TY - JOUR
AU - Etz, Christian D
AB - Abstract Open in new tabDownload slide Open in new tabDownload slide OBJECTIVES Distal aortic perfusion (DaP) is a widely accepted protective adjunct facilitating early reinstitution of visceral perfusion during extended thoracic and thoraco-abdominal aortic repair. DaP has also been suggested to secure distal inflow to the paraspinal collateral network via the hypogastric arteries and thereby reduce the risk of spinal cord ischaemia. However, an increase in cerebrospinal fluid (CSF) pressure is frequently observed during thoracoabdominal aortic aneurysm repair. The aim of this study was to evaluate the effects of DaP on regional spinal cord blood flow (SCBF) during descending aortic cross-clamping and iatrogenic elevation of cerebrospinal fluid pressure. METHODS Eight juvenile pigs underwent central cannulation for cardiopulmonary bypass according to our established experimental protocol followed by aortic cross-clamping of the descending thoracic and abdominal aorta—mimicking sequential aortic clamping—with the initiation of DaP. Thereafter, CSF pressure elevation was induced by the infusion of blood plasma until baseline CSF pressure was tripled. At each time-point, microspheres of different colours were injected allowing for regional SCBF analysis. RESULTS DaP led to a pronounced hyperperfusion of the distal spinal cord [SCBF up to 480%, standard deviation (SD): 313%, compared to baseline]. However, DaP provided no or only limited additional flow to the upper and middle segments of the spinal cord (C1–Th7: 5% of baseline, SD: 5%; Th8–L2: 24%, SD: 39%), which was compensated by proximal flow only at C1–Th7 level. Furthermore, DaP could not counteract an experimental CSF pressure elevation, which led to a further decrease in regional SCBF most pronounced in the mid-thoracic spinal cord segment. CONCLUSIONS Protective DaP during thoraco-abdominal aortic repair may be associated with inadequate spinal protection particularly at the mid-thoracic spinal cord level (‘watershed area’) and result in the adverse effect of a potentially dangerous hyperperfusion of the distal spinal cord segments. Spinal cord injury, Distal perfusion, Paraplegia, Paraparesis, Collateral network INTRODUCTION Spinal cord ischaemia (SCI) can cause permanent paraplegia with a tremendous effect on early postoperative and long-term results, quality of life, and survival after extensive thoraco-abdominal aortic repair [1, 2]. Numerous adjuncts have been developed to reduce the rate of paraplegia, including adjunctive strategies to support spinal cord perfusion [e.g. controlled hypertension, cerebrospinal fluid (CSF) drainage, distal aortic perfusion (DaP)] [3, 4]. Distal perfusion, performed by means of left-heart or cardiopulmonary bypass (CPB), provides flow to the hypogastric arteries but also reduces the afterload caused by aortic cross-clamping and, depending on the configuration of the extracorporeal circuit, enables temperature control and selective visceral perfusion and supports blood oxygenation. Left-heart bypass provides distal perfusion by transporting physiologically oxygenated blood from the left heart (left atrium) to the femoral or iliac artery, facilitates cardiac afterload correction and does not require full heparinization. In the contrary, CPB does require full anticoagulation; however, it enables the use of hypothermia and circulatory arrest, cardiotomy suction from the operative field and, most importantly, oxygenation maintenance. Unless DaP is performed, spinal cord blood supply is provided mostly by the cranial collaterals with limited or no impact of pelvic circulation and, depending on the level of cross-clamping, by very few segmental arteries. This, in addition to steal through back-bleeding from the segmental arteries and increased CSF pressure, compromises spinal cord perfusion and results in up to 22% rate of postoperative SCI [1]. The scientific evidence on the protective effect of DaP is based on retrospective analyses and observational studies. The efficacy of DaP with regard to spinal cord blood flow (SCBF) has never been confirmed in prospective randomized clinical trials [5, 6]. The currently available experimental studies in large animal models analysed DaP in combination with other SCI preventive adjuncts [7, 8]. In the presented experimental series, we aimed to analyse the exclusive effect of DaP, performed by means of CPB, during aortic cross-clamping with or without induced CSF pressure increase. MATERIALS AND METHODS Ethics The Institutional Animal Care and Use Committee and the local Veterinary Office (application number TVV01/18) approved the study. Each experiment was performed in accordance with the principles of the National Society for Medical Research and the Guidelines for the Care and Use of Laboratory Animals [National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals 2011] [9]. Anaesthesia Eight juvenile female German landrace pigs (age from 15 to 20 weeks and mean weight 50.5 ± 4.8 kg) were used for the study. The animals underwent premedication (using atropine—0.02 mg/kg, Pfizer, midazolam—0.5 mg/kg, Pfizer, and later ketamine—15mg/kg, Pfizer) and were transferred to the animal operating room of the Heart Centre Leipzig. A venous catheter was placed into an ear vein for drugs and fluid administration. Electrocardiogram, collateral network near-infrared spectroscopy (cnNIRS) and pulse oximetry optodes were placed. After a bolus injection of fentanyl (2 μg/kg) and preoxygenation, endotracheal intubation was realized. Ventilation was achieved with volume control mode with 50% oxygen, 20 breaths/min frequency and 8 ml/kg tidal volume. Anaesthesia was provided using intravenous propofol (25–35 mg/kg/h) and fentanyl (0.001–0.004 mg/kg/h) administration. To perform continuous blood pressure monitoring and blood sampling, we placed 2 arterial catheters—1 in the right carotid artery and the other 1 in the femoral artery. This was followed by the insertion of an additional venous catheter into the left jugular vein and positioning of the temperature probe in the rectum. The animal was turned to the right side and an X-ray-guided lumbar puncture with introduction of the cerebrospinal drain was performed at the L3–L4 level for the monitoring of intrathecal pressure and plasma injection during the CSF pressure increase stage of the experiment. The temperature of the animal was kept normothermic throughout the whole experiment, with minimal changes compared to the individual baseline (ranging from 38.4 to 39.7°C). There were no steroids administered before or during the experiment. Surgical approach First, an upper left lateral thoracotomy at the 3rd intercostal space was performed. The descending thoracic aorta (DTA) proximal to the T4 segmental artery was mobilized. The pericardium was opened and a 4-Fr catheter for microsphere injections inserted into the left atrium using Seldinger technique. After intravenous injection of heparin (400 IU/kg), cannulation of the DTA with 12-Fr paediatric cannula (Medtronic, Dublin, Ireland) and of the pulmonary trunk with a 18-Fr paediatric venous cannula (MEDOS Medizintechnik, Stolberg, Germany) was performed (Fig. 1). The above-mentioned arterial line was later used for microsphere injections. Afterwards, retroperitoneal space was accessed for mobilization of the abdominal aorta and a 12-Fr Fem-Flex II Femoral arterial cannula (Edwards Lifesciences, Irvine, CA, USA) for DaP and microsphere injections was placed into abdominal aorta in caudal direction. Its position was confirmed by angiography with visualization of the arterial cannula’s tip in the abdominal aorta. Both of the CPB arterial lines had a three-way tap enabling simultaneous injection of microspheres solution (i.e. proximally and distally) during the experiment. Figure 1: Open in new tabDownload slide Experimental set-up, lateral (A) and dorsal (B) view. cnNIRS: collateral network near-infrared spectroscopy; CSF: cerebrospinal fluid; MS: microspheres. Figure 1: Open in new tabDownload slide Experimental set-up, lateral (A) and dorsal (B) view. cnNIRS: collateral network near-infrared spectroscopy; CSF: cerebrospinal fluid; MS: microspheres. Experimental sequence The baseline injection of microspheres (T1) into the left atrium was performed after 10 min of partial CPB at a mean arterial pressure of 50–70 mmHg (Fig. 2). Afterwards, DTA was cross-clamped. Five minutes later, the second injection (T2) of microspheres was completed. Thereafter, the abdominal aorta was cross-clamped distally and distal perfusion was initiated with the flow adjusted to a distal mean pressure of 60 mmHg. Five minutes later, 2 different colours of microspheres were injected simultaneously via the proximal and distal arterial cannulas (T3), to depict the reach and regional distribution of DaP. To evaluate the potential of DaP on spinal cord perfusion when CSF pressure rises, an iatrogenic increase in CSF pressure (×3) by plasma injection through a lumbar catheter was added to the protocol, as described previously [10]. Additional plasma injections were conducted to achieve stable pressure levels for 15 min. The target CSF pressure during this stage was chosen according to our previously performed study. This was followed by the injection (T4) of 2 microsphere colours, again via the proximal and the distal arterial lines (Fig. 2). Figure 2: Open in new tabDownload slide Experimental sequence. CPB: cardiopulmonary bypass; CSF: cerebrospinal fluid; X-clamp: cross-clamp. Figure 2: Open in new tabDownload slide Experimental sequence. CPB: cardiopulmonary bypass; CSF: cerebrospinal fluid; X-clamp: cross-clamp. Tissue harvesting and microspheres quantification At the end of the experiment, the animal was euthanized in deep sedation through exsanguination. The spinal cord was removed en bloc, and the paraspinous muscles were harvested (2 cm3 tissue samples) from the middle part of each cnNIRS segment (mid- and lower-thoracic, upper and lower lumbar segments). For the regional flow analysis, we used a Dye-Track VII+ system with absorbance-dyed polystyrene microspheres (15 μm in size, 3.0 million microspheres of each colour) (Triton Technology Inc., San Diego, USA). Six of the 7 colours were used during the experiment, the remaining colour served as a process control during the measurements. Colour quantification was carried out using Synergy™ H1 Plate Reader (BioTek, Winooski, VT, USA) and Gen5 Software (BioTek). Reference blood was obtained at each of the 4 experimental time-points to adjust the colour intensities to the cardiac output at the time of microspheres administration. For the last 2 measurement-points (T3 and T4), reference blood was sampled at 2 levels: proximally (arterial line in carotid artery) and distally (arterial line in femoral artery). A detailed description of sample handling and regional flow assessment has been published previously [11]. Statistical analysis Data were analysed using SPSS Statistics Version 25.0 and GraphPad Prism Version 8.00. The distribution of continuous variables was evaluated using the D’Agostino–Pearson, the Kolmogorov–Smirnov tests and Q–Q plots. Continuous variables are expressed as mean ± standard deviation and median (interquartile range). Time-dependent repeated measurements (absolute values) were analysed using repeated-measures analysis of variance(ANOVA) (with proximal and distal injections per each of the 3 spinal cord segments, i.e. 6 ANOVAs) with the Tukey’s post hoc test for multiple comparisons. The data used for ANOVA were normally (or almost normally according to Q–Q plots) distributed; the Greenhouse–Geisser method was used to correct the violation of the sphericity assumption. Statistical significance was set at a P-value of ≤0.05 for 2-tailed testing. RESULTS Spinal cord regional perfusion during the experiment The results of the performed microspheres analysis of spinal cord perfusion for each time-point are presented in Table 1 in detail. After DTA cross-clamping, a typical decline in spinal cord perfusion at all levels was observed, with the most pronounced decrease in the L3–S segment [14% of baseline, standard deviation (SD): 11%] (Figs. 3 and 4). Distal cross-clamping of the abdominal aorta and the start of DaP led to marked shift in spinal cord perfusion: SCBP increased in the C1–Th7 (156%, SD: 93%) while the region of Th8–L2 was the least protected resulting in a decrease of SCBP between 24% and 33% (proximal injection of microspheres: 33%, SD: 24%; distal injection of microspheres: 24%, SD: 39%). In the distal spinal cord region (L3–S), hyperperfusion was observed up to 480% of baseline (proximal injection: 96%, SD: 52%; distal injection: 480%, SD: 313%). Figure 3: Open in new tabDownload slide Absolute values of spinal cord blood flow with proximal (A) and distal (B) injections of microspheres at the last 2 time-points of the experiment. The results of the ANOVA and multiple comparisons using Tukey test are presented in Fig. 4 and Supplementary Material, Tables S1 and S2. CPB: cardiopulmonary bypass; CSF: cerebrospinal fluid; DP: distal perfusion. Figure 3: Open in new tabDownload slide Absolute values of spinal cord blood flow with proximal (A) and distal (B) injections of microspheres at the last 2 time-points of the experiment. The results of the ANOVA and multiple comparisons using Tukey test are presented in Fig. 4 and Supplementary Material, Tables S1 and S2. CPB: cardiopulmonary bypass; CSF: cerebrospinal fluid; DP: distal perfusion. Figure 4: Open in new tabDownload slide Changes in regional spinal cord perfusion at all 3 levels as absolute values. The upper line represents the proximal injections, the lower line—the distal injections at the last 2 time-points of the experiment. The microspheres injections at the first 2 time-points (both upper and lower lines) were performed via the left atrium. The results of the ANOVA and multiple comparisons using Tukey test are presented in Supplementary Material, Tables S1 and S2. CPB: cardiopulmonary bypass; CSF: cerebrospinal fluid; DP: distal perfusion. Figure 4: Open in new tabDownload slide Changes in regional spinal cord perfusion at all 3 levels as absolute values. The upper line represents the proximal injections, the lower line—the distal injections at the last 2 time-points of the experiment. The microspheres injections at the first 2 time-points (both upper and lower lines) were performed via the left atrium. The results of the ANOVA and multiple comparisons using Tukey test are presented in Supplementary Material, Tables S1 and S2. CPB: cardiopulmonary bypass; CSF: cerebrospinal fluid; DP: distal perfusion. Table 1: Spinal cord regional blood flow as % of baseline . Baseline (CPB) . Proximal X-clamp . Distal X-clamp + DP . Distal X-clamp + DP . DP + CSF ×3 . DP + CSF ×3 . Proximal injections . Distal injections . Proximal injections . Distal injections . C1–T7 Mean (SD) Median (IQR) 100 61.6 (19.1) 53.8 (48.0–73.1) 156.1 (93.3) 132.0 (85.6–213.9) 5.1 (5.0) 5.3 (0.1–10.0) 102.0 (65.2) 67.9 (65.1–151.5) 19.3 (19.0) 13.2 (3.5–40.0) T8–L2 Mean (SD) Median (IQR) 100 27.3 (19.4) 18.2 (12.7–46.9) 33.4 (24.3) 30.5 (16.9–53.5) 24.0 (38.6) 14.7 (0.9–23.4) 12.8 (9.0) 13.0 (4.7–20.6) 9.9 (13.7) 6.1 (0.1–15.3) L3–S Mean (SD) Median (IQR) 100 14.4 (10.6) 13.5 (5.8–20.8) 96.1 (52.2) 95.2 (56.3–149.9) 479.6 (313.2) 503.7 (155.8–786.2) 58.8 (45.1) 52.5 (37.1–65.9) 467.6 (628.1) 233.0 (87.8–672.0) . Baseline (CPB) . Proximal X-clamp . Distal X-clamp + DP . Distal X-clamp + DP . DP + CSF ×3 . DP + CSF ×3 . Proximal injections . Distal injections . Proximal injections . Distal injections . C1–T7 Mean (SD) Median (IQR) 100 61.6 (19.1) 53.8 (48.0–73.1) 156.1 (93.3) 132.0 (85.6–213.9) 5.1 (5.0) 5.3 (0.1–10.0) 102.0 (65.2) 67.9 (65.1–151.5) 19.3 (19.0) 13.2 (3.5–40.0) T8–L2 Mean (SD) Median (IQR) 100 27.3 (19.4) 18.2 (12.7–46.9) 33.4 (24.3) 30.5 (16.9–53.5) 24.0 (38.6) 14.7 (0.9–23.4) 12.8 (9.0) 13.0 (4.7–20.6) 9.9 (13.7) 6.1 (0.1–15.3) L3–S Mean (SD) Median (IQR) 100 14.4 (10.6) 13.5 (5.8–20.8) 96.1 (52.2) 95.2 (56.3–149.9) 479.6 (313.2) 503.7 (155.8–786.2) 58.8 (45.1) 52.5 (37.1–65.9) 467.6 (628.1) 233.0 (87.8–672.0) Data expressed as mean (SD) and median (IQR). Proximal—microspheres injected into the proximal arterial line; distal—microspheres injected into the distal (distal perfusion) arterial line. CBP: cardiopulmonary bypass; CSF: cerebrospinal fluid; CSF ×3: increase of cerebrospinal fluid pressure to ×3 from the baseline; DP: distal perfusion; IQR: interquartile range; SD: standard deviation; X-clamp: aortic cross-clamping. Open in new tab Table 1: Spinal cord regional blood flow as % of baseline . Baseline (CPB) . Proximal X-clamp . Distal X-clamp + DP . Distal X-clamp + DP . DP + CSF ×3 . DP + CSF ×3 . Proximal injections . Distal injections . Proximal injections . Distal injections . C1–T7 Mean (SD) Median (IQR) 100 61.6 (19.1) 53.8 (48.0–73.1) 156.1 (93.3) 132.0 (85.6–213.9) 5.1 (5.0) 5.3 (0.1–10.0) 102.0 (65.2) 67.9 (65.1–151.5) 19.3 (19.0) 13.2 (3.5–40.0) T8–L2 Mean (SD) Median (IQR) 100 27.3 (19.4) 18.2 (12.7–46.9) 33.4 (24.3) 30.5 (16.9–53.5) 24.0 (38.6) 14.7 (0.9–23.4) 12.8 (9.0) 13.0 (4.7–20.6) 9.9 (13.7) 6.1 (0.1–15.3) L3–S Mean (SD) Median (IQR) 100 14.4 (10.6) 13.5 (5.8–20.8) 96.1 (52.2) 95.2 (56.3–149.9) 479.6 (313.2) 503.7 (155.8–786.2) 58.8 (45.1) 52.5 (37.1–65.9) 467.6 (628.1) 233.0 (87.8–672.0) . Baseline (CPB) . Proximal X-clamp . Distal X-clamp + DP . Distal X-clamp + DP . DP + CSF ×3 . DP + CSF ×3 . Proximal injections . Distal injections . Proximal injections . Distal injections . C1–T7 Mean (SD) Median (IQR) 100 61.6 (19.1) 53.8 (48.0–73.1) 156.1 (93.3) 132.0 (85.6–213.9) 5.1 (5.0) 5.3 (0.1–10.0) 102.0 (65.2) 67.9 (65.1–151.5) 19.3 (19.0) 13.2 (3.5–40.0) T8–L2 Mean (SD) Median (IQR) 100 27.3 (19.4) 18.2 (12.7–46.9) 33.4 (24.3) 30.5 (16.9–53.5) 24.0 (38.6) 14.7 (0.9–23.4) 12.8 (9.0) 13.0 (4.7–20.6) 9.9 (13.7) 6.1 (0.1–15.3) L3–S Mean (SD) Median (IQR) 100 14.4 (10.6) 13.5 (5.8–20.8) 96.1 (52.2) 95.2 (56.3–149.9) 479.6 (313.2) 503.7 (155.8–786.2) 58.8 (45.1) 52.5 (37.1–65.9) 467.6 (628.1) 233.0 (87.8–672.0) Data expressed as mean (SD) and median (IQR). Proximal—microspheres injected into the proximal arterial line; distal—microspheres injected into the distal (distal perfusion) arterial line. CBP: cardiopulmonary bypass; CSF: cerebrospinal fluid; CSF ×3: increase of cerebrospinal fluid pressure to ×3 from the baseline; DP: distal perfusion; IQR: interquartile range; SD: standard deviation; X-clamp: aortic cross-clamping. Open in new tab A tripling of CSF pressure resulted in a decrease in perfusion at all levels most pronounced in the upper and mid-thoracic areas, reaching statistical significance only in the C1–T7 segment with proximally injected microspheres (Fig. 4). The details of ANOVA analysis are presented in the Supplementary Material, Tables S2 and S3. The vital parameters are given in Table 2 and Fig. 5. Figure 5: Open in new tabDownload slide Mean arterial pressure measured in the carotid and the femoral arteries. Data presented as absolute values. Figure 5: Open in new tabDownload slide Mean arterial pressure measured in the carotid and the femoral arteries. Data presented as absolute values. Table 2: Vital parameters during the experiment . Baseline (CPB) . Proximal X-clamp . Distal X-clamp + DP . DP + CSF ×3 . MAP carotid (mmHg) 79.6 (22.1) 106.4 (17.2) 96.4 (19.4) 79.8 (13.7) MAP femoral (mmHg) 56.6 (13.3) 17.3 (3.0) 74.9 (23.3) 67.5 (7.8) CVP (mmHg) 10.6 (2.9) 5.0 (1.8) 5.4 (1.6) 5.1 (1.5) SO2 (%) 98.0 (1.2) 96.8 (3.3) 96.5 (6.4) 97.1 (4.0) CSFP (mmHg) 13.9 (2.2) 11.3 (4.3) 12.0 (3.0) 43.8 (15.8) . Baseline (CPB) . Proximal X-clamp . Distal X-clamp + DP . DP + CSF ×3 . MAP carotid (mmHg) 79.6 (22.1) 106.4 (17.2) 96.4 (19.4) 79.8 (13.7) MAP femoral (mmHg) 56.6 (13.3) 17.3 (3.0) 74.9 (23.3) 67.5 (7.8) CVP (mmHg) 10.6 (2.9) 5.0 (1.8) 5.4 (1.6) 5.1 (1.5) SO2 (%) 98.0 (1.2) 96.8 (3.3) 96.5 (6.4) 97.1 (4.0) CSFP (mmHg) 13.9 (2.2) 11.3 (4.3) 12.0 (3.0) 43.8 (15.8) Data are expressed as mean (SD). CPB: cardiopulmonary bypass; CSF(P): cerebrospinal fluid (pressure); CVP: central venous pressure; DP: distal perfusion; MAP: mean arterial pressure; SD: standard deviation; SO2: oxygen saturation; X-clamp: aortic cross-clamping. Open in new tab Table 2: Vital parameters during the experiment . Baseline (CPB) . Proximal X-clamp . Distal X-clamp + DP . DP + CSF ×3 . MAP carotid (mmHg) 79.6 (22.1) 106.4 (17.2) 96.4 (19.4) 79.8 (13.7) MAP femoral (mmHg) 56.6 (13.3) 17.3 (3.0) 74.9 (23.3) 67.5 (7.8) CVP (mmHg) 10.6 (2.9) 5.0 (1.8) 5.4 (1.6) 5.1 (1.5) SO2 (%) 98.0 (1.2) 96.8 (3.3) 96.5 (6.4) 97.1 (4.0) CSFP (mmHg) 13.9 (2.2) 11.3 (4.3) 12.0 (3.0) 43.8 (15.8) . Baseline (CPB) . Proximal X-clamp . Distal X-clamp + DP . DP + CSF ×3 . MAP carotid (mmHg) 79.6 (22.1) 106.4 (17.2) 96.4 (19.4) 79.8 (13.7) MAP femoral (mmHg) 56.6 (13.3) 17.3 (3.0) 74.9 (23.3) 67.5 (7.8) CVP (mmHg) 10.6 (2.9) 5.0 (1.8) 5.4 (1.6) 5.1 (1.5) SO2 (%) 98.0 (1.2) 96.8 (3.3) 96.5 (6.4) 97.1 (4.0) CSFP (mmHg) 13.9 (2.2) 11.3 (4.3) 12.0 (3.0) 43.8 (15.8) Data are expressed as mean (SD). CPB: cardiopulmonary bypass; CSF(P): cerebrospinal fluid (pressure); CVP: central venous pressure; DP: distal perfusion; MAP: mean arterial pressure; SD: standard deviation; SO2: oxygen saturation; X-clamp: aortic cross-clamping. Open in new tab Collateral network regional perfusion and near-infrared spectroscopy The results of regional blood flow in the paraspinal muscles are graphically presented in Supplementary Material, Fig. S1. No significant changes in regional perfusion were observed after the initiation of distal perfusion (see Supplementary Material, Fig. S1). During the cnNIRS monitoring, no statistically significant oxygenation changes were observed at the mid-thoracic level. At the 3 other levels, the most marked oxygenation decline, however not reaching statistical significance, was depicted after proximal aortic cross-clamping. The cnNIRS values crossed the 70% from baseline threshold only at lower thoracic level after distal aortic cross-clamping and start of distal perfusion (Fig. 6 and Supplementary Material, Fig. S2). There was almost no or limited effect of DaP or additional CSF pressure elevation on cnNIRS values at any level. Figure 6: Open in new tabDownload slide Collateral network near-infrared spectroscopy values at 4 levels. Data presented as % of baseline. For ANOVA with multiple comparisons, see Supplementary Material, Table S2. CBP: cardiopulmonary bypass: CSF ×3: increase of cerebrospinal fluid pressure to ×3 from the baseline; DP: distal perfusion; HIGH LUMB: upper lumber level; LOW THOR: lower thoracic level; LOW LUMB: lower lumbar level; MID-THOR: mid-thoracic level. Figure 6: Open in new tabDownload slide Collateral network near-infrared spectroscopy values at 4 levels. Data presented as % of baseline. For ANOVA with multiple comparisons, see Supplementary Material, Table S2. CBP: cardiopulmonary bypass: CSF ×3: increase of cerebrospinal fluid pressure to ×3 from the baseline; DP: distal perfusion; HIGH LUMB: upper lumber level; LOW THOR: lower thoracic level; LOW LUMB: lower lumbar level; MID-THOR: mid-thoracic level. DISCUSSION The use of multimodal approach in organ, and in particular spinal cord, protection during open thoraco-abdominal repair has led to substantial improvements in operative outcomes. Among various available adjuncts, DaP has become one of the most widely utilized strategies. The method aims to support the collateral flow from the caudal collateral arteries (most importantly, hypogastric arteries) to the spinal cord. This experimental study provides a better understanding of the isolated impact of DaP on SCBF prior to and during induced CSF pressure elevation. Most of the previously published experimental series evaluated the combined effect of DaP and other protective measures. In an experimental study on a chronic canine model, Rose et al. [7] observed no SCI in animals undergoing normothermic or mild hypothermic (30°C) 45-min aortic cross-clamping with DaP pressure above 20 mmHg. The same result was reported for the group of mild hypothermic cross-clamping with low DaP pressure. However, the distal clamp during these experiments was placed directly below the diaphragm. Moreover, the statistical power of the study is limited since each of the groups included only 3 animals; also, no regional perfusion quantification was performed. Laschinger et al. [12] concluded in experiments on dogs that the minimal DaP pressure above 70 mmHg provided better neurological results and thus adequate spinal cord protection, compared to DaP pressure mode of 40 mmHg. Another study by Winnerkvist et al. [8] evaluated the combined impact of DaP and CSF drainage in a canine study with protective effect when DaP and CSF were used or the group with a combination of DaP, CSF drain and retrograde spinal cord perfusion. All 5 animals in the control groups awoke paraplegic compared to only 1 animal with paraparesis in each of the intervention groups. Promising results were achieved in clinical practice using the combination of DaP and CSF drainage, and other adjuncts. Safi et al. demonstrated a decrease in neurologic deficit rates from 16% to 2.4%, with the most evident improvement in Crawford type II results (SCI rate decline from 31% to 6.6%) [13, 14]. DaP was identified as an effective method by Coselli et al., Conrad et al. and many other leading aortic teams [15–19]. Our analysis showed that distal perfusion was associated with a marked increase in SCBF in the lumbar region but limited perfusion improvement at C1–T7 and T8–L2 levels compared to cross-clamping without DaP. However, since the cervical and upper thoracic segments received adequate blood flow from the cranial collaterals, the mid-thoracic level remained the most vulnerable part of the spinal cord during aortic cross-clamping. At the same time, despite the low perfusion levels at upper and mid-spinal cord, its distal segments experienced extreme (up to 500% of baseline) hyperperfusion, known to be another risk factor of SCI [20]. The deliberate elevation of CSF was associated with a further decline of perfusion at most levels, as demonstrated in our previous experiment performed without aortic cross-clamping [10]. Interestingly, cnNIRS oxygenation values did cross the 70% ischaemic threshold at lower thoracic level, which could be used as an indication for DaP pressure adjustment (elevation) during the open thoraco-abdominal repair. This underlines the importance of thorough intraoperative monitoring and multimodal approach in spinal cord ischaemia detection. Roughly similar trends were also seen in regional collateral network perfusion values. One needs to point out that cnNIRS evaluates larger muscle areas compared to microspheres quantification; thus, certain discrepancies could be expected. Limitations The presented study has several limitations. First of all, one needs to consider the differences in the anatomy of the used experimental animals and humans [21]. Moreover, even within the species, certain variations in collateral network and spinal cord blood supply may influence the development of SCI [22]. Since no pre-experimental assessment of each animal’s spinal cord circulation was performed, one cannot exclude the possible presence of this factor leading to variations in response to DaP. However, one should mention that in response to proximal aortic cross-clamping, all the animals followed the similar pattern with a severe decrease of SCBF in all except mid-thoracic level, fully corresponding with previously published data [23, 24]. Thus, the proximal aortic cross-clamping time-point was used in the current experiment as a second, ‘ischaemic’ baseline. The next significant limitation is the variation of microspheres injection sites. The injections at the first 2 time-points of the experiment (baseline and proximal aortic cross-clamping) were performed via left atrium, the other 2 time-points injections (4 colours) were realized through arterial CPB lines. This could be explained by the limited number of microspheres colours: of 7 available in the kit colours, 1 was used as a process control (an important step to assure the quality of perfusion analysis). Thus, the results of ANOVA and following multiple comparisons should be assessed with caution. Also, we did not evaluate the effect of different DaP pressure modes and aimed for a target pressure of 60 mmHg. The target pressure remained unchanged (unadjusted) during the whole experiment. One also needs to mention that, despite its complexity, the study was performed in a relatively small number of animals to draw any definite conclusions. The study analysed the effect of DaP in an acute animal model with open segmental arteries and was one of the initial ones in a large series of animal experiments planned by the current group. No instrumental evaluation of the spinal cord condition (e.g. oedema detection using magnetic resonance imaging) was performed. Further studies are required with (i) occlusion of segmental arteries, simulating open thoraco-abdominal repair without reimplantation of segmental arteries, and (ii) chronic animal model to gain more information about DaP and CSF drainage effect using histological and neurological assessment. CONCLUSIONS Protective DaP during thoraco-abdominal aortic repair should be managed carefully since it may not provide sufficient protection at the mid-thoracic spinal cord level and concomitantly cause profound hyperperfusion of the distal spinal cord segments. Further studies should be performed to elude the effects of various pressure (and pulsatility) adjustments to identify the ideal equilibrium to achieve the best protection of mid-thoracic spinal cord perfusion at the lowest possible cost of distal hyperperfusion—a possible cause for spinal oedema and consequent delayed paraplegia after open thoracoabdominal aortic aneurysm repair. SUPPLEMENTARY MATERIAL Supplementary material is available at EJCTS online. Funding This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement 733203 and from the German Research Foundation under grant number 127/2-1. Conflict of interest: Professor Christian D. Etz holds the Heisenberg-Professorship for Aortic Surgery of the German Research 333 Foundation (DFG) (Project No: 278040814). Presented at the 34th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Barcelona, Spain, 8–10 October 2020. Author contributions Josephina Haunschild: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Software; Validation; Visualization; Writing—original draft; Writing—review & editing. Zara Khachatryan: Data curation; Formal analysis; Investigation; Methodology; Visualization; Writing—original draft. Konstantin von Aspern: Investigation; Methodology; Software; Visualization. Johanna Herajärvi: Investigation; Validation. Susann Ossmann: Formal analysis; Investigation; Methodology. Jörg Naumann: Investigation; Methodology; Resources. Michael A. Borger: Conceptualization; Methodology; Resources; Supervision. Christian D. Etz: Conceptualization; Funding acquisition; Investigation; Project administration; Resources; Software; Supervision; Writing—review & editing. Reviewer information European Journal of Cardio-Thoracic Surgery thanks George J. 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ABBREVIATIONS ABBREVIATIONS CPB Cardiopulmonary bypass CSF Cerebrospinal fluid cnNIRS Collateral network near-infrared spectroscopy DTA Descending thoracic aorta DaP Distal aortic perfusion SCBF Spinal cord blood flow SCI Spinal cord ischaemia SD Standard deviation Author notes † Josephina Haunschild, Zara Khachatryan contributed equally to this work. © The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Effect of cerebrospinal fluid pressure elevation on spinal cord perfusion during aortic cross-clamping with distal aortic perfusion
JF - European Journal of Cardio-Thoracic Surgery
DO - 10.1093/ejcts/ezab167
DA - 2021-04-11
UR - https://www.deepdyve.com/lp/oxford-university-press/effect-of-cerebrospinal-fluid-pressure-elevation-on-spinal-cord-o0rJpMBAW0
SP - 1
EP - 1
VL - Advance Article
IS - 
DP - DeepDyve
ER -