Frank Münch

Noninvasive Control of Adequate Cerebral Oxygenation During Low‐Flow Antegrade Selective Cerebral Perfusion on Adults and Infants in the Aortic Arch Surgery

Abstract  Real‐time readings of the regional oxygen saturation (rSO2) using near‐infrared spectroscopy (NIRS) during the aortic arch surgery can provide an early detection of perfusion or oxygenation abnormalities. Background: Aortic arch repair techniques using low‐flow antegrade selective cerebral perfusion have been standardized to a certain degree. However, some of the often‐stated beneficial effects have never been proven. Especially, the existence of an adequate continuous flow in both cerebral hemispheres during the surgical procedure still remains unclear as the monitoring of an effective perfusion remains a nonstandardized technique. Methods: Seventeen patients underwent surgical reconstruction of the aortic arch due to aortic aneurysm surgery (adult group n = 8 patients) or of the hypoplastic aortic arch due to hypoplastic left heart syndrome (HLHS) or aortic coarctation (infant group n = 9 patients) under general anesthesia and mild hypothermia (adult group 28 °C; infant group 25 °C). Mean weights were 92.75 ± 14.00 kg and 4.29 ± 1.32 kg, and mean ages were 58.25 ± 10.19 years and 55.67 ± 51.11 days in the adult group and the infant group, respectively. The cerebral O2 saturation measurement was performed by continuous plotting of the somatic reflectance oximetry of the frontal regional tissue on both cerebral hemispheres (rSO2, INVOS®; Somanetics Corporation, Troy, MI, USA). Results: During low‐flow antegrade perfusion via innominate artery, continuous plots with similar values of O2 saturation (rSO2) in both cerebral hemispheres were observed, whereas a decrease in the rSO2 values below the desaturation threshold correlated with a displacement or an incorrect positioning of the arterial cannula in the right subclavian artery. Conclusions: Continuous monitorization of the cerebral O2 saturation during aortic arch surgery in adults and infants is a feasible technique to control an adequate cannula positioning and to optimize clinical outcomes avoiding neurological complications related to cerebral malperfusion.

Comparative study on the migration of di-2-ethylhexyl phthalate (DEHP) and tri-2-ethylhexyl trimellitate (TOTM) into blood from PVC tubing material of a heart-lung machine.

Medical devices like blood tubing often consist of PVC material that requires the addition of plasticizers. These plasticizers may migrate into the blood leading to an exposure of the patients. In this study the migration behavior of three different blood tubing sets (PVC material with two different plasticizers and silicone as control material) applied on a heart-lung machine standardly used for cardiopulmonary bypass (CPB) in children was studied. We analyzed the total plasticizer migration by analysis of both, the parent compounds as well as their primary degradation products in blood. Additionally, the total mass loss of the tubing over perfusion time was examined. The PVC tubing plasticized with DEHP (di-2-ethylhexyl phthalate) was found to have the highest mass loss over time and showed a high plasticizer migration rate. In comparison, the migration of TOTM (tri-2-ethylhexyl trimellitate) and its primary degradation products was found to be distinctly lower (by a factor of approx. 350). Moreover, it was observed that the storage time of the tubing affects the plasticizer migration rates. In conclusion, the DEHP substitute TOTM promises to be an effective alternative plasticizer for PVC medical devices particularly regarding the decreased migration rate during medical procedures.

Immunohistochemical evaluation after ex vivo perfusion of rectus abdominis muscle flaps in a porcine model.

Background: The purpose of this study was to investigate whether and how the extracorporal perfusion of muscle flaps with a miniaturized perfusion system could change the expression of the proapoptotic protein caspase 3 and of the ischemia-sensitive protein hypoxia-inducible factor (HIF)-1&agr; as a first step toward the development of a clinically reliable tool for circumventing ischemia problems in free muscle flap transfer. Methods: In this study, 25 porcine rectus abdominis muscles were used and assigned to five different groups. In the baseline group (group I), the muscle flap remained in situ; in groups II and III, the muscle flap was harvested and remained ex vivo without or with subsequent single-shot heparinized flush; and in groups IV and V, the flaps were perfused with either heparinized autologous whole blood or crystalloid fluid (Jonosteril), using a miniaturized perfusion system without Exogen oxygenation. Muscle samples were taken for immunohistochemical evaluation. The proportion of positive cells for HIF-1&agr; and caspase 3 was compared for each group (groups II through V) to the baseline group (group I). Results: The expression of HIF-1&agr; and caspase 3 was increased in both groups without perfusion and was low during in vivo perfusion and extracorporal perfusion with crystalloid fluid. Heparinized autologous whole blood perfusion shows no protective effect, in contrast to the crystalloid fluid. Conclusions: The data of this study indicate that the extracorporal perfusion of muscle flaps with crystalloid fluid is a possible protective strategy against ischemia. Autologous heparinized whole blood seems to have no additional protective effect in a pure perfusion setting without oxygenation.

Online oxygen measurements in ex vivo perfused muscle tissue in a porcine model using dynamic quenching methods

IntroductionTransplantation of autologous free tissue flaps is the best applicable technique for treating large and complex tissue defects and still has one major failure criterion. Tissue—and in particular muscle tissue—is strongly sensitive to ischemia, thus after a critical period of oxygen depletion the risk of a partial or total flap loss is high.Materials and methodsFor that reason a miniaturized ex vivo perfusion system has been developed, that supplies the tissue during operational delays. The purpose of this study was to determine the oxygenation levels during such a perfusion using different perfusates and therefore to objectify if a complementary oxygenation unit is required to improve perfusion quality. The oxygen levels of the tissue, as well of the perfusate, were measured by using minimal invasive optical oxygen sensors that are based on dynamic quenching. The ex vivo perfused tissue was the porcine rectus abdominis muscle.ResultsResults show, that during perfusion with heparinized crystalloid fluid (Jonosteril®) and heparinized autologous whole blood, additional oxygenation of the perfusion reactor led to different ex vivo oxygen tissue saturations, which can be detected by dynamic quenching.ConclusionDynamic quenching methods are a promising and valuable technique to perform online oxygen measurements in ex vivo perfused muscle tissue in a porcine model.

Ischaemia-related cell damage in extracorporeal preserved tissue - new findings with a novel perfusion model.

Tissue undergoing free transfer in transplant or reconstructive surgery always is at high risk of ischaemia‐related cell damage. This study aims at assessing different procedures using an extracorporeal perfusion and oxygenation system to investigate the expression of hypoxia inducible factor (HIF)‐1‐α as marker for hypoxia and of the pro‐apoptotic protein Caspase‐3 in skeletal muscle to elucidate potential improvements in tissue conservation. Twenty‐four porcine rectus abdominis muscles were assigned to five different groups and examined after they had been extracorporeally preserved for 60 min. time. Group I was left untreated (control), group II was perfused with a cardioplegic solution, group III was flushed with 10 ml of a cardioplegic solution and then left untreated. Group IV and V were perfused and oxygenated with either an isotone crystalloid solution or a cardioplegic solution. Among others, immunohistochemistry (Caspase‐3 and HIF‐1‐α) of muscle samples was performed. Furthermore, oxygen partial pressure in the perfusate at the arterial and venous branch was measured. Expression of Caspase‐3 after 60 min. was reduced in all groups compared to the control group. Furthermore, all groups (except group III) expressed less HIF‐1‐α than the control group. Oxygenation leads to higher oxygen levels at the venous branch compared to groups without oxygenation. Using an extracorporeal perfusion and oxygenation system cell damage could be reduced as indicated by stabilized expressions of Caspase‐3 and HIF‐1‐α for 60 min. of tissue preservation. Complete depletion of oxygen at the venous branch can be prevented by oxygenation of the perfusate with ambient air.

Pediatric Extracorporeal Life Support Using a Third Generation Diagonal Pump.

This study reports a single-centre experience of the Medos Deltastream diagonal-pump (DP3) for extracorporeal cardiac, pulmonary, or combined support in a single-center pediatric cohort. Twenty-seven consecutive patients with 28 runs of the DP3 between January 2013 and June 2014 were included for analysis. Median patient age, weight, and duration of support were 278 days (range: 0 days–14.2 years), 7.2 kg (range: 2.5–39 kg), and 8 days (range: 2–69 days). Midline sternotomy (n = 20, 71.4%) or cervical approaches (n = 8, 28.6%) were used for cannulation. The DP3 was employed for either veno-arterial extracorporeal life support (ECLS, n = 16), veno-venous extracorporeal membrane oxygenation (ECMO, n = 5), or ventricular assist devices (right ventricular assist device [RVAD], n = 1; left ventricular assist device [LVAD], n = 1; and univentricular assist device [UNIVAD], n = 5). Three patients initially supported with ECLS were switched to UNIVAD and one patient with UNIVAD was changed to ECLS. Required flow for neonates (n = 8) ranged between 0.2 and 0.75 L/min. Irreversible pump damage occurred in one patient during deairing after air block. Successful weaning, 30 day and hospital survival were 89.3% (n = 25), 85.7% (n = 24), and 71.4% (n = 20). All patients on UNIVAD, who did not require further extracorporeal respiratory assist, survived. In conclusion, the DP3 can be used for individual patient demands and adapted to their most suitable method of support. Meticulous flow adjustments render this pump highly effective for extracorporeal support particularly in pediatric patients.

Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time

Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research.

Myocardial Protection During Aortic Arch Repair in a Piglet Model: Beating Heart Technique Compared With Crystalloid Cardioplegia

BACKGROUND Selective myocardial perfusion enables repair of congenital aortic arch obstruction without cardiac arrest. This study was inspired by the lack of prospective controlled studies of the beating heart (BH) technique compared with cold crystalloid cardioplegia (CC) regarding effects on myocardial performance, ischemic damage, and serum electrolyte levels. METHODS In a prospective study, 20 male piglets weighing 11.1 ± 1.3 kg were operated on using cardiopulmonary bypass (CPB) and underwent 60 minutes of aortic cross-clamping. According to prospective randomization, myocardial protection included either a BH modification with selective myocardial perfusion using an individual roller pump or CC. Hemodynamic performance was evaluated by a conductance catheter technique before and after CPB and calculated in relation to baseline levels. Laboratory analysis included blood levels of troponin T and serum electrolytes. RESULTS Eighteen piglets entered analysis. There were significantly higher slopes of end-systolic pressure-volume relations (168% ± 92% versus 89% ± 16%; p = 0.046) and preload-recruitable stroke work (PRSW) (139% ± 37% versus 103% ± 31%; p = 0.040) in BH piglets compared with those who underwent CC. Laboratory analysis during reperfusion revealed higher levels of troponin T (1.31 ± 0.28 ng/mL versus 0.49 ± 0.17 ng/mL; p < 0.01) and sodium (131 ± 4 mmol/L versus 120 ± 8 mmol/L; p = 0.003) and lower levels of potassium (4.8 ± 0.4 mmol/L versus 6.4 ± 1.0 mmol/L; p = 0.001) with BH compared with CC, whereas no significant differences were calculated at the end of the experiment. CONCLUSIONS The BH technique is associated with improved contractility compared with standard CC. There is comparable ischemic damage in both groups, with an earlier rise in blood levels of troponin T after BH and more fluctuation of serum electrolytes with CC. Evidence of ischemic changes should dissuade one from using the BH technique imprudently.

Improved contractility with tepid modified full blood cardioplegia compared with cold crystalloid cardioplegia in a piglet model

OBJECTIVES Experience regarding warm blood cardioplegia according to Calafiore results from its broad use in adult patients. In this experimental study, tepid (28°C) modified full blood cardioplegia (MBC) was adopted for paediatric use and compared with cold crystalloid cardioplegia (CCC). METHODS Twenty male piglets (mean weight: 11.1 ± 1.0 kg) were operated on cardiopulmonary bypass (CPB) in moderate hypothermia (28°C) and randomized to MBC (n = 8) or CCC (n = 12) for 60 min aortic cross-clamping. Blood levels of myocardial proteins [N-terminal pro-brain natriuretic peptide (NT-pro-BNP), myoglobin, creatine kinase type MB and troponin-I] were investigated at the beginning of the experiment and after CPB. Haemodynamic measurements included thermodilution and conductance-catheter technique inserted through the left ventricle-apex. Pressure-volume loop analysis was performed with dobutamine-stress test and inflow occlusion, enabling preload independent evaluation of myocardial performance. Changes of measured data post-CPB were calculated in relation to baseline-levels (%). RESULTS Baseline and operative data in both groups were similar. During the experiment, cardiac markers showed no significant variations between groups. Pressure-volume loop analysis during stress test revealed a significantly higher preload independent contractility (slope of end-systolic pressure-volume relation: Ees) with MBC compared with CCC (MBC: 123 ± 35% [confidence interval (CI95): 93-153] vs CCC: 78 ± 34% [CI95: 54-102]; P = 0.042), whereas cardiac output was not significantly different between groups {MBC: 122 ± 16% [95% confidence interval (CI95): 109-135] vs CCC: 105 ± 17% [CI95: 93-116]; P = 0.069}. CONCLUSION This randomized animal study proves feasibility and safety of MBC for paediatric use. Haemodynamic evaluation and cardiac markers did not show inferiority to standard CCC. Moreover, MBC seems to be associated with superior contractility post bypass, which encourages us to use MBC in paediatric patients in the near future.

Effect of phospholipid coating on the migration of plasticizers from PVC tubes

Plasticizers in polyvinyl chloride (PVC) are not covalently bound to the polymer and can thus migrate into the contact medium. The presented study investigated the potential effects of phospholipid-lining as anti-coagulation coating (ACC) on the migration rate of plasticizers from PVC tubing into blood. For the in-vitro study, five different groups of tubing sets in six replicates were perfused with sheep blood (Group A: PVC plasticized with di-(2-ethylhexyl) phthalate (DEHP) without ACC, Group B: DEHP-plasticized PVC with ACC, Group C: PVC plasticized with tri-(2-ethylhexyl) trimellitate (TOTM) without ACC, Group D: TOTM-plasticized PVC with ACC, Group E (control group): polyolefin material with ACC but without plasticizers). Both the levels of the unchanged plasticizers in blood and the concentration levels of their primary degradation products were assessed. For DEHP, the primary metabolite MEHP (mono-(2-ethylhexyl) phthalate) was determined. The isomers of MEHTM (mono-(2-ethylhexyl) trimellitate) and DEHTM (di-(2-ethylhexyl) trimellitate), respectively, were investigated as primary metabolites of TOTM. The calculated DEHP equivalents (sum of determined levels of DEHP and MEHP) after 24 h of perfusion displayed a tendency towards lower levels in the tubing sets without ACC (Group A (201 ± 56.4 μmol/L)) compared to the tubing sets with ACC (Group B (253 ± 369 μmol/L)). Significantly different DEHP equivalents between Group A and Group B were found after a perfusion time of 6 h and 10 h, respectively. A similar effect was observed for the TOTM-containing tubing sets. However, the absolute plasticizer migration rate of TOTM (TOTM equivalents) after 24 h of perfusion was found to be significantly lower compared to that of DEHP (with a factor of over 200). The results indicate that phospholipid coating (ACC) rather enhances the migration of plasticizers and of their primary degradation products from PVC tubing into streaming blood. The enhancement effect was found to be slightly greater for TOTM, but as TOTM migrates in significantly lower levels than DEHP in all experimental settings, TOTM is confirmed to be a recommendable alternative plasticizer to DEHP in medical devices.