Christoph Krapf

Remote access perfusion for minimally invasive cardiac surgery: to clamp or to inflate?

OBJECTIVES Endoaortic balloon occlusion (EBO) and aortic transthoracic clamping (TTC) are the dominant methods of remote access perfusion (RAP) in minimally invasive cardiac surgery. The aim of the study was to compare the two methods in terms of feasibility, success and complications. METHODS From June 2001 to November 2011, 307 (median age; range) (57; 16-77 years) and 460 (62; 11-88 years) patients underwent minimally invasive CABG, ASD and mitral valve surgery using EBO and TTC, respectively. Perioperative procedure feasibility, success and postoperative complications were recorded. RESULTS Overall 30-day mortality was 0 and 2 (0.43%) for the EBO and TTC groups, respectively (P = 0.52). Overall and RAP-associated conversions were noted in 21 (6.8%) and 4 (1.3%) patients in the EBO and in 9 (2%) and 6 (1.3%) patients in the TTC groups (P < 0.001, P = 1.00, respectively). Incidence of major complications, including aortic dissection, major vessel perforation, injury of intrapericardial structures, limb ischaemia, myocardial infarction and neurologic events, was similar [EBO: 12 (4%); TTC: 11 (2.4%); P = 0.23]. Minor complications such as minor vessel injury, groin bleeding or lymphatic fistula were noted in 31 (10.1%) and 35 (7.6%), respectively (P = 0.23). Successful RAP procedures defined as absence of RAP-associated conversions and major complications were equal [EBO: 295 (96%); TTC: 449 (97.6%); P = 0.23]. Complications detected during follow-up included pain: 30 of 249 (12%) and 13 of 279 (4.7%) (P = 0.002); sensational disturbances: 60 of 249 (24.1%) and 40 of 278 (14.4%) (P = 0.005) and wound-healing complications: 49 of 249 (19.7%) and 42 of 277 (15.2%) (P = 0.172) for EBO and TTC, respectively. CONCLUSIONS RAP can be successfully and safely implemented in minimally invasive cardiac surgery. EBO and transthoracic clamping of the ascending aorta are performing equally in terms of feasibility and procedural success.

Mechanisms and mediators of inflammation: potential models for skin rejection and targeted therapy in vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) is an effective treatment option for patients suffering from limb loss or severe disfigurement. However, postoperative courses of VCA recipients have been complicated by skin rejection, and long-term immunosuppression remains a necessity for allograft survival. To widen the scope of this quality-of-life improving procedure minimization of immunosuppression in order to limit risks and side effects is needed. In some aspects, the molecular mechanisms and dynamics of skin allograft rejection seem similar to inflammatory skin conditions. T cells are key players in skin rejection and are recruited to the skin via activation of adhesion molecules, cytokines, and chemokines. Blocking these molecules has not only shown success in the treatment of inflammatory dermatoses, but also prolonged graft survival in various models of solid organ transplantation. In addition to T cell recruitment, ectopic lymphoid structures within the allograft associated with chronic rejection in solid organ transplantation might contribute to the strong alloimmune response towards the skin. Selectively targeting the molecules involved offers exciting novel therapeutic options in the prevention and treatment of skin rejection after VCA.

Histomorphometric evaluation of ischemia-reperfusion injury and the effect of preservation solutions histidine-tryptophan-ketoglutarate and University of Wisconsin in limb transplantation.

Background The effect of cold ischemia (CI) in vascularized composite allotransplantation is unknown. We herein assess tissue-specific damage, acceptable CI time, and the effect of preservation solutions in a syngenic rat hindlimb transplant model. Methods Lewis rat limbs were flushed and stored for 2, 10, or 30 hr CI in saline, histidine-tryptophan-ketoglutarate or University of Wisconsin preservation solution before transplantation. Morphologic alterations, inflammation, and damage of the individual tissues were analyzed on day 10 using histomorphology, confocal, light, and transmission-electron microscopy. Results Two-hour CI led to mild inflammation of tissues on day 10, whereas 10-hr and 30-hr CI resulted in massive inflammation and tissue damage. Although muscle was mainly affected after prolonged CI (≥10 hr), nerve was affected in all CI groups. A perineural cell infiltrate, hypercellular appearance, pronounced vacuolization, and mucoid degeneration, appearing as Wallerian degeneration, were observed. Staining with propidium iodide and Syto 16 revealed a decrease in viable muscle cell nuclei in the anterior tibial muscle on day 10 in all groups, which was most pronounced in 10-hr and 30-hr CI animals. Transmission-electron microscopy indicated that a large number of mitochondria were degenerated in the 10-hr and 30-hr CI groups. Histidine-tryptophan-ketoglutarate preservation solution slightly decreased inflammation and tissue damage compared to University of Wisconsin-treated and saline-treated animals, especially in skin and muscle when CI times did not exceed 10 hr. Conclusion Severe inflammation and tissue damage are observed after prolonged CI in muscle and nerve. Ischemia times in vascularized composite allotransplantation should be kept as short as possible and certainly below 10 hr.

Toll-like receptor 3 signalling mediates angiogenic response upon shock wave treatment of ischaemic muscle

AIMS Shock wave therapy (SWT) represents a clinically widely used angiogenic and thus regenerative approach for the treatment of ischaemic heart or limb disease. Despite promising results in preclinical and clinical trials, the exact mechanism of action remains unknown. Toll-like receptor 3, which is part of the innate immunity, is activated by binding double-stranded (ds) RNA. It plays a key role in inflammation, a process that is needed also for angiogenesis. We hypothesize that SWT causes cellular cavitation without damaging the target cells, thus liberating cytoplasmic RNA that in turn activates TLR3. METHODS AND RESULTS SWT induces TLR3 and IFN-β1 gene expression as well as RNA liberation from endothelial cells in a time-dependant manner. Conditioned medium from SWT-treated HUVECs induced TLR3 signalling in reporter cells. The response was lost when the medium was treated with RNase III to abolish dsRNAs or when TLR3 was silenced using siRNAs. In a mouse hind limb ischaemia model using wt and TLR3(-/-) mice (n = 6), SWT induced angiogenesis and arteriogenesis only in wt animals. These effects were accompanied by improved blood perfusion of treated limbs. Analysis of main molecules of the TLR3 pathways confirmed TLR3 signalling in vivo following SWT. CONCLUSION Our data reveal a central role of the innate immune system, namely Toll-like receptor 3, to mediate angiogenesis upon release of cytoplasmic RNAs by mechanotransduction of SWT.

Targeting the Kv1.3 potassium channel for immunosuppression in vascularized composite allotransplantation – a pilot study

Kv1.3‐channels are critically involved in activation and function of effector memory T cells. Blocking Kv1.3‐channels was investigated for its effect on skin rejection in a rat limb‐transplantation‐model. Animals received the Kv1.3‐blocker correolide C systemically or locally as intra‐graft‐treatment in combination with tacrolimus. Systemic (intraperitoneal) administration of correolide C resulted in slight, but significant prolongation of allograft survival compared with untreated and placebo treated controls. In 4/6 correolide C treated animals, histology showed an intact epidermis and a mild infiltrate by day 10. High correolide C plasma trough levels correlated with prolonged allograft survival. A decrease in CD4+ and CD8+ effector memory T cells was observed in allograft skin, peripheral blood and the spleen on day 5. When applied subcutaneously in combination with systemic tacrolimus (30 days+/−anti‐lymphocyte serum) detectable, but insignificant prolongation of graft survival was achieved. 2/5 animals showed an intact epidermis and a mild infiltrate until day 45. Tapering systemic tacrolimus and weaning on day 50 resulted in rejection by day 55, regardless of local correolide C treatment. Subcutaneous injection did not lead to systemic plasma levels. The Kv1.3‐channel is a potential drug target worth exploring in more detail for immunosuppression in vascularized composite allotransplantation.

Aortic dissection type A in alpine skiers.

Patients and Methods. 140 patients with aortic dissection type A were admitted for cardiac surgery. Seventy-seven patients experienced their dissection in the winter season (from November to April). We analyzed cases of ascending aortic dissection associated with alpine skiing. Results. In 17 patients we found skiing-related aortic dissections. Skiers were taller (180 (172–200) cm versus 175 (157–191) cm, P = 0.008) and heavier (90 (68–125) kg versus 80 (45–110) kg, P = 0.002) than nonskiers. An extension of aortic dissection into the aortic arch, the descending thoracic aorta, and the abdominal aorta was found in 91%, 74%, and 69%, respectively, with no significant difference between skiers and nonskiers. Skiers experienced RCA ostium dissection requiring CABG in 17.6% while this was true for 5% of nonskiers (P = 0.086). Hospital mortality of skiers was 6% versus 13% in nonskiers (P = 0.399). The skiers live at an altitude of 170 (0–853) m.a.s.l. and experience their dissection at 1602 (1185–3105; P < 0.001) m.a.s.l. In 82% symptom start was during recreational skiing without any trauma. Conclusion. Skiing associated aortic dissection type A is usually nontraumatic. The persons affected live at low altitudes and practice an outdoor sport at unusual high altitude at cold temperatures. Postoperative outcome is good.

Aorto-Esophageal Fistula After Thoracic Endovascular Aortic Repair: Successful Open Treatment

We present the case of a 56-year-old patient suffering from an aorto-esophageal fistula after complex treatment of acute Type A dissection including thoracic endovascular aortic repair (TEVAR) of the descending aorta. Open surgical descending replacement using a pericardial patch, as well as esophagectomy, was performed. After a long and complicated hospital stay, the patient finally recovered and was discharged in stable condition. By choosing an aggressive surgical approach the patient survived this devastating complication of TEVAR, which is associated with high mortality.

Stroke after emergent surgery for acute type A aortic dissection: predictors, outcome and neurological recovery

OBJECTIVES Despite improvement in operative and cerebral perfusion techniques, cerebral malperfusion and neurological injury remain a dreaded complication of acute type A aortic dissection. We aimed to identify predictors for postoperative stroke and analyse the impact on morbidity, neurological recovery and mid-term survival. METHODS Between 2000 and 2017, 303 (71.9% men, mean age 58.9 ± 13.6 years) patients with acute type A aortic dissection underwent surgical repair. Clinical and imaging data were retrospectively evaluated. Patients were divided into 2 groups depending on the presence of postoperative stroke. RESULTS Postoperative stroke was detected in 15.8% (n = 48) of the patients. Patients with postoperative stroke showed higher rates of preoperative cardiopulmonary resuscitation (stroke: 18.8% vs no stroke: 3.5%, P < 0.001) and malperfusion syndrome (stroke: 47.9% vs no stroke: 22.4%, P < 0.001). Multivariable analysis identified the presence of bovine aortic arch [odds ratio (OR) 2.33, 95% confidence interval (CI) 1.086-4.998; P = 0.030], preoperative cardiopulmonary resuscitation (OR 6.483, 95% CI 1.522-27.616; P = 0.011) and preoperative malperfusion (OR 2.536, 95% CI 1.238-5.194; P = 0.011) as independent predictors for postoperative stroke. Postoperative stroke had a strong impact on morbidity and was associated with higher rates of postoperative complications and a significantly longer hospital stay (stroke: 23 ± 16 days vs no stroke: 17 ± 18 days, P = 0.021). Postoperative stroke was not independently associated with in-hospital mortality (adjusted OR 1.382, 95% CI 0.518-3.687; P = 0.518). There was no difference in mid-term survival between patients with stroke and patients without stroke. CONCLUSIONS This study identified independent preoperative predictors for postoperative stroke. Although postoperative stroke was associated with significant morbidity and postoperative complications, significant impairment in mid-term survival could not be confirmed by the data.