• Title/Summary/Keyword: coronary artery ligation

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Hypothermia Improves Outcomes of Cardiopulmonary Resuscitation After Cardiac Arrest In a Rat Model of Myocardial Infarction (심근경색에 의한 심정지 후 치료적 저체온증으로 호전된 쥐의 심폐소생술 모델)

  • Roh, Sang-Gyun;Kim, Jee-Hee;Moon, Tae-Young;Park, Jeong-Hyun
    • Proceedings of the KAIS Fall Conference
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    • 2011.12a
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    • pp.170-173
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    • 2011
  • Therapeutic hypothermia(TH) improves neurological outcomes and reduces mortality among survivors of out-of-hospital cardiac arrest. Animal and human studies have shown that TH results in improved salvage of the myocardium, reduced infarct size, reduced left ventricular remodeling and better long-term left ventricular function in settings of regional myocardial ischemia. This study is to investigate the effect of TH on post-resuscitation myocardial dysfunction and survival time after cardiac arrest and resuscitation in a rat model of myocardial infarction (MI). Thoracotomies were performed in 10 Male Sprague-Dawley rats weighing 450-550 g. MI was induced by ligation of the left anterior descending coronary artery (LAD). Ninety min after LAD ligation, ventricular fibrillation induction and subsequent cardiopulmonary resuscitation was performed before defibrillation attempts. Animals were randomized to two groups: a) Acute MI-Normothermia b) Acute MI-Hypothermia ($32^{\circ}C$ for 4 h). Myocardial functions, including cardiac output, left ventricular ejection fraction, and myocardial performance index were measured echocardiographically together with duration of survival. Ejection fraction, cardiac output and myocardial performance index were $54.74{\pm}9.16$, $89.00{\pm}8.89$, $1.30{\pm}0.09$ respectively and significantly better in the TH group than those of the normothermic group at the first 4 h after resuscitation($32.20{\pm}1.85$,$41.60{\pm}8.62$,$1.77{\pm}0.19$)(p=0.00). The survival time of the hypothermic group ($31.8{\pm}14.8$ h) was greater than that of the normothermic group($12.3{\pm}6.5$ h, p<0.05). This study suggested that TH attenuated post resuscitation myocardial dysfunction in acute MI and would be a potential strategy in post resuscitation care.

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Methanol Extract of Cassia mimosoides var. nomame Attenuates Myocardial Injury by Inhibition of Apoptosis in a Rat Model of Ischemia-Reperfusion

  • Lim, Sun-Ha;Lee, Jong-Won
    • Preventive Nutrition and Food Science
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    • v.17 no.3
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    • pp.177-183
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    • 2012
  • Interruption of blood flow through coronary arteries and its subsequent restoration triggers the generation of a burst of reactive oxygen species (ROS), leading to myocardial cell death. In this study, we determined whether a methanol extract of Cassia mimosoides var. nomame Makino could prevent myocardial ischemia-reperfusion injury. When radical scavenging activity of the extract was measured in vitro using its ${\alpha}$,${\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) radical quenching ability, the extract showed an activity slightly lower than that of ascorbic acid. Three days after oral administration of the extract (400 mg/kg/day) to rats, myocardial ischemia/reperfusion injury was generated by 30 min of ligation of the left anterior descending coronary artery (LAD), followed by 3 hr reperfusion. Compared with the vehicle-treated group, administration of the extract significantly reduced infarct size (IS) (ratio of infarct area to area at risk) in the extract-treated group by 28.3%. Reduction in the cellular injury was mediated by attenuation of Bax/Bcl-2 ratio by 33.3%, inhibition of caspase-3 activation from procaspase-3 by 40%, and subsequent reduction in the number of apoptotic cells by 66.3%. These results suggest that the extract attenuates myocardial injury in a rat model of ischemia-reperfusion by scavenging ROS, including free radicals, and consequently blocking apoptotic cascades. Therefore, intake of Cassia mimosoides var. nomame Makino might be beneficial for preventing ischemic myocardial injury.

Serial values for hematologic and biochemical analysis after myocardial infarction in rats

  • Lee, Mi-Jin;Tae, Hyun-Jin;Li, Ying-Hua;Yu, Do-Hyeon;Han, In-Ae;Lee, Seok-Won;Ahn, Dong-Choon;Kim, In-Shik;Park, Jin-Ho
    • Korean Journal of Veterinary Service
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    • v.31 no.2
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    • pp.175-186
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    • 2008
  • To diagnose acute myocardial infarction (MI), many cardiac markers have been used in hematologic and biochemical analysis, and many studies have been published for hematologic and biochemical analysis associated with human acute MI. However, after occurrence of acute MI, the serial investigation for values in hematologic and biochemical analysis including chronic MI has rarely been performed. To observe the change of the serial values in hematologic and biochemical analysis, we induced artificial MI. The left main descending artery (LMDA) of the left coronary artery was ligated during the progression (day 1, 3, 5, 7, 14 and 30) of MI. Total 66 Sprague-Dawley rats were divided into the sham group (n=24, thoracotomy without LMDA ligation) and the experimental (MI) group (n=42, with LMDA ligation). And all individual in each group was sacrified at day 1, 3, 5, 7, 14 and 30 for the hematologic and biochemical analysis. In comparison of hematologic analysis between the sham and MI groups, the mean values of red blood cell (RBCs), hemoglobin and hematocrit (HCT) showed a steady increase. In biochemical analysis, the mean values of glucose, cholesterol, total creatine kinase (CK) and isoenzyme MB, and lactate dehydrogenase (LDH) were increased in all MI groups compared with the sham groups. The results of this study suggest that early hematologic and biochemical mean values occurred after acute MI are similar to those of human acute MI. In conclusion, we could observe the alterations and serial values in hematologic and biochemical analysis to the extent of chronic status after acute MI.

KR-39038, a Novel GRK5 Inhibitor, Attenuates Cardiac Hypertrophy and Improves Cardiac Function in Heart Failure

  • Lee, Jeong Hyun;Seo, Ho Won;Ryu, Jae Yong;Lim, Chae Jo;Yi, Kyu Yang;Oh, Kwang-Seok;Lee, Byung Ho
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.482-489
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    • 2020
  • G protein-coupled receptor kinase 5 (GRK5) has been considered as a potential target for the treatment of heart failure as it has been reported to be an important regulator of pathological cardiac hypertrophy. To discover novel scaffolds that selectively inhibit GRK5, we have identified a novel small molecule inhibitor of GRK5, KR-39038 [7-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-2-(2-chlorophenyl)-6-fluoroquinazolin-4(3H)-one]. KR-39038 exhibited potent inhibitory activity (IC50 value=0.02 µM) against GRK5 and significantly inhibited angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes. In the pressure overload-induced cardiac hypertrophy mouse model, the daily oral administration of KR-39038 (30 mg/kg) for 14 days showed a 43% reduction in the left ventricular weight. Besides, KR-39038 treatment (10 and 30 mg/kg/day, p.o.) showed significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure following coronary artery ligation. These results suggest that potent GRK5 inhibitor could effectively attenuate both cardiac hypertrophy and dysfunction in experimental heart failure, and KR-39038 may be useful as an effective GRK5 inhibitor for pharmaceutical applications.

Peiminine inhibits myocardial injury and fibrosis after myocardial infarction in rats by regulating mitogen-activated protein kinase pathway

  • Chen, Peng;Zhou, Dengming;Liu, Yongsheng;Wang, Ping;Wang, Weina
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.2
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    • pp.87-94
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    • 2022
  • Myocardial infarction promotes cardiac remodeling and myocardial fibrosis, thus leading to cardiac dysfunction or heart failure. Peiminine has been regarded as a traditional anti-fibrotic Chinese medicine in pulmonary fibrosis. However, the role of peiminine in myocardial infarction-induced myocardial injury and fibrosis remained elusive. Firstly, rat model of myocardial infarction was established using ligation of the left coronary artery, which were then intraperitoneally injected with 2 or 5 mg/kg peiminine once a day for 4 weeks. Echocardiography and haemodynamic evaluation results showed that peiminine treatment reduced left ventricular end-diastolic pressure, and enhanced maximum rate of increase/decrease of left ventricle pressure (± dP/dt max) and left ventricular systolic pressure, which ameliorate the cardiac function. Secondly, myocardial infarction-induced myocardial injury and infarct size were also attenuated by peiminine. Moreover, peiminine inhibited myocardial infarction-induced increase of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α production, as well as the myocardial cell apoptosis, in the rats. Thirdly, peiminine also decreased the myocardial fibrosis related protein expression including collagen I and collagen III. Lastly, peiminine reduced the expression of p38 and phosphorylation of extracellular signal-regulated kinase 1/2 in rat model of myocardial infarction. In conclusion, peiminine has a cardioprotective effect against myocardial infarction-induced myocardial injury and fibrosis, which can be attributed to the inactivation of mitogen-activated protein kinase pathway.

The Effect of Matrix Metalloproteinase Inhibitor for Left Ventricular Remodeling after Myocardial Infarction in a Rabbit Model (토끼에서 Myocardial Infarction 후 Left Ventricular Remodeling에 대한 Matrix Metalloproteinase의 차단 효과)

  • Kim, Soo-Hyun;Jung, Tae-Eun;Hong, Geu-Ru;Han, Sung-Sae
    • Journal of Chest Surgery
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    • v.40 no.5 s.274
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    • pp.329-340
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    • 2007
  • Background: Matrix Metalloproteinase (MMP) inhibition has emerged as a potential therapeutic strategy for the left ventricular dilatation that occurs after myocardial infarction. This study is designed to evaluate which treatment is better for attenuating the left ventricular remodeling via MMP inhibition 1) during the early, short highly MMP producing period of the initial phase or 2) during most of the period of the initial phase after myocardial infarction. Material and Method: Myocardial infarction was induced by ligation of the left anterior descending coronary artery in rabbits. The experimental group was divided into 3 groups. The myocardial infarction only (MI only) group consisted of 7 cases. The MMP inhibitor administered for 5 days after MI (MMPI 50) group had 6 cases, and these rabbits were given MMP inhibitor for 5 days after myocardial infarction, beginning with the postoperative first day. MMP inhibitor administered for 9 days (MMPI 90) group consisted of 5 cases and these rabbits were given MMPI for 9 days the same manner as above. CG2300 was used as a selective MMPI; this is a potent MMP-2 and -9 inhibitor Two-D echocardiograms were performed on all the groups at the time of preoperative period, the post-operative 1st week, the postoperative 20 week and the postoperative 30 week, and we measured the end-diastolic dimension (EDD), the end-systolic dimension (ESD), and the ejection fraction (EF). Result: The echocardiograms generally showed postoperative left ventricular dilatation in the MI only group. The EDD was increased significantly higher in the postoperative 1 week compared to the preoperative value (p<0.05). The ESD was also increased significantly higher in the postoperative 1st week, the postoperative 20 week and the postoperative 30 week compared to the preoperative value (p<0.05). Left ventricular dilatation was noted to be less In the MMPI 9d group than in the MI only and MMPI 5d groups. In the MMPI 9d group, there was no significant change of EF postoperatively compared to the preoperative period. MMP-2 and MMP-9 were measured from the infarcted myocardial tissue at post-MI 4 weeks by performing western blotting and zymography. The changes the of protein expression and activity of MMP-2 and MMP-9 were not significant in the three MI groups and the normal heart group. Histopathologic examination revealed severe collagen deposition in the MI only group. Collagen accumulation was reduced in both the MMPI groups. The MMPI 9d group revealed an increased number of capillaries. Conclusion: Left ventricular dilatation developed rapidly after, MI from ligation of the coronary artery and MMPI attenuated the ventricular dilatation. The effect of MMPI seemed to have better a result from its usage during most of the period of the initial phase after myocardial infarction. This suggested that increased neovascularization by MMPI may also contribute to attenuation of the left ventricular remodeling.

Early hypothermia improves outcomes of cardiopulmonary resuscitation after cardiac arrest in acute myocardial infarction rat models (급성심근경색 쥐 모델의 심정지 후 조기 저체온 치료가 심폐소생술 결과에 미치는 효과)

  • Park, Jeong-Hyun;Im, Hee-Kyung;Kim, Jee-Hee;Lee, Young-Il
    • The Korean Journal of Emergency Medical Services
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    • v.20 no.2
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    • pp.7-19
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    • 2016
  • Purpose: To investigate the effect of early hypothermia on post-resuscitation myocardial recovery and survival time after cardiac arrest and resuscitation in a rat model of myocardial infarction(MI). Methods: Thoracotomies were performed in 10 male Sprague Dawley rats weighing 450-455g. Myocardial infarction was induced by ligation of the left anterior descending coronary artery. Ninety minutes after arterial ligation, ventricular fibrillation was induced, cardiopulmonary resuscitation was subsequently performed before defibrillation was attempted. Animals were randomized to control group and experimental group(acute MI-normothermia)($32^{\circ}C$ for 4 hours). Duration of survival was recorded. Myocardial functions, including cardiac output, left ventricular ejection fraction, and myocardial performance index were measured using echocardiography. Results: Myocardial function was significantly better in hypothermia group than the control group during the first 4 hours post-resuscitation. The survival time of the experimental group was greater than that of the control group(p<.050). Conclusion: This study suggests that early hypothermia can attenuate post-resuscitation myocardial dysfunction after acute myocardial function, and may be a useful strategy in post-resuscitation care.

Therapeutic Angiogenesis by Intramyocardial Injection of pCK-VEGF165 in Pigs (돼지에서 pCK-VEGF165의 심근내 주입에 의한 치료적 혈관조성)

  • Choi Jae-Sung;Han Woong;Kim Dong Sik;Park Jin Sik;Lee Jong Jin;Lee Dong Soo;Kim Ki-Bong
    • Journal of Chest Surgery
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    • v.38 no.5 s.250
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    • pp.323-334
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    • 2005
  • Background: Gene therapy is a new and promising option for the treatment of severe myocardial ischemia by therapeutic angiogenesis. The goal of this study was to elucidate the efficacy of therapeutic angiogenesis by using VEGF165 in large animals. Material and Method: Twenty-one pigs that underwent ligation of the distal left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF (VEGF) or intramyocardial injection of pCK-Null (Control). Injections were administered 30 days after ligation. Seven pigs died during the trial, but eight pigs from VEGF and six from Control survived. Echo-cardiography was performed on day 0 (preoperative) and on days 30 and 60 following coronary ligation. Gated myocardial single photon emission computed tomography imaging (SPECT) with $^{99m}Tc-labeled$ sestamibi was performed on days 30 and 60. Myocardial perfusion was assessed from the uptake of $^{99m}Tc-labeled$ sestamibi at rest. Global and regional myocardial function as well as post-infarction left ventricular remodeling were assessed from segmental wall thickening; left ventricular ejection fraction (EF); end systolic volume (ESV); and end diastolic volume (EDV) using gated SPECT and echocardiography. Myocardium of the ischemic border zone into which pCK plasmid vector had been injected was also sampled to assess micro-capillary density. Result: Micro-capillary density was significantly higher in the VEGF than in Control ($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2};\;p<0.001$). Segmental perfusion increased significantly from day 30 to day 60 after intramyocardial injection of plasmid vector in VEGF ($48.4\pm15.2\%\;vs.\;53.8\pm19.6\%;\;p<0.001$), while no significant change was observed in the Control ($45.1\pm17.0\%\;vs.\;43.4\pm17.7\%;\;p=0.186$). This resulted in a significant difference in the percentage changes between the two groups ($11.4\pm27.0\%\;increase\;vs.\;2.7\pm19.0\%\;decrease;\;p=0.003$). Segmental wall thickening increased significantly from day 30 to day 60 in both groups; the increments did not differ between groups. ESV measured using echocardiography increased significantly from day 0 to day 30 in VEGF ($22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL;\; p=0.006$) and in Control ($26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL;\;p=0.046$). EF decreased significantly in VEGF ($52.0\pm7.7\%\;vs.\;46.5\pm7.4\%;\;p=0.004$) and in Control ($48.2\pm9.2\%\;vs.\;41.6\pm10.0\%;\;p=0.028$). There was no significant change in EDV. The interval changes (days $30\~60$) of EF, ESV, and EDV did not differ significantly between groups both by gated SPECT and by echocardiography. Conclusion: Intramyocardial injection of pCK-VEGF165 induced therapeutic angiogenesis and improved myocardial perfusion. However, post-infarction remodeling and global myocardial function were not improved.

A Quantitative Ultrastructural Study on the Effects of Ischemia and Reperfusion on the Rat and Cat Hearts (허혈 및 재관류가 흰쥐 및 고양이 심장에 미치는 영향에 관한 형태계측학적 연구)

  • Park, Young-Sik;Uhm, Chang-Sub;Suh, Young-Suk
    • Applied Microscopy
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    • v.22 no.1
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    • pp.42-54
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    • 1992
  • To understand the structural changes of the myocardial myocytes and endothelial cells in ischemic and reperfused heart, and to elucidate their roles in those conditions, the authors observed cat and rat myocardium ultrastructurally and evaluated them with morphometric techniques. In cat, mild ischemia and moderate degree reperfusion injury was induced by ligation of the anterior interventricular branch of left coronary artery and reperfusion. In rat, severe ischemia and irreversible reperfusion iniury was made using in vitro Langendorff techniques. In normal cat myocytes, the volume densities of cytoplasm, myofibrils, mitochondria, sarcoplasmic reticulum and T tubules were $0.11{\pm}0.013,\;0.51{\pm}0.096,\;0.25{\pm}0.082,\;0.09{\pm}0.008,\;0.02{\pm}0.010$ (Mean${\pm}$S.D.) respectively, and the myofibril/mitochondria ratio was $2.33{\pm}1.379$. The numerical density and average volume of mitochondria were $0.76{\pm}0.210/{\mu}m^3$ and $0.33{\pm}0.057{\mu}m^3$ respectively. In normal cat endothelial cells, the volume densities of cytoplasm, cytoplasmic vesicles, tubular systems (including endoplasmic reticulum and Golgi apparatus) and mitochondria were $0.43{\pm}0.023,\;0.28{\pm}0.007,\;0.22{\pm}0.021,\;0.03{\pm}0.014$ respectively. The mean thickness of endothelial cells was $230{\pm}45.2{\mu}m$. The numerical density and average volume of cytoplasmic vesicles were $508{\pm}55.0/{\mu}m^3,\;578{\pm}104.8nm^3$ respectively. In cat myocytes which received mild ischemic injury, the volume densities of organelles were not changed significantly in ischemic and reperfusion states. In reperfusion group myocytes, the numerical density of mitochondria was decreased significantly and the average volume was increased significantly. In endothelial cells, the volume density of tubular system in ischemic group and the average volume of cytoplasmic vesicles in reperfusion group were increased significantly. In rat myocytes which received severe ischemic injury, the volume density and average volume of mitochondria were increased significantly, and the volume density of sarcoplasmic reticulum and numerical density of mitochondria were decreased significantly in both ischemic and reperfusion groups. In ischemic and reperfused endothelial cells, the volume density and numerical density of cytoplasmic vesicles, the volume density of cytoplasm were decreased significantly. The volume densities of tubular system were increased significantly in both ischemic and reperfused groups. The volume density of mitochondria in ischemic group and the average volume of cytoplasmic vesicles in reperfusion group showed significant increase. The authors, based on the above observations, conclude that the mitochondria of myocytes and the cytoplasmic vesicles of endothelia are the first group of targets in ischemic and reperfusion injury and in this respect, the degree of ischemic insult is not significant. The role of myocyte mitochondria in reperfusion injury may be insignificant, but endothelial cells may contribute actively to reperfusion injury.

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Cardioprotective Potential of Gracilaria Verrucosa Extract in Myocardial Infarction-Induced Heart Failure Model (심근 경색 유발 심부전 모델에서 강리 추출물의 심장 보호 가능성)

  • Youn Jae Jang;Hye Yoom Kim;Jung Joo Yoon;Byung Hyuk Han;Je Kuk Yu;Nam Geun Cho;Ho Sub Lee;Dae Gill Kang
    • Herbal Formula Science
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    • v.31 no.3
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    • pp.157-169
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    • 2023
  • Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.