Frequency-specific modulation of oscillatory activity in the rat auditory cortex by vagus nerve stimulation.

BACKGROUND: We previously found that vagus nerve stimulation (VNS) strengthened stimulus-evoked activity in the superficial layer of the sensory cortex but not in the deep layer, suggesting that VNS altered the balance between the feedforward (FF) and feedback (FB) pathways. Band-specific oscillatory activities in the cortex could serve as an index of the FF-FB balance, but whether VNS affects cortical oscillations along sensory pathways through neuromodulators remains unclear. HYPOTHESIS: VNS modulates the FF-FB balance through the cholinergic and noradrenergic systems, which modulate stimulus gain in the cortex. METHODS: We investigated the effects of VNS using electrocorticography in the auditory cortex of 34 Wistar rats under general anesthesia while presenting click stimuli. In the time-frequency analyses, the putative modulation of the FF and FB pathways was estimated using high- and low-frequency power. We assessed, using analysis of variance, how VNS modulates auditory-evoked activities and how the modulation changes with cholinergic and noradrenergic antagonists. RESULTS: VNS increased auditory cortical evoked potentials, consistent with results of our previous work. Furthermore, VNS increased auditory-evoked gamma and beta powers and decreased theta power. Local administration of cholinergic antagonists in the auditory cortex selectively disrupted the VNS-induced increase in gamma and beta power, while noradrenergic antagonists disrupted the decrease in theta power. CONCLUSIONS: VNS might strengthen the FF pathway through the cholinergic system and attenuate the FB pathway through the noradrenergic system in the auditory cortex. Cortical gain modulation through the VNS-induced neuromodulatory system provides new mechanistic insights into the effect of VNS on auditory processing.

Interventricular septal curvature as an additional echocardiographic parameter for evaluating chronic thromboembolic pulmonary hypertension: a single-center retrospective study.

BACKGROUND: Noninvasive estimation of the actual systolic pulmonary artery pressure measured via right-sided heart catheterization (sPAPRHC) is vital for the management of pulmonary hypertension, including chronic thromboembolic pulmonary hypertension (CTEPH). Evaluation related to the interventricular septum (IVS) is generally performed with only visual assessment and has been rarely assessed quantitatively in the field of echocardiography. Thus, this study aimed to investigate the utility of echocardiographic IVS curvature to estimate sPAPRHC in patients with CTEPH. METHODS: Medical records of 72 patients with CTEPH were studied retrospectively. We estimated sPAPRHC using echocardiographic IVS curvature (esPAPcurv) and left ventricular eccentricity index (esPAPLVEI), and compared their ability to predict sPAPRHC with estimated sPAPRHC using tricuspid regurgitant pressure gradient (esPAPTRPG). RESULTS: IVS curvature and LVEI were significantly correlated with sPAPRHC (r = - 0.52 and r = 0.49, respectively). Moreover, the IVS curvature was effective in estimating the sPAPRHC of patients with trivial tricuspid regurgitation (r = - 0.56) and in determining patients with sPAPRHC ≥ 70 mmHg with higher sensitivity (77.0%) compared to those with esPAPTRPG and esPAPLVEI. CONCLUSION: Our results indicate that the echocardiographic IVS curvature could be a useful additional tool for estimating sPAPRHC in CTEPH patients for whom accurate estimation of sPAPRHC using tricuspid regurgitant pressure gradient is challenging.

The effects of pirfenidone in patients with an acute exacerbation of interstitial pneumonia.

INTRODUCTION: The prognosis of patients with an acute exacerbation of interstitial pneumonia (AE-IP) is poor. Pirfenidone (PFD) reduces the disease progression in idiopathic pulmonary fibrosis. OBJECTIVES: The purpose of this study was evaluating whether the administration of PFD improved the outcomes of AE-IP. METHODS: We conducted a retrospective study of 31 patients with AE-IP who did not recover between 7 and 14 days after an initial treatment. Fourteen patients received PFD within 2 weeks (PFD group) of the AE, while 17 patients were treated without PFD (non-PFD group). The patients' clinical data and computed tomography (CT) scores were analyzed. RESULTS: The survival rate in the PFD group was not significantly different from non-PFD group at 30 (78.6% vs 64.7%, P = .46) and 90 days (64.3% vs 52.9%, P = .72). The white blood cell counts in the PFD group were significantly lower on PFD day 14 than on PFD days 1 and 7. The C-reactive protein levels in the PFD group were also significantly lower on PFD day 7 than on PFD day 1. There were no significant differences regarding the changes of the CT scores. CONCLUSIONS: PFD may reduce the inflammation in AE-IP patients undergoing corticosteroid treatment.

Mosaic attenuation pattern in non-contrast computed tomography for the assessment of pulmonary perfusion in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is difficult to diagnose as patients rarely present with specific symptoms. However, a mosaic attenuation pattern (MAP) in chest computed tomography (CT) suggests CTEPH. Areas of increased attenuation are not always visible using default CT settings for the lung. Thus, we examined the utility of non-contrast CT imaging with new settings focusing on MAP (CTMosaic) for the assessment of pulmonary perfusion in patients with CTEPH. The regional perfusion defects visualized using CTMosaic and single-photon-emission CT with fusion of CT images (SPECT/CT) were compared. METHODS: Twenty-seven patients with CTEPH (20 women; aged 62.8±7.9 years) underwent imaging with non-contrast CT and SPECT/CT. We converted non-contrast mediastinal CT images into various CT window settings to identify the MAP, and the CT window setting that could most easily identify the MAP was defined as CTMosaic. We then scored and compared lung segments depending on the degree of perfusion on CTMosaic and SPECT/CT. RESULTS: CTMosaic was identified as the CT window setting in which the window level was -800 Hounsfield units (HU), and the window width was 200 HU. Using CTMosaic, MAP was detected in 366 of 486 segments (75.3%). The agreement between CTMosaic and perfusion defects on SPECT/CT was 84.9%. Weighted kappa statistics demonstrated a good agreement between the two examinations (κ=0.605, 95% confidence interval, 0.502-0.707). CONCLUSIONS: The CTMosaic setting can easily identify an MAP in CTEPH patients. Therefore, this may be useful as a simple and cost-effective evaluation method for blood distribution in patients with CTEPH.

Riociguat for patients with chronic thromboembolic pulmonary hypertension: Usefulness of transitioning from phosphodiesterase type 5 inhibitor.

BACKGROUND: Riociguat, the first approved drug for patients with chronic thromboembolic pulmonary hypertension (CTEPH), is a soluble guanylate cyclase (sGC) Stimulator. It directly stimulates sGC independently of nitric oxide (NO) and increases sGC sensitivity for NO. The safety and efficacy of transitioning from a phosphodiesterase 5 inhibitor (PDE5i) to riociguat is unknown. METHODS AND RESULTS: Twenty-three patients were prospectively enrolled: 8 symptomatic patients with inadequate clinical responses to PDE5i were changed to riociguat (transitioned group); 15 started riociguat anew (new or add-on group). We analyzed the change from baseline to 6-12 months of riociguat treatment for the 6-minute walk distance (6MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI), partial pressure of oxygen in arterial blood (PaO2), brain natriuretic peptide (BNP), World Health Organization (WHO) functional class, safety and adverse events. The mPAP, BNP and WHO functional class significantly improved in total. In the transitioned group, BNP significantly decreased by -116.5±188.6pg/ml (P=0.0156). The 6MWD, mPAP, PVR, CI, and PaO2 improved but not significantly. The baseline condition was significantly more severe in the transitioned than in the new or add-on group. No patients discontinued riociguat. Relatively rapid transitioning from PDE5i to riociguat was safe under careful observation. CONCLUSIONS: Transitioning to riociguat may be safe and effective in CTEPH patients with inadequate clinical responses to PDE5i.

The anticoagulant effects of warfarin and the bleeding risk associated with its use in patients with chronic thromboembolic pulmonary hypertension at a specialist center in Japan: a retrospective cohort study.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulation therapy. However, the bleeding risk and recurrence of venous thromboembolism (VTE) in CTEPH patients who are administered warfarin have not been adequately evaluated. The purpose of this study was to evaluate the risk of clinically relevant bleeding, recurrent VTE, and clinical worsening in patients with CTEPH who were administered warfarin. The clinical records of 72 patients with CTEPH who regularly visited our institution and were administered warfarin were retrospectively reviewed between 1 January 2011 and 31 December 2015. We investigated the incidence of clinically relevant bleeding events, recurrent VTE, and hospitalization for the deterioration of pulmonary hypertension or right heart failure (RHF) during the observation period. The mean observation period for the 72 patients was 3.60 ± 1.60 person-years. Clinically relevant bleeding, RHF, and recurrent VTE occurred in 21 (29.2%), eight (11.1%), and three (4.2%) of 72 patients, respectively, and the incidence rates for these events were 8.1%/person-year, 3.1%/person-year, and 1.2%/person-year, respectively. The incidence rates for the major and non-major bleeding events were 5.0%/person-year and 3.9%/person-year, respectively. The incidence of clinically relevant bleeding events was 20.8%/person-year during medical treatment with a soluble guanylate cyclase stimulator. One of 35 patients (2.9%) during the post-pulmonary endarterectomy period experienced hemoptysis during observation period (> 6 months after pulmonary endarterectomy). No bleeding events occurred during the post-balloon pulmonary angioplasty period. In conclusion, warfarin effectively prevents VTE recurrence in CTEPH patients, but its effects may be associated with a considerable bleeding risk.

Mean Pulmonary Artery Pressure Using Echocardiography in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Mean pulmonary arterial pressure (MPAP) is an important pulmonary hemodynamic parameter used in the management of patients with chronic thromboembolic pulmonary hypertension (CTEPH). We compared echocardiography-derived estimates of MPAP with right heart catheterization (RHC) to identify reliable noninvasive methods of estimating MPAP-derived RHC (MPAPRHC) in these patients. METHODS AND RESULTS: Echocardiography and RHC were performed in 56 patients with CTEPH (60.5±12.0 years; 44 females). We measured the tricuspid regurgitation (TR) pressure gradient (TRPG) using echocardiography. The mean systolic right ventricular (RV)-right atrial (RA) gradient was calculated by tracing the TR time velocity flow. Systolic and mean pulmonary artery pressures (SPAPTRand MPAPTR) estimated from TRPG and mean systolic RV-RA gradient were calculated by adding RA pressure based on the inferior vena cava. MPAPChemlawas calculated using Chemla's formula: 0.61×SPAPTR+2 mmHg. MPAPRHCand pulmonary vascular resistance were 35.9±11.3 mmHg and 6.6±3.6 Wood units, respectively. The mean difference from MPAPRHCand limits of agreement were -1.5 mmHg and -19.6 to 16.5 mmHg for MPAPTR, and -4.6 mmHg and -24.5 to 15.2 mmHg for MPAPChemla. Accuracy within 10 mmHg and 5 mmHg of MPAPRHCwas 80.4% and 46.4% for MPAPTR, and 71.4% and 48.2% for MPAPChemla, respectively. CONCLUSIONS: MPAPTRand MPAPChemlaare reliable estimates for MPAPRHCin patients with CTEPH. (Circ J 2016; 80: 1259-1264).

Noninvasive assessment of pulmonary vascular resistance by echocardiography in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Pulmonary vascular resistance (PVR) is an important parameter in the management of patients with chronic thromboembolic pulmonary hypertension (CTEPH), and numerous noninvasive methods for PVR prediction have been proposed. However, a systematic evaluation of the methods that are specific for CTEPH has not been conducted. We compared a variety of echocardiography-derived prediction indices with direct right heart catheterization (RHC) to identify the most reliable noninvasive indicator of PVR in patients with CTEPH. PATIENTS AND METHODS: Echocardiography and RHC were performed sequentially in 40 patients (mean age: 62.4±11.4 years; 30 females) with CTEPH. We measured the peak flow velocity of tricuspid regurgitation (TRV), tricuspid regurgitation pressure gradient (TRPG), right ventricular outflow tract (RVOT) time-velocity integral (TVIRVOT), left ventricular outflow tract (LVOT) time-velocity integral (TVILVOT), cardiac output at RVOT (CORVOT), and the LVOT (COLVOT) using echocardiography. The parameters TRV/TVIRVOT, TRV/TVILVOT, TRV/CORVOT, TRV/COLVOT, TRPG/TVIRVOT, TRPG/TVILVOT, TRPG/CORVOT, and TRPG/COLVOT were then calculated to predict the PVR. Finally, correlations between these echocardiographic predictors of PVR and the PVR data obtained from RHC (PVRRHC) were assessed. RESULTS: The mean pulmonary arterial pressure and PVRRHC were 32.1±11.4mmHg and 5.4±2.9 Wood units, respectively. TRV/TVIRVOT, TRV/TVILVOT, TRV/COLVOT, TRPG/TVIRVOT, TRPG/TVILVOT, TRPG/CORVOT, and TRPG/COLVOT were all significantly correlated with the PVRRHC, and TRPG/COLVOT was the most strongly correlated with the PVRRHC (r=0.807, p<0.001). CONCLUSIONS: Echocardiographic measurement of TRPG/COLVOT is a reliable noninvasive predictor of PVR in CTEPH patients.