• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.335-345
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• 2022

Pyroptosis is an inflammatory form of programmed cell death that is linked with invading intracellular pathogens. Cardiac pyroptosis has a significant role in coronary microembolization (CME), thus causing myocardial injury. Tanshinone IIA (Tan IIA) has powerful cardioprotective effects. Hence, this study aimed to identify the effect of Tan IIA on CME and its underlying mechanism. Forty Sprague-Dawley (SD) rats were randomly grouped into sham, CME, CME + low-dose Tan IIA, and CME + high-dose Tan IIA groups. Except for the sham group, polyethylene microspheres (42 ㎛) were injected to establish the CME model. The Tan-L and Tan-H groups received intraperitoneal Tan IIA for 7 days before CME. After CME, cardiac function, myocardial histopathology, and serum myocardial injury markers were assessed. The expression of pyroptosis-associated molecules and TLR4/MyD88/NF-κB/NLRP3 cascade was evaluated by qRT-PCR, Western blotting, ELISA, and IHC. Relative to the sham group, CME group's cardiac functions were significantly reduced, with a high level of serum myocardial injury markers, and microinfarct area. Also, the levels of caspase-1 p20, GSDMD-N, IL-18, IL-1β, TLR4, MyD88, p-NF-κB p65, NLRP3, and ASC expression were increased. Relative to the CME group, the Tan-H and Tan-L groups had considerably improved cardiac functions, with a considerably low level of serum myocardial injury markers and microinfarct area. Tan IIA can reduce the levels of pyroptosis-associated mRNA and protein, which may be caused by inhibiting TLR4/MyD88/NF-κB/NLRP3 cascade. In conclusion, Tanshinone IIA can suppress cardiomyocyte pyroptosis probably through modulating the TLR4/MyD88/NF-κB/NLRP3 cascade, lowering cardiac dysfunction, and myocardial damage.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.143-155
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• 2023

Percutaneous coronary intervention and acute coronary syndrome are both closely tied to the frequently occurring complication of coronary microembolization (CME). Resveratrol (RES) has been shown to have a substantial cardioprotective influence in a variety of cardiac diseases, though its function and potential mechanistic involvement in CME are still unclear. The forty Sprague-Dawley rats were divided into four groups randomly: CME, CME + RES (25 mg/kg), CME + RES (50 mg/kg), and sham (10 rats per group). The CME model was developed. Echocardiography, levels of myocardial injury markers in the serum, and histopathology of the myocardium were used to assess the function of the cardiac muscle. For the detection of the signaling of TLR4/MyD88/NF-κB along with the expression of pyroptosis-related molecules, ELISA, qRT-PCR, immunofluorescence, and Western blotting were used, among other techniques. The findings revealed that myocardial injury and pyroptosis occurred in the myocardium following CME, with a decreased function of cardiac, increased levels of serum myocardial injury markers, increased area of microinfarct, as well as a rise in the expression levels of pyroptosis-related molecules. In addition to this, pretreatment with resveratrol reduced the severity of myocardial injury after CME by improving cardiac dysfunction, decreasing serum myocardial injury markers, decreasing microinfarct area, and decreasing cardiomyocyte pyroptosis, primarily by blocking the signaling of TLR4/MyD88/NF-κB and also reducing the NLRP3 inflammasome activation. Resveratrol may be able to alleviate CME-induced myocardial pyroptosis and cardiac dysfunction by impeding the activation of NLRP3 inflammasome and the signaling pathway of TLR4/MyD88/NF-κB.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.4
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• pp.207-211
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• 2004

The purpose of the present study was to evaluate the expression of cardiac marker protein in rabbit cardiac tissue that was exposed to ischemic preconditioning (IPC), or ischemiareperfusion injury (IR) using two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). We compared 2DE gels of control (uninjured) cardiac tissue with those of IPC and IR cardiac tissue. Expression of one protein was detected in IR heart tissue, however the protein was not detected in the samples of control and IPC tissue. To further characterize the detected protein molecule, the protein in the 2D gel was isolated and subjected to trypsin digestion, followed by MALDI-MS. The protein was identified as myoglobin, which was confirmed also by Western blot analysis. These results are consistent with previous studies of cardiac markers in ischemic hearts, indicating myoglobin as a suitable marker of myocardial injury. In addition, the present use of multiple techniques indicates that proteomic analysis is an appropriate means to identify cardiac markers in studies of IPC and IR.

• Journal of Yeungnam Medical Science
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• v.18 no.1
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• pp.13-29
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• 2001

The enzyme activities of creatine kinase (CK), its isoenzyme MB (CK-MB) and of lactate dehydrogenase isoenzyme 1 (LD-1) have been used for years in diagnosing patients with chest pain in order to differentiate patients with acute myocardial infarction (AMI) from non-AMI patients. These methods are easy to perform as automated analyses, but they are not specific for cardiac muscle damage. During the early 90's the situation changed. First, creatine kinase ME mass (CK-MB mass) replaced the measurement of CK-MB activity. Subsequently cardiac-specific proteins, troponin T (cTnT) and troponin I (cTnI) appeared and displacing LD-1 analysis. However, troponin concentrations in blood increase only from four to six hours after onset of chest pain. Therefore a rapid marker such as myoglobin, fatty acid binding protein or glycogen phosphorylase BB could be used in early diagnosis of AMI. On the other hand, CK-MB isoforms alone may also be useful in rapid diagnosis of cardiac muscle damage. Myoglobin, CK-MB mass, cTnT and cTnI are nowadays widely used in diagnosing patients with acute chest pain. Myoglobin is not cardiac-specific and therefore requires supplementation with some other analyses such as troponins to support the myoglobin value. Troponins are very highly cardiac-specific. Only the sera of some patients with severe renal failure, which requires hemodialysis, have elevated cTnT and/or cTnI without there being any evidence of cardiac damage. The latest studies have shown that elevated troponin levels in sera of hemodialysis patients point to an increased risk of future cardiac events in a similar manner to the elevated troponin values in sera of patients with unstable angina pectoris. In addition, the bedside tests for cTnT and cTnI alone- or together with myoglobin and CK-ME mass can be used instead of quantitative analyses in the diagnosis of patients with chest pain. These rapid tests are easy to perform and they do not require expensive instrumentation. For the diagnosis of patient with chest pain, routinely myoglobin and CK-ME mass measurements should be performed whenever they are requested (24 h/day) and cTnT or cTnI on admission to the hospital and then 4-6 and 12 hours later and maintained less than 10% in imprecision.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.5
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• pp.419-423
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• 2014

The purpose of the present study was to investigate cardiac damage biomarkers after a triathlon race in elite and non-elite athlete groups. Fifteen healthy men participated in the study. Based on performance, they were divided into elite athlete group (EG: n＝7) and non-elite athlete group (NEG: n＝8). Participants' blood samples were obtained during four periods: before, immediately, 2 hours and 7 days after finishing the race. creatine kinase (CK), creatine kinase-myoglobin (CK-MB), myoglobin, and lactate dehydrogenase (LDH) were significantly increased in both groups immediately after, and 2 hours after finishing the race (p<.05). CK, CK-MB, and myoglobin were completely recovered after 7 days (p<.05). Hematocrit (Hct) was significantly decreased in both groups (p<.05) 7 days after the race. LDH was significantly decreased in the EG (p<.05) only 7 days after the race. Homoglobin (Hb) was significantly decreased in the NEG (p<.05) only 2 hours after the race. Although cardiac troponin T (cTnT) was significantly increased in the EG but not in the NEG 2hours after the race (p<.05), there was no group-by-time interaction. cTnT was completely recovered in both groups 7 days after the race. In conclusion, cardiac damage occurs during a triathlon race and, is greater in elite than in non-elite. However, all cardiac damage markers return to normal range within 1 week.

• Biomedical Science Letters
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• v.17 no.2
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• pp.113-122
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• 2011

Several studies have reported a relation between serum levels of uric acid and a wide variety of cardiovascular conditions. But, the relationship between serum levels of uric acid and coronary artery disease (CAD) is still controversial. The present study was retrospectively designed to investigate whether CAD can be stratified by the level of uric acid and there are the relationships between preoperative levels of uric acid and perioperative biochemical markers in fifty-adult patients that underwent coronary artery bypass grafting surgery (CABG) and twenty-normal subjects. They were divided into the control, the unstable angina (UA-group) and the myocardial infarction group (MI-group). In preoperative levels of uric acid, the MI-group was higher than control and the UA-group. The MI-group had significantly higher correlations than the UA-group between preoperative levels of uric acid and left ventricular ejection fraction, cardiac markers (creatine kinase, lactate dehydrogenase and brain natriuretic peptide), renal markers (blood urea nitrogen and creatinine) or total leukocyte levels. At postoperative periods, the MI-group had higher relationships of uric acid with aspartate aminotransferase, blood urea nitrogen or creatinine levels. Although there was not statistically significant, the UA-group tended to have higher correlation coefficients than the MI-group between preoperative levels of uric acid and intensive care unit-stay (ICU), or postoperative mechanical ventilation time. These results reflect that increased levels of serum uric acid may be a tool for the diagnosis of coronary heart disease and may be considered as a good predictor in assessing the cardiac and renal functions in patients with myocardial infarction or unstable angina at the preoperative period. However, further studies should be performed in a large patient population.

• 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.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.206-212
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• 2015

Background: Ginseng total saponin (GTS) contains various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The aim of this study was to study the effects of GTS on cardiac injury after global ischemia and reperfusion (I/R) in isolated guinea pig hearts. Methods: Animals were subjected to normothermic ischemia for 60 minutes, followed by 120 minutes of reperfusion. GTS significantly increased aortic flow, coronary flow, and cardiac output. Moreover, GTS significantly increased left ventricular systolic pressure and the maximal rate of contraction ($+dP/dt_{max}$) and relaxation ($-dP/dt_{max}$). In addition, GTS has been shown to ameliorate electrocardiographic changes such as the QRS complex, QT interval, and RR interval. Results: GTS significantly suppressed the biochemical parameters (i.e., lactate dehydrogenase, creatine kinase-MB fraction, and cardiac troponin I levels) and normalized the oxidative stress markers (i.e., malondialdehyde, glutathione, and nitrite). In addition, GTS also markedly inhibits the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, and nuclear factor-${\kappa}B$, and improves the expression of IL-10 in cardiac tissue. Conclusion: These data indicate that GTS mitigates myocardial damage by modulating the biochemical and oxidative stress related to cardiac I/R injury.

• Journal of Life Science
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• v.20 no.10
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• pp.1458-1467
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• 2010

The present study was retrospectively designed to define whether preoperative levels of leukocytes and D-dimer are potentially useful factors in predicting perioperative outcomes of coronary heart disease (CHD). There was no relationship between preoperative leukocyte counts (Pre-OP leukocyte) and preoperative D-dimer levels (Pre-OP D-dimer). Pre-OP leukocyte counts each had positive correlation with cardiac troponin-I, creatine kinase-MB or C-reactive protein (cardiac markers) levels at preoperative and postoperative periods. Pre-OP D-dimer levels were positively associated with each cardiac marker at the same periods. Pre-OP leukocyte counts positively related with aspartate aminotransferase and alanine aminotransferase (liver markers), whereas Pre-OP D-dimer level positively or negatively correlated with bilirubin (liver marker), creatinine (renal marker) or glucose levels at preoperative and/or postoperative periods. Pre-OP leukocyte and Pre-OP D-dimer were inversely associated with Pre-OP high density lipoprotein cholesterol levels or left ventricular ejection fraction. Pre-OP leukocyte counts each had positive correlation operation duration and postoperative mechanical ventilation-time (PMVT), whereas Pre-OP D-dimer levels had positive relationship with PMVT, intensive care unit-staying period and hospitalization. The retrospective data suggest that Pre-OP leukocyte and Pre-OP D-dimer levels may be clinically useful factors for predicting perioperative outcomes in patients with CHD.

• Physical Therapy Rehabilitation Science
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• v.3 no.2
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• pp.107-111
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• 2014

Objective: In the present study, we investigated the protective effects of low-intensity treadmill training in doxorubicin-induced cardiotoxicity rat models. Design: Randomized controlled trial. Methods: In this study, we randomly divided them into four groups. The normal group included non-cardiotoxicity normal control (n=10), the control group included non-treadmill training after doxorubicin-induced cardiotoxicity (n=10), the experimental group I included low-intensity treadmill training (3 m/min) after doxorubicin-induced cardiotoxicity (n=10), and the experimental group II included low-intensity treadmill training (8 m/min) after doxorubicin-induced cardiotoxicity (n=10). Rats in the treadmill training group underwent treadmill training, which began at 2 weeks after first intraperitoneal injection. We determined the body weight change for each rat on days 1 and 21. Biochemical markers (lactate dehydrogenase [LDH], creatine kinase [CK], glutathion, aspartate transaminase [AST], and alanine transaminase [ALT]) concentration in the serum change of rats from all four groups was examined at the end of the experiment. Results: The results showed that the experimental group I and II showed a significant increase in body weight as compared with that of the control group (p<0.05). We observed that the biochemical markers (LDH, CK, glutathion, AST, and ALT) were improved in the experimental group I than the experimental group II (p<0.05). There was no difference between the experimental groups. Conclusions: In conclusion, our data suggest that low-intensity treadmill training applied after doxorubicin treatment protects against cardiotoxicity following treatment, possibly by enhancing antioxidant defenses and inhibiting cardiac muscle cell apoptosis.