Acute type A aortic dissection (ATAAD) is the most fatal form of aortic dissection, associated with high morbidity and mortality rates [1, 2]. In China, total arch replacement (TAR) combined with frozen elephant trunk (FET) implantation has become a widely adopted strategy for treating ATAAD. This approach integrates the advantages of open surgery and endovascular repair, offering favorable outcomes with relatively low morbidity and mortality [3, 4]. Moreover, the use of a single upper hemisternotomy (UHS) has enabled the adoption of minimally invasive techniques in this complex procedure [5].

Previous research has indicated that rewarming from moderate to deep hypothermia may contribute to neurological injury, while mild hypothermia is associated with a lower risk of rewarming-related neurocomplications [6]. Lower antegrade body perfusion (LABP) during aortic arch surgery significantly reduces circulatory arrest time and distal organ ischemia, allowing for higher operative temperatures and improved organ protection [7]. Based on this evidence, we introduced mild hypothermic circulatory arrest (MiHCA) combined with LABP into the management of ATAAD [8]. Despite the promise of this combination, most existing studies on LABP are retrospective and focus on its application under moderate or deep hypothermic conditions. Thus, a lack of prospective data remains to evaluate LABP combined with MiHCA, while the impact of this strategy on major organ outcomes has not been well characterized.

To further investigate the protective effects of MiHCA versus moderate hypothermic circulatory arrest (MoHCA) on major organs, specifically the brain, liver, and kidneys, we conducted a single-center, prospective, non-inferiority trial to assess the safety and efficacy of MiHCA combined with LABP during TAR for ATAAD.

Between July 2020 and August 2022, 307 patients were assessed for eligibility at the General Hospital of Northern Theater Command due to acute type A aortic dissection (ATAAD). A total of 294 patients provided informed consent and were randomized equally into the MI group (n = 147) and the MO group (n = 147) (Fig. 2). Baseline clinical characteristics were comparable between the two groups (Table 1).

Fig. 2.

Patient enrollment flowchart. A total of 307 patients with acute type A aortic dissection (ATAAD) were referred to the General Hospital of Northern Theater Command. Of these, 294 provided informed consent and were randomized equally into the MI group (n = 147) and the MO group (n = 147). Abbreviations: ATAAD, acute type A aortic dissection; MI, mild hypothermic circulatory arrest with lower antegrade body perfusion; MO, moderate hypothermic circulatory arrest.

The main findings of this study were that 24-hour postoperative ALT levels and the incidence of AKI were significantly lower in the MI group compared to the MO group. In contrast, the incidence of TND and PND did not differ significantly between the groups. These results suggest that MiHCA combined with LABP can be safely and effectively implemented, with improved protection of lower-body organs, consistent with previous retrospective studies [8, 9, 10, 11].

Reducing circulatory arrest (CA) time has been widely explored as a key strategy to protect lower-body organs during aortic arch surgery [8, 11, 12, 13]. For example, the use of endo-balloon occlusion combined with femoral artery retrograde perfusion has been shown to significantly shorten CA time while reducing the incidence of AKI at higher CA temperatures [11, 14]. Similarly, retrograde inferior vena caval perfusion has been used to reduce or avoid lower-body ischemia, resulting in non-inferior outcomes regarding postoperative renal failure, liver dysfunction, and AKI [12]. From a mechanistic standpoint, prolonged CA is known to increase the risk of ischemia-reperfusion injury, oxidative stress, and systemic inflammation—key drivers of postoperative organ dysfunction. LABP may mitigate these effects by maintaining distal perfusion during arrest, preserving microvascular integrity, and reducing tissue hypoxia. Additionally, the use of mild hypothermia may help avoid the adverse effects of deep hypothermia and rewarming-related neurological injury, while ensuring adequate metabolic protection. These factors provide a plausible explanation for the lower incidence of AKI and improved hepatic function observed in the MiHCA + LABP group.

Similar to previous research [8, 13], our study employed antegrade perfusion with balloon occlusion. LABP provided oxygenated blood to the lower body, reducing the CA time from 16 to 5 minutes. This was associated with a significant reduction in postoperative ALT levels and a decrease in the incidence of AKI. This protective effect may be attributed to the significant decrease in ischemia time (5 vs. 16 minutes; p = 0.000), with LABP offering perfusion flow comparable to that delivered via a standard 4-branch prosthetic graft. However, while liver injury and overall AKI incidence were improved, the rate of acute renal failure was not significantly different between groups. This may reflect the complexity of renal injury mechanisms and the need for longer-term follow-up or larger sample sizes. Nonetheless, LABP ensured more continuous blood flow to vital organs during the procedure, even at a higher operative temperature. Additionally, the use of LABP allows for a more controlled and less time-constrained distal anastomosis, which can be especially beneficial for less experienced surgeons performing TAR.

Previous studies have shown that mild hypothermia involves only 3–5 °C of rewarming, while moderate-to-deep hypothermia requires 10–20 °C of rewarming, which is associated with a higher risk of rewarming-induced neuroinjury [6]. BSACP has also been shown to provide improved cerebral protection compared to unilateral perfusion [15, 16]. Several surgical teams have successfully performed TAR under mild hypothermia with favorable outcomes [17, 18]. However, this study observed no significant difference in the incidence of TND or PND between the MI and MO groups, despite the MI group showing significantly lower intraoperative regional cerebral oxygen saturation (rSO₂) levels (58% vs. 62%; p = 0.023). This finding may suggest that the modest 2 °C difference in nasopharyngeal temperature between the groups was not sufficient to affect rewarming-related neurological outcomes. Our results are consistent with previous studies, which report no clear neurological advantage of mild hypothermia over moderate in the setting of well-maintained cerebral perfusion. These findings highlight the need for future investigations to more precisely define the threshold at which temperature differences during circulatory arrest translate into clinically meaningful neurological effects.

Finally, our findings confirm that the single UHS approach remains suitable for total arch replacement, even when combined with LABP.

This study has several limitations. First, we compared MiHCA combined with LABP against MoHCA alone, introducing two variables—higher circulatory arrest temperature and LABP—in the MI group. However, based on prior studies demonstrating that LABP under MoHCA already improves outcomes compared to MoHCA alone, and considering that LABP may help counteract the metabolic stress associated with higher temperatures, we treated these combinations as two distinct surgical strategies rather than as isolated variables. Nonetheless, because the individual effects of temperature and LABP were not independently assessed, future studies should include an additional group that receives MoHCA plus LABP to promote more accurate comparisons among the three strategies. Second, the sample size was relatively small, which may have limited the statistical power of some analyses. Therefore, further studies with larger cohorts are necessary to confirm the observed trends and investigate additional clinical effects. Lastly, this was a single-center trial performed by a specialized surgical team, which may limit the generalizability of the results. A multicenter randomized controlled trial is required to evaluate the broader applicability of this approach.

This study supports our previous findings, suggesting that MiHCA combined with LABP via a single UHS is a safe and feasible treatment option for acute type A aortic dissection. LABP significantly shortens the time of circulatory arrest and is associated with reduced postoperative ALT levels and a lower incidence of AKI, indicating improved protection of lower-body organs.

The study protocol and individual participant data supporting the results reported are available from the corresponding authors upon reasonable request.

YL and LX performed the experiments and wrote the manuscript. ZY, YG, LW, BW, and XX assisted in performing the experiments and prepared all the figures. YL designed the study and revised the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work to take public responsibility for appropriate portions of the content and agreed to be accountable for all aspects of the work in ensuring that questions related to its accuracy or integrity.

The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethics Committee of the General Hospital of Northern Theater Command (Approval No. K2020.19). It was prospectively registered with the Chinese Clinical Trial Registry (ChiCTR2000033852) prior to patient enrollment. Written informed consent was obtained from all participants before randomization. This manuscript complies with the CONSORT reporting guidelines.

This work was supported by the Natural Science Foundation of Liaoning Province (2023JH2/101700107 and 2023JH6/100100034).

The authors declare no conflict of interest.