Heart rate variability and exercise capacity of patients with repaired tetralogy of Fallot

Heart rate variability (HRV) has been used as a reliable method to detect cardiac autonomic nervous system activity. Peak oxygen uptake (VO₂ peak) has been a predictor of death for adults with repaired tetralogy of Fallot (TOF). This study investigated the correlation between HRV and exercise capacity in 30 patients with TOF after surgery for total correction. The median age of the patients was 14 years (range, 9–25 years), and the median follow-up period was 11.6 months (range, 5.3–20.2 months). Low- and high-frequency-domain HRV significantly correlated with VO₂ peak (r = 0.56, P = 0.001 and r = 0.44, P = 0.02, respectively). After the 1-year follow-up evaluation, VO₂ peak and HRV analysis did not differ from those at entry to the study. However, low- and high-frequency-domain HRV still correlated significantly with VO₂ peak (r = 0.43, P = 0.03 and r = 0.52, P = 0.007, respectively). Left ventricular early diastolic myocardial velocity was most closely correlated with the VO₂ peak (r = 0.51, P = 0.005). Impaired cardiovascular autonomic control and left ventricular diastolic dysfunction may be responsible for exercise intolerance in patients with repaired TOF. Long-term follow-up evaluation with exercise testing and 24-h Holter monitoring are warranted.     

Effects of left ventricular function on the exercise capacity in patients with repaired tetralogy of Fallot

Background: Tissue Doppler imaging has been recently used to evaluate ventricular function. Peak oxygen uptake (V^?O₂peak) has been demonstrated as a predictor for death in adults with repaired tetralogy of Fallot (TOF). The aim of this study was to determine which Doppler parameters correlated with V^?O₂peak in patients with repaired TOF. Method and Results: Doppler echocardiography, tissue Doppler imaging, and exercise test were performed in 30 patients with TOF after surgical repair. In 30 patients with repaired TOF (median age 14 years, range 9–25 years), 11 patients (37%) were female. Seven patients (median age 12 years) had normal left ventricular diastolic function, whereas the rest of the patients were classified as diastolic dysfunction grade II (median age 15 years; n = 15) and III and IV (median age 18 years; n = 8). The oxygen uptake at anaerobic threshold (V^?O_2AT) and peak exercise in patients with left ventricular diastolic dysfunction was significantly lower than that in those with normal diastolic function. Also, V^?O_2AT and V^?O₂peak in patients with diastolic dysfunction grade III and IV were significantly lower than that in those with diastolic dysfunction grade II. Left ventricular early diastolic myocardial velocity was most closely correlated to V^?O₂peak (r = 0.51; P = 0.005). Peak early ventricular filling velocity to early diastolic myocardial velocity ratio was significantly correlated with V^?O₂peak (r =?0.50; P = 0.006). Conclusion: Left ventricular diastolic dysfunction is correlated with V^?O₂peak. Left ventricular diastolic function should be a routine echocardiographic assessment in patients with repaired TOF. (Echocardiography 2011;28:1019‐1024)     

Calcium channels and iron uptake into the heart

Iron overload can lead to iron deposits in many tissues,particularly in the heart.It has also been shown to be associated with elevated oxidative stress in tissues.Elevated cardiac iron deposits can lead to iron overload cardiomyopathy,a condition which provokes mortality due to heart failure in iron-overloaded patients.Currently,the mechanism of iron uptake into cardiomyocytes is still not clearly understood.Growing evidence suggests L-type Ca2+channels(LTCCs)as a possible pathway for ferrous iron(Fe2+)uptake into cardiomyocytes under iron overload conditions.Nevertheless,controversy still exists since some findings on pharmacological interventions and those using different cell types do not support LTCC’s role as a portal for iron uptake in cardiac cells.Recently,T-type Ca2+channels (TTCC)have been shown to play an important role in the diseased heart.Although TTCC and iron uptake in cardiomyocytes has not been investigated greatly,a recent finding indicated that TTCC could be an important portal in thalassemic hearts.In this review,comprehensive findings collected from previous studies as well as a discussion of the controversy regarding iron uptake mechanisms into cardiomyocytes via calcium channels are presented with the hope that understanding the cellular iron uptake mechanism in cardiomyocytes will lead to improved treatment and prevention strategies,particularly in iron-overloaded patients.     

Glycine-gated chloride channels depress synaptic transmission in rat hippocampus

An inhibitory role for strychnine-sensitive glycine-gated chloride channels (GlyRs) in mature hippocampus is beginning to be appreciated. We have reported previously that CA1 pyramidal cells and GABAergic interneurons recorded in 3- to 4-wk-old rat hippocampal slices express functional GlyRs, dispelling previous misconceptions that GlyR expression ceases in early development. However, the effect of GlyR activation on cell excitability and synaptic circuits in hippocampus has not been fully explored. Using whole cell current-clamp recordings, we show that activation of strychnine-sensitive GlyRs through exogenous glycine application causes a significant decrease in input resistance and prevents somatically generated action potentials in both CA1 pyramidal cells and interneurons. Furthermore, GlyR activation depresses the synaptic network by reducing suprathreshold excitatory postsynaptic potentials (EPSPs) to subthreshold events in both cell types. Blockade of postsynaptic GlyRs with the chloride channel blocker 4, 4'-diisothiocyanatostilbene-2-2'-disulfonic acid (DIDS) or altering the chloride ion driving force in recorded cells attenuates the synaptic depression, strongly indicating that a postsynaptic mechanism is responsible. Increasing the local glycine concentration by blocking reuptake causes a strychnine-sensitive synaptic depression in interneuron recordings, suggesting that alterations in extracellular glycine will impact excitability in hippocampal circuits. Finally, using immunohistochemical methods, we show that glycine and the glycine transporter GlyT2 are co-localized selectively in GABAergic interneurons, indicating that interneurons contain both inhibitory neurotransmitters. Thus we report a novel mechanism whereby activation of postsynaptic GlyRs can function to depress activity in the synaptic network in hippocampus. Moreover, the co-localization of glycine and GABA in hippocampal interneurons, similar to spinal cord, brain stem, and cerebellum, suggests that this property is likely to be a general characteristic of inhibitory interneurons throughout the CNS.     

Granulocyte colony-stimulating factor stabilizes cardiac electrophysiology and decreases infarct size during cardiac ischaemic/reperfusion in swine

Aim: Effects of granulocyte colony‐stimulating factor (G‐CSF) on cardiac electrophysiology during ischaemic/reperfusion (I/R) period are unclear. We hypothesized that G‐CSF stabilizes cardiac electrophysiology during I/R injury by prolonging the effective refractory period (ERP), increasing the ventricular fibrillation threshold (VFT) and decreasing the defibrillation threshold (DFT), and that the cardioprotection of G‐CSF is via preventing cardiac mitochondrial dysfunction. Methods: In intact‐heart protocol, pigs were infused with either G‐CSF or vehicle (n = 7 each group) without I/R induction. In I/R protocol, pigs were infused with G‐CSF (0.33 μg kg^?1 min^?1) or vehicle (n = 8 each group) for 30 min prior to a 45‐min left anterior descending artery occlusion and at reperfusion. Diastolic pacing threshold (DPT), ERP, VFT and DFT were determined in all pigs before and during I/R period. Rat’s isolated cardiac mitochondria were used to test the protective effect of G‐CSF (100 nm ) in H₂O₂‐induced mitochondrial oxidative damage. Results: Neither G‐CSF nor vehicle altered any parameter in intact‐heart pigs. During ischaemic period, G‐CSF significantly increased the DPT, ERP and VFT without altering the DFT. During reperfusion, G‐CSF continued to increase the DPT without altering other parameters. The infarct size was significantly decreased in the G‐CSF group, compared to the vehicle. G‐CSF could also prevent cardiac mitochondrial swelling, decrease ROS production, and prevent mitochondrial membrane depolarization. Conclusion: G‐CSF increases the DPT, ERP and VFT and reduces the infarct size, thus stabilizing the myocardial electrophysiology, and preventing fatal arrhythmia during I/R. The protective mechanism could be via its effect in preventing cardiac mitochondrial dysfunction.     

Effect of rosiglitazone on cardiac electrophysiology, infarct size and mitochondrial function in ischaemia and reperfusion of swine and rat heart

Rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, has been used to treat type 2 diabetes. Despite debates regarding its cardioprotection, the effects of rosiglitazone on cardiac electrophysiology are still unclear. This study determined the effect of rosiglitazone on ventricular fibrillation (VF) incidence, VF threshold (VFT), defibrillation threshold (DFT) and mitochondrial function during ischaemia and reperfusion. Twenty-six pigs were used. In each pig, either rosiglitazone (1 mg kg(-1)) or normal saline solution was administered intravenously for 60 min. Then, the left anterior descending coronary artery was ligated for 60 min and released to promote reperfusion for 120 min. The cardiac electrophysiological parameters were determined at the beginning of the study and during the ischaemia and reperfusion periods. The heart was removed, and the area at risk and infarct size in each heart were determined. Cardiac mitochondria were isolated for determination of mitochondrial function. Rosiglitazone did not improve the DFT and VFT during the ischaemia-reperfusion period. In the rosiglitazone group, the VF incidence was increased (58 versus 10%) and the time to the first occurrence of VF was decreased (3 ± 2 versus 19 ± 1 min) in comparison to the vehicle group (P < 0.05). However, the infarct size related to the area at risk in the rosiglitazone group was significantly decreased (P < 0.05). In the cardiac mitochondria, rosiglitazone did not alter the level of production of reactive oxygen species and could not prevent mitochondrial membrane potential changes. Rosiglitazone increased the propensity for VF, and could neither increase defibrillation efficacy nor improve cardiac mitochondrial function.     

Lipocalin‐2: Its perspectives in brain pathology and possible roles in cognition

Lipocalin‐2 (LCN2) has been known to play an important role in pathological conditions, specifically in response to inflammation, infection and injury to cells. Recently, several research teams have been interested in investigating its association with cognition during the progression of pathology. Previous studies have demonstrated that LCN2 is not correlated with cognitive function under normal physiological conditions, although LCN2 has been negatively associated with cognition and some neuropathologies. Increasing LCN2 production is associated with reduced cognitive performance in a rodent model. However, further studies are needed to explore the potential underlying mechanisms of LCN2 on cognitive dysfunction, as well as its clinical relevance. This review aims to summarise the evidence available from in vitro, in vivo and clinical studies concerning the possible role of LCN2 on cognitive function following the onset of pathological conditions. Any contradictory evidence is also assessed and presented.