Impact of distal aortic perfusion on ‘segmental steal’ depleting spinal cord blood flow—a quantitative experimental approach

Abstract

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OBJECTIVES

Aortic steal is an underestimated risk factor for intraoperative spinal cord ischaemia. A negative effect on spinal cord perfusion in thoraco-abdominal aneurysm repair has been suspected if blood drains away from the cord initiated by a reversal of the arterial pressure gradient. The amount of blood and pressure loss via back-bleeding of segmental arteries and the impact of distal aortic perfusion (DaP) have not been analysed yet. The aim of our study was to quantify ‘segmental steal’ in vivo during simulated thoraco-abdominal aneurysm repair and to determine the impact of DaP on steal and spinal cord perfusion.

METHODS

Ten juvenile pigs were put on cardiopulmonary bypass with DaP and visceral arteries were ligated. ‘Segmental steal’ was quantified by draining against gravity with/without DaP. Blood volume of ‘segmental steal’ was quantified and microspheres were injected for Post mortem spinal cord perfusion analysis. ‘Segmental steal’ was quantified with/without DaP—and with stopped DaP.

RESULTS

Quantification revealed a significantly higher steal on cardiopulmonary bypass with DaP with a mean difference of 24(11) ml/min. In all spinal cord segments, blood flow was diminished during steal drainage on DaP, compared to ‘no steal’. The least perfused region was the low thoracic to upper lumbar segment.

CONCLUSIONS

‘Segmental steal’ is a relevant threat to spinal cord perfusion—even with the utilization of DaP—diminishing spinal cord perfusion. The blood volume lost by back-bleeding of segmental arteries is not to be underestimated and occlusion of segmental arteries should be considered in thoraco-abdominal aneurysm repair.

INTRODUCTION

For decades, spinal cord ischaemia (SCI), clinically resulting in paraparesis and paraplegia, has been the most feared complication after extensive open and endovascular thoraco-abdominal aortic aneurysm repair affecting up to 20% of patients [1]. Since the understanding of spinal cord perfusion has been revised and the idea of one single artery (of Adamkiewicz) has been complemented by the existence of a vast paraspinous collateral network (CN), a re-evaluation of neuroprotection has set in [2]. Priming of the CN by minimally invasive staged segmental artery coil embolization (MIS²ACE) or endovascularly staging aortic repair procedures has already lead to a reduction of the rate of paraplegia in some single pilot studies [3, 4]. However, more evidence is currently being generated by the international PAPAartis trial (NCT03434314) supporting the idea of priming the CN and ensuring spinal cord perfusion by arteriogenesis of the paraspinous arterial network [5]. However, these protective measures are not always applicable, particularly in urgent or emergent cases.

Over 30 years ago, the aortic steal phenomenon was recognized by Wadouh et al. as one potential cause for SCI after open thoraco-abdominal aortic aneurysm repair [6, 7]. It is believed that due to clamping of the descending thoracic aorta (DTA) in open surgery the pressure below the clamp drops rapidly drawing back blood (via the open segmental arteries) into the depressurized aorta (a zone of lower resistance) ‘stealing’ blood from the spinal cord. In endovascular aortic procedures, the drop of pressure in the excluded aneurysm sac once the aortic stent grafts are in place can also lead to ‘suction’ of blood into the depressurized aneurysm sac away from the spinal cord. Both mechanisms may ultimately lead to a hypoperfusion of the spinal cord potentially resulting in spinal cord ischaemia and paraplegia. Other mechanisms thought to be responsible for ‘steal’ are muscle shivering, redistribution of blood into the CN and rewarming with vasoplegia after surgery in systemic hypothermia [8]. However, evidence for these mechanisms is rare.

As very limited evidence has been gathered on the amount of isolated ‘segmental steal’ (excluding steal through the visceral arteries) during cardiopulmonary bypass with distal aortic perfusion (DaP), our aim is to determine the blood volume draining away from the spinal cord via the segmental arteries and its effect on regional spinal cord microperfusion in an established translational large animal model.

MATERIALS AND METHODS

Ethics

The study was approved by the Institutional Animal Care and Use Committee and the local Veterinary Office (application number TVV01/18). 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]. Previous acute animal experiments and expected differences in perfusion analysis by microspheres were used for sample size calculation with a power of 85% ending up a groupsize of 9 pigs plus 10% mortality resulting in 10 pigs per group. Significance was defined as <0.05.

Anaesthesia

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 drug and fluid administration. After a bolus injection of fentanyl (2 μg/kg) and preoxygenation, endotracheal intubation was performed. Ventilation used 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. ECG and pulse oximetry optodes were connected and a temperature probe was placed in the rectum. Two arterial catheters—1 in the right carotid artery and the other one in the femoral artery were placed for continuous blood pressure monitoring and blood sampling. In addition, a venous catheter was inserted into the left jugular vein. The animal was turned to the right side and an X-ray guided lumbar puncture with the introduction of the cerebrospinal drain was performed at the L3–L4 level for monitoring of intrathecal pressure. The animals’ core temperature 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 as previously described [10]. The DTA was mobilized. The pericardium was opened and a 4-F catheter for microsphere injections were inserted into the left atrium using the Seldinger technique. After intravenous injection of heparin (400 IU/kg), cannulation of the DTA with 12-F paediatric cannula (Medtronic, Dublin, Ireland) and of the pulmonary trunk with a 18-F paediatric venous cannula (MEDOS Medizintechnik, Stolberg, Germany) was performed (Fig. 1). The retroperitoneal space was accessed for mobilization of the abdominal aorta and a 12-F Fem-Flex II femoral arterial cannula (Edwards Lifesciences, Irvine, CA, USA) for DaP was placed into the abdominal aorta in the caudal direction. 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. Mobilization of all segmental arteries was realized via 2 additional lateral thoracotomies (see Fig. 1). One drainage tube (with three-way tap for pressure recordings) was inserted into the lower thoracic aorta (level of Th10–12) for the quantification of segmental artery steal against gravity. Mobilization of visceral arteries (coeliac trunc, superior mesenteric artery, renal arteries) and placement of rubber ligatures enabled blockage of visceral back flow.

Experimental sequence

The baseline injection of microspheres (T1) into the left atrium was performed after insertion of all cannulas and 10 min of partial CPB at a mean arterial pressure of 50–70 mmHg (Fig. 2). Afterwards, DTA and abdominal aorta were cross-clamped, distal perfusion was initiated with the flow adjusted to a distal mean pressure of 60 mmHg and all visceral arteries were ligated (to analyse the isolated effect of back-bleeding via the segmental arteries). Segmental steal was quantified (against gravity, without suction to simulate bleeding in the operative field while grafts are sutured for example) every 2 min and blood was re-transfused immediately. Ten minutes later, the second injection (T2) of microspheres was completed. Microspheres were split into 2 equal quantities (1.5 Mio per injection) and injected simultaneously via the proximal and distal arterial cannulas. Afterwards, the steal drainage was clamped and pressure in the clamped aortic segment was measured (to account for back-bleeding until a steady state/pressure is reached). Ten minutes later, microspheres were again injected simultaneously via the proximal and distal arterial cannulas (T3). To evaluate the potential of DaP on ‘segmental steal’, distal perfusion was now stopped (cranial perfusion only). Again, segmental steal was quantified (against gravity, without suction) every 2 min and blood re-transfused. For this step, we hypothesized less segmental steal but also worse spinal cord perfusion from mid-thoracic to low lumbar level. Ten minutes later, microspheres were injected via the proximal cannula (T4). For the last time point, we again clamped the drainage of the ‘aneurysm sac’ and waited for 10 min before MS injection (T5), see Fig. 2.

Tissue harvesting and microspheres quantification

After the last MS injection, the animal was euthanized in deep sedation through exsanguination. The spinal cord was removed enbloc. 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). Five colours were used during the experiment and 1 colour served as a process control during all measurements. Colour quantification was carried out using Synergy™ H1 Plate Reader (BioTek, Winooski, VT, USA) and Gen5 Software (BioTek, Winooski, VT, USA).

Reference blood was obtained at each of the experimental time points to adjust the colour intensities to cardiac output at the time of microspheres administration. 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 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 the repeated-measures ANOVA with the Dunnett’s T3 test for multiple comparisons. The steal 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. For the microsphere data, Levene’s test for the homogeneity of variance was significant; consequently, ANOVA was performed. Statistical significance was set at a P-value of ≤0.05 for two-tailed testing.

RESULTS

Ten juvenile female German landrace pigs (age: 15–20 weeks, mean weight 50 ± 4 kg) were used for the study.

Distal aortic perfusion

DaP was pressure-controlled aiming for a distal mean arterial pressure of 60 mmHg (mimicking most centres clinical standard protocols for DaP). Flow via CPB for DaP was in mean 662 (171) ml/min [median: 685 ml/min; interquartile range (IQR) 500; 800]. Pressure at the site of distal arterial cannula was in mean 134 (28) mmHg (median 125 mmHg; IQR 116; 152). For the control of mean distal arterial pressure, we used an extra arterial line in the femoral artery with a mean arterial pressure during DaP of 59 (9) mmHg (median: 58 mmHg, IQR 52; 66), see Table 1.

Back flow via segmental arteries—with and without distal perfusion

‘Segmental steal’ was measured as blood volume drained via all segmental arteries. The total blood volume of each pig was put into relation to the amount of drained blood (see Table 2). The total volume of ‘segmental steal’ over time is displayed in Fig. 3. Volume was quantified with and without DaP (also see Fig. 4). ‘Segmental steal’ was significantly higher when DaP was running [6.67 (2.7)% of cardiac output vs 3.05 (1.5)%, P = 0.003] with a mean difference of 24 (11) ml/min.

Regional spinal cord perfusion during distal aortic perfusion

Regional spinal cord perfusion was assessed using microsphere injection and tissue analysis at each time point; detailed results are presented in Table 3, Fig. 5 and Supplementary Material, Table S1.

Distal aortic perfusion with and without drainage of ‘segmental steal’

After the initiation of CPB and DaP, with ligation of the visceral arteries and drainage of ‘segmental steal’ against gravity, perfusion at the lower lumbar level did not change significantly [104 (49)%, P = 1.00]. At lower thoracic and upper lumbar levels, however, a significant decrease (>10-fold) to 8 (6)% of baseline was observed (P = 0.002). Perfusion also dropped at cervical and upper thoracic levels but did not reach significance [59.7 (16)%, P = 0.28]. However, once ‘segmental steal’ drainage was stopped and the pressure in the clamped aortic segment increased, spinal cord perfusion increased at all 3 levels, although most pronounced at the cervical to upper thoracic region [C1–Th7: 60 (16)% vs 114 (52)%, P = 0.017; Th8–L2: 8 (6)% vs 15 (13)%, P = 0.63; L3–S: 104 (49)% vs 110 (54)%, P = 1.00]. The only region with close to normal perfusion was the cervical to the upper thoracic spinal cord (C1–Th7).

No distal aortic perfusion, with and without drainage of ‘segmental steal’

When DaP was stopped, overall spinal cord perfusion decreased. Perfusion of the lower lumbar region was significantly worse compared to baseline [baseline: 100 (47)% vs 2 (2)%, P < 0.0001] and compared to DaP with ‘segmental steal’ drainage [DaP, steal drainage: 104 (49)% vs 2 (2) %, P = 0.005]. Once steal drainage was clamped (no DaP), perfusion of this region tripled again but remained low overall (6 ± 4%). The lower thoracic to the upper lumbar spinal cord, also called ‘watershed area’, exhibited an increase in perfusion as soon as drainage of ‘segmental steal’ was stopped, with and without DaP [DaP steal drainage: 8.4 (6)% vs DaP, no steal drainage: 15 (13)%, P = 0.63; no DaP, steal drainage: 5 (5)% vs no DaP, no steal drainage: 12 (9)%, P = 0.59]. However, no significance was reached as perfusion was drastically reduced as soon as the aorta was clamped proximally and distally (remaining between 5% and 15%). The only region with close to normal perfusion was the cervical to upper thoracic spinal cord (C1–Th7).

Once DaP was stopped perfusion decreased to 57 (33)% (with drainage of ‘segmental steal’) and increased again to baseline when no drainage of ‘segmental steal’ was allowed. However, perfusion of the cervical to upper thoracic region was significantly improved with DaP and no drainage of ‘segmental steal’ [DaP, no steal drainage: 114 (52)% vs no DaP, no steal drainage 99 (45)%, P = 0.02]. All absolute values of spinal cord perfusion are displayed in Supplementary Material, Table S2.

DISCUSSION

‘Aortic steal’ due to aortic cross-clamping has been recognized as potentially impeding spinal cord perfusion by a reversal of pressure relations leading to drainage of blood away from the cord over 30 years ago [6, 7]. Some centres still reimplant segmental arteries based on size and the intensity of back-bleeding [12], although the effect on the reduction of SCI is limited [13].

However, up to now scientific data on the absolute blood volume of ‘segmental steal’ especially in relation to the cardiac output and the effect of DaP on steal amount as well as spinal cord perfusion are limited. Our experimental data demonstrate that ‘segmental steal’ during DaP is nearly 7% of cardiac output and 3% when DaP was stopped with a mean difference of 24 (11) ml/min—significantly affecting spinal cord perfusion mostly diminishing blood flow to the lower thoracic and upper lumbar spinal cord due to the lack of pre-existing collaterals in this ‘watershed’ area. Once segmental steal was stopped, bit DaP was running, perfusion at this area doubled (8% vs 15%), without DaP perfusion at lower thoracic/upper lumbar level increased from 2% to 6% when segmental steal was stopped; however, 6% of baseline perfusion is a neglectable portion of perfusion.

An early experimental study in 18 juvenile pigs on spinal cord injury investigated the consequence of cross-clamping on the intra-aortic pressure proximally, distally and in between the clamps as well as on the pressure in the intercostal and lumbar arterial bed [7]. In group 1, the aorta was clamped distal to the subclavian artery and at the level of Th13, whereas in group 2, the aorta was clamped at L1 and S1. Before proximal clamping, pressure in intercostal and lumbar arterial beds was lower than aortic pressure (intercostal bed pressure 58 mmHg vs proximal aortic pressure 80 mmHg)—reflecting the physiologic state—which ultimately is most advantageous for spinal cord perfusion. After proximal cross-clamping, distal arterial pressure as well as both arterial bed pressures decreased (intercostal bed pressure 29 mmHg vs descending aortic pressure 18 mmHg), however remained above distal aortic pressure. Placing a double clamp led to the restoration of intercostal pressure to nearly normal values (from 29 to 52 mmHg). However, lumbar bed pressure fell after the first clamping at the level of L1 from 40 to 17 mmHg and did not recover after the placement of second clamp at the level of S1 (increased to 20 mmHg) remaining higher than the pressure distal to the second clamp (12 mmHg). The authors concluded that after aortic cross-clamping, the blood drains away from the spinal cord instead of supplying it. In our experimental set-up, we did not monitor pressure within the arterial bed, i.e. the pressure is seen by the spinal cord and CN, but we did show that the blood drained away was less once the pressure within the excluded aortic segment increased (in our setting when the steal drainage was clamped) also leading to an improvement of spinal cord perfusion as seen by microsphere analysis.

More than 10 years later, an experimental study by Hellberg et al. [14] in 17 pigs also found that the reduction of steal by placement of a second cross-clamp (above Th12 instead of below L1) lead to better spinal cord perfusion measured by laser flow doppler. The more distal position of the second cross-clamp (below L1) resulted in at least 50% decrease of oxygen tension measured in CSF (P = 0.008) without recovery during the experiment. The results are not surprising as the very vulnerable area between Th10 and L1, also called ‘watershed area’, is reached neither by DaP nor by the proximal collateralization via the subclavian artery. As previously published by our group [10] and also seen in this study, the spinal cord perfusion between Th8 and L2 immediately decreased drastically after placement of the cross-clamps and did not recover after DaP start. Hence, neighbouring spinal cord areas ‘compete’ and contribute to 2 major threats of spinal cord integrity: hypoperfusion (Th8–L2) due to ‘segmental steal’ and hyperperfusion due to DaP (L3–S), even at mean distal aortic pressures of 61 and 57 mmHg. The possible reason for better spinal cord perfusion in the study of Hellberg et al. [14] is probably the backflow of blood via the visceral arteries, when the clamp is placed above the coeliac trunc, and therefore, the less dramatic decrease of pressure within the aorta.

This is supported by one of the rare clinical studies on the topic by Schurink et al. [15] in patients with type III thoraco-abdominal aortic aneurysm receiving endovascular branched aortic repair. Once they cannulated and balloon occlude the last open visceral branch—the coeliac trunc—MEPs decreased by >50%. As soon as the balloon was deflated, MEPs returned to normal values [15]. By occluding the coeliac trunc, the pressure gradient between the aorta and the spinal cord increased and steal phenomena occurred. In our experiment, we decided to ligate the visceral arteries to assess the isolated ‘segmental steal’; therefore, the blood volume measured was the exclusively drawn away from the spinal cord itself. In our analysis of regional spinal cord perfusion, it can also be demonstrated that once the ‘segmental steal’ is not drained, spinal cord perfusion slightly increased (most pronounced in cervical and upper thoracic part) due to an increase in pressure in the aneurysm sac and a decrease in pressure gradient. Thus, in thoraco-abdominal aneurysm repair, once the aneurysm is opened, segmental arteries should be ligated or clipped immediately (or at least blocked with a Fogarty catheter) to reduce steal.

Another retrospective study by Shiiya et al. [16] analysing 116 patients with open descending or thoraco-abdominal aortic repair concluded that steal phenomenon was the most frequent mechanism of intraoperative ischaemia. According to their study SCI could be reversed by stopping back bleeding when a supplemental feeding artery was involved. Whenever a critical feeding artery was involved, ischaemia could only be reversed in 50% of patients by stopping back bleeding. Based on their finding, they believe that there is a correlation between the anatomical pattern of the feeding artery and the mechanism of intraoperative spinal cord ischaemia. We did not examine the impact of segmental artery occlusion on spinal cord perfusion. However, one can see that once the drainage of steal was stopped, perfusion improved along the spinal cord.

A promising new method hopefully preventing permanent SCI is priming the paraspinous CN utilizing staged endovascular repair or MIS²ACE [17]. Segmental artery occlusion has many advantages, e.g. the patient is awake and can communicate neurological symptoms and the number of occluded segmental arteries can be individually determined. Experimental data of our group have shown an improved spinal cord perfusion, especially concerning the vulnerable ‘watershed area’, depending on the sequence of segmental artery occlusion [18]. This area was least perfused in our current experiment; however, we did not occlude any segmental arteries and therefore did not prime the CN. Concerning steal phenomenon in open repair, one of the major benefits of priming the CN by MIS²ACE is the absence of back-bleeding segmental arteries as they have been occluded before, hence, diminishing 1 risk factor for permanent SCI. The currently recruiting PAPAartis trial will shed light on all benefits and limitations of MIS²ACE in open and endovascular aneurysm repair [5]. In patients in need of emergency or urgent thoraco-abdominal aortic aneurysm repair MIS²ACE cannot be performed and clipping/ligation of segmental arteries to reduce back-bleeding can reduce the extent of spinal cord hypoperfusion. A certain degree hypoperfusion in the low thoracic and high lumbar area can be prevented by sequential clamping with partial bypass and systemic hypothermia [19]. In endovascular aneurysm repair, back-bleeding via the segmental arteries into the hypotensive aneurysm sac has been assumed as 1 possible risk factor for delayed paraplegia [8]. MIS²ACE could therefore also reduce the risk of delayed paraplegia (and endoleak); however, adequate clinical data are not yet available.

Limitations

The presented study has several limitations. First, although the anatomy of the pig is close to that of humans, some anatomic differences remain. Furthermore, variations in spinal cord blood supply and paraspinous CN density may have influenced the amount of back-bleeding. Second, we used an acute animal model; thus, we do not have any data on the neurological outcome or histological damage. Due to the complex nature of the experiment and the relatively small number of animals, 1 should be careful in drawing any definite conclusions. The translational value of the experiment is limited due to the routine utilization of sequential clamping in clinical practice; however, we aimed for the first-time quantification of segmental steal.

CONCLUSION

‘Segmental steal’ might be a relevant threat to the spinal cord, especially for the low thoracic and high lumbar region during utilization of DaP diminishing spinal cord perfusion. The blood volume lost by back-bleeding of segmental arteries is not to be underestimated and immediate occlusion of segmental arteries should be considered in open thoraco-abdominal aneurysm repair.

Presented at the 35th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Barcelona, Spain, 13–16 October 2021.

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 Foundation (DFG) (Project-No: 278040814). The authors report no other conflicts of interest.

Data Availability Statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Author contributions

Josephina Haunschild: Conceptualization; Formal analysis; Investigation; Methodology; Software; Validation; Visualization; Writing—original draft. Konstantin von Aspern: Conceptualization; Formal analysis; Methodology; Visualization; Writing—review & editing. Johanna Herajärvi: Investigation; Methodology. Zara Dietze: Data curation; Formal analysis; Methodology; Writing—review & editing. Jörg Naumann: Investigation; Methodology. Susann Ossmann: Conceptualization; Investigation; Methodology. Martin Misfeld: Conceptualization; Writing—review & editing. Michael A. Borger: Conceptualization; Funding acquisition; Resources; Supervision; Writing—review & editing. Christian D. Etz: Conceptualization; Formal analysis; Funding acquisition; Investigation; Project administration; Resources; Supervision; Validation; Writing—review & editing.

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Sven Peterss and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.

REFERENCES

ABBREVIATIONS

ABBREVIATIONS
 
• CN

  Collateral network

 
• DTA

  Descending thoracic aorta

 
• DaP

  Distal aortic perfusion

 
• IQR

  Interquartile range

 
• MIS²ACE

  Minimally invasive staged segmental artery coil embolization

Author notes