Neuroprotective effect of selective hypothermic cerebral perfusion in extracorporeal cardiopulmonary resuscitation: A preclinical studyCentral MessagePerspective
Kerong Zhai, MD,
Mingming Li, MD,
Jian Li, MD,
Shilin Wei, MD,
Zhenzhen Li, MD,
Yanchun Zhang, MD,
Bingren Gao, MD,
Xiangyang Wu, MD, PhD,
Yongnan Li, MD, PhD
Affiliations
Kerong Zhai, MD
Department of Cardiac Surgery, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China; Department of Laboratory of Extracorporeal Life Support, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
Mingming Li, MD
Department of Laboratory of Extracorporeal Life Support, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China; Department of Neurology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
Jian Li, MD
Department of Laboratory of Extracorporeal Life Support, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
Shilin Wei, MD
Department of Cardiac Surgery, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China; Department of Laboratory of Extracorporeal Life Support, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
Zhenzhen Li, MD
Department of Cardiopulmonary Bypass, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
Yanchun Zhang, MD
Department of Cardiac Surgery, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
Bingren Gao, MD
Department of Cardiac Surgery, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
Xiangyang Wu, MD, PhD
Department of Cardiac Surgery, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
Yongnan Li, MD, PhD
Department of Cardiac Surgery, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China; Department of Laboratory of Extracorporeal Life Support, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China; Address for reprints: Yongnan Li, MD, PhD, Department of Cardiac Surgery, Lanzhou University Second Hospital, No. 82, Cuiyingmen, Chengguan District, Lanzhou, China, 730030.
Objective: Neurologic complications seriously affect the survival rate and quality of life in patients with extracorporeal cardiopulmonary resuscitation (ECPR) undergoing cardiac arrest. This study aimed to repurpose selective hypothermic cerebral perfusion (SHCP) as a novel approach to protect the brains of these patients. Methods: Rats were randomly allocated to Sham, ECPR, and SHCP combined ECPR (CP-ECPR) groups. In the ECPR group, circulatory resuscitation was performed at 6 minutes after asphyxial cardiac arrest by extracorporeal membrane oxygenation. The vital signs were monitored for 3 hours, and body and brain temperatures were maintained at the normal level. In the CP-ECPR group, the right carotid artery catheterization serving as cerebral perfusion was connected with the extracorporeal membrane oxygenation device to achieve selective brain cooling (26-28 °C). Serum markers of brain injury and pathomorphologic changes in the hippocampus were evaluated. Three biological replicates further received RNA sequencing in ECPR and CP-ECPR groups. Microglia activation and inflammatory cytokines in brain tissues and serum were detected. Results: SHCP rapidly reduced the brain-targeted temperature and significantly alleviated nerve injury. This was evident from the reduced brain injury serum biomarker levels, lower pathologic scores, and more surviving neurons in the hippocampus in the CP-ECPR group. Furthermore, more differentially expressed genes for inflammatory responses were clustered functionally according to Kyoto Encyclopedia of Genes and Genomes pathway analysis. And SHCP reduced microglia activation and the release of proinflammatory mediators. Conclusions: Our preliminary data indicate that SHCP may serve as a potential therapy to attenuate brain injury via downregulation of neuroinflammation in patients with ECPR.
