Total lung denervation

INTRODUCTION: Targeting the parasympathetic nervous system innervating the airway with pharmacologic products has been proved to improve the clinical outcomes of severe asthma. Bronchial cryo-denervation (BCD) is a novel non-pharmacologic treatment for severe asthma using an endobronchial cryo-balloon administered via bronchoscopy to denervate parasympathetic pulmonary nerves. Preclinical studies have demonstrated that BCD significantly disrupted vagal innervation in the lung. METHODS: A total of 15 patients with severe asthma were enrolled in this prospective, single-center pilot study...

BACKGROUND: Long-term benefits of pulmonary artery denervation (PADN) for patients with combined precapillary and postcapillary pulmonary hypertension (CpcPH) secondary to left heart failure are unknown. OBJECTIVES: The authors sought to report the 3-year clinical results of PADN for patients with CpcPH. METHODS: A total of 98 patients with CpcPH, defined as having mean pulmonary arterial pressure of ≥25 mm Hg, pulmonary capillary wedge pressure of >15 mm Hg, and pulmonary vascular resistance of >3...

BACKGROUND: The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs. intermediate-high-risk PAH patients. METHODS: In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-minute walk distance (6 MWD) from baseline to 6 months...

Aims: This study aimed to assess the long-term effects of pulmonary artery denervation (PADN) on mortality in patients with pulmonary arterial hypertension (PAH). Methods and results: Between March 2012 and March 2018, a total of 120 patients with PAH, who underwent PADN treatment and were prospectively followed up, were analysed. Patients were classified into World Health Organization (WHO) Functional Class I and II (FC 1-2; n=46) and Functional Class III and IV (FC 3-4; n=74) according to their FC prior to PADN...

BACKGROUND: Pulmonary hypertension (pH) is a progressive and fatal disease with poor long-term prognosis and high mortality. Although great progress has been made in current treatment methods, the survival rate is still poor. Therefore, we need to find an effective treatment for pH. OBJECTIVE: pH is a type of refractory, progressive, and fatal pulmonary vascular disease which involves a variety of clinical conditions and may complicate most cardiovascular and respiratory diseases...

BACKGROUND: Endoscopic and surgical interventions may be beneficial for selected patients with emphysema. Rates of treatment failure decrease when the predictors for successful therapy are known. The aim of the study was to evaluate the number of patients with severe emphysema who were not eligible for any intervention, and the reasons for their exclusion. METHODS: The study was a retrospective analysis of 231 consecutive patients with advanced emphysema who were considered for interventional therapy in 2016 at the Thoraxklinik, Heidelberg, Germany...

BACKGROUND: Lung transplant patients experience a high risk of airway infections and microbial colonization of the lung due to constant exposure to the environment through inhaled microorganisms, denervation, reduced ciliary transport, and decreased cough. METHODS: In this nationwide prospective study on Swedish lung transplant patients, we evaluated the microbiological panorama of bacteria, fungi, and virus found in bronchoalveolar lavage fluid (BALF) obtained the first year after lung transplantation (LTx)...

Bronchoscopic lung volume reduction (BLVR) procedure has expanded the treatment spectrum of patients with end-stage emphysema. These treatments include valve, coil, thermal vapor ablation, bio-lung volume reduction, targeted lung denervation, and airway bypass stent. This short review provides an up-to-date information on BLVR treatments, their clinical benefits, and an overview of complications. BLVR treatments generally affect dyspnea by reducing hyperinflation and residual volume (RV). Benefits of treatment are associated with improvement in lung function parameters (forced expiration volume in the first second, total lung capacity, RV, and 6-minute walking test) and quality of life...

Background: Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD which ablates parasympathetic pulmonary nerves running along the outside of the two main bronchi with the intent of inducing permanent bronchodilation. The goal of this study was to evaluate the feasibility and long-term safety of bilateral TLD during a single procedure. Patients and methods: This prospective, multicenter study evaluated 15 patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV1 ] 30%-60%) who underwent bilateral TLD treatment following baseline assessment without bronchodilators...

The effects of lung afferents denervation on cardiovascular regulation can be assessed on bilateral lung transplantation patients. The high-frequency component of heart rate variability is known to be synchronous with breathing frequency. Then, if heart beat is neurally modulated by breathing frequency, we may expect disappearance of high frequency of heart rate variability in bilateral lung transplantation patients. On 11 patients and 11 matching healthy controls, we measured R-R interval (electrocardiography), blood pressure (Portapres® ) and breathing frequency (ultrasonic device) in supine rest, during 10-min free breathing, 10-min cadenced breathing (0·25 Hz) and 5-min handgrip...

Hydroxypropyl-β-cyclodextrin (HPβCD) is a complexation agent used to enhance drug solubilization and formulation stability. Although its toxicity is well characterized, its cardiovascular effects are less known. To investigate them, HPβCD was infused intravenously over 10 min in anesthetized dogs (10-40% (w/v, i.e. 200-800 mg/kg) in non-denervated animals and at 40% in denervated animals). HPβCD increased renal arteriolar resistance and decreased renal blood flow at all doses, almost immediately after infusion start, more drastically in females...

Vagally mediated afferent feedback and compliant lungs (surfactant system) play vital roles in the establishment of adequate alveolar ventilation and pulmonary gas exchange at birth. Although the significance of vagal innervation in the establishment of normal breathing patterns is well recognized, the precise role of lung innervation in the maturation of the surfactant system remains unclear. The specific aim of the present study was to investigate whether vagal denervation compromises the surfactant system during fetal development...

In this study, we examined the usefulness of arterial blood gas variables, as changed by the hypoxic stimulus, in discerning various experimentally-induced conditions of diaphragm weakness in anesthetized cats. We defined three experimental situations (models): (i) intact muscle, statistical Class I, (ii) four degrees of muscle dysfunction (after sequential diaphragm denervation), Classes II-V, and (iii) entirely paralyzed muscle, Class VI. Responses to a hypoxic stimulus in the above-mentioned conditions were evaluated by using the methods of the pattern recognition theory...

The success of heart-lung transplant experiments in subprimate models has been limited because most techniques include total pulmonary denervation, which causes respiratory problems, blood loss, and subsequent death. Using 20 subprimates (12 domestic swine and 8 mongrel dogs), we tested a heterotopic heart-single lung transplant method intended to preserve unilateral pulmonary innervation and to reduce blood loss. After native right pneumonectomy, the donor heart and right lung were transplanted en bloc. Anastomotic sites included the right primary bronchus, the superior vena cava, and the aorta...

We report a case of persistent twitching of the latissimus dorsi muscle following a posterolateral thoracotomy, which continued despite several attempts at control including denervation, and was ultimately cured by total resection of the muscle.

Vagal denervation performed in the intrathoracic region in newborn lambs leads to hypoxemia and decreased respiratory system compliance (Crs), which could result from atelectasis and/or pulmonary edema. The objective of the present study was to quantify the relative roles of alveolar derecruitment and pulmonary edema as underlying cause(s) of respiratory failure. Vagal denervation was performed in the intrathoracic region and below the recurrent laryngeal nerves in six newborn lambs within 24 h of birth, whereas six were sham operated...

Recently, Wong et al. (Wong KA, Bano A, Rigaux A, Wang B, Bharadwaj B, Schurch S, Green F, Remmers JE, and Hasan SU, J Appl Physiol 85: 849-859, 1998) demonstrated that fetal lambs that have undergone vagal denervation prenatally do not establish adequate alveolar ventilation shortly after birth. In their study, however, vagal denervation was performed prenatally and the deleterious effects of vagal denervation on breathing patterns and gas exchange could have resulted from the prenatal actions of the neurotomy...

There are many mechanisms underlying the hypertension which occurs after thoracic transplantation. Previous disease, effects of cyclosporin, tacrolimus and steroid immunosuppression and cardiac denervation are major contributory factors. Abnormal sodium and water balance is an important common mediating factor. A new approach is clearly needed for classifying the severity of hypertension in these patients taking into account day-night variation and total blood pressure (BP) load. This would allow improved strategies for investigation and treatment...

BACKGROUND: There are conflicting data regarding whether the primary source of afferent input for the vagal cardiopulmonary reflex emanates from receptors located in the ventricles, atria, and/or lungs. This study evaluated the effects of total cardiac deafferentation on the reflex control of efferent renal sympathetic nerve activity (RSNA) in response to a stimulus that affected all vagal receptors in the cardiopulmonary region. METHODS AND RESULTS: Experiments were performed in 14 chloralose-anesthetized dogs with sinoaortic denervation...

In mechanically ventilated awake and sleeping humans, it has been shown that increasing inspiratory flow rate (V'I) exerted a reflex excitatory effect on respiratory output. Mechanoreceptors located in intercostal muscles or within the lung have been suggested as possible pathways that may mediate the excitatory effect of V'I. To test this, five patients with bilateral lung transplantation (LTP) and eight quadriplegics with spinal cord transection at the level of C6-C7 (QP) were studied. Patients were connected to a volume cycle ventilator in the assist volume-control mode and V'I was randomly changed...