Double Lung Transplant Patients Research Articles

Lung transplant survival with past and concomitant cardiac revascularization

Coronary artery disease is common among lung transplant (LTx) candidates and has historically been viewed as a contraindication to the procedure. Survival outcomes of lung transplant recipients with concomitant coronary artery disease who had prior or perioperative revascularization remain a topic of conversation. A retrospective analysis of all single and double lung transplant patients from Feb, 2012 to Aug, 2021 at a single center was performed (n=880). Patients were split into 4 groups: (1) those who received a preoperative percutaneous coronary intervention, (2) those who received preoperative coronary artery bypass grafting, (3) those who received coronary artery bypass grafting during transplantation, and (4) those who had lung transplantation without revascularization. Groups were compared for demographics, surgical procedure, and survival outcomes using STATA Inc. A p value<0.05 was considered significant. Most patients receiving LTx were male and white. Pump type (p = 0.810), total ischemic time (p= 0.994), warm ischemic time (p = 0.479), length of stay (p =0.751), and lung allocation score (p = 0.332) were not significantly different between the four groups. The no revascularization group was younger than the other groups (p<0.01). The diagnosis of Idiopathic Pulmonary Fibrosis was predominant in all groups except the no revascularization group. The pre-coronary artery bypass grafting group had a higher portion of single LTx procedures (p = 0.014). Kaplan-Meier analysis showed no significantly different survival rates after post-LTx between the groups (p = 0.471). Cox Regression analysis showed diagnosis significantly impacted survival rates (p 0.009). Preoperative or intraoperative revascularization did not affect survival outcomes in lung transplant patients. Selected patients with coronary artery disease may benefit when intervened during lung transplant procedures.

Corticotropin releasing hormone as an identifier of bronchiolitis obliterans syndrome

Lung transplantion (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS), an inflammation of the small airways in chronic rejection of a lung allograft. There is great clinical need for a minimally invasive biomarker of BOS. Here, 644 different proteins were analyzed to detect biomarkers that distinguish BOS grade 0 from grades 1–3. The plasma of 46 double lung transplant patients was analyzed for proteins using a high-component, multiplex immunoassay that enables analysis of protein biomarkers. Proximity Extension Assay (PEA) consists of antibody probe pairs which bind to targets. The resulting polymerase chain reaction (PCR) reporter sequence can be quantified by real-time PCR. Samples were collected at baseline and 1-year post transplantation. Enzyme-linked immunosorbent assay (ELISA) was used to validate the findings of the PEA analysis across both time points and microarray datasets from other lung transplantation centers demonstrated the same findings. Significant decreases in the plasma protein levels of CRH, FERC2, IL-20RA, TNFB, and IGSF3 and an increase in MMP-9 and CTSL1 were seen in patients who developed BOS compared to those who did not. In this study, CRH is presented as a novel potential biomarker in the progression of disease because of its decreased levels in patients across all BOS grades. Additionally, biomarkers involving the remodeling of the extracellular matrix (ECM), such as MMP-9 and CTSL1, were increased in BOS patients.

Post-Reperfusion Pulmonary Artery Pressure is a Clinical Marker of Primary Graft Dysfunction Risk Following Lung Transplant

<h3>Purpose</h3> Primary graft dysfunction is a known risk factor of early mortality after lung transplant (LT). PGD represents ischemia-reperfusion injury in the allograft, which subsequently causes capillary leaks. Clinical models which identify patients at high risk for PGD are limited. We hypothesize high systolic pulmonary artery pressure (sPA pressure) after reperfusion in LT is a clinical marker for those at risk of developing PGD. <h3>Methods</h3> This is a retrospective review of a single site institutional lung transplant database. We included consecutive lung transplant patients from March 2020 through September 2021. Only double lung transplant patients were included, and patients with pre-transplant ECMO use were excluded as ECMO flow could impact sPA pressures. PGD was defined according to modified ISHLT criteria. Receiver operating characteristic (ROC) curve was used to find the cut off value for PGD. <h3>Results</h3> 51 patients were included in this study. PGD occurred in 43.1% (n = 22). One-year survival was reduced in recipients with PGD (p=0.005). The ROC curve of post-reperfusion sPA pressures showed 41 mmHg was the cut off for PGD (sensitivity 0.89, specificity 0.72, area under curve (AUC) 0.84), which is significantly superior to the ROC curve of pre-LT sPA pressures (sensitivity 0.44, specificity 0.68, AUC 0.54, p<0.01). The ROC curve of the difference between patient pre- and post-reperfusion sPA pressures has a sensitivity 0.86, specificity 0.68, AUC 0.71. <h3>Conclusion</h3> Patients with elevated sPA pressure after reperfusion are at increased risk of PGD after LT. Post-reperfusion sPA pressure is more indicative of PGD risk than pre-LT sPA pressure. Using post-reperfusion sPA pressure as a complementary clinical marker of PGD would allow earlier intervention in PGD, which could subsequently improve survival in these LT patients.

Prior and Perioperative Revascularization Impact on Survival in Lung Transplant Patients

<h3>Purpose</h3> Survival outcomes of lung transplant recipients with concomitant coronary artery disease who had prior or perioperative revascularization remains a topic of conversation. We hypothesized concomitant-CABG can be a safe and viable option during lung transplantation in a select group of patients. <h3>Methods</h3> A retrospective analysis of all single and double lung transplant patients from Feb-2012 to Aug-2021 (n=868) was performed. Patients were split into 4 groups: (1) those who received a preoperative percutaneous coronary intervention (n=58), (2) those who received pre-operative coronary artery bypass grafting (CABG) (n=39), (3) those who received concomitant CABG during transplantation (n=51), and (4) those who had lung transplantation without revascularization (n=720). Groups were compared for demographics, surgical procedure, and survival outcomes using STATA Inc. P-value <0.05 was considered significant. <h3>Results</h3> Throughout all groups, a majority of patients receiving LTx were males (p<0.01) and ethnically white (p<0.01). The no revascularization group was significantly younger than the other groups (p<0.01). The diagnosis of IPF constituted the largest portion of all groups except the no revascularization group (p<0.01). In terms of transplant type, the pre-CABG group had a higher portion of single LTx procedures (p=0.014). The antero-axillary thoracotamy approach was the most utilized approach in all groups except Con-CABG (p=0.014). Kaplan-Meier analysis showed that survival rates post-LTx were not significantly different between the groups (p=0.471). Cox Regression analysis showed diagnosis significantly impacted survival rates (p=0.009). <h3>Conclusion</h3> These results continue to suggest that preoperative or intraoperative revascularization did not affect survival outcomes in lung transplant patients. Select patients with coronary artery disease may benefit when intervened during lung transplant procedure with similar outcomes to patients without intervention.

Comparative Performance Analysis of Donor-Derived Cell-Free DNA to Detect Acute Rejection in Single and Double Lung Transplant Recipients

<h3>Purpose</h3> Plasma donor-derived cell-free DNA (ddcfDNA) is a sensitive biomarker for acute rejection (AR). However, its performance remains unknown for single (SL) vs double lung (DL) transplant recipients, where differences in lung mass may affect interpretation. In this study, we aim to distinguish the performance characteristics of ddcfDNA to detect AR in SL vs DL transplant patients. <h3>Methods</h3> Lung transplant recipients (n=105) enrolled in two prospective cohort studies were adjudicated for acute cellular rejection (ACR) and antibody mediated rejection (AMR). <b>Measurement:</b> 337 serially-collected plasma samples were assayed for ddcfDNA by shotgun sequencing. <b>Analysis:</b> Area-under-the-receiver-operating-characteristic-curves (AUROC) of ddcfDNA and performance characteristics for the detection of AR were calculated separately for both DL and SL transplant recipients; cfDNA values were not doubled for SL transplant as in prior studies. <h3>Results</h3> The AUROC for ddcfDNA to detect AR was 0.86 and 0.89 in DL and SL transplants, respectively. The optimal ddcfDNA threshold of 0.54% for SL transplant showed a 92% sensitivity and 80% specificity for detecting AR. For DL transplant, the optimal threshold of 1.1% showed 78% sensitivity and 83% specificity for detecting AR. When ddcfDNA was doubled for single lung transplant, the 1.1% threshold showed 92% sensitivity and 80% specificity for detecting rejection. The AUROC for detection of AMR was 0.91 for both DL and SL transplants. However, the AUROC for detection of ACR was 0.73 for DL and 0.87 for SL transplants. <h3>Conclusion</h3> Plasma ddcfDNA showed similar accuracy to detect AR in both SL and DL transplant recipients, however, the accuracy of ddcfDNA for the detection of ACR appears higher in SL vs DL transplant recipients. Correcting ddcfDNA levels in SL transplant patients by doubling their value appears to be a reasonable method of preserving the performance characteristics of the test for the detection of acute rejection.

Chronic lung allograft dysfunction phenotype and prognosis by machine learning CT analysis.

Chronic lung allograft dysfunction (CLAD) is the principal cause of graft failure in lung transplant recipients and prognosis depends on CLAD phenotype. We used a machine learning computed tomography (CT) lung texture analysis tool at CLAD diagnosis for phenotyping and prognostication compared with radiologist scoring. This retrospective study included all adult first double lung transplant patients (January 2010-December 2015) with CLAD (censored December 2019) and inspiratory CT near CLAD diagnosis. The machine learning tool quantified ground-glass opacity, reticulation, hyperlucent lung and pulmonary vessel volume (PVV). Two radiologists scored for ground-glass opacity, reticulation, consolidation, pleural effusion, air trapping and bronchiectasis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of machine learning and radiologist for CLAD phenotype. Multivariable Cox proportional hazards regression analysis for allograft survival controlled for age, sex, native lung disease, cytomegalovirus serostatus and CLAD phenotype. 88 patients were included (57 bronchiolitis obliterans syndrome (BOS), 20 restrictive allograft syndrome (RAS)/mixed and 11 unclassified/undefined) with CT a median 9.5 days from CLAD onset. Radiologist and machine learning parameters phenotyped RAS/mixed with PVV as the strongest indicator (area under the curve (AUC) 0.85). Machine learning hyperlucent lung phenotyped BOS using only inspiratory CT (AUC 0.76). Radiologist and machine learning parameters predicted graft failure in the multivariable analysis, best with PVV (hazard ratio 1.23, 95% CI 1.05-1.44; p=0.01). Machine learning discriminated between CLAD phenotypes on CT. Both radiologist and machine learning scoring were associated with graft failure, independent of CLAD phenotype. PVV, unique to machine learning, was the strongest in phenotyping and prognostication.

Tacrolimus-Induced Bradykinesia Secondary to Phenoconversion in an Elderly Post-Bilateral Lung Transplant Patient

OBJECTIVE: To report pharmacogenomics post-related bradykinesia secondary to phenoconversion in an elderly post-bilateral lung transplant patient.SUMMARY: The patient was a 68-year-old double lung transplant patient taking the immunosuppressant and CYP3A4/5 substrate tacrolimus concomitantly with 2 CYP3A4/5 inhibitor medications, fluconazole and diltiazem. This drug combination post-dosing resulted in debilitating bradykinesia 1-2 hours after dosing, increasing the risk of falls and possible increased mortality and morbidity risk.CONCLUSION: Taking tacrolimus in combination with CYP3A4/5 inhibitors may increase neurologic adverse effects resulting in increased fall and associated increased mortality and morbidity risk.

Reply to Yan and Muller, "Captisol and GS-704277, but Not GS-441524, Are Credible Mediators of Remdesivir's Nephrotoxicity".

We thank Yan VC and Muller FL (1) for taking their valuable time to comment on our article.….

Prior and Perioperative Revascularization Does Not Affect Survival in Lung Transplant Patients

Coronary artery disease is common in lung transplant patients and has historically been viewed as a contraindication to the procedure. Although this mindset is changing, the effect of prior or perioperative revascularization on lung transplant survival outcomes is not adequately established. We performed a single-center retrospective analysis of all single and double lung transplant patients from 2012 to 2018 (n= 468). Patients were split into 4 groups: (1) patients who received a preoperative percutaneous coronary intervention (n= 34), (2) those who received coronary artery bypass grafting (CABG) before transplantation (n= 25), (3) those that received concomitant CABG during transplantation (n= 29), and (4) those who had lung transplantation with no need for revascularization (n= 380). Groups were compared for demographics, surgical procedure, and survival outcomes. The no-revascularization group was statistically younger than the rest (P= .001). The lung allocation score trended toward being higher in the concomitant coronary artery bypass group (P= .03). All groups were predominantly diagnosed with idiopathic pulmonary fibrosis. The proportion of patients with chronic obstructive pulmonary disease was greatest in the group not requiring revascularization (P= .001). Patients with previous CABG were more likely to receive a single lung transplant than a double one (21 versus 4; P= .054). Length of stay, posttransplant survival, and postoperative adverse events were similar among all groups. Results suggest that preoperative or intraoperative revascularization does not negatively affect survival in lung transplant patients; lung recipients with coronary artery disease have comparable survival when adequately revascularized.

Extracorporeal Photopheresis Improves Survival Probability and Lowers Hospital-Related Expenses In Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome

Purpose Extracorporeal photopheresis (ECP) is used at the Medical University of Vienna as an empiric treatment option for lung transplant recipients suffering from bronchiolitis obliterans syndrome (BOS). The objective of the present retrospective investigation was to evaluate hospital-related costs and the clinical value of ECP when applied as an adjunct to the local standard therapy of BOS compared to standard treatment alone. Methods The patient population consisted of 32 double-lung transplant recipients who had been diagnosed with BOS. Sixteen matched pairs, each pair comprising of one ECP-treated patient and one control patient was built (matched population). Preselect pair-match criteria were weighted. The primary matching criterion was the BOS grade at diagnosis. Secondary matching factors were the year of transplantation, age at transplantation, and gender. Results Study groups were identical in demographic characteristics and clinical parameters at baseline. Over the observation period of up to 15.5 years, survival probability was improved by approximately 30% in the ECP treated patients as compared to matched controls (see Figure A; p Conclusion Compared to standard BOS-directed therapies, ECP improves significantly survival probability in double-lung transplant patients diagnosed with BOS. ECP exerts a significant impact on the number of total re-admissions to the hospital, the total days of care, and the total patient days. Thus, ECP has proved highly effective and cost saving in the treatment of lung transplant patients presenting with BOS.

Pretransplant gastroesophageal reflux compromises early outcomes after lung transplantation

Gastroesophageal reflux disease (GERD) is implicated as a risk factor for bronchiolitis obliterans syndrome after lung transplantation, but its effects on acute rejection, early allograft function, and survival are unclear. Therefore, we sought to systematically understand the time-related impact of pretransplant GERD on graft function (spirometry), mortality, and acute rejection early after lung transplantation. From January 2005 to July 2008, 215 patients underwent lung transplantation; 114 had preoperative pH testing, and 32 (28%) had objective evidence of GERD. Lung function was assessed by forced 1-second expiratory volume (FEV(1); percent of predicted) in 97 patients, mortality by follow-up (median, 2.2 years), and acute rejection by transbronchial biopsy. Pretransplant GERD was associated with decreased FEV(1) early after lung transplantation (P = .01) such that by 18 months, FEV(1) was 70% of predicted in double lung transplant patients with GERD versus 83% among non-GERD patients (P = .05). A similar decrease was observed in single lung transplantation (50% vs 60%, respectively; P = .09). GERD patients had lower survival early after transplant ( P = .02)-75% versus 90%. Presence of GERD did not affect acute rejection (P = .6). For lung transplant recipients, pretransplant GERD is associated with worse early allograft function and survival, but not increased acute rejection. The compromise in lung function is substantial, such that FEV(1) after double lung transplant in GERD patients approaches that of single lung transplant in non-GERD patients. We advocate thorough testing for GERD before lung transplantation; if identified, aggressive therapy early after transplant, including fundoplication, may prove efficacious.

A Comparison of Atrial Arrhythmias After Heart or Double-Lung Transplantation at a Single Center: Insights Into the Mechanism of Post-Operative Atrial Fibrillation

We compared the incidence of atrial arrhythmias in double-lung transplant patients versus heart transplant patients to gain insight into factors that contribute to post-operative atrial fibrillation (AF). Atrial fibrillation is a common complication after thoracic surgery. Pulmonary vein isolation is an effective treatment for AF. Heart or double-lung transplantation surgery both involve pulmonary vein isolation because of suture lines. We reviewed the records of 174 consecutive heart transplant patients and 122 double-lung transplant patients at the Columbia Presbyterian Medical Center between January 2005 and June 2008. Electrocardiograms during atrial arrhythmia episodes were reviewed by an electrophysiologist. Clinical variables, biopsy results, immunosuppressive regimens, and echocardiographic measurements were collected from the perioperative time period and at the time of arrhythmia occurrence. In the heart transplant group, 8 (4.6%) patients had AF (group A). In the lung transplant group, 23 (18.9%) patients had AF (group B; p < 0.001). The incidence of AF in a comparison group of 131 patients with normal left ventricular function who underwent coronary artery bypass graft surgery was 19.8%. Immunosuppressive regimens and clinical variables were similar for both groups. Echocardiographic data revealed no significant cardiac abnormalities in 74% of group B compared with 25% of group A (p < 0.05), and 78% of biopsy results in group B were normal, whereas only 25% of group A results were normal (p < 0.05). In heart transplant recipients, AF is uncommon and occurs in the setting of myocardial dysfunction and graft rejection. In contrast, AF is more common after lung transplantation despite the absence of graft rejection and cardiac dysfunction. Pulmonary vein isolation alone cannot explain the discrepancy in AF incidence between heart transplant recipients and double-lung transplant recipients. Cardiac autonomic denervation may have a protective effect for heart transplant patients in the post-operative setting.

Impact of PAF antagonist BN 52021 (Ginkolide B) on post-ischemic graft function in clinical lung transplantation

Background: Platelet activating factor (PAF) is associated with ischemia/reperfusion injury (I/R) after lung transplantation. Following promising experimental results, this prospective trial investigated the potential effect of PAF antagonist BN 52021 (ginkolide B) on clinical Euro-Collins (EC)-based lung preservation. Methods We analyzed 8 double-lung transplant patients in each of 3 groups. In the low-dose group (LDG), donor lungs were perfused with EC containing 2 mg/kg BN 52021, whereas we used 10 mg/kg in the high-dose group (HDG) and placebo in the control group (CG). Before reperfusing the first lung, we administered intravenously 120 mg BN 52021 (LDG), 600 mg BN 52021 (HDG), or placebo (CG). Hemodynamics in terms of pulmonary arterial pressure, pulmonary vascular resistance and serial determinations of the alveolo-arterial oxygen difference (AaDO 2) were recorded. We measured blood levels of PAF pre-operatively and post-operatively, after 10 minutes and after 3, 8, 24, 48, and 144 hours. Results Within 32 hours, we noted a tendency toward better AaDO 2 in the LDG and the HDG compared with the CG ( p > 0.05). We observed a significant improvement of AaDO 2 after 3 hours (HDG, p = 0.033) and 8 hours (LDG, p = 0.024), with poorest values in the CG. The PAF concentrations were lowest in the HDG, with significant deterioration 10 minutes after reperfusion. In contrast, placebo led to higher PAF levels. We measured significantly lower PAF concentrations (HDG vs CG) at 10 minutes and at 6 days post-operatively. Conclusions Use of high-dose PAF antagonist BN 52021 can easily be combined with clinical preservation methods and may help optimize pulmonary function with reduced PAF levels, in the early post-ischemic period.

Quantitative 3D VUSE pulmonary MRA

The purposes of this study were to quantitatively evaluate a free-breathing three-dimensional (3D) variable angle uniform signal excitation (VUSE) magnetic resonance angiography (MRA) technique in normal volunteers, to demonstrate breathold 3D VUSE MRA in a normal volunteer, and to investigate the ability of the free-breathing 3D VUSE MRA technique to quantify differential flow in lung transplant patients. A free-breathing 3D VUSE MRA pulse sequence was run on the right lungs of 15 normal volunteers and both lungs of eight single or double lung transplant patients. A breathold scan was also used on one volunteer. No contrast agents were used. Normal lung MRA images were analyzed for maximum level of branching observed and minimum distance between distal vessels seen and the pleura. In patients, differential flow was determined with a program that counted the number of MRA pixels over a threshold signal level in each lung. These values were compared to radionuclide perfusion (Q) scan results. Average observed branching order in normal lung images was 5.9 ± 0.7. Average distance between the most peripheral vessels seen and the pleura was 0.9 cm. Differential blood flow measured by pulmonary MRA was well correlated with that measured by Q scan (R 2 = 0.84, p < 0.005). In addition to providing good visualization of normal pulmonary vessels, this technique was demonstrated to provide accurate estimates of differential blood flow in lung transplant patients free of serious lung scarring.

Role of vagal feedback from the lung in hypoxic-induced tachycardia in humans

We assessed the cardiovascular responses to systemic normocapnic hypoxia in five normal subjects, five double lung transplant patients with lung denervation and intact hearts, and five patients with denervated hearts. Progressive normocapnic hypoxia was induced over 10-15 min and maintained for 2-3 min each at 90, 87, 84, and 80% arterial O2 saturation (SaO2). Normal subjects showed the most pronounced mean increase in heart rate (dHR/dSaO2 = 0.86 +/- 0.13 beat/min per 1% SaO2). Three lung-denervated subjects had normal tachycardiac responses (1.6, 0.9, and 0.69 beats/min per 1%), whereas the other two had distinctly lower responses (0.34 and 0.39 beat/min per 1%). Most of the lung-denervated subjects also showed a significant tachycardia with even mild hypoxia; none showed a bradycardiac response to any level of hypoxia. In the heart-denervated group, hypoxic tachycardia was significantly lower than normal (0.29 +/- 0.13 beat/min per 1%). We conclude that vagal feedback from the lungs is not required for the normal chronotropic response to hypoxia in humans; however, this mechanism may contribute significantly to the marked variability in hypoxic-induced tachycardia found among human subjects. These data in humans contrast with the progressive bradycardiac response to hypoxia reported in vagally denervated (or nonhyperpneic) dogs and cats.

Nutrition in the pediatric double lung transplant patient with cystic fibrosis.

Cystic fibrosis (CF) is the most common lethal genetic disease in the white population. The pulmonary infections and pancreatic insufficiency make CF a medically challenging disease. Although the importance of nutrition in the CF patient is known, approximately 50% of CF patients are in less than the 10th percentile for weight and height as reported by the 1991 CF Foundation Registry of 114 CF Centers in the United States. This paper addresses the nutritional status of 10 pediatric CF patients who underwent double lung transplant at Children's Hospital of Pittsburgh between August 1991 and May 1993. Patients who survived beyond 1 year gained a significant amount of weight sooner after transplant than those who survived less than 1 year. Gastrostomy tube feedings were more effective than oral intake for weight gain after transplant. CF patients with pancreatic insufficiency have more difficulty with adjustment of doses of immunosuppressive agents for reasons that are not clearly understood.

Apnoea following normocapnic mechanical ventilation in awake mammals: a demonstration of control system inertia.

1. Inhibition of inspiratory muscle activity from volume-related feedback during mechanical ventilation has been shown previously. To determine if this neuromechanical inhibition displays a memory effect, the duration of expiration immediately following cessation of mechanical ventilation was assessed in eight normal subjects. The subjects were passively mechanically ventilated via a nasal mask until the end-tidal CO2 (PET,CO2) was a minimum of 30 mmHg and inspiratory effort was no longer detected, as evidenced by stabilization of mouth pressure and disappearance of surface diaphragm EMG activity. The ventilator output was held constant at a mean tidal volume (VT) of 1.0 l and breath duration of 4.6 s and PET,CO2 was increased 1-1.5 mmHg/min (via increased inspired CO2 fraction, FI,CO2) until inspiratory muscle activity returned. The PET,CO2 at which activation first occurred was defined as the CO2 recruitment threshold (PCO2,RT). The mechanical ventilation protocol was repeated and the PET,CO2 increased 1-1.5 mmHg/min until it was a mean of 1.1 mmHg above spontaneous PET,CO2 and 3.6 mmHg below PCO2,RT. After 4-6 min of mildly hypercapnic mechanical ventilation, the mechanical ventilation was terminated. 2. Following termination of mechanical ventilation, the duration of the subsequent apnoea was 14.6 +/- 2.8 s (mean +/- S.E.M.) or 453 +/- 123% > spontaneous TE and 178 +/- 62% > the TE chosen by the subject during 'assist control' ventilation at VT = 1.0 l. 3. To test the hypothesis that the apnoea following cessation of mechanical ventilation was due to a vagally mediated memory effect, the study was repeated in five double-lung transplant patients with similar PCO2,RT to normal subjects. These pulmonary vagally denervated patients also displayed an apnoea (14.5 +/- 4.0 s) upon cessation of mechanical ventilation (at a PET,CO2 2.0 mmHg > eupnoea and 2.4 mmHg < PCO2,RT), that was 367 +/- 162% > spontaneous TE. 4. We also found significant apnoea in the awake dog immediately following mildly hypercapnic passive mechanical ventilation, and this was similar before and after bilateral vagal blockade (15.7 +/- 1.3 and 19.7 +/- 4.7 s, respectively). 5. We conclude that neuromechanical inhibition of inspiratory muscle activity, produced by passive mechanical ventilation at high VT, exhibits a memory effect reflected in TE prolongation, which persists in the face of substantial increases in chemoreceptor stimuli. This effect is not dependent on vagal feedback from lung receptors. 6. We hypothesize that this persistent apnoea represents an inherent 'inertia', characteristic of the ventilatory control system.(ABSTRACT TRUNCATED AT 400 WORDS)

Time dependence of flow-volume curves.

Time dependence of flow-volume curves.

Reinnervation of the reimplanted canine lung.

ArticleReinnervation of the reimplanted canine lung.L H Edmunds Jr, J A Nadel, and P D GrafL H Edmunds Jr, J A Nadel, and P D GrafPublished Online:01 Nov 1971https://doi.org/10.1152/jappl.1971.31.5.722MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByEffects of bilateral lung transplantation on cardiac autonomic modulation and cardiorespiratory coupling: a prospective study21 May 2021 | Respiratory Research, Vol. 22, No. 1Printed, Flexible Lactate Sensors: Design Considerations Before Performing On-Body Measurements23 September 2019 | Scientific Reports, Vol. 9, No. 1Pulmonary SurgeryMucociliary FunctionCough Reflex in Lung Transplant Recipients3 December 2011 | Lung, Vol. 190, No. 1Lung Transplantation and Lung Volume Reduction Surgery1 July 2011Pulmonary surgeryCholinergic Mechanisms and Anticholinergic Therapy in Respiratory DiseasesRestoration of Cough Reflex in Lung Transplant RecipientsChest, Vol. 134, No. 2Motor and sensory re-innervation of the lung and heart after re-anastomosis of the cervical vagus nerve in rats6 June 2007 | The Journal of Physiology, Vol. 581, No. 3Pulmonary Physiology PosttransplantMagnitude estimation of inspiratory resistive loads by double-lung transplant recipientsWeiying Zhao, A. Daniel Martin, and Paul W. Davenport1 February 2003 | Journal of Applied Physiology, Vol. 94, No. 2Invited Review: Plasticity in the control of breathing following sensory denervationH. V. Forster1 February 2003 | Journal of Applied Physiology, Vol. 94, No. 2Detection of inspiratory resistive loads in double-lung transplant recipientsWeiying Zhao, A. Daniel Martin, and Paul W. Davenport1 November 2002 | Journal of Applied Physiology, Vol. 93, No. 5Respiratory-related evoked potentials elicited by inspiratory occlusions in double-lung transplant recipientsWeiying Zhao, A. Daniel Martin, and Paul W. Davenport1 September 2002 | Journal of Applied Physiology, Vol. 93, No. 3Muscarinic Receptor Subtypes and Anticholinergic Therapy30 May 2013Anaesthesia for patients after lung transplantationCanadian Journal of Anaesthesia, Vol. 44, No. 2Ventilatory response to exercise in diabetic subjects with autonomic neuropathyC. Tantucci, P. Bottini, M. L. Dottorini, E. Puxeddu, G. Casucci, L. Scionti, and C. A. Sorbini1 November 1996 | Journal of Applied Physiology, Vol. 81, No. 5Relief of the ‘air hunger’ of breathholding. A role for pulmonary stretch receptorsRespiration Physiology, Vol. 103, No. 3Sympathetic reinnervation of unilaterally denervated rat lungActa Physiologica Scandinavica, Vol. 154, No. 1Airway Mucus and Epithelial Function in a Canine Model of Single Lung AutotransplantationChest, Vol. 107, No. 1Assessment of Airway Tone in Asthma: Comparison Between Double Lung Transplant Patients and Healthy SubjectsAmerican Review of Respiratory Disease, Vol. 148, No. 5Ventilatory response to exercise after heart and lung denervation in humansRespiration Physiology, Vol. 92, No. 3Frequency of mechanical ventilation and respiratory activity after double lung transplantationRespiration Physiology, Vol. 92, No. 3References and further readingReduced-size porcine lung transplantation: Long-term studies of pulmonary vascular resistanceThe Annals of Thoracic Surgery, Vol. 53, No. 4The reversibility of impaired mucociliary function after lung transplantationThe Journal of Thoracic and Cardiovascular Surgery, Vol. 102, No. 6Pulmonary reflexes after human heart-lung transplantationRespiratory Medicine, Vol. 85Anesthetic considerations for patients undergoing double-lung transplantationJournal of Cardiothoracic Anesthesia, Vol. 4, No. 4Bronchial Responsiveness after Human Heart-Lung TransplantationChest, Vol. 97, No. 6Lung transplantationCurrent Problems in Surgery, Vol. 26, No. 10Mucociliary function in autotransplanted, allotransplanted, and sleeve resected lungsThe Journal of Thoracic and Cardiovascular Surgery, Vol. 98, No. 4Cardiopulmonary response to dynamic exercise after heart and combined heart-lung transplantation.Heart, Vol. 61, No. 3Bronchial reactivity to methacholine after combined heart-lung transplantation.Thorax, Vol. 43, No. 12The effect of human heart-lung transplantation upon breathing at rest and during sleepRespiration Physiology, Vol. 72, No. 2Cardiopulmonary Function at Maximum Tolerable Constant Work Rate Exercise Following Human Heart-Lung TransplantationChest, Vol. 92, No. 3Allgemeines zur Physiologie und Pathophysiologie der OrgantransplantationThe role of upper airways and of sensoric receptors on reflex bronchoconstrictionResearch in Experimental Medicine, Vol. 174, No. 3Effects of dichlorvos (DDVP) inhalation on the activity of acetylcholinesterase in the bronchial tissue of ratsArchives of Toxicology, Vol. 42, No. 3Acetylcholinesterase-positive nerves of the rhesus monkey bronchial tree.Thorax, Vol. 30, No. 2The Adult Respiratory Distress SyndromeBronchial mucus after lung autotransplantation in dogsThe Journal of Thoracic and Cardiovascular Surgery, Vol. 67, No. 3PARASYMPATHETIC NERVOUS CONTROL OF AIRWAY SMOOTH MUSCLEAnnals of the New York Academy of Sciences, Vol. 221, No. 1 Pulmonary ReaLobar pulmonary arterial blood flow in reimplanted canine lungsThe Journal of Thoracic and Cardiovascular Surgery, Vol. 65, No. 2Physiology and Pharmacology of the Transplanted Lung More from this issue > Volume 31Issue 5November 1971Pages 722-7 https://doi.org/10.1152/jappl.1971.31.5.722PubMed4940496History Published online 1 November 1971 Published in print 1 November 1971 Metrics