Dynamic optical coherence tomography evaluation in locally advanced basal cell carcinoma during sonidegib treatment.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the Caucasian population. It has a multifactorial pathogenesis, in which constitutive activation of the Sonic Hedgehog signalling (SHH) pathway (via mutations in PTCH1 or SMO genes) represents by far the most common genetic aberration. The introduction of vismodegib and sonidegib, two SHH pathway inhibitors, changed the therapeutic approach of locally advanced and metastatic BCCs. EADO's (European Association of Dermato-Oncology) new staging system refers to these as 'difficult-to-treat' BCCs. OBJECTIVE: The aim was to evaluate sonidegib's effectiveness in patients affected by difficult-to-treat BCCs by using non-invasive diagnostic techniques. METHODS: We retrospectively evaluated 14 patients (4 females, 10 males; mean age 77 ± 11 years) affected by difficult-to-treat BCCs treated with oral sonidegib 200 mg/day that were followed with total body videodermoscopy (V-Track, Vidix 4.0) and dynamic optical coherence tomography (D-OCT, VivoSight Dx) since May 2022. Considering the risk of rhabdomyolysis routine blood tests, especially for creatine kinase concentrations, were performed. All treated patients were inserted in the BasoCare database, which aims to offer support to patients taking sonidegib. Complete and partial responses were evaluated by the overall reduction of the number of lesions and their individual sizes. Safety was evaluated by assessing the occurrence and severity of adverse reactions. RESULTS: Eighty per cent achieved complete clearance and 75% reduction of diameter. D-OCT scans performed at every follow-up showed concordance with clinical appearance and demonstrated reduction of hyporeflective structures, that is, islets of tumour cells and overall improvement of morphology. CONCLUSION: Sonidegib can be considered an effective treatment option in cases where surgery or radiotherapy would be unfeasible or has previously failed, although pigmented lesions did not show complete clearance, suggesting that there are factors other than the SHH pathway involved in tumour growth. Videodermoscopy and D-OCT were useful in the quick and seamless follow-up of lesions and added valuable information in assessing efficacy.

Device profile of the Inspiris Resilia valve for aortic valve replacement: overview of its safety and efficacy.

INTRODUCTION: The Inspiris Resilia tissue valve was recently introduced into clinical practice. This review summarizes the pre-clinical and clinical studies leading to this new bioprosthesis. AREAS COVERED: The novel Resilia tissue was tested extensively in a large animal model. The clinical use of the tissue started in 2011 with the European Feasibility study, followed by a North-American multi-center study. Since 2017, the Inspiris Resilia valve has been in full commercial use. Further prospective evaluations and registries are ongoing. EXPERT OPINION: The Inspiris Resilia valve was clinically introduced after pre-clinical tests revealed superiority compared to contemporary therapy such as the Perimount valve. Prospective long-term follow-up studies on Resilia are ongoing since 2011 and reveal no major complications. Full 5-year data show no signs of early degeneration, but longer follow-up is certainly still needed. Several prospective registries are actively monitoring the outcome with the Inspiris Resilia valve now. The novel tissue, designed to mitigate calcification and increase durability, together with the expandable stent, facilitating potential future valve-in-valve (ViV) procedures, are the cutting-edge aspects. Clinical use in younger patients is currently ongoing: their follow-up and outcome will determine the added value of this valve.

Infective endocarditis in patients after percutaneous pulmonary valve implantation with the stent-mounted bovine jugular vein valve: Clinical experience and evaluation of the modified Duke criteria.

AIMS: Percutaneous pulmonary valve implantation (PPVI) has proven good hemodynamic results. As infective endocarditis (IE) remains a potential complication with limited available clinical data, we reviewed our patient records to improve future strategies of IE prevention, diagnosis and treatment. METHODS: Medical records of all patients diagnosed with Melody® valve IE according to the modified Duke criteria were retrospectively analyzed in three Belgian tertiary centers. RESULTS: 23 IE episodes in 22 out of 240 patients were identified (incidence 2.4% / patient year) with a clear male predominance (86%). Median age at IE was 17.9 years (range 8.2-45.9 years) and median time from PPVI to IE was 2.4 years (range 0.7-8 years). Streptococcal species caused 10 infections (43%), followed by Staphylococcus aureus (n = 5, 22%). In 13/23 IE episodes a possible entry-point was identified (57%). IE was classified as definite in 15 (65%) and as possible in 8 (35%) cases due to limitations of imaging. Echocardiography visualized vegetations in only 10 patients. PET-CT showed positive FDG signals in 5/7 patients (71%) and intracardiac echocardiography a vegetation in 1/1 patient (100%). Eleven cases (48%) had a hemodynamically relevant pulmonary stenosis at IE presentation. Nine early and 6 late percutaneous or surgical re-interventions were performed. No IE related deaths occurred. CONCLUSIONS: IE after Melody® valve PPVI is associated with a relevant need of re-interventions. Communication to patients and physicians about risk factors is essential in prevention. The modified Duke criteria underperformed in diagnosing definite IE, but inclusion of new imaging modalities might improve diagnostic performance.

Partial volume and motion correction in cardiac PET: First results from an in vs ex vivo comparison using animal datasets.

BACKGROUND: In a previous study on ex vivo, static cardiac datasets, we investigated the benefits of performing partial volume correction (PVC) in cardiac 18F-Fluorodeoxyglucose(FDG) PET datasets. In the present study, we extend the analysis to in vivo cardiac datasets, with the aim of defining which reconstruction technique maximizes quantitative accuracy and, ultimately, makes PET a better diagnostic tool for cardiac pathologies. METHODS: In vivo sheep datasets were acquired and reconstructed with/without motion correction and using several reconstruction algorithms (with/without resolution modeling, with/without non-anatomical priors). Corresponding ex vivo scans of the excised sheep hearts were performed on a small-animal PET scanner (Siemens Focus 220, microPET) to provide high-resolution reference data unaffected by respiratory and cardiac motion. A comparison between the in vivo cardiac reconstructions and the corresponding ex vivo ground truth was performed. RESULTS: The use of an edge-preserving prior (Total Variation (TV) prior in this work) in combination with motion correction reduces the bias in absolute quantification when compared to the standard clinical reconstructions (- 0.83 vs - 3.74 SUV units), when the end-systolic gate is considered. At end-diastole, motion correction improves absolute quantification but the PVC with priors does not improve the similarity to the ground truth more than a regular iterative reconstruction with motion correction and without priors. Relative quantification was not influenced much by the chosen reconstruction algorithm. CONCLUSIONS: The relative ranking of the algorithms suggests superiority of the PVC reconstructions with dual gating in terms of overall absolute quantification and noise properties. A well-tuned edge-preserving prior, such as TV, enhances the noise properties of the resulting images of the heart. The end-systolic gate yields the most accurate quantification of cardiac datasets.

Cancer After Heart Transplantation: A 25-year Single-center Perspective.

BACKGROUND: Cancer is a major cause of morbidity and mortality after heart transplantation. METHODS: We studied 541 heart transplant patients from a single center over a period of 25 years, with a mean follow-up of 10.7 years. We determined incidence, type, risk factors, and prognosis for cancer after heart transplantation. RESULTS: Cancer was diagnosed in 181 patients, at a mean of 7.7 years after transplantation. Cumulative incidence of cancer at 5, 10, and 20 years was 14%, 29%, and 60%, respectively. The most frequent cancers were spinocellular skin cancer (22%), basocellular skin cancer (19%), lung cancer (16%), lymphoma (11%) and prostate cancer (10%). Age at transplantation > 50 years (hazard ratio, 2.9; P < .001) and male recipient gender (hazard ratio, 1.7; P = .038) were significant risk factors for posttransplant malignancy on multivariate Cox proportional hazards analysis. Median patient survival after diagnosis of cancer was 2.9 years for patients with noncutaneous cancer, versus 13.1 years for patients with only skin cancer (P < .001).

Concha bullosa related headache disability.

OBJECTIVE: Rhinogenic headache (RH) is a headache or facial pain syndrome secondary to mucosal contact points in the sino-nasal cavities, in the absence of inflammatory signs, hyperplastic mucosa, purulent discharge, sino-nasal polyps or masses. It may result from pressure on the nasal mucosa due to anatomical variations among which the pneumatization of the middle turbinate, concha bullosa, a variant of the development of ethmoidal cells, is the most commonly observed. Clinical practice suggests a close correlation between concha bullosa, mucosal contacts and rhinogenic headache, with high impact on the QoL. However diagnostic and therapeutic difficulties still remain. Aim of the present study is to evaluate the impact of medical or surgical care on the QoL of patients suffering from concha bullosa related headache from the patients' perspective. PATIENTS AND METHODS: One-hundred-two subjects with concha bullosa and headache anamnesis were randomized into two groups and given medical or surgical treatment. To assess the Quality of life (QoL) we used visual analogue scale and for the first time, the migraine disability score before and after treatment. RESULTS: After treatment the severity of the headache decreased as well as the discomfort in the surgical group compared with medical group. CONCLUSIONS: The improvement of symptoms and QoL suggests that the endoscopic surgical plastic may promote the rapid resolution of concha bullosa related headache improving the and reducing health care costs.

20 years of arterial switch operation for simple TGA.

BACKGROUND: Arterial switch operation became the golden treatment for simple transposition of the great arteries (sTGA). We describe our experience with the arterial switch operation regarding long-term outcome and the need for re-intervention. Nevertheless, supravalvular pulmonary stenosis (SPS) remains a concern in the long run. We assess the evolution of SPS over time and evaluate the effect of technical modifications on SPS during our experience. METHODS: We performed a retrospective study on 133 patients operated with ASO for TGA between October 1991 and November 2009. Last report method was used. We reviewed our pediatric cardiology and cardiac surgery database to examine the echocardiographic data and electrocardiograms. A mean follow-up of 9.2 years (+/- 5.83 SD) was reached. RESULTS: One (0.8%) patient deceased postoperatively due to cardiogenic shock. The overall actuarial freedom from reoperation (open and percutaneous) was 88.1%, 78.5% and 76.9% at 1, 5 and 10 years. SPS needed to be treated in 17 patients. Valve regurgitation at final investigation was maximal moderate in 5 patients for the aortic valve, 10 for pulmonary valve and 3 in tricuspid valve. CONCLUSIONS: ASO shows excellent long-term results in sTGA with a very low morbidity and mortality and is therefore the procedure of choice. Re-intervention rate is determined by SPS. Since the extensive mobilization of the pulmonary arteries and the creation of a longer neo-pulmonary root, reduction in SPS was seen with no re-interventions in the second half of the group. To obtain a final comparison with the atrial switch operation, a longer Follow-up is necessary.

Cost of 1-year left ventricular assist device destination therapy in chronic heart failure: a comparison with heart transplantation.

OBJECTIVE: To analyse overall cost involved with destination therapy (DT) in comparison to transplantation (HTX) and bridging to transplantation. METHODS: Three groups of patients at one hospital were considered for this cost analysis: (1) patients included in the BENEMACS study starting May 2009 (n = 6); (2) all patients from May 2009 till May 2010 undergoing heart transplantation (n = 19); or (iii) undergoing Heartmate II implantation as a bridge to transplant (n = 13). Patients undergoing bridging were more sick (lower Intermacs class). DT patients were older (64±8 years). Cost was derived from actual hospital invoices, device, organ procurement and medical cost, and follow-up care during 1 year from implantation. Costs are presented in euro, by their mean values and standard deviation. RESULTS: One-year survivals were 83, 84, and 77%, respectively, for DT, HTX, and bridging. Costs for initial and re-hospitalizations were not different between groups. Costs for medical follow-up and medication were significantly higher for transplanted patients. The 1-year total cost was €85 531±19 823 for HTX, €125 108±32 399 for bridging, and €137 068±29 007 for DT. As 42% of the transplanted patients were bridged, the cost of the medical pathway HTX was €138 076±19 823. Assuming a 5-year survival and a similar yearly follow-up cost, the average cost per year is €42 153 for HTX, €53 637 for transplantation including the bridging cost, and €47 487 for DT. CONCLUSION: Direct transplantation without bridging is the most cost-efficient treatment. The cost per patient per year for DT is similar to HTX considering its bridging activity.

Long-term outcome after treatment of isolated pulmonary valve stenosis.

BACKGROUND: Few data are available on very long-term follow-up after treatment for isolated pulmonary valve stenosis (PVS), either surgically or by percutaneous balloon angioplasty (PBA). METHODS AND RESULTS: All patients with isolated PVS were selected from our database of congenital heart defects. Their records were reviewed systematically. We identified 79 surgically treated patients with a median follow-up of 22.5 years (range 0-45 years) and 139 PBA patients with median follow-up of 6.0 years (range 0-21 years). Echocardiographic and catheterization parameters indicate excellent results of both techniques in relieving the transpulmonary gradient. However, after initial surgery 20.3% of patients needed a cardiac re-intervention: 81% for severe pulmonary valve regurgitation, but none for residual pulmonary stenosis. After initial PBA a cardiac re-intervention was needed in 9.4% of patients. In 85% the indication was residual pulmonary stenosis, in none of them pulmonary regurgitation, although almost all patients developed a mild pulmonary regurgitation. Freedom of re-intervention after surgery was 98.4%, 93.5%, 87.7%, 70.9% and 55.7% at 5, 10, 20, 30 and 40 years postoperatively. Freedom of re-intervention in the PBA group was 95.1%, 87.5% and 84.4% at 5, 10 and 20 years post-procedure. CONCLUSIONS: Both surgery and PBA are safe and successful in relieving the acute transpulmonary gradient. Long-term results of surgery are worse than previously thought due to severe PR. After PBA re-interventions for residual stenosis are frequently needed and the incidence of mild PR is high. Very long-term results of PBA are still unknown.

Failure of epicardial pacing leads in congenital heart disease: not uncommon and difficult to predict.

AIMS: We evaluate the incidence of epicardial lead failure and try to identify risk factors in patients with congenital heart disease. METHODS: All patients with a congenital heart defect and an epicardial pacing system, implanted within a timeframe of 25 years, were included in this study. Patients' medical records and lead data were reviewed. Lead failure was defined as the primary endpoint. RESULTS: In total 198 active epicardial leads (atrial 40, ventricular 158) were implanted in 93 patients (median age at implantation 4.4 years (range 0-58.6)). During a total follow-up of 1235 lead-years, 29 lead failures (14.6%, 4 atrial, 25 ventricular) were documented in 22 patients (23.7%). Lead failure occurred at a median time period of 4.8 years (range 1.2-24.1) after implantation. Five-year freedom of lead failure was 88%. The only independent predictor for lead failure was the age at implantation (HR 0.44; 95%CI 0.20-0.97, p = 0.04), other characteristics failed to predict lead failure. Sudden cardiac death occurred in four patients (4.3%), in one a lead failure was documented. CONCLUSION: A high incidence of epicardial lead failures is found in patients with congenital heart disease. Unfortunately, it is difficult to predict this potentially life-threatening complication.

Late recovery of atrioventricular conduction after pacemaker implantation for complete heart block in congenital heart disease: fact or fluke?

OBJECTIVES: Pacemaker implantation is a standard recommendation for patients with persistent complete heart block with congenital heart disease. This study was performed to determine the incidence and clinical significance of late recovery of atrioventricular (AV) conduction following pacemaker implantation. METHODS: A retrospective study of patients with congenital heart disease needing pacemaker implantation was performed between 1977 and 2008 at our institution. The postoperative course of all patients with complete heart block, in whom a permanent pacemaker was implanted, was followed on a semi-annual basis by clinical follow-up. RESULTS: A total of 56 patients with complete heart block underwent pacemaker implantation. Indications for pacemaker implantation could be categorized in primary AV conduction block (n = 28 ; 50%) and surgically-induced AV conduction block (n = 28 ; 50%). After pacemaker insertion, recovery of AV conduction was recognized in two patients. The first patient was operated for atrial septal defect type ostium secundum with complete heart block preoperatively. AV block resolved 2 days after pacemaker implantation. The second patient underwent mitral valve replacement. Postoperatively, the patient developed second degree heart block, which progressed 3 years later into complete heart block. A recovery of AV conduction was seen 7.5 years later. In these patients, no late recurrence of complete heart block was found during follow-up after 8 and 4 months, respectively. CONCLUSIONS: Recovery of AV conduction was observed in one patient with primary AV conduction block and in one patient with complete heart block after congenital heart surgery. Lifelong cardiac pacing in these specific subsets of patients may not be necessary.

Transapical left ventricular access for difficult to reach interventional targets in the left heart.

OBJECTIVE: Interventional targets may be virtually "excluded" due to vascular access problems or complex previous surgical procedures. This study reviews our experience using transapical ventricular puncture to gain direct access to the systemic ventricle. PATIENTS: Patient 1 (74 years, 2 previous sternotomies), patient 2 (66 years, 5 previous sternotomies), and patient 5 (69 years, 3 previous sternotomies) with prosthetic valves had paravalvular mitral valve leaks. Patient 3 (6.3 years, 2 previous sternotomies) with an extracardiac Fontan conduit, had a significant residual leak after two previous surgical attempts of patch closure of a severely regurgitant right atrioventricular valve. Patient 4 (10 months) had failure of standard ablation of the posteroseptal region of the mitral valve with persistent life-threatening episodes of ventricular tachycardia. METHODS: Procedures were performed under general anesthesia. Entry site was percutaneous in three patients and in two (and one conversion) a mini-thoracotomy was used. Sheaths were placed (6 F) using standard Seldinger technique, followed by the procedure as required. Direct surgical closure of the puncture site was done in 4 patients and in patient 3, a percutaneous vascular occlusion device was used. RESULTS: Easy and immediate access was obtained in all patients. The paravalvular leaks were crossed within seconds and completely closed with Amplatzer occluders. In patient 3 the valve was crossed using a Brokenbrough needle and a 12-mm Amplatzer device was placed in the patch leak. Patient 4 was successfully ablated using a 7-F irrigated catheter endo- and epicardially. Complications were in the percutaneous puncture group: in one patient a coronary artery was punctured and in one a hemothorax developed. CONCLUSION: Direct left ventricular puncture offers a very useful alternative access site in selected patients to reach "inaccessible" targets for certain percutaneous interventions in patients where standard approaches may be impossible or difficult.

Modification of the arterial anastomotic technique improves survival in porcine single lung transplant model.

BACKGROUND: Lung transplantation is a valuable therapeutic option for selected patients with end-stage pulmonary disease. However, this treatment is complicated by ischaemia-reperfusion injury (IRI) of the lung in 10-20% of the recipients. We developed an unilateral porcine lung transplant model to study IRI and describe our experience with two different arterial anastomotic techniques. MATERIAL & METHODS: Twenty four domestic pigs [n = 6 x (donor + recipient)/group] were used in this study. Donor lungs were harvested using an antegrade flush with cold Perfadex and stored in the same solution for +/- 8 hours. Recipient animals underwent a left thoracotomy. After native pneumonectomy, the left donor lung was transplanted in the following order: 1. left atrial cuff; 2. bronchus; 3 pulmonary artery. 2 The outcome in recipients from historical groups differing in anastomotic technique was compared. An end-to-end anastomosis on the left pulmonary artery was performed in group I versus a patch anastomosis on the main pulmonary artery in group II. One hour after reperfusion, the right pulmonary artery and main bronchus were ligated forcing the recipient to survive on the transplanted lung only. The animals were further observed for 6 hours. RESULTS: Survival 6 hours after exclusion of the right lung was 33% (2/6) in group I versus 83% (5/6) in group II. Animals in group I died of right heart failure manifested by acute dilation of the right ventricle following ligation of the hilum of the right lung. CONCLUSION: Single lung transplantation with exclusion of the contralateral native lung is a critical model. Arterial end-to-end anastomosis resulted in an increased right ventricular afterload. The use of a patch technique improved the compliance of the arterial anastomosis and decreased early mortality. This transplant model is currently used in our laboratory to assess new methods for pulmonary preservation.

Na(+)/H(+)-exchange inhibition and aprotinin administration: promising tools for myocardial protection during minimally invasive CABG.

OBJECTIVE: Minimally invasive coronary artery bypass grafting (CABG), carried out on the warm beating heart, does not allow conventional myocardial protection. The objective was to investigate the possibility of enhancing tolerance to ischemia during short episodes of coronary artery occlusion, based on a pharmacological approach using a selective Na(+)/H(+)-exchange inhibitor (cariporide) or a serine protease inhibitor (aprotinin). METHODS: Four groups (n=6 in each group) of sheep were subjected to 20 min of normothermic regional ischemia (first lateral branch of the circumflex artery occlusion) followed by 1 h of reperfusion. Regional wall thickening was measured using sonomicrometry, and expressed as the percentage of thickening fraction compared with baseline. Group I was the control with no treatment, group II received cariporide (1 mg/kg administered over 2 min prior to ischemia), group III was treated with aprotinin (2.10(6) kallikrein inactivation units (KIU) load followed by 500.000 KIU/h). Group IV was treated with a combination of cariporide and aprotinin at the same concentrations as in groups II and III, respectively. RESULTS: Wall thickening measurements showed that, compared with control, cariporide was largely able to suppress secondary loss of wall thickening after initial recovery during early reperfusion. Wall thickening in the ischemic/reperfused myocardial area improved from 10+/-31 to 51+/-17% at 1 h of reperfusion (P=0.002). Aprotinin improved wall thickening at the end of 1 h of reperfusion to 70+/-13% (P=0.0001). However, in this group, there was a transient loss of regional contractility similar in amplitude and time course to the one observed in the control group. A combination of cariporide and aprotinin suppressed transient contractile loss and resulted in improved wall thickening at the end of 1 h of reperfusion (65+/-22%, P=0.0002 vs. control). This value was not significantly different from the cariporide (P=0.263) or aprotinin (P=0.704) group. CONCLUSION: These data indicate that both Na(+)/H(+)-exchange inhibition and aprotinin administration are promising tools for cardioprotection during minimally invasive CABG. A combination of both treatments is able to adequately suppress loss of contractility during early reperfusion as a consequence of reperfusion injury, and results in significantly improved wall thickening at the end of 1 h of reperfusion.

Separation of two groups of oestrogen mimicking compounds using micellar electrokinetic chromatography.

Two groups of compounds are being investigated due to their reported oestrogen mimicking characteristics in the environment. Separation of phenolic compounds and synthetic oestrogens using micellar electrokinetic chromatography is reported. Photodiode array detection is used for both separations. A standard separation buffer can be used for both groups of compounds including zwitterionic buffer cyclohexylamino-1-propanesulfonic acid, 20 mM at pH 11.5. It was found necessary to include 15% acetonitrile and 25 mM sodium dodecyl sulfate to aid separation and maintain analytes in solution. Optimum separations are achieved using 20 kV with hydrodynamic injection for 5 s. The relative standard deviation (RSD) for reproducibility was investigated for a mixture of phenols and synthetic oestrogens. For these compounds RSD was found to be <0.6% in all cases. Peak efficiencies ranged from 76,000 to 150,000 theoretical plates for different analytes. Application to environmental samples is discussed.

Extended preservation of ischemic pulmonary graft by postmortem alveolar expansion.

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: Peak airway pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and wet to dry weight ratio were measured during delayed hypothermic crystalloid flush in rabbit lungs (n = 6) at successive intervals after death comparing cadavers with lungs left deflated (group 1), inflated with room air (group 2) or 100% oxygen (group 4), or ventilated with room air (group 3), or 100% nitrogen (group 5), or 100% oxygen (group 6). RESULTS: There was a gradual increase in mean pulmonary artery pressure and pulmonary vascular resistance with longer postmortem intervals in all study groups (p = not significant, group 1 versus group 2 versus group 3). There was also a gradual increase in peak airway pressure and wet-to-dry weight ratio over time in all groups, which reflected edema formation during flush (airway pressure, from 14.5 +/- 1.0 cm H2O to 53.7 +/- 12.2 cm H2O, and wet-to-dry weight ratio, from 3.6 +/- 0.1 to 11.5 +/- 1.2, in group 1 at 0 and 6 hours postmortem, respectively; p < 0.05). Compared with group 1, however, the increase in groups 2 and 3 was much slower (airway pressure, 20.9 +/- 0.5 cm H2O and 18.8 +/- 1.2 cm H2O, and wet-to-dry weight ratio, 5.2 +/- 0.3 and 4.6 +/- 0.4 at 6 hours postmortem, respectively; p < 0.05 versus group 1 and p = not significant, group 2 versus group 3). Airway pressure and wet-to-dry weight ratio did not differ between groups 2 and 4 or between groups 3, 5, and 6. CONCLUSIONS: These data suggest that (1) pulmonary edema will develop in atelectatic lungs if hypothermic flush is delayed for 2 hours after death, (2) postmortem inflation is as good as ventilation in prolonging warm ischemic tolerance, (3) inflation with oxygen or ventilation with nitrogen or oxygen is no different from that with room air, and (4) therefore, prevention of alveolar collapse appears to be the critical factor in protecting the lung from warm ischemic damage independent of continued oxygen delivery.

External cooling of warm ischemic rabbit lungs after death.

BACKGROUND: If lungs could be retrieved for transplantation after circulatory arrest, the shortage of donors might be significantly alleviated. However, in such non-heart-beating donors, there is great concern that even a short period of warm ischemia will be deleterious for lung tissue, jeopardizing the transplant recipient. It was the purpose of this study to look for the efficacy of different methods of lung cooling inside a cadaver after circulatory arrest. METHODS: New Zealand white rabbits were sacrificed with an intravenous overdose of pentobarbital and left at room temperature. Subcutaneous, rectal, lung core, lung surface, and endobronchial temperatures were measured at intervals after death. Cooling of the lung during ischemia differed between groups (n = 6 in each group): lungs left deflated at room temperature (24 degrees C) (group 1 = control non-heart-beating donors), lungs ventilated with cooled (4 degrees C) room air (group 2), lungs left deflated plus topical cooling (1 degree C) of both the cadaver and its lungs (group 3), and lungs flushed in situ immediately after circulatory arrest with a cold (4 degrees C) crystalloid solution followed by ex vivo deflated storage in cold (1 degree C) saline solution (group 4 = control heart-beating donors). RESULTS: There was a slow decline in lung core, lung surface, and endobronchial temperatures toward room temperature in group 1 (1.5 degrees +/- 0.0 degree C/h, 1.8 degrees +/- 0.2 degree C/h, and 1.9 degrees +/- 0.1 degree C/h, respectively). In contrast, all three lung temperatures immediately ( < 5 minutes) dropped to less than 10 degrees C in group 4. Hypothermic ventilation (group 2) decreased endobronchial temperature (p < 0.05 at 30 minutes) but not lung surface, rectal, or subcutaneous temperature when compared with group 1. Cooling rate for lung surface and endobronchial temperatures during the first 4 hours after death was faster (p < 0.01) in group 3 (6.6 degrees +/- 0.3 degree C/h and 6.1 degrees +/- 0.2 degree C/h, respectively) when compared with group 2 (2.5 degrees +/- 0.3 degree C/h and 3.9 degrees +/- 0.1 degree C/h, respectively), but slower (p < 0.001) when compared with group 4 (9.2 degrees +/- 0.1 degree C/h and 8.7 degrees +/- 0.1 degree C/h, respectively). CONCLUSIONS: These data demonstrate that in the non-heart-beating donor, (1) in situ cold flush will result in immediate cooling of the lung, (2) ventilation with cooled air will only accelerate the decline in endobronchial temperature but has no effect on lung surface temperature, and (3) topical cooling of the cadaver is more efficacious in decreasing lung temperature than hypothermic ventilation.

Delay of adenosine triphosphate depletion and hypoxanthine formation in rabbit lung after death.

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: Adenosine triphosphate (ATP) and hypoxanthine levels were measured postmortem in rabbit lungs comparing deflation (group 1), ventilation with room air (group 2), inflation with room air (group 3), ventilation with oxygen (group 4), ventilation with cooled air (group 5), deflation plus cadaver cooling (group 6), and cooling by pulmonary arterial flush (group 7). RESULTS: The level of ATP dropped to 25.9% and HYP increased elevenfold at 30 minutes in group 1 but remained constant during 24 hours in group 7. The ATP catabolism beyond 2 hours postmortem appeared less in group 2 compared with group 3 (3.58 +/- 1.24 versus 0.39 +/- 0.08 mumol/g dry weight for ATP and 3.03 +/- 0.49 versus 7.64 +/- 0.94 mumol/g dry weight for hypoxanthine at 24 hours, respectively; p < 0.05). Cadaver cooling significantly slowed ATP catabolism. Changes in ATP level were similar in groups 2, 4, and 5. CONCLUSIONS: These data suggest that in the non-heart-beating cadaver (1) cooling, ventilation, and inflation can delay ATP catabolism; (2) postmortem ventilation but not inflation for more than 2 hours will inhibit further ATP breakdown; (3) ventilation with either oxygen or cooled air is not more beneficial than room air ventilation; and (4) cold flush more than cadaver cooling will prevent ATP depletion.