The metabolic syndrome (MetS) is associated with a threefold increase risk of cardiovascular disease (CVD) mortality partly due to increased arterial stiffening. We compared the effects of aerobic ...exercise training on arterial stiffening/mechanics in MetS subjects without overt CVD or type 2 diabetes. MetS and healthy control (Con) subjects underwent 8 wk of exercise training (ExT; 11 MetS and 11 Con) or remained inactive (11 MetS and 10 Con). The following measures were performed pre- and postintervention: radial pulse wave analysis (applanation tonometry) was used to measure augmentation pressure and index, central pressures, and an estimate of myocardial efficiency; arterial stiffness was assessed from carotid-femoral pulse-wave velocity (cfPWV, applanation tonometry); carotid thickness was assessed from B-mode ultrasound; and peak aerobic capacity (gas exchange) was performed in the seated position. Plasma matrix metalloproteinases (MMP) and CVD risk (Framingham risk score) were also assessed. cfPWV was reduced (P < 0.05) in MetS-ExT subjects (7.9 ± 0.6 to 7.2 ± 0.4 m/s) and Con-ExT (6.6 ± 1.8 to 5.6 ± 1.6 m/s). Exercise training reduced (P < 0.05) central systolic pressure (116 ± 5 to 110 ± 4 mmHg), augmentation pressure (9 ± 1 to 7 ± 1 mmHg), augmentation index (19 ± 3 to 15 ± 4%), and improved myocardial efficiency (155 ± 8 to 168 ± 9), but only in the MetS group. Aerobic capacity increased (P < 0.05) in MetS-ExT (16.6 ± 1.0 to 19.9 ± 1.0) and Con-ExT subjects (23.8 ± 1.6 to 26.3 ± 1.6). MMP-1 and -7 were correlated with cfPWV, and both MMP-1 and -7 were reduced post-ExT in MetS subjects. These findings suggest that some of the pathophysiological changes associated with MetS can be improved after aerobic exercise training, thereby lowering their cardiovascular risk.
New Findings
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What is the central question of this study?
Metabolic syndrome (MetS) is associated with a threefold increase in risk of cardiovascular disease mortality, which may be mediated, in ...part, by impaired left ventricular systolic function. The severity of left ventricular and arterial dysfunction during dynamic exercise in individuals with MetS without diabetes and/or overt cardiovascular disease has not previously been explored.
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What is the main finding and its importance?
Cardiovascular function was characterized at rest and during peak exercise using echocardiography and gas exchange. During exercise, individuals with MetS displayed impaired left ventricular contractility, a blunted arterial–ventricular coupling reserve and limited aerobic capacity. These findings provide insight into the pathophysiological changes that may occur to predispose individuals with MetS to an increased risk of cardiovascular disease.
Metabolic syndrome (MetS) is the manifestation of a cluster of cardiovascular risk factors and is associated with a threefold increase in the risk of cardiovascular morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to examine comprehensively the LV and arterial responses to exercise in individuals with MetS without diabetes and/or overt cardiovascular disease in comparison to a healthy control population. Cardiovascular function was characterized using Doppler echocardiography and gas exchange in individuals with MetS (n= 27) versus healthy control subjects (n= 20) at rest and during peak exercise. At rest, individuals with MetS displayed normal LV systolic function but reduced LV diastolic function compared with healthy control subjects. During peak exercise, individuals with MetS had impaired contractility, pump performance and vasodilator reserve capacity versus control subjects. A blunted contractile reserve response resulted in diminished arterial–ventricular coupling reserve and limited aerobic capacity in individuals with MetS versus control subjects. These findings are of clinical importance, because they provide insight into the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of cardiovascular morbidity and mortality.
Abstract only
Metabolic Syndrome (MetS) is a cluster of cardiovascular (CV) risk factors associated with functional limitations and an increased risk of CV mortality. Resting diastolic function is ...thought to be altered in MetS and may contribute to increased CV risk and functional deficiency. Using echocardiography we explored the relationship between resting diastolic function and left ventricular (LV) contractile reserve capacity, assessed by the change from rest to peak exercise in end‐systolic elastance (ΔEes), in Mets (n=21) and healthy controls (n=13). MetS had resting diastolic dysfunction and a 15% decrease in ΔEes (p<0.05) vs. controls. Univariate analysis, used to examine the correlation between ΔEes and resting diastolic function revealed that ΔEes was related to LV end‐diastolic pressure (EDP), the transmitral to mitral annular early diastolic velocity ratio (E/e’), the diastolic stiffness constant (β), and the isovolumetric relaxation time constant (τ) (p<0.05). We used multivariate analysis to examine the relationship between ΔEes and diastolic function after adjusting for age and metabolic risk score (MRS: the sum of risk points selected for specific CV risk factors). After adjusting for age and MRS, ΔEes remained associated with LV EDP, E/e’, β, and τ (p<0.05), suggesting a link between resting diastolic dysfunction and altered CV reserve in metabolic disease states. AHA 11CRP7370056, 5T32HL090610–04.
Cardiac responses to beta-adrenergic receptor stimulation are depressed with pressure overload-induced cardiac hypertrophy. We investigated whether exercise training could modify beta-adrenergic ...receptor responsiveness in a model of spontaneous hypertension by modifying the beta-adrenergic receptor desensitizing kinase GRK2 and the abundance and phosphorylation of some key Ca2+ cycling proteins.
Female spontaneously hypertensive rats (SHR; age, 4 months) were placed into a treadmill running (SHR-TRD; 20 m/min, 1 h/d, 5 d/wk, 12 weeks) or sedentary group (SHR-SED). Age-matched Wistar Kyoto (WKY) rats were controls. Mean blood pressure was higher in SHR versus WKY (P<0.01) and unaltered with exercise. Left ventricular (LV) diastolic anterior and posterior wall thicknesses were greater in SHR than WKY (P<0.001) and augmented with training (P<0.01). Langendorff LV performance was examined during isoproterenol (ISO) infusions (1x10(-10) to 1x10(-7) mol/L) and pacing stress (8.5 Hz). The peak LV developed pressure/ISO dose response was shifted rightward 100-fold in SHR relative to WKY. The peak ISO LV developed pressure response was similar between WKY and SHR-SED and increased in SHR-TRD (P<0.05). SHR-TRD showed the greatest lusitropic response to ISO (P<0.05) and offset the pacing-induced increase in LV end-diastolic pressure and the time constant of isovolumic relaxation (tau) observed in WKY and SHR-SED. Improved cardiac responses to ISO in SHR-TRD were associated with normalized myocardial levels of GRK2 (P<0.05). SHR displayed increased L-type Ca2+ channel and sodium calcium exchanger abundance compared with WKY (P<0.001). Training increased ryanodine receptor phosphorylation and phospholamban phosphorylation at both the Ser16 and Thr17 residues (P<0.05).
Exercise training in hypertension improves the inotropic and lusitropic responsiveness to beta-adrenergic receptor stimulation despite augmenting LV wall thickness. A lower GRK2 abundance and an increased phosphorylation of key Ca2+ cycling proteins may be responsible for the above putative effects.
The complexes {FeHC(3,5-Me2pz)32}(BF4)2 (1), {FeHC(pz)32}(BF4)2 (2), and {FePhC(pz)2(py)2}(BF4)2 (3) (pz = 1-pyrazolyl ring, py = pyridyl ring) have been synthesized by the reaction of the ...appropriate ligand with Fe(BF4)2·6H2O. Complex 1 is high-spin in the solid state and in solution at 298 K. In the solid phase, it undergoes a decrease in magnetic moment at lower temperatures, changing at ca. 206 K to a mixture of high-spin and low-spin forms, a spin-state mixture that does not change upon subsequent cooling to 5 K. Crystallographically, there is only one iron(II) site in the ambient-temperature solid-state structure, a structure that clearly shows the complex is high-spin. Mössbauer spectral studies show conclusively that the magnetic moment change observed at lower temperatures arises from the complex changing from a high-spin state at higher temperatures to a 50:50 mixture of high-spin and low-spin states at lower temperatures. Complexes 2 and 3 are low-spin in the solid phase at room temperature. Complex 2 in the solid phase gradually changes over to the high-spin state upon heating above 295 K and is completely high-spin at ca. 470 K. In solution, variable-temperature 1H NMR spectra of 2 show both high-spin and low-spin forms are present, with the percentage of the paramagnetic form increasing as the temperature increases. Complex 3 is low-spin at all temperatures studied in both the solid phase and solution. An X-ray absorption spectral study has been undertaken to investigate the electronic spin states of {FeHC(3,5-Me2pz)32}(BF4)2 and {FeHC(pz)32}(BF4)2. Crystallographic information: 2 is monoclinic, P21/n, a = 10.1891(2) Å, b = 7.6223(2) Å, c = 17.2411(4) Å, β = 100.7733(12)°, Z = 2; 3 is triclinic, P1̄, a = 12.4769(2) Å, b = 12.7449(2) Å, c = 13.0215(2) Å, α = 83.0105(8)°, β = 84.5554(7)°, γ = 62.5797(2)°, Z = 2.
The purpose of this study was to examine whether exercise training, superimposed on compensated-concentric hypertrophy, could increase myocardial hypoperfusion-reperfusion (H/R) tolerance. Female ...Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (age: 4 mo; N = 40) were placed into a sedentary (SED) or exercise training (TRD) group (treadmill running; 25 m/min, 1 h/day, 5 days/wk for 16 wk). Four groups were studied: WKY-SED (n = 10), WKY-TRD (n = 10), SHR-SED (n = 10), and SHR-TRD (n = 10). Blood pressure and heart rate were determined, and in vitro isolated heart performance was measured with a retrogradely perfused, Langendorff isovolumic preparation. The H/R protocol consisted of a 75% reduction in coronary flow for 17 min followed by 30 min of reperfusion. Although the rate-pressure product was significantly elevated in SHR relative to WKY, training-induced bradycardia reduced the rate-pressure product in SHR-TRD (P < 0.05) without an attenuation in systolic blood pressure. Heart-to-body weight ratio was greater in both groups of SHR vs. WKY-SED (P < 0.001). Absolute and relative myocardial tolerance to H/R was greater in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05). Endurance training superimposed on hypertension-induced compensated hypertrophy conferred no further cardioprotection to H/R. Postreperfusion 72-kDa heat shock protein abundance was enhanced in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05) and was highly correlated with absolute left ventricular functional recovery during reperfusion (R2= 0.86, P < 0.0001). These data suggest that both compensated hypertrophy associated with short-term hypertension and endurance training individually improved H/R and that increased postreperfusion 72-kDa heat shock protein abundance was, in part, associated with the cardioprotective phenotype observed in this study.
We tested how hypertension-induced compensated hypertrophy, both alone and coupled with exercise training, affects left ventricular (LV) Ca(2+) responsiveness during acidosis.
Four-month-old female, ...spontaneously hypertensive rats (SHR) (N = 23) were assigned to a sedentary (SHR-SED) or treadmill-trained (SHR-TRD) group (60% VO(2peak), 5 d.wk(-1), 6 months), while Wistar-Kyoto rats (WKY) (N = 12) served as normotensive controls. LV performance was established in response to supraphysiologic Ca(2+) infusion (4 mmol.L(-1)) alone and concomitant with isoproterenol (ISO) (1 x 10 mol.L(-1)) at pH 7.4 and 6.8.
HR, rate-pressure product (RPP), and blood pressure were greater in SHR than in WKY (P < 0.05). HR and RPP were attenuated with training. Heart weight and LV anterior wall thickness (diastole) were increased in SHR relative to WKY (P < 0.05) and augmented with training. ISO + 4 mmol.L(-1) Cao resulted in similar LV performance at pH 7.4. At pH 6.8, LV developed pressure was greater in both SHR groups (P < 0.05) versus WKY rats and a twofold increase in the Ca(2+)o rescued LV performance to the greatest extent in SHR-TRD. During acidosis, the added stimulus of ISO coupled with elevated Ca(2+)(o) improved WKY LV performance to near baseline (P < 0.05). Neither elevated Ca(2+)(o) nor ISO was effective in rescuing LV performance in SHR-SED during acidosis. Phospholamban phosphorylation at Ser(16) and Thr(17) residues were positively correlated with LV functional recovery. Regulatory proteins such as the Na(+)/H(+) exchanger, Na(+)/Ca(2+) exchanger, and the L-type Ca(+) channel were not correlated with LV function.
Myocardial tolerance to acidosis is improved during the adaptive phase of compensatory hypertrophy. Furthermore, exercise training in SHR induced a myocardial phenotype that preserved Ca(2+) responsiveness during acidosis.
Hypertension and exercise independently induce left ventricular (LV) remodeling and alter LV function. The purpose of this study was to determine systolic and diastolic LV pressure-volume ...relationships (LV-PV) in spontaneously hypertensive rats (SHR) with and without LV hypertrophy, and to determine whether 6 mo of exercise training modified the LV-PV in SHR. Four-month-old female SHR (n = 20), were assigned to a sedentary (SHR-SED) or treadmill-trained (SHR-TRD) group (approximately 60% peak O2 consumption, 5 days/wk, 6 mo), while age-matched female Wistar-Kyoto rats (WKY; n = 13) served as normotensive controls. The LV-PV was determined using a Langendorff isolated heart preparation at 4 (no hypertrophy: WKY, n = 5; SHR, n = 5) and 10 mo of age (hypertrophy: WKY, n = 8; SHR-SED, n = 8; SHR-TRD, n = 7). At 4 mo, the LV-PV in SHR was similar to that observed in WKY controls. However, at 10 mo of age, a rightward shift in the LV-PV occurred in SHR. Exercise training did not alter the extent of the shift in the LV-PV relative to SHR-SED. Relative systolic function, i.e., relative systolic elastance, was approximately 50% lower in SHR than WKY at 10 mo of age (P < 0.05). Doppler-derived LV filling parameters early wave (E), atrial wave (A), and the E/A ratio were similar between groups. LV capacitance was increased in SHR at 10 mo (P < 0.05), whereas LV diastolic chamber stiffness was similar between groups at 10 mo. Hypertrophic remodeling at 10 mo of age in female SHR is manifest with relative systolic decompensation and normal LV diastolic function. Exercise training did not alter the LV-PV in SHR.
The reaction of Cd
2(thf)
5(BF
4)
4 with two equiv. of TlHB(3-Bu
t
pz)
3 (pz=pyrazolyl ring) produces the intermediate {HB(3-Bu
t
pz
3Cd}BF
4 that reacts with potassium thiocyanate to yield HB(3-Bu
t
...pz)
3Cd(NCS) (
1). The solid state structure shows that the sterically demanding 3-
tert-butyl groups enforce the formation of a tetrahedral, monomeric complex, the first four-coordinate cadmium(II)-thiocyanate complex to be structurally characterized. The decomposition of this compound produced (Bu
t
Hpz)
2Cd(NCS)
2
n
(
2) as shown by X-ray crystallography. It was not possible to form a lead(II) complex analogous to
1, but using less sterically demanding ligands allowed the preparation of {HB(3,5-Me
2pz)
3Pb(μ-NCS)}
2 (
3), and {HB(pz)
3Pb(μ-NCS)}
n
(
4). The former has a dimeric structure with both μ-NCS-
S,
N and μ-NCS-
S,
S bridging SCN
− ligands and the latter has a infinite 2-D layered array in which three nonequiv. {HB(pz)
3Pb}
+ groups sandwich a layer of SCN
− ligands. Using neutral 2,6-pyridyl-diimine ligands (pydim) having bulky 2,6-dimethylphenyl substituents, parallel complexes of both metals were prepared. The cadmium complex, (pydim)Cd (NCS)
2BF
4
2 (
5) is dimeric with normal μ-NCS-
S,
N bridging groups. The structure of the lead(II) analog, (pydim)Pb(NCS)BF
4 (
6) is monomeric with an N-bound, isothiocyanate ligand and a four-coordinate lead(II). The structure of
6 is very different from
5, presumably because of the stereoactive lone pair on lead(II).
A series of mono-thiocyanate complexes of cadmium(II) and lead(II) supported by coordination to bulky ligands, such as HB(3-Bu
t
pz)
3Cd(NCS) (pz=pyrazolyl), {HB(3,5-Me
2pz)
3Pb(μ-NCS)}
2, (pydim)Cd (NCS)
2BF
4
2 (pydim=2,6-bis(2,6-dimethylphenylimino)pyridine) and (pydim)Pb(NCS)BF
4 have been prepared and structurally characterized. Both HB(3-Bu
t
pz)
3Cd(NCS) and (pydim)Pb(NCS)BF
4 are unusual examples of four-coordinate cadmium–lead(II)-thiocyanate complexes.
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