Effect of Aerobic Exercise on Left Ventricular Connexin43 Expression and Distribution in Juvenile and Young Adult Rats

Background: Gap Junction (GJ) plays a role in supporting the heart electricity. Connexin43 (Cx43) as the main protein constituent of GJ in left cardiac ventricle, will increase in number and slightly redistributed to the lateral sides of cardiomyocytes after aerobic exercise in adulthood. The effects of aerobic exercise that begin at childhood are not well known.Objective: This study aims to observe the effect of aerobic exercise which started from childhood on left ventricle Cx43 distribution.Methods: This study was conducted on 28 male Juvenile (4 weeks) and young adult (8 weeks) rats, divided into 7 groups: 1) Juvenile rats undergoing 4 weeks of exercise (E-J4); 2) Control E-J4 (C-J4); 3) Juvenile rats undergoing 8 weeks of exercise (E-J8); 4) Control EJ-8 (C-J8); 5) Juvenile rats undergoing 12 weeks of exercise (E-J12; 6); Young adult rats undergoing 8 weeks of exercise (E-Yo8); 7) Control E-J12 and E-Yo8 (C-JY128). Exercise group will undergo different length of duration, starting from week 4 until 12 weeks. Cx43 was identified by immunohistochemical staining and analyzed with ImageJ software. Comparison was analyzed using independent t-test.Results: Insignificant lower of total Cx43 expression in E-J4 (64200.45 + 4243.676 total area, p >0.05) compared to control. In contrast, a significant higher of total Cx43 expression was observed in EJ-8, EJ-12 and E-Yo8 (80152.95 + 3760.481, p = 0.001; 75596.775 + 3976.333, p = 0,002; 81216.85+ 2475.768, p = 0,000). Slightly higher of lateral Cx43 redistribution occurred in all aerobic exercise, with significant lateralization in E-J8 and E-Yo8.Conclusion: Aerobic exercise increases Cx43 and slightly redistributed to lateral myocytes under normal condition both in juvenile and young adult rats

Perubahan Aktivitas Listrik Jantung pada Tikus yang Diberi Latihan Fisik Aerobik Serta Henti Latih

AbstrakLatar Belakang: Latihan fisik aerobik telah lama diketahui memberikan pengaruh yang baik kepada tubuh,  latihan fisik aerobik yang rutin dan dalam jangka waktu lama dapat membuat jantung mengalami remodeling. Proses remodeling ini bukan hanya terjadi pada struktur tetapi juga pada kelistrikan jantung, beberapa studi menunjukkan remodeling listrik jantung yang terjadi mengakibatkan berbagai bentuk aritmia, dan belum banyak yang diketahui tentang remodeling listrik jantung setelah henti latih.Metode: Pemeriksaan EKG dilakukan pada tikus Wistar jantan yang telah menjalani latihan fisik aerobik  selama empat minggu dan 12 minggu. Pemeriksaan EKG juga dilakukan lagi setelah empat minggu periode henti latih. Kecepatan alat treadmill yang digunakan adalah 20 m/menit, dengan lama durasi latihan selama 20 menit dengan diselingi masa istirahat selama 90 detik setiap lima menit tikus tersebut berlari.Hasil: Tidak terdapat perbedaan bermakna untuk voltase dan durasi gelombang P pada semua kelompok perlakuan. Terjadi peningkatan voltase gelombang R pada kelompok latihan fisik aerobik empat minggu dan 12 minggu (p<0,05). Tidak terdapat perbedaan bermakna untuk voltase gelombang R pada kelompok henti latih. Terdapat pemanjangan durasi segmen dan interval PR pada kelompok latihan fisik aerobik empat minggu dan 12 minggu (terutama pada kelompok latihan fisik aerobik 4 minggu dengan p<0,05). Tidak terdapat perbedaan bermakna durasi segmen dan interval PR pada kelompok henti latih. Terjadi pemanjangan durasi repolarisasi ventrikel (durasi gelombang T, interval QT) pada kelompok latihan fisik aerobik empat minggu dan 12 minggu (terutama pada kelompok latihan fisik aerobik 4 minggu, p<0,05). Tidak terdapat perbedaan bermakna untuk durasi gelombang T, interval QT pada kelompok henti latih. Terjadi penurunan frekuensi denyut jantung istirahat pada kelompok latihan fisik aerobik empat minggu dan 12 minggu (terutama pada kelompok latihan fisik empat minggu, p<0,05). Tidak terdapat perbedaan bermakna untuk frekuensi denyut jantung istirahat pada kelompok henti latih.Kesimpulan: Terjadi perubahan aktivitas listrik jantung (interval QT, interval PR, durasi gelombang T dan voltase gelombang R), perubahan frekuensi denyut jantung istirahat tikus Wistar jantan setelah latihan fisik aerobik selama empat minggu dan 12 minggu. Henti latih mengembalikan perubahan aktivitas listrik jantung dan perubahan frekuensi denyut jantung istirahat tersebut.Kata kunci: Aktivitas listrik jantung, EKG, latihan fisik aerobik, henti latih    AbstractBackground: Aerobic training have long been known to give a good impact to body, aerobic training if been done routinely and with long period of time will make remodeling process to the heart. This remodeling process is not only occur in structure but also in heart electrical activity, several study reveal that this electrical activity may cause many form of aritmia, there also evidence that structural remodeling that also cause electrical changes is a persistent process, if structural remodeling persistent process, what will happen to heart electrical activity of this persistent structural remodeling after detraining is still less known. Methods: Electrocardiogram (ECG) is conducted in male Wistar rat that have completed 4 weeks, 12 weeks aerobic training, 4 weeks and 12 weeks aerobic training with 4 weeks detraining. The speed that been use is 20 m/minute with 20 minute training duration and 90 second intermitten resting interval for every 5 minute training. Results: There is no difference for P wave voltage and duration in all groups. R wave voltage is increase in 4, 12 weeks aerobic training group (p < 0.05). There is no significant difference for R wave voltage in detraining group. PR segment and interval is prolonged in 4, 12 weeks aerobic training group (especially in 4 weeks aerobic training group, p < 0.05). There is no significant difference for PR segment and interval in detraining group. Ventricular repolarization time (T wave duration, QT interval) is prolonged in 4, 12 weeks aerobic training group (especially in 4 weeks aerobic training group, p < 0.05). There is no significant difference for T wave duration and QT interval in detraining group. Resting heart rate is lower in 4, 12 weeks aerobic training group (especially in 4 weeks aerobic training group, p<0.05). There is no significant difference for resting heart rate in detraining group.Conclusion: Male Wistar rat heart electrical activity (QT interval, PR interval, T wave duration time and R wave voltage) and resting heart rate change after 4 weeks and 12 weeks aerobic training. Detraining restore that changes. Keywords: Heart electrical activity, Electrocardiogram (ECG), Aerobic training, Detraining Keywords: Heart electrical activity, ECG, Aerobic training, Detrainin

THE IMPACT OF COBALAMIN DEFICIENCY ON HEART FUNCTION; A STUDY ON ABNORMALITIES IN ELECTROCARDIOGRAPHY PATTERNS

Objective: Cobalamin deficiency may cause a lack of dietary methyl donors, which alter the heart metabolism. Cobalamin deficiency is common in patients with malnutrition, gastric ulcers, diabetes mellitus, and alcoholism. Most studies on cobalamin deficiency are focused on its relationship with oxidative stress and atherogenesis. Therefore, this study aims to find the correlation between cardiomyocyte’s energy metabolism in cobalamin deficiency and the risk of heart abnormalities through analysis of electrocardiography (ECG) patterns. Methods: Adult male Sprague-Dawley rats (aged 24-28 w) were divided into 2 groups: the control group and cobalamin-deficient group. The control group was given standard diet while the treatment group received a modified diet, type AIN-93M (deficient in cobalamin), for a period of 16 w. ECG was performed in both groups on the last day of the 16-week period. Enzyme-linked immunosorbent assay (ELISA) test was also performed to evaluate plasma Hcy and B12 levels in each group at the end of the treatment period. Results: At the end of the 16-week period, higher Hcy level and lower plasma B12 level were observed in the treatment group when compared to the control group. ECG patterns showed sinus rhythms in both groups, with a higher QRS amplitude and duration in the treatment group. Two of the seven rats in the treatment group developed cardiac arrhythmia. Conclusions: Cobalamin deficiency impairs the heart’s energy metabolism with left ventricular enlargement and arrhythmia

EFFECT OF AEROBIC EXERCISE ON SHORT-AND LONG-TERM MEMORY IN ADULT MALE WISTAR RATS

Objective: Memory is an essential function of cognition in humans, but an age- and disease-related deterioration of this function is common. The currently known treatments have high failure rates, and thus, the slowing down of memory degeneration at an early age is the preferred preventive approach. Exercise, specifically aerobic exercise, has been proven to enhance memory via various pathways, such as neurogenesis, angiogenesis, and growth factor expression. The aim of this study is to assess the effect of aerobic exercise on short-term and long-term memory function in rats. Methods: Twenty-four male Wistar rats aged 7 mo were randomly distributed into four groups: Control, short-term memory (C-S); Control, long-term memory (C-L); Aerobic, short-term memory (A-S); and Aerobic, long-term memory (A-L). The aerobic groups received exercise treatment for 30 min each five times per week, at a treadmill speed of 20 m/min. The treatment duration was 8 w. Short-term memory was assessed using the forced alteration Y-maze test, and long-term memory was assessed using the object location task. Results: The findings showed that rats placed under the aerobic exercise regimen had significantly better long-term memory function at the end of 8 w (p = 0.006), while no significant difference was observed in short-term memory function between the aerobic exercise group and the control group. Conclusion: The present study shows that aerobic exercise is beneficial in improving long-term memory function in rats

Consumption of Hibiscus sabdariffa dried calyx ethanol extract improved redox imbalance and glucose plasma in vitamin B12 restriction diet in rats

This study aimed to evaluate the effect of Hibiscus sabdariffa L. dried calyx ethanolic (HSE) extract on the redox imbalance and glucose plasma of vitamin B12 restriction Sprague-Dawley rats. The rat was fed a Vitamin B12 Restriction Diet for 16 weeks and treated with HSE as the treatment group. One group was fed a restriction diet not treated with HSE as a positive control group, and another was fed a control chow diet not treated with HSE as a negative control group. Vitamin B12, MDA, SOD activity enzyme, and glucose levels were evaluated in this study. The extract had a significant antioxidant capacity in terms of reducing the production of free radical scavenging activity. The HSE can repair the skewed redox imbalance and oxidative damage generated by a vitamin B12-deficient diet in the rat liver. The result of fasting glucose plasma levels, in 16 weeks showed both significantly different in all groups. In Sprague-Dawley rats with vitamin B12 restriction treated with HSE, a decrease in the glucose plasma in week sixteen was observed, together with a reduction of hepatic redox imbalance. Treatment with HSE protected hepatocytes from oxidative damage caused by vitamin B12 deficiency

Ekspresi Protein Foxo1 dan Gen Glukosa 6 Fosfatase pada Tikus dengan Diet Restriksi Vitamin B12

Pada penelitian awal didapatkan diet restriksi vitamin B12 menyebabkan hiperhomosisteinemia dan resistensi insulin, yang ditandai oleh hiperglikemia dan meningkatnya nilai Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Dengan menggunakan sampel jaringan biologik tersimpan, hati tikus Spraque-Dawley dari penelitian tersebut, penelitian lanjutan ini bertujuan mengetahui penyebab hiperglikemia, dalam hubungannya dengan proses glukoneogenesis, dengan melihat ekspresi forkhead box protein-O1 (FoxO1) dan gen glukosa 6 fosfatase (G6Pc). Adapun sampel terdiri dari 4 kelompok: kelompok kontrol dan tiga kelompok dengan diet restriksi vitamin B12 masing-masing selama 4, 8, dan 12 minggu. Ekspresi FoxO1 diperiksa dengan metode kuantitatif Western-Blot, sedangkan gen G6Pc diperiksa dengan metode real-time Polymerase Chain Reaction (rt-PCR). Hasil yang diperoleh, tidak terdapat perbedaan bermakna ekspresi FoxO1 (P > 0,05) dan gen G6Pc (P > 0,05) antara kelompok tikus kontrol dan kelompok diet restriksi vitamin B12. Hal ini menunjukkan, hiperglikemia pada diet restriksi vitamin B12 tidak terkait dengan glukoneogenesis. Pada kondisi resistensi insulin, insulin masih dapat meneruskan efek metaboliknya melalui jalur lain, seperti melalui reseptor yang memiliki kemiripan struktur dan fungsi dengan reseptor insu   lin. Penyebab-penyebab lain terjadinya hiperglikemia seperti gangguan utilisasi glukosa oleh sel dan gangguan proses glikogenesis perlu diteliti lebih lanjut.Pada penelitian awal didapatkan diet restriksi vitamin B12 menyebabkan hiperhomosisteinemia dan resistensi insulin, yang ditandai oleh hiperglikemia dan meningkatnya nilai Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Dengan menggunakan sampel jaringan biologik tersimpan, hati tikus Spraque-Dawley dari penelitian tersebut, penelitian lanjutan ini bertujuan mengetahui penyebab hiperglikemia, dalam hubungannya dengan proses glukoneogenesis, dengan melihat ekspresi forkhead box protein-O1 (FoxO1) dan gen glukosa 6 fosfatase (G6Pc). Adapun sampel terdiri dari 4 kelompok: kelompok kontrol dan tiga kelompok dengan diet restriksi vitamin B12 masing-masing selama 4, 8, dan 12 minggu. Ekspresi FoxO1 diperiksa dengan metode kuantitatif Western-Blot, sedangkan gen G6Pc diperiksa dengan metode real-time Polymerase Chain Reaction (rt-PCR). Hasil yang diperoleh, tidak terdapat perbedaan bermakna ekspresi FoxO1 (P > 0,05) dan gen G6Pc (P > 0,05) antara kelompok tikus kontrol dan kelompok diet restriksi vitamin B12. Hal ini menunjukkan, hiperglikemia pada diet restriksi vitamin B12 tidak terkait dengan glukoneogenesis. Pada kondisi resistensi insulin, insulin masih dapat meneruskan efek metaboliknya melalui jalur lain, seperti melalui reseptor yang memiliki kemiripan struktur dan fungsi dengan reseptor insulin. Penyebab-penyebab lain terjadinya hiperglikemia seperti gangguan utilisasi glukosa oleh sel dan gangguan proses glikogenesis perlu diteliti lebih lanjut

EFFECT OF HIBISCUS SABDARIFFA LINN METHANOLIC EXTRACT ON HEART HYPERTROPHY INDEX AND PGC-1α IN OVERTRAINED RAT

Objective: Studies have shown that prolonged physical exercise increases ventricular wall mass. Physiologically, this increase is followed by an increase of mitochondrial biogenesis. However, increases of ventricular mass in some cardiovascular diseases are not followed by an increase of PPARγ coactivator-1α (PGC-1α), a marker of mitochondrial biogenesis. No data regarding cardiac PGC-1α during an excessive physical exercise program that causes pathological conditions (overtraining) are available. Thus, we aimed to determine the effect of overtraining on cardiac hypertrophy index and PGC-1α level. Furthermore, we aimed to elucidate the cardio protective effect of Hibiscus sabdariffa Linn. (HSL) administration on these cardiac parameters. Methods: Twenty-five male adult Wistar rats aged 8–10 w were randomly divided into five groups: control (C), control-HSL (C-HSL), aerobic training (A), overtraining (OT), and overtraining-HSL (OT-HSL). Treatments were conducted five times a week, for 11 w. Differences in heart mass were determined by measuring ratios of ventricular weight to body weight (hypertrophy index). PGC-1α levels were measured using an ELISA method. Results: We found that overtraining increased ventricular wall mass; however, it did not increase cardiac PGC-1α levels, whereas mild-aerobic exercise robustly increased cardiac levels of PGC-1α. Furthermore, administration of a methanol extract of HSL did not show any significant effect on cardiac mass or PGC-1α level. Conclusion: Thus, our study showed that ventricular hypertrophy elicited by overtraining conditions was not followed by an increase in cardiac PGC-1α, and administration of H. sabdariffa extract did not ameliorate this condition

Combination of Aerobic Exercise and Continuous Environmental Enrichment Improves Adult Male Rats’ Spatial Memory: Study on Hippocampal Insulin Like Growth Factor 1 (IGF-1) and Fibroblast Growth Factor 2 (FGF-2) Expression

BACKGROUND: Memory declines with the progression of age through the neurodegeneration process. Aerobic exercise and environmental enrichment can delay neurodegeneration by improving neuroplasticity via expression of insulin like growth factor 1 (IGF-1), fibroblast growth factor 2 (FGF-2) and other proteins. Combination treatment of aerobic exercise and continuous environmental enrichment and their effect on the expression of IGF-1 and FGF-2 which were expected to improve memory function has not been studied previously. Thus, this study aimed to observe it.METHODS: This is an experimental research using 24 male Wistar rats (Rattus norvegicus, 300-400 g, age 7-8 months) divided randomly into 4 groups: control (C), aerobic exercise (A), continuous (EE), and combination of aerobic exercise and continuous environmental enrichment (A-EE). At the end of an 8-week treatment, rats were sacrificed, and an enzyme-linked immunosorbent assay (ELISA) examination was performed to assess hippocampal IGF-1 and FGF-2 levels.RESULTS: In the 8th week, A-EE group showed the best improvement in rats’ spatial memory (47.84±10.6 %) followed by EE group (45.03±4.1 %), A group (38.61±3.8 %), and C group (22.76±7.12 %). However, A-EE group’s hippocampal IGF-1 (16.21±7.56 ng/mg protein) and FGF-2 (1.29±0.57 ng/mg protein) expression were not higher than other groups.CONCLUSION: Improvement in memory function in the combination group is a result of induction of various growth factors’ expression in the hippocampus, including IGF-1 and FGF-2, but the primary pathway of memory function improvement may be from other growth factors.KEYWORDS: spatial memory, aerobic exercise, environmental enrichment, hippocampus, IGF-1, FGF-

EFFECT OF HIBISCUS SABDARIFFA LINN ON IL-6 AND TNF- α LEVELS IN OVERTRAINED RAT HEART

Objective: This study aims to determine the effect of Hibiscus sabdariffa Linn. (HSL) administration on the interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels in rat heart. Overtraining was proven to increase the IL-6 and TNF-α levels in the blood, and HSL had anti-inflammatory and anti-oxidant properties. However, no studies have been conducted on the effect of methanolic extract of HSL administration on the IL-6 and TNF-α levels in overtrained rat heart. Methods: This study used 25 male adult Wistar rats aged 8–10 w and weighing 200–250 g. The rats were randomly divided into five groups: control (C), control H. sabdariffa Linn (C+HSL), overtraining (OT), overtraining H. sabdariffa Linn (OT+HSL), and aerobic (A). Treatment was given 5 times a week for 11 w. At the end of the study, the IL-6 and TNF-α levels were measured using a standard ELISA kit. Results: IL-6 and TNF-α levels in the heart were the highest in the overtraining group. The group that received HSL administration showed the lowest TNF-α and IL-6 levels. Conclusion: HSL could be a used to protect the heart from an inflammatory state, particularly in an overtraining condition

Superior mesenteric artery blood flow in infants of very preterm and very low birthweight and its related factors

Abstract Background Significant hemodynamic changes in preterm infants during early life could have consequences, especially on the intestinal blood flow. Alteration of superior mesenteric artery (SMA) blood flow may lead to impairment in gut function and feeding intolerance. Objectives To assess SMA blood flow velocity in very preterm and/or very low birth weight (VLBW) infants in early life and to elucidate the factors influencing them. Methods This is a cross-sectional study conducted in NICU at Cipto Mangunkusumo Hospital, Jakarta. Superior mesenteric artery (SMA) blood flow was evaluated by peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) measurement using Color Doppler US at < 48 hours after birth. Maternal and neonatal data that could be potentially associated with SMA blood flow were obtained. Bivariate analyses were conducted with a P value of < 0.05 considered significant. Results We examined 156 infants eligible for the study. PSV, EDV, and RI of SMA blood flow were not related to both gestational age and birth weight. Infant with small for gestational age (SGA) showed significantly lower EDV median [15.5 (range 0.0-32.8) vs 19.4 (range 0.0-113.0)] and higher RI [0.80 (range 0.58-1.00) vs 0.78 (range 0.50-1.00)] compared to appropriate for gestational age (AGA).  Infants born from mother with preeclampsia showed lower PSV median [(78.2 (range 32.0-163.0) vs 89.7 (range 29.2-357.0)]) and EDV [16.2 (range 0.0-48.5) vs 19.4 (range 0.0-113.0)] compared to without PE, while absent/reverse end-diastolic velocity (AREDV) revealed a lower EDV median [16.9 (range 0.0 – 32.4) vs 19.4 (range 0.0 – 113.0)] compared to no AREDV. Furthermore, infants with hs-PDA showed lower EDV median [16.2 (range 0.0-113.0) vs 19.4 (range 0.0-71.1)] but higher RI median [0.80 (range 0.50-1.00) vs 0.78 (range 0.55-1.00)] compared to non hs-PDA. No difference in SMA blood flow across other factors was observed