P6341Impact of left-ventricular hemodynamics on treadmill exercise intolerance in conscious rats: pilot evaluation in animals with diastolic dysfunction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B S Ferguson ◽  
N Bennett ◽  
C Zambataro ◽  
R Shimkunas ◽  
C L Del Rio
Keyword(s):  
Heart Rate ◽  
Blood Glucose ◽  
Diastolic Dysfunction ◽  
Exercise Capacity ◽  
Acute Exercise ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Exercise Intolerance ◽  
Volitional Exhaustion

Abstract Introduction Exercise intolerance is a clinical hallmark of patients with hypertrophic cardiomyopathy and/or impaired diastolic function. Elevated LV filling pressures, particularly in response to acute exercise bouts, are thought to play a role limiting exercise capacity in ventricles with abnormal relaxation/compliance. However, it is experimentally difficult to obtain in vivo hemodynamic measures necessary for the evaluation of centrally mediated dysfunction. Leveraging radio-telemetry, we evaluated central hemodynamic parameters as mediators of exercise intolerance in obese ZSF1 rats with diabetes, hypertension, and diastolic dysfunction. Methods Both ZSF1 (637+12g, n=8) and age-matched (28 weeks) healthy control (CTRL, 543+14g, n=4, P<0.05) rats were instrumented for telemetric left-ventricular pressure (LVP) recordings. Following surgical recovery rats were familiarized to treadmill running and subsequently challenged with an exercise protocol aimed at increasing heart rate by 200 beats/min (5° incline, 15 m/min, increased by 3 m/min every 2-min) until volitional exhaustion. LV pressures were collected continuously during cage resting, treadmill resting, and post-exercise until heart rate returned to baseline. Additionally, resting echocardiographic and blood glucose measures were collected. Results At rest, ZSF1 rats had preserved ejection fraction (73+6 vs 79+9%), elevated (P<0.05) blood glucose (237+83 vs 94+23 mg/dL), end-systolic (147+18 vs 103+13 mmHg), and end-diastolic pressures (16+3 vs 9+3 mmHg), with preserved indexed end-diastolic volumes (670+95 vs 741+89 μL/kg), suggesting impaired diastolic compliance. ZSF1 rats terminated exercise prematurely (8:26+1:20 vs 10:27+1:18 min, P<0.05), indicating a limitation in exercise capacity. This early volitional exhaustion was noted while end-diastolic pressures were not further increased (17+7 mmHg), suggesting that other pathological derangement may play a role modulating exercise capacity. For instance, ZSF1 rats tended to have a blunted increase in the systolic index dP/dt40 (+2589+1450 vs +3938+749 mmHg/s, P<0.1) despite achieving comparable increases in HR (193+34 vs 196+38 bpm) with exercise. Conclusion This pilot study demonstrates the feasibility for evaluation of left-ventricular hemodynamics during exercise in rodents with diastolic dysfunction, establishing a platform to evaluate both the mechanisms of exercise intolerance as well as potential therapeutic approaches to rescue exercise capacity. Acknowledgement/Funding MyoKardia

Effects of hyperthyroidism on muscle blood flow during exercise in rats

1995 ◽  
Vol 268 (1) ◽  
pp. H330-H335 ◽  
Author(s):  
R. M. McAllister ◽  
J. C. Sansone ◽  
M. H. Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Citrate Synthase ◽  
Muscle Blood Flow ◽  
Left Ventricular ◽  
Submaximal Exercise ◽  
Treadmill Running ◽  
Exercise Intolerance ◽  
Blood Flows

Hyperthyroidism is associated with exercise intolerance. Previous research, however, has shown that cardiac output is either normal or enhanced during exercise in the hyperthyroid state. We therefore hypothesized that blood flow to working skeletal muscle is augmented in hyperthyroid animals during in vivo submaximal exercise and, consequently, that noncardiovascular factors are responsible for intolerance to exercise. To test this hypothesis, rats were made hyperthyroid (Hyper) over 6–12 wk with injections of triiodothyronine (300 micrograms/kg). Hyperthyroidism was evidenced by left ventricular hypertrophy [euthyroid (Eut), 2.12 +/- 0.05 mg/g body wt; Hyper, 2.78 +/- 0.06; P < 0.005], 25–60% increases in citrate synthase activities in Hyper hindlimb muscles over those of Eut rats, and higher preexercise heart rates (Eut, 415 +/- 18 beats/min; Hyper, 479 +/- 19; P < 0.025). Regional blood flows were determined by the radiolabeled microsphere method, preexercise, and at 1–2 min of treadmill running at 15 m/min (0% grade). Total hindlimb muscle blood flow preexercise was unaffected (Eut, 31 +/- 4 ml.min-1.(100) g-1, n = 11; Hyper, 40 +/- 6, n = 9; not significant) but was higher (P < 0.025) in Hyper (127 +/- 17, n = 9) compared with Eut (72 +/- 11, n = 9) during treadmill running. During exercise, flows to individual muscles and muscle sections were approximately 50–150% higher in Hyper compared with Eut rats. Visceral blood flows were largely similar between groups. These findings indicate that hyperthyroidism is associated with augmented blood flow to skeletal muscle during submaximal exercise. Thus hypoperfusion of skeletal muscle does not account for the poor exercise tolerance characteristic of hyperthyroidism.

Abstract 2199: Left Ventricular Diastolic Function Impacts Age Based Differences in Exercise Capacity

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jasmine Grewal ◽  
Robert B McCully ◽  
Carolyn S Lam ◽  
Garvan C Kane ◽  
Patricia A Pellikka
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Exercise Capacity ◽  
Multivariate Analyses ◽  
Large Population ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Exercise Echocardiography ◽  
Clinical Predictors ◽  
The Impact

Limited information exists regarding the echocardiographic and clinical predictors of exercise capacity and their effects on exercise with advancing age or by sex. We hypothesized that LV diastolic function (DF) impacts exercise capacity to a greater degree with advancing age. This was a prospective cohort study of consecutive patients undergoing routine exercise echocardiography with the Bruce protocol (n=2955). DF assessments at rest and exercise were performed. Those with echocardiographic exercise-induced ischemia and significant valvular disease were excluded. Univariate and multivariate analyses were conducted to determine the strongest echocardiographic and clinical predictors of exercise capacity (METs). Results were reported as unstandardized β coefficient (Standard Error) as outlined beside each variable. Age and sex interactions of these predictors with exercise capacity were determined. The strongest independent multivariate predictors of exercise capacity were female vs. male sex [−1.98 (0.07), p<0.0001], body mass index >30 kg/m 2 [−1.24 (0.08), p<0.0001], age per 10 year increment [−0.85 (0.01), p<0.0001], mild resting diastolic dysfunction vs. normal [−0.70 (0.10), p<0.0001], and moderate/severe resting diastolic dysfunction vs. normal [−1.3 (0.13), p<0.0001]. LV filling pressures measured by a resting E/e’ ≥ 15 [−0.42 (0.14), p=0.004] or exercise E/e’≥ 15 [−0.31 (0.14), p<0.0001] similarly predicted a reduction in exercise capacity, each in separate multivariate analyses. The impact of impaired relaxation and left ventricular filling pressures on exercise capacity increased with advancing age (p<0.001 and p=0.02 respectively), and was most marked after age 50. These predictors had a similar negative effect on exercise capacity among men and women (p=NS). In conclusion, in this large population referred for exercise echocardiography and not limited by ischemia, resting DF and resting/exercise LV filling pressures independently predicted exercise capacity. The increasingly potent effect of impaired relaxation and exercise LV filling pressures with advancing age suggest that DF plays an important role in the development of exercise intolerance in the elderly.

Effects of forskolin on inotropic performance and phospholamban phosphorylation in exercise-trained hypertensive myocardium

2007 ◽  
Vol 102 (2) ◽  
pp. 628-633 ◽  
Author(s):  
Stephen C. Kolwicz ◽  
Hajime Kubo ◽  
Scott M. MacDonnell ◽  
Steven R. Houser ◽  
Joseph R. Libonati
Keyword(s):  
Heart Rate ◽  
Adenylyl Cyclase ◽  
Spontaneously Hypertensive Rat ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Chronic Hypertension ◽  
Wistar Kyoto ◽  
Developed Pressure ◽  
Phospholamban Phosphorylation

β-Adrenergic receptor (β-AR) responsiveness is downregulated in left ventricular (LV) hypertrophy induced by chronic hypertension. While exercise training in hypertension enhances β-AR responsiveness, the role of adenylyl cyclase remains unclear. The purpose of the present study was to test whether treadmill running in the spontaneously hypertensive rat (SHR) model improves LV responsiveness to forskolin (FOR) or the combination of FOR + isoproterenol (FOR+ISO). Female SHR (16-wk) were randomly placed into sedentary (SHR-SED; n = 7) or treadmill-trained (SHR-TRD; n = 8) groups. Wistar-Kyoto (WKY; n = 7) animals acted as normotensive controls. Langendorff, isovolumic LV performance was established at baseline and during incremental FOR infusion (1 and 5 μmol/l) and FOR+ISO (5 μmol/l + 1×10−8 mol/l). Heart rate, systolic blood pressure, and heart-to-body weight ratio were lower in WKY relative to both SHR groups ( P < 0.05). LV performance and heart rate significantly increased in all groups to a similar extent with incremental FOR infusion. However, in the presence of 5 μmol/l FOR, ISO increased LV developed pressure, positive change in LV pressure, and negative change in LV pressure to a greater extent in SHR-TRD relative to SHR-SED ( P < 0.05). Phospholamban phosphorylation at the Thr17 was greater in SHR-TRD relative to SHR-SED and WKY ( P < 0.05). Absolute LV developed pressure was moderately correlated with phospholamban phosphorylation at both the Ser16 ( r = 0.64; P < 0.05) and Thr17 ( r = 0.52; P < 0.05). Our data suggest that the adenylyl cyclase step in the β-AR cascade is not downregulated in the early course of hypertension and that the enhanced β-AR responsiveness with training is likely mediated at levels other than adenylyl cyclase. Our data also suggest that β-AR inotropic responsiveness in the presence of direct adenylyl cyclase agonism is improved in trained compared with sedentary SHR hearts.

Abstract 215: The Role of Titin in Cardiac Function: Studies in Two Genetically Engineered Mouse Models With Disparate Titin’s Size

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Mei Methawasin ◽  
Kirk R Hutchinson ◽  
John E Smith ◽  
Henk L Granzier
Keyword(s):  
Mouse Model ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Exercise Capacity ◽  
Mouse Models ◽  
Wheel Running ◽  
Left Ventricular ◽  
Genetically Engineered ◽  
Passive Stiffness ◽  
Genetically Engineered Mouse Models

Titin, a myofilament that acts as a molecular spring in the sarcomere, is considered the main contributor to passive stiffness of cardiomyocytes and is responsible for cardiac diastolic function. Increased titin stiffness is related to diastolic dysfunction and HFpEF (Heart Failure with preserved Ejection Fraction). Alteration in size of titin’s spring region leads to changes in cardiomyocyte and left ventricular (LV) chamber stiffness. We tested the effect of alteration in titin’s size in two genetically engineered mouse models. We investigated the effect of shortening titin’s spring region in a mouse model in which I-band/A-band region of titin’s spring has been deleted (TtnΔIAjxn ), in comparison to the effect of lengthening titin’s spring region in a mouse model deficient in titin splicing factor (Rbm20ΔRRM). Integrative approaches were used from single cardiomyocyte mechanics to pressure-volume analysis and exercise study. Study of skinned LV cardiomyocytes revealed that cellular passive stiffness was inversely related to the size of titin. Cellular passive stiffness was increased in TtnΔIAjxn homozygous (-/-) (~ 110 % higher than wildtype (WT)) and was reduced in a graded manner in Rbm20ΔRRM heterozygous (+/-) and -/- cardiomyocytes (~61% and ~87% less than WT). This effect was carried through at the LV chamber level which could be demonstrated in pressure volume (PV) analysis as an increased end-diastolic pressure-volume relationship (EDPVR) in TtnΔIAjxn -/- (~110% higher than WT’s hearts) and reduced EDPVR in Rbm20ΔRRM +/- and -/- (~57% and ~48% less than WT’s hearts). Free-wheel running studies revealed a running deficiency in TtnΔIAjxn -/- mice but an increase in exercise capacity in Rbm20ΔRRM +/– mice. Conclusions: Functional studies from the cellular to in-vivo LV chamber levels showed that mice with shortening of titin’s spring region had increased LV stiffness, diastolic dysfunction and reduced exercise capacity, while mice with lengthening titin’s spring region had compliant LV and increased exercise capacity. Thus, our work supports titin’s important roles in LV diastolic function and suggests that modification of the size of titin’s spring region could be a potential therapeutic strategy for HFpEF.

Verification phase as a useful tool in the determination of the maximal oxygen uptake of distance runners

2006 ◽  
Vol 31 (5) ◽  
pp. 541-548 ◽  
Author(s):  
Adrian W. Midgley ◽  
Lars R. McNaughton ◽  
Sean Carroll
Keyword(s):  
Heart Rate ◽  
Oxygen Uptake ◽  
Maximal Oxygen Uptake ◽  
Peak Oxygen Uptake ◽  
Treadmill Running ◽  
Distance Runners ◽  
Peak Heart Rate ◽  
Incremental Test ◽  
Volitional Exhaustion

This study investigated the utility of a verification phase for increasing confidence that a “true” maximal oxygen uptake had been elicited in 16 male distance runners (mean age (±SD), 38.7  (± 7.5 y)) during an incremental treadmill running test continued to volitional exhaustion. After the incremental test subjects performed a 10 min recovery walk and a verification phase performed to volitional exhaustion at a running speed 0.5 km·h–1 higher than that attained during the last completed stage of the incremental phase. Verification criteria were a verification phase peak oxygen uptake ≤ 2% higher than the incremental phase value and peak heart rate values within 2 beats·min–1 of each other. Of the 32 tests, 26 satisfied the oxygen uptake verification criterion and 23 satisfied the heart rate verification criterion. Peak heart rate was lower (p = 0.001) during the verification phase than during the incremental phase, suggesting that the verification protocol was inadequate in eliciting maximal values in some runners. This was further supported by the fact that 7 tests exhibited peak oxygen uptake values over 100 mL·min–1 (≥ 3%) lower than the peak values attained in the incremental phase. Further research is required to improve the verification procedure before its utility can be confirmed.

Role of Diastole in Left Ventricular Function, II: Diagnosis and Treatment

2004 ◽  
Vol 13 (6) ◽  
pp. 453-466 ◽  
Author(s):  
Shannan K. Hamlin ◽  
Penelope S. Villars ◽  
Joseph T. Kanusky ◽  
Andrew D. Shaw
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Left Atrial ◽  
Diastolic Heart Failure ◽  
Systolic Heart Failure ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Radiographic Findings ◽  
Ventricular Compliance

Left ventricular diastolic dysfunction plays an important role in congestive heart failure. Although once thought to be lower, the mortality of diastolic heart failure may be as high as that of systolic heart failure. Diastolic heart failure is a clinical syndrome characterized by signs and symptoms of heart failure with preserved ejection fraction (0.50) and abnormal diastolic function. One of the earliest indications of diastolic heart failure is exercise intolerance followed by fatigue and, possibly, chest pain. Other clinical signs may include distended neck veins, atrial arrhythmias, and the presence of third and fourth heart sounds. Diastolic dysfunction is difficult to differentiate from systolic dysfunction on the basis of history, physical examination, and electrocardiographic and chest radiographic findings. Therefore, objective diagnostic testing with cardiac catheterization, Doppler echocardiography, and possibly measurement of serum levels of B-type natriuretic peptide is often required. Three stages of diastolic dysfunction are recognized. Stage I is characterized by reduced left ventricular filling in early diastole with normal left ventricular and left atrial pressures and normal compliance. Stage II or pseudonormalization is characterized by a normal Doppler echocardiographic transmitral flow pattern because of an opposing increase in left atrial pressures. This normalization pattern is a concern because marked diastolic dysfunction can easily be missed. Stage III, the final, most severe stage, is characterized by severe restrictive diastolic filling with a marked decrease in left ventricular compliance. Pharmacological therapy is tailored to the cause and type of diastolic dysfunction.

Assessment and clinical relevance of the dynamic parameters of ventricular repolarization in patients with grade I left ventricular diastolic dysfunction

2019 ◽  
Vol 97 (6) ◽  
pp. 577-580
Author(s):  
Antoinette Oliveira Blackman ◽  
José Sobral Neto ◽  
Melchior Luiz Lima ◽  
Tânia Maria Andrade Rodrigues ◽  
Otoni Moreira Gomes
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Diastolic Dysfunction ◽  
Qt Dispersion ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Ventricular Repolarization ◽  
Premature Ventricular Complex ◽  
Increased Risk ◽  
Ventricular Diastolic Dysfunction

Imbalance in ventricular repolarization parameters are related to increased risk of severe arrhythmia and sudden cardiac death. There is limited research regarding markers to detect patients at risk in this early stage. We aimed to assess the influence of grade I left ventricular diastolic dysfunction on repolarization parameters in asymptomatic patients. Ambulatory patients with grade I left ventricular diastolic dysfunction were studied and compared with a control group. We assessed the QT dispersion circadian variation, heart rate variability in the time and frequency domains, and dynamics of QT using a 12-lead Holter. In the diastolic dysfunction group, 8 (30%) patients had QT dispersion > 80 ms. One (3.8%) patient presented premature ventricular complex > 10/h. The comparison between the 2 groups showed that the difference between the standard deviation of normal-to-normal intervals and low frequency power in both groups was statistically significant. We therefore conclude that increased parameters of ventricular repolarization and depressed heart rate variability reflect an imbalance in autonomic responses in patients with grade I left ventricular diastolic dysfunction without cardiovascular symptoms, enabling the identification of patients that are at a higher risk for cardiovascular events.

Skeletal muscle and cardiac changes with training in patients with angina pectoris

1982 ◽  
Vol 243 (5) ◽  
pp. H830-H836 ◽  
Author(s):  
R. J. Ferguson ◽  
A. W. Taylor ◽  
P. Cote ◽  
J. Charlebois ◽  
Y. Dinelle ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Heart Rate ◽  
Oxygen Consumption ◽  
Angina Pectoris ◽  
Exercise Capacity ◽  
Left Ventricular ◽  
Exercise Heart Rate ◽  
Type I ◽  
Muscle Adaptations ◽  
Skeletal Muscle Adaptations

Cardiovascular and skeletal muscle adaptations were studied before and after 6 mo of physical training in patients with coronary artery disease and exertional angina pectoris. Symptom-limited exercise capacity increased by 41% (470 +/- 30 to 665 +/- 35 kg.m.min-1; n = 29, P less than 0.001) with training as did skeletal muscle succinate dehydrogenase activity (1.75 +/- 0.24 to 3.31 +/- 0.24 IU; n = 23, P less than 0.001) and the areas of muscle fibers (type I from 43.6 +/- 3.3 to 54.4 +/- 3.3 micrometers 2 X 10(2); n = 21, P less than 0.05 and type II from 43.9 +/- 2.4 to 57.2 +/- 5.1 micrometers 2 X 10(2); P less than 0.01). At the same submaximal exercise intensity (mean 355 +/- 100 km.m.min-1), plasma catecholamines (1.31 +/- 0.14 to 1.07 +/- 0.09 ng.ml-1; n = 13, P less than 0.05), heart rate (115 +/- 3 to 97 +/- 3 beats/min; n = 29, P less than 0.001), and systolic blood pressure (171 +/- 4 to 143 +2- 4 mmHg; n = 29, P less than 0.001) were significantly reduced after training. Maximal coronary sinus blood flow (192 +/- 10 to 208 +/- 9 ml.min-1; n = 29, P less than 0.05) and left ventricular oxygen consumption (23.2 +/- 1.5 to 25.8 +/- 1.6 ml.min-1; n = 24, P less than 0.05) were increased by 8 and 11%, respectively, after training. The improvement in exercise capacity with training in patients with exercise is secondary to a reduction in myocardial oxygen requirements during subangina levels of exercise and partly to a small increase in maximal myocardial oxygen consumption. The skeletal muscle adaptations with training were not related to other indices of training such as the reduced exercise heart rate or increased symptom-limited exercise capacity.

scholarly journals Sustained Liver Glucose Release in Response to Adrenaline Can Improve Hypoglycaemic Episodes in Rats under Food Restriction Subjected to Acute Exercise

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Lucas K. R. Babata ◽  
Maria M. D. Pedrosa ◽  
Rosângela F. Garcia ◽  
Márcia V. Peicher ◽  
Vilma Aparecida Ferreira de Godoi
Keyword(s):  
Blood Glucose ◽  
Food Restriction ◽  
Acute Exercise ◽  
Severe Hypoglycaemia ◽  
Exercise Session ◽  
Glucose Release ◽  
Blood Glucose Profile ◽  
Liver Glycogenolysis ◽  
Liver Response

Background. As the liver is important for blood glucose regulation, this study aimed at relating liver glucose release stimulated by glucagon and adrenaline toin vivoepisodes of hypoglycaemia.Methods. The blood glucose profile during an episode of insulin-induced hypoglycaemia in exercised and nonexercised male Wistar control (GC) and food-restricted (GR, 50%) rats and liver glucose release stimulated by glucagon and adrenaline were investigated.Results. In the GR, the hypoglycaemic episodes showed severe decreases in blood glucose, persistent hypoglycaemia, and less complete glycaemic recovery. An exercise session prior to the episode of hypoglycaemia raised the basal blood glucose, reduced the magnitude of the hypoglycaemia, and improved the recovery of blood glucose. In fed animals of both groups, liver glucose release was activated by glucagon and adrenaline. In fasted GR rats, liver glycogenolysis activated by glucagon was impaired, despite a significant basal glycogenolysis, while an adrenaline-stimulated liver glucose release was recorded.Conclusions. The lack of liver response to glucagon in the GR rats could be partially responsible for the more severe episodes of hypoglycaemia observedin vivoin nonexercised animals. The preserved liver response to adrenaline can partially account for the less severe hypoglycaemia in the food-restricted animals after acute exercise.

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