Development, preclinical evaluation and validation of a novel quick vascular closure device for transluminal, cardiac and radiological arterial catheterization.

Following percutaneous coronary intervention, vascular closure devices (VCDs) are increasingly used to reduce time to ambulation, enhance patient comfort, and reduce potential complications compared with traditional manual compression. Newer techniques include complicated, more or less automated suture devices, local application of pads or the use of metal clips and staples. These techniques often have the disadvantage of being time consuming, expensive or not efficient enough. The VCD failure rate in association with vascular complications of 2.0-9.5%, depending on the type of VCD, is still not acceptable. Therefore, the aim of this study is to develop a self-expanding quick vascular closure device (QVCD) made from a bioabsorbable elastic polymer that can be easily applied through the placed introducer sheath. Bioabsorbable block-co-polymers were synthesized and the chemical and mechanical degradation were determined by in vitro tests. The best fitting polymer was selected for further investigation and for microinjection moulding. After comprehensive haemocompatibility analyses in vitro, QVCDs were implanted in arterial vessels following arteriotomy for different time points in sheep to investigate the healing process. The in vivo tests proved that the new QVCD can be safely placed in the arteriotomy hole through the existing sheath instantly sealing the vessel. The degradation time of 14 days found in vitro was sufficient for vessel healing. After 4 weeks, the remaining QVCD material was covered by neointima. Overall, our experiments showed the safety and feasibility of applying this novel QVCD through an existing arterial sheath and hence encourage future work with larger calibers.

Aortic Elongation and Stanford B Dissection: The Tübingen Aortic Pathoanatomy (TAIPAN) Project.

OBJECTIVE/BACKGROUND: Aortic elongation has not yet been considered as a potential risk factor for Stanford type B dissection (TBD). The role of both aortic elongation and dilatation in patients with TBD was evaluated. METHODS: The aortic morphology of a healthy control group (n = 236) and patients with TBD (n = 96) was retrospectively examined using three dimensional computed tomography imaging. Curved multiplanar reformats were used to examine aortic diameters at defined landmarks and aortic segment lengths. RESULTS: Diameters at all landmarks were significantly larger in the TBD group. The greatest diameter difference (56%) was measured in dissected descending aortas (p < .001). The segment with the most considerable difference between the study groups with regard to elongation was the non-dissected aortic arch of patients with TBD (36%; p < .001). Elongation in the aortic arch was accompanied by a diameter increase of 21% (p < .001). In receiver-operating curve analysis, the area under the curve was .85 for the diameter and .86 for the length of the aortic arch. CONCLUSIONS: In addition to dilatation, aortic arch elongation is associated with the development of TBD. The diameter and length of the non-dissected aortic arch may be predictive for TBD and may possibly be used for risk assessment in the future. This study provides the basis for further prospective evaluation of these parameters.

Non-invasive measurement of renal perfusion and oxygen metabolism to predict postoperative acute kidney injury in neonates and infants after cardiopulmonary bypass surgery.

BACKGROUND: The pathophysiology of acute kidney injury (AKI) after cardiopulmonary bypass surgery for congenital heart disease is not completely understood. The aim of this study was to carry out a prospective analysis of the diagnostic value of non-invasive monitoring of renal oxygenation and microcirculation by combining laser Doppler flowmetry and tissue spectrometry. METHODS: In 50 neonates and infants who underwent repair (n = 31) or neonatal palliation (n = 19) of congenital heart disease with cardiopulmonary bypass, renal oxygenation, and microcirculatory flow, the approximate renal metabolic rate of oxygen and Doppler-based renal resistive index were determined after surgery. Correlations between these parameters and the occurrence of AKI according to the Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease criteria were investigated. RESULTS: Acute kidney injury occurred in 45% of patients after repair and in 32% after palliation. Renal oxygenation was significantly lower and the approximate renal metabolic rate of oxygen significantly higher in patients with AKI (P < 0.05). The microcirculatory flow was significantly higher in patients with AKI after neonatal palliation (P < 0.05), whereas renal resistive index was significantly higher in patients with AKI after repair (P < 0.05). The sensitivity of renal oxygenation, metabolic rate of oxygen, microcirculation, and resistive index in predicting AKI was 78-80, 73-78, 64-83, and 71-74%, respectively, with a specificity of 63-65, 54-75, 64-78, and 46-74% (area under the curve: 0.73-0.75, 0.68-0.83, 0.52-0.68, and 0.60-0.75), respectively. CONCLUSIONS: Monitoring of renal oxygen metabolism allows early prediction of AKI in infants after cardiac surgery. In contrast, renal resistive index does not allow prediction of AKI after neonatal palliation with aortopulmonary shunt establishment.

Pitfalls in Echocardiography: Coarctation of the Aorta Presenting as Dilated Cardiomyopathy (DCM).

Purpose: The morphologic spectrum of aortic coarctation extends from discrete isthmic obstruction to tubular hypoplasia of the entire aortic arch. Neonates with coarctation frequently present with congestive heart failure and critically reduced perfusion of the descending aorta following ductal closure. During the recent years we observed several infants with coarctation who presented beyond the neonatal period with dilated cardiomyopathy (DCM). We reviewed our patients with coarctation to determine whether this presentation represents an exception or is relevant for the differential diagnosis of children with DCM. Materials and Methods: From 1/2001 to 12/2013 74 babies with isolated coarctation were diagnosed in our institution. 50 patients presented in the neonatal period and 24 patients beyond the first month. Results: 5/74 infants presented after the neonatal period with poorly contractile, dilated left ventricles. Echocardiographic detection of the coarctation was facilitated by application of the ductal view and by Doppler interrogation of the celiac artery revealing a significantly diminished systolic flow velocity. All patients underwent resection of the coarctation and end-to-end anastomosis of the aorta. Postoperative normalization of left ventricular function was observed within a median interval of 2 months. Conclusion: Coarctation of the aorta presenting as DCM accounted for 21 % of our infants with coarctation who presented beyond the neonatal period and 7 % of those in the first year of life. The stenosis was difficult to detect because of its distal location and normal configuration of the aortic arch. Isthmic coarctation should be included in the differential diagnosis of infants with DCM and requires careful examination of the isthmic region in these children.

Acute aortic dissection type A.

BACKGROUND: Acute aortic dissection type A (AADA) is a life-threatening vascular emergency. Clinical presentation ranges from pain related to the acute event, collapse due to aortic rupture or pericardial tamponade, or manifestations of organ or limb ischaemia. The purpose of this review was to clarify important clinical issues of AADA management, with a focus on diagnostic and therapeutic challenges. METHODS: Based on a MEDLINE search the latest literature on this topic was reviewed. Results from the German Registry for Acute Aortic Dissection Type A (GERAADA) are also described. RESULTS: Currently, the perioperative mortality rate of AADA is below 20 per cent, the rate of definitive postoperative neurological impairment approaches 12 per cent and the long-term prognosis after surviving the acute phase of the disease is good. Many pathology- and therapy-associated factors influence the outcome of AADA, including prompt diagnosis with computed tomography and better cerebral protection strategies during aortic arch reconstruction. Endovascular technologies are emerging that may lead to less invasive treatment options. CONCLUSION: AADA is an emergency that can present with a wide variety of clinical scenarios. Advances in the surgical management of this complex disease are improving outcomes.

Iatrogenic neonatal type B aortic dissection: comprehensive MRI-based diagnosis and follow-up.

Neonatal aortic dissection is rare and most frequently iatrogenic. Decision making and appropriate imaging are highly challenging for pediatric cardiologists and radiologists. We present MRI and echocardiographic findings in the follow-up at 6 months of age of a boy with a conservatively treated iatrogenic neonatal aortic dissection (type B). To evaluate the morphology of the aortic arch and descending aorta, we carried out multidirectional time-resolved three-dimensional flow-analysis and contrast-enhanced MR angiography (CE-MRA). The MRI and Doppler echocardiographic results were closely comparable. Three-dimensional visualization helped assess details of blood flow acceleration and alteration caused by the dissection, and played a key role in our deciding not to treat surgically.

Clinical experience with the VentrAssist left ventricular assist device.

INTRODUCTION: Left ventricular mechanical assist device (LVAD) support is well established as a bridge to transplantation and as an alternative to transplantation in patients with end-stage heart failure. There are currently various LVAD systems available based on different types of pump technology. We present the VentrAssist LVAD, a centrifugal pump, and focus on a surgical implantation technique that may help reduce the complications typically associated with VAD surgery. METHODS AND RESULTS: 412 patients underwent VentrAssist LVAD implantation between June 2003 and January 2009 worldwide. The overall rate of success was 81 % (i.e., ongoing, HTX, or recovery). Interestingly hemolysis is greatly reduced with this intracorporeal centrifugal LVAD compared to other VAD systems with other pump designs. Our surgical implantation technique and strategy may contribute to reducing complications. CONCLUSION: The VentrAssist is a powerful and effective LVAD; its use can considerably reduce hemolysis. Long-term follow-up is necessary to determine whether the VentrAssist is appropriate as a bridge to transplant as well as feasible for long-term application.

Partial mechanical long-term support with the CircuLite Synergy pump as bridge-to-transplant in congestive heart failure.

BACKGROUND: Full mechanical support with a left ventricular assist device (LVAD) is often limited to very sick patients, as the only survival option. This European multicenter study analyzes the effect of partial mechanical support as bridge-to-transplant in a less sick heart failure patient group. METHODS: The CircuLite Synergy device is implanted via a small right-sided thoracotomy with an inflow cannula in the left atrium and an outflow graft connected to the right subclavian artery without the use of extracorporeal circulation. The pump itself sits in a "pacemaker" pocket subcutaneously in the right clavicular groove. It is able to pump up to 3.0 l/min and partially unload the left ventricle. RESULTS: The device was implanted in 25 patients on the cardiac transplant waiting list (20 males), aged 55.5 +/- 9.6 yrs with an ejection fraction of 21.6 +/- 6.0 %, a mean arterial pressure of 73.5 +/- 8.5 mmHg, a pulmonary capillary wedge pressure of 27.2 +/- 7.8 mmHg and cardiac index of 1.9 +/- 0.4 l/min/m (2). Duration of support ranged from 6 to 238 days. Right heart catheterization showed significant hemodynamic improvement in the short- and intermediate-term after implantation with increases in arterial pressure from 72.6 +/- 11.0 to 79.4 +/- 8.6 mmHg ( P = 0.04) and in cardiac index from 2.0 +/- 0.4 to 2.7 +/- 0.6 l/min/m (2) ( P = 0.003) with a reduction in pulmonary capillary wedge pressure from 28.5 +/- 6.0 to 19.7 +/- 6.9 mmHg ( P = 0.012). CONCLUSIONS: The CircuLite Synergy device is a partial support pump, which is easy to implant and which provides hemodynamic benefits in bridging heart failure patients to cardiac transplant.

Immunohistochemical study of remodeling of myocardial lymphatic and blood microvascular structures in terminal heart failure: differences between ischemic and dilated cardiomyopathy.

This study investigated (cardiac) remodeling of the myocardial microvasculature in patients with terminal heart failure due to ischemic (ICM) and dilative (DCM) cardiomyopathy. Seventeen transmural left-ventricular (LV) biopsies (9 ICM and 8 DCM), taken from heart transplant recipients at transplantation (n=4) or during ventricular assist device implantation (n=13) were investigated by immunohistostaining for VEGFR-1 and VEGFR-2 as capillary markers and VEGFR-3, D2-40, PROX-1 and LYVE-1 as lymphatic markers. Results were compared to LV biopsies from 7 donor hearts (control). Compared to control, DCM hearts showed a significantly higher density of LYVE-1 positive lymphatics (p < 0.05), whereas no difference was seen for other markers. ICM hearts showed a significantly higher density of D2-40 positive lymphatics (p < 0.01) and a lower density of VEGFR-2 capillaries compared to control (p < 0.05). In comparison to normal donor hearts, ICM and DCM hearts showed a significantly different pattern of microvascular receptor expression. As distinct patterns were seen in ICM and DCM, the effect of microvascular remodeling may be substantially different between two clinically important causes of cardiomyopathy. Further research should be aimed at defining the impact of extracellular matrix composition and VEGF-related angiogenesis on the myocardial microvasculature at various stages of heart failure.

The management of acute limb ischemia.

Acute limb ischemia (ALI) is one of the most common vascular emergencies and characterized by sudden worsening of limb perfusion mainly caused by embolization of thrombotic masses or acute graft occlusion. It is a serious condition with potential thread to limb viability accompanied by significant mortality, morbidity and costs. This article provides an overview of etiology, classification and treatment options of ALI ischemia with special focus on the issue of postreperfusion syndrome. The concept of reperfusion injury following limb ischemia and a system for controlled limb reperfusion to offset postreperfusion synsrome is described in detail.

Protective effects of inhaled carbon monoxide in pig lungs during cardiopulmonary bypass are mediated via an induction of the heat shock response.

BACKGROUND: Cardiopulmonary bypass (CPB) may cause acute lung injury leading to increased morbidity and mortality after cardiac surgery. Preconditioning by inhaled carbon monoxide reduces pulmonary inflammation during CPB. We hypothesized that inhaled carbon monoxide mediates its anti-inflammatory and cytoprotective effects during CPB via induction of pulmonary heat shock proteins (Hsps). METHODS: Pigs were randomized either to a control group, to standard CPB, to carbon monoxide+CPB, or to quercetin (a flavonoid and unspecific inhibitor of the heat shock response)+control, to quercetin+CPB, and to quercetin+carbon monoxide+CPB. In the carbon monoxide groups, lungs were ventilated with 250 ppm carbon monoxide in addition to standard ventilation before CPB. At various time points, lung biopsies were obtained and pulmonary Hsp and cytokine concentrations determined. RESULTS: Haemodynamic parameters were largely unaffected by CPB, carbon monoxide inhalation, or administration of quercetin. Compared with standard CPB, carbon monoxide inhalation significantly increased the pulmonary expression of the Hsps 70 [27 (SD 3) vs 69 (10) ng ml(-1) at 120 min post-CPB, P<0.05] and 90 [0.3 (0.03) vs 0.52 (0.05) after 120 min CPB, P<0.05], induced the DNA binding of heat shock factor-1, reduced interleukin-6 protein expression [936 (75) vs 320 (138) at 120 min post-CPB, P<0.001], and decreased CPB-associated lung injury (assessed by lung biopsy). These carbon monoxide-mediated effects were inhibited by quercetin. CONCLUSIONS: As quercetin, a Hsp inhibitor, reversed carbon monoxide-mediated pulmonary effects, we conclude that the anti-inflammatory and protective effects of preconditioning by inhaled carbon monoxide during CPB in pigs are mediated by an activation of the heat shock response.

Acquired von Willebrand syndrome in congenital heart disease surgery: results from an observational case-series.

Essentials Bleeding complications during congenital heart disease surgery in neonatal age are very common. We report the perioperative incidence of acquired von Willebrand syndrome (aVWS) in 12 infants. aVWS was detected in 8 out of 12 neonates and infants intraoperatively after cardiopulmonary bypass. Ten patients received von Willebrand factor concentrate intraoperatively and tolerated it well. SUMMARY: Background Cardiac surgery of the newborn and infant with complex congenital heart disease (CHD) is associated with a high rate of intraoperative bleeding complications. CHD-related anatomic features such as valve stenoses or patent arterial ducts can lead to enhanced shear stress in the blood stream and thus cause acquired von Willebrand syndrome (aVWS). Objective To evaluate the intraoperative incidence and impact of aVWS after cardiopulmonary bypass (CPB) in neonates and infants with complex CHD. Patients/Methods We conducted a survey of patients aged < 12 months undergoing complex cardiac surgery in our tertiary referral center. Twelve patients, whose blood samples were analyzed for aVWS before CPB and immediately after discontinuation of CPB on a routine basis, were eligible for the analysis. von Willebrand factor antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo), collagen binding activity (VWF:CB), VWF:multimers and factor VIII activity (FVIII:C) were determined. Results aVWS was diagnosed by VWF multimer analysis in 10 out of 12 patients (83%) prior to surgery and intraoperatively at the end of CPB in 8 out of 12 patients (66%). Ten patients received VWF/FVIII concentrate intraoperatively as individual treatment attempts during uncontrolled bleeding. They tolerated it well without intraoperative thrombotic events. One patient suffered a transient postoperative cerebral sinuous vein thrombosis. Conclusions aVWS is of underestimated incidence in complex CHD surgery. These data may offer a new approach to reduce the risk of severe bleedings and to achieve hemostasis during high-risk pediatric cardiac surgery by tailoring the substitution with von Willebrand factor concentrate.

[Flow-sensitive in-vivo 4D MR imaging at 3T for the analysis of aortic hemodynamics and derived vessel wall parameters]. / Die Analyse aortaler Hämodynamik und Gefässwandparameter mittels fluss-sensitiver in-vivo 4D-MRT bei 3 Tesla.

Modern phase contrast MR imaging at 3 Tesla allows the depiction of 3D morphology as well as the acquisition of time-resolved blood flow velocities in 3 directions. In combination with state-of-the-art visualization and data processing software, the qualitative and quantitative analysis of hemodynamic changes associated with vascular pathologies is possible. The 4D nature of the acquired data permits free orientation within the vascular system of interest and offers the opportunity to quantify blood flow and derived vessel wall parameters at any desired location within the data volume without being dependent on predefined 2D slices. The technique has the potential of overcoming the limitations of current diagnostic strategies and of implementing new diagnostic parameters. In light of the recent discussions regarding the influence of the wall shear stress and the oscillatory shear index on the genesis of arteriosclerosis and dilatative vascular processes, flow-sensitive 4D MRI may provide the missing diagnostic link. Instead of relying on experience-based parameters such as aneurysm size, new hemodynamic considerations can deepen our understanding of vascular pathologies. This overview reviews the underlying methodology at 3T, the literature on time-resolved 3D MR velocity mapping, and presents case examples. By presenting the pre- and postoperative assessment of hemodynamics in a thoracic aortic aneurysm and the detailed analysis of blood flow in a patient with coarctation we underline the potential of time-resolved 3D phase contrast MR at 3T for hemodynamic assessment of vascular pathologies, especially in the thoracic aorta.

Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult.

OBJECTIVE: Hyperoxic cardiopulmonary bypass is widely used during cardiac operations in the adult. This management may cause oxygenation injury induced by oxygen-derived free radicals and nitric oxide. Oxidative damage may be significantly limited by maintaining a more physiologic oxygen tension strategy (normoxic cardiopulmonary bypass). METHODS: During elective coronary artery bypass grafting, 40 consecutive patients underwent either hyperoxic (oxygen tension = 400 mm Hg) or normoxic (oxygen tension = 140 mm Hg) cardiopulmonary bypass. At the beginning and the end of bypass this study assessed polymorphonuclear leukocyte elastase, nitrate, creatine kinase, and lactic dehydrogenase, antioxidant levels, and malondialdehyde in coronary sinus blood. Cardiac index was measured before and after cardiopulmonary bypass. RESULTS: There was no difference between groups with regard to age, sex, severity of disease, ejection fraction, number of grafts, duration of cardiopulmonary bypass, or ischemic time. Hyperoxic bypass resulted in higher levels of polymorphonuclear leukocyte elastase (377 +/- 34 vs 171 +/- 32 ng/ml, p = 0.0001), creatine kinase 672 +/- 130 vs 293 +/- 21 U/L, p = 0.002), lactic dehydrogenase (553 +/- 48 vs 301 +/- 12 U/L, p = 0.003), antioxidants (1.97 +/- 0.10 vs 1.41 +/- 0.11 mmol/L, p = 0.01), malondialdehyde (1.36 +/- 0.1 micromol/L,p = 0.005), and nitrate (19.3 +/- 2.9 vs 10.1 +/- 2.1 micromol/L, p = 0.002), as well as reduction in lung vital capacity (66% +/- 2% vs 81% +/- 1%,p = 0.01) and forced 1-second expiratory volume (63% +/- 10% vs 93% +/- 4%, p = 0.005) compared with normoxic management. Cardiac index after cardiopulmonary bypass at low filling pressure was similar between groups (3.1 +/- 0.2 vs 3.3 +/- 0.3 L/min per square meter). [Data are mean +/- standard error (analysis of variance), with p values compared with an oxygen tension of 400 mm Hg.] CONCLUSIONS: Hyperoxic cardiopulmonary bypass during cardiac operations in adults results in oxidative myocardial damage related to oxygen-derived free radicals and nitric oxide. These adverse effects can be markedly limited by reduced oxygen tension management. The concept of normoxic cardiopulmonary bypass may be applied to surgical advantage during cardiac operations.

A technique of heterotopic, infrarenal heart transplantation with double anastomosis in mice.

Mouse heart transplantation is frequently used to investigate mechanisms of rejection and immune response. A fully vascularized technique is presented in which the graft ascending aorta is anastomosed end-to-side to the recipient's aorta and the pulmonary aorta is anastomosed end-to-side to the inferior vena cava using 11-0 Ethilon suture. We suggest that this double anastomosis technique is a valuable tool to investigate immune mechanisms in mice.

Protection of acutely ischemic myocardium by controlled reperfusion.

The goal of revascularization after acute occlusion of a coronary artery is the return of contractile function and the reduction of mortality. Although reperfusion of ischemic myocardium is a prerequisite for return of function, it may, in itself, cause further injury. Controlled blood cardioplegic reperfusion reduces this "reperfusion injury" and provides maximal myocardial protection. In this article, we review recent advances in surgically controlled reperfusion and speculate on future prospects for myocardial protective techniques in patients with acute coronary artery occlusion.

Minimal-invasive, video-assisted vein harvesting for cardiac and vascular surgical procedures.

Harvesting of the saphenous vein is a routine procedure in coronary and peripheral vascular surgery. It is usually performed using a continuous long skin incision. Minor complications are reported in up to 24% (hematoma, wound dehiscence, infection, pain) and major problems necessitating surgical interventions (bleeding, abscess) in less than 1%. These complications lead to a prolonged hospital stay. To reduce these complications we have used a new endoscopic, video-assisted technique in 17 patients. Harvesting of the total length of the saphenous vein is possible with only one 2-3 cm long incision proximally the knee joint. We conclude that this technique is safe, may reduce the morbidity of saphenous vein harvesting and is associated with a perfect cosmetic result.

Pulmonary artery banding with a novel percutaneously, bidirectionally adjustable device.

Pulmonary artery banding is commonly performed as a palliative procedure in complex congenital heart disease, when pulmonary blood flow is increased. However, the hemodynamics may change postoperatively requiring readjustment of the band, which may necessitate a second operation. We report a new system for pulmonary artery banding which allows precise placement of the band intraoperatively, as well as bidirectional percutaneous adjustment of the band postoperatively. Via left lateral thoracothomy the new device was implanted without complications into a neonate with congestive heart failure due to tricuspid atresia (IIc) and coarctation of the aorta. Although optimal placement of the band had been achieved intraoperatively the band had to be tightened 25 h after the operation and released 85 h after the operation in order to optimize hemodynamics. The bidirectionally adjustable device for banding of the pulmonary artery is superior to previously used devices with either no or unidirectional adjustability of the band because it is safe and easy to implant and has the potential to reduce the number of reoperations associated with this type of procedure.

Effects of ultrafiltration and peritoneal dialysis on proinflammatory cytokines during cardiopulmonary bypass surgery in newborns and infants.

OBJECTIVES: To assess the impact of balanced ultrafiltration and peritoneal dialysis (PD) on plasma and urinary cytokines and renal dysfunction after cardiopulmonary bypass (CPB) surgery in newborns and infants. METHODS: Twenty-three newborns and infants weighing less than 7 kg and scheduled for operation on congenital malformation were enrolled in this descriptive open clinical study. All patients received conventional ultrafiltration in the CPB rewarming period. Eleven newborns underwent Tenckhoff-catheter implantation in the operation theatre as a routine institutional procedure and received PD after admission to the ICU (the PD [+] group). No PD was used in another 12 patients (the PD [-] group). Interleukins (IL) 6 and 8 were measured four times pre- and post-operatively. Kidney function was assessed by creatinine clearances and urine protein and enzyme analyses. RESULTS: All patients had an uneventful clinical course. Age (10+/-2 days, PD [+] vs. 96+/-19 days, PD [-]), CPB duration (215+/-23 vs. 143+/-20 min), and degree of hypothermia (26+/-1.3 vs. 31+/-0.1 degrees C) differed significantly between the groups. Age, CPB duration and ultrafiltration influenced post-operative IL-levels in an analysis of variance. While there were few differences immediately after the end of ultrafiltration, post-operative levels of IL-6 and IL-8 were higher and more sustained in the newborns (PD [+]) than in the older infants (PD [-]). The median amount of IL-6 and IL-8 removed by ultrafiltration came to 28 and 59% compared to the amount of IL-6 and IL-8 remaining in the blood at the end of CPB. IL-clearance by ultrafiltration was more than 1000-fold and by PD more than 100-fold as effective as IL-clearance by the kidney. While the kidneys showed an unselective mixed glomerular and tubular pattern of injury, during CPB higher serum IL-concentrations correlated with lower urinary IL-clearances in both study groups. CONCLUSIONS: Ultrafiltration and PD are highly effective in removing proinflammatory cytokines. Impaired kidney function was associated with proinflammatory IL-serum concentrations. Thus, we raise the hypothesis that glomerular-filtered proinflammatory ILs damage the proximal tubular cells of the kidney in newborns and infants, thus contributing to post-operative renal dysfunction. Conversely, we conclude that removing proinflammatory ILs by ultrafiltration and PD acts renoprotectively. A future prospective randomised study could demonstrate whether this can indeed improve clinical outcome.

Bronchial artery perfusion during cardiopulmonary bypass does not prevent ischemia of the lung in piglets: assessment of bronchial artery blood flow with fluorescent microspheres.

OBJECTIVE: Blood supply of the lungs during total cardiopulmonary bypass (CPB) is limited to flow through the bronchial arteries. This study was undertaken to assess the bronchial artery blood flow during CPB with fluorescent microspheres in a piglet model. METHODS: We subjected ten piglets (mean weight 5.0+/-0.5 kg) to 120 min of normothermic, total CPB without aortic cross-clamping, followed by 60 min of post-bypass perfusion. Fluorescent microspheres were injected into the left atrium or the aortic cannula or distal to the cannula to assess bronchial artery blood flow before, during and after CPB. The reference samples were taken from the descending aorta. We compared the different sites of injection. Tissue samples of the lungs were taken before and 60 min after CPB. RESULTS: Before CPB, total bronchial artery perfusion was 43.6+/-14.1 ml/min (4.8+/-1.3% of cardiac output) as by injection distal to the aortic cannula. These values were not different when microspheres were injected into the left atrium or the aortic cannula. There was no difference in scatter or in the amount of microspheres in the reference samples among the three injections sites. During CPB, bronchial artery perfusion was significantly decreased (4.4+/-2.4 ml/min vs. 40.0+/-5.0 ml/min before CPB) and returned to baseline values 60 min after CPB. Light microscopy of the tissue samples revealed alveolar septal thickening and a decrease in alveolar surface area after 60 min of reperfusion which was associated with a decreased capacity to oxygenate blood. CONCLUSIONS: (1) Bronchial artery blood flow can quantitatively be assessed during CPB when microspheres are injected into the ascending aorta and the reference samples are taken from the descending aorta. (2) Despite adequate perfusion pressure bronchial artery blood flow is decreased substantially during CPB. (3) The decrease in blood flow and the ultrastructural changes present at the end of CPB suggest the presence of low-flow ischemia of the lung during total CPB.