Aortic diastolic pressure decay modulates relation between worsened aortic stiffness and myocardial oxygen supply/demand balance after resistance exercise

High-intensity resistance exercise (RE) increases aortic stiffness and decreases the index of myocardial oxygen supply/demand balance (Buckberg index, BI); there is a correlation between the changes in these parameters. Central hemodynamics during diastole can explain the correlation. We aimed to investigate whether the aortic diastolic decay index mediates the association between changes in aortic stiffness and BI by high-intensity RE. We evaluated the effect of high-intensity RE on aortic stiffness, BI, aortic decay index, and their associations in 52 young men. Subjects were studied under parallel experimental conditions on two separate days. The order of experiments was randomized between RE (5 sets of 10 repetitions at 75% of 1-repetition maximum) and sham control (seated rest). Aortic pulse wave velocity (PWV; index of aortic stiffness), BI, and aortic decay index were measured in all subjects. Aortic decay index was quantified by fitting an exponential curve: P( t) = P0e−λ t (where λ is decay index, P0 is end-systolic pressure and t is time from end-systole). Aortic PWV and decay index increased and BI decreased after RE. RE conditions showed that change in the aortic decay index was associated with changes in aortic PWV and changes in aortic PWV were related to changes in BI, although the PWV-BI relationship was not significant after accounting for decay index change. Mediation analysis revealed the mediating effect of the aortic decay index on the relationship between changes in aortic PWV and BI. The present findings suggest that high-intensity RE-induced aortic stiffening worsens myocardial viability by accelerating aortic diastolic exponential decay. NEW & NOTEWORTHY Aortic pulse wave velocity (PWV) and diastolic decay index increased and Buckberg index (BI) decreased after resistance exercise (RE). Mediation analysis revealed a mediating effect of aortic decay index on the relationship between changes in aortic PWV and BI. The present study provides evidence that high-intensity RE-induced aortic stiffening accelerates aortic decay and aortic decay can account for the relationship between aortic stiffening and a deteriorated surrogate marker of myocardial oxygen supply/demand balance induced by high-intensity RE.

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Both β1- and β2-adrenoceptors contribute to feedforward coronary resistance vessel dilation during exercise

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00135.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. H921-H929 ◽

Cited By ~ 28

Author(s):

Fen Gao ◽

Vincent J. de Beer ◽

Maaike Hoekstra ◽

Chuanshi Xiao ◽

Dirk J. Duncker ◽

...

Keyword(s):

Oxygen Consumption ◽

Myocardial Oxygen Consumption ◽

Oxygen Supply ◽

Left Ventricular ◽

Coronary Resistance ◽

Coronary Vasodilation ◽

Clockwise Rotation ◽

Resistance Vessel ◽

The Relationship ◽

Myocardial Oxygen Supply

During exercise, β-feedforward coronary vasodilation has been shown to contribute to the matching of myocardial oxygen supply with the demand of the myocardium. Since both β1- and β2-adrenoceptors are present in the coronary microvasculature, we investigated the relative contribution of these subtypes to β-feedforward coronary vasodilation during exercise as well as to infusion of the β1-agonist norepinephrine and the β1- and β2-agonist isoproterenol. Chronically instrumented swine were studied at rest and during graded treadmill exercise (1–5 km/h) under control conditions and after β1-blockade with metoprolol (0.5 mg/kg iv) and β1/β2-blockade with propranolol (0.5 mg/kg iv). The selectivity and degree of β-blockade of metoprolol and propranolol were confirmed using isoproterenol infusion (0.05–0.4 μg· kg−1·min−1) under resting conditions. Isoproterenol-induced coronary vasodilation was mediated through the β2-adrenoceptor, whereas norepinephrine-induced coronary vasodilation was principally mediated through the β1-adrenoceptor. Exercise resulted in a significant increase in left ventricular norepinephrine release and epinephrine uptake. β1-Adrenoceptor blockade with metoprolol had very little effect under resting conditions. However, during exercise, metoprolol attenuated the increase in myocardial oxygen supply in excess of the reduction in myocardial oxygen demand, as evidenced by a progressive decrease in coronary venous Po2. Consequently, metoprolol caused a clockwise rotation of the relationship between myocardial oxygen consumption and coronary venous Po2. Additional β2-adrenoceptor blockade with propranolol further inhibited myocardial oxygen supply during exercise, resulting in a further clockwise rotation of the relationship between myocardial oxygen consumption and coronary venous Po2. In conclusion, both β1- and β2-adrenoceptors contribute to the β-feedforward coronary resistance vessel dilation during exercise.

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Tumor Necrosis Factor Alpha-Mediated Inflammation and Remodeling of the Extracellular Matrix Underlies Aortic Stiffening Induced by the Common Chemotherapeutic Agent Doxorubicin

Hypertension ◽

10.1161/hypertensionaha.120.16759 ◽

2021 ◽

Vol 77 (5) ◽

pp. 1581-1590

Author(s):

Zachary S. Clayton ◽

Vienna E. Brunt ◽

David A. Hutton ◽

Abigail G. Casso ◽

Brian P. Ziemba ◽

...

Keyword(s):

Elastic Modulus ◽

Aortic Stiffness ◽

Pulse Wave ◽

Ex Vivo ◽

Aortic Pulse Wave Velocity ◽

Wall Stiffness ◽

Tnf Α ◽

Aortic Stiffening ◽

Necrosis Factor

Aortic stiffening is a major independent risk factor for cardiovascular diseases, kidney dysfunction, and cognitive impairment. Doxorubicin chemotherapy-treated cancer survivors have greater aortic stiffness relative to healthy controls, but the mechanisms by which doxorubicin induces arterial stiffening are unknown. We tested the hypothesis that doxorubicin increases aortic stiffness by increasing intrinsic mechanical wall stiffness due to proinflammatory signaling-induced adverse structural changes, including collagen deposition (fibrosis), elastin fragmentation, and formation of AGEs (advanced glycation end products). In vivo aortic stiffness (assessed via aortic pulse wave velocity), aortic intrinsic wall stiffness (ex vivo assessment of elastic modulus), and potential underlying mechanisms were assessed 4 weeks after administration of doxorubicin (10 mg/kg) or vehicle (saline) in young adult male C57BL6/J mice. Aortic pulse wave velocity increased by ~30% following doxorubicin (pre: 341±18 versus post: 431±28 cm/s, mean±SEM, P =0.001) and aortic elastic modulus was ~100% higher following doxorubicin (5438±445 kPa) versus vehicle (2659±433 kPa; P =0.003). These effects of doxorubicin were associated with an ~3-fold greater formation of AGEs ( P =0.01) and an ~50% reduction in elastin ( P =0.01), whereas collagen deposition was unaffected. Doxorubicin increased aortic proinflammatory cytokines ( P =0.03) without a compensatory increase in the anti-inflammatory cytokine interleukin-10. Direct ex vivo exposure of aorta rings to doxorubicin mimicked the increase in aortic elastic modulus observed in vivo with doxorubicin, whereas TNF-α (tumor necrosis factor-α) inhibition prevented this response. Doxorubicin induces aortic stiffening in vivo due, in part, to an increase in intrinsic wall stiffness associated with elastin degradation and AGEs formation and mediated by TNF-α-dependent vascular inflammation.

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