Arterial blood pressure (BP) is regulated via the interaction of various local, humoral, and neural factors. In humans, the major neural pathway for acute BP regulation involves the baroreflexes. In ...response to baroreceptor activation/deactivation, as occurs during transient changes in BP, key determinants of BP, such as cardiac period/heart rate (via the sympathetic and parasympathetic nervous system) and vascular resistance (via the sympathetic nervous system), are modified to maintain BP homeostasis. In this review, the effects of aging on both the parasympathetic and sympathetic arms of the baroreflex are discussed. Aging is associated with decreased cardiovagal baroreflex sensitivity (i.e., blunted reflex changes in R-R interval in response to a change in BP). Mechanisms underlying this decrease may involve factors such as increased levels of oxidative stress, vascular stiffening, and decreased cardiac cholinergic responsiveness with age. Consequences of cardiovagal baroreflex impairment may include increased levels of BP variability, an impaired ability to respond to acute challenges to the maintenance of BP, and increased risk of sudden cardiac death. In contrast, baroreflex control of sympathetic outflow is not impaired with age. Collectively, changes in baroreflex function with age are associated with an impaired ability of the organism to buffer changes in BP. This is evidenced by the reduced potentiation of the pressor response to bolus infusion of a pressor drug after compared to before systemic ganglionic blockade in older compared with young adults.
Age-predicted maximal heart rate revisited Tanaka, Hirofumi; Monahan, Kevin D; Seals, Douglas R
Journal of the American College of Cardiology,
January 2001, 2001, 2001-Jan, 2001-01-00, 20010101, Letnik:
37, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
OBJECTIVES
We sought to determine a generalized equation for predicting maximal heart rate (HRmax) in healthy adults.
BACKGROUND
The age-predicted HRmaxequation (i.e., 220 − age) is commonly used as ...a basis for prescribing exercise programs, as a criterion for achieving maximal exertion and as a clinical guide during diagnostic exercise testing. Despite its importance and widespread use, the validity of the HRmaxequation has never been established in a sample that included a sufficient number of older adults.
METHODS
First, a meta-analytic approach was used to collect group mean HRmaxvalues from 351 studies involving 492 groups and 18,712 subjects. Subsequently, the new equation was cross-validated in a well-controlled, laboratory-based study in which HRmaxwas measured in 514 healthy subjects.
RESULTS
In the meta-analysis, HRmaxwas strongly related to age (r = −0.90), using the equation of 208 − 0.7 × age. The regression equation obtained in the laboratory-based study (209 − 0.7 × age) was virtually identical to that obtained from the meta-analysis. The regression line was not different between men and women, nor was it influenced by wide variations in habitual physical activity levels.
CONCLUSIONS
1) A regression equation to predict HRmaxis 208 − 0.7 × age in healthy adults. 2) HRmaxis predicted, to a large extent, by age alone and is independent of gender and habitual physical activity status. Our findings suggest that the currently used equation underestimates HRmaxin older adults. This would have the effect of underestimating the true level of physical stress imposed during exercise testing and the appropriate intensity of prescribed exercise programs.
► High dietary intake of flavanols reduces cardiovascular risk in humans. ► Effects of flavanols on the vascular endothelium may underlie these effects. ► Brachial artery flow-mediated dilation is a ...powerful method to assess endothelial function. ► Cocoa/chocolate ingestion dose-dependently increases flow-mediated dilation in humans. ► Mechanisms underlying these effects likely involve nitric oxide.
Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans. Collectively, the preponderance of evidence indicates that FMD is a powerful surrogate measure for firm cardiovascular endpoints, such as cardiovascular-related mortality, in humans. Thus, literally thousands of studies have utilized this technique to document group differences in FMD, as well as to assess the effects of various interventions on FMD. In regards to the latter, numerous studies indicate that both acute and chronic ingestion of cocoa/chocolate increases FMD in humans. Increases in FMD after cocoa/chocolate ingestion appear to be dose-dependent such that greater increases in FMD are observed after ingestion of larger quantities. The mechanisms underlying these responses are likely diverse, however most data suggest an effect of increased nitric oxide bioavailability. Thus, positive vascular effects of cocoa/chocolate on the endothelium may underlie (i.e., be linked mechanistically to) reductions in cardiovascular risk in humans.
Peripheral conduit artery flow-mediated dilatation decreases with ageing in humans. The underlying mechanisms and efficacy
of preventive strategies are unknown. Brachial artery flow-mediated ...dilatation was determined at baseline and after ascorbic
acid (vitamin C) intravenous infusion and chronic supplementation (500 mg day â1 for 30 days) in three groups of healthy men: young sedentary ( n = 11; 25 ± 1 years, mean ± s.e.m. ), older sedentary ( n = 9; 64 ± 2), and older endurance-exercise trained ( n = 9; 64 ± 2). At baseline, flow-mediated dilatation (normalized for the hyperaemic stimulus) was â¼45% lower in the older (0.015
± 0.001) versus young (0.028 ± 0.004) sedentary men ( P < 0.01), but was preserved in older exercising men (0.028 ± 0.004). Ascorbic acid infusion increased plasma concentrations
> 15-fold in all groups and restored flow-mediated dilatation in the sedentary older men (to 0.023 ± 0.002; P > 0.1 versus other groups), with no effects in the other two groups. Oral ascorbic acid supplementation did not affect flow-mediated dilatation
in any group. Brachial artery endothelium-independent dilatation (sublingual nitroglycerin) did not differ among the groups
at baseline nor change with ascorbic acid administration. These results provide the first evidence for an important role of
oxidative stress in both the impairment in peripheral conduit artery flow-mediated dilatation with sedentary human ageing
and the preservation of flow-mediated dilatation with physically active ageing.
A reduction in compliance of the large-sized cardiothoracic (central) arteries is an independent risk factor for the development of cardiovascular disease with advancing age.
We determined the role ...of habitual exercise on the age-related decrease in central arterial compliance by using both cross-sectional and interventional approaches. First, we studied 151 healthy men aged 18 to 77 years: 54 were sedentary, 45 were recreationally active, and 53 were endurance exercise-trained. Central arterial compliance (simultaneous B-mode ultrasound and arterial applanation tonometry on the common carotid artery) was lower (P:<0.05) in middle-aged and older men than in young men in all 3 groups. There were no significant differences between sedentary and recreationally active men at any age. However, arterial compliance in the endurance-trained middle-aged and older men was 20% to 35% higher than in the 2 less active groups (P:<0.01). As such, age-related differences in central arterial compliance were smaller in the endurance-trained men than in the sedentary and recreationally active men. Second, we studied 20 middle-aged and older (53+/-2 years) sedentary healthy men before and after a 3-month aerobic exercise intervention (primarily walking). Regular exercise increased central arterial compliance (P:<0.01) to levels similar to those of the middle-aged and older endurance-trained men. These effects were independent of changes in body mass, adiposity, arterial blood pressure, or maximal oxygen consumption.
Regular aerobic-endurance exercise attenuates age-related reductions in central arterial compliance and restores levels in previously sedentary healthy middle-aged and older men. This may be one mechanism by which habitual exercise lowers the risk of cardiovascular disease in this population.
In sedentary humans endothelium-dependent vasodilation is impaired with advancing age contributing to their increased cardiovascular risk, whereas endurance-trained adults demonstrate lower ...age-related risk. We determined the influence of regular aerobic exercise on the age-related decline in endothelium-dependent vasodilation.
In a cross-sectional study, 68 healthy men 22 to 35 or 50 to 76 years of age who were either sedentary or endurance exercise-trained were studied. Forearm blood flow (FBF) responses to intra-arterial infusions of acetylcholine and sodium nitroprusside were measured by strain-gauge plethysmography. Among the sedentary men, the maximum FBF response to acetylcholine was 25% lower in the middle aged and older compared with the young group (P:<0.01). In contrast, there was no age-related difference in the vasodilatory response to acetylcholine among the endurance-trained men. FBF at the highest acetylcholine dose was almost identical in the middle aged and older (17.3+/-1.3 mL/100 mL tissue per minute) and young (17.7+/-1.4 mL/100 mL tissue per minute) endurance-trained groups. There were no differences in the FBF responses to sodium nitroprusside among the sedentary and endurance- trained groups. In an exercise intervention study, 13 previously sedentary middle aged and older healthy men completed a 3-month, home-based aerobic exercise intervention (primarily walking). After the exercise intervention, acetylcholine-mediated vasodilation increased approximately 30% (P:<0.01) to levels similar to those in young adults and middle aged and older endurance-trained men.
Our results indicate that regular aerobic exercise can prevent the age-associated loss in endothelium-dependent vasodilation and restore levels in previously sedentary middle aged and older healthy men. This may represent an important mechanism by which regular aerobic exercise lowers the risk of cardiovascular disease in this population.
Knowledge and control of surface charge or potential is important for tailoring colloidal interactions. In this work, we compare widely used zeta potential (ζ) measurements of charged lipid vesicle ...surface potential to direct measurements using the surface force apparatus (SFA). Our measurements show good agreement between the two techniques. On varying the fraction of anionic lipids dimyristoylphosphatidylserine (DMPS) or dimyristoylphosphatidylglycerol (DMPG) mixed with zwitterionic dimyristoylphosphatidylcholine (DMPC) from 0 to 100 mol % we observed a near-linear increase in membrane surface charge or potential up to 20–30 mol % charged lipids beyond which charge saturation occurred in physiological (high) salt conditions. Similarly, in low salt concentrations, a linear increase in charge/potential was found but only up to ∼5–10 mol % charged lipids beyond which the surface charge or potential leveled off. While a lower degree of ionization is expected due to the lower dielectric constant (ε ∼ 4) of the lipid acyl chain environment, increasing intramembrane electrostatic repulsion between neighboring charged lipid head groups at higher charge loading contributes to charge suppression. Measured potentials in physiological salt solutions were consistent with predictions using the Gouy-Chapman-Stern-Grahame (GCSG) model of the electrical double layer with Langmuir binding of counterions, but in low salt conditions, the model significantly overestimated the surface charge/potential. The much lower ionization in low salt (maximum ∼1–2% of total lipids ionized) instead was consistent with counterion condensation at the bilayer surface which limited the charge that could be obtained. The strong interplay between membrane composition, lipid headgroup ionization, electrolyte concentration, and solution pH complicates exact prediction and tuning of membrane surface charge for applications. However, the theoretical frameworks used here can provide guidelines to understand this interplay and establish a range of achievable potentials for a system and predict the response to triggers like pH and salt concentration changes.
•Insufficient drug uptake by tumors is the major problem of systemic chemotherapy.•Systemic drug dose increase offered limited benefits and resulted in toxicities.•Loco-regional delivery increased ...drug doses in tumors with low systemic toxicity.•Although very high doses in tumors achieved, survival benefits are not sufficient.•We review new RRH approach applications in loco-regional cancer treatment.
Insufficient drug uptake by solid tumors remains the major problem for systemic chemotherapy. Many studies have demonstrated anticancer drug effects to be dose-dependent, although dose-escalation studies have resulted in limited survival benefit with increased systemic toxicities. One solution to this has been the idea of loco-regional drug treatments, which offer dramatically higher drug concentrations in tumor tissues while minimizing systemic toxicity. Although loco-regional delivery has been most prominent in cancers of the liver, soft tissues and serosal peritoneal malignancies, survival benefits are very far from desirable. This review discusses the evolution of loco-regional treatments, the present approaches and offers rapidly reversible hydrophobization of drugs as the new future direction.
Loco-regional cancer drug therapies have been advanced to increase drug concentrations in tumors while minimizing systemic toxicity. We review benefits and limitations of current approaches and discuss a rapidly reversible hydrophobization of drugs for solid tumor treatment.
Excess dietary salt intake is a major contributing factor to the pathogenesis of salt-sensitive hypertension. Strong evidence suggests that salt-sensitive hypertension is attributed to renal ...dysfunction, vascular abnormalities, and activation of the sympathetic nervous system. Indeed, sympathetic nerve transections or interruption of neurotransmission in various brain centers lowers arterial blood pressure (ABP) in many salt-sensitive models. The purpose of this article is to discuss recent evidence that supports a role of plasma or cerebrospinal fluid hypernatremia as a key mediator of sympathoexcitation and elevated ABP. Both experimental and clinical studies using time-controlled sampling have documented that a diet high in salt increases plasma and cerebrospinal fluid sodium concentration. To the extent it has been tested, acute and chronic elevations in sodium concentration activates the sympathetic nervous system in animals and humans. A further understanding of how the central nervous system detects changes in plasma or cerebrospinal fluid sodium concentration may lead to new therapeutic treatment strategies in salt-sensitive hypertension.
Cardiovascular-related mortality peaks during cold winter months, particularly in older adults. Acute physiological responses, such as increases in blood pressure, in response to cold exposure may ...contribute to these associations. To determine whether the blood pressure-raising effect (pressor response) of non-internal body temperature-reducing cold stress is greater with age, we measured physiological responses to 20 min of superficial skin cooling, via water-perfused suit, in 12 younger 25 +/- 1 (SE) yr old and 12 older (65 +/- 2 yr old) adults. We found that superficial skin cooling elicited an increase in blood pressure from resting levels (pressor response; P < 0.05) in younger and older adults. However, the magnitude of this pressor response (systolic and mean blood pressure) was more than twofold higher in older adults (P < 0.05 vs. younger adults). The magnitude of the pressor response was similar at peripheral (brachial) and central (estimated in the aorta) measurement sites. Regression analysis revealed that aortic pulse wave velocity, a measure of central arterial stiffness obtained before cooling, was the best predictor of the increased pressor response to superficial skin cooling in older adults, explaining approximately 63% of its variability. These results indicate that there is a greater pressor response to non-internal body temperature-reducing cold stress with age in humans that may be mediated by increased levels of central arterial stiffness.
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