Document Type : Original Article

Authors

Tbilisi State Medical University, 33Vazha-Pshavela Ave, Tbilisi, Georgia

Abstract

The objective of this study was to explore the alterations in end-systolic and end-diastolic volumes of the left ventricle in 12-13-week-old rats subjected to a six-week regimen of dosed swimming exercise. Swimming exercise in rats is widely acknowledged as a reliable method to study cardiac parameters and the adaptive capacity of the heart. In our investigation, we engaged 12-13-week-old male rats in a six-week dosed swimming exercise program, followed by weekly echocardiographic assessments to monitor changes in systolic and diastolic volumes of the left ventricle. We studied the echocardiographic data of the rats to evaluate the changes dynamics in systolic and diastolic volumes of the left ventricle in the study groups. The rats were divided into two groups: (1) a control group, which did not receive any load (n=6); and (2) a study group, undergoing daily 60-minute swimming exercises for six weeks with a load equivalent to 4% of their body weight attached to their tails (n=6). Significant changes in left ventricular volumes were observed solely in the study group, which endured 60 minutes of exercise with a 4% body mass load. This research marks a significant stride forward in understanding the pathogenic mechanisms influencing heart rhythm, particularly those arising from physical exertion and pathological shifts in the systolic and diastolic volumes of the left ventricle.

Graphical Abstract

Alterations in Left Ventricular End-Systolic and End-Diastolic Volumes in 12-13-Week-Old Laboratory Rats Subjected to Dosed Swimming Exercise

Keywords

Introduction

In response to various stimuli, along with other adaptive mechanisms, the heart has developed an ability to modulate the systolic and diastolic volumes of the left ventricle as an adaptive mechanism against damaging factors [1-4]. This alteration in contraction strength and volume occurs in response to both pathological conditions (e.g., valvular defects and cardiomyopathies) and physiological stimuli, such as dosed loading with physical exercise [5-7]. The molecular basis for changes in heart rhythm and left ventricular volumes remains partially unclear, with some authors suggesting the interplay of genetic and environmental factors [8-10]. Dosed long-term exercise in rats elicits changes in key cardiological parameters such as left ventricular systolic and diastolic volumes, cardiac output, left ventricular weight, and ventricular wall thickness [11-13]. The heart's adaptive response to physical exertion hinges on the intensity, duration, and variations in left ventricular systolic and diastolic volumes [14-16]. Swimming exercise is considered as an optimal physiological trigger for studying alterations in rat cardiac parameters [17, 18]. In our study, we subjected 12-13-week-old male rats to a 6-week dosed swimming exercise regimen and conducted weekly echocardiographic monitoring [19, 20].

Materials and Methods

Our research material consisted of 12-13-week-old male rats (n=12), which were housed under standard conditions (12-hour light/dark cycle, 22 °C temperature, feeding according to a specific diet [15], and unlimited water access). The loading was administered during the rats' dark phase circadian rhythm (07:00-19:00 in our study). The rats were divided into two groups: (1) a control group that did not undergo any load (n=6); and (2) a study group that was subjected to a daily 60-minute swimming exercise for 6 weeks, with a load equivalent to 4% of their body weight attached to their tails. All procedures carried out on the rats complied with internationally recognized guidelines and ethical norms.

All rats were weighed weekly to accurately assess weight fluctuations and calculate the weight to be attached to the rat's tail during swimming (4% of body weight).

Control group rats were placed in the swimming apparatus thrice weekly, ensuring the environment emulated the one designated for the study rats. Weekly monitoring was conducted using an echocardiograph specifically designed for experimental animals, adhering to international guidelines for rat echocardiographic research [21 ,22].

The animal studies adhered to the bioethics protocols provided by the World Medical Association's Helsinki Declaration of 2013.

Statistical analysis

Data from the study were analyzed using specialized software. Metrics from each of the two groups in the study were independently evaluated before conducting a comparative analysis.

Results and Discussion

The study investigated the effect of prolonged physical exertion on the cardiac adaptation capabilities of 12-13-week-old male rats, with a specific focus on alterations in the left ventricular systolic and diastolic volumes. The participating rats, which had an average weight of 250 g, were subjected to a six-week regimen of swimming exercise, with a load equivalent to 4% of their body weight for 60 minutes daily.

The obtained results demonstrate a consistent decrease in both diastolic and systolic volumes of the left ventricle in all rats over the six-week period. The control group's decline appeared more gradual, while the study group, subjected to a sustained exercise load equivalent to 4% of their body weight, exhibited a more pronounced decrease.

When comparing the two groups, the control group had a relatively stable reduction trend in the left ventricular diastolic volume (Figures 1 and 2). For example, Rat 1 in the control group showed an average weekly reduction of 0.075 ml, while Rat 1 from the study group displayed a more rapid decrease, averaging about 0.108 ml per week (Table 1 and 2).

An identical trend was observed in the systolic volume changes (Figures 3 and 4). Here, the weekly average decrease for Rat 1 in the control group was around 0.04 ml, while Rat 1 from the study group had a more significant average decrease of 0.073 mL (Table 3 and 4).

Conclusion

The present study underscores the potential of dosed swimming exercise in driving alterations in left ventricular systolic and diastolic volumes in 12-13-week-old male rats. Following a six-week regimen of daily, 60-minute swimming exercise, carrying a load equivalent to 4% of their body weight, the experimental group exhibited significant changes in their left ventricular volumes. This change was apparent from the second week onward, with a trend towards a decrease in both systolic and diastolic volumes. By the fourth week, coinciding with the onset of hypertrophy, a pronounced decrease in left ventricular volume was noticed.

These findings offer a crucial insight into how sustained physical exercise, specifically in the form of dosed swimming, may induce physiological adaptations in the heart. It particularly sheds light on the change dynamics in systolic and diastolic volumes of the left ventricle. The results thus contribute significantly to our understanding of the heart's adaptive response under physical exertion, adding to our knowledge about pathogenic mechanisms linked with alterations in myocardial contractile force and ventricular volumes.

Therefore, the main added value of this study is providing an experimental model for exploring cardiac adaptations to physical stress. This model can be instrumental in advancing our understanding of cardiac health and diseases, potentially leading to improved preventative and therapeutic strategies. Moreover, the study highlights the need for further investigations to elucidate the molecular basis behind these exercise-induced changes, which remain partially unclear.

Acknowledgments

The authors would like to express their profound gratitude to Tbilisi State Medical University for their invaluable support in fostering the pursuit of doctoral studies. Their efforts in heightening the allure of advanced research and studies, as well as their provision of essential scientific grants for conducting experimental work, are greatly appreciated. Further appreciation is extended to the Department of Normal Human Anatomy at Tbilisi State Medical University for their unwavering support and collaboration throughout this endeavor.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' Contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.

Orcid

Nikoloz Vachadze

https://orcid.org/0009-0003-1285-322X

Anzor Gogiberidze

https://orcid.org/0000-0001-8722-192X

 

HOW TO CITE THIS ARTICLE

Nikoloz Vachadze, Anzor Gogiberidze, Ramaz Khetsuriani, Marina Pailodze, Elene Shvangiradze, Nino Pruidze. Alterations in Left Ventricular End-Systolic and End-Diastolic Volumes in 12-13-Week-Old Laboratory Rats Subjected to Dosed Swimming Exercise. J. Med. Chem. Sci., 2023, 6(11) 2727-2734.

DOI: https://doi.org/10.26655/JMCHEMSCI.2023.11.17

URL: https://www.jmchemsci.com/article_175312.html

[1]. Calvert J.W., Condit M.E., Aragon J.P., Nicholson C.K., Moody B.F., Hood R.L., Sindler A.L., Gundewar S., Seals D.R., Barouch L.A., Lefer D.J., Exercise Protects Against Myocardial Ischemia-Reperfusion Injury via Stimulation of β3-Adrenergic Receptors and Increased Nitric Oxide Signaling: Role of Nitrite and Nitrosothiols, Circulation Research, 2011, 108:1448 [Crossref], [Google Scholar], [Publisher]
[2]. Kemi O.J., Wisloff U., Mechanisms of exercise-induced improvements in the contractile apparatus of the mammalian myocardium, Acta physiologica, 2010, 199:425 [Crossref], [Google Scholar], [Publisher]
[3]. Ascensão A., Ferreira R., Magalhães J., Exercise-induced cardioprotection – biochemical, morphological and functional evidence in whole tissue and isolated mitochondria, International Journal of Cardiology, 2007, 117:16 [Crossref], [Google Scholar], [Publisher]
[4]. Konhilas J.P., Maass A.H., Luckey S.W., Stauffer B.L., Olson E.N., Leinwand L.A., Sex modifies exercise and cardiac adaptation in mice, American Journal of Physiology-Heart and Circulatory Physiology, 2004, 287:H2768 [Crossref], [Google Scholar], [Publisher]
[5]. Rippi Moreno A.C., Alborghetti Nai G., Pancera Laurindo C., Rego Gregorio K.C., Olean-Oliveira T., Souza Teixeira M.F., Monteiro Seraphim P. Resistance training prevents right ventricle hypertrophy in rats exposed to secondhand cigarette smoke. PLoS ONE, 2020, 15:e0236988 [Crossref], [Google Scholar], [Publisher]
[6]. Michna H., Knisel W., Hartmann G., Lochs H., Schober P.H., Cardiac hypertrophy in male rats after high-resistance training, The Journal of Applied Physiology, 1988, 64:684
[7]. Yoshida T, Tabony AM, Galvez S, Mitch WE, Higashi Y, Sukhanov S, Delafontaine P. Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia, The International Journal of Biochemistry & Cell Biology, 2013, 45:2322 [Crossref], [Google Scholar], [Publisher]
[8]. Bocalini D.S., dos Santos L., Antonio E.L., Serra A.J., Tucci P.J.F., Levy R.F., Exercise training-induced enhancement in myocardial mechanics is lost after 2 weeks of detraining in rats, European Journal of Applied Physiology, 2010, 109:909 [Crossref], [Google Scholar], [Publisher]
[9]. Wang B., Xu M., Li W., Li X., Exercise training preserves ischemic preconditioning in aged rat hearts by restoring the myocardial polyamine pool, Oxidative Medicine and Cellular Longevity, 2014, 2014:457429 [Crossref], [Google Scholar], [Publisher]
[10]. Dolinsky V.W., Jones K.E., Sidhu R.S., Haykowsky M., Czubryt M.P., Gordon T., Dyck J.R., Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats, Journal of Physiology, 2012, 590:2783 [Crossref], [Google Scholar], [Publisher]
[11]. Jackson M.J., McArdle A., Age-related changes in skeletal muscle reactive oxygen species generation and adaptive responses to reactive oxygen species, Journal of Physiology, 2011, 589:2139 [Crossref], [Google Scholar], [Publisher]
[12]. Thompson P.D., Buchner D., Piña I.L., Balady G.J., Williams M.A., Marcus B.H., Berra K., Blair S.N., Costa F., Franklin B., Fletcher G.F., Gordon N.F., Pate R.R., Rodriguez B.L., Yancey A.K., Wenger N.K., Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), Circulation, 2003, 107:3109 [Crossref], [Google Scholar], [Publisher]
[13]. Cadenas S., ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection, Free Radical Biology & Medicine, 2018, 117:76 [Crossref], [Google Scholar], [Publisher]
[14]. Bellafiore M., Sivverini G., Palumbo D., Macaluso F., Bianco A., Palma A., Farina F., Increased cx43 and angiogenesis in exercised mouse hearts, The International Journal of Sports Medicine, 2007, 28:749 [Crossref], [Google Scholar], [Publisher]
[15]. Slezak J., Tribulova N., Pristacova J., Hudecova S., Krizanova O., Okruhlicova L., Weismann P., Shainberg A., Kolar F., Hydrogen peroxide changes in ischemic and reperfused heart. Cytochemistry and biochemical and X-ray microanalysis, American Journal of Pathology, 1995, 147:772 [Google Scholar], [Publisher]
[16]. Uusimaa P., Risteli J., Niemelä O., Lumme J., Ikäheimo M., Jounela A., Peuhkurinen K., Collagen scar formation after acute myocardial infarction: relationships to infarct size, left ventricular function, and coronary artery patency, Circulation, 1997, 96:2565 [Crossref], [Google Scholar], [Publisher]
[17]. Akazawa H., Komuro I., Roles of cardiac transcription factors in cardiac hypertrophy, Circulation Research, 2003, 92:1079 [Crossref], [Google Scholar], [Publisher]
[18]. Marfella R., Di Filippo C., Esposito K., Nappo F., Piegari E., Cuzzocrea S., Berrino L., Rossi F., D'Amico M., Giugliano D., Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice, Diabetes, 2004, 53:454 [Crossref], [Google Scholar], [Publisher]
[19]. Garnier A., Fortin D., Deloménie C., Momken I., Veksler V., Ventura-Clapier R., Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles, The Journal of Physiology, 2003, 551:491 [Crossref], [Google Scholar], [Publisher]
[20]. Wagner P.D., Skeletal muscle angiogenesis. A possible role for hypoxia, Advances in Experimental Medicine and Biology, 2001, 502:21 [Crossref], [Google Scholar], [Publisher]
[21]. Hauton D., Evans R.D., Utilisation of triacylglycerol and non-esterified fatty acid by the working rat heart: myocardial lipid substrate preference, Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 2001, 1533:99 [Crossref], [Google Scholar], [Publisher]
[22]. Coats A.J., Ethical authorship and publishing, International Journal of Cardiology, 2009, 131:149 [Crossref], [Google Scholar], [Publisher]