Hsin-Fu Lin

Endothelial ischemia-reperfusion injury in humans: association with age and habitual exercise

Advancing age is a major risk factor for coronary artery disease. Endothelial dysfunction accompanied by increased oxidative stress and inflammation with aging may predispose older arteries to greater ischemia-reperfusion (I/R) injury. Because coronary artery ischemia cannot be induced safely, the effects of age and habitual endurance exercise on endothelial I/R injury have not been determined in humans. Using the brachial artery as a surrogate model of the coronary arteries, endothelial function, assessed by brachial artery flow-mediated dilation (FMD), was measured before and after 20 min of continuous forearm occlusion in young sedentary (n = 10, 24 ± 2 yr) and middle-aged (n = 9, 48 ± 2 yr) sedentary adults to gain insight into the effects of primary aging on endothelial I/R injury. Young (n = 9, 25 ± 1 yr) and middle-aged endurance-trained (n = 9, 50 ± 2 yr) adults were also studied to determine whether habitual exercise provides protection from I/R injury. Fifteen minutes after ischemic injury, FMD decreased significantly by 37% in young sedentary, 35% in young endurance-trained, 68% in middle-aged sedentary, and 50% in middle-aged endurance-trained subjects. FMD returned to baseline levels within 30 min in young sedentary and endurance-trained subjects but remained depressed in middle-aged sedentary and endurance-trained subjects. Circulating markers of antioxidant capacity and inflammation were not related to FMD. In conclusion, advancing age is associated with a greater magnitude and delayed recovery from endothelial I/R injury in humans. Habitual endurance exercise may provide partial protection to the endothelium against this form of I/R injury with advancing age.

Contribution of blood viscosity in the assessment of flow-mediated dilation and arterial stiffness

Flow-mediated dilation (FMD) is a non-invasive index of endothelial function. In an attempt to standardize FMD for shear stimulus, shear rate (velocity/diameter), rather than shear stress (viscosity*velocity/diameter), is commonly used as a surrogate measure, although it is limited by individual differences in blood viscosity. The purpose of this study was to determine the contribution of whole blood viscosity to FMD and other key measures of vascular function. Blood viscosity, FMD, carotid artery compliance, and carotid–femoral pulse wave velocity (cfPWV) were measured in 98 apparently healthy adults varying widely in age (18–63 years). Whole blood viscosity was not significantly correlated with FMD, cfPWV, or carotid artery compliance. Shear rate was a stronger correlate with FMD than shear stress that takes blood viscosity into account (r = 0.43 vs 0.28). No significant differences were observed between whole blood viscosity and traditional risk factors for cardiovascular disease. Age was positively correlated with cfPWV (r = 0.65, p < 0.001) and negatively correlated with FMD (r = −0.24, p < 0.05) and carotid artery compliance (r = −0.45, p < 0.01). Controlling for viscosity did not reduce the strength of these relations. These results indicate that whole blood viscosity does not significantly impact measures of vascular function and suggests that the common practice to use shear rate, rather than shear stress, in the adjustment of FMD is valid.

Preliminary assessment of an automatic screening device for peripheral arterial disease using ankle-brachial and toe-brachial indices.

Background and objectivesAnkle–brachial index (ABI) is currently recommended for the screening of peripheral arterial disease. However, this method becomes less reliable in the presence of calcified, incompressible arteries, as they result in an erroneously elevated ABI, and an additional measure termed the toe–brachial index (TBI) is recommended. The evaluation of ABI, and in particular TBI, typically requires significant technical skill and often involves referral to a vascular laboratory. This present situation reveals the need for a valid and reliable, automatic, noninvasive device that will provide both ABI and TBI at the level of the primary care physician. The aim of this study was to evaluate the accuracy and reliability of such a device, the Vasera VS-1500AT, in the assessment of toe, ankle, and brachial systolic blood pressures. Materials and methodsThis study involved the assessment of 80 limbs from 40 normotensive and hypertensive individuals (17 men and 23 women) with a mean age of 45±18 years. ResultsThere was a statistically significant correlation (r=0.92) between toe systolic blood pressures obtained manually with photoplethysmography compared with those obtained through the automated device. The same significant correlation was also seen between the two with ankle (r=0.87) and brachial (r=0.88) systolic blood pressures. ConclusionThese strong correlations demonstrate that further investigation of this device is warranted regarding its use as a screening tool for the assessment of peripheral arterial disease. The automation provided by this device could potentially eliminate variability in these measurements thereby allowing for screening and diagnosis to be done without referral to a vascular laboratory.

Delayed Onset Vascular Stiffening Induced by Eccentric Resistance Exercise and Downhill Running

Objectives: Eccentric exercise induces muscle stiffening and soreness as well as unfavorable changes in macrovascular function. We tested the hypothesis that systemic eccentric exercise could evoke greater arterial stiffening than local eccentric resistance exercise. Design and Intervention: Twenty healthy young men were randomly assigned into either the downhill running (DR) and the eccentric resistance exercise (RE) group followed by a crossover design with an exercise and sham control trial. Main Outcome Measures: Carotid–femoral pulse wave velocity (cfPWV), central hemodynamic measures, and biomarkers were obtained. Results: Muscle soreness and plasma creatine kinase concentrations increased similarly after exercise in both groups. The cfPWV increased significantly at 48 hours post-exercise in both groups and remained elevated at 72 hours in DR. C-reactive protein (CRP) was elevated at 24 and 48 hours in DR, and 48 hours in RE. The increases in cfPWV were associated with the corresponding elevations in CRP in DR (r = 0.70, P < 0.05). There were no changes in arterial wave reflection measures. Conclusions: Both systemic and localized eccentric exercise modes induced delayed onset vascular stiffening with more prolonged changes observed in downhill running. The effect on arterial stiffening was associated, at least in part, with systemic inflammatory responses.

Panax ginseng and Salvia miltiorrhiza supplementation during eccentric resistance training in middle-aged and older adults: A double-blind randomized control trial.

BACKGROUND Muscle damage induced by an acute bout of eccentric exercise results in transient arterial stiffening. In this study, we sought to determine the effects of progressive eccentric resistance exercise training on vascular functions, and whether herb supplementation would enhance training adaptation by ameliorating the arterial stiffening effects. METHODS By using a double-blinded randomized placebo-controlled design, older adults were randomly assigned to either the Panax ginseng and Salvia miltiorrhiza supplementation group (N=12) or the placebo group (N=11). After pre-training testing, all subjects underwent 12 weeks of unilateral eccentric-only exercise training on knee extensor. RESULTS Maximal leg strength and muscle quality increased in both groups (P<0.05). Relative increases in muscle mass were significantly greater in the placebo group than in the herb supplement group. Eccentric exercise training did not elicit any significant changes in muscle damage, oxidative and inflammatory biomarkers. There were no significant changes in blood pressure or endothelium-dependent vasodilation. None of the measures of arterial stiffness changed significantly with eccentric resistance training in both groups. CONCLUSIONS These results suggest that Chinese herb supplementation does not appear to modulate vascular, and inflammatory adaptations to eccentric exercise training in middle-aged and older adults. However, Chinese herb supplementation abolished the increase in muscle mass induced by eccentric resistance training. (Trial registration: ClinicalTrials.gov: NCT02007304. Registered Dec. 5, 2013).