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Purpose: The purpose of the present study was to examine the effects of long lasting chronic resistive training on circulating s-klotho s and IGF-1 levels in young adult. Methods: 50 national level powerlifters and 50 age matched untrained young adults (27.1±1.0 and 26.5±1.0 years respectively). Following overnight fasting forearm vein blood samples were taken, circulating s- Klotho were examined by means of a-klotho Enzyme Linked Immunosorbent Assay ELISA kit. A chemiluminescent immunometric method was applied in order to define serum IGF-1 levels. Results: No significant differences were seen between the weightlifters and untrained young adults for s-Klotho (421.0±76.0 and 435.2 ±89.0 pg·mL-1 respectively). However, IGF-1 levels were significantly (p

Purpose: To examine the aerobic energy portion utilized during the Wingate Anaerobic Test. Methods: Power output was compared with direct values obtained from measured oxygen uptake (VO2), in 14 (14.4 ± 1.0 yrs) healthy adolescents and 14 young adults (26.0 ± 1.0 yrs). Results: All subjects completed the exercise challenges without ECG abnormality. At rest, significant (P

Different studies support the notion that chronic aerobic exercises training can influence the circulating levels of soluble-Klotho (s-Klotho) and insulin-like growth factor 1 (IGF-I). The effects of s-Klotho include improving the quality of life, alleviating the negative impact of age on the body’s work capacity, and possibly increasing longevity. This review provides an overview of the latest findings in this field of research in humans. The different modes of dynamic exercise and their impact on circulating levels of s-Klotho and IGF-I in young adult athletes, untrained young adults, trained healthy older adults, untrained healthy older adults, and coronary artery disease (CAD) patients are reviewed and discussed. Together these findings suggest that long-lasting (chronic) aerobic exercise training is probably one of the antiaging factors that counteract the aging and CAD process by increasing the circulating s-Klotho and lowering the IGF-I levels. However, following anaerobic exercise training the opposite occurs. The exact metabolic and physiological pathways involved in the activity of these well-trained young and master sportsmen should be further studied and elucidated. The purpose of this review was to provide a clarification regarding the roles of s-Klotho and intensities and durations of different exercise on human health.

Background: End-stage renal disease (ESRD) reduces performance of cardiopulmonary function and peak oxygen uptake (VO2 peak). The possible roles of oxygen delivery and oxygen extraction as limiting factors of exercise tolerance in ESRD patients were assessed.Methods: A cross-sectional study was conducted with twenty-two ESRD patients who underwent a peak cardiopulmonary and echocardiograph exercise test via leg cycle ergometry.Results: During exercise, elevated lactic acid occurred at a mean workload of 68.6 ± 5.7 Watts, corresponding to 78% of their respective peak work capacity. At peak exercise, in all measured variables except for systolic blood pressure, ESRD patients did not achieve normally predicted values. Heart rate, left ventricular end diastolic and systolic volumes, stroke volume, cardiac output, VO2 peak, arteriovenous oxygen difference, and workload were below normal values, while diastolic blood pressure, mean blood pressure and total peripheral resistance were above normal values.Conclusions: In ESRD patients, values for both oxygen delivery and extraction were far below the recorded values in normal. This suggests diminished central cardiopulmonary responses as well as reduced peripheral capacity to extract oxygen at the muscle level. Findings support the concept and possible importance of exercise rehabilitation programs in the approach for treatment of ESRD patients.

Purpose: The present study looked at gender difference in oxygen delivery-extraction at maximal oxygen uptake in healthy adolescents. Methods: 36 adolescent males (14.9 ± 1.1 years) and 33 adolescent females (15.0 ± 1.1 years) underwent a maximal oxygen uptake test and a two dimensional direct m-mode echocardiography performed on a bicycle ergometry. Arteriovenous oxygen difference was defined by utilizing the Fick equation. Results: At rest, males compared to females had significantly (p

The purpose of this paper is to find out whether serum oxidizability potential measured before an exercise test (EXT) correlates with age and ischemic heart disease severity. Oxidizability potential was determined in 3 age groups, in gr. I patients $$ {\hbox{range}} = {45} - {7}0{\hbox{years}} $$ , and in gr. III patients > 70 years. Included subjects had chronic ischemic heart disease (IHD) and underwent a symptom-limited EXT upon initiation of a cardiac rehabilitation program. The thermo-chemiluminescence (TCL) assay was used to assess serum oxidizability potential. This assay is based on heat-induced oxidation of serum, leading to the formation of electronically excited species in the form of unstable carbonyls, which further decompose into stable carbonyls and light energy (low chemiluminescence). Measured photons emission is represented by a kinetic curve which is described by its amplitude and slope (=ratio). We assessed the correlations of TCL ratio with age, exercise duration, metabolic equivalents (METS), maximal heart rate (mHR), maximal systolic BP, >1 mm S-T depression, diabetes, hypertension, smoking, left ventricular ejection fraction (LVEF)> or r = 0.82), mHR (r = 0.77) and with exercise-induced S-T segment shift (r = 0.86, p p = 0.041, and in particular, in gr. III patients with low LVEF%. The TCL ratio (%) in gr. III was 188.7 ± 14.5, 192 ± 17 in gr. II, and 214 ± 13 in gr. I (p 45% (p p = NS), due to the fact these patients had a much lower LVEF% and a lower exercise capacity. Serum oxidizability potential is associated with age, EXT parameters, results, and IHD severity. TCL ratio is an “easy-to-measure marker” that might be incorporated into risk assessment and prediction in aged IHD patients.

Objectives: To study possible correlation between Endothelin-1, Matrix-metallo-proteinase- 9, and Myeloperoxidase serum activity and coronary CT angiography findings of atherosclerotic coronary artery disease in intermediate - high risk asymptomatic subjects. Methods: 65 consecutive asymptomatic subjects, 53 males and 12 females, mean age 58.8 +/-10.9 s.d., referred by their primary practitioner for the evaluation of coronary artery atherosclerotic disease by Cardiac CT exam were selected for the study. One serum sample was drawn from each participant and examined for the levels of Endothelin -1, MMP-9, MPO serum activity. Obstructive coronary artery disease was defined as at least 50 percent stenosis of one or more coronary segments. Plaques were identified as calcified or soft according to the CT Hounsfield attenuation number. Results: The Endothelin activity level was significantly elevated in subjects with significant obstructive coronary artery disease (p=0.022). Furthermore, high Endothelin activity level was found to correlate with calcified plaque burden (p=0.006), and to be an independent determinant of lesion severity (R2 = 0.124, R2 change = 0.006, p= 0.008) Conclusions: Endothelin-1 may be a marker of significant obstructive coronary disease and calcified plaque burden in asymptomatic subjects. The significance of MMP-9 and MPO as markers of atherosclerosis in such subjects has not been definitely clarified.

Functional Gly482Ser (rs8192678) and T294C (rs2016520) polymorphisms in the peroxisome proliferator-activated receptor γ coactivator-1 (PPARGC1A) and peroxisome proliferatoractivated receptor δ (PPARD) genes, respectively, have been associated with mRNA and/or protein activity. The aim of this study was to determine their frequency distribution among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy control subjects. There were no differences between the endurance athletes, the sprinters and the control group across the PPARD T294C genotypes (P =0.62). Similarly, no statistical differences were found between the subgroups of elite-level endurance athletes (those who had represented Israel in a world track and field championship or in the Olympic Games) and national-level endurance athletes (P =0.3), or between elite-level and national-level sprinters (P =0.9). However, a combined influence of these two polymorphisms on endurance performance was found. The PPARD CC+PPARGC1A Gly/Gly genotypes were more frequently found in the elite endurance athletes than in national-level endurance athletes (P

We evaluated the effects of long-term beta-blocker treatment on the balance between oxygen delivery and extraction at peak oxygen uptake (VO2) and at target heart rate training (anaerobic threshold).Fifteen patients with coronary artery disease performed paired peak cardiopulmonary and submaximal exercise tests on a cycle ergometer with and without atenolol treatment. Thirty minutes following the submaximal tests, participants pedaled 10 minutes at a workload corresponding to that of the anaerobic threshold attained. Arterial oxygen was defined from echocardiography and venous oxygen content.At rest, stroke volume, heart rate, and cardiac output were lower (P.05), whereas arteriovenous oxygen difference [(a - v)O2] was higher with the use of atenolol (P.05). At peak exercise, heart rate, lactate, and systolic blood pressure were lower (P.05), whereas (a - v)O2 was higher (P.05) with the use of atenolol. At anaerobic threshold, stroke volume, heart rate, cardiac output, and systolic blood pressure were lower (P.05), whereas (a - v)O2 was higher (P.05) with the use of atenolol. Absolute VO2 and workload during maximal (P = .67 and P = .49, respectively) and submaximal (P = .13 and P = .44, respectively) exercises were similar between conditions.Results demonstrate that atenolol treatment in patients with coronary artery disease does not alter VO2 and workload at the anaerobic threshold and peak exercise because of an increase in oxygen extraction and stroke volume in the face of reduced heart rate. These findings indicate that with long-term beta-adrenergic receptor blockade, there is interplay between oxygen delivery and extraction, suggesting a link between cardiac hemodynamic responses and skeletal muscle metabolic adaptations.

PURPOSE We evaluated left ventricular contractility during upright isometric exercise, in heart transplant recipients (HTRs) and in healthy controls, using ejection fraction and end-systolic pressure/volume ratio indexes. METHODS Fifteen healthy men (40 +/- 13 years) and 10 HTRs (42 +/- 12 years) underwent dead lift (DL) test at 30% of maximal effort for 3 minutes. Echocardiographic variables were measured during the final 45 seconds. RESULTS During DL test, HTRs were significantly different (P < .01) from controls in all parameters except end-diastolic volume. DL test had lower mean values of ejection fraction (49.9% +/- 8.3% vs 67.0% +/- 4.3%, respectively) and left ventricular end-systolic pressure/volume ratio (3.5 +/- 0.7 vs 5.5 +/- 1.2, respectively) whereas higher values of end-systolic volume (51.0 +/- 9.4 mL vs 34.1 +/- 5.3 mL, respectively). Importantly, an intergroup effect was found in end-systolic pressure/volume ratio, further signifying differential response of HTRs. End-systolic pressure/volume ratio increased consistently (P < .001) in both groups, whereas the overall main effect of ejection fraction response was not significant. CONCLUSIONS Left ventricular function during upright isometric exercise displays differential pattern of response in HTRs in comparison with healthy controls. However, cardiac contractility in HTRs remained stable at peak systolic blood pressure produced by the isometric DL exercise. Results suggest that both ejection fraction and end-systolic pressure/volume ratio indexes can be used for assessment of ventricular function in patients after heart transplantation.

Rationale: Aerobic exercise and Klotho gene expression reduce the risk of cardiovascular events in patients with prior coronary artery disease (CAD) thus, aerobic exercise may create a decreased risk of mortality. Objective: The purpose of the present study was to compare the association between s-klotho serum levels and IGF-1 levels in 3 groups: 60 untrained coronary artery disease patients (CAD) age 52.6 ± 2 years, 60 active participants with CAD in supervised aerobic programs for at least 12 months (4-5 times•wk-1) age 53.0 ± 2 years, and 40 untrained healthy males, age 53.6 ± 1.5 years to assess association of aerobic training and s-klotho activity. Methods and results: Blood samples were drawn from a forearm vein after overnight fasting, s-Klotho levels in the serum were analyzed using an α-klotho Enzyme Linked Immunosorbent Assay ELISA kit, while, IGF-1 was measured by a chemiluminescent immunometric method. Significant (p>0.05) differences were noted between the aerobically trained CAD patients and both untrained groups: CAD patients and healthy subjects with regard to s- Klotho (491 ± 66, 386 ± 70 and 418 ± 81 pg•mL-1 respectively), IGF-1 (82 ± 12, 106 ± 21 and 98 ± 14 nmol•L-1 respectively) and maximal oxygen uptake (42.1 ± 4.5, 31.9 ± 3.9 and 35.8 ± 2.9 mL•kg-1•min-1 respectively). Conclusions: S-Klotho and aerobic exercise training are factors that may promote upgrading capacities of the CAD patients. Inflection of Klotho expression through aerobic training represents a relationship that may contribute to the explanation of the effects of aerobic activity on CAD patients. In addition, findings suggest that atenolol treatment does not influence s-Klotho and IGF-1 levels in CAD patients treated with atenolol.

BACKGROUND Carvedilol, a beta1 and beta2 as well as an alpha1 adrenoreceptor antagonist with multiple hemodynamic, anti-ischemic and anti-oxidant properties, is widely accepted for the treatment of hypertension and congestive heart failure (CHF). It has been shown to improve morbidity and mortality in CHF. OBJECTIVES To assess whether the anti-oxidant effect of carvedilol has an impact on the clinical course in post-myocardial infarction (MI) CHF. METHODS Thirty-nine recent MI patients, aged 60.5 +/- 7 years, New York Heart Association functional class (FC) II-III, and left ventricular ejection fraction (LVEF) 29 +/- 3.8%, underwent oxygen free radical (OFR) assessment using the thiobarbituric acid reactive substances, thermochemoluminescence and conjugated dienes methods. OFR was determined at baseline, 1, 3, 12, and 24 h after 3.125, 6.25 and 12.5 mg carvedilol, and after 6 months of treatment. Brain natriuretic peptide (BNP), LVEF, FC change, 6-min walk test (6MW) and quality of life scores were evaluated before and after 6 months. RESULTS Two patterns of OFR activity were found. In 29 patients (group 1) a significant and consistent reduction in OFR following administration of each dose of carvedilol was found, significantly correlating with each of the outcome parameters. In ten patients (group 2), no change in OFR was found, nor in any of the other outcomes. At 6 months, FC improved in 23 patients from group 1 (79.3%) and only in one (10%) from group 2 (P

In this study we assess the influence of disease status on hemodynamic and cardiac output values, as measured by oxygen utilization at peak aerobic exercise, in heart transplant recipients (HTRs) and coronary artery disease patients (CAD).Fifteen CAD patients and 13 HTRs (40.2 +/- 12.6 and 41.7 +/- 11.7 years, respectively) underwent a peak cardiopulmonary exercise test on bicycle ergometry. Arterial oxygen was defined on the basis of echocardiography and venous oxygen content.At rest, except for cardiac output, oxygen uptake and lactate levels, all variables were significantly (p0.01) different between groups. At peak exercise, compared with HTRs, CAD patients had significantly (p0.0001) higher values for cardiac output (12.4 +/- 0.8 and 20.2 +/- 1.7 liters/min, respectively), stroke volume (87.3 +/- 5.4 and 129.3 +/- 9.7 ml, respectively) and oxygen uptake (22.7 +/- 3.6 and 29.7 +/- 2.7 ml/kg/min, respectively) (p0.01), whereas (a - v)O2 was significantly lower (127.0 +/- 4.3 and 141.9 +/- 6.4 O2 ml/liter, respectively; p0.0001).The differences in oxygen utilization at peak exercise may be attributed to differences in energy metabolism, namely higher oxygen extraction in HTRs, compensating for the dramatically reduced oxygen delivery. It is further suggested that CAD patients and HTRs respond to a greater extent to maximal aerobic testing by reducing their left ventricular systolic function despite increased after-load.

PURPOSE: The effect of gender on paraoxonase activity was determined in 37 ischemic heart disease patients who underwent a 12-week aerobic exercise training program. METHODS: Paraoxonase activity was measured by its arylesterase activity (spectrophotometrically, at 250°C, wavelength 270 nm). RESULTS: A 16.7% increase in paraoxonase activity was found following the 12-week exercise program. In addition, there was a significant gender effect with higher mean paraoxonase levels among women during both preexercise (20.8%) and postexercise (24.2%) testing. CONCLUSIONS: Aerobic exercise training was found to be an effective means in inducing plasma levels elevation of the antioxidative, antiatherogenic paraoxonase in patients with coronary artery disease, and particularly in female patients.

Left ventricular function was evaluated in 14 adolescents (13.1 ± 1 years) at maximal oxygen uptake and at peak Wingate anaerobic test by means of echocardiography. Significant (p < .05) differences between aerobic and Wingate test bouts were found for: cardiac output (15.5 ± 1.2 and 12.2 ± 1.1 L/min, respectively); left ventricular end-systolic pressure—volume ratio (5.2 ± 0.8 and 6.0 ± 0.7, respectively); ejection fraction (72.2 ± 5.2 and 65.2 ± 5.1%, respectively); and mean arterial blood pressure (102.9 ± 10.8 and 111.1 ± 11.3 mmHg, respectively). Data suggest that left ventricular function at peak Wingate anaerobic test was markedly lower from that observed at peak aerobic exercise as a result of a higher afterload response.

Physical activity may lower the risk for coronary artery disease (CAD) by mitigating inflammation, which plays a key role in the pathophysiology of atherosclerosis. The purpose of this study was to determine the effect of aerobic exercise training on levels of pro- and anti-inflammatory cytokines, IL-1, IL-6, IL-10, INF-gamma, and C-reactive protein (CRP), in CAD patients participating in a cardiac rehabilitation program.Twenty-eight patients, age 64+/-7.1 years, participated in a 12-week aerobic exercise training program at 70-80% of individual maximal heart rate. Training resulted in a significant reduction of all pro-inflammatory cytokines, CRP from 7.5+/-4.2 to 3.9+/-3.5 mg/l, p0.001, IL-1, 0.33+/-0.23 to 0.51+/-0.12 pg/ml, p=0.014, IL-6, 2.50+/-1.50 to 1.44+/-0.57 pg/ml, p=0.002, INF-gamma, 18.63+/-3.31 to 16.77+/-2.49 pg/ml, p0.001, as well as a significant increase in the anti-inflammatory, cytokine IL-10, from 1.61+/-1.40 to 2.29+/-2.01 pg/ml, p=0.008. Baseline CRP levels were 36% (p=0.006) higher among diabetes mellitus patients and training was associated with a 40.5% CRP reduction in these patients compared to 19% reduction in non-diabetics, p0.01. At baseline 72% of patients were in a high risk category (CRP3 mg/l), 28% in an intermediate (CRP=1-3 mg/l), with none in a low risk category (1 mg/l). Following exercise training, 11% were in the low risk, 50% in the intermediate and 39% in the high risk category, indicating 46% reduction in the number of subjects in the high risk category.Aerobic exercise training in CAD patients is an effective mean in inducing reduction in CRP, IL-1, IL-6, INF-gamma levels, and increase in IL-10, thus, possibly improving coronary risk profile.

The present study compared and evaluated left ventricular function and contractility at peak incremental aerobic type exercise and all-out explosive anaerobic effort in young healthy trained subjects.Twenty-two young healthy trained subjects (19 +/- 1 yr) were studied by two-dimensional direct M-mode echocardiography at peak aerobic and at peak all-out anaerobic exercises, performed on cycle ergometer.All subjects completed the study without any electrocardiographic abnormalities. Significant (P0.05) differences between the aerobic and the anaerobic efforts were noted for peak cardiac output (24 +/- 2.0 and 15.0 +/- 1.1 L x min (-1), respectively), left ventricular pressure-volume ratio (5.8 +/- 0.6 and 4.7 +/- 0.5 respectively), end systolic volume (33 +/- 4 and 42 +/- 5 mL, respectively), ejection fraction (79 +/- 7 and 66 +/- 5%, respectively), and total peripheral resistance (TPR) (367 +/- 90 and 704 +/- 90 dynes x s(-1) x cm(- 5), respectively).These data suggest that left ventricular at peak all out anaerobic effort differed markedly from those observed at peak aerobic exercise. These differences are presumably due to the different after-load responses between the two exercise modes. Therefore, it is suggested that anaerobic-type effort should be performed with great caution in normal young healthy subjects.

Typical structural features of the athlete's heart as defined by echocardiography have been extensively described; however, information concerning extracardiac structures such as the inferior vena cava (IVC) is scarce. Fifty-eight top-level athletes and 30 healthy members of a matched control group underwent a complete Doppler echocardiographic study. IVC diameter was determined in the subxiphoid approach 10 to 20 mm away from its junction to the right atrium. Measures reflect the median values between maximal inspiratory and expiratory values. IVC respiratory collapsibility index was determined as well. IVC in athletes was 2.31 +/- 0.46 cm compared with 1.14 +/- 0.13 cm in the control group (P.001). Swimmers had an IVC diameter of 2.66 +/- 0.48 cm compared with 2.17 +/- 0.41 cm in other athletes (P.05). The IVC was normal (l.7 cm) in 5.2%, dilated (1.7 to 2.5 cm) in 70.7%, and very dilated (/=2.6 cm) in 24.1% of athletes. The collapsibility index was 58% +/- 6.4% in athletes compared with 70.2% +/- 4.9% in the control group (P. 001). Correlation was found between IVC size and VO(2) max (r = 0.81, P.001) and the right ventricle (r = 0.81, P.001) and with collapsibility index (r = -0.57, P.05). Multiple regression analysis showed the impact of VO(2) max, cardiac index, and right ventricular and left ventricular end-diastolic dimensions on IVC diameter. IVC dilatation probably represents adaptation of an extracardiac structure to chronic strenuous exercise in top-level, elite athletes.

The present study compared the direct intra-arterial method with the indirect conventional sphygmomanometer during all-out anaerobic exercise, in young healthy subjects. Systolic and diastolic blood pressures were measured by intraarterial means and by auscultation. Fourteen young healthy males (23+/-2 yrs) were measured at rest and during all-out anaerobic exercise. Comparisons were made with simultaneously determined intra-arterial catheter and auscultation measurements. The data suggest that indirect systolic pressure is highly correlated with the direct method at rest (r = 0.684), with mean of 107+/-7 and 101+/-6 mmHg, respectively, and during all-out anaerobic exercise (r = 0.87), with mean of 197+/-11 and 191+/-9 mmHg, respectively. Indirect diastolic blood pressure correlates well with intra-arterial at rest (r = 0.62), with mean of 84+/-11 and 77+/-9 mmHg, respectively. However, during all-out anaerobic exercise, the correlation coefficient between the direct and the indirect methods was low (r = 0.36), with mean of 101+/-12 and 103+/-9 mmHg, respectively. These results suggest that when utilizing an all-out anaerobic exercise, the indirect method is not valid for assessment of diastolic pressure. In addition, although the anaerobic test is a dynamic type of exercise, its blood pressure responses for both direct and indirect methods were similar to those seen during isometric exercise.

Patients with chronic congestive heart failure (CHF) have impaired oxygen delivery to working muscles. The Dead Sea, the lowest site on earth, is distinguished by natural oxygen enrichment, low humidity, high barometric pressure, and temperature with increased bromide and magnesium concentrations in the inspired air. The aim of this study is to examine the effects of descent to the Dead Sea on patients with CHF. Twelve patients with CHF and 4 age-matched healthy controls underwent complete echocardiographic studies at rest as well as treadmill and metabolic stress tests, both in Haifa, 130 m above sea level and 3 days after descent to the Dead Sea, 402 m below sea level. Significant changes in parameters at the Dead Sea compared with Haifa included time on treadmill, which increased from 612+/-198 to 672+/-1 86 seconds (p

PURPOSE: The aim of this study was to determine the proportion of patients with acute myocardial infarction (AMI) excluded from thrombolytic therapy on a national basis and to evaluate the prognosis of these patients by reasons of ineligibility and according to the alternative therapies that they received during hospitalization. PATIENTS AND METHODS: During a national survey, 1,014 consecutive patients with AMI were hospitalized in all the 25 coronary care units operating in Israel. RESULTS: Three hundred and eighty-three patients (38%) were treated with a thrombolytic agent and included in the GUSTO study. Ineligible patients for GUSTO were treated: (1) without any reperfusion therapy (n = 449), (2) by mechanical revascularization (n = 97), or (3) given 1.5 million units of streptokinase (n = 85) outside of the GUSTO protocol. The in-hospital and 1-year post-discharge mortality rates were 6% and 2% in patients included in the GUSTO study; 6% and 5% in those mechanically reperfused; 15% and 10% in those treated with thromoblysis despite ineligibility for the GUSTO trial, and 15% and 13% among patients not treated with any reperfusion therapy. CONCLUSIONS: Ineligibility for thrombolysis among patients with AMI remains high. Patients ineligible for thrombolysis according to the GUSTO criteria, but nevertheless treated with a thrombolytic agent were exposed to an increased risk.

The study's purpose was to analyze the effects of exercise training on exercise tolerance and left ventricular systolic function and structure in heart failure patients with preserved, mild, and moderate to severe reduction of left ventricular ejection fraction (LVEF).Ninety-eight patients with moderate to severe (n = 34), mild (n = 33), and preserved (n = 31) LVEF were randomly assigned to exercise training plus usual care (n = 65) or usual care alone (n = 33) in a randomization ratio of 2:1. Left ventricular function, left ventricular dimensions, and exercise tolerance were assessed before and after each intervention.Exercise tolerance and LVEF increased with exercise training in all patient groups, whereas they remained unchanged after usual care alone. Exercise training increased the mean ratio of early to late mitral inflow velocities (E/A ratio) and decreased deceleration time (DT) of early filling in patients with mild and preserved LVEF. In patients with moderate to severe systolic dysfunction and advanced diastolic dysfunction (DT160 ms), exercise training decreased E/A ratio and increased DT, both of which were unchanged after usual care alone. In the remaining patients (DT160 ms), exercise training also improved mitral inflow patterns. Exercise training decreased left ventricular dimensions in patients with mild and moderate to severe reduction of LVEF but not in patients with preserved LVEF.These results indicate that exercise training can improve the course of heart failure independent of the degree of baseline left ventricular dysfunction.

β1-adrenergic receptors (ADRB1) and Gαs proteins (GNAS) play important roles in the regulation of cardiac function. The present study sought to investigate whether ADRB1 Arg389Gly (rs1801253), GNAS -1211 G/A (rs6123837) and GNAS 2291 C/T (rs6026584) variants are associated with left ventricular function and exercise tolerance in heart failure patients. 61 heart failure patients completed a 6-month exercise-training programme. Left ventricular ejection fraction (LVEF), mitral inflow velocities (deceleration time, and E/A ratio) and exercise tolerance (METs) were assessed at baseline and following exercise training. There were no associations between the studied variants and LVEF or E/A ratio measured at baseline and after exercise training. Deceleration time of early mitral flow was higher at baseline in GNAS -1211G allele carriers compared with -1211A allele homozygotes (P

A national study was performed in early 1992 in the 25 operating coronary care units in Israel, which enabled the assessment of whether the therapeutic management of patients with acute myocardial infarction was affected by patient gender. During a 2-month period, 1,014 consecutive patients with acute myocardial infarction were hospitalized. Thrombolytic therapy was given to 47% of men (362 of 769), and 43% of women (106 of 245) (p = NS). After adjustment for age, no gender differences in the administration of thrombolytic therapy were noted (odds ratio 0.95; 95% confidence interval 0.73–1.23). Coronary angiography was more frequently performed in men (22%) than in women (16%) (p

This study compared end-systolic pressure-volume relationship (P/V) versus wall stress index (WS) as a tool for the evaluation of ventricular contractile state during upright isometric exercise. Both indices of contractility exhibit significant (p < 0.001) increase during exercise compared to resting values. The correlation coefficients for the two indices of contractility were r = -0.45 for exercise and r = -0.70 for rest. Both were significant at the p < 0.01 level. The correlation of the difference scores between rest and exercise as computed by both indices was low (-0.20) and insignificant. These data suggest that changes in contractility from rest to exercise as measured by one index do not reflect the pattern of individual differences that are measured by means of the other index. However, from a reliability point of view, it seems appropriate to prefer the use of P/V index over the WS index in order to determine contractile state.

Functional Gly482Ser (rs8192678) and T294C (rs2016520) polymorphisms in the peroxisome proliferator-activated receptor gamma coactivator-1 (PPARGC1A) and peroxisome proliferator-activated receptor delta (PPARD) genes, respectively, have been associated with mRNA and/or protein activity. The aim of this study was to determine their frequency distribution among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy control subjects. There were no differences between the endurance athletes, the sprinters and the control group across the PPARD T294C genotypes (P = 0.62). Similarly, no statistical differences were found between the subgroups of elite-level endurance athletes (those who had represented Israel in a world track and field championship or in the Olympic Games) and national-level endurance athletes (P = 0.3), or between elite-level and national-level sprinters (P = 0.9). However, a combined influence of these two polymorphisms on endurance performance was found. The PPARD CC + PPARGC1A Gly/Gly genotypes were more frequently found in the elite endurance athletes than in national-level endurance athletes (P0.000). In the cohort of endurance athletes, the odds ratio of the 'optimal genotype' for endurance athletes (PPARD CC + PPARGC1A Gly/Gly + PPARGC1A Gly/Ser) being an elite-level athlete was 8.32 (95% confidence interval 2.2-31.4). In conclusion, the present study suggests that PPARD T294C is not associated with endurance performance. However, a higher frequency of the PPARGC1A Gly/Gly + PPARD CC genotype is associated with elite-level endurance athletes.

The aim of this study was to determine the frequency distribution of nuclear respiratory factor 2 ( NRF2) intron 3 A/G polymorphism (rs7181866) among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy controls. Results showed that there was a significantly higher proportion of the AG genotype, rather than the AA genotype, in the group of endurance athletes compared with the sprinters ( P = 0.014) and controls ( P = 0.0008). However, the sprinters’ genotype and allele frequencies were similar to those of the control group ( P = 0.62 for genotype distribution percentage). These results were even more pronounced when we compared between the subgroups of 20 elite endurance athletes (those who had represented Israel in a world track-and-field championship or in the Olympic Games) and 54 national-level endurance athletes. In the group of elite endurance athletes the G allele was more frequent than in the national-level endurance athletes ( P = 0.047). We conclude that 1) in Israeli athletes the NRF2 AG genotype is more frequent in elite endurance athletes than in sprinters, and 2) within the endurance group the NRF2 AG genotype and the G allele are more frequent in elite athletes, suggesting a positive association between the AG genotype, and possibly the G allele, and the likelihood of being an elite endurance athlete.

The temporal behavior of the coronary microcirculation in acute myocardial infarction may affect outcome. Diastolic deceleration time and early systolic flow reversal derived from coronary artery blood flow velocity patterns reflect microcirculatory function.To assess left anterior descending coronary artery flow velocity patterns using Doppler transthoracic echocardiography after primary percutaneous coronary intervention, in patients with anterior AMI.Patterns of flow velocity patterns of the LAD were obtained using transthoracic echocardiography-Doppler in 31 consecutive patients who presented with anterior AMI. Measurements were done at 6 hours, 36-48 hours, and 5 days after successful PPCI. Measurements of DDT and pressure half times (Pt%), as well as observation for ESFR were performed.In the first 2 days following PPCI, the average DDT (600 +/- 340 msec) was shorter than on day 5 (807 +/- 332 msec) (P0.012), FVP in the first 2 days were dynamic and bidirectional: from short DDT (600 msec) to long DDT (600 msec) and vice versa. On day 5 most DDTs became longer. Pt1/2 at 6 hours was not different than at day 2 (174 +/- 96 vs. 193 +/- 99 msec, P = NS) and became longer on day 5 (235 +/- 98 msec, P = 0.012). Bidirectional patterns were also observed in the ESFR in 6 patients (19%) at baseline, in 4 (13%) at 36 hours, and in 2 (6.5%) on day 5 after PPCI.Flow velocity patterns of the LAD after PPCI in AMI are dynamic and reflect unpredictable changes in microcirculation.

Endurance exercise is usually prescribed with caution for hypertensive patients because of the possible adverse effects of increased blood pressure on cardiorespiratory function. Cardiopulmonary responses were studied in 11 young (37 +/- 4 years) and 10 elderly (65 +/- 4 years) male subjects during treadmill exercise with wrist weights (WW) and with no weights (NW) at constant 60% of their maximal heart rate for 8 min at each exercise condition. The results revealed that both groups had similar responses at rest. During maximal stress test, heart rate, oxygen consumption and minute ventilation were significantly (p less than 0.01) higher in the younger subjects. During 60% WW and NW exercises heart rate, oxygen consumption and minute ventilation were significantly (p less than 0.01) lower in the elderly than in the younger group. Diastolic and mean arterial blood pressures were significantly (p less than 0.01) higher in both groups during WW compared to NW exercise. However, minute ventilation and rate-perceived exertion were significantly (p less than 0.01) higher during NW compared to WW exercise. These measurements indicated a similar pattern of hemodynamics in younger and elderly hypertensive responders, with variable respiratory responses to endurance exercise. In addition, careful observation of blood pressure during exercise with WW is recommended for both groups where an increased afterload is contraindicated. We recommend the usage of controlled WW exercise for hypertensive responders of all age groups as part of their rehabilitative program.

Background: Aging-related changes occur mainly in the cardiopulmonary system and skeletal muscles, bringing about a reduction in physical performance. Consequently, maximal oxygen uptake (VO2max) decreases. Objectives: The current study investigated exercise oxygen utilization during maximal aerobic exercise in trained and untrained elderly. Methods: Fifteen trained (59.3 ± 1.1 years) and 15 untrained (60.1 ± 1.1 years) elderly underwent a peak cardiopulmonary exercise test on a bicycle ergometer. Arterial O2 was defined from echocardiograph and venous oxygen content. Results: At rest, trained compared to untrained elderly had significantly (p < 0.05) higher values of end diastolic volume (108.1 ± 5.8 and 100.7 ± 6.2 ml, respectively) and stroke volume (68.1 ± 4.3 and 57.3 ± 6.5 ml, respectively), while heart rate (68.7 ± 9.3 and 81.3 ± 8.2 beats · min–1, respectively), and mean arterial blood pressure (90.6 ± 6.9 and 95.4 ± 7.2 mm Hg, respectively) were significantly lower. At peak aerobic test, the trained elderly, compared to the untrained subjects, achieved significantly (p < 0.05) higher values of end diastolic volume (156.1 ± 8.2 and 134.1 ± 7.6 ml, respectively), stroke volume (123.0 ± 7.9 and 96.0 ± 4.8 ml, respectively), cardiac output (20.2 ± 1.5 and 15.0 ± 1.3 liters·min–1, respectively) and oxygen uptake (42.1 ± 2.1 and 31.1 ± 2.4 ml·kg–1·min–1, respectively), while diastolic blood pressure (70.3 ± 5.6 and 77.5 ± 4.2 mm Hg, respectively) and total peripheral resistance [4.3 ± 0.8 and 5.9 ± 1.41 (dyn·s–1·cm–5)·10–1, respectively], were significantly (p < 0.05) lower. Conclusions: The present study suggests that the differences between trained and untrained elderly in absolute oxygen uptake of the working muscles and peak power output at maximal exercise test are due to physical activity status. The higher aerobic capacity in the trained elderly is related to increased cardiovascular function and to a lesser extent to increased muscle mitochondria concentration and capillarity. Although untrained elderly have reduced maximal oxygen uptake at peak aerobic exercise, intrinsic regulation of mitochondrial function does not seem to be significantly altered because of aging associated physical inactivity. Therefore, untrained elderly can partially compensate for their lower cardiac output by increasing oxygen extraction to levels comparable with those of trained elderly.

To determine whether serum B-type natriuretic peptide measured at rest and peak exercise and DeltaBNP contribute to the predictive value and diagnostic accuracy of exercise test in the diagnosis of myocardial ischemia.Ventricular myocytes release BNP in response to increased wall stress that occurs in acute ischemia. During exercise testing, transient myocardial ischemia could also cause acute myocardial stress and changes in circulating BNP.BNP was measured before and immediately after exercise testing with radionuclide imaging in 203 consecutive subjects referred for chest pain evaluation. Tested subjects were classified as ischemic and non-ischemic based on exercise results, and no ischemia, mild-moderate, and severe ischemia according to perfusion scan results. A logistic regression model, constructed of an ROC and an AUC (area under the curve), was used.Ischemic ECG changes (or =1 mm, horizontal S-T shift) were detected in the treadmill exercise test in 127 subjects (62.6%), and 76 (37.4%) had neither ST segment shift nor chest pain. Baseline BNP was higher in the ischemic group compared to the non-ischemic group (p=0.044); peak BNP was also higher in the ischemic group (p=0.025), as was DeltaBNP (p=0.0126). Of these 127 subjects, 106 (52% of all) had abnormal perfusion scan results. In the ischemic group, the median baseline, peak exercise BNP, and DeltaBNP values from baseline to peak were higher than in the non-ischemic group. In the severe ischemic group these variables were approximately three-fold higher than in the mild-moderate ischemic group (p0.0001 for baseline; p0.0001 for peak; and p0.0001 for DeltaBNP). Rest, peak exercise, and DeltaBNP values were significantly higher in patients with previous myocardial infarction (p0.001) and in patients treated with beta blockers; peak exercise BNP was higher in hypertensives and diabetics (p0.05). The ROC convergence model showed that the AUC for peak-exercise BNP was best able to discriminate and predict severe ischemia and no ischemia, while DeltaBNP from rest to peak exercise discriminated best between mild-moderate and severe ischemia.Peak exercise BNP and DeltaBNP improved the sensitivity, specificity, positive likelihood ratio, predictive value, and diagnostic accuracy of severe ischemia detection during an exercise test. The contribution of BNP determination during exercise was, however, less impressive than previously reported by others.

PURPOSE Deterioration in left ventricular function is a more sensitive marker of myocardial ischemia during exercise than ST segment depression. The current study was designed to evaluate left ventricular function during one-repetition-maximum (1-RM) strength testing and resistance exercise in cardiac patients with moderate left ventricular dysfunction. METHODS Using echocardiographic methods, left ventricular function was evaluated in 15 patients with left ventricular dysfunction (age, 65 +/- 6.5 years; ejection fraction, 42.1 +/- 5.8). Measurements were performed during 1-RM testing and resistance exercise (20%, 40%, and 60% of 1-RM using 10 to 15 repetitions) on the one-arm biceps curl (BIC) and bilateral knee extension exercises and compared with measurements of left ventricular function during the symptom-limited graded exercise test (SL-GXT). RESULTS During the knee extension exercise, there was a slight but significant reduction (P< or =.05) in ejection fraction values at the end of 60% 1-RM, as compared with rest and previous workloads. Significant increases in systolic blood pressure and left ventricular end-systolic volume ratio values (P< or =.05) from rest to exercise were observed across test modes and for all workloads. The prevalence of new wall motion abnormalities during knee extension and BIC 1-RM strength testing was comparable with that observed during SL-GXT. The greatest increase in new wall motion abnormalities was seen during 60% 1-RM of knee extension exercise, as compared with prior workloads, BIC exercises, and SL-GXT. CONCLUSIONS Despite an increase in occurrence of ischemic changes during the highest resistance exercise workloads and with larger muscle mass, the findings are small in magnitude and do not suggest reduced cardiac performance.

Increased oxidative state has been previously demonstrated in several trials of myocardial reperfusion using a single-agent thrombolytic therapy. Combination therapy with Abciximab, a platelet glycoprotein IIb/IIIa inhibitor and reduced-dose t-PA (tissue Plasminogen Activator) has been suggested to improve myocardial reperfusion. However, its effect on radical activity has not been studied yet.

Background: All-out anaerobic exercise may be dangerous for the older population, due to hypoxia and inappropriate blood pressure response. Objectives: This study compared and evaluated left ventricular function at peak all-out anaerobic effort in 12 well-trained older (58 ± 1 years) and 12 young men (22 ± 1 years). Methods: Subjects were studied by echocardiography at peak all-out anaerobic exercise, on a cycle ergometer. Results: Seven older subjects experienced ECG abnormalities. Significant (p < 0.05) differences between the older group and the young group, respectively, were noted for: cardiac output (9.8 ± 0.9 and 15.8 ± 0.9 l·min–1), left ventricular end-systolic pressure-volume ratio (4.7 ± 0.8 and 4.4 ± 4.9), left ventricular end-diastolic volume (104.8 ± 6.9 and 125.7 ± 6.2 ml), ejection fraction (67.1 ± 6.0 and 59.8 ± 5.5%), left ventricular end-systolic pressure volume ratio (4.4 ± 0.4 and 4.8 ± 0.3 ratio), and total peripheral resistance (966.0 ± 84.0 and 660 ± 82.8 dyn·s–1·cm–5). Conclusions: Data suggest that during all-out anaerobic exercise, forces opposing ejection were not reduced enough to avoid left ventricular dysfunction and ECG abnormalities in the older subjects. This is attributed to functional changes with age in the myocardium and associated blood vessels, leading to impairment of left ventricular function and blunted inotropic and chronotropic responses to catecholamine. Therefore, an all-out anaerobic-type effort should not be given to an older subject due to the great hazardous potential.

Apparent life-threatening event (ALTE) is a term used to define an event of unknown cause after an infant is found limp, cyanotic, bradycardic, and/or requires resuscitation. Eight to 15% of children with ALTE die of sudden infant death syndrome. Obstructive sleep apnea, bradycardia, gastroesophageal reflux, and laryngotracheal abnormalities are frequently associated with ALTE. Wide QT dispersion is associated with sudden death in heart failure and increased risk of ventricular fibrillation in acute myocardial infarction. Here, we assess QT dispersion in infants with ALTE and its correlation to clinical and electrocardiographic indices. The study included eighty nine infants (age 2.14 +/- 1.8 months, 46 males and 43 females) referred with ALTE to the pediatric emergency room and 18 controls (age 2.77 +/- 2.2 months) who underwent electrocardiogram assessment of QTmin, QTmax, QT dispersion (QT-D), and as well as QTmin, QTmax, and QT-D corrected for heart rate (QTcmin, QTcmax, QTC-D, respectively). All infants were referred at the usual diagnostic tests-the gastroesophageal reflux test, apnea monitoring, Holter ECG monitoring, electroencephalogram, and Doppler echocardiography. QT-D, QTc-D, and QTc-min were significantly greater in the ALTE group (p < 0.01). Greater QTc-D was found in males compared to females (p < 0.001). QT-D and QTc-D showed little or no correlation with age of infant or positivity of diagnostic tests. QTc has been found by multiple regression analysis to be the independent variable with the greatest impact on QTc-D (beta = -0.68, p < 0.001).

PURPOSE The purpose of the present study was to examine the effect of aerobic exercise training on the immune system in coronary artery disease patients treated with beta-blockers. METHODS Twenty-five patients (46.1 +/- 2 yr) treated with atenolol, a beta-blocker agent, for 3 months before exercising were divided randomly into two groups: 15 underwent an aerobic exercise training program for 12 wk at 65-70% of their work capacity, whereas the other 10 patients served as controls. RESULTS After training, levels of CD4 and CD8 cells were significantly (P < 0.05) higher and concomitantly the CD4/CD8 ratio decreased significantly (P < 0.05) in the exercising group compared with the control group. CONCLUSIONS Data suggest that coronary artery disease patients exercising aerobically at 65-70% of their work capacity gain a statistically significant higher lymphocyte T cell function as compared with their untrained counterparts.

It is well appreciated that several neurohormones and signaling cascades are activated that promote long-term deterioration of cardiac function and structure. Activation of the renin-angiotensin-aldosterone system (RAAS) and the adrenergic system is closely related to heart failure. Common gene variants that encode neurohormonal, adrenergic and intracellular proteins have been demonstrated to modulate the course and consequences of heart failure. However, the literature is replete with conflicting results and it remains uncertain as to whether particular gene variants predispose heart failure. Therefore, the main purpose of this review was to discuss the effects of single nucleotide polymorphisms (SNPs) that are located in genes encoding elements of the RAAS and the adrenergic system on the predisposition to and survival from heart failure. Most studies indicate that common SNPs encoding elements of the RAAS and the adrenergic system do not predispose individuals to heart failure. Conversely, it has been demonstrated that ARB1 Arg389Gly, GRK5 Gln41Leu, ACE I/D, CYP11B2 C-344T and AGTR1 A+1166C modulate pharmacological responses and have a considerable impact on cardiac-related survival. It should not be expected, however, that a single polymorphism determines survival, given that multiple gene products and environmental factors contribute to the pathogenesis of heart failure. Therefore, future studies should consider the interaction effects of multiple genes in populations that are as homogeneous as possible with respect to environmental characteristics.

A prospective, randomized study compared the effects of equivalent intravenous doses of three slow calcium-channel blockers (verapamil, diltiazem, and amlodipine) on rest and exercise haemodynamics in 30 ischemic heart disease patients. Following a stable control period during which rest and exercise (supine bicycle) hemodynamics were assessed, equivalent hypotensive doses of each compound were administered over 20 minutes and rest/exercise parameters were assessed 10 minutes later. At rest all agents similarly reduced systemic blood pressure; the fall in systemic vascular resistance and the increase in cardiac indices was ranked: amlodipine greater than diltiazem greater than verapamil. The heart rate increase for amlodopine differed from verapamil and diltiazem (+19.4% vs. +1.5% vs. -7%; p less than 0.01). On exercise, similarly greater falls in the systemic vascular resistance index followed amlodipine, compared with verapamil and diltiazem (p less than 0.05). Only amlodipine significantly reduced the exercise pulmonary artery occlusion pressure (PAOP). Exercise cardiac stroke volume improved after diltiazem and amlodipine. In terms of cardiac performance, both amlodipine and diltiazem produced an improvement, whereas verapamil depressed cardiac pumping activity. Thus, hemodynamic differences between slow-calcium-channel blocking drugs may be demonstrated in humans. These differences would be compatible with a predominant peripheral vascular site of action for amlodipine, in contrast with mixed cardiac and peripheral sites for diltiazem and verapamil.