• Applied Microscopy
• /
• v.23 no.1
• /
• pp.139-163
• /
• 1993

Background: It has been well established and is now no longer a controversial issue that ischemia produces a series of inflammatory reactions and the ischemic myocardium cannot survive without adequate restoration of coronary flow, ie, reperfusion. Nevertheless, controversies that intravascular pluggings (IVP) by polymorphonuclear leukocytes (PMNs) or platelets may cause contractile dysfunction in ischemia and even in repefusion still remain. Accordingly, we attempted to examine the intravascular plug fomation as well as the ultrastructural changes in myocytes and microvessels and to determine the relation among them. Methods: 1) Human (n= 10, 39-63 years of age; 3 females and 7 males): left ventricular myocardium (LVM) was biopsied from chronic ischemic heart disease patient during bypass surgery. 2) Calf (Holstein-Friesian species, n=4): Circumflex branch of the left coronary artery (LCx) was occluded (ischemia) for 45 minutes and recanalized (reperfusion) for 3 and 6 hours, respectively and LVMs were biopsied after occlusion and recanalization, respectiverly. 3) Rat (Sprague-Dawley species, n=20): Left coronary artery (LCA) was occluded for 20 minutes and recanalized for an hour as the method described by Selye et al., (1960) and hearts were removed after occlusion and recanalization, respectively. 4) Pig (landrace type, n=7): Anterior ascending branch of the left coronary artery (LAD) was coccluded for 45 minutes and recanalized for 2 hours and LVMs were biopsied after occlusion and recanalization, repectively. All of the LVMs were routinely prepared for transmissiom electron microscopy. Rseults: In human, most of the LVM showed irreversible ultrastructural changes in myocytes and frequent IVPs by PMNs or platelets without any significant correlation with age or sex. In the animal LVM, myocytes showed reversible ultrastructural changes with slight variations in accordance with the species, duration of ischemia and reperfusion or site of biopsy, however, injuries were more severe in the subendocardial myocytes and IVPs by PMNs or platelets were frequently observed. Ultrastructural changes in the myocytes seemed to be gradually improved by recanalization, howerver, IVPs were still observed after recanalization. Conclusion: These results suggest that microvessels are more resistant to ischemic insult than the myocytes themselves and IVP by PMNs and platelets may play an important role to produce ischemic or reperfusion injuries. Thus, it is favorable that angioplasty is preceded by thrombolysis and it is likely that restoration of myocardial function requires relarively long period of time even after recanalization.

• Journal of Veterinary Clinics
• /
• v.32 no.6
• /
• pp.486-490
• /
• 2015

Two-demensional echocardiography is routinely used for evaluation of cardiac function. Visualization of the endocardial border is essential for the assessment of global and regional left ventricular with cardiac disease. SonoVue$^{TM}$ is a microbubble contrast agent that consists of sulfur hexafluoride-filled microbubbles in a phospholipid shell. There were many studies about contrast echocardiographic examination using SonoVue$^{TM}$ contrast agent, and various doses of SonoVue$^{TM}$ were used. To our knowledge, in published veterinary medicine, there was not reported for diagnostic efficient dose of SonoVue$^{TM}$ to evaluate contrast enhanced left ventricular endocardial border delineation (LVEBD). The purpose of this study is to compare the visualization time of LVEBD and find efficient dose of SonoVue$^{TM}$ for using various doses in dogs. Ten healthy Beagles were recruited to the study. Three different doses (0.03 ml/kg, 0.05 ml/kg and 0.1 ml/kg) of SonoVue$^{TM}$ were injected. Endocardial segments were assigned based on previously established methodology, where by the four-chamber views of the LV were divided into 6 segments. In this study, Contrast enhancement of the LVEBD after each injection was evaluated visually at the time point of overall contrast enhancement (Segmental scoring 5+) in the LV by three investigators in a blind manner. Statistical analysis was performed with SPSS version 14.0. All data were analyzed using one-way ANOVA, the multiple comparison Scheffe test. When data for the three offsite readers were combined, mean durations of useful contrast were $3.54({\pm}2.14)$, $6.15({\pm}2.61)$, and $24.39({\pm}11.10)$ seconds for the 0.03 ml/kg, 0.05 ml/kg, and 0.1 ml/kg SonoVue$^{TM}$ doses, respectively. After injection of contrast agent, there were no significant change in side effects such as urticaria, angioedema, hypersensitivity reactions, and digestive system disorders. This study suggests that efficient dose of SonoVue$^{TM}$ contrast agent for improvement of the left ventricle visualization is 0.1 ml/kg. The duration of useful enhancement of LVEBD and the reproducibility were also the highest at the 0.1 ml/kg dosage.

• Biomolecules & Therapeutics
• /
• v.6 no.4
• /
• pp.358-363
• /
• 1998

Intravenous lipid emulsion is used extensively as a major component of parenteral nutrition for patients in the surgical intensive care unit. Abnormal cardiovascular function related to lipid infusion has been reported although conflicting results exist. In the present study, we investigated the effects of intravenous emulsions of long-chain triglyceride (LCT) and medium-chain triglyceride (MCT) on myocardial ischemia/ reperfusion injury and on platelet aggregation in rat. There was no difference between LCT and MCT considering the effects on left ventricular developed pressure (LVDP) and coronary flow rate (CFR) before and after ischemia/reperfusion in isolated rat heart. On the other hand, a difference was found between LCT and MCT with regard to their effects on heart rate (HR) and end diastolic pressure (EDP) after ischemia/reperfusion. After ischemia/reperfusion, HR was significantly (P<0.05) reduced and EDP significantly (P<0.05) inc.eased by LCT (18$\pm$2.0% and 42.8$\pm$8.9%, respectively), but not by MCT Ex vivo platelet aggregation induced by collagen was reduced by LCT infusion, but not by MCT These findings suggest that MCT may have slightly more favorable effect than LCT on the myocardial function after ischemia/reperfusion in rat.

• Biomolecules & Therapeutics
• /
• v.28 no.5
• /
• pp.482-489
• /
• 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.

• Korean Circulation Journal
• /
• v.54 no.4
• /
• pp.172-186
• /
• 2024

Background and Objectives: Long-term pathological myocardial hypertrophy (MH) seriously affects the normal function of the heart. Dronedarone was reported to attenuate left ventricular hypertrophy of mice. However, the molecular regulatory mechanism of dronedarone in MH is unclear. Methods: Angiotensin II (Ang II) was used to induce cell hypertrophy of H9C2 cells. Transverse aortic constriction (TAC) surgery was performed to establish a rat model of MH. Cell size was evaluated using crystal violet staining and rhodamine phalloidin staining. Reverse transcription quantitative polymerase chain reaction and western blot were performed to detect the mRNA and protein expressions of genes. JASPAR and luciferase activity were conducted to predict and validate interaction between forkhead box O3 (FOXO3) and protein kinase inhibitor alpha (PKIA) promoter. Results: Ang II treatment induced cell hypertrophy and inhibited sirtuin 1 (SIRT1) expression, which were reversed by dronedarone. SIRT1 overexpression or PKIA overexpression enhanced dronedarone-mediated suppression of cell hypertrophy in Ang II-induced H9C2 cells. Mechanistically, SIRT1 elevated FOXO3 expression through SIRT1- mediated deacetylation of FOXO3 and FOXO3 upregulated PKIA expression through interacting with PKIA promoter. Moreover, SIRT1 silencing compromised dronedarone-mediated suppression of cell hypertrophy, while PKIA upregulation abolished the influences of SIRT1 silencing. More importantly, dronedarone improved TAC surgery-induced MH and impairment of cardiac function of rats via affecting SIRT1/FOXO3/PKIA axis. Conclusions: Dronedarone alleviated MH through mediating SIRT1/FOXO3/PKIA axis, which provide more evidences for dronedarone against MH.

• Journal of Cardiovascular Imaging
• /
• v.30 no.1
• /
• pp.25-34
• /
• 2022

BACKGROUND: The purpose of this study was to assess the utility of a handheld device (HH) used during common daily practice and its agreement with the results of a standard echocardiography study (STD) performed by experienced sonographers and echocardiographer. METHODS: A prospective follow-up was conducted in an adult outpatient echocardiography clinic. Experienced sonographers performed the STD and an experienced echocardiographer performed the HH. STD included 2-dimensional images, Doppler and hemodynamics analysis. Hemodynamic assessment was not performed with the HH device because the HH does not include such technology. The images were interpreted by blinded echocardiographers, and the agreement between the reports was analyzed. RESULTS: A total of 108 patients were included; and the concordance for left ventricle (LV) ejection fraction (EF), wall motion score index, LV and right ventricle (RV) function, RV size, and mitral and aortic stenosis was excellent with κ values greater than 0.80. Wall motion abnormalities had good concordance (κ value 0.78). The agreement for LV hypertrophy, mitral and aortic regurgitation was moderate, and tricuspid and pulmonary regurgitation agreements were low (κ values of 0.26 and 0.25, respectively). CONCLUSIONS: In a daily practice scenario with experienced hands, HH demonstrated good correlation for most echocardiography indications, such as ventricular size and function assessment and stenosis valve lesion analyses.

• Korean Journal of Radiology
• /
• v.22 no.3
• /
• pp.324-333
• /
• 2021

Objective: The clinical course of an individual patient with heart failure is unpredictable with left ventricle ejection fraction (LVEF) only. We aimed to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived myocardial fibrosis extent and to determine the cutoff value for event-free survival in patients with non-ischemic cardiomyopathy (NICM) who had severely reduced LVEF. Materials and Methods: Our prospective cohort study included 78 NICM patients with significantly reduced LV systolic function (LVEF < 35%). CMR images were analyzed for the presence and extent of late gadolinium enhancement (LGE). The primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, heart transplantation, implantable cardioverter-defibrillator discharge for major arrhythmia, and hospitalization for congestive heart failure within 5 years after enrollment. Results: A total of 80.8% (n = 63) of enrolled patients had LGE, with the median LVEF of 25.4% (19.8-32.4%). The extent of myocardial scarring was significantly higher in patients who experienced MACE than in those without any cardiac events (22.0 [5.5-46.1] %LV vs. 6.7 [0-17.1] %LV, respectively, p = 0.008). During follow-up, 51.4% of patients with LGE ≥ 12.0 %LV experienced MACE, along with 20.9% of those with LGE ≤ 12.0 %LV (log-rank p = 0.001). According to multivariate analysis, LGE extent more than 12.0 %LV was independently associated with MACE (adjusted hazard ratio, 6.71; 95% confidence interval, 2.54-17.74; p < 0.001). Conclusion: In NICM patients with significantly reduced LV systolic function, the extent of LGE is a strong predictor for long-term adverse cardiac outcomes. Event-free survival was well discriminated with an LGE cutoff value of 12.0 %LV in these patients.

• Pediatric Infection and Vaccine
• /
• v.5 no.2
• /
• pp.267-275
• /
• 1998

Purpose : We have studied the changes of cardiac troponin I(cTnI) level and left ventricular ejection fraction(LVEF) before and after treatment of IVGG to evaluate the efficacy of single high dose of intravenous gammaglobulin(IVGG)(2.0gm/kg) therapy for improving cardiac function and clinical symptoms and signs in patients with clinically suspected acute myocarditis. Methods : The patients consisted of 18 cases who admitted increased cTnI with clinically suspected acute myocarditis caused by viral infection, Kawasaki disease and fever unknown origin(FUO) from Jan. 1995 to Jun. 1998. The control group consisted of 20 cases suffered from hand-foot-mouth disease, herpangina and high fever with rash. The level of cTnI was measured by Chemiluminiscent immunoassay method(normal<0.1ng/ml) and cardiac function was evaluated by left ventricular ejection fraction(LVEF)(normal 64~83%) by echocardiogram. Results : The level of cTnI increased to $0.306{\pm}0.209ng/ml$ and LVEF decreased to $60.1{\pm}1.6%$ before treatment of IVGG significantly as compared with control group(P<0.05). All cases were returned to normal range of LVEF($71.4{\pm}3.7%$) and decreased cTnI significantly($0.089{\pm}0.082ng/ml$) after treated with IVGG within 1 week in patients group(P<0.05). Conclusion : The single high dose of IVGG(2.0gm/kg) therapy was rapid and effective improvement of cardiac function and clinical symptoms and signs of acute myocarditis, and the measurement of serum cTnI and LVEF may help to diagnose and evaluate efficacy of IVGG on it.

• Journal of Chest Surgery
• /
• v.29 no.3
• /
• pp.255-262
• /
• 1996

The donor pool for heart transplants is severely limited and there is still a legal problem of brain death. This study assessed the function of hearts "absolute anoxic" for ten minutes after asphyxia by perfusing the hearts on a Langendorfr apparatus for 45 minutes with Krebs-Henseleit buffier at 37 t at 80 cm H2O. Forty isolated rat hearts were divided into four groups. Ten control hearts (group 1) were perfused on the circuit without intervening ischemia. Ten hearts (group 2) were harvested, quickly flushed with 5cc of cold University of Wisconsin solution, and stored in the same cold solution for 4 hours. Ten hearts (group 3) were excised, quickly flushed with 5 u of cold Stanford cardioplegic solution and stored in cold saline solution for 4 hours. Ten asphyxiated hearts (group 4) had warm ischemia for ten minutes and were perfused with 5u of cold Stanford cardioplegia containing 7,500 units of urokinase to dissolve intravascular clots, and stored in cold saline solution for 1.5 hours. Time of spontaneous defibrillation (TSD) after perfusion was significantly longer in group 2, group 3 and group 4 than in group 1. TSD in group 3 and group 4 was significantly longer in comparison to that of group 2. Left ventricular developed pressure(LVDP) at 15 minutes was significantly lower in group 3 and group 4 than in group 1 and group 2. In group 4, LVDP at 30 minutes and 45 minutes was significantly lower compared with that in group 1 . In conclusion, asphyxiated rat hear;ts which had absolute anoxia for 10 minutes after as hyxia showed relatively satisfactory cardiac function. function.

• Journal of Chest Surgery
• /
• v.35 no.5
• /
• pp.336-342
• /
• 2002

Background: Recently, cell transplantation has been extensively investigated to improve heart function in dysfunctional heart. This study was designed to compare the effects of smooth muscle cells (SMC) and heart cells (HC) transplantation in dilated cardiomyopathic hamsters. Material and Method: HC and SMC were isolated from heart and ductus deferens of BIO 53.58 hamsters, and cultured for transplantation. HC and SMC or culture medium were transplanted into the left ventricle of 17 weeks old adult hamsters in HC transplanted (HCTx), SMC transplantation (SMCTX), and control groups (Con) (N = 10 each). Cyclosporine (5 mg/Kg) was administered subcutaneously for HCTx. Sham operated hamsters (N=10) underwent the surgery but did not receive an injection. At 4 weeks after transplantation, heart function was evaluated in all groups using a Langendorff perfusion apparatus. Result: Histology showed severe focal myocardial necrosis in all groups. HCTx and SMCTx formed huge muscle tissue in dilated myocardium. SMCTx and HCTx had better heart function than Con and sham (p<0.01). And SMCTx had better peak systolic pressure (p<0.05) antral developed pressure (p<0.05) than HCTx. But sham and Con did not any statistical make difference. Conclusion: SMCTx and HCTx formed muscle tissue and improved ventricular function in hamsters with dilated cardiomyopathy And SMCTx showed better heart function in peak systolic pressure and developed pressure than HCTx.