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Biomedical subjects

L Demopoulos

Publications and source records attributed to L Demopoulos.

12 recordsLinked to original sources
PubMed2001

Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization.

BACKGROUND: In the setting of percutaneous coronary revascularization, agents in the class known as platelet glycoprotein IIb/IIIa inhibitors have significantly reduced the incidence of death or nonfatal myocardial infarction at 30 days. We assessed whether there are differences in safety or efficacy between two such inhibitors, tirofiban and abciximab. METHODS: Using a double-blind, double-dummy design at 149 hospitals in 18 countries, we randomly assigned patients to receive either tirofiban or abciximab before undergoing percutaneous coronary revascularization with the intent to perform stenting. The primary end point was a composite of death, nonfatal myocardial infarction, or urgent target-vessel revascularization at 30 days. The trial was designed and statistically powered to demonstrate the noninferiority of tirofiban as compared with abciximab. RESULTS: The primary end point occurred more frequently among the 2398 patients in the tirofiban group than among the 2411 patients in the abciximab group (7.6 percent vs. 6.0 percent; hazard ratio, 1.26; one-sided 95 percent confidence interval of 1.51, demonstrating lack of equivalence, and two-sided 95 percent confidence interval of 1.01 to 1.57, demonstrating the superiority of abciximab over tirofiban; P=0.038). The magnitude and the direction of the effect were similar for each component of the composite end point (hazard ratio for death, 1.21; hazard ratio for myocardial infarction, 1.27; and hazard ratio for urgent target-vessel revascularization, 1.26), and the difference in the incidence of myocardial infarction between the tirofiban group and the abciximab group was significant (6.9 percent and 5.4 percent, respectively; P=0.04). The relative benefit of abciximab was consistent regardless of age, sex, the presence or absence of diabetes, or the presence or absence of pretreatment with clopidogrel. There were no significant differences in the rates of major bleeding complications or transfusions, but tirofiban was associated with a lower rate of minor bleeding episodes and thrombocytopenia. CONCLUSIONS: Although the trial was intended to assess the noninferiority of tirofiban as compared with abciximab, the findings demonstrated that tirofiban offered less protection from major ischemic events than did abciximab.

Abciximab↗
PubMed2000

Effect of indomethacin on blood pressure lowering by captopril and losartan in hypertensive patients.

NSAIDs are known to attenuate the effects of some antihypertensive medications. It is not known whether the new class of angiotensin II receptor antagonists is similarly affected. We conducted a multicenter study assessing the effect of indomethacin on the antihypertensive effects of losartan and captopril. After 4 weeks of placebo washout, hypertensive patients received 6 weeks of active antihypertensive therapy with either 50 mg losartan once daily (n=111) or 25 mg captopril twice daily for 1 week, which was increased to 50 mg twice daily for 5 weeks (n=105). This was followed by 1 week of concomitant therapy with indomethacin (75 mg daily). The primary outcome measure was the change in mean 24-hour ambulatory diastolic blood pressure after the addition of indomethacin. Both captopril and losartan significantly lowered ambulatory diastolic blood pressure (losartan -5.3 mm Hg, P:<0.001; captopril -5.6 mm Hg, P:<0.001) after 6 weeks of therapy. Indomethacin significantly attenuated the 24-hour ambulatory diastolic blood pressure for both losartan (2.2 mm Hg, P:<0.05) and captopril (2.7 mm Hg, P:<0.001) and also attenuated the effect of captopril on trough sitting diastolic blood pressure. Changes in daytime diastolic blood pressure (7:00 AM to 11:00 PM) were similar to the 24-hour response in both groups. Nighttime diastolic blood pressure (11:01 PM to 6:59 AM) was significantly attenuated in captopril-treated patients (2.0 mm Hg, P:<0.05), but losartan was unaffected (0.4 mm Hg). Thus, concurrent treatment with indomethacin similarly attenuates the 24-hour antihypertensive response to losartan and captopril.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Modulation of vascular endothelial gene expression by physical training in patients with chronic heart failure.

BACKGROUND: Abnormalities of the skeletal muscle vasculature, such as endothelial dysfunction and reduced microvascular density, can be reversed by physical training in patients with chronic heart failure. The molecular mechanisms that mediate the beneficial effects of physical training on the vascular endothelium are unknown. METHODS: Endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) gene expression in the skeletal muscle, peak oxygen consumption (VO2) and calf peak reactive hyperemia were measured before and after 12 weeks of supervised physical training in 10 patients with chronic heart failure. Five patients with heart failure of similar severity who did not participate in the training program served as controls. RESULTS: The effects of physical training on eNOS and VEGF gene expression were heterogeneous. eNOS gene expression increased 3-4 fold in 4 patients while it remained constant in 6 patients. VEGF gene expression increased significantly in all patients who were not treated with beta-adrenergic blockade and remained constant in all patients who were treated with beta-adrenergic blockade. In contrast, physical training increased peak VO2 and calf peak reactive hyperemia in all patients. Mean peak VO2 increased from 13.13 +/- 2.21 to 16.19 +/- 2.69 ml/kg/min (p < 0.001) and calf peak reactive hyperemia increased from 19.7 +/- 2.3 to 29.6 +/- 4.0 ml*min(-1)*100 ml(-1) (p < 0.001). CONCLUSIONS: A supervised program of physical training that consistently enhanced peak VO2 and vascular reactivity in patients with chronic heart failure increased or left eNOS and VEGF gene expression unchanged in skeletal muscle. Changes in vascular endothelial gene expression may contribute to the benefits of training on vascular endothelial function but are not solely responsible for these benefits.

Aged↗
PubMed1999

Economics, health-related quality of life, and cost-effectiveness methods for the TACTICS (Treat Angina With Aggrastat [tirofiban]] and Determine Cost of Therapy with Invasive or Conservative Strategy)-TIMI 18 trial.

Concern over escalating health care costs has led to increasing focus on economics and assessment of outcome measures for expensive forms of therapy. This is being investigated in the Treat Angina With Aggrastat [tirofiban] and Determine Cost of Therapy with Invasive or Conservative Strategy (TACTICS)-TIMI 18 trial, a randomized trial comparing outcome of patients with unstable angina or non-Q-wave myocardial infarction treated with tirofiban and then randomized to an invasive versus a conservative strategy. Hospital and professional costs initially and over 6 months, including outpatient costs, will be assessed. Hospital costs will be determined for patients in the United States from the UB92 formulation of the hospital bill, with costs derived from charges using departmental cost to charge ratios. Professional costs will be determined by accounting for professional services and then converted to resource units using the Resource Based Relative Value Scale and then to costs using the Medicare conversion factor. Follow-up resource consumption, including medications, testing and office visits, will be carefully measured with a Patient Economic Form, and converted to costs from the Medicare fee schedule. Health-related quality of life will be assessed with a specific instrument, the Seattle Angina Questionnaire, and a general instrument, the Health Utilities Index at baseline, 1, and 6 months. The Health Utilities Index will also be used to construct a utility. By knowing utility and survival, quality-adjusted life years will be determined. These measures will permit the performance of a cost-effectiveness analysis, with the cost-effectiveness of the invasive strategy defined and the difference in cost between the invasive and conservative strategies divided by the difference in quality-adjusted life years. The economic and health-related quality of life aspects of TACTICS-TIMI 18 are an integral part of the study design and will provide a comprehensive understanding of the impact of invasive versus conservative management strategies on a broad range of outcomes after hospitalization for unstable angina or non-Q-wave myocardial infarction.

Angina Pectoris↗
PubMed1997

Nonselective beta-adrenergic blockade with carvedilol does not hinder the benefits of exercise training in patients with congestive heart failure.

BACKGROUND: Long-term beta-adrenergic blockade does not appear to be associated with drug-induced training in patients with congestive heart failure (CHF); whether exercise training can increase peak aerobic capacity in patients with CHF who are treated with beta-adrenergic blockers is currently unknown. METHODS AND RESULTS: We studied 23 patients with CHF who were treated with carvedilol or propranolol in addition to ACE inhibitors, furosemide, and digoxin. Of the patients treated with carvedilol, 8 underwent exercise training and 8 remained sedentary. All 7 patients treated with propranolol underwent exercise training. Peak oxygen consumption (mL.kg-1.min-1) was serially measured in trained and sedentary patients. Peak reactive hyperemia (mL.min-1.100 mL-1) was determined in the calf and forearm immediately before and after 12 weeks of training. The peak oxygen consumption of trained patients treated with either carvedilol or propranolol increased from 12.9 +/- 1.4 to 16.0 +/- 1.6 (P < .001) and 12.4 +/- 1.0 to 15.7 +/- 0.9 (P < .001) mL.kg-1.min-1, respectively, whereas it did not change in the sedentary patients. Peak reactive hyperemia increased significantly in the calves but not the forearms of trained patients. CONCLUSIONS: Long-term, nonselective beta-adrenergic blockade with carvedilol or propranolol does not prevent patients with CHF from deriving systemic and regional benefits from physical training.

Adaptation, Physiological↗
PubMed1997

Exercise training in patients with severe congestive heart failure: enhancing peak aerobic capacity while minimizing the increase in ventricular wall stress.

OBJECTIVES: The aims of the study were to 1) assess the effects of 12 weeks of exercise training at low work loads (i.e., corresponding to < or = 50% of peak oxygen consumption [Vo2]) on peak Vo2 and hyperemic calf blood flow in patients with severe congestive heart failure; and 2) evaluate left ventricular diastolic pressure and wall stress during exercise performed at work loads corresponding to < or = 50% and 70% to 80% of peak Vo2. BACKGROUND: Whether the benefits of exercise training can be achieved at work loads that result in lower left ventricular diastolic wall stress than those associated with conventional work loads is unknown in patients with severe congestive heart failure. METHODS: Sixteen patients with severe congestive heart failure trained at low work loads for 1 h/day, four times a week, for 12 weeks. Peak Vo2 and calf and forearm reactive hyperemia were measured before and during training. Nine of the 16 patients underwent right heart catheterization and echocardiography during bicycle exercise at low and conventional work loads (i.e., 50% and 70% to 80% of peak Vo2, respectively). RESULTS: The increase in left ventricular diastolic wall stress was substantially lower during exercise at low work loads than during exercise at conventional work loads, (i.e., [mean +/- SEM] 23.3 +/- 7.4 vs. 69.6 +/- 8.1 dynes/cm2 (p < 0.001). After 6 and 12 weeks of training, peak Vo2 increased from 11.5 +/- 0.4 to 14.0 +/- 0.5 and 15.0 +/- 0.5 ml/kg per min, respectively (p < 0.0001 vs. baseline for both). Peak reactive hyperemia significantly increased in the calf but not in the forearm. The increases in peak Vo2 and calf peak reactive hyperemia correlated closely (r = 0.61, p < 0.02). CONCLUSIONS: In patients with severe congestive heart failure, peak Vo2 is enhanced by exercise training at work loads that result in smaller increases in left ventricular diastolic wall stress than those observed at conventional work loads.

Aged↗
PubMed1994

Peripheral factors in the management of congestive heart failure.

Maladaptive changes in the periphery largely account for the symptomatology of patients with congestive heart failure (CHF). A decline in the systolic function of the left ventricle precipitates activation of neural and humoral systems to provide circulatory support. These include sympathetic release of norepinephrine, increases in angiotensin II, elevated levels of circulating arginine vasopressin, and impairment of the counterregulatory function of atrial natriuretic peptide. The resultant circulatory changes are ultimately responsible for the declining function of the peripheral vasculature and skeletal muscles of patients with CHF. In the peripheral vasculature, impaired vasodilatory capacity results from excess vessel wall stiffness, endothelial dysfunction, and structural abnormalities. The skeletal muscles develop poor aerobic capacity as a result of a change in predominant fiber type and excess reliance on glycolytic metabolic pathways. Physical deconditioning induced by symptoms tends to further promote these peripheral changes. Therapeutic interventions with symptomatic and prognostic benefits have essentially been targeted at the periphery. Angiotensin converting enzyme inhibitors may act by normalizing electrolyte and water balance, improving vascular endothelial function, and reversing structural changes in peripheral vessels. Exercise training appears to exert its benefit at the level of the vascular endothelium. Advances in the therapy of CHF depend on a greater understanding of changes in the periphery.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure.

BACKGROUND: Since organic nitroesters and endothelium-derived nitric oxide mediate vasodilation through a final common pathway, that is, by activation of soluble guanylate cyclase in vascular smooth muscle, nitroglycerin (NTG) could specifically enhance the endothelium-dependent vasodilatory response to acetylcholine (Ach) in patients with congestive heart failure (CHF) and endothelial cell dysfunction. Accordingly, the net effects of an intra-arterial infusion of NTG (10(-9) mol/L) on endothelium-dependent and endothelium-independent vasodilation were assessed in the forearm circulation of patients with CHF. METHODS AND RESULTS: The forearm blood flow responses to intra-arterial administration of graded concentrations of Ach (10(-7) to 10(-5) mol/L) were determined by venous occlusion plethysmography (mL/min per 100 mL) in 18 patients with CHF and 5 age-matched normal subjects before and during intra-arterial infusion of NTG (10(-9) mol/L) for 20 minutes. In eight patients, the duration of the infusion of NTG (n = 5) or vehicle control solution (n = 3) was extended to 12 hours with measurement of the forearm blood flow responses to Ach at 20 minutes, 4 hours, and 12 hours. In five additional patients, forearm blood flow response to intra-arterial administration of two doses of phentolamine (0.05 and 0.5 mg) were determined before and during a 20-minute NTG infusion. Regional administration of NTG 10(-9) mol/L did not change resting forearm blood flow in either normal subjects or patients with CHF. Before administration of NTG 10(-9) mol/L, intra-arterial infusions of Ach 10(-7), 10(-5) and 10(-5) mol/L increased forearm blood flow to 14.7 +/- 6.2, 20.2 +/- 4.7, and 38.4 +/- 7.9 mL/min per 100 mL in normal subjects and to 4.1 +/- 0.8, 5.0 +/- 1.1, and 10.6 +/- 2.3 mL/min per 100 mL in patients with CHF. After administration of NTG 10(-9) mol/L for 20 minutes, the vasodilatory response to Ach significantly increased to 5.6 +/- 1.0, 6.9 +/- 1.6, and 17.7 +/- 3.4 mL/min per 100 mL in patients with CHF but did not change in normal subjects. The enhanced forearm blood flow responses to administration of Ach observed after 20 minutes of NTG administration in patients with CHF were sustained throughout a 12-hour NTG infusion. In contrast, regional administration of NTG did not change the vasodilatory responses to phentolamine. CONCLUSIONS: NTG, when administered intra-arterially for 20 minutes at a dose that does not affect resting forearm blood flow, specifically increased the vasodilatory response to intra-arterial administration of Ach in patients with CHF but not in normal subjects. The vasodilatory response to Ach was consistently enhanced by low-dose NTG throughout a 12-hour period. The vasodilating effects of organic nitroesters on the peripheral vasculature of patients with CHF may result in part from an interaction with the vascular endothelium.

Acetylcholine↗
PubMed1994

Pathophysiological correlates of increased serum tumor necrosis factor in patients with congestive heart failure. Relation to nitric oxide-dependent vasodilation in the forearm circulation.

BACKGROUND: Tumor necrosis factor-alpha (TNF alpha), which we and others have shown to be elevated in patients with severe congestive heart failure (CHF), is involved in the regulation of nitric oxide metabolism. Whether increased concentrations of TNF alpha affect nitric oxide-mediated vasodilation in patients with CHF has not been studied previously. METHODS AND RESULTS: Serum concentrations of TNF alpha, interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined in venous blood (pg/mL) from 17 patients with stable New York Heart Association classes II and III CHF (mean age, 58 +/- 11 years; mean left ventricular ejection fraction, 19.5 +/- 7.3) and 17 age-matched normal subjects with enzyme-linked immunosorbent assays (detection limit of assays, 20 pg/mL). Forearm blood flows were determined with plethysmography (mL/min per 100 mL) in 17 patients and 7 normal subjects in response to brachial artery administration of graded concentrations of acetylcholine (10(-6) mol/L and 10(-5) mol/L) and nitroglycerin (10(-7) mol/L and 10(-6) mol/L). Serum concentrations of TNF alpha were above the detection limits of the assay in 10 of 17 patients with CHF (mean serum concentration, 39.4 +/- 3.8 pg/mL). Forearm blood flow responses to acetylcholine and nitroglycerin were significantly greater in these 10 patients than in the 7 patients without detectable serum TNF alpha and were closely correlated with TNF alpha serum concentrations (r > or = .81, P < .01 and r > or = .65, P < .05 respectively). In 1 of 17 normal subjects, the serum concentration of TNF alpha was just above the detection limit of the assay. Serum concentrations of IL-2 were above the detection limit of the assay in 14 of 17 patients with CHF (mean serum concentration, 112 +/- 19 pg/mL). IL-2 was not detected in the serum of normal subjects. Serum concentrations of IL-1 and IL-6 were below the detection limit of the assays in all patients and normal subjects assayed. CONCLUSIONS: Increased TNF alpha concentrations are closely correlated with forearm blood flow responses to regional administration of acetylcholine and nitroglycerin. The significant correlation between serum concentrations of TNF alpha and forearm blood flow responses to acetylcholine and nitroglycerin suggests that both the inducible and the constitutive forms of nitric oxide synthase are involved in the regulation of peripheral vasomotor tone in patients with CHF.

Adult↗
PubMed1992

Autonomic manipulation influences both temporal and frequency analyses of late potentials.

Previous studies of late potentials have not standardized the autonomic milieu at the time of testing. We studied the effects of autonomic manipulation in seven patients with previous Q wave myocardial infarction. Late potentials were evaluated using standard temporal (TD) and spectral temporal mapping techniques (STM) in the drug free state, and during separate intravenous administration of each of the following: isoproterenol, esmolol, and atropine. Isoproterenol was titrated to achieve a heart rate of 130% of baseline. Esmolol was infused at a rate of 250 micrograms/kg per minute, after a loading dose of 500 micrograms/kg. Atropine was given as a 2-mg bolus. In addition, five patients who received no drug infusions acted as controls, undergoing four serial signal-averaging studies in the baseline state: a "baseline" study, and then three additional studies at time intervals similar to those incurred by the study patients. Therefore, a total of 21 TD and 21 STM tests were done in the study group (seven patients; three drugs per patient) during the drug infusions, and 15 TD and 15 STM tests were done in the control group (five patients; three "nonbaseline" tests per patient). A change (normal to abnormal, or vice versa) in TD during a drug infusion occurred in 24% of the tests. No such change occurred in the control group (P < 0.01). A change in STM during a drug infusion occurred in 38% of tests, versus 13% of tests in the control group (P = 0.14). Overall, six of seven patients had a change in TD and/or STM diagnosis with infusion of one or more of the study drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Pitfalls in the diagnosis of thoracic aortic aneurysm by transesophageal echocardiography.

A 74-year-old man underwent transesophageal echocardiography to evaluate the possibility of dissection of the descending aorta. The study demonstrated a round lumen that contained an echogenic mass mimicking aortic aneurysm with thrombus. However, computerized tomographic scanning identified the lumen as the pleural cavity containing a collapsed lung. The esophagus was on the right side of the spine, and the transesophageal technique could not visualize the descending aorta.

Aged↗