Paediatric aortic valve replacement: a meta-analysis and microsimulation study.

AIMS: To support decision-making in children undergoing aortic valve replacement (AVR), by providing a comprehensive overview of published outcomes after paediatric AVR, and microsimulation-based age-specific estimates of outcome with different valve substitutes. METHODS AND RESULTS: A systematic review of published literature reporting clinical outcome after paediatric AVR (mean age <18 years) published between 1/1/1990 and 11/08/2021 was conducted. Publications reporting outcome after paediatric Ross procedure, mechanical AVR (mAVR), homograft AVR (hAVR), and/or bioprosthetic AVR were considered for inclusion. Early risks (<30d), late event rates (>30d) and time-to-event data were pooled and entered into a microsimulation model. Sixty-eight studies, of which one prospective and 67 retrospective cohort studies, were included, encompassing a total of 5259 patients (37 435 patient-years; median follow-up: 5.9 years; range 1-21 years). Pooled mean age for the Ross procedure, mAVR, and hAVR was 9.2 ± 5.6, 13.0 ± 3.4, and 8.4 ± 5.4 years, respectively. Pooled early mortality for the Ross procedure, mAVR, and hAVR was 3.7% (95% CI, 3.0%-4.7%), 7.0% (5.1%-9.6%), and 10.6% (6.6%-17.0%), respectively, and late mortality rate was 0.5%/year (0.4%-0.7%/year), 1.0%/year (0.6%-1.5%/year), and 1.4%/year (0.8%-2.5%/year), respectively. Microsimulation-based mean life-expectancy in the first 20 years was 18.9 years (18.6-19.1 years) after Ross (relative life-expectancy: 94.8%) and 17.0 years (16.5-17.6 years) after mAVR (relative life-expectancy: 86.3%). Microsimulation-based 20-year risk of aortic valve reintervention was 42.0% (95% CI: 39.6%-44.6%) after Ross and 17.8% (95% CI: 17.0%-19.4%) after mAVR. CONCLUSION: Results of paediatric AVR are currently suboptimal with substantial mortality especially in the very young with considerable reintervention hazards for all valve substitutes, but the Ross procedure provides a survival benefit over mAVR. Pros and cons of substitutes should be carefully weighed during paediatric valve selection.

Retrograde flush is more protective than heparin in the uncontrolled donation after circulatory death lung donor.

BACKGROUND: Formation of microthrombi after circulatory arrest is a concern for the development of reperfusion injury in lung recipients from donation after circulatory death (DCD) donors. In this isolated lung reperfusion study, we compared the effect of postmortem heparinization with preharvest retrograde pulmonary flush or both. METHODS: Domestic pigs (n = 6/group) were sacrificed by ventricular fibrillation and left at room temperature for 1 h. This was followed by 2.5 h of topical cooling. In control group [C], no heparin and no pulmonary flush were administered. In group [R], lungs were flushed with Perfadex in a retrograde way before explantation. In group [H], heparin (300 IU/kg) was administered 10 min after cardiac arrest followed by closed chest massage for 2 min. In the combined group, animals were heparinized and the lungs were explanted after retrograde flush [HR]. The left lung was assessed for 60 min in an ex vivo reperfusion model. RESULTS: Pulmonary vascular resistance at 50 and 55 min was significantly lower in [R] and [HR] groups compared with [C] and [H] groups (P < 0.01 and P < 0.001) and at 60 min in [R], [H], and [HR] groups compared with [C] group (P < 0.001). Oxygenation, compliance, and plateau airway pressure were more stable in [R] and [HR] groups. Plateau airway pressure was significantly lower in [R] group compared with the [H] group at 60 min (P < 0.05). No significant differences in wet-dry weight ratio were observed between the groups. CONCLUSIONS: This study suggests that preharvest retrograde flush is more protective than postmortem heparinization to prevent reperfusion injury in lungs recovered from donation after circulatory death donors.

Aortic Valve Embryology, Mechanobiology, and Second Messenger Pathways: Implications for Clinical Practice.

During the Renaissance, Leonardo Da Vinci was the first person to successfully detail the anatomy of the aortic root and its adjacent structures. Ever since, novel insights into morphology, function, and their interplay have accumulated, resulting in advanced knowledge on the complex functional characteristics of the aortic valve (AV) and root. This has shifted our vision from the AV as being a static structure towards that of a dynamic interconnected apparatus within the aortic root as a functional unit, exhibiting a complex interplay with adjacent structures via both humoral and mechanical stimuli. This paradigm shift has stimulated surgical treatment strategies of valvular disease that seek to recapitulate healthy AV function, whereby AV disease can no longer be seen as an isolated morphological pathology which needs to be replaced. As prostheses still cannot reproduce the complexity of human nature, treatment of diseased AVs, whether stenotic or insufficient, has tremendously evolved, with a similar shift towards treatments options that are more hemodynamically centered, such as the Ross procedure and valve-conserving surgery. Native AV and root components allow for an efficient Venturi effect over the valve to allow for optimal opening during the cardiac cycle, while also alleviating the left ventricle. Next to that, several receptors are present on native AV leaflets, enabling messenger pathways based on their interaction with blood and other shear-stress-related stimuli. Many of these physiological and hemodynamical processes are under-acknowledged but may hold important clues for innovative treatment strategies, or as potential novel targets for therapeutic agents that halt or reverse the process of valve degeneration. A structured overview of these pathways and their implications for cardiothoracic surgeons and cardiologists is lacking. As such, we provide an overview on embryology, hemodynamics, and messenger pathways of the healthy and diseased AV and its implications for clinical practice, by relating this knowledge to current treatment alternatives and clinical decision making.

Off-label use of stretchable polytetrafluoroethylene: overexpansion of synthetic shunts.

PURPOSE: To describe our experience with balloon dilatation and stenting of modified systemic-to-pulmonary artery (PA) shunts in relation to an assessment and interpretation of the mechanical properties of thin-walled expandable polytetrafluoroethylene (ePTFE) stretch vascular grafts. METHODS: Our pediatric cardiology/cardiac surgery database was reviewed to identify all infants and children with a modified systemic-to-PA shunt who underwent cardiac catheterization. Reports and images were reviewed. Thin-walled stretchable and regular Gore-Tex vascular grafts were mechanically compared using tensiometry. RESULTS: 11 patients underwent dilatation or stenting procedures of a systemic-to-PA shunt. No major complications occurred and none of our patients died during or due to this intervention. High pressures in balloons and stents with diameters larger than the graft were used. Shunt diameters and oxygen saturation levels increased from 2.05 +/- 1.25 mm to 4.75 +/- 0.88 mm and with 12 +/- 6.8%, respectively. In 6 patients re-catheterizations were performed. Four patients died, all with patent shunts. The fail-stress and the fail-strain in the circumferential direction of the stretchable graft were significantly higher than in the non-stretchable graft. CONCLUSIONS: Dilatation and stenting of stenosed modified systemic-to-PA shunts is feasible and safe. Dilatation and stenting of these shunts to calibers larger than those provided by the manufacturer is possible. Results of our technical study posit a great advantage for the use of the thin-walled stretch configuration of ePTFE.

Retrograde flush following warm ischemia in the non-heart-beating donor results in superior graft performance at reperfusion.

BACKGROUND: The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. The presence of postmortem thrombi, however, is a concern for the development of primary graft dysfunction. In this isolated lung reperfusion study, we looked at the need and the best route of preharvest pulmonary flush. METHODS: Domestic pigs were sacrificed by ventricular fibrillation and divided in 3 groups (n = 6 per group). After 1 h of in situ warm ischemia, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted after an anterograde flush (AF) through the pulmonary artery. Finally, in group III, lungs were explanted after a retrograde flush (RF) via the left atrium. After 3 h of cold storage, the left lung was assessed for 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. RESULTS: Pulmonary vascular resistance (dynes x sec x cm(-5)) was 1145 +/- 56 (RF) versus 1560 +/- 123 (AF) and 1435 +/- 95 (NF) at 60 min of reperfusion (P < 0.05). Oxygenation and compliance were higher and plateau airway pressure was lower in RF versus AF and NF, although the difference did not reach statistical significance. No differences in W/D were observed between groups after reperfusion. Histological examination revealed fewer microthrombi in the left lung in RF compared with AF and NF. CONCLUSION: RF of lungs from NHBD improves graft function by elimination of microthrombi from the pulmonary vasculature, resulting in lower pulmonary vascular resistance upon reperfusion.

Ovine models for chronic heart failure.

PURPOSE: Testing and optimizing of surgical therapies for chronic heart failure (CHF) requires large animal models. CHF has been induced in several large animal species. Sheep have modest body mass increase and demonstrate docile behavior and are therefore a preferred species in research on surgical therapies for CHF METHODS: A literature search for existing ovine CHF models was performed, using search terms "sheep" and "heart failure". Relevant secondary references were traced. RESULTS: Rapid ventricular pacing produces rapid-onset CHFE Its severity ranges from moderate left ventricular failure to severe biventricular failure, depending on length and frequency of pacing. Its counterpart in human CHF is tachycardia-induced HF since it is reversible upon cessation of pacing. Myocardial damage models include CHF induced by cardiototoxic drugs and ischemia. Ischemia-based models include coronary microembolization, occlusion and ischemia/reperfusion models. The microembolization model is relevant to diabetic cardiomyopathy. Coronary occlusion models exhibit variable functional impairment, some with aneurysm formation, and some with mitral valve regurgitation, depending on occlusion localization. They are relevant to CHF following non-reperfused myocardial infarction. Coronary occlusion/reperfusion models are relevant to the occurrence of human ãã despite coronary artery recanalization. Pressure overload of left and right ventricle is induced by aortic and pulmonary artery banding, respectively. Hypertrophy precedes CHF as in patients with valve stenosis and hypertension. Volume overload is induced by valve damage or shunt creation. Atrioventricular valve regurgitation is the most important clinical counterpart. CONCLUSION: Several ovine CHF models exist. Since they exhibit important cardiac pathology differences, the choice of model should be based on the specific experimental question.

How to obtain and maintain favorable results after heart transplantation: keys to success?

We compared survival in our heart recipients with survival rates reported by the International Society of Heart and Lung Transplantation (ISHLT) Registry. As recipient and donor characteristics are changing over time, we studied four different eras. In order to differentiate between short- and long-term survival, we analyzed both overall survival and survival at one year. Obviously, this exercise is only relevant when baseline donor and recipient characteristics are comparable, as these differences may affect the outcome in opposite directions. To overcome this potential bias as much as possible, we calculated the Index for Mortality Prediction After Cardiac Transplantation (IMPACT)-scores and the Donor Risk Index (DRI). Looking to our results, we found that our DRIs in the different eras are almost equal to those obtained from the United Network for Organ Sharing database in the very same eras. Our IMPACT-scores, on the other hand, seem higher than those reported by ISHLT. Survival after transplantation and conditional on 1-year survival was higher than the outcome reported by the ISHLT Registry. As our operation technique and post-transplant immunosuppressive schedule did not differ from most centers, we speculated on potential factors that might contribute to our positive results. Patient selection and a relatively short waiting time are important contributors to the overall survival benefit. Our centralized follow-up may also have played an important role. Finally, the indefinite compulsory health insurance coverage in our country and easy access to different screening programs might also have influenced our outcome in a positive way. We are well aware that with challenges like donor organ shortage, more and more patients on mechanical circulatory support (MCS) will affect outcomes in the future.

Retrograde flush following topical cooling is superior to preserve the non-heart-beating donor lung.

OBJECTIVE: The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. Formation of microthrombi after circulatory arrest, however, is a major concern for the development of reperfusion injury. We looked at the effect and the best route of pulmonary flush following topical cooling in NHBD. METHODS: Non-heparinized pigs were sacrificed by ventricular fibrillation and divided into three groups (n=6 per group). After 1h of in situ warm ischaemia and 2.5h of topical cooling, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted following an anterograde flush (AF) through the pulmonary artery with 50 ml/kg Perfadex (6 degrees C). Finally, in group III, lungs were retrieved after an identical but retrograde flush (RF) via the left atrium. Flush effluent was sampled at intervals to measure haemoglobin concentration. Performance of the left lung was assessed during 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) of both lungs was calculated as an index of pulmonary oedema. IL-1beta and TNF-alpha protein levels in bronchial lavage fluid from both lungs were compared between groups. RESULTS: Haemoglobin concentration (g/dl) was higher in the first effluent in RF versus AF (3.4+/-1.1 vs 0.6+/-0.1; p<0.05). Pulmonary vascular resistance (dynes x s x cm(-5)) was 975+/-85 RF versus 1567+/-98 AF and 1576+/-88 NF at 60 min of reperfusion (p<0.001). Oxygenation (mmHg) and compliance (ml/cmH(2)O) were higher (491+/-44 vs 472+/-61 and 430+/-33 NS, 22+/-3 vs 19+/-3 and 14+/-1 NS, respectively) and plateau airway pressure (cmH(2)O) was lower (11+/-1 vs 13+/-1 and 13+/-1 NS) after RF versus AF and NF, respectively. No differences in cytokine levels or in W/D ratios were observed between groups after reperfusion. Histology demonstrated microthrombi more often present after AF and NF compared to RF. CONCLUSION: Retrograde flush of the lung following topical cooling in the NHBD results in a better washout of residual blood and microthrombi and subsequent reduced pulmonary vascular resistance upon reperfusion.

Comparative study of donor lung injury in heart-beating versus non-heart-beating donors.

OBJECTIVE: The use of non-heart-beating donors (NHBD) has been advocated as an alternative to overcome the critical organ shortage in lung transplantation despite the warm ischemic period that may result in primary graft dysfunction. On the contrary, brain death in the heart-beating donor (HBD) may be an underestimated risk factor for donor lung injury. We postulated that 60 min of warm ischemia in the NHBD is less detrimental to the lung than the pathophysiological changes after brain death in the HBD. In this study we compared the quality of lungs from HBD versus NHBD in an isolated reperfusion model. METHODS: Pigs (n=10 per group) were divided into three groups. In group I (HBD), brain death was induced by acute inflation of an intracranial epidural balloon catheter. In group II (CONTROL), the balloon was not inflated. In group III (NHBD), cardiac arrest was induced by myocardial fibrillation. After 5 h of in situ mechanical ventilation, lungs in HBD and CONTROL were preserved with a cold antegrade flush. In NHBD, unflushed grafts were explanted after 1 h of warm ischemia and 4 h of topical cooling in the cadaver. Graft performance was evaluated during 1 h in an isolated ventilation and reperfusion model. Extravascular lung water content (EVLW) was calculated. All data are reported as mean+/-SEM. RESULTS: A significant autonomic storm was observed in HBD following balloon inflation. During ex vivo assessment, pulmonary vascular resistance (PVR) at 60 min in HBD (2634+/-371 dynes cm(-5)) was significantly higher as compared with that of CONTROL and NHBD (1894+/-137 dynes s cm(-5) and 1268+/-111 dynes s cm(-5), respectively; p<0.05). Plateau airway pressure (Plateau AwP) was also higher in HBD (17+/-1cmH2O) compared with that of CONTROL (12+/-1 cmH2O; p<0.05) and NHBD (14+/-1 cmH2O; not significant). No significant differences were observed between HBD, CONTROL and NHBD in EVLW (79+/-1%, 79+/-0% and 78+/-1%, respectively), and in PO2/FiO2 (564+/-58 mmHg, 622+/-14 mmHg and 578+/-26 mmHg, respectively). CONCLUSIONS: These data indicate that 1-h warm ischemic lungs in our model are less susceptible to ischemia-reperfusion injury than lungs retrieved 5 h after brain death. This study further supports the use of lungs from NHBD for pulmonary transplantation.

Simultaneous valve replacement and venous patch repair of superior mesenteric artery aneurysm due to infective endocarditis: a case report.

BACKGROUND: Peripheral mycotic aneurysm development is a rare systemic complication of infective endocarditis. CASE REPORT: We report on a case of a mycotic aneurysm of the superior mesenteric artery in a 66-year-old man with infective endocarditis of the mitral valve. After the mitral valve was replaced by a mechanical valve, a laparotomy was performed. The mycotic aneurysm was excised and the vessel was repaired by sewing an autologous venous patch at the neck of the aneurysm. Five years after the operation, the patient is doing fine, with a normal morphology and patency of the superior mesenteric artery. CONCLUSION: Our case demonstrates that simultaneous valve surgery and repair of a superior mesenteric artery mycotic aneurysm by sewing a vein patch in the neck of the artery is a viable treatment option.

IL-1beta in bronchial lavage fluid is a non-invasive marker that predicts the viability of the pulmonary graft from the non-heart-beating donor.

BACKGROUND: Viability testing of the pulmonary graft retrieved from the non-heart-beating donor (NHBD) is mandatory for successful outcome after lung transplantation. Functional assessment by ex vivo reperfusion, however, remains a cumbersome procedure. In this study, therefore, we wanted to investigate the possible value of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) measured in bronchial lavage fluid (BLF) in predicting functional outcome of the pulmonary graft after reperfusion. METHODS: Domestic pigs (29.9 +/- 0.56 kg) were sacrificed and divided in 5 groups (n = 5/group). In the non-ischemic group (NHBD-0), the heart-lung block was explanted immediately. In the other groups the animals were left untouched with increasing time intervals (1 hour = NHBD-1; 2 hours = NHBD-2; 3 hours = NHBD-3). Thereafter both lungs were cooled topically via chest drains up to a total ischemic interval of 4 hours. Finally, in the heart-beating donor group lungs were flushed and stored for 4 hours (4 degrees C) [HBD]. BLF samples were taken from the right lung in all groups after explantation for measurement of IL-1beta and TNF-alpha and the left lung was prepared for evaluation in an isolated reperfusion circuit. Haemodynamic, aerodynamic and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. RESULTS: Graft function deteriorated with increasing time intervals after death. A strong correlation was found between the increase of IL-1beta concentration measured in BLF and the increase in pulmonary vascular resistance (r = 0.80), mean airway pressure (r = 0.74) and wet-to dry weight ratio (r = 0.78); (p < 0.0001, for all parameters). No significant differences in TNF-alpha levels in BLF were observed amongst groups (p = 0.933). CONCLUSIONS: IL-1beta in BLF prior to reperfusion correlated well with graft function and may therefore be a useful, non-invasive marker that can predict the viability of the pulmonary graft from the NHBD.

Should we ventilate or cool the pulmonary graft inside the non-heart-beating donor?

BACKGROUND: The ideal preservation method during the warm ischemic period in the non-heart-beating donor (NHBD) remains unclear. In this study we compare the protective effect of ventilation vs cooling of the non-perfused pulmonary graft. METHODS: Domestic pigs (30.8 +/- 0.35 kg) were divided into 3 groups. In Group I, lungs were flushed with cold Perfadex solution, explanted and stored in saline (4 degrees C) for 4 hours (HBD, n = 5). Pigs in the 2 study groups were killed by myocardial fibrillation and left untouched for 1 hour. Lungs in Group II were ventilated (NHBD-V, n = 5) for 3 hours. Lungs in Group III were topically cooled (NHBD-TC, n = 5) in situ for 3 hours with saline (6 degrees C) infused via intra-pleural drains. Thereafter, the left lungs from all groups were prepared for evaluation. In an isolated circuit the left lungs were ventilated and reperfused via the pulmonary artery (PA) with autologous, hemodiluted, deoxygenated blood. Hemodynamic, aerodynamic and oxygenation parameters were measured at 37.5 degrees C and a PA pressure of 20 mm Hg. The wet:dry weight ratio (W/D) was calculated after reperfusion. RESULTS: Pulmonary vascular resistance, oxygenation index and W/D weight ratio were significantly worse in NHBD-V (3,774 +/- 629 dyn sec cm(-5), 3.43 +/- 0.5, 6.98 +/- 0.42, respectively) compared with NHBD-TC (1,334 +/- 140 dyn sec cm(-5), 2.47 +/- 0.14, 5.72 +/- 0.24, respectively; p < 0.01, p < 0.05 and p < 0.05, respectively) and HBD (1,130 +/- 91 dyn sec cm(-5), 2.25 +/- 0.09, 5.23 +/- 0.49, respectively; p < 0.01, p < 0.01 and p < 0.05, respectively groups). No significant differences were observed, however, in any of these parameters between NHBD-TC and HBD (p = 0.46, p = 0.35 and p = 0.12, respectively). CONCLUSION: These results indicate that cooling of the pulmonary graft inside the cadaver is the preferred method in an NHBD protocol. It is also confirmed that 1 hour of warm ischemia does not diminish graft function upon reperfusion.

How long can we preserve the pulmonary graft inside the nonheart-beating donor?

BACKGROUND: The use of lungs from nonheart-beating donors (NHBD) might significantly alleviate the organ shortage. Extending the preharvest interval in NHBD would facilitate distant organ retrieval. We hypothesized that prolonged topical cooling inside NHBD after 60 minutes of initial warm ischemia would not affect the pulmonary graft. METHODS: Domestic pigs were anesthetized and divided into three groups (n = 6 in each group). In the control group (HBD), lungs were flushed, explanted, and further stored in low potassium dextran solution (4 degrees C) for 4 hours. In the two study groups pigs were sacrificed by myocardial fibrillation and left untouched for 1 hour. Chest drains were then inserted for topical lung cooling (6 degrees C) for 3 hours (NHBD-TC3) or 6 hours (NHBD-TC6). The left lung in all groups was then prepared for evaluation. In an isolated circuit lungs were ventilated and reperfused through the pulmonary artery. Hemodynamic, aerodynamic, and oxygenation variables were measured 35 minutes after onset of controlled reperfusion. Wet-to-dry weight ratio was calculated. RESULTS: No significant differences were observed among the three groups in pulmonary vascular resistance (p = 0.38), mean airway pressure (p = 0.39), oxygenation index (p = 0.62), and wet-to-dry weight ratio (p = 0.09). CONCLUSIONS: These data confirm that 1 hour of warm ischemia does not affect the pulmonary graft from NHBD compared with HBD. The preharvest interval can be safely extended up to 7 hours postmortem by additional topical cooling of the graft inside the cadaver. This technique may facilitate distant organ retrieval in NHBD.

Non-heart-beating donors.

The widespread application of lung transplantation is limited by the shortage of suitable donor organs resulting in longer waiting times for listed patients with a substantial risk of dying before transplantation. To overcome this critical organ shortage, some transplant programs have now begun to explore the use of lungs from circulation-arrested donors, so called non-heart-beating donors (NHBDs). This review outlines the different categories of NHBDs, the relevant published experimental data that support the use of lungs coming from these donors and the clinical experience worldwide so far. Techniques for NHBD lung preservation and pretransplant functional assessment are reviewed. Ethical issues involved in transplanting lungs from asystolic donors are discussed.

Partial mechanical circulatory support in an ovine model of post-infarction remodeling.

BACKGROUND: Full unloading of the left ventricle (LV) in chronic heart failure (CHF) induces reversal of LV dilation and geometric distortion. In this study we describe the partial unloading effects in ischemic CHF. METHODS: Six weeks after myocardial infarction, sheep were randomized to partial support ("pump," n = 5), as provided by the CircuLite Synergy micro-pump, or to no therapy ("sham," n = 6) for an additional 6 weeks. At baseline, and at 6 and 12 weeks after infarction, pressure-volume (PV) recordings were made. Systolic and diastolic functions were characterized by the end-systolic volume (ESV) where LV end-systolic pressure reached 90 mm Hg (V90), and the end-diastolic volume (EDV) where LV end-diastolic pressure reached 15 mm Hg (V15), respectively. Magnetic resonance imaging (MRI) was performed 6 and 12 weeks after infarction. During autopsy at 12 weeks, isolated LVs were weighed. Histologically, the degree of fibrosis in the non-infarcted area was assessed using systematic randomized sampling, and myocyte hypertrophy was measured by the mean linear intercept method. RESULTS: At 6 weeks, PV measurements showed a V90 and V15 increase (p = NS between groups). Six weeks later, V90 and V15 increased in the sham group. In the pump group, V90 decreased but V15 did not change significantly. At 6 weeks, MRI indicated no significant difference between groups. Six weeks later, in the sham group, EDV and ESV increased significantly. In the pump group, EDV decreased significantly and ESV trended to decrease. Sphericity index increased in the sham group and decreased in the pump group, although not significantly. Explanted LV masses were significantly higher in the sham group than in the pump group. The pump group had a decrease in fibrosis and less myocyte hypertrophy. CONCLUSION: Partial support 6 weeks after major myocardial infarction halts and reverses ventricular dilation and hypertrophy.

The mode of death in the non-heart-beating donor has an impact on lung graft quality.

OBJECTIVE: We hypothesised that the agonal phase prior to cardiac death may negatively influence the quality of the pulmonary graft recovered from non-heart-beating donors (NHBDs). Different modes of death were compared in an experimental model. METHODS: Non-heparinised pigs were divided into three groups (n=6 per group). Animals in group I [FIB] were sacrificed by ventricular fibrillation resulting in immediate circulatory arrest. In group II [EXS], animals were exsanguinated (45+/-11 min). In group III [HYP], hypoxic cardiac arrest (13+/-3 min) was induced by disconnecting the animal from the ventilator. Blood samples were taken pre-mortem in HYP and EXS for measurement of catecholamine levels. After 1 h of in situ warm ischaemia, unflushed lungs were explanted and stored for 3 h (4 degrees C). Left lung performance was then tested during 60 min in our ex vivo reperfusion model. Total protein concentration in bronchial lavage fluid was measured at the end of reperfusion. RESULTS: Pre-mortem noradrenalin (mcg l(-1)) concentration (baseline: 0.03+/-0) increased to a higher level in HYP (50+/-8) vs EXS (15+/-3); p=0.0074. PO(2) (mmHg) at 60 min of reperfusion was significantly worse in HYP compared to FIB (445+/-64 vs 621+/-25; p<0.05), but not to EXS (563+/-51). Pulmonary vascular resistance (dynes s cm(-5)) was initially higher in EXS (p<0.001) and HYP (NS) vs FIB (15824+/-5052 and 8557+/-4933 vs 1482+/-61, respectively) but normalised thereafter. Wet-to-dry weight ratio was higher in HYP compared to FIB (5.2+/-0.3 vs 4.7+/-0.2, p=0.041), but not to EXS (4.9+/-0.2). Total protein (g l(-1)) concentration was higher, although not significant in HYP and EXS vs FIB (18+/-6 and 13+/-4 vs 4.5+/-1.3, respectively). CONCLUSION: Pre-mortem agonal phase in the NHBD induces a sympathetic storm leading to capillary leak with pulmonary oedema and reduced oxygenation upon reperfusion. Graft quality appears inferior in NHBD lungs when recovered in controlled (HYP) vs uncontrolled (EXS and FIB) setting.

Pediatric heart support with a newly developed catheter based pulsatile 12F rotary blood pump: an animal study.

BACKGROUND: To evaluate mechanical and hematological compatibility of a pediatric, temporary left heart support system in a lamb model as a less traumatic alternative to the widely used ECMO. METHODS: A small, pulsatile rotary blood pump (target flow 0.5l/m at 80 mm Hg pressure head at 120 pulses per min) was inserted in six lambs (15.1+/-1 kg) via a left thoracotomy, through a purse string in the arcus aortae. With fluoroscopy the tip (=inflow) of the catheter was positioned in the outflow tract of the left ventricle. The outflow part was positioned immediately above the aortic valve. Animals were extubated at the end of the procedure. Mechanical and hematological parameters were followed for 14 days. RESULTS: Five animals survived a 2-week follow-up. One animal died because of empyema on day 6. Flow maintained stable (0.8+/-0.2l/m) in all animals during the evaluation period. Free hemoglobin as a parameter of hemolysis and hematocrit remained also stable. Necropsy revealed minimal fibrous reaction on one aortic valve leaflet in one animal and small hematoma formation in three. All animals showed mild signs of endothelial damage on the aortic arch at the level of the motor housing. One animal showed signs of old kidney infarction suggesting possible embolization during placement. CONCLUSION: This newly developed, catheter based, pediatric heart support system generates a stable flow for 14 days without compromising hematological stability and with acceptable tissue damage due to positioning of the catheter.

N-acetyl cysteine attenuates the inflammatory response in warm ischemic pig lungs.

BACKGROUND: Lungs donated after cardiac death (DCD) may significantly reduce current organ shortage. However, the warm ischemic period following circulatory arrest may enhance ischemia-reperfusion injury (IRI). We investigated the possible therapeutic effect of N-acetyl cysteine (NAC), a potent anti-oxidative agent on IRI in a porcine ex vivo lung reperfusion model. MATERIALS AND METHODS: NAC (50 mg/kg) was nebulized to pigs (n = 6/group) prior to sacrifice (NAC-DCD). In DCD-NAC, animals received NAC 15 min after death. Control animals did not receive an aerosol (DCD). Interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-8, lactate dehydrogenase activity and thiobarbituric acid reactive substances were measured and cells were counted in broncho-alveolar lavage from the right lung after a 3-h warm plus 1-h cold ischemic interval. RESULTS: There were no differences in cells between groups, however cell death was lower in NAC-DCD (10.3 +/- 1.5%) and DCD-NAC (7.83 +/- 1.8%) compared to DCD (18.0 +/- 3.8%). IL-1beta levels (111.5 +/- 28.8 pg/mL and 92.2 +/- 51.0 pg/mL versus 250.3 +/- 56.6 pg/mL) and lactate dehydrogenase activity (1258.0 +/- 440.9 U/L and 1606.0 +/- 289.0 U/L versus 2848.0 +/- 760.9 U/L) were significantly lower in NAC-DCD and DCD-NAC compared with DCD, respectively. These postischemic inflammatory markers correlated with functional parameters upon reperfusion of the left lung, reported in a previous study. CONCLUSIONS: Administration of NAC prior to or shortly after circulatory arrest results in a marked reduction of inflammation during the warm ischemic phase.

pH 48 h after onset of extracorporeal membrane oxygenation is an independent predictor of survival in patients with respiratory failure.

Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure in patients with severe respiratory failure, unresponsive to conventional therapy. We reviewed our series of 70 ECMO runs (April 1997 to December 2005) in patients with respiratory distress, refractory to standard ventilation. Survival at 90 days was 42.7%. Besides age, we found no statistical significant difference in patient demographics or preoperative patient data between survivors and nonsurvivors. Univariate analyses indicated that pH values at 24 and 48 h after onset of ECMO were significantly higher in survivors. In multivariate analysis, age and pH at 48 h remained independent predictors of survival. ECMO in respiratory failure saves lives. No other demographic or preoperative, patient-related parameter than age was identified as predictor of survival. Although there was no difference in pH at onset of ECMO, blood gas analysis at 48 h revealed pH as an independent predictor of survival.

Impact of warm ischemia on different leukocytes in bronchoalveolar lavage from mouse lung: possible new targets to condition the pulmonary graft from the non-heart-beating donor.

BACKGROUND: The use of non-heart-beating donors (NHBDs) for lung transplantation is a possible alternative for increasing the number of organs available. The warm ischemic period after circulatory arrest may contribute to a higher degree of primary graft dysfunction, resulting from ischemia-reperfusion injury (IRI). A better understanding of the role of inflammatory cells during the warm ischemic interval may be useful for developing new therapeutic strategies against IRI. METHODS: Mice were divided in 7 groups (n = 6/group). In 3 groups, ischemia was induced by clamping the hilum of the left lung for 30, 60 or 90 minutes (Groups [30I], [60I] or [90I], respectively). In 3 more groups, the lung was reperfused for 4 hours after identical ischemic intervals (Groups [30I+R], [60I+R] or [90I+R], respectively). Surgical impact was evaluated in a sham group ([sham]). Total and differential cell counts and interleukin-1beta (IL-1beta) protein levels in bronchoalveolar lavage (BAL) were determined and their correlations were investigated. RESULTS: Total cell, macrophage and lymphocyte numbers and IL-1beta protein levels increased progressively with longer ischemic intervals. A significant rise in BAL macrophages and lymphocytes was observed between [60I] and [90I] (p < 0.01 and p < 0.001, respectively). BAL neutrophils only increased after reperfusion with longer ischemic intervals. A positive correlation was found in the ischemic groups between IL-1beta levels and the number of macrophages (r = 0.62; p = 0.0012) and the number of lymphocytes (r = 0.68; p = 0.0002). A positive correlation was found in the reperfusion groups between IL-1beta levels and the number of neutrophils (r = 0.48; p = 0.044). CONCLUSIONS: This study demonstrates for the first time that BAL macrophages and lymphocytes increase significantly during warm ischemia and correlate with IL-1beta levels.