Effects of early intravenous low-dose of metoprolol on cardiac sympathetic activities and electrophysiological properties in myocardial infarction heart.

This study observed the effects of early intravenous low-doses of metoprolol on cardiac sympathetic activities and electrophysiological properties in myocardial infarction (MI) dogs. Thirty two mongrel dogs with the first diagonal branch of the left anterior descending coronary artery ligated were randomly divided into three groups: The low-dose group was given metoprolol 0.6 mg/kg immediately by intravenous injection (n=12); the target-dose group was given metoprolol 1.6 mg/kg (n=12), and the control group was injected with normal saline at the same dose of the target-dose group (n=8). Norepinephrine (NE) and epinephrine (E) levels in the coronary sinus (CS) blood as well as the ventricular effective refractory period (ERP) were all measured during the experiments. We found that NE and E concentrations in the three groups were all increased compared with the previous measurement before ligation. ERP values after MI were significantly decreased in all three groups compared with the first measurements. The three groups all exhibited uneven shortness of ERP among different regions, with significant shortness in infarcted area. Furthermore, there was no difference between the low and target-dose of metoprolol in the reduction of regional ERP, and the same effect was also observed in induced arrhythmias. In conclusion, a lower dose of metoprolol performed similarly as target-dose in reducing the catecholamine concentrations in dogs with MI. Our study demonstrated that a lower dose of metoprolol may be reasonable compared with the target-dose in ß-blocker therapy due to similar effect and lower toxicity.

Outcomes of percutaneous coronary intervention in patients ≥ 75 years: one-center study in a Chinese patient group.

OBJECTIVE: To investigate the clinical and perioperative characteristics of patients ≥ 75 who undergoing percutaneous coronary intervention (PCI) and to evaluate the risk factors related to short-term post-PCI mortality in this specific patients group. METHODS: 1,035 consecutive subjects who underwent PCI from December 2011 to November 2013 were divided into four categories: (1) patients with stable angina (SA) ≥ 75 years (n = 58); (2) patients with SA < 75 years (n = 218); (3) patients with acute coronary syndrome (ACS) ≥ 75 years (n = 155); (4) patients with ACS < 75 years (n = 604). A multivariable logistic regression analysis was conducted to detect risk factors of six-month mortality in patients ≥ 75 years who had undergone PCI. Clinical comorbidities, in-hospital biochemical indicators, perioperative data, in-hospital and six-month outcomes were analyzed and compared among the four groups. RESULTS: Compared with the younger group, patients ≥ 75 years were more likely to have hypertension, history of stroke, chronic obstructive pulmonary disease, peripheral vascular disease, cardiogenic shock and malignant arrhythmia, and they were admitted to hospital with relative lower weight, hemoglobin, albumin, triglyceride, higher creatinine, uric acid, urea nitrogen and pro-BNP. Left main artery lesions, multi-vessel, calcified lesions, chronic totally occlusion were also more likely to be seen in the elderly group. Univariate analysis revealed that age ≥ 85 years, cardiogenic shock or severe arrhythmia at admission, emergency PCI, prior stroke and chronic kidney disease were related to six-month mortality in elderly patients ≥ 75 years who underwent PCI. Multivariable logistic regression showed that cardiogenic shock or severe arrhythmia at admission, chronic kidney disease and prior stroke were independent risk factors predicting six-month mortality in elderly patients ≥ 75 years who had undergone PCI. CONCLUSIONS: Our data showed that, compared with patients under 75 years, elderly patients (≥ 75 years) who had undergone PCI had a relative higher risk of mortality, and more often accompanied with multi-comorbidities, severer admission conditions and complex coronary lesions. Better evaluation of risk factors and more intensively care should be taken to patients ≥ 75 years who had undergone PCI therapy to reduce complications.

A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias.

Dilated cardiomyopathy (DCM) is the most prevalent type of primary myocardial disease, which is the third most common cause of heart failure and the most frequent reason for heart transplantation. Aggregating evidence demonstrates that genetic risk factors are involved in the pathogenesis of idiopathic DCM. Nevertheless, DCM is of remarkable genetic heterogeneity and the genetic defects underpinning DCM in an overwhelming majority of patients remain unknown. In the present study, the whole coding exons and splice junction sites of the NKX2-5 gene, which encodes a homeodomain transcription factor crucial for cardiac development and structural remodeling, were sequenced in 130 unrelated patients with idiopathic DCM. The available relatives of the index patient harboring an identified mutation and 200 unrelated ethnically matched healthy individuals used as controls were genotyped for the NKX2-5 gene. The functional effect of the mutant NKX2-5 was characterized in contrast to its wild-type counterpart using a dual-luciferase reporter assay system. As a result, a novel heterozygous NKX2-5 mutation, p.S146W, was identified in a family with DCM inherited as an autosomal dominant trait, which co-segregated with DCM in the family with complete penetrance. Notably, the mutation carriers also had arrhythmias, such as paroxysmal atrial fibrillation and atrioventricular block. The missense mutation was absent in 400 reference chromosomes and the altered amino acid was completely conserved evolutionarily among species. Functional analysis revealed that the NKX2-5 mutant was associated with a significantly reduced transcriptional activity. The findings expand the mutational spectrum of NKX2-5 linked to DCM and provide novel insight into the molecular mechanisms underlying DCM, contributing to the antenatal prophylaxis and allele-specific management of DCM.

Effects of mid-myocardial pacing on transmural dispersion of repolarization and arrhythmogenesis.

INTRODUCTION: Epicardial (Epi) activation of the left ventricular (LV) wall increases transmural dispersion of repolarization (TDR), which creates a substrate for the development of ventricular arrhythmia. We hypothesize that pacing from the LV mid-myocardium may decrease the TDR and occurrence of arrhythmias. METHODS AND RESULTS: A transmural electrocardiogram and transmembrane action potentials were simultaneously recorded from Epi, mid-myocardial (M), and endocardial (Endo) layers of the arterially perfused canine LV wedge preparations (n= 8). Transmural dispersion of repolarization varied when the preparations were paced at each layer, respectively (Endo pacing, 35.6 ± 6.6 ms; M pacing, 34.9 ± 7.3 ms; Epi pacing, 72.4 ± 4.9 ms; P< 0.001). A significant difference was noted in TDR between M pacing and Epi pacing (P< 0.001), but not between M pacing and Endo pacing (P= 0.831). This result was reproducible in the presence of ischaemia-reperfusion experiments (n= 8). Transmural dispersion of repolarization was amplified as compared with non-ischaemic experiments and differed when preparations were paced at each layer (Endo pacing, 62.8 ± 13.8 ms; M pacing, 63.3 ± 13.3 ms; Epi pacing, 111.1 ± 17.7 ms; P< 0.001). There was again no significant difference between Endo pacing and M pacing (P= 0.948). However, as pacing was shifted from M to Epi, there was a significant increase in TDR (P< 0.001). Ventricular arrhythmias were induced in two of eight ischaemic preparations during Epi pacing, but did not occur in either M or Endo pacing. CONCLUSION: Mid-myocardial pacing can significantly decrease the TDR and prevent the occurrence of ventricular arrhythmias as compared with Epi pacing.

Catheter ablation of cardiac fat pads attenuates Bezold-Jarisch reflex in dogs.

BACKGROUND: Bezold-Jarisch reflex (BJR) plays an important role in the pathophysiology of several cardiovascular disorders. Radiofrequency catheter ablation (RFCA) of the vagal ganglia in cardiac fat pads (FPs) may attenuate BJR. The purpose of this study was to examine the effects of RFCA of the cardiac FPs on veratridine-induced BJR in dogs. METHODS AND RESULTS: This study was performed in 30 pentobarbital-anesthetized and open-chest dogs: control group received no ablation (n = 15); and ablation group (n = 15) received epicardial ablation of the 3 FPs located near the right pulmonary vein, the inferior vena cava, and the aortic root. The BJR was induced by injection of veratridine (15 µg/kg) into the left ventricle. Before injection of veratridine, there were no significant differences in heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), left ventricle end-diastolic pressure (LVEDP), left ventricular peak systolic and diastolic velocity (±dp/dt(max)) between these 2 groups (P > 0.05). However, the veratridine-induced decrease of HR in ablation group was significantly lower than that in control group (22.9 ± 8.5 bpm vs 93.3 ± 18.4 bpm, P < 0.01). There were no differences in the reduction of SAP, DAP, MAP, LVSP, LVEDP and dp/dt(max) between both groups (P > 0.05). CONCLUSIONS: RFCA of the cardiac FPs significantly attenuated veratridine-induced cardio-vagal component but not the vasodepressor component of the BJR. This might have therapeutic implications in BJR-related disorders such as cardio-inhibitory vasovagal syncope.