Joerg Haberstroh

Effect on Intimal Hyperplasia of Dexamethasone Released from Coated Metal Stents Compared with Non-Coated Stents in Canine Femoral Arteries

AbstractPurpose: Polymer-coated, dexamethasone (DXM)-releasing stents were tested in order to assess the efficacy of DXM released locally for the prevention of stent restenosis due to intimal hyperplasia. Methods: Strecker stents coated with a biodegradable membrane containing DXM were implanted percutaneously into the femoral artery in 14 dogs. The contralateral artery received a conventional non-coated stent serving as control. The drugs are eluted by degradation of the carrier membrane. Follow-up intraarterial digital subtraction angiography (DSA) was obtained at 3, 6, 9, 12, and 24 weeks with subsequent autopsy. Specimens for gross and microscopic pathology were obtained and histomorphometry was performed. Results: Four of 14 DXM-coated stents showed thrombotic occlusion within the first 3 weeks; ten DXM-coated stents remained patent. At follow-up DSA, DXM-coated stents showed a significantly wider lumen than the non-coated stents. At morphometry there was less intimal hyperplasia over DXM-coated stents than over non-coated stents (p<0.05). Conclusion: DXM-coated stents reduce neointimal hyperplasia in dogs when compared with non-coated stents.

Successful orthotopic pig heart transplantation from non-heart-beating donors.

BACKGROUND With the aim to expand the severely limited donor pool by use of non-heart-beating donors we developed a technique for successful transplantation of hearts after 30 minutes of normothermic ischemia without donor pretreatment. METHODS In control groups hearts were transplanted in a conventional fashion using crystalloid cardioplegia (Group I, n = 6) or BCP (Group II, n = 8) for induction of cardiac arrest. In the ischemic groups hearts were harvested after 30 minutes of normothermic ischemia, perfused with blood cardioplegia (BCP) (Group III, n = 9) or BCP containing the Na(+)-H(+)-exchange inhibitor HOE 642 (Group IV, n = 8) and transplanted orthotopically. RESULTS All animals could be weaned from cardiopulmonary bypass. Low dose inotropic support was necessary in the ischemic groups only. Recovery of the maximal left ventricular stroke work index (LVSWImax) in Groups I vs II was 62.6+/-19.6% vs 73.3+/-23.3% (NS), maximal right ventricular stroke work index (RVSWImax) averaged 61.1+/-18.8 vs 87.8+/-31.7% (NS) as compared to the preoperative level. In the ischemic groups (III vs IV) LVSWImax was 27.3+/-11.7 vs 59.5+/-32.4% (p = 0.038), RVSWImax was 27.4+/-20.9 vs 64.2+/-46.6% (NS). CONCLUSIONS The results indicate that (a) successful pig heart transplantation after 30 minutes of normothermic ischemia is possible without donor pretreatment, and (b) that HOE 642 improves posttransplant LVSWImax significantly.

Orthotopic transplantation of pig hearts harvested after 30 min of normothermic ischemia: controlled reperfusion with blood cardioplegia containing the Na+-H+-exchange inhibitor HOE 642

OBJECTIVES The aim of our study was to develop a surgical technique for a successful transplantation of hearts harvested after 30 min of normothermic ischemia without donor pretreatment. Successful transplantation of ischemic compromised hearts could help to expand the severely limited donor pool. We used the pig model because this species is very susceptible to myocardial ischemia. Na+-H+-exchange (NHE) inhibitors have shown excellent protective properties in several in vitro and in vivo models of myocardial ischemia and reperfusion. METHODS In group I (n=12) hearts were harvested after 30 min of normothermic ischemia following cardiac arrest induced by exsanguination. Hearts were perfused with warm blood cardioplegia and transplanted orthotopically. In group II (n=9) controlled reperfusion with cold leucocyte-depleted blood cardioplegia was performed after 30 min of normothermic ischemia. In group III (n=8) the same procedure was performed as in group II but blood cardioplegia contained 1 mmol/l HOE 642. RESULTS In group I massive myocardial oedema was observed and none of the animals could be weaned from cardiopulmonary bypass (CPB). In contrast, all animals in groups II and III could be weaned from CPB with low dose inotropic support. In groups II and III the contractility of the hearts, expressed as maximal left and right ventricular stroke work index was significantly impaired after transplantation as compared with the preoperative value. Supplementation of blood cardioplegia with HOE 642 resulted in a significantly better recovery of the LVSWImax (Group II vs. III). CONCLUSIONS Successful transplantation of pig hearts is possible after 30 min of normothermic ischemia without donor pretreatment if a controlled reperfusion with cold leucocyte-depleted blood cardioplegia is performed. HOE 642 given during reperfusion only improves posttransplant left ventricular function.

Vein Graft-Coated Vascular Stents: A Feasibility Study in a Canine Model

AbstractPurpose: To evaluate different vein grafts for luminal coating of endovascular stents in normal canine arteries. Methods: Twenty-four tantalum Strecker stents were coated with either autologous (n= 10), denatured heterologous (n= 11), or denatured homologous vein grafts (n= 3). The carotid artery (n= 11) and the iliac artery (n= 13) were stented using a transfemoral approach. Angiograms were performed at days 0, 7, and 21, and months 3, 6, and 9. All grafts underwent histological examination. Results: Eight of 10 autologous vein grafts showed patency during the whole observation period of 9 months, without histological signs of inflammation. Denatured heterologous vein grafts revealed acute (n= 3), subacute (n= 5), or delayed (n= 3) vessel occlusion. Hyaloid transformation of the vein graft and lympho-plasmacellular formations were seen. Denatured homologous vein grafts showed acute vessel occlusion. Although significant inflammatory tissue response was seen, no host-versus-graft reaction was present. Conclusion: Autologous vein graft-coated stents showed good biocompatibility in canine arteries. Preparation was cumbersome and required surgical venae-sectio. Denatured vein grafts, however, were limited by inflammatory reactions.

Thoracic endovascular stent grafting inhibits aortic growth: an experimental study.

OBJECTIVE Dilatation of the aorta at the landing zone site may be exaggerated by the radial force of stent grafts potentially limiting long-term results of endovascular therapy. We evaluated growth patterns and morphology of the thoracic aorta in young piglets after thoracic stent-graft placement. METHODS Eight domestic piglets (37+/-2 kg) had an endovascular stent graft placed in the proximal descending thoracic aorta using retroperitoneal access. At implantation, the stent was oversized by 10%. Aortic size was documented after thoracotomy by intraoperative measurement and angiography. Subsequently the piglets were grown to adult size (181+/-42 kg). At explantation 6-15 months later, CT scan and surgical evaluation for endoleaks, defined as perigraft flow, was performed. Histopathological assessment of the explanted aorta was performed in stented and non-stented segments and compared to five normal porcine aortas. RESULTS No endoleak (perigraft flow) or stent migration occurred even in 230kg pigs. The stent grafts expanded to full size, but there was no further growth in the stented area. The aortic diameter increased significantly by 32+/-9% 1cm proximal to the stents (p=0.0012) and by 45+/-13% 1cm distal to the stents (p=0.0033). The stented area grew less than the proximal (p=0.0011) and distal aorta (p<0.0001). In all pigs, the distal aorta was larger than the proximal overstented segment. Histology of the stented aorta showed significant thickening of the intima (p=0.018) and media (p=0.006) with neointimal formation and segmental fibrosis of the inner 1/3 of the media with loss of smooth muscle cells and compression of the elastic fibers but normal architecture in the outer 2/3 of the media. CONCLUSIONS Endovascular stent grafting may inhibit growth of the nonatherosclerotic normal aorta and lead to intimal hyperplasia and focal fibrosis in the inner media part adjacent to the stent. Stent-graft interaction with aortic tissue over time is important and should receive more detailed evaluation. Testing this interaction in an animal model of nonatherosclerotic dilative aortic disease could be of great interest.

Mapping of sheep sensory cortex with a novel microelectrocorticography grid.

Microelectrocorticography (µECoG) provides insights into the cortical organization with high temporal and spatial resolution desirable for better understanding of neural information processing. Here we evaluated the use of µECoG for detailed cortical recording of somatosensory evoked potentials (SEPs) in an ovine model. The approach to the cortex was planned using an MRI‐based 3D model of the sheeps brain. We describe a minimally extended surgical procedure allowing placement of two different µECoG grids on the somatosensory cortex. With this small craniotomy, the frontal sinus was kept intact, thus keeping the surgical site sterile and making this approach suitable for chronic implantations. We evaluated the procedure for chronic implantation of an encapsulated µECoG recording system. During acute and chronic recordings, significant SEP responses in the triangle between the ansate, diagonal, and coronal sulcus were identified in all animals. Stimulation of the nose, upper lip, lower lip, and chin caused a somatotopic lateral‐to‐medial, ipsilateral response pattern. With repetitive recordings of SEPs, this somatotopic pattern was reliably recorded for up to 16 weeks. The findings of this study confirm the previously postulated ipsilateral, somatotopic organization of the sheeps sensory cortex. High gamma band activity was spatially most specific in the comparison of different frequency components of the somatosensory evoked response. This study provides a basis for further acute and chronic investigations of the sheeps sensory cortex by characterizing its exact position, its functional properties, and the surgical approach with respect to macroanatomical landmarks. J. Comp. Neurol. 522:3590–3608, 2014.

Investigations on the new free radical scavenger polynitroxyl-albumin to prevent ischemia and reperfusion injury after orthotopic heart transplantation in the pig model

OBJECTIVE Nitroxides have strong antioxidant capacity but their effectiveness is limited by their rapid intracellular inactivation. Polynitroxyl-Albumin (PNA) is capable of regenerating inactivated nitroxide. We tested the effect of PNA against reperfusion injury in heart transplantation. METHODS Pig hearts were transplanted orthotopically. In the control group (n=9) reperfusion was performed without reperfusion modifications. In the experimental group (n=10) 1 ml/kg PNA was given before cross-clamp release. RESULTS Hemodynamic performance was impaired after transplantation in both groups without significant intergroup differences. Plasma malonedialdehyde levels were significantly diminished in the PNA group as compared to the controls. CK-MB levels in both groups were increased within the first 2 h of reperfusion without significant intergroup differences. In contrast, there were found significant higher values of myocardial specific lactate dehydrogenase (LD1) in the controls versus PNA group. CONCLUSIONS PNA was able to reduce lipid peroxidation and attenuate free radical activity. Contractile dysfunction could no be improved, indicating that (a) the radical scavenging effect was to weak or (b) other mechanisms than free oxygen radicals are responsible for myocardial damage in this experimental model.

Heterotopic transplantation of cryopreserved tracheae in a rat model

INTRODUCTION The successful use of cryopreserved tracheal allografts in canine models suggests their use in humans. The grade of genetic difference, the mechanism of revascularisation and the method of cryopreservation are not clearly defined. The purpose of our study was to investigate the rejection of tracheal transplants in a standardised heterotopic rat model using different forms of cryopreservation. METHODS Tracheae from Brown Norway rats were implanted into the omentum from Brown Norway rats or Lewis rats. We transplanted fresh isografts or allografts and pretreated isografts or allografts. Cryopreservation was performed in a medium containing 10% dimethyl sulphoxide at -80 degrees C for 28 days (I) or -196 degrees C for 84 days (II) or without medium at -80 degrees C for 28 days (III). The transplants were excised after 7 and 21 days, respectively. RESULTS Histological examinations revealed normal structure and function of isografts after 21 days. In the cryopreserved isograft, the epithelium had disappeared and the tracheal lumen was partially obstructed by a non-compact fibrous tissue. In the fresh allografts, the epithelium was replaced by aggressive fibrous tissue, infiltrating the membranous part of the trachea and occluding the tracheal lumen. The cartilage was vital without any sign of rejection. In the cryopreserved allografts, the tracheal lumen was obstructed by dense fibrous tissue with an inflammatory reaction. The cartilage of cryopreserved allografts (II) and (III) had lost the nuclei corresponding to non-vital tissue. Only in the cryopreserved allografts (I) did we find nodular regeneration at the edges of the cartilaginous bow. CONCLUSIONS The heterotopic transplantation model allows the study of the mechanisms leading to tracheal obstruction. Cryopreservation was found to have no clear advantage in reducing transplant immunogenicity. Cryopreservation leads to significant damage to the cartilage, the intensity of which is dependent on the mode of cryopreservation.

Development of a New Intravascular Low-Profile Device for Exclusion of Aortic Aneurysm: An Experimental Pilot Study

AbstractPurpose: To present a new intravascular device for the treatment of aorto-iliac aneurysms. Methods: This new device was tested in five dogs with abdominal aortic aneurysm created experimentally by overdilation of a balloon-expandable stent with a 16 or 18 mm wide PTA balloon catheter. The design of the device is based on a self-expanding aortic stent which consists of two stretchable circular frames filled with a textile Dacron mesh membrane that is suspended horizontally into the infrarenal abdominal aorta proximally to the aneurysm. The frames are part of a preshaped double helical structure that is introduced longitudinally through a catheter in a parallel fashion and forming the desired shape at the vessel site to be occluded. Two iliac stent-grafts are introduced in a low-profile status through the membrane sealing the aneurysm sac and holding the stent-grafts in place. After stent-graft expansion, a new bifurcation located more proximally than the natural one is created. The follow-up of the dogs was performed clinically and angiographically, and specimens were evaluated histomorphologically. Results: The membrane device can be introduced through a 9 Fr vascular sheath. Technical success was achieved in four of five dogs. Nine of ten stent-grafts could be fixed securely within the membrane, thus preventing dislocation. Aneurysms were excluded immediately, and blood flow to the external iliac arteries was restored by the stent-grafts. At 6–9 months follow-up of technically successful implanted devices, there were no endoleaks, no migration, no stenoses at contact sites between the implant material and vascular wall, and no stenosis or occlusion of the stent-grafts. At microscopic evaluation, the interspace between the membranes was filled with thrombotic material, thus ensuring exclusion of the aneurysm. Conclusion: This new device was found to be flexible, low profile and useful in excluding abdominal aortic aneurysm in the experimental setting.

Standardized model of porcine resuscitation using a custom-made resuscitation board results in optimal hemodynamic management

Aim Standardized modeling of cardiac arrest and cardiopulmonary resuscitation (CPR) is crucial to evaluate new treatment options. Experimental porcine models are ideal, closely mimicking human‐like physiology. However, anteroposterior chest diameter differs significantly, being larger in pigs and thus poses a challenge to achieve adequate perfusion pressures and consequently hemodynamics during CPR, which are commonly achieved during human resuscitation. The aim was to prove that standardized resuscitation is feasible and renders adequate hemodynamics and perfusion in pigs, using a specifically designed resuscitation board for a pneumatic chest compression device. Methods and results A “porcine‐fit” resuscitation board was designed for our experiments to optimally use a pneumatic compression device (LUCAS® II, Physio‐Control Inc.), which is widely employed in emergency medicine and ideal in an experimental setting due to its high standardization. Asphyxial cardiac arrest was induced in 10 German hybrid landrace pigs and cardiopulmonary resuscitation was performed according to ERC/AHA 2015 guidelines with mechanical chest compressions. Hemodynamics were measured in the carotid and pulmonary artery. Furthermore, arterial blood gas was drawn to assess oxygenation and tissue perfusion. The custom‐designed resuscitation board in combination with the LUCAS® device demonstrated highly sufficient performance regarding hemodynamics during CPR (mean arterial blood pressure, MAP 46 ± 1 mmHg and mean pulmonary artery pressure, mPAP of 36 ± 1 mmHg over the course of CPR). MAP returned to baseline values at 2 h after ROSC (80 ± 4 mmHg), requiring moderate doses of vasopressors. Furthermore, stroke volume and contractility were analyzed using pulse contour analysis (106 ± 3 ml and 1097 ± 22 mmHg/s during CPR). Blood gas analysis revealed CPR‐typical changes, normalizing in the due course. Thermodilution parameters did not show persistent intravascular volume shift. Conclusion Standardized cardiopulmonary resuscitation is feasible in a porcine model, achieving adequate hemodynamics and consecutive tissue perfusion of consistent quality.