2010 Vol. 7, No. 4
Objective To investigate the effect of body weight on the induction of mild hypothermia in a rabbit model of asphyxia cardiac arrest. Methods Twenty-four rabbits were randomized into two groups: the ice bag group and the intravenous 4℃ saline group. Cardiac arrest was induced and after 3 minutes of cardiac arrest, cardiopulmonary resuscitation was begun. Simultaneously, mild hypothermia was induced by putting an ice bag over the abdomen or infusion of 4℃ saline via an ear vein. A 2℃ decrease of rectal temperature was considered as the completion of hypothermia induction. Induction times were recorded, compared, and analyzed with respect to body weight. Results All rabbits had restoration of spontaneous circulation (ROSC) and ROSC lasted during the experiment. Induction time in the ice bag group was significantly shorter than that in the intravenous 4℃ saline group (22.8±4.7 min VS 42.5±4.0 min, P< 0.001). Induction time significantly correlated with body weight in the ice bag group (Pearson Correlation: r = 0.725, P = 0.029), but not in the intravenous 4℃ saline group (Pearson Correlation: P = 0.418). Conclusions In a rabbit model, induction of mild hypothermia with an ice bag is faster than with intravenous 4℃ saline; induction time positively correlates with body weight when an ice bag is used, but not when intravenous 4℃ saline used. The effect of body weight should be considered when choosing an appropriate method to achieve early induction of mild hypothermia (J Geriatr Cardiol 2010; 7:161-165).
Objective The current study aimed to evaluate whether the induction of macrophage inflammatory cytokines by Ox-LDL is related to the expression of ABCA1 pathway. Methods After THP1/PMA macrophages were transfected with ABCA1 antisense oligonucleotides (100nmol/L) followed by treatment with Ox-LDL (30mg/L), the expressions of ABCA1, ICAM-1 and MCP-1 mRNA and protein were determined by real-time fluorescent quantitative RT-PCR, Western blot or ELISA. Results Ox-LDL induced expressions of ABCA1, ICAM-1, and MCP-1 at both mRNA and protein levels from THP1/PMA macrophages. Transfection with ABCA1 antisense oligonucleotides reduced ABCA1 mRNA levels after 3 and 6 hours and protein levels after 12 and 24 hours. The expression of ICAM-1 and MCP-1 induced by Ox-LDL was also decreased after inhibition of ABCA1 protein expression by ABCA1 antisense oligonucleotide decreased. Conclusion The induction of macrophage inflammatory cytokines by Ox-LDL is partially dependent on expression of ABCA1. Our studies disclose new functions of ABCA1 in macrophages (J Geriatr Cardiol 2010; 7:166-170).
Objective To characterize early afterdepolarizations (EADs) caused triggered activity (TA) among calsequestrin-2 (CASQ2) knock-in (CASQ2 KI) mice and its relationship with aging. Methods Electrophysiological properties of ventricular myocytes from 3-month (mo, young), 9-mo (adult-1) and 12-mo (adult-2) in wild-type (WT) and CASQ2 KI mice were investigated with patch-clamp technique. Results The incidences of EADs and TA in CASQ2 KI cardiomyocytes increased with increasing age. In contrast, WT mice cardiomyocytes showed no significant change in matched-age groups. Compared with that in 3-mo CASQ2 KI mice, the 50% repolarization of action potential (APD50) showed prolongation in both 9-mo and 12-mo ones (9.2±0.9 ms of 9-mo and 10.3±1.2 ms of 12-mo vs. 5.6±0.3 ms of 3-mo), while the 90 % repolarization of action potential (APD90) was similar among 3 age groups. Compared with 3-mo mice, the 9-mo and 12-mo CASQ2 KI mice showed markedly reduced transient outward potassium current (Ito) densities but increased L-type calcium current (ICa-L) densities. Conlcusion This study suggested that events of EADs and TA in CASQ2 KI mice increased with increasing age. It might be associated partly with the augment of cellular calcium concentration and the prolongation of APD50 induced by decrease of Ito and increase of ICa-L in adult CASQ2 KI mice (J Geriatr Cardiol 2010; 7:171-175).
Objective To investigate the effects of captopril on cardiac function and levels of energy-rich phosphates in pressure overload induced left ventricular hypertrophy rats. Methods One hundred and twenty SD rats were randomly divided into three groups: sham operation group (SH group, n=40),coarctation of abdominal aorta group (CAA group, n=40) and captopril treatment 1mg?100g-1?d-1) group (CAP group, n=40). Left ventricular end-diastolic pressure (LVEDP), left ventricular mass index (LVMI), levels of energy-rich phosphates and morphological changes of the myocardial mitochondria were compared at the 6th and 8th week after operation. Results At 6th week, in CAA group, LVMI and LVEDP were increased and ±dp/dtmax was decreased, while ATP and ADP were decreased and AMP was increased (P<0.01). These changes were much obvious at 8th week (P<0.01). Compared with those of CAA group, the parameters of heart function and energy-rich phosphates (ATP, ADP, AMP, TAN) in CAP group were improved significantly(P<0.01) at the 6th and 8th week. In CAP group, the parameters of heart function and energy-rich phosphates (ADP, AMP, TAN) were much better at 8th week than those at 6th week. The morphological change of mitochondria was less in CAP group than that in CAA group. Conclusion Captopril significantly improves myocardial energy metabolism in pressure overload rats and protects the function of myocardial mitochondria (J Geriatr Cardiol 2010; 7:176-179).
Objectives This study aimed at investigating the cellular mechanism of isoproterenol (ISO) on delayed afterdepolarizations (DADs) and triggered activity (TA) of the noninfarcted myocardium in the myocardial infarcted rabbit model.Methods Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 wk (healed myocardial infarction, HMI). Myocytes were isolated from regions of the noninfarcted left ventricular free wall. ISO was added to cellular surface by perfusion way. Action potentials and ion currents were recorded with whole-cell patch clamp. Results The results showed that treatment with ISO induced more DADs and TA events in HMI myocytes. Iti and ICa-L of myocytes treated with ISO were increased significantly compared with HMI cells, which contributed to DADs-related triggered arrhythmia. Conclusions The results suggested that more arrhythmia events of DADs and TA developed in myocytes with ISO treatment. The underlying mechanism was associated with the augment of Iti and calcium influxing (J Geriatr Cardiol 2010; 7:180-183).
Age-associated changes in cardiovascular structure/function are implicated in the markedly increased risk for cardiovascular disease in older persons. Aging not only prolongs exposure to several other cardiovascular risks, but also leads to intrinsic cardiac changes, which reduces cardiac functional reserve, predisposes the heart to stress and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, including left ventricular hypertrophy, fibrosis and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenuated in mice overexpressing catalase targeted to mitochondria (mCAT). These findings demonstrate the critical role of mitochondrial reactive oxygen species (ROS) in cardiac aging and support the potential application of mitochondrial antioxidants to cardiac aging and age-related cardiovascular diseases.
Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgenic mice over-expressing a constitutively active form of calcineurin or NFAT3, developed obviously hypertrophy and heart failure or sudden death proving its pathogenic role. Here we used literatures on MEDLINE (2000-2011), systematically reviewed the new development of calcineurin signaling pathway in myocardial hypertrophy (J Geriatr Cardiol 2010; 7:189-192).