPH Oxidasas , Especies Reactivas de Oxígeno , Acridinas/metabolismo , Animales , Compuestos de Bifenilo/farmacología , Óxidos N-Cíclicos , Inhibidores de la Ciclooxigenasa/farmacología , Espectroscopía de Resonancia por Spin del Electrón , Transporte de Electrón , Endotelio Vascular/enzimología , Radicales Libres , Glutatión/metabolismo , Inhibidores de la Lipooxigenasa/farmacología , Mediciones Luminiscentes , Masculino , Metaloporfirinas/farmacología , NAD/metabolismo , NADP/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico Sintasa/farmacología , Compuestos Onio/farmacología , Oxidación-Reducción , Estrés Oxidativo , Consumo de Oxígeno , Pirazinas/farmacología , Conejos , Proteínas Recombinantes de Fusión/metabolismo , Marcadores de Spin , Superóxido Dismutasa/farmacología , Superóxidos/metabolismo , Transcripción Genética , Cicatrización de Heridas , Xantina Oxidasa/farmacologíaRESUMEN
Increased monocyte adherence to the vessel wall is one of the earliest events in atherosclerosis. The mechanism by which hypercholesterolemia causes alterations in endothelial adhesiveness for monocytes is unclear. This study sought to determine if monocyte adhesion molecule expression is affected by low-density lipoprotein (LDL)-cholesterol levels. Patients with hypercholesterolemia and stable coronary artery disease were compared with those without major cardiovascular risk (control). Patients with hypercholesterolemia were treated with simvastatin 20--40 mg/day for 8--10 weeks. Blood samples were examined with flow cytometry assays at baseline and after cholesterol-lowering therapy. Monocyte CD11b and CD14 adhesion molecule expression, measured as fluorescence intensity, were significantly (P<0.0001) higher in hypercholesterolemic patients before the study (176.9+/-9.8 and 138.0+/-4.8, respectively) when compared with that in control subjects (97.2+/-8.1 and 84.0+/-6.4, respectively). Both decreased markedly with treatment: to 118.8+/-6.9 and 103.1+/-3.9, respectively. Monocyte L-selectin expression was significantly lower in patients with hypercholesterolemia before treatment (43.0+/-3.0) when compared with control subjects (79.9+/-2.7), and it increased markedly with treatment (54.2+/-2.5). LDL levels correlated directly with both CD11b and CD14 expression and correlated inversely with L-selectin expression. These data show that hypercholesterolemia affects monocyte adhesion molecule expression which, in turn, decreases with statin-induced plasmatic cholesterol reduction. Such perturbations in monocyte function likely represent a proinflammatory response to hypercholesterolemia and may have a role in the early progression of atherogenesis.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Moléculas de Adhesión Celular/sangre , Hipercolesterolemia/sangre , Hipercolesterolemia/tratamiento farmacológico , Monocitos/metabolismo , Simvastatina/uso terapéutico , Adulto , Enfermedad Coronaria/complicaciones , Femenino , Humanos , Hipercolesterolemia/complicaciones , Selectina L/sangre , Receptores de Lipopolisacáridos/sangre , Antígeno de Macrófago-1/sangre , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
Although the systemic hemodynamic effects of vasodilators such as nitroprusside, phentolamine and nitrates are well known, relatively little information is available regarding their effects upon the function and metabolism of ischemic myocardium. Experimental and clinical studies indicate that vasodilators improve the mechanical performance of regional ischemic myocardium, probably by simultaneous reduction of peripheral resistance and reduction of the degree of ischemia. The majority of evidence, although still controversial, seems to indicate that myocardial perfusion can also be increased, particularly when coronary collateral vessels are present. Concomitant reduction in preload contributes to reduced oxygen demand, as evidenced by findings of reduced oxygen extraction. Thus, the balance of the oxygen supply and demand may be improved as indicated by decreases in lactate production. In addition, limited evidence in experimental animals and man suggests that vasodilators may also reduce the extent of myocardial injury as measured by S-T segment mapping and the creatine phosphokinase (CPK) release technique. However, these effects are contingent upon the arterial pressure response, and directionally opposite results may be anticipated if hypotension occurs. Since the mechanism of action of vasodilators is reasonably well understood, vasodilator therapy can be administered safely in anticipation of both improvement in total cardiac performance and a decrease in severity of ischemia.
Asunto(s)
Corazón/fisiopatología , Miocardio/metabolismo , Vasodilatadores/farmacología , Animales , Circulación Colateral/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Electrocardiografía , Hemodinámica/efectos de los fármacos , Humanos , Lactatos/biosíntesis , Nitroprusiato/farmacología , Nitroprusiato/uso terapéutico , Consumo de Oxígeno/efectos de los fármacos , Vasodilatadores/uso terapéuticoRESUMEN
Changes in systemic oxygen delivery after acute myocardial infarction were investigated in 21 patients. In seven patients with shock, circulatory failure was characterized by a significant reduction in cardiac index, a decrease in oxygen transport and oxygen consumption and an increase in concentration of blood lactate; a decrease in the affinity of hemoglobin for oxygen (increased P50) was also noted. The P50 averaged 28.8 plus or minus 0.87 (standard error of the mean) torr in patients with shock and 26.0 plus or minus 0.45 torr (P less than 0.05) in patients without circulatory failure. However, there was no significant difference in oxygen extraction from arterial blood between the two groups. The time course of the changes in P50, cardiac index and oxygen consumption was separately examined in 12 patients. In six patients with shock, P50 increased by an average of 4.6 plus or minus 2.05 torr (P less than 0.05) and this augmentation accounted for an estimated 18 percent increase in oxygen release. Maximal P50 values were observed after 24 hours of circulatory failure. In the absence of shock, no consistent changes in P50, cardiac index or oxygen consumption were observed. These data indicate that a reduction in oxygen delivery after acute myocardial infarction is followed by a compensatory increase in P50. This change in P50 accounts for increases in oxygen availability independently of changes in cardiac output.
Asunto(s)
Hemoglobinas/metabolismo , Infarto del Miocardio/metabolismo , Consumo de Oxígeno , Oxihemoglobinas/metabolismo , Choque Cardiogénico/metabolismo , Anciano , Gasto Cardíaco , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Presión Parcial , Choque Cardiogénico/sangreRESUMEN
The performance characteristics of both ischemic and "adjacent" and "remote" nonischemic myocardium were studied in open chest dogs by three mercury-in-Silastic length gauges sutured to the anterior surface of the left ventricle before and after occlusion of the distal left anterior descending coronary artery. The adjacent gauge was separated from the ischemic segment by one large nonoccluded diagonal branch of the left anterior descending artery. Remote myocardium was separated from the ischemic area by two such branches. At the time of occlusion epicardial S-T segment elevation appeared in the ischemic region but not in the adjacent or remote regions. Immediately after occlusion, typical changes of ischemic dysfunction appeared. Late systolic lengthening, depression of systolic shortening and increased diastolic compliance occurred consistently and simultaneously in ischemic and adjacent regions and inconsistently in the remote region. Five minutes after occlusion, fiber shortening was depressed to 21, 58 and 67 percent of control values in ischemic, adjacent and remote regions, respectively. Heart rate did not change, and mean arterial pressure decreased slightly. These changes persisted over time. In 11 of these dogs, end-diastolic pressure was maintained constant 20 minutes after occlusion. Systolic shortening was depressed to 40 and 74 percent of control values in the ischemic and adjacent regions, respectively. In six dogs, end-diastolic pressure was varied form 5 to 20 mm Hg by rapid volume loading during the control state and 30 minutes after occlusion. Systolic shortening in ischemic, adjacent and remote regions was depressed to 20, 40 and 65 percent of control values, respectively. The severity of all functional alterations after coronary occlusion was directly related to proximity to the ischemic region. These results indicate that depression of left ventricular function after coronary occlusion may be partially related to previously unrecognized depression of function in apparently "nonischemic" myocardium.
Asunto(s)
Hemodinámica , Animales , Presión Sanguínea , Gasto Cardíaco , Perros , Frecuencia Cardíaca , Ventrículos Cardíacos/fisiopatologíaRESUMEN
Although intracoronary thrombosis often occurs after angioplasty and may affect its outcome, the accuracy of arteriography for identification of mural thrombi is unclear. This study analyzed the relationship between arteriographic abnormalities immediately before death and the histologic extent of thrombosis in 77 dogs submitted to balloon injury of intact left anterior descending coronary arteries. Survival time after angioplasty was 120 min. The incidence of mural thrombosis, defined on serial histologic sections, was 65.0 percent. A positive diagnosis of intracoronary thrombus at arteriography (AT+) was based on the presence of any of the following signs: filling defects, retention of contrast material, and slowed or interrupted flow. Seventeen dogs were AT+, and 60 were AT-. The overall sensitivity of arteriography was 34 percent, and the specificity was 100 percent. Even considering as significant only thrombi greater than 25.0 percent of the arterial lumen area, 11 of 27 dogs were AT- despite thrombus sizes between 27 percent and 75 percent of lumen area (sensitivity, 59 percent); arteriography consistently missed smaller thrombi (22 of 23 dogs were AT-). Arterial diameters and balloon-induced injury were similar between AT- and AT+ dogs. Scanning electron microscopy depicted a fibrin-poor thrombus in 14 of 19 AT+ dogs and a fibrin-rich thrombus in five, whereas all seven AT+ dogs had fibrin-rich thrombi. Logistic regression analysis showed a correlation between thrombus size and arteriographic positivity, whereas the presence of fibrin and slowed flow of contrast material did not independently predict positive arteriographic results. Thus, arteriography is inaccurate for identification of mural thrombosis after angioplasty, mostly because of its poor sensitivity.
Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Angiografía Coronaria , Trombosis Coronaria/diagnóstico por imagen , Animales , Plaquetas/patología , Cinerradiografía , Trombosis Coronaria/patología , Vasoespasmo Coronario/patología , Vasos Coronarios/patología , Perros , Eritrocitos/patología , Femenino , Fibrina , Fluoroscopía , Masculino , Microscopía Electrónica de Rastreo , Flujo Sanguíneo Regional , Sensibilidad y EspecificidadRESUMEN
To compare the efficiency of two methods of myocardial protection--blood cardioplegia and warm reperfusion with aspartate-glutamate enrichment of the solution versus intermittent aortic crossclamping--we randomized 60 patients for coronary artery bypass grafting. Hemodynamic parameters and hospital mortality were the end points. Pathologic antecedents and preoperative clinical conditions were similar in both group I (blood cardioplegia, 30 patients) and group II (aortic crossclamping, 30 patients). An average of 2.9 grafts per patient were performed in group I and 3.1 in group II. Duration of extracorporeal circulation was 100 +/- 28 minutes in group I and 85 +/- 23 minutes in group II (p < 0.05). The total time of aortic crossclamping was 62.8 +/- 24.5 minutes in group I and 44.3 +/- 14.9 minutes in group II (p < 0.05). There were comparable increases in cardiac index in group I and group II from the preoperative period to the first postoperative day, but none of these changes reached statistical significance. There were two deaths, one in the cardioplegia group (3.3%) and another in the intermittent aortic crossclamping group (3.3%). In conclusion, in myocardial revascularization, intermittent aortic crossclamping and blood cardioplegia with warm reperfusion enriched with aspartate-glutamate solution are methods of similar efficiency.