Patients with Parkinson's disease (PD) exhibit attenuated cardiovascular responses to exercise. The underlying mechanisms that are potentially contributing to these impairments are not fully understood. Therefore, we sought to test the hypothesis that patients with PD exhibit blunted cardiovascular responses to isolated muscle metaboreflex activation following exercise. For this, mean blood pressure, cardiac output, and total peripheral resistance were measured using finger photoplethysmography and the Modelflow method in 11 patients with PD [66 ± 2 yr; Hoehn and Yahr score: 2 ± 1 a.u.; time since diagnosis: 7 ± 1 yr; means ± SD) and 9 age-matched controls (66 ± 3 yr). Measurements were obtained at rest, during isometric handgrip exercise performed at 40% maximal voluntary contraction, and during postexercise ischemia. Also, a cold pressor test was assessed to confirm that blunted cardiovascular responses were specific to exercise and not representative of generalized sympathetic responsiveness. Changes in mean blood pressure were attenuated in patients with PD during handgrip (PD: ∆25 ± 2 mmHg vs. controls: ∆31 ± 3 mmHg; P < 0.05), and these group differences remained during postexercise ischemia (∆17 ± 1 mmHg vs. ∆26 ± 1 mmHg, respectively; P < 0.01). Additionally, changes in total peripheral resistance were attenuated during exercise and postexercise ischemia, indicating blunted reflex vasoconstriction in patients with PD. Responses to cold pressor test did not differ between groups, suggesting no group differences in generalized sympathetic responsiveness. Our results support the concept that attenuated cardiovascular responses to exercise observed in patients with PD are, at least in part, explained by an altered skeletal muscle metaboreflex. NEW & NOTEWORTHY Patients with Parkinson's disease (PD) presented blunted cardiovascular responses to exercise. We showed that cardiovascular response evoked by the metabolic component of the exercise pressor reflex is blunted in patients with PD. Furthermore, patients with PD presented similar pressor response during the cold pressor test compared with age-matched controls. Altogether, our results support the hypothesis that attenuated cardiovascular responses to exercise observed in patients with PD are mediate by an altered skeletal muscle metaboreflex.

Isolated muscle metaboreflex activation with posthandgrip exercise ischemia (PEI) increases sympathetic nerve activity and partially maintains the exercise-induced increase in blood pressure, but a smaller heart rate (HR) response occurs. The cardiopulmonary baroreceptors, mechanically sensitive receptors that respond to changes in central blood volume and pressure, are strongly associated with changes in body position and upon activation elicit reflex sympathoinhibition. Here, we tested the hypothesis that postural changes modulate the sympathetically mediated cardiac response to PEI in humans. Beat-to-beat HR (electrocardiography) and blood pressure (finger photoplethysmography) were continuously measured, and cardiac function was assessed by echocardiography in 13 healthy men (21 ± 3 yr). After a 15-min rest period, 90-s static handgrip at 40% maximum voluntary contraction was performed followed by 3 min of PEI. Four trials were randomly conducted during either seated or supine position with and without β-adrenergic blockade (25 mg atenolol). During PEI under control conditions, HR remained elevated from baseline in the seated [change (Δ): 4 ± 1 beats/min] but not in the supine (change: -1 ± 1 beats/min) position. Similarly, stroke volume and cardiac output were increased from baseline in the seated (∆13.0 ± 2.4 ml and ∆1.1 ± 0.2 l/min, respectively) but not in the supine (∆2.5 ± 2.9 ml and ∆0.13 ± 0.20 l/min, respectively) position. During β-adrenergic blockade, HR, stroke volume, and cardiac output remained unchanged in both conditions. We conclude that sympathetically mediated cardiac responses to PEI are influenced by changes in body position. These findings indicated that muscle metaboreflex and cardiopulmonary baroreflex have an interactive influence on the neural control of cardiovascular function in humans. NEW & NOTEWORTHY In the present study, we demonstrated that muscle metaboreflex activation increases heart rate, stroke volume, and cardiac output in the seated position but not in the supine position and not after β-adrenergic blockade. These findings indicate that sympathetically mediated cardiac responses to isolated muscle metaboreflex activation after exercise are modulated by central blood volume mobilization.

RUNNING TITLECholesterol efflux capacity and atherosclerosis in elderly. ABBREVIATIONSANCOVA, analysis of covariance; CAC, coronary artery calcium; CEC, cholesterol efflux capacity; CRP, Creactive protein; HDL-C, HDL cholesterol; FMD, flow mediated dilation; IMT, intima-media thickness; LDL-C, LDL cholesterol; TC, total cholesterol; TL, telomere length; WHO, world health organization. AbstractSeveral studies revealed that traditional risk factors are less effective in predicting CVD risk in the elderly, suggesting the need to identify new biomarkers. Here we evaluated the association between serum cholesterol efflux capacity (CEC), an atheroprotective property of HDL recently identified as a novel marker of CVD risk, and atherosclerotic burden in a cohort of very old, healthy individuals. Serum CEC values were not significantly correlated neither with calcium score nor with markers of vulnerable plaque, such as positive remodeling, hypodensity, spotty calcification or napking-ring sign. In addition, no association was detected between CEC and telomere length, a marker of biological aging that has been linked to atherosclerosis extent. Interestingly, elderly subjects presented a remarkably higher CEC (+30.2%; p<0.0001) compared to values obtained from a cohort of sex-matched, free of cardiovascular events, middle-aged individuals. In conclusion, serum CEC is not related to traditional risk factors in very old, free of cardiovascular events subjects, but has significantly higher values compared to a healthy, younger population. Whether this improved HDL functionality may represent a protective factor in CVD onset has to be established in future studies.

The arterial baroreflex has dominant control over multiunit muscle sympathetic nerve activity (MSNA) burst occurrence, but whether this extends to all single units or is influenced by resting blood pressure status is unclear. In 22 men (32 ± 8 yr), we assessed 68 MSNA single units during sequential bolus injections of nitroprusside and phenylephrine (modified Oxford). Sympathetic baroreflex sensitivity (sBRS) was quantified as the weighted negative linear regression slope between diastolic blood pressure (DBP) and single-unit spike firing probability and multiple spike firing. Strong negative linear relationships ( r ≥ −0.50) between DBP and spike firing probability were observed in 63/68 (93%) single units (−2.27 ± 1.27%·cardiac cycle−1·mmHg−1 [operating range, 18 ± 8 mmHg]). In contrast, only 45/68 (66%) single units had strong DBP-multiple spike firing relationships (−0.13 ± 0.18 spikes·cardiac cycle−1·mmHg−1 [operating range, 14 ± 7 mmHg]). Participants with higher resting DBP (65 ± 3 vs. 77 ± 3 mmHg, P < 0.001) had similar spike firing probability sBRS (low vs. high, −2.08 ± 1.08 vs. −2.46 ± 1.42%·cardiac cycle−1·mmHg−1, P = 0.33), but a smaller sBRS operating range (20 ± 6 vs. 16 ± 9 mmHg, P = 0.01; 86 ± 24 vs. 52 ± 25% of total range, P < 0.001) and a higher proportion of single units without arterial baroreflex control outside this range [6/31 (19%) vs. 21/32 (66%), P < 0.001]. Participants with higher resting DBP also had fewer single units with arterial baroreflex control of multiple spike firing (79 vs. 53%, P = 0.04). The majority of MSNA single units demonstrate strong arterial baroreflex control over spike firing probability during pharmacological manipulation of blood pressure. Changes in single-unit sBRS operating range and control of multiple spike firing may represent altered sympathetic recruitment patterns associated with the early development of hypertension. NEW & NOTEWORTHY Muscle sympathetic single units can be differentially controlled during stress. In contrast, we demonstrate that 93% of single units maintain strong arterial baroreflex control during pharmacological manipulation of blood pressure. Interestingly, the operating range and proportion of single units that lose arterial baroreflex control outside of this range are influenced by resting blood pressure levels. Altered single unit, but not multiunit, arterial baroreflex control may represent changes in sympathetic recruitment patterns in early stage development of hypertension.

Our report is illustrative as it emphasizes that a thorough diagnostic investigation should be done in cases of sudden cardiac arrest during the perioperative period, even in patients that appear to be healthy.