Biomedical subjects
Ulrich F W Franke
Publications and source records attributed to Ulrich F W Franke.
Endobronchial donor pre-treatment with ventavis: is a second administration during reperfusion beneficial to optimize post-ischemic function of non-heart beating donor lungs?
BACKGROUND: Lung retrieval from non-heart-beating donors (NHBD) has been introduced into clinical practice successfully. However, because of potentially deleterious effects of warm ischemia on microvascular integrity, use of NHBD lungs is limited by short tolerable time periods before preservation. Recently, improvement of NHBD graft function was demonstrated by donor pre-treatment using aerosolized Ventavis (Schering Inc., Berlin, Germany). Currently, there is no information whether additional application of this approach in reperfusion can further optimize immediate graft function. MATERIAL AND METHODS: Asystolic pigs (n = 5/group) were ventilated for 180-min of warm ischemia (groups 1-3). In groups 2 and 3, 100 microg Ventavis were aerosolized over 30-min using an ultrasonic nebulizer (Optineb). Lungs were then retrogradely preserved with Perfadex and stored for 3-h. After left lung transplantation and contralateral lung exclusion, grafts were reperfused for 6-h. Only in group 3, another dose of 100 microg Ventavis was aerosolized during the first 30-min of reperfusion. Hemodynamics, pO2/FiO2 and dynamic compliance were monitored continuously and compared to controls. Intraalveolar edema was quantified stereologically, and extravascular-lung-water-index (EVLWI) was measured. Statistics comprised ANOVA analysis with repeated measurements. RESULTS: Dynamic compliance was significantly lower in both Ventavis groups, but additional administration did not result in further improvement. Oxygenation, pulmonary hemodynamics, EVLWI and intraalveolar edema formation were comparable between groups. CONCLUSIONS: Alveolar deposition of Ventavis in NHBD lungs before preservation significantly improves dynamic lung compliance and represents an important strategy for improvement of preservation quality and expansion of warm ischemic intervals. However, additional application of this method in early reperfusion is of no benefit.
Donor pretreatment using the aerosolized prostacyclin analogue iloprost optimizes post-ischemic function of non-heart beating donor lungs.
BACKGROUND: Ischemia-reperfusion injury accounts for one-third of early deaths after lung transplantation. To expand the limited donor pool, lung retrieval from non-heart beating donors (NHBD) has been introduced recently. However, because of potentially deleterious effects of warm ischemia on microvascular integrity, use of NHBD lungs is limited by short tolerable time periods before preservation. After intravenous prostanoids are routinely used to ameliorate reperfusion injury, the latest evidence suggests similar efficacy of inhaled prostacyclin. Therefore, the impact of donor pretreatment with the prostacyclin analogue iloprost on postischemic NHBD lung function and preservation quality was evaluated. METHODS: Asystolic pigs (5 per group) were ventilated for 180 minutes of warm ischemia (Group 2). In Group 3, 100 microg iloprost was aerosolized during the final 30 minutes of ventilation with a novel mobile ultrasonic nebulizer. Lungs were then retrogradely preserved with Perfadex and stored for 3 hours. After left lung transplantation and contralateral lung exclusion, hemodynamics, rO2/FiO2, and dynamic compliance were monitored for 6 hours and compared with sham-operated controls (Group 1). Pulmonary edema was determined both stereologically and by wet-to-dry weight ratio (W/D). Statistics comprised analysis of variance with repeated measures and Mann-Whitney test. RESULTS: Flush preservation pressures, dynamic compliance, inspiratory pressures, and W/D were significantly superior in iloprost-treated lungs, and oxygenation and pulmonary hemodynamics were comparable between groups. Stereology revealed a trend toward lower intraalveolar edema formation in iloprost-treated lungs compared with untreated grafts. CONCLUSIONS: Alveolar deposition of Iloprost and NHBD lungs before preservation ameliorates postischemic edema and significantly improves lung compliance. This easily applicable innovation approach, which uses a mobile ultrasonic nebulizer, offers an important strategy for improvement of pulmonary preservation quality and might expand the pool of donor lungs.
Experimental lung transplantation: impact of preservation solution and route of delivery.
BACKGROUND: Optimal preservation of allograft integrity is essential to reduce post-ischemic organ dysfunction after lung transplantation. Retrograde organ preservation leads to homogeneous intrapulmonary distribution and eliminates intravascular thrombi. So far, no comparative studies exist with regard to preservation quality following retrograde preservation with Perfadex and Celsior after extended cold-ischemia intervals. METHODS: In an in vivo pig model, 5 lungs each were preserved for 27 hours using antegrade or retrograde perfusion techniques with Celsior (Ce(ant)/CE(ret)) and Perfadex (PER(ant)/PER(ret)). After left lung transplantation and contralateral lung exclusion, hemodynamics, oxygenation and dynamic compliance were monitored for 6 hours and compared with sham-operated controls. Pulmonary edema was determined stereologically. Statistics consisted of analysis of variance (ANOVA) with repeated measures. RESULTS: Mortality of all Celsior-protected lungs was 100% due to severe reperfusion injury with profound lung edema. In contrast, organ preservation with PER(ant) led to sufficient graft function without mortality. Preservation quality after retrograde administration of Perfadex resulted in optimized oxygenation capacity compared with PER(ant) (p = 0.046). Furthermore, intra-alveolar edema was reduced and generally comparable with sham controls. In general, retrograde preservation led to continuous washout of small blood and fibrin clots from the pulmonary capillary system. CONCLUSIONS: Perfadex solution provided sufficient lung preservation for 27 hours of cold ischemia, and its retrograde application led to significant functional and histologic improvement compared with antegrade perfusion. In contrast, preservation with Celsior solution resulted in lethal post-ischemic outcome, regardless of the route of administration, and therefore must be considered unsuitable for extended lung procurement.
Inhalative pre-treatment of donor lungs using the aerosolized prostacyclin analog iloprost ameliorates reperfusion injury.
BACKGROUND: Lung transplantation is effective for end-stage pulmonary disease, but its successful application is still limited by organ shortage and sub-optimal preservation techniques. Therefore, optimal allograft protection is essential to reduce organ dysfunction, especially in the early post-operative period. Intravenous prostanoids are routinely used to ameliorate reperfusion injury. However, the latest evidence suggests similar efficacy using inhaled prostacyclin. Thus, we evaluated the impact of donor pre-treatment using the prostacyclin analog, iloprost, on post-ischemic function of Perfadex-protected allografts. METHODS: In Group 1, 5 pig lungs were preserved with Perfadex (PER group) solution and stored for 27 hours. In Group 2, 100 microg of iloprost was aerosolized over 30 minutes using a novel mobile ultrasonic nebulizer (Optineb) before identical organ harvest (PER-ILO group). After left lung transplantation and contralateral lung exclusion, hemodynamic variables, Po2/Fio2 and dynamic compliance were monitored for 6 hours and compared with sham-operated controls. Pulmonary edema was determined stereologically and by wet-to-dry (W/D) weight ratio. Statistical assessment included analysis of variance (ANOVA) with repeated measures. RESULTS: Dynamic compliance and pulmonary vascular resistance (PVR) were superior in iloprost-treated compared with untreated organs (p < 0.05), whereas oxygenation was comparable between groups. W/D ratio revealed a significantly smaller amount of lung water in PER-ILO organs (p = 0.048), whereas stereologic data showed a trend toward less intra-alveolar edema. CONCLUSIONS: Endobronchial application of iloprost in donor lungs before Perfadex preservation decreases post-ischemic edema and significantly improves lung compliance and vascular resistance. This innovative approach is easily applicable in the clinical setting and offers a new strategy for improvement of pulmonary allograft preservation.
Technical feasibility of Impella Recover 100 microaxial left ventricular assist device placement after biologic aortic valve replacement (21 mm) for postcardiotomy failure.
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Innovative pulmonary preservation of non-heart-beating donor grafts in experimental lung transplantation.
OBJECTIVE: Lung transplantation is limited by scarcity of donor organs. Lung retrieval from non-heart-beating donors (NHBD) might have the potential to extend the donor pool and has been reported recently. However, no studies in NHBD exist using the novel approach of retrograde preservation with Perfadex solution. METHODS: Asystolic heparinized pigs (n = 5/group) were continuously ventilated for 90, 180 or 300 min of warm ischemia. Lungs were then retrogradely preserved with Perfadex and stored at 4 degrees C in inflation. After 3 h of additional cold ischemia, left lung transplantation was performed. Hemodynamics, pO(2)/F(i)O(2) and dynamic compliance were monitored for 5 h. Intrapulmonary lung water was determined by both global wet-to-dry lung weight ratio (W/D ratio) and standard stereological examination of relative volume fractions of intraalveolar edema. All results were compared to sham-operated controls and to lungs obtained from standard heart-beating donors after retrograde preservation with Perfadex and 27 h of cold ischemia. Statistics comprised ANOVA analysis with repeated measures and Mann-Whitney tests. RESULTS: No mortality was observed. During flush preservation of NHBD lungs, continuous elimination of blood clots via the pulmonary artery was observed. Oxygenation, compliance, intraalveolar edema fraction and W/D ratio were comparable between groups, whereas PVR was significantly lower in sham-controls. CONCLUSIONS: Use of NHBD lungs is feasible and results in similar postischemic outcome when compared to sham-controls and standard preservation procedures even after 5 h of pre-harvest warm ischemia. Especially, the NHBD with high-risk constellations for intravascular coagulation might benefit from retrograde preservation by elimination of thrombi from the pulmonary circulation. This innovative technique might also be considered in situations, where brain-dead organ donors become hemodynamically unstable prior to onset of organ harvest. Further trials with longer warm and cold ischemic periods are initiated to further elucidate this promising approach of donor pool expansion.
Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases using a novel in vivo pig model: II. High-dose cisplatin is well tolerated by the native lung tissue.
OBJECTIVE: Efficacy of in vivo isolated lung perfusion (ILP) with cisplatin could be shown in different rodent tumor models. Despite the use of this alternative therapeutical strategy in very few patients with lung metastases, there are no systematic studies regarding the tolerance of the native lung tissue in large animal models or humans. METHODS: In a novel ILP pig model, groups with two different concentrations of cisplatin (group CP150: 150 mg/m(2) cisplatin, n=5; group CP300: 300 mg/m(2) cisplatin, n=5) were compared with a control group (n=5) and a Sham group (n=5) concerning the influence on hemodynamic, ventilatory and gas exchange parameters as well as on structural integrity of the lung. In the additional CP300-HT group the potentially cumulative effect of hyperthermia and high-dose cisplatin perfusion was evaluated (300 mg/m(2) cisplatin, 41.5 degrees C, n=5). Following the ILP of the left lung for 40 min, right main bronchus and right pulmonary arteries were clamped and survival as well as lung function parameters were dependent on the previously perfused lung for the 6-h-reperfusion period. Quantification of histological acute lung injury was performed using the score of Chiang. ANOVA, ANOVA with repeated measures and Pearson's correlation estimation were applied for statistical evaluation. RESULTS: All animals survived ILP and the entire reperfusion period. Platinum levels of the perfusate and lung tissue showed a significant correlation with the dose given (P<0.001) but no correlation with the very low plasma levels in all groups (P=0.825). ILP resulted in a slight deterioration of most functional parameters compared to the Sham group. Although there were no differences between the perfusion groups regarding hemodynamic and ventilatory parameters, gas exchange parameters (pO(2)/FiO(2)-index, pCO(2), AADO(2)) demonstrated a trend toward dose-related functional impairment. Histological evaluation confirmed a dose-depending damage of lung tissue (P<0.001, correlation coefficient 0.670). The hyperthermic ILP with high-dose cisplatin led to improved gas exchange parameters and a reduction of morphological lung damage. CONCLUSIONS: In vivo ILP with high-dose cisplatin represents a safe procedure in this pig model. Hyperthermic perfusion up to 41.5 degrees C was beneficial to reduce the acute lung injury. The promising results of this study might be used for initiation of clinical trials as an alternative treatment in patients with a very poor prognosis.
Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases using a novel in vivo pig model: I. Influence of perfusion pressure and hyperthermia on functional and morphological lung integrity.
OBJECTIVE: Despite favorable experimental results and an encouraging early experience in humans, isolated lung perfusion (ILP) for treatment of metastases is still not established clinically. The complexity of the procedure as well as poor knowledge regarding the technical necessities of lung perfusion represents major limitations. METHODS: In this novel in vivo pig model, ILP of the left lung was performed for 40 min followed by the exclusion of the right lung. Survival and all monitored parameters of hemodynamics, ventilation and gas exchange were exclusively dependent on the previously perfused left lung for the 6-h reperfusion period. Furthermore, histological examination was assessed. In the first protocol influence of different perfusion pressures (PP) on the native lung tissue was investigated (LPG, n=6, PP<25 mmHg; HPG, n = 8, PP> or =25 mmHg). In the second protocol the influence of normothermic (T-38; n=5; t=38 degrees C), mild (T-40; n=5; t=40 degrees C) and moderate hyperthermic (T-41.5; n=5; t=41.5 degrees C) perfusion temperature was evaluated. Results were compared to those of a sham-operated control group (SG, n=5). RESULTS: ILP led to a slight deterioration of all functional as well as histological parameters in all groups. HPG resulted in impairment regarding all monitored parameters compared to LPG and SG. Significant differences between HPG and SG were found for cardiac index (P=0.026) and pulmonary vascular resistance index (PVRI, P=0.026). Histological scoring revealed significantly higher grade of lung injury for HPG animals (P=0.001). Functional parameters did not differ between normothermic and hyperthermic perfusion groups. However, animals of the T-38 group demonstrated significantly increased PVRI (P=0.004). Histological examination revealed significantly higher scores of acute lung injury for all perfusion groups compared to the Sham group (P<0.001). CONCLUSIONS: The results of this novel large animal model represent the first available demonstration that increased PP in a setting of ILP will result in deleterious effects on lung function and morphology. However, mild to moderate hyperthermia is well tolerated by the native lung tissue.
Experimental lung preservation with Perfadex: effect of the NO-donor nitroglycerin on postischemic outcome.
OBJECTIVE: Optimal preservation of postischemic graft function is essential in lung transplantation. Antegrade flush perfusion with modified Euro-Collins solution represents the standard technique worldwide. However, growing evidence suggests the superiority of extracellular-type Perfadex solution (Vitrolife AB, Gothenburg, Germany) over Euro-Collins solution. During ischemia and reperfusion, endogenous pulmonary nitric oxide synthesis is decreased, and therefore therapeutic stimulation of the nitric oxide pathway might be beneficial in ameliorating ischemia-reperfusion damage. However, research mainly focuses on nitric oxide supplementation of intracellular solutions, and no studies exist in which the effect of nitroglycerin on Perfadex preservation quality is evaluated. METHODS: Eight rat lungs each were preserved with Perfadex solution with or without nitroglycerin (0.1 mg/mL) and compared with low-potassium Euro-Collins solution. Postischemic lungs were reventilated and reperfused, and oxygenation capacity, pulmonary vascular resistance, and peak inspiratory pressures were monitored continuously. Stereological analysis was used for evaluation of pulmonary edema and assessment of the vasculature. Statistics were performed by using different analysis of variance models. RESULTS: The oxygenation capacity of the Perfadex-preserved groups was higher compared with that of the low-potassium Euro-Collins solution group (P <.03). By using nitroglycerin, flush-perfusion time was reduced, and Perfadex solution with nitroglycerin-protected lungs showed superior oxygenation capacity compared with that seen in Perfadex solution-protected organs (P <.01). Furthermore, pulmonary vascular resistance and peak inspiratory pressures were improved in the nitroglycerin group (P <.01). Stereology revealed comparable intrapulmonary edema between groups and a trend toward less vasoconstricted vasculature in Perfadex with nitroglycerin-protected lungs. CONCLUSIONS: Perfadex solution provides superior lung preservation in terms of postischemic oxygenation capacity than Euro-Collins solution. Supplementation of the nitric oxide pathway by nitroglycerin further enhances functional outcome of Perfadex-preserved organs and might be an easily applicable tool in clinical lung transplantation.
Intermittent antegrade warm myocardial protection compared to intermittent cold blood cardioplegia in elective coronary surgery--do we have to change?
OBJECTIVE: Intermittent antegrade warm blood cardioplegia (IAWBC) is a simple and cost-effective method of myocardial preservation. However, there are only few prospective trials comparing this type of cardioplegia to established cardioplegic strategies in elective on-pump coronary surgery with respect to myocardial protection and outcome. METHODS: In a prospective, randomized trial IAWBC (33 degrees C) (n=100) was compared to intermittent antegrade cold (4 degrees C) blood cardioplegia (n=100), regarding clinical outcome and myocardial protection using cardiac troponin-I (cTNI) and creatine kinase MB isoenzyme (CK-MB) measurements to assess ischemia. RESULTS: Preoperative parameters were comparable in both groups. Results demonstrated no differences in-between the groups regarding mortality (2.0% both), incidence of perioperative myocardial infarction (2 versus 3%), need for intra-aortic balloon pump (3 versus 4%), length of ICU stay (2.0+/-2.5 versus 2.1+/-3.0 days) and incidence of postoperative atrial fibrillation (41 versus 34%). However, the necessity of defibrillation after cardiac arrest (18 versus 43%, P<0.001) was significantly less frequent and of lower intensity (3.4+/-10.8 versus 10.8+/-20.6 J, P<0.001) in the IAWBC-group. Postoperatively the ischemia markers were significantly lower in the IAWBC-group, cTNI within the first 72 h (from P<0.001 to P=0.013) and even CK-MB within the first 24 h (from P=0.004 to P<0.011). CONCLUSION: IAWBC is a safe and simple method in elective on-pump coronary artery bypass surgery. Significantly lower ischemic markers suggest an improved myocardial protection compared to cold blood cardioplegia in these patients.