Diagnostic and prognostic value of angiography-derived index of microvascular resistance: a systematic review and meta-analysis.

Background: The angiography-derived index of microvascular resistance (A-IMR) is a novel tool for diagnosing coronary microvascular dysfunction (CMD) addressing limitation of unavailability. However, the clinical value of A-IMR remains controversial. Methods: A systematic review and meta-analysis was conducted. PubMed, EMBASE, Cochrane Library and Web of Science were searched for relevant studies. Studies that reported estimates of A-IMR's diagnostic accuracy (with thermodilution-based IMR as the reference test) and/or predictions of adverse cardiovascular events were selected. Pooled sensitivity, specificity, area under the summary receiver operating characteristic curve (sROC) were calculated to measure diagnostic performance; pooled hazard/risk ratio (HR/RR) and 95% confidence interval (95% CI) of major adverse cardiovascular events (MACE) or other independent adverse events were calculated to measure prognostic effect. This study was registered with PROSPERO (CRD42023451884). Results: A total of 12 diagnostic studies pooling 1,642 vessels and 12 prognostic studies pooling 2,790 individuals were included. A-IMR yielded an area under sROC of 0.93 (95% CI: 0.91, 0.95), a pooled sensitivity of 0.85 (95% CI: 0.79, 0.89) and a pooled specificity of 0.89 (95% CI: 0.83, 0.93) for the diagnosis of CMD. CMD diagnosed using A-IMR was associated with higher risks of MACE (HR, 2.73, 95% CI: 2.16, 3.45), CV death (RR, 2.39, 95% CI: 1.49, 3.82) and heart failure hospitalization (HR, 2.30, 95% CI: 1.53, 3.45). Conclusion: A-IMR demonstrated high diagnostic accuracy for CMD and showed a strong prognostic capability in predicting the risk of adverse CV outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023451884, PROSPERO (CRD42023451884).

Clinical benefits of oral anticoagulants in atrial fibrillation patients with dementia: a systematic review and meta-analysis.

Background: The management of atrial fibrillation (AF) with oral anticoagulants (OAC) is generally recommended to reduce the risk of stroke. However, the decision to prescribe these medications for patients with AF and dementia remains controversial. Methods: A systematic review and meta-analysis of retrospective cohort studies were conducted. The search encompassed PubMed, Cochrane Library, Web of Science, and Embase databases from inception until May 1st, 2023, with language limited to English. Eligible studies included comparisons between exposure to OAC vs. non-OAC in the AF population with dementia or cognitive impairment. Studies that compared the effects of direct oral anticoagulants (DOAC) and vitamin-K antagonists were also included. The primary outcome was all-cause mortality, and the secondary outcomes were ischemic stroke and major bleeding. This study was registered with PROSPERO (No. CRD42023420678). Results: A total of five studies (N = 21,962 patients) met the eligibility criteria and were included in this review. The follow-up duration ranged from 1 to 4 years. Meta-analysis demonstrated that OAC treatment was associated with a lower risk of all-cause mortality in AF patients with dementia with a hazard ratio (HR) of 0.79 and a 95% confidence interval (CI) ranging from 0.68 to 0.92, compared to non-OAC treatment. No statistical differences were observed in the risk of major bleeding (HR = 1.12, 95% CI: 0.88-1.42) or ischemic stroke (HR = 0.77, 95% CI: 0.58-1.00). Three studies reported comparisons between DOAC and warfarin; however, pooled analysis was not performed due to heterogeneity. Conclusion: The use of OACs in individuals diagnosed with both AF and dementia holds the potential to reduce all-cause mortality rates, thereby improving the overall clinical prognosis within this specific population. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023420678, PROSPERO identifier, CRD42023420678.

Integrin αvß3 and EGFR dual-targeted [64Cu]Cu-NOTA-RGD-GE11 heterodimer for PET imaging in pancreatic cancer mouse model.

PURPOSE: Radiolabeled heterodimeric peptide has emerged as a highly promising targeting strategy for PET imaging due to their superior properties. RGD and GE11 are two peptides binding to receptor integrin αvß3 and EGFR, respectively, which both overexpress in many different types of tumors. This study focuses on the synthesis and evaluation of a RGD and GE11-containing heterodimeric radiotracer [64Cu]Cu-NOTA-RGD-GE11 for PET imaging of tumors that simultaneously overexpress integrin αvß3 and EGFR. PROCEDURES: [64Cu]Cu-NOTA-RGD-GE11 was prepared by the conjugation of RGD-PEG4-NOTA-N3 and GE11-PEG4-BCN via metal-free click chemistry, followed by radiolabeling with 64Cu. Cell uptake and efflux studies, saturation binding assay, the animal PET/CT and biodistribution studies were conducted to characterize the biological properties of [64Cu]Cu-NOTA-RGD-GE11. RESULTS: [64Cu]Cu-NOTA-RGD-GE11 was synthesized with a radiochemical purity of >97 % and molar activity of 23 GBq/µmol at the end of synthesis. [64Cu]Cu-NOTA-RGD-GE11 showed moderate hydrophilicity, good stability in mouse serum and high specific uptake by the human pancreatic cancer cell line (BxPC3) in the in vitro studies. Compared to the two monomeric counterparts [64Cu]Cu-NOTA-RGD and [64Cu]Cu-NOTA-GE11, [64Cu]Cu-NOTA-RGD-GE11 demonstrated significantly improved tumor uptakes (e.g. 4.63 ± 0.25 %ID/g vs 1.24 ± 0.18 %ID/g and 0.77 ± 0.13 %ID/g, 2 h after injection, p < 0.05) in the subsequent in vivo evaluation in mice bearing BxPC3 xenograft. Tumor uptake could be blocked in the presence of both non-radioactive c(RGDyK) and GE11 peptides, indicating good tumor specificity of [64Cu]Cu-NOTA-RGD-GE11 in vivo. CONCLUSION: The results suggested that the as-developed [64Cu]Cu-NOTA-RGD-GE11 could serve as a potential PET tracer for the noninvasive imaging of integrin αvß3 and EGFR expression in tumors.

Silver Nanocrystal Array with Precise Control via Star-like Copolymer Nanoreactors.

Silver nanocrystal arrays had attracted much attention due to the unique plasmonic effect of their ordered nanostructure and the synergy among adjacent nanocrystals. Conventional preparation methods had several limitations, such as high cost, harsh preparation conditions, and complicated influencing factors, which could not be employed to fabricate the nanocrystal arrays in highly controlled fashion. To solve these issues, we reported ordered arrays of different Ag nanocrystals with precise control prepared by utilizing amphiphilic star-like poly(4-vinylpyridine)-block-polystyrene diblock copolymers as nanoreactors synthesized by sequential atom transfer radical polymerization. Moreover, this unimolecular nanoreactor method based on star-like copolymers with stable and predesigned nanostructures was proved to be a universal approach to prepare other nanocrystal arrays. This strategy had low cost, simple process flow, wide applicability, and structural stability that could fabricate nanocrystal array with precise control and continuously prepare more complex nanostructure units in a large scale to meet different functions and applications.

Effect of Sodium-Glucose Cotransporter 2 Inhibitors for Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with a high risk of mortality and frequent hospitalization. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have favorable cardiovascular protective effect and could decrease the risk of mortality and hospitalization in patients with heart failure with reduced ejection fraction. However, the effect of SGLT2 inhibitors for HFpEF has not been well studied. Purpose: The aim of this meta-analysis is to systematically assess the effects of SGLT2 inhibitors in patients with HFpEF. Methods: MEDLINE, EMBASE, Ovid, Cochrane Library, Chinese National Knowledge Infrastructure Database, VIP database, Chinese Biomedical Database, and Wanfang Database were searched from inception to November 2021 for randomized controlled trials (RCTs) of SGLT2 inhibitors for HFpEF. Risk bias was assessed for included studies according to Cochrane handbook. The primary outcome was the composite of first hospitalization for heart failure (HHF) or cardiovascular mortality. First HHF, cardiovascular mortality, total HHF, all-cause mortality, exercise capacity, ventricular diastolic function, and adverse events were considered as secondary endpoints. PROSPERO registration: CRD42021291122. Results: A total of 12 RCTs including 10,883 patients with HFpEF (SGLT2 inhibitors group: 5,621; control group: 5,262) were included. All included RCTs were at low risk of bias. Meta-analysis showed that SGLT2 inhibitors significantly reduced the composite of first HHF or cardiovascular mortality (HR:0.78, 95% CI: [0.70, 0.87], P< 0.00001, I 2 = 0%), first HHF (HR:0.71, 95% CI: [0.62, 0.83], P < 0.00001, I 2 = 0%), total HHF (RR:0.75, 95% CI: [0.67, 0.84], P<0.00001, I 2 = 0%), E/e' (MD: -1.22, 95% CI: [-2.29, -0.15], P = 0.03, I 2 = 59%) and adverse events (RR:0.92, 95% CI: [0.88, 0.97], P = 0.001, I 2 = 0%). No statistical differences were found in terms of cardiovascular mortality, all-cause mortality, NT-proBNP, BNP and 6-min walk test distance. Conclusion: SGLT2 inhibitors significantly improve cardiovascular outcomes with a lower risk of serious adverse events in patients with HFpEF. However, these findings require careful recommendation due to the small number of RCTs at present. More multi-center, randomized, double-blind, placebo-controlled trials are needed. Systematic Review Registration: [https://www.crd.york.ac.Uk/prospero/], identifier [CRD42021291122].

Efficacy and safety of Wuling capsule for insomnia disorder: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Wuling capsule has been used in treatment of insomnia disorder in China for decades, but the reported treatment efficacy of different studies was not consistent. This study intended to evaluate the efficacy and safety of Wuling capsule for insomnia disorder, so as to provide evidence for clinical application. METHODS: Eight databases (MEDLINE, EMBASE, Ovid, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, Chinese Biomedical Database and Wanfang) were searched from inception to September 14, 2021. Randomized controlled trials (RCTs) comparing Wuling capsule with controls in adults with insomnia disorder were eligible. The primary outcome was sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI), and the secondary outcomes were severity of insomnia disorder measured by Sleep Dysfunction Rating Scale (SDRS) and adverse events. This study was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. RESULTS: Nineteen RCTs with a total of 1850 participants were included. In terms of sleep quality assessed by PSQI, Wuling capsule significantly lowered PSQI score (MD: -1.92, 95% CI: [-2.34, -1.50], P < 0.00001, I2 = 95%) compared to controls, and the effect of Wuling capsule was significantly better than control no matter when Wuling capsule as monotherapy (MD: -1.71, 95% CI: [-2.33, -1.09], P < 0.00001, I2 = 97%) or as adjunctive therapy (MD: -2.10, 95% CI: [-2.66, -1.55], P < 0.00001, I2 = 90%). Wuling capsule was more effective for the treatment duration lasted 8 weeks (MD: -2.57, 95% CI: [-3.52, -1.62], P < 0.00001, I2 = 93%) than 4 weeks (MD: -1.68, 95% CI: [-2.13, -1.22], P < 0.00001, I2 = 95%). In terms of severity of insomnia disorder measured by SDRS, Wuling capsule significantly reduced SDRS score (MD: -4.21, 95% CI: [-4.95, -3.46], P < 0.00001, I2 = 0%) compared to benzodiazepines. Wuling capsule significantly reduced adverse events compared to controls (RR: 0.47, 95% CI: [0.34, 0.65], P < 0.00001, I2 = 43%). CONCLUSION: Wuling capsule can safely and effectively improve sleep quality in patients with insomnia disorder. However, these findings require careful recommendation due to the high heterogeneity and high risk of bias in the included trials. Clinical trials with higher quality designs are needed.

Effect of Sodium Tanshinone IIA Sulfonate Injection on Blood Lipid in Patients With Coronary Heart Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Lipid-lowering therapy is very important in secondary prevention of coronary heart disease (CHD). In many clinical trials, it has been found that Sodium Tanshinone IIA Sulfonate Injection (STS) have a lipid-lowering effect while reducing major cardiovascular events in patients with CHD. However, up to now, there is no system review on the effectiveness and safety of STS affecting blood lipids. Purpose: The aim of this review is to systematically assess the effects of STS on blood lipid levels in patients with CHD. Methods: Until Mar 2021, five databases (PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database) were searched for randomized controlled trials (RCTs) about STS treating patients with CHD. Risk bias was assessed for included studies according to Cochrane handbook. The primary outcome was total cholesterol (TC). The secondary outcomes were triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and adverse events (AEs). Results: A total of 27 trials including 2,445 CHD patients met the eligibility criteria. Most trials had high risks in random sequence generation, allocation concealment, blinding of patients and personal, blinding of outcome assessment. Meta-analysis showed that STS significantly reduced plasma TC levels [MD = -1.34 mmol/l 95% CI (-1.59, -1.09), p < 0.00001, I 2 = 98%], TG levels [MD = -0.49 mmol/l 95% CI (-0.62, -0.35), p < 0.00001, I 2 = 97%], LDL-c levels [MD = -0.68 mmol/l (-0.80, -0.57), p < 0.00001, I 2 = 96%], increased HDL-c levels [MD = 0.26 mmol/l (0.15, 0.37), p < 0.00001, I 2 = 97%], without increasing the incidence of AEs [RR = 1.27 95% CI (0.72, 2.27), p = 0.94, I 2 = 0%] in patients with CHD. Conclusion: STS can safely and effectively reduce plasma TC, TG and LDL-c levels in patients with CHD, and improve plasma HDL-c levels. However, these findings require careful recommendation due to the low overall quality of RCTs at present. More multi-center, randomized, double-blind, placebo-controlled trials which are designed follow the CONSORT 2010 guideline are needed.

Prognostic value of neutrophil gelatinase-associated lipocalin and glycosylated hemoglobin for non-ST-segment elevation myocardial infarction patients with single concomitant chronic total occlusion following primary percutaneous coronary intervention: A prospective observational study.

To investigate factors predicting the onset of major adverse cardiovascular and cerebrovascular events (MACCEs) after primary percutaneous coronary intervention (pPCI) for patients with non-ST-segment elevation infarction (NSTEMI) and single concomitant chronic total occlusion (CTO). Neutrophil gelatinase-associated lipocalin (NGAL) and glycosylated hemoglobin (HbA1c) both play essential role in cardiovascular and cerebrovascular homoeostasis. However, current knowledge of its predictive prognostic value is limited.422 patients with NSTEMI and CTO (59.7 ±â€Š12.4 years, 74.2% men) who underwent successful pPCI were enrolled and followed for 2 years. Multivariate cox regression analysis and receiver operating characteristic (ROC) curve analysis were performed to determine the factors predicting MACCEs.140 patients (33.2%) experienced MACCEs in the follow-up period. Multivariate cox regression analysis found when we process the model with NGAL at admission, low left ventricular ejection fraction (LVEF, HR = 0.963, 95% CI 0.940 to 0.987, P = .003) and fasting blood glucose (HR = 1.078, 95% CI 1.002 to 1.159, P = .044), but not NGAL at admission, were independent predictors of 2 years MACCEs. While HbA1C (HR = 1.119, 95% CI 1.014 to 1.234, P = .025), LVEF (HR = 0.963, 95% CI 0.939 to 0.987, P = .003), estimated glomerular filtration rate (HR = 1.020, 95% CI 1.006 to 1.035, P = .006) and NGAL value 7 day (HR = 1.020, 95% CI 1.006 to 1.035, P = .006) showed their predictive value in another model. ROC analysis indicated NGAL 7 day (AUC = 0.680, P = .0054 and AUC = 0.622, P = .0005) and LVEF (AUC = 0.691, P = .0298 and AUC = 0.605, P = .0021) could predict both in-hospital and 2 years MACCEs, while higher NGAL at admission could only predict poorer in-hospital prognosis (AUC = 0.665, P = .0103). Further analysis showed the prognostic value of NGAL was particularly remarkable among those HbA1C<6.5%.Patients with NSTEMI and single concomitant CTO receiving pPCI with higher NGAL on 7 days during hospitalization are more likely to suffer 2 years MACCEs, particularly in those with lower HbA1C.

Prediction of all-cause mortality with hypoalbuminemia in patients with heart failure: a meta-analysis.

Objective: The prognostic utility of serum albumin level for mortality in heart failure patients has received considerable attention. This meta-analysis sought to examine the prognostic significance of hypoalbuminemia for prediction of all-cause mortality in patients with heart failure. Materials and methods: Pubmed and Embase databases were systematically searched up to 10 March 2019 to identify eligible studies. Epidemiological studies reporting a multivariable-adjusted risk estimate of all-cause mortality associated with hypoalbuminemia in acute or chronic heart failure patients were included. Results: Nine studies from 10 articles involving 16,763 heart failure patients were included in the final analysis. Hypoalbuminemia was associated with an increased in-hospital mortality (risk ratio [RR] 4.90; 95% confidence interval [CI] 2.96-8.10) and long-term all-cause mortality (RR 1.75; 95% CI 1.35-2.27) in acute heart failure patients. Chronic heart failure patients with hypoalbuminemia exhibited a 3.5-fold (95% CI 1.29-9.73) higher risk for long-term all-cause mortality. Conclusions: Hypoalbuminemia is possibly an independent predictor of all-cause mortality in patients with acute or chronic heart failure. However, the current findings should be further confirmed in future prospective studies. Moreover, future well-designed randomized controlled trials would be required to investigate whether correcting hypoalbuminemia in heart failure patients has potential to improve survival outcome.

Acute coronary syndrome secondary to allergic coronary vasospasm (Kounis Syndrome): a case series, follow-up and literature review.

BACKGROUND: Kounis syndrome (KS) is the concurrence of acute coronary syndrome associated with mast-cell and platelet activation in the setting of hypersensitivity and allergic or anaphylactic insults. Many drugs and environmental exposures had been reported as inducers, but various inducers and the mechanism of KS remained unknown till now. The widely used traditional Chinese medicine (TCM) as a potential sensitizer were scarcely reported to induce allergic vasospasm due to the ignorance of the linkage between traditional medicine allergy and vasospasm. CASE PRESENTATION: We described 5 rare cases of KS including unreported triggers of TCM and abortion, reported the treatment strategy and 1~4 years' follow-up results, and tried to probe into the etiology of KS. Case 1 and case 2 for the first time reported acute ST-segment elevation myocardial infarction (STEMI) caused by Chinese herbs related allergic coronary vasospasm. Case 3 reported recurrent angina following allergen contact and wheezing, indicating the internal linkage of coronary vasospasm and allergic asthma. Case 4 described a childbearing-age woman suffered refractory ischemic chest pain due to coronary vasospasm in a special period of post-abortion, the attacks suddenly disappeared when her menopause recovered. Case 5 described an isolated episode of allergic coronary vasospasm under exposure of smoking and stress, which was successfully prevented by avoiding the exposures. CONCLUSION: Kounis syndrome is not rare but rarely recognized and under-diagnosed. It is necessary to recognize KS and various inducers, especially for the patients suffering refractory vasospastic cardiac attacks concentrating in special periods. Blood test of eosinophil might contribute to diagnose KS and anti-allergic agents might be helpful for controlling KS attacks.

Inhibitory effects of PGA1 and TRI on the apoptosis of cardiac microvascular endothelial cells of rats.

The present study investigated the protective effects and molecular mechanism of prostaglandin A1 (PGA1) and triptolide (TRI) on apoptosis of cardiac microvascular endothelial cells (CMVECs) in rats. CMVECs of rats were isolated and then cultured. MTT method was used to select and establish a cell hypoxia reoxygenation cell model. The cells were divided into four groups: Normoxia control group (C, normal oxygen), hypoxia reoxygenation group (H/R, hypoxia for 12 h/reoxygenation for 6 h), PGA1 group (H/R+PGA1) and TRI group (H/R+TRI). The growth of cells in each of the group was observed. B-cell lymphoma 2 (Bcl-2) mRNA expression in CMVECs and expression of Bcl-2 mRNA after PGA1 and TRI treatment were determined by RT-PCR. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Bcl-2 mRNA decreased significantly after hypoxia stimulation of CMVECs of rats. The expression of Bcl-2 mRNA was significantly higher in comparison to hypoxia stimulation group after treatment with PGA1 and TRI (P<0.01). The elevated effect of PGA1 on Bcl-2 mRNA was stronger than that of the TRI group (P<0.05). The number of CMVECs reduced significantly after hypoxia. By contrast, DNA fragmentation and the number of endothelial cell apoptosis were increased significantly. However, Bcl-2 mRNA expression decreased significantly, after PGA1 and TRI treatments. Furthermore, the number of apoptotic cells reduced and Bcl-2 mRNA expression increased (P<0.01). PGA1 and TRI significantly upregulated the expression of Bcl-2 mRNA, inhibited the activation of CMVECs and were able to achieve the protective effect on apoptosis of CMVECs in hypoxia-oxygenated rats.

Effect of Dialysis on Antiplatelet Drug Efficacy in Uremic Patients with Coronary Heart Disease.

BACKGROUND: Coronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease. METHODS: This study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation. RESULTS: The mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42 ± 3.32%, respectively (t= -1.278, P= 0.213). The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87 ± 5.10% and 61.94 ± 5.90%, respectively (t = 1.425, P= 0.167). There was no significant difference in the inhibition rates of platelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel. CONCLUSION: Dialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease.

Electrophysiologic characteristics and radiofrequency ablation of focal atrial tachycardia arising from non-coronary sinuses of Valsalva in the aorta.

OBJECTIVES: Focal atrial tachycardia (AT) arising from non-coronary cusp (NCC) is very rare, and the experience in catheter ablation of this kind of tachycardia remains limited. This study describes the electrophysiologic characteristics and radiofrequency ablation of AT arising from NCC. METHODS AND RESULTS: The study population consisted of five consecutive patients (three females and two males; age 37-68 years) with AT arising from NCC. The morphology of P waves was described as positive, negative, isoelectric, or biphasic (positive-negative or negative-positive). The atrial mapping was performed during tachycardia to define the earliest atrial activation site. Mean tachycardia cycle length of AT in five patients was 363 +/- 44 ms. P-wave morphology was predominantly upright or biphasic in lead II, III, and aVF, inverted in aVR. Positive P-wave morphology was seen in lead aVL in all five patients. The precordial leads were negative-positive in V(1) and V(2), negative-positive or positive in lead V(3)-V(5), and positive in lead V(6). All the five patients underwent successful radiofrequency ablation within NCC. During a follow up of > 3 months, no patient presented with a recurrence. CONCLUSIONS: This study demonstrated that mapping and ablation of focal AT arising from NCC is safe and effective. When earliest activation was recorded in the proximal electrode of the His-bundle catheter, but radiofrequency ablation in this region cannot successfully eliminated the tachycardia, the AT should be considered to arise from NCC especially when P-wave morphology was initially negative with a late positive component in right precordial leads, upright or biphasic in inferior leads.

Effects of unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm on synaptic plasticity in the hippocampal CA1 area in vivo.

Repeated vivid recalls or flashbacks of traumatic memories and memory deficits are the cardinal features of post-traumatic stress disorder (PTSD). The underlying mechanisms are not fully understood yet. Here, we examined the effects of very strong fear conditioning (20 pairings of a light with a 1.5-mA, 0.5-s foot shock) and subsequent reexposure to the conditioning context (chamber A), a similar context (chamber B), and/or to the fear conditioned stimulus (CS) (a light) on synaptic plasticity in the hippocampal CA1 area in anesthetized Sprague-Dawley rats. The conditioning procedure resulted in very strong conditioned fear, as reflected by high levels of persistent freezing, to both the contexts and to the CS, 24 h after fear conditioning. The induction of long-term potentiation (LTP) was blocked immediately after fear conditioning. It was still markedly impaired 24 h after fear conditioning; reexposure to the conditioning chamber A (CA) or to a similar chamber B (CB) did not affect the impairment. However, presentation of the CS in the CA exacerbated the impairment of LTP, whereas the CS presentation in a CB ameliorated the impairment so that LTP induction did not differ from that of control groups. The induction of long-term depression (LTD) was facilitated immediately, but not 24 h, after fear conditioning. Only reexposure to the CS in the CA, but not reexposure to either chamber A or B alone, or the CS in chamber B, 24 h after conditioning, reinstated the facilitation of LTD induction. These data demonstrate that unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm can have profound effects on hippocampal synaptic plasticity, which may aid to understand the mechanisms underlying impairments of hippocampus-dependent memory by stress or in PTSD.