[show abstract][hide abstract] ABSTRACT: Introducción. El efecto vasodilatador de la cafeína en las arterias de modelos animales ya ha sido demostrado. Se desconocen estudios con la misma metodología in vitro utilizando arterias humanas. Objetivos. Evaluar los efectos vasoactivos in vitro de la cafeína en la arteria mamaria interna de humanos. Materiales y métodos. Se utilizaron 80 anillos de arteria mamaria interna (n=20 pacientes). La funcionalidad del endotelio se evaluó con acetilcolina a una concentración de 3,16x10 -6 M, de nitroglicerina con dosis acumulativas de 10 –11 M a 10 –4 M y de cafeína con concentraciones acumulativas de 10 –8 M a 10 –4 M. Resultados. La nitroglicerina indujo un porcentaje máximo de relajación de 87,4±12,3%, la cafeína, de 86,9±21,0% en arterias con endotelio funcional y de 71,6±28,6% en arterias con disfunción endotelial. No se encontraron diferencias entre los tres grupos (p=0,289). Tampoco se encontraron diferencias en la EC 50 en arterias con endotelio funcional (1,66x10 -5 ±1,57x10 -5 M) y arterias disfuncionales (7,75x10 -5 ±14,64x10 -5 M). La nitroglicerina resultó más potente que la cafeína (EC 50 = 4,30x10 -9 ±4,35x10 -9 M) (p=0,013). Conclusiones. Aunque la nitroglicerina fue un vasodilatador más potente, la cafeína tuvo un fuerte efecto vasodilatador arterial in vitro independientemente de la funcionalidad del endotelio en arterias humanas. Palabras clave: cafeína/uso terapéutico, revascularización miocárdica, vasodilatación, aorta, ateroesclerosis, endotelio, acetilcolina.
Biomédica: revista del Instituto Nacional de Salud 05/2013; 28(2). · 0.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: The heart's venous drainage system has been the object of observations and research for several centuries. Its anatomic and histological characteristics, as well as its distribution and architecture, make the cardiac venous system a uniquely organized structure within the organism. An understanding of its physiology helps in comprehending some of the mechanisms by which, under special conditions, the myocardium tolerates ischemia. The heart's venous system has become important today as a route for administering pharmacologic therapy, gene therapy, growth factors, and stem cells to the myocardium. Access through the coronary sinus is a common practice in modern electrophysiology.
The Journal of invasive cardiology 02/2013; 25(2):98-105. · 1.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: The use of statins and medicated stents (MS) is the best available therapy for the treatment of severe coronary disease in selected cases. However, the vascular effects of the simultaneous use of both therapies are unknown.
An experimental study was carried out on 60 NZ rabbits with advanced atherosclerosis, distributed in four groups of 15 animals each. Group 1: Control. Group 2: paclitaxel-eluting stent (PES) in the thoracic aorta. Group 3: Atorvastatin 2.5mg/day po+PES implant, and Group 4: Atorvastatin 2.5mg/day po. They were followed up at 30, 60 and 90 days. Histo-morphometric analyses were carried out.
A total of 60 PES were successfully implanted. One animal from Group 3 died due to respiratory infection. PES increased the lumen diameter and area, as well as the vessel area; atorvastatin induced a potent plaque regression. In the PES group, the lumen diameter was 4.25±0.0mm, lumen area was 14.2±0.4mm(2), vessel area was 16.7±0.0mm(2), and plaque/media area ratio was 0.1±0.0. In the PES+atorvastatin group the measurements were 4.9±0.1mm (p<0.001), 18.6±0.8mm(2) (p=0.005), 21.6±0.9mm(2) (p=0.007) and 0.8±0.08 (p=0.032), respectively.
Our results confirm the potent synergistic mechanical effect of the PES and plaque regression of the statins in an animal model with advanced atherosclerosis.
Clinica e Investigacion en Arteriosclerosis 01/2013; 25(1):16-24.
[show abstract][hide abstract] ABSTRACT: The lens of the eye is one of the most radiosensitive tissues in the body, and exposure of the lens to ionizing radiation can cause cataract. Cumulative X-ray doses to the lenses of interventional cardiologists and associated staff can be high. The International Commission on Radiological Protection recently noted considerable uncertainty concerning radiation risk to the lens. This study evaluated risk of radiation cataract after occupational exposure in interventional cardiology personnel. Comprehensive dilated slit-lamp examinations were performed in interventional cardiologists, associated workers and controls. Radiation exposures were estimated using experimental data from catheterization laboratories and answers to detailed questionnaires. A total of 116 exposed and 93 similarly aged nonexposed individuals were examined. The relative risk of posterior subcapsular opacities in interventional cardiologists compared to unexposed controls was 3.2 (38% compared to 12%; P < 0.005). A total of 21% of nurses and technicians had radiation-associated posterior lens changes typically associated with ionizing radiation exposure. Cumulative median values of lens doses were estimated at 6.0 Sv for cardiologists and 1.5 Sv for associated medical personnel. A significantly elevated incidence of radiation-associated lens changes in interventional cardiology workers indicates there is an urgent need to educate these professionals in radiation protection to reduce the likelihood of cataract.
Radiation Research 10/2010; 174(4):490-5. · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial.
International journal of vascular medicine 01/2010; 2010:834060.
[show abstract][hide abstract] ABSTRACT: There is little information about the direct effect of caffeine in human blood vessels. The purpose of this study was to evaluate the direct vascular effect of caffeine on human internal mammary artery (IMA) and the involvement of potassium channels in this response. Segments of IMA were obtained from 29 patients who underwent coronary artery bypass graft surgery. They were cut into rings, suspended between two wire hooks in organ bath chambers and constricted submaximally with norepinephrine. Caffeine (3.16x10(-9) to 10(-4) mol/L) was added in a cumulative fashion to rings with or without functional endothelium and concentration response curves were constructed. The response to caffeine was also evaluated after incubation with adenosine 3',5'-triphosphate (ATP)-dependent potassium channel blocker glibenclamide, voltage-dependent potassium channel blocker 4-aminopyridine and large-conductance calcium-activated potassium channel inhibitor tetraethylammonium. Caffeine produced a potent, concentration-dependent relaxation of IMA. The relaxant responses did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation with different potassium channel inhibitors (glibenclamide, 4-aminopyridine and tetraethylammonium) did not cause significant alterations in the relaxant responses to caffeine. These results suggest that the vasodilatory response to caffeine in human IMA is independent of endothelial function and is not mediated by potassium channels.
[show abstract][hide abstract] ABSTRACT: The vasodilator effect of caffeine in animal models arteries has been demonstrated previously. However, studies with the same methodology using human arteries in vitro have not been performed.
The in vitro vasoactive effects of caffeine was evaluated on human internal mammary arteries.
Internal mammary artery rings were used (n = 20). Endothelial function was evaluated with acetylcholine at a concentration of 3.16 x 10 -6 M, nitroglycerine at cumulative concentrations of 10 -11 M to 10 -4 M and caffeine with cumulative concentrations of 10 -8 M to 10 -4 M.
Nitroglycerin produced a maximum relaxation percentage of 87.4 +/- 12.3%, caffeine a percentage of 86.9 +/- 21.0% in arteries with functional endothelium, and of 71.6 +/- 28.6% in arteries with endothelial dysfunction. No differences were detected among the three groups ( p=0.289). Similarly, no differences were found between EC 50 in arteries with functional endothelium (1.66 x 10 -5 +/-1.57 x 10 -5 M) and dysfunctional arteries (7.8 x 10 -5 +/-14.6 x 10 -5 M). Nitroglycerine proved more potent than caffeine (EC 50 = 4.3 x 10 -9 +/-4.4 x 10 -9 M) ( p=0.013).
Although nitroglycerin was a more potent vasodilator, caffeine had a strong arterial vasodilator effect regardless of endothelial function in human arteries.
Biomédica: revista del Instituto Nacional de Salud 07/2008; 28(2):298-304. · 0.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: Introduction
The effects of caffeine on arteries with endothelial dysfunction and atherosclerosis are unknown.
To evaluate the in-vitro vasoactive effects of caffeine on aortic rings from atherosclerotic rabbits. Methodology. Atherosclerosis was induced in rabbits (n = 10) fed an atherogenic diet (1% cholesterol) (group 1). The control group (n = 10) received a cholesterol-free diet (group 2). At 16 weeks we evaluated serum cholesterol, and all the animals were sacrificed. Thoracic aorta rings were obtained for vasoreactivity studies and morphometric analyses. Agonists were nitroglycerine, acetylcholine, and caffeine at 3 doses corresponding to one, 2 and 3 triple espressos.
Arterial relaxation with acetylcholine in arteries from healthy rabbits (22.5 ± 16.8%) was greater than in arteries from atherosclerotic rabbits (3.6 ± 3.7%; p = 0.006). Although the vasodilator effect of caffeine was dependent on the concentration (p < 0.001), no differences were found between arteries from healthy rabbits (75.73 ± 11.20%) and those from diseased rabbits (68.19 ± 15.07%; p = 0.238). Nitroglycerine generated less relaxation than caffeine, both in arteries from healthy rabbits (32.78 ± 12.30%) and from diseased rabbits (73.48 ± 18.93%; p < 0.001). The EC50 (half maximal effective concentration) was similar for both vasodilators (p = 0.178). The aortic lesions in group 1 consisted of early plaques. The endothelial covering (CD31) was 92.2 ± 5.6% and 92 ± 4.8% respectively (p = 0.927).
Caffeine exerts a potent arterial vasodilator effect in-vitro regardless of the presence or absence of atherosclerosis.
Clínica e Investigación en Arteriosclerosis. 04/2008; 20(2).
[show abstract][hide abstract] ABSTRACT: RESUMO Fundamentos: A resposta de reparação vascular é um importante fator no desenvolvimento de reestenose e trom-bose no stent. O presente estudo foi planejado para ava-liar a reparação vascular com stents não-farmacológicos (SNF) comparados a stents com liberação de everolimus (SLE) e de beta-estradiol (SLB) em um modelo experimen-tal de fibroateroma de capa fina (FACF) em animais com aterosclerose crônica. Método: Foram analisados 16 coe-lhos hipercolesterolêmicos da raça Nova Zelândia acompa-nhados por quatro anos. Desses animais, 6 receberam SNF, 5 receberam SLE e 5, SLB (Guidant, Santa Clara, Califórnia, Estados Unidos). Um stent com polímero tam-bém foi implantado em cada animal. Resultados: Análises histológicas realizadas aos 28 dias, comparando FACF de novo com FACF com implante de SNF, SLE e SLB, demons-traram que os stents com polímero induziram escores mais altos de fibrina e hemorragia. Os SLB induziram escores mais altos de inflamação e fibrina e escores mais baixos de endotelização. Os SLE induziram escores mais altos de inflamação, fibrina e hemorragia. SLB e SLE induziram escores de reparação semelhantes. A porcen-tagem das áreas de colágeno tipo I foi semelhante nos quatro tipos de stents. A porcentagem das áreas de colágeno tipo III foi mais alta com SNF quando comparados ao polímero e aos stents farmacológicos. Conclusão: Os stents farmacológicos estão associados a inflamação reduzida, mas crescente, deposição de fibrina e hemorragia, que parecem estar relacionadas aos efeitos vasculares do polímero.
[show abstract][hide abstract] ABSTRACT: Introduction
The effects of androgens on atherosclerosis and its clinical manifestations are controversial. The objective of this study was to compare the morphologic and functional characteristics and gene expression associated with reverse metabolism of cholesterol in castrated and non-castrated atherosclerotic rabbits.
Forty male NZ rabbits were distributed in four groups: 1: non-castrated with a normal diet; 2: castrated with a normal diet; 3: non-castrated with an atherogenic diet, and 4: castrated with an atherogenic diet. Measurements of total cholesterol, free testosterone, in vitro vascular relaxation, histomorphometric analyses of the thoracic aorta and expression of the IL-1β, LRX-α and ABCA1 genes were carried out in each rabbit.
Castration decreased levels of total testosterone (2.1 ± 0.3 vs. 0.8 ± 0.4 ng/mL; P=.024). In animals with a normal diet (groups 1 and 2), castration increased expression of IL-1β (0.71 ± 0.07 vs. 0.77 ± 0.06; P<.001), decreased that of LXR-α (0.77 ± 0.008 vs. 0.41 ± 0.01; P<.001) and increased that of ABCA1 (0.2±0.008 vs. 0.31±0.08; P<.001). In animals with an atherogenic diet (groups 3 and 4), castration was associated with a larger plaque area (0.9 ± 1.3 vs. 2.6 ± 2.3 mm2; P=.026), plaque area/vessel area ratio (0.08 ± 0.1 vs. 0.25 ± 0.1; P<.001), plaque area/media area ratio (0.2 ± 0.2 vs. 0.4 ± 0.3; P=.003), greater expression of IL-1 (0.93 ± 0.05 vs. 1.1 ± 0.02; P<.001), reduction of LXR-α (1.45 ± 0.01 vs. 1.29 ± 0.01; P<.001), and reduction of ABCA1 (0.22 ± 0.1 vs. 0.20 ± 0.02; P<.001).
This study shows that in the presence of atherosclerosis induced by hypercholesterolemia, endogenous testosterone could have an attenuating or protective effect on atherogenesis.
Clínica e Investigación en Arteriosclerosis. 12/2007; 19(6).
[show abstract][hide abstract] ABSTRACT: Levosimendan, an inotropic drug that enhances myocardial contractility through myofilment calcium sensitazion, induces peripheral vasodilation via opening ATP-dependent K(+) channels. It is unknown whether this drug can be used for the treatment of perioperative vasospasm of arterial conduits used for coronary artery bypass grafting.
We investigated the effects of levosimendan on human internal mammary artery (IMA) specimens taken from patients undergoing coronary artery bypass surgery. The rings were carefully prepared and placed between two wire hooks in organ bath chambers and then constricted submaximally with norepinephrine and thromboxane A(2) analog (U46619). Nitroglycerin, milrinone, and levosimendan were separately added in a cumulative fashion and concentration response curves for relaxation were constructed. In parallel experiments, the response to levosimendan was evaluated on rings with and without functional endothelium. Levosimendan prevention of norepinephrine-induced contraction was also estimated.
Nitroglycerin, milrinone, and levosimendan completely reversed the contraction of the IMA segments induced by U46619 and norepinephrine. Levosimendan produced a potent, concentration-dependent preventive effect on the norepinephrine-induced contraction of IMA. The responses to levosimendan were similar in preparations with or without endothelium.
Anesthesia and analgesia 12/2006; 103(5):1094-8. · 3.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Atherosclerosis is the main cause of coronary and cerebrovascular disease which, in turn, are the most common causes of mortality and morbidity in the western world. Recent publications suggest that infective microorganisms may play an important role in the genesis and progression of atherosclerosis. According to seroepidemiological and direct detection reports, Chlamydia pneumoniae is the most plausible candidate. Nevertheless, the mechanisms by which the microorganism induces its pathological effect have not yet been conclusively determined; hence, the need exists to explore different detection techniques of C. pneumoniae on arteries.
The purpose of the current study was to detect the presence of C. pneumoniae in aortic tissue samples from 14 patients submitted to aortic replacement surgery. Detection method involved kdtA gene amplification coupled with an in vitro hybridization assay.
Samples of aortic tissue for DNA extraction and C. pneumoniae detection by PCR-in vitro hybridization were randomly obtained from each of 14 aorta specimens.
C. pneumoniae was detected in 12 (85.7%) of the 14 aortic tissue samples.
This result indicates a frequent association of C. pneumoniae with aortic tissue disease. Further studies are required to determine if this proportion of positive samples persists within larger samples.
Biomédica: revista del Instituto Nacional de Salud 01/2006; 25(4):511-7. · 0.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: Growth of atherosclerotic plaques is accompanied by neovascularization from vasa vasorum microvessels extending through the tunica media into the base of the plaque and by lumen-derived microvessels through the fibrous cap. Microvessels are associated with plaque hemorrhage and may play a role in plaque rupture. Accordingly, we tested this hypothesis by investigating whether microvessels in the tunica media, the base of the plaque, and the fibrous cap are increased in ruptured atherosclerotic plaques in human aorta.
Microvessels, defined as CD34-positive tubuloluminal capillaries recognized in cross-sectional and longitudinal profiles, were quantified in 269 advanced human plaques by bicolor immunohistochemistry. Macrophages/T lymphocytes and smooth muscle cells were defined as CD68/CD3-positive and alpha-actin-positive cells. Total microvessel density was increased in ruptured plaques when compared with nonruptured plaques (P=0.0001). Furthermore, microvessel density was increased in lesions with severe macrophage infiltration at the fibrous cap (P=0.0001) and at the shoulders of the plaque (P=0.0001). In addition, microvessel density was also increased in lesions with intraplaque hemorrhage (P=0.04) and in thin-cap fibroatheromas (P=0.038). Logistic regression analysis identified plaque base microvessel density (P=0.003) as an independent correlate to plaque rupture.
Thus, neovascularization as manifested by the localized appearance of microvessels is increased in ruptured plaques in the human aorta. Furthermore, microvessel density is increased in lesions with inflammation, with intraplaque hemorrhage, and in thin-cap fibroatheromas. Microvessels at the base of the plaque are independently correlated with plaque rupture, suggesting a contributory role for neovascularization in the process of plaque rupture.
[show abstract][hide abstract] ABSTRACT: The inclusion of statins and stents in coronary disease management during the 1980s has marked a dramatic change in the natural history of the disease. Separately, each of these therapies have progressed rapidly and have achieved a prime position in the current armamentarium. The simultaneous use of statins in patients undergoing percutaneous coronary revascularization procedures with stent implantation has shown a significant beneficial synergistic effect by reducing ischemia and necrosis, and improving coronary blood flow in patients with stable coronary disease, as well as in acute coronary syndromes. The use of high dose statins in conjunction with coronary angioplasty with stent implantation has shown great efficacy and safety in patients with severe coronary disease.
Clinica e Investigacion en Arteriosclerosis 25(3):112-122.