scholarly journals Cardiac function is preserved following 4 weeks of voluntary wheel running in a rodent model of chronic kidney disease

2014 ◽  
Vol 117 (5) ◽  
pp. 482-491 ◽  
Author(s):  
James M. Kuczmarski ◽  
Christopher R. Martens ◽  
Jahyun Kim ◽  
Shannon L. Lennon-Edwards ◽  
David G. Edwards
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Voluntary Wheel Running ◽  
Low Volume ◽  
Voluntary Wheel

The purpose of this investigation was to determine the effect of 4 wk of voluntary wheel running on cardiac performance in the 5/6 ablation-infarction (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary wheel running would be effective in preserving cardiac function in AI. Male Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI. Animals were maintained over a total period of 8 wk following AI and sham surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk voluntary wheel-running intervention/sedentary control period. Cardiac performance was assessed using an isolated working heart preparation. Left ventricular (LV) tissue was used for biochemical tissue analysis. In addition, soleus muscle citrate synthase activity was measured. AI-WR rats performed a low volume of exercise, running an average of 13 ± 2 km, which resulted in citrate synthase activity not different from that in sham animals. Isolated AI-SED hearts demonstrated impaired cardiac performance at baseline and in response to preload/afterload manipulations. Conversely, cardiac function was preserved in AI-WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO) synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In addition, LV H2O2 in AI-WR was similar to that of sham and associated with increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2. The findings of the current study suggest that a low-volume exercise intervention is sufficient to maintain cardiac performance in rats with CKD, potentially through a mechanism related to improved redox homeostasis and increased NO.

scholarly journals Voluntary wheel running improves cardiac function in a rodent model of chronic kidney disease (884.15)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
James Kuczmarski ◽  
Christopher Martens ◽  
Jahyun Kim ◽  
Shannon Lennon‐Edwards ◽  
David Edwards
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Wheel Running ◽  
Rodent Model ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

scholarly journals Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD)

2019 ◽  
Vol 30 (10) ◽  
pp. 1898-1909 ◽  
Author(s):  
Keith G. Avin ◽  
Matthew R. Allen ◽  
Neal X. Chen ◽  
Shruthi Srinivasan ◽  
Kalisha D. O’Neill ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Rat Model ◽  
Wheel Running ◽  
Serum Biochemistry ◽  
Left Ventricular ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Voluntary Wheel Running ◽  
Exercise Interventions ◽  
Voluntary Wheel

BackgroundReduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality.MethodsWe tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy/+ IU) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2–3 of CKD. We then measured the effects of wheel running on serum biochemistry, tissue weight, voluntary grip strength, maximal aerobic capacity (VO2max), body composition and bone micro-CT and mechanics.ResultsWheel running improved serum biochemistry with decreased creatinine, phosphorous, and parathyroid hormone in the rats with CKD. It improved muscle strength, increased time-to-fatigue (for VO2max), reduced cortical porosity and improved bone microarchitecture. The CKD rats with voluntary wheel access also had reduced kidney cystic weight and reduced left ventricular mass index.ConclusionsVoluntary wheel running resulted in multiple beneficial systemic effects in rats with CKD and improved their physical function. Studies examining exercise interventions in patients with CKD are warranted.

scholarly journals Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease

2014 ◽  
Vol 307 (4) ◽  
pp. F418-F426 ◽  
Author(s):  
Christopher R. Martens ◽  
James M. Kuczmarski ◽  
Jahyun Kim ◽  
John J. Guers ◽  
M. Brennan Harris ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Function ◽  
Wheel Running ◽  
Area Under The Curve ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Voluntary Wheel Running ◽  
Sprague Dawley Rats ◽  
Voluntary Wheel

Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor l-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent ⅚ ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN+ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10−9-10−5 M) as indicated by a reduced area under the curve (AUC; 44.56 ± 9.01 vs 100 ± 4.58, P < 0.05) and reduced maximal response (Emax; 59.9 ± 9.67 vs. 94.31 ± 1.27%, P < 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[3H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN+ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with l-arginine.

scholarly journals Skeletal muscle metabolic responses to physical activity are muscle type specific in a rat model of chronic kidney disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Keith G. Avin ◽  
Meghan C. Hughes ◽  
Neal X. Chen ◽  
Shruthi Srinivasan ◽  
Kalisha D. O’Neill ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Rat Model ◽  
Mitochondrial Respiration ◽  
Wheel Running ◽  
Muscle Metabolism ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

AbstractChronic kidney disease (CKD) leads to musculoskeletal impairments that are impacted by muscle metabolism. We tested the hypothesis that 10-weeks of voluntary wheel running can improve skeletal muscle mitochondria activity and function in a rat model of CKD. Groups included (n = 12–14/group): (1) normal littermates (NL); (2) CKD, and; (3) CKD-10 weeks of voluntary wheel running (CKD-W). At 35-weeks old the following assays were performed in the soleus and extensor digitorum longus (EDL): targeted metabolomics, mitochondrial respiration, and protein expression. Amino acid-related compounds were reduced in CKD muscle and not restored by physical activity. Mitochondrial respiration in the CKD soleus was increased compared to NL, but not impacted by physical activity. The EDL respiration was not different between NL and CKD, but increased in CKD-wheel rats compared to CKD and NL groups. Our results demonstrate that the soleus may be more susceptible to CKD-induced changes of mitochondrial complex content and respiration, while in the EDL, these alterations were in response the physiological load induced by mild physical activity. Future studies should focus on therapies to improve mitochondrial function in both types of muscle to determine if such treatments can improve the ability to adapt to physical activity in CKD.

scholarly journals The Copenhagen chronic kidney disease echo study (COInCYDE)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Landler ◽  
S Bro ◽  
B Feldt-Rasmussen ◽  
D Hansen ◽  
A.L Kamper ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Funding Source ◽  
Ckd Stage ◽  
Significant Difference ◽  
Stage 1

Abstract Background The cardiovascular mortality of patients with chronic kidney disease (CKD) is 2–10 times higher than in the average population. Purpose To estimate the prevalence of abnormal cardiac function or structure across the stages CKD 1 to 5nonD. Method Prospective cohort study. Patients with CKD stage 1 to 5 not on dialysis, aged 30 to 75 (n=875) and age-/sex-matched controls (n=173) were enrolled consecutively. All participants underwent a health questionnaire, ECG, morphometric and blood pressure measurements. Blood and urine were analyzed. Echocardiography was performed. Left ventricle (LV) hypertrophy, dilatation, diastolic and systolic dysfunction were defined according to current ESC guidelines. Results 63% of participants were men. Mean age was 58 years (SD 12.6 years). Mean eGFR was 46.7 mL/min/1,73 m (SD 25.8) for patients and 82.3 mL/min/1,73 m (SD 13.4) for controls. The prevalence of elevated blood pressure at physical exam was 89% in patients vs. 53% in controls. Patients were more often smokers and obese. Left ventricular mass index (LVMI) was slightly, albeit insignificantly elevated at CKD stages 1 & 2 vs. in kontrols: 3.1 g/m2, CI: −0.4 to 6.75, p-value 0.08. There was no significant difference in LV-dilatation between patients and controls. Decreasing diastolic and systolic function was observed at CKD stage 3a and later: LVEF decreased 0.95% (CI: −1.5 to −0.2), GLS increased 0.5 (CI: 0.3 to 0.8), and OR for diastolic dysfunction increased 3.2 (CI 1.4 to 7.3) pr. increment CKD stage group. Conclusion In accordance to previous studies, we observe in the CPHCKD cohort study signs of early increase of LVMI in patients with CKD stage 1 & 2. Significant decline in systolic and diastolic cardiac function is apparent already at stage 3 CKD. Figure 1. Estimated GFR vs. GLS & histogram of GLS Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): The Capital Region of Denmark

Abstract 1509: Exercise Training Started Before Myocardial Infarction Improves Survival but Aggravates Left Ventricular Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monique C de Waard ◽  
Dirk J Duncker
Keyword(s):  
Myocardial Infarction ◽  
Exercise Training ◽  
Wheel Running ◽  
Left Ventricular ◽  
Lv Function ◽  
Cardiac Events ◽  
Cross Sectional ◽  
Voluntary Wheel Running ◽  
Lv Dysfunction ◽  
Voluntary Wheel

Introduction: Regular physical activity in patients with established coronary heart disease not only reduces the incidence of cardiac events, but also reduces the risk of all-cause mortality. Recently, we showed in mice that exercise training (EX) started immediately after myocardial infarction (MI) ameliorates left ventricular (LV) dysfunction. Here we tested the hypothesis that additional exercise training prior to an acute MI, i.e. a higher level of physical fitness at the time of MI, is associated with improved survival and attenuated LV dysfunction after MI. Methods and Results: MI was induced by permanent coronary ligation in 128 C57Bl/6 mice and subsequently followed by 8 weeks of voluntary wheel running (MI-EX) or sedentary housing (MI). In a third group, voluntary wheel running was started two weeks before induction of MI (EX-MI-EX). Sham operated mice served as controls. EX after MI had no effect on survival, infarct size, LV hypertrophy or dilation (Table ). However, EX improved LV function, reflected in enhanced LV fractional shortening (FS), rate of rise in LV pressure at 30 mmHg (LVdP/dt P30 ), and decreased pulmonary congestion and right ventricular weight (RVW). When EX was started prior to MI, post-MI survival nearly doubled and mice ran an average post-MI distance of ~7km/d compared to ~5km/d in MI-EX mice. Infarct cross-sectional area was larger, which was principally due to an increased infarct thickness (0.15±0.02mm EX-MI-EX vs 0.11±0.01mm MI; P =0.06). Surprisingly, however, LV hypertrophy and dysfunction were aggravated in the EX-MI-EX group compared to MI-EX. Conclusion: In line with our hypothesis, EX started prior to MI improved survival. However, contrary to our hypothesis, the improved survival was associated with a deterioration of LV dysfunction. The latter may have been the result of survival and hence inclusion of mice with the most severe LV dysfunction.

Effects of voluntary activity and genetic selection on muscle metabolic capacities in house mice Mus domesticus

2000 ◽  
Vol 89 (4) ◽  
pp. 1608-1616 ◽  
Author(s):  
Philippe Houle-Leroy ◽  
Theodore Garland ◽  
John G. Swallow ◽  
Helga Guderley
Keyword(s):  
Lactate Dehydrogenase ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Genetic Selection ◽  
House Mice ◽  
Male Mice ◽  
Selected Lines ◽  
Voluntary Wheel Running ◽  
Selection For ◽  
Voluntary Wheel

Selective breeding is an important tool in behavioral genetics and evolutionary physiology, but it has rarely been applied to the study of exercise physiology. We are using artificial selection for increased wheel-running behavior to study the correlated evolution of locomotor activity and physiological determinants of exercise capacity in house mice. We studied enzyme activities and their response to voluntary wheel running in mixed hindlimb muscles of mice from generation 14, at which time individuals from selected lines ran more than twice as many revolutions per day as those from control (unselected) lines. Beginning at weaning and for 8 wk, we housed mice from each of four replicate selected lines and four replicate control lines with access to wheels that were free to rotate (wheel-access group) or locked (sedentary group). Among sedentary animals, mice from selected lines did not exhibit a general increase in aerobic capacities: no mitochondrial [except pyruvate dehydrogenase (PDH)] or glycolytic enzyme activity was significantly ( P < 0.05) higher than in control mice. Sedentary mice from the selected lines exhibited a trend for higher muscle aerobic capacities, as indicated by higher levels of mitochondrial (cytochrome- c oxidase, carnitine palmitoyltransferase, citrate synthase, and PDH) and glycolytic (hexokinase and phosphofructokinase) enzymes, with concomitant lower anaerobic capacities, as indicated by lactate dehydrogenase (especially in male mice). Consistent with previous studies of endurance training in rats via voluntary wheel running or forced treadmill exercise, cytochrome- c oxidase, citrate synthase, and carnitine palmitoyltransferase activity increased in the wheel-access groups for both genders; hexokinase also increased in both genders. Some enzymes showed gender-specific responses: PDH and lactate dehydrogenase increased in wheel-access male but not female mice, and glycogen phosphorylase decreased in female but not in male mice. Two-way analysis of covariance revealed significant interactions between line type and activity group; for several enzymes, activities showed greater changes in mice from selected lines, presumably because such mice ran more revolutions per day and at greater velocities. Thus genetic selection for increased voluntary wheel running did not reduce the capability of muscle aerobic capacity to respond to training.

Exercise training, glucose transporters, and glucose transport in rat skeletal muscles

1992 ◽  
Vol 262 (1) ◽  
pp. C9-C14 ◽  
Author(s):  
K. J. Rodnick ◽  
E. J. Henriksen ◽  
D. E. James ◽  
J. O. Holloszy
Keyword(s):  
Glucose Transport ◽  
Endurance Exercise ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Fiber Type ◽  
Type I ◽  
Voluntary Wheel Running ◽  
Glut1 Protein ◽  
Voluntary Wheel

It was previously found that voluntary wheel running induces an increase in the insulin-sensitive glucose transporter, i.e., the GLUT4 isoform, in rat plantaris muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425-1429, 1990). The present study was undertaken to determine whether 1) the increase in muscle GLUT4 protein is associated with an increase in maximally stimulated glucose transport activity, 2) a conversion of type IIb to type IIa or type I muscle fibers plays a role in the increase in GLUT4 protein, and 3) an increase in the GLUT1 isoform is a component of the adaptation of muscle to endurance exercise. Five weeks of voluntary wheel running that resulted in a 33% increase in citrate synthase activity induced a 50% increase in GLUT4 protein in epitrochlearis muscles of female Sprague-Dawley rats. The rate of 2-deoxy-glucose transport maximally stimulated with insulin or insulin plus contractions was increased approximately 40% (P less than 0.05). There was no change in muscle fiber type composition, evaluated by myosin ATPase staining, in the epitrochlearis. There was also no change in GLUT1 protein concentration. We conclude that an increase in GLUT4, but not of GLUT1 protein, is a component of the adaptive response of muscle to endurance exercise and that the increase in GLUT4 protein is associated with an increased capacity for glucose transport.

Artificial selection for high activity favors mighty mini-muscles in house mice

2003 ◽  
Vol 284 (2) ◽  
pp. R433-R443 ◽  
Author(s):  
Philippe Houle-Leroy ◽  
Helga Guderley ◽  
John G. Swallow ◽  
Theodore Garland
Keyword(s):  
Muscle Mass ◽  
Aerobic Capacity ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Relative Mass ◽  
Selected Lines ◽  
Voluntary Wheel Running ◽  
Total Body Mass ◽  
Selection For ◽  
Voluntary Wheel

After 14 generations of selection for voluntary wheel running, mice from the four replicate selected lines ran, on average, twice as many revolutions per day as those from the four unselected control lines. To examine whether the selected lines followed distinct strategies in the correlated responses of the size and metabolic capacities of the hindlimb muscles, we examined mice from selected lines, housed for 8 wk in cages with access to running wheels that were either free to rotate (“wheel access” group) or locked (“sedentary”). Thirteen of twenty individuals in one selected line (line 6) and two of twenty in another (line 3) showed a marked reduction (∼50%) in total hindlimb muscle mass, consistent with the previously described expression of a small-muscle phenotype. Individuals with these “mini-muscles” were not significantly smaller in total body mass compared with line-mates with normal-sized muscles. Access to free wheels did not affect the relative mass of the mini-muscles, but did result in typical mammalian training effects for mitochondrial enzyme activities. Individuals with mini-muscles showed a higher mass-specific muscle aerobic capacity as revealed by the maximal in vitro rates of citrate synthase and cytochrome c oxidase. Moreover, these mice showed the highest activities of hexokinase and carnitine palmitoyl transferase. Females with mini-muscles showed the highest levels of phosphofructokinase, and males with mini-muscles the highest levels of pyruvate dehydrogenase. As shown by total muscle enzyme contents, the increase in mass-specific aerobic capacity almost completely compensated for the reduction caused by the “loss” of muscle mass. Moreover, the mini-muscle mice exhibited the lowest contents of lactate dehydrogenase and glycogen phosphorylase. Interestingly, metabolic capacities of mini-muscled mice resemble those of muscles after endurance training. Overall, our results demonstrate that during selection for voluntary wheel running, distinct adaptive paths that differentially exploit the genetic variation in morphological and physiological traits have been followed.

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