Enhanced chronotropic and inotropic responses of rat myocardium to cholinergic stimulus with aging

1992 ◽  
Vol 70 (12) ◽  
pp. 1618-1624 ◽  
Author(s):  
Na Su ◽  
Njanoor Narayanan
Keyword(s):  
Muscarinic Receptor ◽  
Heart Function ◽  
Specific Binding ◽  
Adrenergic Stimulation ◽  
Chronotropic Response ◽  
Related Difference ◽  
Age Related ◽  
Rat Hearts ◽  
Inotropic Responses ◽  
The Impact

The ability of the heart to respond to adrenergic stimulation diminishes with aging, and this may be one of the factors contributing to the age-associated decline in cardiac stress responsiveness. On the other hand, little is known about the impact of aging on the responsiveness of the heart to cholinergic stimulation. In this study, we determined the chronotropic and inotropic responses of the isolated, Langendorff-perfused hearts from adult (6–8 months) and aged (28–30 months) rats to cholinergic agonists so as to assess age-related alterations in postsynaptic cholinergic control of heart function. The results showed the following. (i) In isolated perfused spontaneously beating rat hearts, the negative chronotropic response to acetylcholine (10−9–10−5 M) was up to 4-fold greater in the aged compared with adult hearts; this age-related difference was less marked (2-fold) but not abolished in the presence of a maximally effective concentration (5 μM) of the cholinesterase inhibitor eserine. (ii) The cholinesterase-resistant agonist carbachol (10−9–2.5 × 10−6 M) elicited a 2- to 3-fold greater negative chronotropic response in the aged compared with adult hearts. (iii) In isolated perfused, electrically paced (4 Hz) rat hearts, carbachol (10−9–10−3 M) elicited a concentration-dependent negative inotropic response, which was 2-fold greater in the aged compared with adult heart at all carbachol concentrations, (iv) Acetylcholinesterase activities (micromoles per gram per hour) were 50–60% lower in the aged atria (83 ± 21) and ventricles (24 ± 6) than in adult atria (210 ± 20) and ventricles (47 ± 7). (v) No significant age-related difference was observed in the specific binding of (–)-[3H]quinuclidinyl benzilate to muscarinic receptor sites in atria or ventricles. These findings demonstrate a striking enhancement in the responses of the heart to cholinergic stimulus with aging, which can be attributed in part, but not solely to age-associated decline in cholinesterase activity. Age-associated alterations in muscarinic receptor linked events may also underlie the cholinergic hypersensitivity of the aging heart.Key words: aging, muscarinic receptor, cardiac performance in vitro, cholineresterase activity.

Effects of age on muscarinic cholinergic receptors in rat myocardium

1983 ◽  
Vol 61 (8) ◽  
pp. 822-829 ◽  
Author(s):  
Njanoor Narayanan ◽  
Jo-Anne Derby
Keyword(s):  
Young Adult ◽  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Specific Binding ◽  
Ventricular Myocardium ◽  
Aged Rats ◽  
Adult Rats ◽  
Related Difference ◽  
Age Related ◽  
Receptor Sites

Atrial and ventricular myocardium from young (3–4 months old), young adult (7–8 months old), and aged (24–25 months old) rats were used to study the influence of age on cardiac cholinergic muscarinic receptors. The density of muscarinic receptors (expressed as fmol/mg protein or pmol/g tissue), determined by the specific binding of [3Hjquinuclidinyl benzyl ate ([3H]QNB), was significantly greater (24–29%) in atria of aged rats compared with that in atria of young or young adult rats. The muscarinic receptor density in ventricles was found to be essentially similar in all age groups studied. Antagonist as well as agonist binding characteristics of muscarinic receptor sites were examined in atria and ventricles from young and aged rats. No significant age-related difference was observed in the dissociation constant (KD) of atrial or ventricular receptors for the antagonist ligand [3H]QNB (KD apparent (nM): 1.04 ± 0.16 and 0.91 ± 0.12, respectively, for young and aged atria; 0.75 ± 0.08 and 0.76 ± 0.10, respectively, for young and aged ventricles). Similarly, the concentrations of muscarinic antagonist atropine and agonist carbachol causing 50% inhibition of [3H]QNB binding to the receptor sites (IC50) in atria and ventricles were not altered by age. Age-related difference was also not evident in the Hill coefficients for [3H]QNB, atropine, and carbachol. These results indicate that diminished responsiveness of the aged heart to vagal stimulation and exogenously administered cholinergic agents reported in the literature cannot be attributed to an age-related reduction in the number of cardiac muscarinic receptors or their affinities toward agonist or antagonist ligands.

Effects of aging on sarcoplasmic reticulum function and contraction duration in skeletal muscles of the rat

1996 ◽  
Vol 271 (4) ◽  
pp. C1032-C1040 ◽  
Author(s):  
N. Narayanan ◽  
D. L. Jones ◽  
A. Xu ◽  
J. C. Yu
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Soleus Muscle ◽  
Pump Function ◽  
Related Difference ◽  
Contraction Duration ◽  
Age Related ◽  
Isometric Twitch ◽  
Effects Of Aging ◽  
The Impact

The impact of aging on the Ca2+ pump function of skeletal muscle sarcoplasmic reticulum (SR) was investigated using SR-enriched membrane vesicles isolated from the slow-twitch soleus muscle (SM) and the relatively fast-twitch gastrocnemius muscle (GM) isolated from adult (6-8 mo old) and aged (26-28 mo old) Fischer 344 rats. In addition, isometric twitch characteristics of SM and GM were determined in situ in adult and aged rats under anesthesia. The rates of ATP-supported Ca2+ uptake by SM SR was markedly lower ( approximately 50%) in the aged compared with adult at varying Ca2+ (0.11-8.24 microM) concentrations. Kinetic analysis of the data revealed age-associated decrease in maximum activity reached (Vmax) and increase in the concentration of Ca2+ giving half of Vmax. In contrast, no significant age-related difference was observed in ATP-supported Ca2+ uptake activity of GM SR. The Ca(2+)-stimulated adenosinetriphosphatase (ATPase) activities and the amount of Ca(2+)-ATPase protein did not vary significantly with aging in SM or GM SR. Also, no significant age-related difference was observed in the content of the ryanodine receptor (Ca(2+)-release channel) or the Ca2+ binding protein, calsequestrin in SM and GM SR. In isometrically contracting SM, the time to peak force, half-relaxation time, and contraction duration were significantly prolonged in the aged compared with adult, whereas there was no age-related difference in maximum developed force. None of these isometric twitch parameters differed significantly with age in the GM. These results demonstrate that the effects of aging on skeletal muscle contractile properties and SR function are muscle specific. Furthermore, the data strongly suggest that impairment in SR Ca2+ pump function, apparently due to uncoupling of ATP hydrolysis from Ca2+ transport, contributes to the age-associated slowing of relaxation in the soleus muscle.

scholarly journals Impact of age on the development of fatigue during large and small muscle mass exercise

2018 ◽  
Vol 315 (4) ◽  
pp. R741-R750 ◽  
Author(s):  
Joshua C. Weavil ◽  
Thomas J. Hureau ◽  
Taylor S. Thurston ◽  
Simranjit K. Sidhu ◽  
Ryan S. Garten ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Relative Intensity ◽  
Femoral Nerve ◽  
Central Fatigue ◽  
Peak Power Output ◽  
Active Muscle ◽  
Task Failure ◽  
Related Difference ◽  
Age Related ◽  
The Impact

To examine the impact of aging on neuromuscular fatigue following cycling (CYC; large active muscle mass) and single-leg knee-extension (KE; small active muscle mass) exercise, 8 young (25 ± 4 years) and older (72 ± 6 years) participants performed CYC and KE to task failure at a given relative intensity (80% of peak power output). The young also matched CYC and KE workload and duration of the old (iso-work comparison). Peripheral and central fatigue were quantified via pre-/postexercise decreases in quadriceps twitch torque (∆Qtw, electrical femoral nerve stimulation) and voluntary activation (∆VA). Although young performed 77% and 33% more work during CYC and KE, respectively, time to task failure in both modalities was similar to the old (~9.5 min; P > 0.2). The resulting ΔQtw was also similar between groups (CYC ~40%, KE ~55%; P > 0.3); however, ∆VA was, in both modalities, approximately double in the young (CYC ~6%, KE ~9%; P < 0.05). While causing substantial peripheral and central fatigue in both exercise modalities in the old, ∆Qtw in the iso-work comparison was not significant (CYC; P = 0.2), or ~50% lower (KE; P < 0.05) in the young, with no central fatigue in either modality ( P > 0.4). Based on iso-work comparisons, healthy aging impairs fatigue resistance during aerobic exercise. Furthermore, comparisons of fatigue following exercise at a given relative intensity mask the age-related difference observed following exercise performed at the same workload. Finally, although active muscle mass has little influence on the age-related difference in the rate of fatigue at a given relative intensity, it substantially impacts the comparison during exercise at a given absolute intensity.

scholarly journals Impact of age and sex correction on the diagnostic performance of dopamine transporter SPECT

2020 ◽  
Author(s):  
Helen Schmitz-Steinkrüger ◽  
Catharina Lange ◽  
Ivayla Apostolova ◽  
Franziska L. Mathies ◽  
Lars Frings ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Diagnostic Performance ◽  
Specific Binding ◽  
Clinical Sample ◽  
Performance Measure ◽  
Specific Binding Ratio ◽  
Parkinsonian Syndromes ◽  
Age Related ◽  
The Impact ◽  
Age And Sex

Abstract Purpose The specific binding ratio (SBR) of 123I-FP-CIT (FP-CIT) in the putamen decreases with age by about 5% per decade and most likely is about 10% higher in females. However, the clinical utility of age and sex correction of the SBR is still a matter of debate. This study tested the impact of age and sex correction on the diagnostic performance of the putamen SBR in three independent patient samples. Methods Research sample: 207 healthy controls (HC) and 438 Parkinson’s disease (PD) patients. Clinical sample A: 183 patients with neurodegenerative parkinsonian syndrome (PS) and 183 patients with non-neurodegenerative PS from one site. Clinical sample B: 84 patients with neurodegenerative PS and 38 patients with non-neurodegenerative PS from another site. Correction for age and sex of the putamen SBR was based on linear regression in the HC or non-neurodegenerative PS, separately in each sample. The area under the ROC curve (AUC) was used as performance measure. Results The putamen SBR was higher in females compared to males (PPMI: 14%, p < 0.0005; clinical sample A: 7%, p < 0.0005; clinical sample B: 6%, p = 0.361). Age-related decline of the putamen SBR ranged between 3.3 and 10.4% (p ≤ 0.019). In subjects ≥ 50 years, age and sex explained < 10% of SBR between-subjects variance. Correction of the putamen SBR for age and sex resulted in slightly decreased AUC in the PPMI sample (0.9955 versus 0.9969, p = 0.025) and in clinical sample A (0.9448 versus 0.9519, p = 0.057). There was a small, non-significant AUC increase in clinical sample B (0.9828 versus 0.9743, p = 0.232). Conclusion These findings do not support age and sex correction of the putaminal FP-CIT SBR in the diagnostic workup of parkinsonian syndromes. This most likely is explained by the fact that the proportion of between-subjects variance caused by age and sex is considerably below the symptom threshold of about 50% reduction in neurodegenerative PS.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

scholarly journals The impact of vascular risk factors on the thickness and volume of the choroid in AMD patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elżbieta Krytkowska ◽  
Aleksandra Grabowicz ◽  
Katarzyna Mozolewska-Piotrowska ◽  
Zofia Ulańczyk ◽  
Krzysztof Safranow ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vascular Risk Factors ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Vascular Risk ◽  
Average Volume ◽  
Central Ring ◽  
Age Related ◽  
The Impact ◽  
Wet Amd

AbstractDisturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (β =  + 0.18, p = 0.0007, β =  + 0.18, p = 0.0008, respectively) and to dry AMD (β =  + 0.17, p = 0.00003 for both ATC and AVC and β =  − 0.30 p < 0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs =  − 0.13, p < 0.05; Rs =  − 0.12; p < 0.05, Rs =  − 0.12; p < 0.05, respectively) while IHD duration negatively correlated with AV (Rs =  − 0.15, p < 0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease.

Impact of Cochlear Implantation on Neurocognitive Subdomains in Adult Cochlear Implant Recipients

2021 ◽  
pp. 1-10
Author(s):  
Christiane Völter ◽  
Lisa Götze ◽  
Imme Haubitz ◽  
Janine Müther ◽  
Stefan Dazert ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implant ◽  
Cochlear Implantation ◽  
Verbal Fluency ◽  
Homogeneous Population ◽  
Delayed Recall ◽  
Hearing Status ◽  
Age Related ◽  
Significant Difference ◽  
The Impact

<b><i>Introduction:</i></b> Age-related hearing loss affects about one-third of the population worldwide. Studies suggest that hearing loss may be linked to cognitive decline and auditory rehabilitation may improve cognitive functions. So far, the data are limited, and the underlying mechanisms are not fully understood. The study aimed to analyze the impact of cochlear implantation on cognition in a large homogeneous population of hearing-impaired adults using a comprehensive non-auditory cognitive assessment with regard to normal-hearing (NH) subjects. <b><i>Material and Methods:</i></b> Seventy-one cochlear implant (CI) candidates with a postlingual, bilateral severe or profound hearing loss aged 66.3 years (standard deviation [SD] 9.2) and 105 NH subjects aged 65.96 years (SD 9.4) were enrolled. The computer-based neurocognitive tool applied included 11 subtests covering attention (M3), short- and long-term memory (recall and delayed recall), working memory (0- and 2-back, Operation Span [OSPAN] task), processing speed (Trail Making Test [TMT] A), mental flexibility (TMT B), inhibition (cFlanker and iFlanker), and verbal fluency. CI patients underwent a neurocognitive testing preoperatively as well as 12 months postoperatively. Impact of hearing status, age, gender, and education on cognitive subdomains was studied. Additionally, after controlling for education and age, cognitive performance of CI subjects (<i>n</i> = 41) was compared to that of NH (<i>n</i> = 34). <b><i>Results:</i></b> CI users achieved significantly better neurocognitive scores 12 months after cochlear implantation than before in most subtests (M3, [delayed] recall, 2-back, OSPAN, iFlanker, and verbal fluency; all <i>p</i> &#x3c; 0.05) except for the TMT A and B. A significant correlation could be found between the postoperative improvement in speech perception and in the attentional task M3 (<i>p</i> = 0.01). Hearing status (<i>p</i> = 0.0006) had the strongest effect on attention, whereas education had a high impact on recall (<i>p</i> = 0.002), OSPAN (<i>p</i> = 0.0004), and TMT A (<i>p</i> = 0.005) and B (<i>p</i> = 0.003). Inhibition was mainly age-dependent with better results in younger subjects (<i>p</i> = 0.016). Verbal fluency was predicted by gender as females outperformed men (<i>p</i> = 0.009). Even after controlling for age and education NH subjects showed a significantly better performance than CI candidates in the recall (<i>p</i> = 0.03) and delayed recall (<i>p</i> = 0.01) tasks. Postoperatively, there was no significant difference between the 2 groups anymore. <b><i>Conclusion:</i></b> Impact of cochlear implantation on neurocognitive functions differs according to the cognitive subdomains. Postoperatively, CI recipients performed as good as age- and education-matched NH subjects.

scholarly journals Incidence of diabetes mellitus among people living with and without HIV in British Columbia, Canada between 2001 and 2013: a longitudinal population-based cohort study

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e048744
Author(s):  
Andreea Bratu ◽  
Taylor McLinden ◽  
Katherine Kooij ◽  
Monica Ye ◽  
Jenny Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
British Columbia ◽  
Cohort Study ◽  
Population Based ◽  
Incidence Rates ◽  
Trend Test ◽  
People Living With Hiv ◽  
Age Related ◽  
Hiv Serostatus ◽  
The Impact

IntroductionPeople living with HIV (PLHIV) are increasingly at risk of age-related comorbidities such as diabetes mellitus (DM). While DM is associated with elevated mortality and morbidity, understanding of DM among PLHIV is limited. We assessed the incidence of DM among people living with and without HIV in British Columbia (BC), Canada, during 2001–2013.MethodsWe used longitudinal data from a population-based cohort study linking clinical data and administrative health data. We included PLHIV who were antiretroviral therapy (ART) naïve at baseline, and 1:5 age-sex-matched persons without HIV. All participants had ≥5 years of historic data pre-baseline and ≥1 year(s) of follow-up. DM was identified using the BC Ministry of Health’s definitions applied to hospitalisation, physician billing and drug dispensation datasets. Incident DM was identified using a 5-year run-in period. In addition to unadjusted incidence rates (IRs), we estimated adjusted incidence rate ratios (IRR) using Poisson regression and assessed annual trends in DM IRs per 1000 person years (PYs) between 2001 and 2013.ResultsA total of 129 PLHIV and 636 individuals without HIV developed DM over 17 529 PYs and 88,672 PYs, respectively. The unadjusted IRs of DM per 1000 PYs were 7.4 (95% CI 6.2 to 8.8) among PLHIV and 7.2 (95% CI 6.6 to 7.8) for individuals without HIV. After adjustment for confounding, HIV serostatus was not associated with DM incidence (adjusted IRR: 1.03, 95% CI 0.83 to 1.27). DM incidence did not increase over time among PLHIV (Kendall trend test: p=0.9369), but it increased among persons without HIV between 2001 and 2013 (p=0.0136).ConclusionsAfter adjustment, HIV serostatus was not associated with incidence of DM, between 2001 and 2013. Future studies should investigate the impact of ART on mitigating the potential risk of DM among PLHIV.

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