Influenza Vaccination Rate and Factors Associated With Compliance Among Health Care Employees in Large and Medium Acute Care Hospitals.

Annual influenza epidemics are associated with high morbidity and mortality worldwide, with vaccinations being the main preventive intervention; however, the compliance rate of health care employees remains low. Study aims were to examine vaccination rates among physicians and nurses in surgical and medicine wards, compare between medium and large tertiary hospitals, and identify factors associated with increased vaccination rates. Structured questionnaires were distributed. A total of 238/339 (70.2%) were vaccinated. In multivariate analysis, respiratory illness during precedent winter (odds ratio [OR] 3.146, P = .007), working in a medium hospital (OR 2.4, P = .003), and an attending resident with an infectious diseases subspecialty (OR 20.473, P = .007) were associated with a higher vaccination rate. Institutional email or portal messages were associated with decreased vaccination rates (OR = 0.259, P = .007). The leading reason for vaccination was "to stay healthy" (73.5%). Recruiting experts in the field, providing up-to-date information, and increasing management's involvement could encourage vaccination among health care employees.

The role of ventricular-arterial coupling in cardiac disease and heart failure: assessment, clinical implications and therapeutic interventions. A consensus document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association.

Ventricular-arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non-invasive measurement of the ratio of arterial (Ea) to ventricular end-systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo-arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis.

Role of Paced Breathing for Treatment of Hypertension.

PURPOSE OF REVIEW: Hypertension remains to be a major contributor to global morbidity and mortality. Despite a plethora of pharmacological options available, an abundance of patients have uncontrolled blood pressure thus creating the need for additional strategies, including non-pharmacologic approaches. In this review, we discuss the antihypertensive effect of slow and deep respiration by increasing baroreflex sensitivity. RECENT FINDINGS: Asking patients to carry out paced breathing sessions unaccompanied by a personal coach or unaided by a device may be unfeasible. Among proposed breathing techniques, RESPeRATE is a US Food and Drug Administration-certified device that assists slow breathing. In this review, we consider the mechanisms through which guided breathing mechanisms may impact on blood pressure control and alternative techniques. Guided breathing techniques along with lifestyle therapies may be helpful as a first step for patients with mild hypertension and prehypertension who do not suffer from cardiovascular disease, renal disease, or diabetes. Drug therapy must be considered after a couple of months if non-pharmacological therapy was unsuccessful. Device-guided paced breathing (DGB) may be recommended for those who cannot obtain full control of their hypertension with medical therapy alone or cannot tolerate potential side effects of pharmacologic treatment. Also, patients with well-controlled hypertension who may wish to try to reduce medication burden may be candidates for DGB. Patients with white coat or labile hypertension who are interested in biofeedback techniques could also be considered.

Lipoprotein-associated phospholipase A2, and subsequent cardiovascular events and mortality among patients with coronary heart disease.

OBJECTIVE: The objective of this study is to evaluate the relevance of Lp-PLA2 to risk prediction among coronary heart disease (CHD) patients. METHODS: Lp-PLA2 activity was measured in 2538 CHD patients included in the Bezafibrate Infarction Prevention (BIP) study. RESULTS: Adjusting for patient characteristics and traditional risk factors, 1 standard deviation of Lp-PLA2 was associated with a hazard ratio (HR) of 1.12 (95% confidence interval (CI): 1.00-1.25) for mortality and 1.03 (0.93-1.14) for cardiovascular events. Lp-PLA2 did not significantly improve model discrimination, or calibration nor result in noteworthy reclassification. CONCLUSIONS: Our results do not support added value of Lp-PLA2 for predicting cardiovascular events or mortality among CHD patients beyond traditional risk factor.

[EVALUATION OF THE ASSOCIATION BETWEEN ANTIHYPERTENSIVE TREATMENT AND DEVELOPMENT OF STROKE].

INTRODUCTION: An ischemic stroke is an event that occurs due to cerebral vascular disease and is directly related to the degree of vascular damage. This process is associated with atherosclerosis progression and is influenced by the presence of cardiovascular risk factors. AIMS: One of the goals of our research was to examine whether specific medications used for treating hypertension are associated with the development of strokes. METHODS: In a retrospective study of patients who were hospitalized between the years 2003-2008 due to a cerebrovascular accident (CVA) or a transient ischemic attack (TIA), 916 cases of stroke patients were reviewed. The patients were examined for the presence of background diseases including cardiovascular risk factors (hypertension, diabetes, dyslipidemia, renal failure, coronary artery disease). RESULTS: In the study, the most common stroke type was ischemic stroke (70.2%), one quarter of the patients (24.6%) suffered from TIA, and the smallest number of patients had hemorrhagic stroke (5.2%). The study demonstrated a discrepancy between the blood pressure level that was measured in the ER and the type of stroke. Also no correlation was observed between the blood pressure level measured in the ER, and the appearance of a recurring stroke. CONCLUSIONS: According to the analyzed data, no priority could be given to any of the six groups of drugs that treat hypertension in preventing a recurring event of stroke. However, the drug combinations of diuretics and ACEI, and that of CCB with ACEI were preferred to all other drug combinations. For more accurate assessment of the level of balance of cardiovascular risk factors and medications against the disease, it is necessary to extend the survey, as well as perform a prospective randomized study.

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society.

While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

RESPeRATE: the role of paced breathing in hypertension treatment.

Despite a good adherence to lifestyle modifications and antihypertensive drugs, hypertension remains resistant in more than one-third of patients, thus creating the need for additional strategies, including non-pharmacologic approaches. Slow and deep breathing ("paced breathing") associated in the past with meditation has a direct antihypertensive effect by increasing baroreflex sensitivity. With the method of guiding the pace of breathing, a US Food and Drug Administration-certified device, RESPeRATE, may offer an easy, efficient, inexpensive, and noninvasive option for treating hypertension. Multiple studies showed a significant reduction of blood pressure when RESPeRATE was evaluated in a home and office setting. In conclusion, this review outlines the pathophysiologic background of paced respiration, describes RESPeRATE clinical trials, and presents briefly other guided breathing alternatives.

Treatment of hypertension and metabolic syndrome: lowering blood pressure is not enough for organ protection, new approach-arterial destiffening.

Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage. Until now, the main approach to reduce CVRF-induced end organ damage was by normalization of CVRFs; this approach was found effective to reduce damage and cardiovascular (CV) events. However, a residual risk always remained even when CVRFs were optimally balanced. An additional risk factor which has an immense effect on the progression of end organ damage is aging. Aging is accompanied by gradual stiffening of the arteries which finally leads to CV events. Until recently, the process of arterial aging was considered as unmodifiable, but this has changed. Arterial stiffening caused by the aging process is similar to the changes seen as a result of CVRF-induced arterial damage. Actually, the presence of CVRFs causes faster arterial stiffening, and the extent of damage is proportional to the severity of the CVRF, the length of its existence, the patient's genetic factors, etc. Conventional treatments of osteoporosis and of hormonal decline at menopause are potential additional approaches to positively affect progression of arterial stiffening. The new approach to further decrease progression of arteriosclerosis, thus preventing events, is the prevention of age-associated arterial structural changes. This approach should further decrease age-associated arterial stiffening. A totally new promising approach is to study the possibility of affecting collagen, elastin, and other components of connective tissue that participate in the process of arterial stiffening. Reduction of pulse pressure by intervention in arterial stiffening process by novel methods as breaking collagen cross-links or preventing their formation is an example of future directions in treatment. This field is of enormous potential that might be revolutionary in inducing further significant reduction of cardiovascular events.

Arterial elasticity in obese subjects with coronary slow flow phenomenon.

BACKGROUND: Coronary slow flow phenomenon (CSFP) is a functional and structural disease that is diagnosed by coronary angiogram. OBJECTIVES: To evaluate the possible association between CSFP and small artery elasticity in an effort to understand the pathogenesis of CSFP. METHODS: The study population comprised 12 patients with normal coronary arteries and CSFP and 12 with normal coronary arteries without CSFP. We measured conjugated diene formation at 234 nm during low density lipoprotein (LDL) oxidation, as well as platelet aggregation. We estimated, noninvasively, arterial elasticity parameters. Mann-Whitney nonparametric test was used to compare differences between the groups. Data are presented as mean +/- standard deviation. RESULTS: Waist circumference was 99.2 +/- 8.8 cm and 114.9 +/- 10.5 cm in the normal flow and CSFP groups, respectively (P = 0.003). Four patients in the CSFP group and one in the normal flow group had type 2 diabetes. Area under the curve in the oral glucose tolerance test was 22% higher in the CSFP than in the normal group (P = 0.04). There was no difference in systolic and diastolic blood pressure, plasma concentrations of total cholesterol, triglycerides, high density lipoprotein, LDL and platelet aggregation parameters between the groups. Lag time required until initiation of LDL oxidation in the presence of CuSO4 was 17% longer (P = 0.02) and homocysteine fasting plasma concentration was 81% lower (P = 0.05) in the normal flow group. Large artery elasticity was the same in both groups. Small artery elasticity was 5 +/- 1.5 ml/mmHg x 100 in normal flow subjects and 6.1 +/- 1.9 ml/mmHg x 100 in the CSFP patients (P = 0.02). CONCLUSIONS: Patients with CSFP had more metabolic derangements. Arterial stiffness was not increased in CSFP.

Differential clinical profile of candesartan compared to other angiotensin receptor blockers.

The advantages of blood pressure (BP) control on the risks of heart failure and stroke are well established. The renin-angiotensin system plays an important role in volume homeostasis and BP regulation and is a target for several groups of antihypertensive drugs. Angiotensin II receptor blockers represent a major class of antihypertensive compounds. Candesartan cilexetil is an angiotensin II type 1 (AT[1]) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Oral candesartan 8-32 mg once daily is recommended for the treatment of adult patients with hypertension. Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy, and migraine in different populations of adult patients including patients with coexisting type 2 diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in BP treatment, is a highly selective compound with high potency, a long duration of action, and a tolerability profile similar to placebo. The most important and recent data from clinical trials regarding candesartan cilexetil will be reviewed in this article.

Effect of long-term treatment with antioxidants (vitamin C, vitamin E, coenzyme Q10 and selenium) on arterial compliance, humoral factors and inflammatory markers in patients with multiple cardiovascular risk factors.

BACKGROUND: Antioxidant supplementations have the potential to alleviate the atherosclerotic damage caused by excessive production of reactive oxygen species (ROS). The present study evaluated the effects of prolonged antioxidant treatment on arterial elasticity, inflammatory and metabolic measures in patients with multiple cardiovascular risk factors. METHODS: Study participants were randomly assigned to two groups. Group 1 received oral supplementation with 2 capsules per day of Mid Life Guard, SupHerb, Israel. In each capsule vitamin C (500 mg) vitamin E (200 iu), co-enzyme Q10 (60 mg) and selenium (100 mcg), Group 2 received matching placebo(SupHerb) for 6 months. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, hs-CRP, endothelin, aldosterone, plasma renin activity and Homeostasis model assessment-insulin resistance (HOMA-IR). Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota). RESULTS: Antioxidant-treated patients exhibited significant increases in large arterial elasticity index (LAEI) as well as small arterial elasticity index (SAEI). A significant decline HbA1C and a significant increase in HDL-cholesterol were also observed. In the placebo group, significant changes in LAEI, SAEI or metabolic measures were not observed. CONCLUSIONS: Antioxidant supplementation significantly increased large and small artery elasticity in patients with multiple cardiovascular risk factors. This beneficial vascular effect was associated with an improvement in glucose and lipid metabolism as well as decrease in blood pressure.

Effect of Long-Term L-Arginine Supplementation on Arterial Compliance and Metabolic Parameters in Patients with Multiple Cardiovascular risk Factors: Randomized, Placebo-Controlled Study.

OBJECTIVES:: This study was designed to determine the effect of long-term L-arginine supplementation on arterial compliance, inflammatory and metabolic parameters in patients with multiple cardiovascular risk factors. METHODS:: In this randomized, placebo-controlled trial, 90 patients were randomly assigned to two groups: Group 1 received daily oral L-arginine, Group 2 received matching placebo capsules. Patients were evaluated for lipid profile, glucose, HbA1C, insulin, hs-CRP, renin and aldosterone .Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota). RESULTS:: Although large artery elasticity index (LAEI) did not differ significantly between the groups at baseline (10.64.3 vs.11.64.5 ml/mm HgX100, p=0.346), at the end of the study LAEI was significantly greater in patients treated with L-arginine than in the placebo group (12.73.4 vs. 8.02.8 ml/mm HgX10, p<0.0001). Systemic vascular resistance was significantly lower in patients treated with L-arginine than in the placebo group after 6 months. Small artery elasticity index (SAEI) did not differ significantly between the groups at baseline or at the end of the study. Serum aldosterone decreased significantly in Group 1 from 10.76.3 to 8.45.0 ng/ml (p=0.008), but did not change in the placebo group. CONCLUSION:: L-arginine supplementation improves LAEI in patients with multiple cardiovascular risk factors. This improvement was associated with a decrease in systolic blood pressure, peripheral vascular resistance as well as a decrease in aldosterone levels. The results suggest that long term L-arginine supplementation has beneficial vascular effects in pathologic disease states associated with endothelial dysfunction.

Effect of the urotensin receptor antagonist palosuran in hypertensive patients with type 2 diabetic nephropathy.

The urotensin system has been hypothesized to play an important role in the pathophysiology of diabetic nephropathy. In this multicenter, randomized, double-blind, placebo-controlled, 2-period crossover study, the effects of the urotensin receptor antagonist palosuran on urinary albumin excretion and blood pressure in hypertensive patients with type 2 diabetic nephropathy treated with a single blocker of the renin-angiotensin-aldosterone system were assessed. Patients with 24-hour albuminuria >0.5 and <3.0 g, systolic blood pressure >135 and <170 mm Hg, and/or diastolic blood pressure >85 and <110 mm Hg received both palosuran 125 mg BID and placebo for 4 weeks each. Fifty-four patients (20% women; mean age: 61.6 years, blood pressure: 155/84 mm Hg, and albuminuria: 1016 mg per 24 hours) were included in the per-protocol analysis. Palosuran did not affect albuminuria, blood pressure, glomerular filtration rate, or renal plasma flow significantly. These results question whether urotensin receptor antagonism represents a new treatment strategy in this high-risk patient population.

Atrial fibrillation and long-term prognosis in patients hospitalized for heart failure: results from heart failure survey in Israel (HFSIS).

AIMS: Atrial fibrillation (AF) and heart failure (HF) commonly coexist, and each adversely affects the other. The aim of the study was to prospectively evaluate the impact of AF and its subtypes on management, and early and long-term outcome of hospitalized HF patients. METHODS AND RESULTS: Data were prospectively collected on HF patients hospitalized in all public hospitals in Israel as part of a national survey (HFSIS). Atrial fibrillation patients were subdivided into intermittent and chronic AF subgroups. During March-April 2003, we enrolled 4102 HF patients, of whom 1360 (33.2%) had AF [600 (44.1%) intermittent, 562 (41.3%) chronic]. Patients with AF were older (76.9 +/- 10.5 vs. 71.7 +/- 12.6 years, P = 0.0001), males, with preserved LV systolic function. Crude mortality rates for AF patients were progressively and consistently higher during hospitalization and during the 4-year follow-up period, especially in the chronic AF group (P = 0.0001). After covariate adjustment, AF was associated with increased 1-year mortality [HR 1.19, 95% CI (1.03-1.36)]. CONCLUSION: AF was present in a third of hospitalized HF patients, and identified a population with increased mortality risk, largely due to co-morbidities.

Arterial elasticity in cardiovascular disease: focus on hypertension, metabolic syndrome and diabetes.

Arterial stiffness is an independent risk factor for premature cardiovascular morbidity and mortality that can be evaluated by noninvasive methods and can be reduced by good clinical management. The present chapter examines the association between arterial stiffness and cardiovascular risk factors including hypertension, metabolic syndrome, diabetes, advanced renal failure, hypercholesterolemia and obesity. The mechanisms responsible for the structural and functional modifications of the arterial wall are also described. We deal with parameters related to arterial compliance, focusing on two of them, pulse wave velocity and the augmentation index, useful in rapid assessment of arterial compliance by the bedside. Data that highlight the role of aortic pulse wave velocity and the augmentation index as independent factors in predicting fatal and nonfatal cardiovascular events in different populations are briefly presented. A number of lifestyle changes and traditional antihypertensive agents that improve arterial compliance are finally discussed. Novel therapies, such as statins, thiazolidindinediones, phosphodiesterase inhibitors and inhibitors or breakers of advanced glycation end product cross-links between colagen and elastin hold substantial promise.

Clinical and hemodynamic effects of bosentan dose optimization in symptomatic heart failure patients with severe systolic dysfunction, associated with secondary pulmonary hypertension--a multi-center randomized study.

OBJECTIVE: To evaluate the effects of bosentan on echo-derived hemodynamic measurements, and clinical variables in symptomatic heart failure (HF) patients. METHOD: Multi- center, double-blind, randomized (2:1), placebo-controlled study comparing bosentan (8-125 mg b.i.d.) to placebo in patients with New York Heart Association class IIIb-IV HF, left ventricular ejection fraction <35% and systolic pulmonary artery pressure (SPAP) >40 mm Hg. Primary and secondary endpoints were change from baseline to 20 weeks in SPAP and cardiac index, respectively. Safety endpoints were treatment emergent adverse events (AEs), change in body weight, hemoglobin, hematocrit, systolic blood pressure and diuretic use. RESULTS: Ninety-four patients enrolled: 60 to bosentan, 34 to placebo. There was no significant difference between the 2 arms in SPAP change (0.1 +/- 11.5 mm Hg , 95% confidence limit (CL) -5.4 to 5.2, p = 0.97), cardiac index shift (0.12 +/- 0.45, 95% CL -0.09 to 0.33 , p = 0.24 ) or any of the other 22 echocardiographic measurements obtained. Therapy-duration was longer in the placebo arm, while more patients in the bosentan arm experienced adverse and serious AEs. CONCLUSION: In HF patients with left ventricular dysfunction and secondary pulmonary hypertension, bosentan did not provide any measurable hemodynamic benefit, and was associated with more frequent AEs, requiring drug discontinuation.

Vascular elasticity of systemic lupus erythematosus patients is associated with steroids and hydroxychloroquine treatment.

We studied the large and small artery elasticity (AE) and systemic vascular resistance (SVR) of systemic lupus erythematosus (SLE) patients according to treatment profile. Forty-one SLE patients (90% female, mean age 48.7 +/- 2.4 years) were compared to 96 healthy controls. The large and small AE and the SVR were derived from radial artery waveforms (model CR-2000, HDI Inc.). Patients were categorized into groups according to treatment: steroid (12), hydroxychloroquine (HCQ) (9), steroid+HCQ (16), and no-steroids-no-HCQ (4). The steroid group had reduced large AE and increased SVR as compared to the HCQ group (8.3 mmHg x mL x 10 and 18.4 dyne x sec x 10(-3) versus 13.7 and 14.4, respectively). Mean large AE and the SVR of the HCQ group was similar to that of the controls (11.8 mmHg x mL x 10 and 14.5 dyne x sec x 10(-3), respectively). Mean large AE and SVR of the steroid+HCQ group were better than the steroid group (10.4 mmHg x mL x 10 and 16.0 dyne x sec x 10(-3)). Patients that received steroids had higher rates of hypertension (36%) and diabetes (1%) compared to rest of the patients (15% and 0%, respectively). Small AE, blood pressure, CRP, and SLEDAI were similar between the groups. Among SLE patients, steroid treatment was associated with the highest degree of vascular damage, and HCQ was associated with the lowest degree of vascular damage. It is possible that the steroids are responsible in part to the increased large-vessel manifestations observed in these patients, and that HCQ might have a protective effect on the vessel wall.

Adenosine and TNF-alpha exert similar inotropic effect on heart cultures, suggesting a cardioprotective mechanism against hypoxia.

When cardiomyocytes were subjected to hypoxia, tumor necrosis factor-alpha (TNF-alpha; 3-50 ng/ml) or adenosine (1-100 microM), decreased hypoxic damage as was detected by lactate dehydrogenase (LDH) release, MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) absorbance, ROS (reactive oxygen species) measurement or desmin immunostaining. This cardioprotection was not prevented in TNF-alpha-treated cultures by 5-hydroxydecanoic acid (5-HD). Our aim was to elucidate whether adenosine and TNF-alpha mediate a similar protective mechanism against hypoxia in primary heart cultures and in H9c2 cardiomyocytes. Adenosine and TNF-alpha are known for their negative inotropic effects on the heart. We have suggested that deoxyglucose uptake reflects heart contractility in cell cultures; therefore, we assayed its accumulation under various conditions. Treatment for 20 min with adenosine, R-PIA [(-)-N(6)-phenylisopropyladenosine] (10 microM), or TNF-alpha reduced (3)H-deoxyglucose uptake in primary heart cultures and also in H9c2 cardiomyocytes by 30-50%. Isoproterenol accelerated (3)H-deoxyglucose uptake by 50%. Adenosine, R-PIA, or TNF-alpha attenuated the stimulatory effect of isoproterenol on (3)H-deoxyglucose uptake to control levels. Hypoxia reduced (3)H-deoxyglucose uptake by 50%, as in the treatment of the hypoxic cultures with TNF-alpha or adenosine. Glibenclamide (2 microM), 5-HD (300 microM), or diazoxide (50 microM) increased (3)H-deoxyglucose uptake by 50-80%. Adenosine (100 microM) and TNF-alpha (50 ng/ml) stimulated (86)Rb efflux. Glibenclamide attenuated this effect. We demonstrate that TNF-alpha, like adenosine, accelerated Ca(2+) uptake into the sarcoplasmic reticulum (SR) by 50-100% and therefore prevented cardiomyocyte Ca(2+) overload. Our findings further suggest that TNF-alpha, as well as adenosine, may mediate an adaptive effect in the heart by preventing Ca(2+) overload via activation of SR Ca-ATPase (SERCA(2)a).