The effects of aerobic and anaerobic exercises on circulating soluble-Klotho and IGF-I in young and elderly adults and in CAD patients.

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.

GNAS A-1121G variant is associated with improved diastolic dysfunction in response to exercise training in heart failure patients.

ß1-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<0.05). Exercise training attenuated deceleration time in -1211G allele carriers (P<0.05) but not in -1211A allele homozygotes. Moreover, ADRB1 389Gly homozygotes had a greater training-induced increase in exercise tolerance than 389Arg homozygotes (P=0.04). This study shows that the functional GNAS -1121 G/A polymorphism is associated with diastolic function at baseline and in response to exercise training in heart failure patients. Furthermore, our data suggest that ADRB1 Arg389Gly polymorphism may influence exercise tolerance.

Do PPARGC1A and PPARalpha polymorphisms influence sprint or endurance phenotypes?

Functional Gly482Ser (rs8192678) and G/C (rs4253778) polymorphisms in the Peroxisome proliferator-activated receptor gamma coactivator1 (PPARGC1A) and Peroxisome proliferator-activated receptor alpha (PPARalpha) genes, respectively, have been associated with mRNA and protein activity. The aim of this study was to determine their frequency distribution among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy controls. Results showed that there was a significant difference in PPARGC1A Ser482Gly polymorphism genotype frequencies between endurance athletes and sprinters (P=0.005) as well as between endurance athletes and controls (P=0.0003). However, the sprinters' genotype and allele frequencies were similar to that of the control group. A significantly lower proportion of PPARGC1A Ser482 allele (0.25) was noted for the endurance athletes compared with controls (0.43, P=0.0001). Endurance athletes showed a trend of a higher yet a not significant proportion of the PPARalpha GG genotype compared with sprinters (P=0.051). As we compared between the subgroups of top-level endurance athletes and top-level sprinters, as well as between those of top-level and national-level endurance athletes, we reached more prominent results. In conclusion, our data indicate that a lower frequency of the Ser482 allele and possibly a higher frequency of the GG genotype are associated with increased endurance performance ability.

Is there an ACE ID - ACTN3 R577X polymorphisms interaction that influences sprint performance?

Functional R577X (rs.1815739) and ID (rs.5186) polymorphisms in the alpha-actinin-3 ( ACTN3) and the angiotensin converting enzyme (ACE) genes, respectively, have been associated with sprint performance. The aim of this study was to determine their effect on sprint performance among 81 Israeli sprinters and 240 healthy controls. Results revealed that the ACE II genotype+ ACTN3 R allele (P=0.003 for sprinters vs. controls), and the ACTN3 RR genotype +ACE I allele (P=0.001 for sprinters vs. controls) might be the genotype for sprinters. In the whole cohort the probability of ACTN3 RR genotype+ ACE I allele being a sprinter (odds ratio 2.67, 95% confidence interval 1.45-4.93) and of ACE II genotype+ ACTN3 R allele being a sprinter (odds ratio 3.57, 95% confidence interval 1.78-7.15) was significantly higher than that in the controls. In conclusion, the above data suggest that ACE ID/ ACTN3 R577X genotype combination is associated with sprint ability. However, ACE ID/ ACTN3 R577X genotype combination is not related to the level of performance.

ACTN3 R577X polymorphism and Israeli top-level athletes.

A common genetic variation in the alpha-actinin-3 ( ACTN3) gene causes a replacement of an arginine (R) with a premature stop codon (X) at amino-acid 577 (rs1815739). While the R allele has been found to be associated with power-oriented performance, the XX genotype may be linked with endurance ability. To test this hypothesis, we studied the distribution of ACTN3 genotypes in 155 Israeli athletes (age=35.9+12.2 years) classified by sport (endurance runners and sprinters) and in 240 sedentary individuals. The sprinters' allele frequencies (AF: R/X=0.7/0.3) and 577RR genotype distribution percentage (GD: RR=52%) differed markedly from those of the endurance athletes (AF: R/X=0.53/0.47, p=0.000007; GD: RR=18%, p=0.00009) and the control group (AF: R/X=0.55/0.45, p=0.0002; GD: RR=27.3%, p=0.000003). A comparison between the top-level and national-level sprinters revealed that the R allele occurs more often in the top-level sprinters. A significantly higher proportion of the XX genotype was observed in endurance athletes (34%) compared with controls (18%, p=0.02) and sprinters (13%, p=0.002). However, top-level and national level endurance athletes had similar allele and genotype frequencies. We conclude that the ACTN3 R allele is associated with top-level sprint performance and the X allele and XX genotypes may not be critical but rather additive to endurance performance.

Diagnostic accuracy of serum B-type natriuretic peptide for myocardial ischemia detection during exercise testing with spect perfusion imaging.

OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p<0.0001 for baseline; p<0.0001 for peak; and p<0.0001 for DeltaBNP). Rest, peak exercise, and DeltaBNP values were significantly higher in patients with previous myocardial infarction (p<0.001) and in patients treated with beta blockers; peak exercise BNP was higher in hypertensives and diabetics (p<0.05). 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. CONCLUSIONS: 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.

QT dispersion in infants with apparent life-threatening events syndrome.

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).

Left ventricular contractility and function at peak aerobic and anaerobic exercises.

PURPOSE: 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. METHODS: 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. RESULTS: All subjects completed the study without any electrocardiographic abnormalities. Significant (P < 0.05) 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). CONCLUSIONS: 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.

Dilated inferior vena cava: a common echocardiographic finding in highly trained elite athletes.

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 (/=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.

Direct vs. indirect blood pressure measurement at peak anaerobic exercise.

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.

Effects of low altitude on exercise performance in patients with congestive heart failure after healing of acute myocardial infarction.

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 <0.05); the Borg scale decreased by 1 to 2 grades (p <0.05); and oxygen saturation increased by 3% throughout exercise (p <0.05). Systolic blood pressure decreased by 9 mm Hg at rest (p <0.05) and increased by 14 mm Hg at peak exercise at the Dead Sea in patients with CHF (p <0.05). Cardiac output at rest increased by 300 ml/min (p <0.05). Maximum oxygen consumption (VO2max) increased by 126 ml/ min (p <0.05), and even more so in patients with more severe exercise-induced oxygen desaturations, which was associated with lower peak minute ventilation to CO2 production ratio (p <0.05). Thus, descent to the Dead Sea acutely improved exercise performance due to better oxygenation and loading conditions in patients with CHF.

[Circadian fluctuations in the success and efficacy of streptokinase thrombolytic therapy in acute myocardial infarction].

This study was designed to assess possible diurnal fluctuations in the efficacy of thrombolysis with streptokinase. 156 consecutive patients treated with streptokinase during the period 1.1.95-1.7.96 were studied retrospectively. Success or failure of thrombolysis was determined according to the accepted clinical and angiographic criteria starting at midnight, 12 times at 2-hour intervals, then 8 times at 3-hour intervals, and then 6 times at 4-hour intervals. A definite peak for successful thrombolysis was found in the late afternoon and early evening hours. Between 16:00-20:00 PM, in 30.23% successful thrombolysis were observed, compared to 6.98% between 20:00-24:00 PM (p < 0.05) and in 10.53% between 00.00-04:00 AM (p < 0.05). Multiple regression analysis showed that the independent factor with the greatest impact on successful reperfusion was the actual time until thrombolysis (p = 0.037); then came the interval from pain onset to streptokinase administration (p = 0.020), while age and gender had much lesser impacts (p = 0.328 and 0.215, respectively), and individual risk factors even less. These findings may have several clinical implications: dose adjustment for the time of day may be required, with larger doses needed during morning hours, or preference for primary coronary angioplasty to avoid increase in bleeding complications due to higher doses of thrombolytic agents.

Circadian fluctuations in the efficacy of thrombolysis with streptokinase.

This study was designed to investigate possible diurnal fluctuations in the efficacy of thrombolysis with streptokinase and whether they follow the circadian periodicity which has already been well documented for the time of onset of acute myocardial infarction, transient myocardial ischaemia, sudden cardiac death, thrombotic stroke, and for the efficacy of thrombolysis with tissue-type plasminogen and urokinase. A total of 156 consecutive patients treated with streptokinase were studied retrospectively; success or failure of thrombolysis was determined according to accepted clinical and angiographic criteria. A definite time peak for successful thrombolysis could be detected at the late afternoon and early evening hours; between 16.00 and 20.00 h, 30.2% of all successful thrombolysis cases were observed compared with 7.0% between 20.00 and 24.00 (p < 0.05) or 10.5% between 00.00 and 04.00 (p < 0.05). Between 16.00 and 20.00 h, 75.8% of treated patients had successful thrombolysis compared to 15.2% of failed treatments and 9% equivocal results (p < 0.001). Multiple regression analysis showed that the independent factor with the major impact on successful reperfusion was the actual time of thrombolysis (p = 0.037), followed by the time delay from pain onset to streptokinase administration (p = 0.020), while age and gender had much lesser impact (p = 0.328 and 0.215, respectively) and the individual risk factors even less. These findings may have several clinical implications; dose adjustment for the time of day may be required, with higher doses during morning hours, or preference for primary coronary angioplasty in order to avoid the increase in bleeding complications related to higher doses of thrombolytic agents.

[Thrombolysis in myocardial infarction-outcome optimization methods]. / Tromboliticheskaia terapia infarcta miokarda-podkhody k optimizatsii.

Early reperfusion in acute myocardial infarction (AMI) has been shown to reduce the extent of myocardial necrosis and to improve short and long term prognosis. Gender, smoking, age and site of infarct location may be regarded as prognostic factors for the outcome of AMI and of thrombolytic therapy with streptokinase (STK). The aim of this study was to identify factors, which are related to the results of thrombolytic therapy by STK in AMI. 156 patients (122 males and 34 females) treated with STK were retrospectively analyzed: they were subdivided into 3 groups according to the presumed success of thrombolytic therapy based on the accepted clinical and angiographic TIMI flow criteria. Group 1 = successful (88 patients), group 2 = probably successful (20 patients) and group 3 = failed thrombolysis (48 patients). Multiple regression analysis showed that Killip class (p = 0.0005), time from pain onset to thrombolysis initiation (p = 0.02) and the time of the day in which thrombolysis began (p = 0.037) are independent major predictive factors for successful thrombolytic therapy by STK in AMI. Gender, age, smoking and some risk factors are not of similar predictive power. These results may guide us in the optimization of thrombolytic therapy by STK in AMI, different dose regimens for different times of day and probably preference for primary PTCA in the early morning hours.

[Circadian fluctuations of the signal-averaged electrocardiography].

Circadian periodicity for the time of onset of acute myocardial infarction has been shown; the early morning peak of infarction coincides with the onset of other related phenomena, including sudden cardiac death, ventricular arrhythmias, thrombotic stroke, etc. Late potentials detected by the signal-averaged ECG are considered to be independent markers of vulnerability to ventricular arrhythmias. The signal-averaged ECG enables the amplifying and recording of small bioelectric signals of cardiac origin, while eliminating extraneous electrical "noise." To determine whether late potentials are themselves subject to circadian influence, 31 patients (age range 41-79) who had had an old or recent myocardial infarction underwent late potential assessment by the signal-averaged ECG. 4 indices were studied: duration of late LPD potentials (LPD), total QRS duration (TQRS), and root mean square voltage of the last 40 msec, and of the last 50 msec (RMS 40 and RMS 50). These indices were assessed 3 times, during the early morning hours, at noon and during the evening. Morning LPD differed significantly from noon and evening LPD and the morning RMS 40 similarly differed from noon and evening values. TQRS and RMS 50, even though remaining in the normal range, also showed a tendency to abnormal values during morning hours. These findings could possibly be related to the early morning incidence peaks of severe ventricular arrhythmia and sudden cardiac death, since abnormal late potentials constitute the physiopathological basis for certain ventricular arrhythmias.

The outcome of patients with acute myocardial infarction ineligible for thrombolytic therapy. Israeli Thrombolytic Survey Group.

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 inhospital 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.