Fast Hypothermia Induced by Continuous Renal Replacement Therapy Alleviates Renal and Intestinal Injury After Cardiac Arrest in Swine

Abstract Background: Renaland intestinal damagelead tomultiple organ dysfunction and death after cardiopulmonary resuscitation (CPR), and can be partly mitigated by therapeutic hypothermia. Currently, continuous renal replacement therapy (CRRT) was demonstrated to be an effectiveway to induce hypothermia. In the present study, we aimed to investigate the influence of CRRT cooling on renal and intestinal damage after CPR based on a porcine model.Methods: 32swine were subjected to ventricular fibrillation for 8 min, while defibrillation was performed at 5 min of CPR. All pigs were randomly allocated to receive CRRT (n = 9), surface cooling (SC, n = 9), normothermia (NT, n = 9) or sham control (Control, n = 5)at 5 min post resuscitation. In the CRRT group, the pigs werecooled by the combination of8-hr CRRT and16-hr SC,a rate of 180 ml/min of blood flow was initially set with the infusion line submerged in 4 °C of ice water. In the SC group, pigs were cooled by the 24-hr SC.As to theNT and Controlgroups, thetemperatures were maintained at a normal range. The levels of creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (IFABP) and diamine oxidase (DAO) in serum were measured at baseline and at 1, 3, 6, 12, 24and30h post resuscitation. Additionally, tissues of kidney and intestine were harvested, from which the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), the contents of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and theapoptosis levels were analyzed.Results:After resuscitation, the blood temperature decreasedsignificantlymore rapidlyin the CRRT group than in the SC group (9.8±1.6vs. 1.5±0.4 ℃/h, P <0.01). The levels of Cr, BUN, IFABP and DAOafter resuscitation were significantly lower in the two hypothermic groupscompared with the NT group. Furthermore, from pathological evidence, cooling induced by CRRTalleviated post-resuscitation renaland intestinal injury compared to SC.Conclusion:Fast hypothermia induced by continuous renal replacement therapy was superior to surface cooling in mitigating renal and intestinal injury post resuscitation.

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Fast Hypothermia Induced by Continuous Renal Replacement Therapy Alleviates Renal and Intestinal Injury after Cardiac Arrest in Swine

10.21203/rs.3.rs-36500/v1 ◽

2020 ◽

Author(s):

Jiefeng Xu ◽

Lin Shi ◽

Jiangang Wang ◽

Chunshuang Wu ◽

Qijiang Chen ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Multiple Organ ◽

Intestinal Injury ◽

Intestinal Damage ◽

Surface Cooling ◽

Fatty Acid Binding ◽

Blood Temperature ◽

Infusion Line

Abstract Background: Renal and intestinal damage lead to multiple organ dysfunction and death after cardiopulmonary resuscitation (CPR), and can be partly mitigated by therapeutic hypothermia. Currently, continuous renal replacement therapy (CRRT) was demonstrated to be an effective way to induce hypothermia. In the present study, we aimed to investigate the influence of CRRT cooling on renal and intestinal damage after CPR based on a porcine model.Methods: 32 swine were subjected to ventricular fibrillation for 8 min, while defibrillation was performed at 5 min of CPR. All pigs were randomly allocated to receive CRRT (n = 9), surface cooling (SC, n = 9), normothermia (NT, n = 9) or sham control (Control, n = 5) at 5 min post resuscitation. In the CRRT group, the pigs were cooled by the combination of 8-hr CRRT and 16-hr SC, a rate of 180 ml/min of blood flow was initially set with the infusion line submerged in 4 °C of ice water. In the SC group, pigs were cooled by the 24-hr SC. As to the NT and Control groups, the temperatures were maintained at a normal range. The levels of creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (IFABP) and diamine oxidase (DAO) in serum were measured at baseline and at 1, 3, 6, 12, 24 and 30h post resuscitation. Additionally, tissues of kidney and intestine were harvested, from which the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), the contents of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and the apoptosis levels were analyzed. Results: After resuscitation, the blood temperature decreased significantly more rapidly in the CRRT group than in the SC group (9.8 ± 1.6 vs. 1.5 ± 0.4 ℃/h, P < 0.01). The levels of Cr, BUN, IFABP and DAO after resuscitation were significantly lower in the two hypothermic groups compared with the NT group. Furthermore, from pathological evidence, cooling induced by CRRT alleviated post-resuscitation renal and intestinal injury compared to SC.Conclusion: Fast hypothermia induced by continuous renal replacement therapy was superior to surface cooling in mitigating renal and intestinal injury post resuscitation.

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Abstract 202: Fast Hypothermia Induced by Continuous Renal Replacement Therapy Alleviates Systemic Inflammation and Intestinal Injury After Cardiopulmonary Resuscitation in Swine

Circulation ◽

10.1161/circ.138.suppl_2.202 ◽

2018 ◽

Vol 138 (Suppl_2) ◽

Author(s):

Jiefeng Xu ◽

Qijiang Chen ◽

Xiaohong Jin ◽

Chunshuang Wu ◽

Zilong Li ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Cardiopulmonary Resuscitation ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Systemic Inflammation ◽

Serum Levels ◽

Multiple Organ ◽

Intestinal Injury ◽

Surface Cooling ◽

Fatty Acid Binding

Introduction: Systemic inflammation and intestinal injury contribute to post-resuscitation multiple organ dysfunction and death in cardiac arrest victims, and they can be partly alleviated by therapeutic hypothermia. Recently, continuous renal replacement therapy (CRRT) was shown to be an effective cooling method to induce fast hypothermia. In this study, we investigated the effects of CRRT cooling (CRRT-C) on systemic inflammation and intestinal injury after cardiopulmonary resuscitation (CPR) in swine. Hypothesis: Fast hypothermia induced by CRRT-C would alleviate post-resuscitation systemic inflammation and intestinal injury better than surface cooling (SC). Methods: Twenty-seven male domestic swine weighing 36 ± 2 kg were utilized. Ventricular fibrillation was induced for 8 mins while defibrillation was attempted after 5 mins of CPR. At 5 mins after resuscitation, the animals were randomized to receive either CRRT-C, SC or normotherma (NT). In the two hypothermic groups, the animals were cooled by either the combination of 8-hr CRRT and 16-hr SC or the whole 24-hr SC. In animals treated with CRRT-C, a higher rate of 180 ml/min of blood flow was initially set with the infusion line submerged in 4 °C of ice water. The temperature was normally maintained in the NT group. Results: After resuscitation, the rate of temperature decrease was significantly faster in the CRRT-C group than in the SC group (9.8±1.6 vs. 1.5±0.4 °C/h, p <0.01). The serum levels of tumor necrosis factor-α, interleukin-6, intestinal fatty acid binding protein and diamine oxidase after resuscitation were significantly lower in the two hypothermic groups compared with the NT group. However, post-resuscitation systemic inflammation and intestinal injury were further significantly alleviated in the CRRT-C group compared to the SC group (Table). Conclusion: Fast hypothermia induced by CRRT-C was superior to SC in alleviating post-resuscitation systemic inflammation and intestinal injury.

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