Peak Hyperemic Blood Flow Research Articles

Aerobic Versus Resistance Training Effects on Ventricular-Arterial Coupling and Vascular Function in the STRRIDE-AT/RT Trial.

Background: The goal was studying the differential effects of aerobic training (AT) vs. resistance training (RT) on cardiac and peripheral arterial capacity on cardiopulmonary (CP) and peripheral vascular (PV) function in sedentary and obese adults.Methods: In a prospective randomized controlled trial, we studied the effects of 6 months of AT vs. RT in 21 subjects. Testing included cardiac and vascular ultrasoundography and serial CP for ventricular-arterial coupling (Ees/Ea), strain-based variables, brachial artery flow-mediated dilation (BAFMD), and peak VO2 (pVO2; mL/kg/min) and peak O2-pulse (O2p; mL/beat).Results: Within the AT group (n = 11), there were significant increases in rVO2 of 4.2 mL/kg/min (SD 0.93) (p = 0.001); O2p of 1.9 mL/beat (SD 1.3) (p = 0.008) and the brachial artery post-hyperemia peak diameter 0.18 mm (SD 0.08) (p = 0.05). Within the RT group (n = 10) there was a significant increase in left ventricular end diastolic volume 7.0 mL (SD 9.8; p = 0.05) and percent flow-mediated dilation (1.8%) (SD 0.47) (p = 0.004). Comparing the AT and RT groups, post exercise, rVO2 2.97, (SD 1.22), (p = 0.03), O2p 0.01 (SD 1.3), (p = 0.01), peak hyperemic blood flow volume (1.77 mL) (SD 140.69) (p = 0.009), were higher in AT, but LVEDP 115 mL (SD 7.0) (p = 0.05) and Ees/Ea 0.68 mmHg/ml (SD 0.60) p = 0.03 were higher in RT.Discussion: The differential effects of AT and RT in this hypothesis generating study have important implications for exercise modality and clinical endpoints.

Divergent endothelial function but similar platelet microvesicle responses following eccentric and concentric cycling at a similar aerobic power output.

Endothelial function and microvesicle concentration changes after acute bouts of continuous eccentric exercise have not been assessed previously nor compared with concentric exercise at similar aerobic power outputs. This method of training may be useful among some clinical populations, but acute responses are not well described. As such, 12 healthy males completed 2 experimental sessions of either 45 min of eccentric or concentric cycling at a matched aerobic power output below the ventilatory threshold. Brachial artery vascular function was assessed throughout 5 min of forearm ischemia and 3 min thereafter, before and at 5 and 40 min of recovery following each exercise session [flow-mediated dilation (FMD)]. Venous blood samples were acquired before each vascular function assessment. FMD significantly decreased after eccentric cycling by 40 min of recovery (P < 0.05), but was unaltered after concentric exercise. No differences in peak hyperemic blood flow velocity occurred neither between modalities nor at any time point (P > 0.05). Platelet-derived microvesicles increased by ~20% after both exercise modalities (P < 0.05) while endothelial-derived microvesicles were unchanged (P > 0.05). Moderate relationships with cardiac output, a surrogate for shear stress, and norepinephrine were apparent (P < 0.05), but there were no relationships with inflammatory or acute phase proteins. In summary, eccentric endurance exercise induced macrovascular endothelial dysfunction; however, endothelial activation determined by endothelial microvesicles did not occur suggesting that this modality may induce oxidative stress but no significant endothelial damage. In addition, the increase in platelet microvesicle concentrations may induce beneficial microvascular adaptations as suggested by previous research.NEW & NOTEWORTHY Continuous eccentric cycling exercise induces substantial skeletal muscle, tendon, and bone strain providing a potentially beneficial stimulus among clinical populations. This modality also induces temporary endothelial dysfunction but no apparent damage or activation of the endothelium indicated by microvesicle production, whereas proangiogenic platelet microvesicles are released similarly following both concentric and eccentric cycling and may relate to the shear stress and catecholamine response to exercise.

Calibration of diffuse correlation spectroscopy blood flow index with venous-occlusion diffuse optical spectroscopy in skeletal muscle.

We investigate and assess the utility of a simple scheme for continuous absolute blood flow monitoring based on diffuse correlation spectroscopy (DCS). The scheme calibrates DCS using venous-occlusion diffuse optical spectroscopy (VO-DOS) measurements of arm muscle tissue at a single time-point. A calibration coefficient (γ) for the arm is determined, permitting conversion of DCS blood flow indices to absolute blood flow units, and a study of healthy adults (N=10) is carried out to ascertain the variability of γ. The average DCS calibration coefficient for the right (i.e., dominant) arm was γ=(1.24±0.15)×10(8) (mL·100 mL(−1)·min(−1))/(cm(2)/s). However, variability can be significant and is apparent in our site-to-site and day-to-day repeated measurements. The peak hyperemic blood flow overshoot relative to baseline resting flow was also studied following arm-cuff ischemia; excellent agreement between VO-DOS and DCS was found (R(2)=0.95, slope=0.94±0.07, mean difference=−0.10±0.45). Finally, we show that incorporation of subject-specific absolute optical properties significantly improves blood flow calibration accuracy.

Relationship between leg muscle capillary density and peak hyperemic blood flow with endurance capacity in peripheral artery disease

The aim of this study was to determine if skeletal muscle capillary density is lower in patients with peripheral artery disease (PAD) and if capillary density relates to functional limitations. PAD patients with intermittent claudication (IC) have a decreased exercise tolerance due to exercise-induced muscle ischemia. Despite the apparent role diminished arterial flow has in this population, the degree of walking pain and functional limitation is not entirely explained by altered hemodynamics of the affected limbs. We hypothesized that skeletal muscle capillary density is lower in PAD and is related to the functional impairment observed in this population. Sixty-four patients with PAD and 56 controls underwent cardiopulmonary exercise testing and a gastrocnemius muscle biopsy. A subset of these patients (48 PAD and 47 controls) underwent peak hyperemic flow testing via plethysmography. Capillary density in PAD patients was lower compared with controls (P < 0.001). After adjustment for several baseline demographic imbalances the model relating capillary density to peak oxygen consumption (Vo(2)) remained significant (P < 0.001). In PAD subjects, capillary density correlated with peak Vo(2), peak walking time (PWT), and claudication onset time (COT). Peak hyperemic blood flow related to peak Vo(2) in both PAD and control subjects. PAD is associated with lower capillary density, and capillary density is related to the functional impairment as defined by a reduced peak Vo(2), PWT, and COT. These findings suggest that alterations in microcirculation may contribute to functional impairment capacity in PAD.

Abstract 5521: Rosuvastatin Prevents Ischemia and Reperfusion-Induced Endothelial Dysfunction by a COX-2 Dependent Mechanism

BACKGROUND: Animal studies have demonstrated that rosuvastatin (RSV) can limit the damage induced by ischemia-reperfusion (IR) in the cardiac, cerebral and mesenteric circulation. It remains unknown whether this beneficial effect of RSV can also be demonstrated in humans, and by what mechanism this may occur. METHODS AND RESULTS: Twenty healthy volunteers were randomized to a single dose of oral RSV (40 mg) or placebo. 24 hours later, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference in pre-IR FMD between groups (P=NS). In the placebo group, FMD was significantly blunted after IR (FMD pre-IR: 6.4+/−0.4%, post-IR: 1.1+/−1.2%, P&lt;0.01). This impairment in FMD with IR was prevented with RSV (Table ; FMD before IR: 7.5+/−1.0%; after IR: 6.2+/−1.2%, P =NS compared with RSV before IR; P&lt;0.05 vs. placebo). In a separate protocol, 18 healthy volunteers received the cyclooxygenase-2 (COX-2) inhibitor celecoxib (200mg BID p.o.) for 5 days. On day 4, subjects were randomized to a single dose of RSV (40mg) or placebo and 24 hours later underwent the same protocol as above. Pretreatment with celecoxib completely abolished RSV’s protective effect (Table ; FMD pre-IR: 8.0±2.2%, post-IR: 1.4±2.0%, P&lt;0.001 before versus after IR, P=NS vs. placebo). IR did not modify resting arterial diameter, baseline blood flow or peak hyperemic blood flow during FMD in either protocol (Table ; P=NS for all). CONCLUSIONS: The present findings demonstrate, for the first time in humans, the ability of RSV to pharmacologically prevent the development of IR-induced endothelial dysfunction. In addition, these data demonstrate the importance of COX-2 in the manifestation of this preconditioned phenotype, evidence that also provides potential mechanistic insight into the observed cardiovascular toxicity with COX-2 inhibitors.

Measurement of Flow-Mediated Vasodilation of the Brachial Artery A Comparison of Measurements in the Seated and Supine Positions

Measurement of flow-mediated vasodilation (FMD) is used to assess endothelial function in humans and according to the guidelines, subjects must remain supine during the study. However, measurement of FMD while seated would be more comfortable and convenient for patients, so the purpose of this study was to determine the effect of the patient's position on FMD results. High-resolution ultrasonography, a linear array transducer (13 MHz) and an arm-holding device were used to measure arterial diameter in response to reactive hyperemia (FMD, cuff inflated to 50 mmHg above systolic blood pressure for 5 min) and in response to sublingual nitroglycerine (NTG, 75 microg) in 31 subjects, which included those with cardiovascular diseases. There was no significant difference between basal or peak hyperemic blood flow in the seated or supine position. Basal brachial artery diameter, FMD and vascular response to NTG were similar in both positions (basal diameter: 3.8+/-0.4 vs 3.9+/-0.4 mm, FMD: 7.3+/-4.3% vs 7.2+/-4.5%, NTG: 13.1+/-5.1% vs 12.8+/-5.6%). The findings suggest that measurement of FMD in the seated position is as useful as measuring it in the supine position for assessing endothelial function. This flexibility of position is better for patients and physicians, and should lead to more widespread measurement of FMD.

Contributions of vascular tone and structure to elastic properties of a medium-sized artery.

Isobaric compliance and distensibility of the radial artery were recently reported to be normal or slightly increased in untreated hypertensive patients. However, these findings provide no information on the intrinsic mechanical properties of the wall material. To address this question, we determined intima-media wall thickness, wall-to-lumen ratio, and incremental elastic modulus in the radial artery of 25 untreated hypertensive patients with blood pressure of 150 +/- 14/103 +/- 6 mm Hg (mean +/- SD) and 25 matched control subjects with blood pressure of 118 +/- 9/79 +/- 6 mm Hg. High-resolution echotracking for assessment of internal diameter and intima-media wall thickness was combined with measurements of blood flow velocity by Doppler and blood pressure by photoplethysmography. In addition, isobaric compliance and distensibility and incremental elastic modulus were measured at peak diameter during reactive hyperemia after a 5-minute brachial occlusion. No significant difference was found between the two groups for isobaric compliance or distensibility at baseline or during hyperemia. However, incremental elastic modulus at 100 mg Hg tended to be lower in hypertensive patients than control subjects (1.9 +/- 1.1 versus 2.5 +/- 1.2 mm Hg x 10(4), P = .1) in resting conditions. Hypertensive patients and control subjects had similar internal diameters (2.47 +/- 0.32 versus 2.41 +/- 0.35 microm), but intima-media wall thickness and wall-to-lumen ratio were significantly increased in hypertensive patients compared with control subjects (0.268 +/- 0.032 versus 0.236 +/- 0.025 mm -P < or = .01- and 0.220 +/- 0.038 versus 0.195 +/- 0.028 -P < or = .05-, respectively). Peak hyperemic blood flow response (hypertensive patients versus control subjects: 349% versus 360% increase from baseline) and reactive hyperemic dilation (7.2% versus 7.9%) were similar in amplitude and duration in the two groups. These results suggest that wall thickening is an adaptive process that reduces wall tension in hypertensive patients while preserving a normal mechanical behavior of the radial artery. This is most likely accomplished by modification of the incremental elastic modulus of wall components rather than by a change in vascular tone.

788-4 Does Low Level Training Increase Peak Aerobic Capacity in Patients with Congestive Heart Failure?

Conventional high level exercise training at a workload consistent with 75% of peak oxygen consumption (pVO 2 , ml/min/kg) in patients with congestive heart failure (CHF) improves peak aerobic capacity and limb vasodilatory capacity. However, training at this workload may promote left ventricular dilatation in patients with CHF by prolonged exposure to substantially elevated filling pressure (PCWP). Whether training at low level, I.e., at a workload consistent with &lt;50% pVO 2 , would result in limited increases in PCWP while still improving peak aerobic capacity and peripheral vasodilatory function is unknown. Accordingly, 15 patients with stable advanced CHF underwent measurement of 1) the PCWP response to low vs high level exercise, and 2) the change in peak aerobic capacity and limb vasodilatory capacity resulting from participation in a low level training program. PCWP was measured by right heart catheterization at rest, and during low and high level exercise. Patients then performed 12 weeks of low level training, utilizing a semi-recumbent bicycle. Pre- and post-training evaluations included pVO 2 , calf and forearm peak hyperemic blood flow (PHBF, ml/min/100 ml), and resting heart rate (HR, b/min). 1)PCWP rose to 20 mmHg during low level exercise (Δ54% vs rest), and 34 mmHg during high level exercise (Δ162% vs rest). 2)Pre- and post-training data are as follows: pVO 2 calf PHBF forearm PHBF HR pre-train 99 18 23 99 post-train 14.1 36 20 80 p value 0.02 &lt;0.01 NS 0.02 1) The rise in PCWP is significantly less during low level exercise than during high level exercise. 2) Training at a workload consistent with ≤50% of pVO 2 significantly improves peak aerobic capacity. 3) PHBF in the trained calf increases 100% from baseline, while it does not change in the untrained forearm. Enhanced vasodilatory responses in exercising muscle may be an important contributor to improved peak aerobic capacity. Thus, low level training produces benefits similar to high level training with only a moderate rise in PCWP, and may therefore provide less of a stimulus for ventricular dilatation.

Myocardial reactive hyperemia in the newborn

Adenosine may be an important metabolic regulator of coronary blood flow during active hyperemia in the newborn. In this study, the adenosine uptake blocker dipyridamole (DPY) and receptor antagonist theophylline (THEO) were used to assess the role of adenosine in the reactive hyperemic response of the neonatal heart. Eighteen anesthetized, open-chest lambs were instrumented with aortic and coronary sinus catheters as well as an extracorporeal shunt to the circumflex coronary artery incorporating a 2.0-mm electromagnetic flow transducer. Ten-second occlusions of the circumflex coronary artery catheter were performed, and the resulting reactive hyperemia was used to determine peak hyperemic blood flow (PHF), duration of hyperemia, and the blood flow repayment. These values were determined prior to treatment and 30 min following administration of a saline vehicle, DPY (0.2 mg/kg) or THEO (5 mg/kg). DPY resulted in increases in PHF from 220 ± 12 to 247 ± 14 ml/min/100 g heart tissue ( P < 0.05), durations of hyperemia from 29 ± 2 to 38 ± 2 sec ( P < 0.01), and blood flow repayments from 65 ± 2 to 102 ± 4 ml/100 g ( P < 0.001). THEO resulted in decreases in PHF from 224 ± 15 to 198 ± 12 ml/min/100 g ( P < 0.05), durations of hyperemia from 28 ± 2 to 22 ± 2 sec ( P < 0.05), and blood flow repayments from 64 ± 2 to 46 ± 2 ml/100 g ( P < 0.01). The data indicate that DPY enhances reactive hyperemia while antagonism of adenosine with THEO attenuates it. These results suggest that adenosine plays a role in mediating reactive hyperemia in the newborn heart.