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Abstrak :
Latar Belakang : Beberapa penelitian terbaru memperlihatkan bahwa apoptosis terjadi pada beberapa keadaan jantung patologis seperti pada keadaan kerusakan ?iskemia-reperfusi?, infark miokardium dan gagal jantung. Di sisi lain terdapat penelitian yang memperlihatkan bahwa latihan fisik dapat menurunkan apoptosis kardiomiosit. Dari beberapa jenis latihan fisik, latihan fisik aerobik merupakan latihan yang paling dianjurkan karena diyakini efektif dalam mencegah dan bahkan sebagai terapi rehabilitasi pada penyakit kardiovaskular. Keadaan henti latih pasca latihan fisik ternyata dapat mengembalikan seluruh atau sebagian adaptasi yang sudah terbentuk setelah latihan fisik. Tujuan : Penelitian ini bertujuan ingin melihat bagaimana pengaruh latihan fisik aerobik dan henti-latih terhadap apoptosis kardiomiosit ventrikel kiri dengan menggunakan protein caspase-3 sebagai parameter apoptosis. Desain : Penelitian ini menggunakan studi eksperimental in vivo pada tikus Metode : identifikasi protein caspase-3 pada jaringan ventrikel kiri jantung tikus dengan pemeriksaan pulasan imunohistokimia pada 8 kelompok tikus ( kelompok kontrol 4 minggu (K4M), kontrol 8 minggu (K4MD), kontrol 12 minggu (K12M), kontrol 16 minggu (K12MD) dan kelompok perlakuan latihan aerobik 4 minggu (AR4M), perlakuan latihan aerobik 12 minggu (AR12M), perlakuan latihan aerobik 4 minggu diikuti dengan henti-latih 4 minggu (AR4MD) serta kelompok latihan aerobik 12 minggu diikuti dengan henti-latih 4 minggu(AR12MD)). Hasil : Analisis data menunjukan peningkatan persentase ekspresi caspase-3 kelompok pasca latihan fisik aerobik (K4M 6,40%1,78 dan AR4M 65,38%2,54, p<0,001; K12M 5,72%0,88 dan AR12M 41,81%3,21, p<0,001; K4MD 8,64%±3,59 dan AR4MD 66,55%±1,88; K12MD 7,35%±2,06 dan AR12MD 46,78%±2,45, p<0,001). Kecenderungan Peningkatan persentase ekspresi caspase-3 kelompok pasca henti latih (AR4M 65,38%2,54 dan AR4MD 66,55%1,88%, p=1,000; AR12M 41,81%3,21dan AR12MD 46,78%±2,45, p=0,230). Ekspresi caspase 3 kelompok latihan aerobik 4 minggu lebih tinggi dibanding kelompok latihan aerobik 12 minggu (AR4M 65,38%2,54 dan AR12M 41,81%3,21, p<0,001). Kesimpulan : latihan fisik aerobik tidak menurunkan apoptosis kardiomiosit ventrikel kiri jantung tikus dan program henti latih tidak meningkatkan apoptosis kardiomiosit ventrikel kiri jantung tikus.

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Background: Recent studies showed that apoptosis occurs in several pathological heart condition as in myocardial ischemia-reperfusion injury, myocardial infarction and heart failure. It has been also research showing that physical exercise can reduce apoptosis on cardiomyocyte. Of some kind of physical exercise, aerobic exercise is an exercise that is most recommended because it is believed to be effective in preventing and even as a rehabilitation therapy on cardiovascular disease. Detraining was able to restore all or part of adaptation that has been formed after the exercise. Objective: This study aimed to see the effect of aerobic exercise and detraining on left ventricular cardiomyocyte apoptosis using caspase-3 protein as a parameter of apoptosis. Design: This study used an experimental in vivo study on rats. Methods: Caspase-3 protein in rat cardiac left ventricular tissue is identified by immunohistochemistry staining conducted on 4 sedentary control group ( 4 weeks control group (K4M), 8 weeks control group (K4MD), 12 weeks control group (K12M), 16 weeks control (K12MD)) and 4 treatment groups ( 4 & 12 weeks post aerobic exercise group (AR4M, AR12M) and 4&12 weeks post aerobic exercise followed by 4 weeks detraining (AR4MD,AR12MD)). Results: Analysis of the data shows an increase percentage of caspase-3 expression on post-aerobic exercise group (K4M 6,40%1,78 and AR4M 65,38%2,54, p<0,001; K12M 5,72%0,88 and AR12M 41,81%3,21, p<0,001; K4MD 8,64%±3,59 and AR4MD 66,55%±1,88; K12MD 7,35%±2,06 and AR12MD 46,78%±2,45, p<0,001) The data also shows tendency an increase percentage of caspase-3 expression on detraining group (AR4M 65,38%2,54 and AR4MD 66,55%1,88%, p=1,000; AR12M 41,81%3,21 and AR12MD 46,78%±2,45, p=0,230). Percentage of caspase-3 expression on post-4 weeks aerobic exercise group is higher than post-12 weeks aerobic exercise (AR4M 65,38%2,54 and AR12M 41,81%3,21, p<0,001). Conclusion: Aerobic physical exercise does not decrease left ventricular cardiomyocyte apoptosis and does not improve left ventricular cardiomyocyte apoptosis.

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Latar belakang : Overtraining berdampak buruk terhadap kesehatan karena dapat menyebabkan kematian mendadak pada atlet muda. Berdasarkan data epidemiologi ditemukan bahwa kejadian kematian mendadak (suddent cardiac death) pada atlet muda, penyebab paling banyak adalah gangguan kardiovaskular. Tubuh melakukan adaptasi terhadap beban berlebih, berupa remodelling (morfologi dan elektrofisiologi). Remodeling elektrofisiologis yaitu perubahan pada gap junction, berupa perubahan ekspresi Cx43 yang yang mengakibatkan gangguan penghantaran konduksi listrik. Selama latihan fisik dapat terbentuk ROS yang akan menginduksi permeabilitas mitokondria sehingga terjadi kebocoran sitokrom c, selanjutnya akan mengaktifkan kaskade apoptosis. Metode : Penelitian ini dilakukan pada 6 jaringan kardiomiosit tikus Wistar kelompok kontrol dan overtraining. Ekspresi Cx43 dan caspase-3 diamati melalui pulasan imunohistokimia dan diukur dengan image J. Hasil : Hasil penelitian ini menunjukkan peningkatan bermakna pada ekspresi Cx43 total overtraining (43644.57±27711.03) dibandingkan kelompok kontrol (13002.37±3705.41). Tidak ditemukan perbedaan bermakna ekspresi caspase-3 pada kedua kelompok meskipun diperoleh hasil lebih tinggi pada kelompok overtraining (14.15%±10.54%) dibandingkan kelompok kontrol (2,63%±3.56%). Kesimpulan : Overtraining meningkatkan ekspresi Cx43 total tetapi tidak terbukti meningkatkan caspase-3 pada kardiomiosit ventrikel kiri tikus. ......Background: overtraining has bad effect for health, overtraining can cause sudden death in young athlete, reports of sudden death incidences in young athlete claim that cardiovascular disease is the cause. The heart can face the excess load by remodeling as it?s adaptation mechanism. There is 2 type remodeling, morphology and electrophysiology. Remodeling electrophysiology is a change on Cx43 expression which can interfere the heart?s electrical conduction. Free radical which formed from physical exercise can induce mitochondrial permeability that lead leakage of cytochrome c, so that so that activate the apoptosis cascade. Methods: This study conducted on 12 Wistar rat?s cardiomyocytes tissue that divided into control and overtraining group. Cx43 expression and caspase-3 was observed through immunohistochemical staining and measured by image J. Results: There was significant increase in the expression of Cx43 total overtraining (43644.57 ± 27711.03) compared to the control group (13002.37 ± 3705.41). Found no significant differences in the expression of caspase-3 in both groups although the result was higher in the group of overtraining (14,15% ± 10,54%) compared to the control group (2,63% ± 3,56%). Conclusion: Overtraining increase total Cx43 expression but not proven to increase caspase-3 in the rat left ventricular cardiomyocytes.

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Pendahuluan: Berdasarkan intensitas, durasi, dan bagaimana energi untuk kerja otot dihasilkan, latihan fisik dibagi menjadi latihan fisik aerobik dan anaerobik. Beberapa penelitian menunjukkan adanya hubungan antara latihan fisik dengan perubahan panjang telomer sel darah putih SDP , dan sel otot jantung. Pemendekan telomer SDP sering dihubungkan dengan penyakit kronik tidak menular, salah satunya penyakit kardiovaskular. Di Indonesia belum ada penelitian yang membandingkan pengaruh latihan fisik aerobik dan anaerobik terhadap perubahan panjang telomer SDP dan sel otot jantungTujuan: Membandingkan efek latihan fisik aerobik dan anaerobik terhadap perubahan panjang telomer SDP dan sel otot jantungMetode: Penelitian ini menggunakan 24 tikus putih jantan berusia 11-13 bulan, berat rata-rata 300 gram. Dibagi secara acak dalam 3 kelompok: 1 kontrol; 2 latihan fisik aerobik; 3 latihan fisik anaerobik. Latihan fisik dilakukan 5 kali/minggu selama 4 dan 12 minggu. Perhitungan panjang telomer relatif menggunakan Real-Time PCR.Hasil: Secara signifikan terdapat perbedaan panjang telomer relatif SDP kelompok aerobik 4 minggu dan 12 minggu dibanding kontrol 4 minggu p=0,012 dan p=0,009 . Tidak terdapat perbedaan bermakna kelompok anaerobik 4 dan 12 minggu dibanding kontrol 4 minggu p=0,208 dan p=0,141 . Tidak terdapat perbedaan bermakna panjang telomer relatif sel otot jantung kelompok aerobik maupun anaerobik dibanding kontrol.Kesimpulan: Latihan fisik aerobik memberikan efek lebih baik dibanding anaerobik dalam perubahan panjang telomer SDP. Sedangkan latihan fisik aerobik maupun anaerobik tidak mempengaruhi perubahan panjang telomer sel otot jantung.Kata Kunci: Latihan fisik aerobik, latihan fisik anaerobik, telomer, sel darah putih, sel otot jantung

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Introduction Aerobic and anaerobic physical exercise are two types of physical exercise that differ based on the intensity, interval, and type of muscle fibers incorporated. Telomere length TL of leukocyte, a measure of replicative senescence, decreases with aging. Recent evidence supports that telomere length of leukocytes may be inversely correlated with the risk of several age related diseases. In Indonesia, there has been no specific research to find out the effect of aerobic and anaerobic physical exercise on changes in telomere length of leukocyte and cardiomyocyte.Methods This study was conducted on 24 male white rats Rattus norvegicus 250 300 grams age 11 13 months, randomly allocated into 3 groups 1 control 2 aerobic physical exercise APE and 3 anaerobic physical exercise AnPE . Physical exercise was performed 5 times a week, for 4 and 12 weeks. Measurement of relative telomere length using Real Time PCR.Result Relative leukocyte TL was found significantly longer in 4 and 12 weeks APE group compared to 4 week control p 0,012 and p 0,009 . Relative leukocyte TL was found not significantly different between 4 and 12 weeks AnPE group compared 4 weeks control group p 0,208 and p 0,141 . Cardiomyocyte relative telomere length APE and AnPE are no significantly better compare to control group.Conclusion Leukocyte TL is preserved in group of APE.Keywords Aerobic physical exercise, anaerobic physical exercise, telomere length, leukocyte, cardiomyocyte.

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ABSTRAK
Latar Belakang: Obesitas merupakan salah satu masalah kesehatan utama yang banyak ditemukan di negara maju maupun negara berkembang. Obesitas menjadi salah satu faktor risiko timbulnya penyakit kardiovaskular. Diketahui bahwa populasi obesitas memiliki kadar plasma BNP yang rendah dibanding kelompok normal. BNP adalah suatu hormon yang disintesis oleh miosit atrium yang berperan dalam meregulasi hemodinamik tubuh. Selain itu BNP memiliki efek anti fibrosis dan anti hipertrofi pada jantung. Dipikirkan bahwa adanya gangguan sintesis BNP di miosit jantung sebagai salah satu penyebab. Maka, penelitian ini bertujuan untuk melihat profil ekspresi mRNA BNP, NPR-A dan NPR-C pada populasi obesitas. Metode: Studi potong lintang dilakukan di Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita (RSJPDHK). Jaringan miosit tersimpan yang sudah dilakukan ekstraksi RNA dibagi menjadi 2 kelompok berdasarkan IMT, kelompok obesitas (IMT ≥27) dan kelompok normal (IMT <27) dan sesuai kriteria inklusi dan eksklusi. RNA kedua kelompok dilakukan sintesis cDNA, ekstraksi protein dan Real-Time PCR untuk mendapatkan mean ΔCt. Kemudian dilakukan penghitungan menggunakan metode Livak untuk mendapatkan nilai ekspresi relatif mRNA. Data kemudian di analisis statistik menggunakan SPSS 20. Hasil Penelitian: Sebanyak 48 pasien diikutsertakan dalam penelitian ini dengan jumlah kelompok normal 34 orang dan kelompok obesitas 14 orang. Hasil ekspresi mRNA BNP, NPR-A dan NPR-C lebih rendah pada kelompok obesitas dibanding kelompok normal. Namun, tidak didapatkan perbedaan bermakna ekspresi mRNA BNP (p 0,768), NPR-A (p 0,838) dan NPR-C (p 0,768) antara kelompok obesitas dibanding kelompok normal. Kesimpulan: Penelitian ini tidak menemukan perbedaan ekspresi mRNA BNP, NPR-A dan NPR-C yang bermakna antara kelompok obesitas dengan kelompok normal.

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ABSTRACT
Background: Obesity is presenting as a significant health problem across the world. Obesity is a risk factor for cardiovascular diseases. The plasma level of B-type natriuretic peptide (BNP) has been identified to be lower in obese people compare to normal. As we know, BNP is one of the cardiac hormones synthesized by atrial myocyte that plays a role in hemodynamic regulations. In addition, BNP exerts its anti fibrotic and anti hypertrophic effects in the heart. It has been hypothesized that one of the possible mechanism responsible for this inverse relationship is the impaired synthesize of BNP by cardiomyocytes. Therefore, the aim of our study is to evaluate the mRNA expression profile of BNP, Natriuretic peptide receptor type-A (NPR-A) and Natriuretic peptide receptor type-C (NPR-C) in cardiomyocytes of obese population. Method: A cross-sectional study was conducted in Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita (RSJPDHK). Cardiomyocytes that have been performed the RNA extraction proses were divided into 2 groups, Obese group (BMI ≥27) and Normal group (BMI <27), according to BMI and inclusion and exclusion criteria. Synthesize cDNA, protein extraction and Real-Time PCR were performed in order to have the mean of ΔCt. Livak method was used to determine the relative expression mRNA value. SPSS 20 for Windows was used for the purpose of statistical analyses. Results: 48 patients were included in this study that consist of 34 patients in normal group and 14 patients in obese group. The mRNA expression of BNP, NPR-A and NPRC were lower in obese group compared to normal group. However, there was no significant difference between groups. Conclusion: In conclusion, there is no significant difference of mRNA expression of BNP, NPR-A and NPR-C between obese and normal group.;Background: Obesity is presenting as a significant health problem across the world. Obesity is a risk factor for cardiovascular diseases. The plasma level of B-type natriuretic peptide (BNP) has been identified to be lower in obese people compare to normal. As we know, BNP is one of the cardiac hormones synthesized by atrial myocyte that plays a role in hemodynamic regulations. In addition, BNP exerts its anti fibrotic and anti hypertrophic effects in the heart. It has been hypothesized that one of the possible mechanism responsible for this inverse relationship is the impaired synthesize of BNP by cardiomyocytes. Therefore, the aim of our study is to evaluate the mRNA expression profile of BNP, Natriuretic peptide receptor type-A (NPR-A) and Natriuretic peptide receptor type-C (NPR-C) in cardiomyocytes of obese population. Method: A cross-sectional study was conducted in Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita (RSJPDHK). Cardiomyocytes that have been performed the RNA extraction proses were divided into 2 groups, Obese group (BMI ≥27) and Normal group (BMI <27), according to BMI and inclusion and exclusion criteria. Synthesize cDNA, protein extraction and Real-Time PCR were performed in order to have the mean of ΔCt. Livak method was used to determine the relative expression mRNA value. SPSS 20 for Windows was used for the purpose of statistical analyses. Results: 48 patients were included in this study that consist of 34 patients in normal group and 14 patients in obese group. The mRNA expression of BNP, NPR-A and NPRC were lower in obese group compared to normal group. However, there was no significant difference between groups. Conclusion: In conclusion, there is no significant difference of mRNA expression of BNP, NPR-A and NPR-C between obese and normal group.

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Latar belakang: Latihan fisik anaerobik adalah latihan fisik yang dilakukan dalam waktu singkat dengan intensitas tinggi dan dapat merangsang apoptosis pada kardiomiosit ventrikel kiri. Penelitian ini bertujuan untuk menganalisis ekspresi apoptosis kardiomiosit pasca latihan serta pasca henti latih latihan fisik anaerobik. Metode : Identifikasi Caspase-3 dilakukan dengan cara pulasan imunohistokimia dan analisis kuantitatif persentase Caspase-3 yang dilakukan pada kelompok kontrol 4,8,12 dan 16 minggu, kelompok perlakuan latihan fisik anaerobik 4 dan 12 minggu serta henti latih 4 minggu pasca latihan (minggu ke 8 dan 16). Hasil: Analisis data menunjukkan peningkatan persentase caspase-3 pada kelompok latihan fisik anaerobik 4 dan 12 minggu dengan p=0,027. Penurunan persentase capase-3 pasca henti latih yang bermakna juga ditemukan antara kelompok latihan fisik anaerobik 4 minggu dengan kelompok henti latih 4 minggu (p=0,0001) dan antara kelompok latihan anaerobik 12 minggu dengan kelompok henti latih 16 minggu (p=0,0001).

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Introduction : Anaerobic physical exercise is a high intensity physical exercise performed in a short time. This exercise can stimulate apoptosis in left ventricular cardiomyocytes. The aims of this study is to analyze the expression of cardiomyocyte apoptosis after anaerobic exercise and detraining. Methods : Caspase-3 expression is identified by immunohistochemistry labeling and quantitative analysis of the percentage of Caspase-3 in the control group 4,8,12 and 16 weeks, groups with 4 and 12 weeks of anaerobic physical exercise, and groups after 4 weeks of detraining ( week 8 and 16). Conclucion: Data analyses showed a significant increase in the percentage of caspase-3 in the 4 and 12 weeks anaerobic physical exercise groups with p = 0.027. The percentage of Capase-3 after detraining showed a significant decline between the groups of 4 weeks of anaerobic physical exercise and detraining with p = 0.0001 and between groups of 12 weeks of anaerobic exercise and detraining with p = 0, 0001.

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Calcium is crucial in governing contractile activities of myofilaments in cardiomyocytes, any defeats in calcium homeostasis of the cells would adversely affect heart pumping action. The characterization of calcium handling properties in human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMCs) is of significant interest and pertinent to the stem cell and cardiac regenerative field because of their potential patient-specific therapeutic use.