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Biomedical subjects

J A Lopez

Publications and source records attributed to J A Lopez.

At least 55 records · Page 3Linked to original sources
PubMed1994

Transesophageal electrocardiography and adenosine in the diagnosis of wide complex tachycardia.

The diagnosis of wide complex tachycardia based on surface electrocardiography can be difficult. Misdiagnosis occurs frequently and is commonly associated with increased morbidity and mortality. We describe a case of wide QRS complex tachycardia in which transesophageal electrocardiography and intravenous adenosine were used to obtain a reliable diagnosis. These are safe and readily available tools for elucidating the mechanism of wide complex tachyarrhythmias in hemodynamically stable patients.

Adenosine↗
PubMed1994

[Effects of leukocytes on vascular tonus].

Numerous epidemiologic studies described an association between the risk of cardiovascular complications and the blood leukocyte count. In addition, an abnormal activation of leukocytes obtained from the coronary venous blood has been found in patients with unstable angina pectoris and acute myocardial infarction. These observations suggest that the elevated leukocyte count and activation is not an epiphenomenon but instead that leukocytes play a role in the pathogenesis of cardiovascular complications. Several in vitro and in vivo experiments were presented demonstrating that activated leukocytes (granulocytes and mononuclear cells) may influence vascular tone by direct and indirect mechanisms. Under certain conditions, activated leukocytes induce a significant vasoconstriction, a phenomenon which is not yet fully understood. This direct contractile effect of activated leukocytes on vascular tone may contribute to the pathogenesis of cardiovascular complications e.g. in patients with coronary artery disease.

Animals↗
PubMed1993

Penile vascular evaluation of men with Peyronie's disease.

A penile vascular evaluation was performed upon 95 consecutive men with Peyronie's disease (19 potent and 76 impotent) and 100 consecutive impotent men without Peyronie's disease to gain further understanding of the pathophysiology of erectile dysfunction in patients with Peyronie's disease. Only 1 of the 19 potent patients with Peyronie's disease had abnormal arterial blood flow by duplex ultrasonography and none had evidence of veno-occlusive dysfunction by either duplex ultrasonography or dynamic infusion cavernosometry/cavernosography. In contrast, 36% of the impotent men with Peyronie's disease had abnormal arterial blood flow and 59% had evidence of veno-occlusive dysfunction. There was no significant difference in historical risk factors for impotence between the impotent patients with Peyronie's disease and the control population of impotent patients. However, the presence of veno-occlusive dysfunction in the control population (16%) was significantly less than that of the impotent Peyronie's disease patients (p < 0.001). Although patients with Peyronie's disease may suffer impotence due to arterial occlusive disease, our results indicate that the principal cause of impotence in this patient population is veno-occlusive dysfunction.

Adult↗
PubMed1993

Vasoconstriction in response to activated leukocytes: implications for vasospasm.

Three sets of experiments are presented demonstrating that activated leukocytes produce significant vasoconstriction. (1) Responses to human mononuclear leukocytes were studied in intact femoral arteries in vitro. Vasoconstriction of about 35-40% of the maximal effect obtained with KCl was found with mononuclear cells activated by thrombin or complement component C5a, but not with unactivated mononuclear cells. This vasoconstriction was endothelium-independent, and could not be inhibited by radical scavengers or by pre-treatment of the cells with inhibitors of the cyclooxygenase or lipoxygenase pathway. Additional experiments suggest that this contractile effect is partially mediated by the release of a stable factor. (2) Vascular responses to intra-arterial complement C5a (10 and 100 micrograms) were studied in the blood-perfused hind limb of normal and atherosclerotic monkeys in vivo. C5a injection produced pronounced constriction of the hind limb large arteries in atherosclerotic, but not in normal animals. Perfusion of the hind limb with a cell-free blood substitute almost abolished C5a-induced vasoconstriction. These findings suggest that C5a induces vasoconstriction by activation of blood cells, probably leukocytes. (3) Vascular responses to the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP), were studied in the human coronary circulation. Intracoronary fMLP (1 x 10(-8) moles) produced a transient increase in blood flow velocity and a significant decrease of the diameter of the epicardial arteries. This effect was accompanied by a decrease in leukocyte count in the coronary sinus blood. These studies suggest that activated leukocytes produce vasoconstriction by the release of vasoactive factor(s), and thus may contribute to the pathogenesis of cardiovascular complications in patients with atherosclerosis.

Animals↗
PubMed1992

Role of carbohydrate modification in the production and secretion of human granulocyte macrophage colony-stimulating factor in genetically engineered and normal mesenchymal cells.

Colony-stimulating factors (CSFs) are a group of acidic glycoproteins which stimulate the proliferation and differentiation of hematopoietic progenitor cells in vitro and stimulate hemopoiesis in vivo. Human GM-CSF contains two N-linked carbohydrate side chains of the complex acidic type and several sites of O-linked carbohydrate clustered on serine and threonine residues near the N-terminus of the molecule. Previous studies have failed to detect a significant functional role for the carbohydrate modification characteristic of human GM-CSF. Using permanent cell lines and transient expression systems which produce moderate to high levels of native or carbohydrate-deficient forms of the growth factor, the role of carbohydrate modification in the biosynthesis and secretion of GM-CSF was studied. Unlike a number of other secreted glycoproteins, the transient time and secretory efficiency of several carbohydrate-deficient mutants of GM-CSF are indistinguishable from those of the native growth factor in BHK, 293, COS, and ldlD cells. Furthermore, normal human endothelial cells and fibroblasts, which normally produce the growth factor, can synthesize and secrete GM-CSF that lacks all forms of carbohydrate modification. These studies help to point out the range of roles played by carbohydrate modification in the biosynthesis, assembly, and secretion of glycoprotein hormones.

Animals↗
PubMed1992

Activation of leukocytes with complement C5a is associated with prostanoid-dependent constriction of large arteries in atherosclerotic monkeys in vivo.

Activated leukocytes release a variety of substances which have been shown in vitro to modulate vascular tone. The chemotactic peptide complement C5a is a physiological activator of leukocytes. We injected human recombinant complement C5a (10 and 100 micrograms) into the blood-perfused hind limb of normal and atherosclerotic cynomolgus monkeys and examined vascular responses. In both normal and atherosclerotic monkeys, the high dose of C5a produced about 65% decrease in leukocyte cell count in venous blood drainage from the hind limb. Injection of C5a produced a pronounced increase in resistance of large arteries (segment from iliac artery to dorsal pedal artery) in atherosclerotic, but not in normal monkeys. The constrictor effect of C5a in atherosclerotic monkeys was abolished by the thromboxane A2 receptor antagonist SQ 29,548 (2 mg/kg i.v.). The platelet-activating factor antagonist WEB 2086 (5 mg/kg, i.v.) did not alter vascular responses to C5a. We conclude that activation of leukocytes produces constriction of large arteries in atherosclerotic, but not normal, monkeys in vivo. This response may be mediated in part by release of thromboxane A2.

Animals↗
PubMed1992

Vascular responses to activated leukocytes after regression of atherosclerosis.

Activation of leukocytes in vivo produces marked constriction of large arteries in atherosclerotic, but not in normal, monkeys. We tested the hypotheses that vasoconstrictor responses to activated leukocytes in vivo may be abnormal during hypercholesterolemia before the development of atherosclerotic lesions and that responses may return to normal after the regression of atherosclerosis. Leukocytes were activated by injection of the chemotactic peptide formyl-methionine-leucine-phenylalanine (fMLP) into the blood-perfused hind limb of four groups of cynomolgus monkeys: monkeys fed a normal diet (normal group, n = 18), monkeys fed an atherogenic diet for 3-4 months (hypercholesterolemic group, n = 6), monkeys fed an atherogenic diet for 20 months (atherosclerotic group, n = 19), and monkeys fed an atherogenic diet for 18 months, followed by a normal diet for 20 months (regression group, n = 14). Baseline resistance of large arteries was 1.5 +/- 0.2 (mean +/- SEM), 2.0 +/- 0.6, 3.5 +/- 0.4 (p less than 0.05 versus normal), and 1.7 +/- 0.2 mm Hg/ml/min per 100 g tissue for the normal, hypercholesterolemic, atherosclerotic, and regression groups, respectively. Injection of fMLP did not change resistance of large arteries in normal or hypercholesterolemic monkeys. Injection of fMLP increased resistance of large arteries by 3.0 +/- 0.7 mm Hg/ml/min per 100 g tissue in atherosclerotic monkeys and by 1.3 +/- 0.4 mm Hg/ml/min per 100 g tissue in regression monkeys (p less than 0.05 versus atherosclerotic and normal). Thus, abnormal vasoconstriction in response to activation of leukocytes persists, but to a lesser extent, after regression. In contrast, vasoconstrictor responses to serotonin, which were potentiated in atherosclerotic monkeys, were normal after regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Duplex ultrasound findings in men with Peyronie's disease.

Peyronie's disease is a fibrotic process involving the penis, which presents with painful erections, penile chordee, and, less frequently, impotence. Duplex Doppler ultrasound is particularly well suited to the evaluation of these patients, since it can provide information about Peyronie's plaque and the penile vasculature noninvasively. Duplex ultrasound examinations were performed on 30 impotent and three potent men with Peyronie's disease. Presenting symptoms included painful erections in 30% and abnormal curvature in 93%. A plaque was palpable in 31 (94%) of the patients. Ultrasound evaluation revealed evidence of a plaque in only 13 (39%) patients. The majority of these plaques were visualized as hyperechoic areas with or without shadowing. Some isoechoic plaques were identified due to significant thickening of the dorsal tissues. Doppler analysis of cavernosal artery blood flow revealed evidence of arterial disease in eight (27%) of the impotent patients. Although ultrasonography was not as sensitive as palpation in identifying Peyronie's plaques, ultrasonography was better able to determine the depth of fibrosis extension into the corpora.

Erectile Dysfunction↗
PubMed1991

Effects of sympathetic nerves on collateral vessels in the limb of atherosclerotic primates.

This study was performed to examine effects of sympathetic nerves on collateral vessels in the limb. We studied normal (N) and atherosclerotic (AS) cynomolgus monkeys that were fed atherogenic diet for 21 months. A common iliac artery was ligated 13 months before hemodynamic measurements. Using histofluorescence microscopy, a plexus of noradrenergic nerves was identified in the adventitia of collateral vessels. We measured blood flow to the limb with microspheres, and the pressure gradient from aorta to the iliac artery beyond the occlusion. The lumbar sympathetic chain was stimulated electrically at 3 Hz (SNS-3) and 15 Hz (SNS-15). In normal monkeys, conductance of collateral vessels (in ml/min per 100 g per 100 mm Hg) was 19 +/- 3.6 (mean +/- SE) during control, 14 +/- 1.6 during SNS-3, and 9.8 +/- 0.9 during SNS-15 (P less than 0.05 vs control). In AS monkeys, collateral conductance was 12 +/- 2.9 during control, 7.5 +/- 1.7 during SNS-3 and 3.9 +/- 1.8 during SNS-15 (P less than 0.05). In summary, collateral vessels in the limb are innervated and sympathetic stimulation produces pronounced constriction of collateral vessels in both normal and atherosclerotic monkeys. Thus, the effectiveness of collateral vessels in maintaining blood flow to the limb may be compromised by increased activity of sympathetic nerves.

Animals↗
PubMed1991

Interpretation and quantification of penile blood flow studies using duplex ultrasonography.

Duplex ultrasound scanning of the penis combined with intracorporeal pharmacological stimulation of an erection provides an accurate, relatively noninvasive functional assessment of cavernous artery blood flow. Various criteria described for normal have been based on either blood flow velocity alone or the combination of blood flow velocity and arterial dilatation of each cavernous artery. Unfortunately, less than 20% of impotent men have classical arterial anatomy and the aforementioned normal criteria do not take into account the various possible anatomical and acquired anomalies that can exist. In addition, the multiplicity of parameters used to describe normal are cumbersome to use for patient comparison and statistical analysis. In this study, 4 indexes were developed to express the results of a duplex ultrasound penile blood flow study and they were tested in an impotent population comprised of 75 men with arterial disease and 33 men with impotence due to neurogenic or psychogenic causes. A significant difference was observed between these 2 groups using all 4 indexes (p less than 0.001). However, the penile blood flow index, which incorporated velocity and dilatation, performed best as determined by sensitivity, specificity and receiver operating characteristics. Based on the results of this study, the penile blood flow index, which represents the summation of the percentage of dilatation and peak blood flow velocity of each cavernous artery, provides an accurate reflection of total penile blood flow as measured by duplex ultrasound.

Arteries↗
PubMed1991

Regression of atherosclerosis. A role for calcium antagonists.

The key processes responsible for plaque in atherosclerosis are cholesterol accumulation, caused by increased net uptake of atherogenic lipoproteins; cell proliferation and recruitment, caused by mitogenic and chemotactic activity; extracellular matrix expansion and collagen accumulation, caused by increased intimal cell synthesis; and high rates of cell death, caused by increased metabolic needs of tissue in an unfavorable milieu. Cell death is associated with neovascularization, dense fibrosis, and calcification, with the subsequent plaque complications of hemorrhage and thrombosis. An additional functional feature of atherosclerosis, even in prestenotic stages, is severe vasomotor abnormalities, caused in part by endothelial dysfunction. Reversal of atherosclerosis involves interrupting these processes. Calcium antagonists may block specific stages of atherogenesis. Anticalcifying agents (diphosphonates, thiophenes, and metallic ions) inhibit accumulation of connective tissue. Calcium channel blockers reduce endothelial injury and intimal permeability, block proliferation of intimal cells, inhibit lipid accumulation by a number of mechanisms, and reduce exaggerated vasoconstrictor responses. Thus, calcium antagonists may promote regression of lesions beyond what can be achieved by reducing risk factors alone.

Animals↗
PubMed1991

Acetylcholine-induced vasodilatation in rabbit hindlimb in vivo is not inhibited by analogues of L-arginine.

Nitric oxide (NO) or related nitroso compounds are an endothelium-derived relaxing factor (EDRF), originating from metabolism of L-arginine, L-Arginine analogues with chemically altered guanidino moity are potent and specific inhibitors of EDRF(NO) release. We evaluated effects of two L-arginine analogues, NG-monomethyl-L-arginine (L-NMMA, 100 microM) and N omega-nitro-L-arginine (L-NARG, 30 microM), on acetylcholine-, substance P-, and nitroglycerin-induced relaxation in the blood-perfused rabbit hindlimb in vivo and femoral arteries in vitro. L-NMMA and L-NARG selectively inhibited the vasodilator response to acetylcholine in rabbit femoral arteries in vitro, whereas endothelium-independent response to nitroprusside increased. L-NMMA (1.6 mg/min ia) in the blood-perfused rabbit hindlimb in vivo increased vascular resistance in the hindlimb by 23 +/- 3% (means +/- SE; n = 10) but did not inhibit the vasodilator responses to acetylcholine or substance P. L-NARG (10 mg/kg iv) increased systemic blood pressure by 26 +/- 3% (n = 7) and vascular hindlimb resistance by 22 +/- 9% (n = 8), and blood flow to hindlimb musculature, measured with microspheres, decreased by 46 +/- 5% (n = 6). Pretreatment with L-NARG, however, did not impair vasodilator responses to acetylcholine and substance P. These findings are consistent with the view that basal tone in resistance vessels in the rabbit hindlimb may be mediated by nitroso compounds, whereas agonist-stimulated vasodilation may be mediated by other mechanisms that do not involve the NO-synthesizing enzyme.

Acetylcholine↗
PubMed1991

Effects of atherosclerosis and regression on vascular responses to products of activated platelets in primates.

We aggregated human platelets in vitro and examined vascular responses to injection of the supernatant in atherosclerotic primates. Platelets were washed, suspended, and aggregated with thrombin. Thrombin was then inactivated with D-Phe-Pro-ArgCH2Cl, and the suspension was centrifuged. The supernatant was injected intra-arterially into the perfused hindlimb within 30 s after aggregation of platelets. We studied normal cynomolgus monkeys, atherosclerotic monkeys that were fed atherogenic diet for 18 mo, and regression monkeys that were fed an atherogenic diet for 18 mo followed by a normal diet for 20 mo. Products of activated human platelets produced vasodilation in normal monkeys, as effects of platelet-derived vasodilators (presumably adenine nucleotides) may override platelet vasoconstrictor products. Vasodilator responses to platelet products were impaired in atherosclerotic monkeys, probably as a result of endothelial dysfunction. Regression of atherosclerosis restored vasodilator responses to platelet products toward normal. These data suggest that the predominant response to human platelet products is vasodilatation. Atherosclerosis impairs vasodilator responses to human platelet products, and regression of atherosclerosis restores responses toward normal.

Adenosine↗
PubMed1991

Hemodynamic determinants of vascular changes in hypertension and atherosclerosis.

Several new concepts are reviewed concerning structural and functional changes in atherosclerotic and hypertensive blood vessels. First, in regard to modulation of vascular changes, atherosclerosis appears to progress more slowly during hypotension than during normotension. This finding may have implications for the optimal level of blood pressure. Second, structural "remodeling" of the vessel wall occurs in both atherosclerosis and hypertension. Remodeling helps to preserve the arterial lumen despite intimal proliferation in atherosclerosis. In contrast, remodeling (which differs from vascular hypertrophy) reduces the vascular lumen in chronic hypertension. Third, functional changes impair active vasodilator responses in both atherosclerotic and hypertensive vessels, in part by endothelium-dependent mechanisms. Finally, we propose that leukocytes as well as platelets may be important cellular mediators of spasm in atherosclerotic arteries.

Animals↗
PubMed1991

Mechanisms of contraction induced by human leukocytes in normal and atherosclerotic arteries.

Activation of leukocytes results in the release of a variety of vasoactive substances that may modulate vascular tone. We studied the effect of human polymorphonuclear (PMN) and mononuclear (MONO) leukocytes on quiescent femoral arteries in vitro. Arteries were obtained from normal and atherosclerotic cynomolgus monkeys. In normal arteries, stimulation of PMNs (3 and 5 x 10(6) cells/ml) with either thrombin (5 units/ml) or complement C5a (0.5 micrograms/ml) resulted in endothelium-independent contraction (approximately 25% of maximum contraction with 80 mM KCl). Vasocontraction was augmented in the presence of superoxide dismutase (150 units/ml) and was significantly impaired in the presence of the hydroxyl radical scavengers mannitol (20 mM) and deferoxamine (1 mM). Catalase (1,200 units/ml) or L-alanine (20 mM) did not modify this effect of PMNs. In contrast to PMNs, vasocontraction in response to MONOs was not altered by the addition of radical scavengers. Pretreatment of PMNs and MONOs with indomethacin (10 microM) or nordihydroguaiaretic acid (20 microM) did not influence vascular responses. Supernatant of thrombin-stimulated PMNs and MONOs also produced vasocontraction (approximately two thirds of the effect of intact cells). This vasocontractor factor (or factors) was heat stable (30 minutes, 95 degrees C) and had a molecular weight less than 1,000 as determined by ultrafiltration. Stimulation of MONOs or PMNs (3 and 5 x 10(6) cells/ml) produced a similar response in normal arteries. In contrast, the constrictor response in atherosclerotic arteries to MONOs (5 x 10(6) cells/ml) was significantly greater than to PMNs. We conclude that stimulated human PMNs and MONOs contract arteries in vitro by release of at least two factors. One factor appears to be heat stable, with a molecular weight less than 1,000. The vascular response to PMNs, but not to MONOs, appears to involve the generation of hydroxyl radicals. The response to MONOs is greater than the response to PMNs in atherosclerotic, but not in normal, arteries.

Animals↗