[OCT analysis of in-stent neointima over 5 years post-DES implantation].

Objective: To investigate the characteristics of neointimal hyperplasia (NIH) in patients with in-stent restenosis (ISR) over 5 years post-drug-eluting stent (DES) implantation based on optical coherence tomography (OCT). Methods: In this cross-sectional study, patients with DES-ISR who underwent OCT examination at PLA General Hospital between March 2010 and March 2022 were retrospectively included. All patients were divided into≤5 years DES-ISR group and>5 years DES-ISR group according to the time interval after DES implantation. Quantitative and qualitative analyses were conducted on OCT images to compare the clinical data and lesion characteristics of two patient groups. Furthermore, the independent clinical predictive factors of in-stent neoatherosclerosis (ISNA) were analyzed by multivariable logistic regression. Results: A total of 230 DES-ISR patients with 249 lesions were included, with an age of (63.1±10.4) years and 188 males (81.7%). The median interval after DES implantation was 6 (2, 9) years. There were 117 patients (122 ISR lesions) in the≤5 years DES-ISR group, and 113 patients (127 ISR lesions) in the>5 years DES-ISR group. Compared with≤5 years DES-ISR,>5 years DES-ISR showed more heterogeneous patterns (65.4% (83/127) vs. 48.4% (59/122), P=0.007), diffuse patterns (46.5% (59/127) vs. 31.2% (38/122), P=0.013), macrophage accumulations (44.1% (56/127) vs. 31.2% (38/122), P=0.035) in NIH and higher prevalence of ISNA (83.5% (106/127) vs. 72.1% (88/122), P=0.031). According to multivariable logistic regression, the independent predictive factor for ISNA was female (OR=0.44, 95%CI 0.21-0.90, P=0.026). Female (OR=0.48, 95%CI 0.23-0.99, P=0.046) and low-density lipoprotein cholesterol level (OR=1.62, 95%CI 1.01-2.59, P=0.046) were independent predictive factors, respectively, for lipid ISNA. Calcified ISNA was independently associated with time interval of post-DES implantation (OR=1.18, 95%CI 1.07-1.29, P=0.001). Conclusion: DES-ISR patients with a time interval of>5 years after stent implantation have a higher prevalence of ISNA and more complex lesions. Gender, the level of low-density lipoprotein cholesterol, and the time interval post-DES implantation are independently correlated with ISNA, lipid ISNA, and calcified ISNA.

[Efficacy of intravascular ultrasound versus coronary angiographic guided drug-eluting stent implantation in the treatment of left main coronary artery disease: a meta-analysis].

Objective: To compare the efficacy of intravascular ultrasound (IVUS) and coronary angiography guided drug eluting stent (DES) implantation for the treatment of left main coronary artery (LMCA) lesions. Methods: Randomized controlled trials (RCT) and observational studies, which compared IVUS with coronary angiography guided DES implantation for the treatment of LMCA lesions published before August 2021 were searched in PubMed, Embase and Cochrane Library databases. Baseline data, interventional procedures and endpoint events of each study were collected. The primary endpoint was major cardiovascular adverse events (MACE), and the secondary endpoints were all-cause death, cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and target vessel revascularization (TVR). The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration Risk of Bias tool were used to evaluate the quality of the included studies. Results: Nine studies were included, including 3 RCT and 6 observational studies, with a total of 5 527 cases of LMCA. All the 6 observational studies had NOS scores≥6, and the 3 RCT had a low risk of overall bias. The results of meta-analysis showed that compared with coronary angiography guided group, MACE rate (OR=0.55, 95%CI 0.47-0.66, P<0.001), all-cause death (OR=0.56, 95%CI 0.43-0.74, P<0.001), cardiac death (OR=0.43, 95%CI 0.30-0.61, P<0.001), MI (OR=0.64, 95%CI 0.52-0.79, P<0.001), TLR (OR=0.49, 95%CI 0.28-0.86, P=0.013) and TVR (OR=0.77, 95%CI 0.60-0.98, P=0.037) were all significantly lower in the IVUS guided group. Conclusions: Compared with angiography guided, IVUS guided PCI with DES implantation in LMCA lesions could significantly reduce the risk of MACE, death, MI, TLR and TVR. IVUS is thus superior to coronary angiography for guiding PCI treatment among patients with LMCA.

[A Meta-analysis of Pin1 gene polymorphism at -842 loci and cancer susceptibility].

Objective: Using Meta-analysis to evaluate the association between Pin1 gene polymorphism at -842 loci and cancer susceptibility. Methods: Pin1, polymorphism, tumor, variant and cancer as key words were used to systematically search for the case-control research on the association between the -842G/C polymorphisms of Pin1 and cancer susceptibility through China National Knowledge Infrastructure (CNKI), Wanfang Data, Embase and PubMed. The time of literatures was up to April 2(nd), 2019. Heterogeneity test, combined risk of cancer with the -842 C allele of Pin1, publication bias test and sensitivity analysis were performed by using Stata 12.0 software. Results: A total of 144 articles were retrieved. According to the inclusion criteria, a total of 11 articles were included (2 Chinese documents and 9 English documents). There were 5 667 cases and 6 120 controls in eligible articles. The heterozygous model showed that Pin1 (-842G/C) polymorphism was associated with cancer susceptibility, and the pooled OR (95%CI) value was 0.78 (0.61, 0.99). Subgroup analysis by cancer type suggested that the Pin1 (-842G/C) polymorphism could significantly decrease the incidence of breast cancer and lung cancer under the heterozygous model (GC vs GG), dominant model (GC+CC vs GG) and allele model (C vs G). The pooled OR (95%CI) values were 0.73 (0.58, 0.92), 0.71 (0.57, 0.89), and 0.73 (0.60, 0.89) in breast cancer and 0.64 (0.52, 0.78), 0.64 (0.53, 0.78), and 0.67 (0.55, 0.80) in lung cancer. The variant -842 C allele could significantly increase the risk of nasopharyngeal carcinoma under the homozygote model (CC vs GG) and recessive model (CC vs GG+GC). The pooled OR (95%CI) values were 2.22 (1.03-4.75) and 2.47 (1.16-5.26). No significant association was observed in squamous cell carcinoma. Conclusion: This Meta-analysis demonstrated that Pin1gene polymorphism at -842 was associated with cancer susceptibility.

Conversion of an inactive cardiac dihydropyridine receptor II-III loop segment into forms that activate skeletal ryanodine receptors.

A 25 amino acid segment (Glu666-Pro691) of the II-III loop of the alpha1 subunit of the skeletal dihydropyridine receptor, but not the corresponding cardiac segment (Asp788-Pro814), activates skeletal ryanodine receptors. To identify the structural domains responsible for activation of skeletal ryanodine receptors, we systematically replaced amino acids of the cardiac II-III loop with their skeletal counterparts. A cluster of five basic residues of the skeletal II-III loop (681RKRRK685) was indispensable for activation of skeletal ryanodine receptors. In the cardiac segment, a negatively charged residue (Glu804) appears to diminish the electrostatic potential created by this basic cluster. In addition, Glu800 in the group of negatively charged residues 798EEEEE802 of the cardiac II-III loop may serve to prevent the binding of the activation domain.

Acute graded hypercapnia increases collateral coronary blood flow in a swine model of chronic coronary artery obstruction.

OBJECTIVE: To evaluate the effect of acute hypercapnia on regional myocardial blood flow in a swine model of chronic, single-vessel coronary artery obstruction. Permissive hypercapnia is being used frequently in critical care settings. One possible detrimental effect of hypercapnia is the initiation of coronary "steal" in patients with coronary artery disease. The effects of hypercapnia on collateral coronary blood flow in the setting of coronary obstruction have not been defined. DESIGN: Prospective controlled experimental study. SETTING: Institutional animal research facility. SUBJECTS: Eight juvenile swine weighing 25-30 kg. INTERVENTIONS: Collateral coronary circulation was induced in eight piglets by banding the proximal left anterior descending coronary artery for 8-10 wks followed by total ligation. Graded hypercapnia (mean Paco2, 81 torr [10.80 kPa; Paco2 = 81 torr] and 127 torr [16.93 kPa; Paco2 = 127 torr]) was induced by increasing inspiratory carbon dioxide under isoflurane anesthesia (1 minimum alveolar concentration). MEASUREMENTS AND MAIN RESULTS: Animals were attached to instruments to measure pulmonary and systemic hemodynamics, regional myocardial blood flow, and cardiac output. Regional myocardial blood flow was determined using radiolabeled microspheres. Cardiac output, mean arterial pressure, and coronary perfusion pressure were unchanged at both levels of hypercapnia compared with baseline values. Heart rate was increased at Paco2 [HI] (p < .05). Regional blood flow was increased at both levels of hypercapnia in the collateral-dependent and normally perfused myocardium (p < .05; as high as 56% for subendocardium and as high as 106% for subepicardium at Paco2 [HI]). The intercoronary blood flow ratio remained unaltered. The transmural flow ratio was reduced at Paco2 [HI] (P < .05). During hypercapnia, regional lactate extraction remained unaltered, and regional oxygen extraction was unchanged or reduced despite the increase in oxygen consumption. CONCLUSIONS: In this swine model of chronic single-vessel coronary artery obstruction, acute hypercapnia does not induce coronary steal from collateral-dependent myocardium, but it does increase global coronary blood flow.

Comparison of nifedipine and metoprolol on collateral coronary blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia.

PURPOSE: This study compared the effects of nifedipine and metoprolol on collateral-dependent myocardial blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia. METHODS: Collateral coronary circulation was induced in 15 three-week-old piglets by banding of the proximal left anterior descending coronary artery (LAD). After 8-10 wk, the distal LAD was ligated and the open-chest pigs were randomized to receive infusions of either saline, nifedipine (5 micrograms.kg-1.min-1) or metoprolol (10 micrograms.kg-1.min-1) for 30 min during isoflurane anaesthesia (2%). Transient ischaemia was induced by 30 sec occlusion of the left circumflex artery. Arterial blood pressures, heart rate and regional myocardial blood flow (radiolabelled microspheres technique) were measured at the end of drug infusion (baseline) and one minute after transient ischaemia. RESULTS: No differences in the blood flow to the collateral-dependent (CD) myocardium or haemodynamic variables were observed at baseline among the three groups. Following transient ischaemia, in the nifedipine but not in the metoprolol group, blood flow to the CD myocardium was reduced by 28 +/- 24% in the epicardium (P < 0.05) and 56 +/- 20% in the endocardium (P < 0.01), resulting from intercoronary and transmural steal. This was associated with a moderate increase (10%, P < 0.05) in the heart rate in the nifedipine group. CONCLUSIONS: In a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia, the collateral coronary blood flow was maintained in the presence of metoprolol, but reduced in the presence of nifedipine following transient ischaemia due to intercoronary and transmural steal.

Age-related alterations in the phosphorylation of sarcoplasmic reticulum and myofibrillar proteins and diminished contractile response to isoproterenol in intact rat ventricle.

Previous studies have shown that the inotropic response of the heart to beta-adrenergic stimulation declines with aging. This alteration has been attributed partly to an age-related impairment in the activation of the beta-adrenoceptor-G protein-adenylate cyclase complex. To further understand the mechanisms underlying the age-related deficit, the present study compared beta-adrenergic-mediated contractile response, cAMP accumulation, and phosphorylation of sarcoplasmic reticulum and myofibrillar proteins in isolated perfused hearts from adult (6-8 months) and aged (28-30 months) Fischer 344 rats. In isometrically contracting, electrically paced (240 beats per minute) hearts perfused at constant flow rate (9 ml/min per gram ventricle), the baseline contractile performance differed significantly between adult and aged hearts. Thus, contraction duration was prolonged (approximately 15%, p < 0.001) in the aged relative to the adult heart, and this was due to increases in time to peak tension and relaxation time. Further, developed peak tension, normalized per gram ventricular wet weight, was significantly lower (approximately 20%, p < 0.05) in the aged compared with the adult heart. In these isolated perfused heart preparations, beta-adrenergic stimulation with isoproterenol (ISO, 0.001-1 microM) evoked concentration-dependent positive inotropic and lusitropic responses, both of which were significantly lower (15-20%, p < 0.05-0.001) in the aged compared with the adult heart. These age-related differences were manifested as relatively smaller ISO-induced increases in 1) developed peak tension, 2) maximum rate of tension development (+dT/dt), and 3) maximum rate of relaxation (-dT/dt) in the aged compared with the adult heart. The ISO-induced abbreviation of time to half relaxation was also less marked in the aged heart. Under similar experimental conditions, ISO (0.1 microM)-induced increase in tissue cAMP content was also lower (approximately 18%, p < 0.05) in the aged heart. ISO (0.1 microM)-induced phosphorylation of the sarcoplasmic reticulum protein phospholamban and myofibrillar protein troponin I was significantly diminished (approximately 38% and 25% decline, respectively, for phospholamban and troponin I; p < 0.05-0.001) in the aged compared with the adult heart. No significant age-related difference was, however, evident in ISO-induced phosphorylation of C protein of myofibrils. These data suggest that age-related decrements in beta-adrenergic-mediated cAMP accumulation and phosphorylation of phospholamban and troponin I contribute to the diminished contractile responses of the aged heart to beta-adrenergic stimulation.

Effects of aging on phospholamban phosphorylation and calcium transport in rat cardiac sarcoplasmic reticulum.

Acceleration of cardiac relaxation upon beta adrenergic stimulation is due, in part, to enhancement in the rate of Ca2+ sequestration by the sarcoplasmic reticulum (SR) Ca2+ pump resulting from cAMP-mediated phosphorylation of the SR protein phospholamban. Our previous studies have shown that in rat myocardium, beta adrenergic activation of adenylate cyclase and the Ca2+ pump activity of SR decline with aging (Mech. Ageing Dev., 19 (1982) 127-139; 38 (1987) 127-143). In the present study, the effect of aging on phospholamban phosphorylation and consequent changes in SR Ca2+ pump activity were evaluated using cardiac SR from 6 (young adult), 12 (adult) and 28 (aged) months old rats. No age-related differences were observed in the rate or maximum level of phospholamban phosphorylation by exogenous cAMP-dependent protein kinase. The rates of ATP-dependent Ca2+ uptake by SR from young adult and aged rats were stimulated upon phospholamban phosphorylation, the percentage stimulation of Ca2+ uptake at varying Ca2+ concentrations (0.24-11.9 microM) was not diminished with aging. However, the rates of Ca2+ uptake by phosphorylated and unphosphorylated SR were remarkably lower (35-50%) in the aged. Regardless of the age of rats, the stimulatory effect of phosphorylation on Ca2+ uptake by SR was due to increase in Vmax of Ca2+ transport with no appreciable changes in K0.5 for Ca2+. These findings imply that in spite of the age-associated decline in SR Ca2+ pump activity, the ability of phospholamban to undergo cAMP-mediated phosphorylation and the relative responsiveness of the SR Ca2+ pump to phospholamban phosphorylation are not diminished in the aging heart.