Protective effect of caffeine administration on myocardial ischemia/reperfusion injury in rats.

Many studies have examined the association between coffee consumption and risk of cardiovascular disease, but the results remain controversial. Caffeine is one of the main biologically active compounds of coffee. The aim of this study was to investigate the potential role of caffeine on myocardial ischemia/reperfusion (I/R) injury in the rats. We administered caffeine (25 mg/kg per day) or saline in rats for 4 weeks before myocardial ischemia/reperfusion operation. Compared with the sham group, caffeine treatment decreased ischemia-associated infarct size, serum creatine kinase, and lactate dehydrogenase 3-h reperfusion after 30-min ischemia. Myocardial neutrophil infiltration (assessed by myeloperoxidase activity) was significantly decreased compared with the control group. Meanwhile, caffeine reduced the myocardial apoptosis and suppressed the activation of caspase 3 during myocardial I/R. Importantly, we observed a strong poly(ADP-ribose) polymerase (PARP) activation during myocardial I/R, and caffeine administration inhibited PARP activation and attenuated the expression of PARP-related proinflammatory mediators such as inducible nitric oxide synthetase, IL-6, and TNF-α, all of which may be correlated with downregulated nuclear factor κB activity. We concluded that caffeine protected against myocardial I/R injury by inhibiting inflammation and apoptosis.

[Transmural heterogeneity of calcium handling proteins in the mechanism of porcine model of ventricular fibrillation].

OBJECTIVE: To investigate the role of heterogeneous expression of calcium handling proteins and spatial heterogeneity of APD restitution in the maintenance mechanism of ventricular fibrillation. METHODS: During programmed electrical simulation, APD restitution curves in the endocardium and epicardium of LV were constructed by plotting APD100 and diastolic interval. APD alternans, delayed after depolarization events were recorded simultaneously. Endocardial and epicardial myocytes were isolated from LV base and apex. Real time-PCR and Western blotting were performed to determine the relative messenger RNA and protein expression levels of calcium handling proteins. RESULTS: The normal hearts have spatial heterogeneity of action potential restitution property and transmural heterogeneity of calcium handling proteins. The slopes of the APD restitution curve in the endocardium were significantly steeper than those in epicardium, and the slopes of APD curve at the LV apex were significantly steeper than those in LV base. However, delayed after depolarization events with larger amplitude and earlier onset consistently occurred in the endocardium of LV base. After programmed electrical simulation, the expression of messenger RNA of RyR2, SERCA2a except for Calstabin2 significantly decreased (by 57% and 41%, respectively, P < 0.05) in the endocardium of the base, while the expression of RyR2, SERCA2a, Calstabin2 significantly increased (by 90%, 78%and 64%, respectively, P < 0.05) in the epicardium of LV base. Although transmural heterogeneity of calcium handling proteins at the LV apex were also observed after rapid pacing, there is no significant differences in the transmural heterogeneity at the LV apex compared to the LV base. The base of LV has unique calcium handling properties. CONCLUSIONS: It has been shown that Calcium cycling could modulate APD restitution property in the intact heart. The interaction between action potential and calcium dynamics instabilities is one of the most important reasons why simple criterion such as the APD restitution slope > 1 may fail to accurately predict the onset of APD alternans.

Autologous transplantation of bone marrow mononuclear cells improved heart function after myocardial infarction.

AIM: To investigate whether autologous transplantation of adult stem cells could improve post-infarcted heart function. METHODS: Bone marrow mononuclear cells (MNCs) were isolated from adult rabbits' tibias after coronary ligation. These cells were exposed to 5-azacytidine 10 micromol/L for 24 h on the third day of culture. After being labeled with bromodeoxyuridine (BrdU), the cells were auto-transplanted into bordering zone of the infarcted area at 2 weeks after injury. The animals were killed at 3 days, 2 weeks, 1 month, and 2 months after transplantation, respectively. The left ventricular functions, capillary density, and cardiac nerve density were measured and the differentiation of the engrafted cells was determined by immunostaining. RESULTS: BrdU-labeled MNCs were well aligned with the host cardiomyocytes. Parts of them were incorporated into capillary and arteriolar vessel walls. In addition to inducing angiogenic ligands (basic fibroblast growth factor, vascular endothelial growth factor) and inflammation cytokines (interleukin 1-beta) during the early period of MNCs implantation, MNCs induced 2.0-fold increase in capillary density as well. Moreover, GAP43-positive and TH-positive nerve density were markedly higher in the MNCs-treated groups than that in the non-treated hearts. Left ventricular ejection fraction, LV+dp/dt(max), and LV-dp/dt(max) were 47%, 67%, and 55% in MNCs-treated heart respectively, which was higher than that of the control heart, whereas left ventricular end-diastolic volume, left ventricular end-diastolic diameter, and left ventricular end-diastolic pressure were 45%, 22%, and 50% respectively in MNCs-treated heart, which was lower than that of the control heart at 2 months after cell transplantation. CONCLUSION: Autologous transplantation of MNCs induced angiogenesis and nerve sprouting and improved left ventricular diastolic function.