Effects of chronic swimming training on cardiac sarcolemmal function and composition

Cardiac contractile function is dependent on the integrity and function of the sarcolemmal membrane. Swimming exercise training is known to increase cardiac contractile performance. The purpose of the present study was to examine whether a swimming exercise program would alter sarcolemmal enzyme activity, ion flux, and composition in rat hearts. After approximately 11 wk of exercise training, cardiac myosin and actomyosin Ca2+-adenosinetriphosphatase (ATPase) activity was significantly higher in exercised rat hearts than in sedentary control rat hearts. Glycogen content was increased in plantaris and gastrocnemius muscles from exercised animals as was succinic dehydrogenase activity in gastrocnemius muscle of exercised rats in comparison to sedentary rat preparations. Sarcolemmal vesicles were isolated from hearts of exercise-trained and control rats. Sarcolemmal Na+-K+-ATPase and K+-p-nitrophenylphosphatase activities, Na+-Ca2+ exchange, and passive Ca2+ binding did not differ between the two groups. ATP-dependent Ca2+ uptake and 5′-nucleotidase activity were elevated in the cardiac sarcolemmal vesicles isolated from exercised animals compared with sedentary control rats. Sarcolemmal phospholipid composition was not altered by the exercise training. Our results demonstrate that swimming training in rats does not affect most parameters of cardiac sarcolemmal function or composition. However, the elevated sarcolemmal Ca2+ pump activity in exercised rats may help to reduce intracellular Ca2+ and augment cardiac relaxation rates. The enhanced 5′-nucleotidase activity may stimulate adenosine production, which could affect myocardial blood flow. The present results further our knowledge on the subcellular response of the heart to swimming training in the rat.

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Detecting Validated Intracellular ROS Generation with 18F-dihydroethidine-Based PET

Molecular Imaging and Biology ◽

10.1007/s11307-021-01683-0 ◽

2021 ◽

Author(s):

Edward C. T. Waters ◽

Friedrich Baark ◽

Zilin Yu ◽

Filipa Mota ◽

Thomas R. Eykyn ◽

...

Keyword(s):

Oxidative Stress ◽

Contractile Function ◽

Ex Vivo ◽

Glutathione Depletion ◽

Ros Generation ◽

Cardiac Contractile ◽

Rat Hearts ◽

Intracellular Ros ◽

Cardiac Contractile Dysfunction

Abstract Purpose To determine the sensitivity of the 18F-radiolabelled dihydroethidine analogue ([18F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress. Procedures The sensitivity of [18F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [18F]DHE (50–150 kBq.min−1) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress. Results [18F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [18F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation. Conclusion [18F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.

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Isolated ventricular myocytes from copper-deficient rat hearts exhibit enhanced contractile function

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.2.h476 ◽

2001 ◽

Vol 281 (2) ◽

pp. H476-H481 ◽

Cited By ~ 7

Author(s):

Loren E. Wold ◽

Jack T. Saari ◽

Jun Ren

Keyword(s):

Cardiac Fibrosis ◽

Copper Deficiency ◽

Ventricular Myocytes ◽

Contractile Function ◽

Detection System ◽

Cardiac Contractile Function ◽

Acetoxymethyl Ester ◽

Cardiac Contractile ◽

Rat Hearts ◽

Intracellular Ca

Dietary copper deficiency leads to cardiac hypertrophy, cardiac fibrosis, derangement of myofibrils, and impaired cardiac contractile and electrophysiological function. The purpose of this study was to determine whether impaired cardiac function from copper deficiency is due to depressed contractile function at the single myocyte level. Male Sprague-Dawley rats were fed diets that were either copper adequate (5.59–6.05 μg copper/g body wt; n = 11) or copper deficient (0.29–0.34 μg copper/g body wt; n = 11) for 5 wk. Ventricular myocytes were dispersed and mechanical properties were evaluated using the SoftEdge video-based edge-detection system. Intracellular Ca2+ transients were examined using fura 2-acetoxymethyl ester. Myocytes were electrically stimulated to contract at 0.5 Hz. Properties evaluated included peak shortening (PS), time to peak shortening (TPS), time to 90% relengthening (TR90), and maximal velocities of shortening and relengthening (±d L/d t). Myocytes from the copper-deficient rat hearts exhibited significantly enhanced PS values associated with shortened TR90 measurements compared with those from copper-adequate rat hearts. The ±d L/d t values were enhanced and the intracellular Ca2+ transient decay rate was depressed in myocytes from copper-deficient rats. These data indicate that impaired cardiac contractile function that is seen in copper-deficient whole hearts might not be due to depressed cardiac contractile function at the single cell level but rather to other mechanisms such as cardiac fibrosis.

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Garlic Oil Alleviates MAPKs- and IL-6-mediated Diabetes-related Cardiac Hypertrophy in STZ-induced DM Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/neq075 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 18

Author(s):

Sheng-Huang Chang ◽

Chung-Jung Liu ◽

Chia-Hua Kuo ◽

Hong Chen ◽

Wen-Yuan Lin ◽

...

Keyword(s):

Cardiac Hypertrophy ◽

Natriuretic Peptide ◽

Contractile Function ◽

Diabetic Rats ◽

Diabetic Rat ◽

Contractile Dysfunction ◽

Garlic Oil ◽

Cardiac Contractile ◽

Rat Hearts ◽

Cardiac Contractile Dysfunction

Garlic oil has been reported to protect the cardiovascular system; however, the effects and mechanisms behind the cardioprotection of garlic oil on diabetes-induced cardiaomyopathy are unclear. In this study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether garlic oil could protect the heart from diabetes-induced cardiomyopathy. Wistar STZ-induced diabetic rats received garlic oil (0, 10, 50 or 100 mg kg−1body weight) by gastric gavage every 2 days for 16 days. Normal rats without diabetes were used as control. Cardiac contractile dysfunction and cardiac pathologic hypertrophy responses were observed in diabetic rat hearts. Cardiac function was examined using echocardiography. In addition to cardiac hypertrophy-related mitogen-activated protein kinases (MAPK) pathways (e.g., p38, c-Jun N-terminal kinases (JNK) and extracellularly responsive kinase (ERK1/2)), the IL-6/MEK5/ERK5 signaling pathway was greatly activated in the diabetic rat hearts, which contributes to the up-regulation of cardiac pathologic hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), and leads to cardiac contractile dysfunction. Garlic oil treatment significantly inhibited the up-regulation in MAPK (e.g., p38, JNK and ERK1/2) and IL-6/MEK5/ERK5 signaling pathways in the diabetic rat hearts, reducing the levels of cardiac pathologic hypertrophy markers such as ANP and BNP, and improving the cardiac contractile function. Collectively, data from these studies demonstrate that garlic oil shows the potential cardioprotective effects for protecting heart from diabetic cardiomyopathy.

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Sprint training attenuates myocyte hypertrophy and improves Ca2+ homeostasis in postinfarction myocytes

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.2.544 ◽

1998 ◽

Vol 84 (2) ◽

pp. 544-552 ◽

Cited By ~ 30

Author(s):

Xue-Qian Zhang ◽

Yuk-Chow Ng ◽

Timothy I. Musch ◽

Russell L. Moore ◽

R. Zelis ◽

...

Keyword(s):

Myocardial Infarction ◽

Citrate Synthase ◽

Contractile Function ◽

Sprint Training ◽

Cardiac Contractile Function ◽

Myocyte Hypertrophy ◽

Cellular Hypertrophy ◽

Cardiac Contractile ◽

Rat Hearts ◽

Exercise Activity

Zhang, Xue-Qian, Yuk-Chow Ng, Timothy I. Musch, Russell L. Moore, R. Zelis, and Joseph Y. Cheung. Sprint training attenuates myocyte hypertrophy and improves Ca2+ homeostasis in postinfarction myocytes. J. Appl. Physiol. 84(2): 544–552, 1998.—Myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) had decreased Na+/Ca2+exchange currents ( I Na/Ca; 3 Na+ out:1 Ca2+ in) and sarcoplasmic reticulum (SR)-releasable Ca2+contents. These defects in Ca2+regulation may contribute to abnormal contractility in MI myocytes. Because exercise training elicits positive adaptations in cardiac contractile function and myocardial Ca2+ regulation, the present study examined whether 6–8 wk of high-intensity sprint training (HIST) would ameliorate some of the cellular maladaptations observed in post-MI rats with limited exercise activity (Sed). In MI rats, HIST did not affect citrate synthase activities of plantaris muscles but significantly increased the percentage of cardiac α-myosin heavy chain (MHC) isoforms (57.2 ± 1.9 vs. 49.3 ± 3.5 in MI-HIST vs. MI-Sed, respectively; P ≤ 0.05). At the single myocyte level, HIST attenuated cellular hypertrophy observed post-MI, as evidenced by reductions in cell lengths (112 ± 4 vs. 130 ± 5 μm in MI-HIST vs. MI-Sed, respectively; P ≤ 0.005) and cell capacitances (212 ± 8 vs. 242 ± 9 pF in MI-HIST vs. MI-Sed, respectively; P ≤ 0.015). Reverse I Na/Ca was significantly lower ( P ≤ 0.0001) in myocytes from MI-Sed rats compared with those from rats that were sham operated and sedentary. HIST significantly increased reverse I Na/Ca( P ≤ 0.05) without affecting the amount of Na+/Ca2+exchangers (detected by immunoblotting) in MI myocytes. SR-releasable Ca2+ content, as estimated by integrating forward I Na/Ca during caffeine-induced SR Ca2+ release, was also significantly increased ( P ≤ 0.02) by HIST in MI myocytes. We conclude that the enhanced cardiac output and stroke volume in post-MI rats subjected to HIST are mediated, at least in part, by reversal of cellular maladaptations post-MI.

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Prolonged responsiveness to ouabain in hypertrophied rat heart: physiological and biochemical evidence

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1986.250.6.h923 ◽

1986 ◽

Vol 250 (6) ◽

pp. H923-H931 ◽

Cited By ~ 3

Author(s):

L. G. Lelievre ◽

J. M. Maixent ◽

P. Lorente ◽

C. Mouas ◽

D. Charlemagne ◽

...

Keyword(s):

Rat Heart ◽

Contractile Function ◽

Relative Proportion ◽

Pressure Overload ◽

Inotropic Effect ◽

Inotropic Response ◽

Rat Hearts ◽

Heart Preparation ◽

Low Sensitivity ◽

Sarcolemmal Vesicles

The inotropic effect of ouabain on cardiac hypertrophy was evaluated on an isolated Langendorff rat heart preparation with performances registrated by means of an intraventricular balloon. These effects were compared with the drug action on the sarcolemma-bound Na+-K+-ATPase activity. On both normal and pressure-overload induced hypertrophied rat hearts (ventricular wt-to-body wt ratios of 2.1 and 3.3, respectively) the inotropic effect of ouabain (10(-9)-10(-4) M) was evaluated at 0.25 mM external Ca2+. Compared with normal hearts, the recovery of a normal contractile function after the inotropic response was significantly slower in hypertrophied hearts. This was valid with the two protocols applied. During a 30-min washout period, the inotropic response remained nearly unchanged in hypertrophied hearts, whereas it was almost completely reversed in control groups. Sarcolemmal vesicles from both heart groups exhibited high Na+-K+-ATPase activities (sp. act.: 105 +/- 16 mumol X h-1 X mg-1). In both normal and hypertrophied cardiac sarcolemmal preparations, the Na+-K+-ATPase was heterogeneous, with high- and low-sensitivity forms. Their relative proportion was two-to-one. In both heart groups, their respective apparent affinities for ouabain were similar (inhibitory concentration of 50% = 10(-8) and 10(-6) M, respectively). The release of ouabain from these two sites was measured, in washout experiments, by the rates of enzyme relief from inhibition. High- and low-sensitivity forms in hypertrophied heart preparations released ouabain at seven- and threefold lower rates, respectively, than the corresponding forms present in normal cardiac sarcolemmal vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effects of ischemic metabolites and chronic exercise on cardiac myocyte function

10.32469/10355/4150 ◽

2005 ◽

Author(s):

◽

Aaron C. Hinken

Keyword(s):

Exercise Training ◽

Cardiac Function ◽

Cardiac Myocyte ◽

Striated Muscle ◽

Contractile Function ◽

Work Capacity ◽

Altered Expression ◽

Cardiac Contractile ◽

Generating Capacity ◽

Cardiac Contractile Dysfunction

During times of low blood flow (ischemia), concentrations of wastes increase in tissues, which can lead to decreased striated muscle contractile function. Acute cardiac contractile dysfunction during ischemia is likely mediated by build-up of inorganic phosphate (P[i]) and protons (i.e., decreased pH). The focus of this dissertation is examination of the myofibrillar mechanisms by which ischemic metabolites alter the work capacity of cardiac myocytes, which ultimately comprise ventricular pump function. In addition, contractile properties and changes thereto with metabolite concentration were investigated in myocytes expressing either of the two isoforms of myosin heavy chain (ÃŒ-MyHC and Î³-MyHC), that show altered expression in response to chronic ischemia. Studies demonstrated differential response to metabolites with P[i] and Hâº alone and together decreasing power generating capacity of ÃŒ-MyHC while only in combination did they diminished Î³-MyHC myocyte power. The greater tolerance toward ischemic conditions in Î³-MyHC myocytes was attributed to a P[i] and Hâº induced increase in the velocity of loaded shortening. In contrast to ischemia, changes following exercise training are thought to improve cardiac function. A pig model of exercise training was examined to determine if changes intrinsic to the myofilaments were partially responsible for changes in global cardiac function. Increased peak power generating capacity was observed in myocytes from exercise trained animals as compared to sedentary controls, which coincided with an increase in PKA-induced phosphorylation of myofibrillar proteins. Overall, these results provide evidence for myofibrillar mechanisms that, in part, underlie changes in myocardial performance associated with acute and chronic ventricular stress.

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Sprint training normalizes Ca2+ transients and SR function in postinfarction rat myocytes

Journal of Applied Physiology ◽

10.1152/jappl.2000.89.1.38 ◽

2000 ◽

Vol 89 (1) ◽

pp. 38-46 ◽

Cited By ~ 28

Author(s):

Lian-Qin Zhang ◽

Xue-Qian Zhang ◽

Yuk-Chow Ng ◽

Lawrence I. Rothblum ◽

Timothy I. Musch ◽

...

Keyword(s):

Myocardial Infarction ◽

Sarcoplasmic Reticulum ◽

Contractile Function ◽

Half Time ◽

Sprint Training ◽

Cardiac Contractile Function ◽

Cardiac Contractile ◽

Rat Hearts ◽

Intracellular Ca ◽

Rat Myocytes

Previous studies have shown that myocytes isolated from sedentary (Sed) rat hearts 3 wk after myocardial infarction (MI) undergo hypertrophy, exhibit altered intracellular Ca2+ concentration ([Ca2+]i) dynamics and abnormal contraction, and impaired sarcoplasmic reticulum (SR) function manifested as prolonged half-time of [Ca2+]idecline. Because exercise training elicits positive adaptations in cardiac contractile function and myocardial Ca2+ regulation, the present study examined whether 6–8 wk of high-intensity sprint training (HIST) would restore [Ca2+]i dynamics and SR function in MI myocytes toward normal. In MI rats, HIST ameliorated myocyte hypertrophy as indicated by significant ( P ≤ 0.05) decreases in whole cell capacitances [Sham-Sed 179 ±12 ( n = 20); MI-Sed 226 ± 7 ( n = 20); MI-HIST 183 ± 11 pF ( n = 19)]. HIST significantly ( P < 0.0001) restored both systolic [Ca2+]i [Sham-Sed 421 ± 9 ( n = 79); MI-Sed 350 ± 6 ( n = 70); MI-HIST 399 ± 9 nM ( n = 70)] and half-time of [Ca2+]i decline (Sham-Sed 0.197 ± 0.005; MI-Sed 0.247 ± 0.006; MI-HIST 0.195 ± 0.006 s) toward normal. Compared with Sham-Sed myocytes, SR Ca2+-ATPase expression significantly ( P < 0.001) decreased by 44% in MI-Sed myocytes. Surprisingly, expression of SR Ca2+-ATPase was further reduced in MI-HIST myocytes to 26% of that measured in Sham-Sed myocytes. There were no differences in calsequestrin expression among the three groups. Expression of phospholamban was not different between Sham-Sed and MI-Sed myocytes but was significantly ( P < 0.01) reduced in MI-HIST myocytes by 25%. Our results indicate that HIST instituted shortly after MI improves [Ca2+]idynamics in surviving myocytes. Improvement in SR function by HIST is mediated not by increased SR Ca2+-ATPase expression, but by modulating phospholamban regulation of SR Ca2+-ATPase activity.

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When one says yes and the other says no: Does calcineurin participate in physiologic cardiac hypertrophy?

AJP Advances in Physiology Education ◽

10.1152/advan.00104.2021 ◽

2021 ◽

Author(s):

Jonathan A. Ritchie ◽

Jun Quan Ng ◽

Ole J. Kemi

Keyword(s):

Exercise Training ◽

Cognitive Processing ◽

Myocardial Hypertrophy ◽

Contractile Function ◽

Real Life ◽

Current Evidence ◽

Cardiac Contractile Function ◽

Cardiac Contractile ◽

Underlying Mechanisms ◽

Response To Exercise

Developing engaging activities that build skills for understanding and appreciating research is important for undergraduate and postgraduate science students. Comparing and contrasting opposing research studies does this, and more: it also appropriately for these cohorts challenges higher-level cognitive processing. Here, we present and discuss one such scenario, that of calcineurin in the heart and its response to exercise training. This scenario is further accentuated by the existence of only 2 studies. The background is that regular aerobic endurance exercise training stimulates the heart to physiologically adapt to chronically increase its ability to produce a greater cardiac output to meet the increased demand for oxygenated blood in working muscles, and this happens by 2 main mechanisms: 1) increased cardiac contractile function and 2) physiologic hypertrophy. The major underlying mechanisms have been delineated over the last decades, but one aspect has not been resolved: the potential role of calcineurin in modulating physiologic hypertrophy. This is partly because the existing research has provided opposing and contrasting findings, one line showing that exercise training does activate cardiac calcineurin in conjunction with myocardial hypertrophy, but another line showing that exercise training does not activate cardiac calcineurin even if myocardial hypertrophy is blatantly occurring. Here, we review and present the current evidence in the field and discuss reasons for this controversy. We present real-life examples from physiology research and discuss how this may enhance student engagement and participation, widen the scope of learning, and thereby also further facilitate higher-level cognitive processing.

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