Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post–Cardiac Arrest Rat: A Novel Metabolic Phenotype

Abstract

BackgroundThe concept that resuscitation from cardiac arrest (CA) results in a metabolic injury is broadly accepted, yet patients never receive this diagnosis. We sought to find evidence of metabolic injuries after CA by measuring O2 consumption and CO2 production (VCO 2) in a rodent model. In addition, we tested the effect of inspired 100% O2 on the metabolism.Methods and ResultsRats were anesthetized and randomized into 3 groups: resuscitation from 10‐minute asphyxia with inhaled 100% O2 (CA–fraction of inspired O2 [FIO2] 1.0), with 30% O2 (CA‐FIO 2 0.3), and sham with 30% O2 (sham‐FIO 2 0.3). Animals were resuscitated with manual cardiopulmonary resuscitation. The volume of extracted O2 (VO 2) and VCO 2 were measured for a 2‐hour period after resuscitation. The respiratory quotient (RQ) was RQ=VCO 2/VO 2. VCO 2 was elevated in CA‐FIO 2 1.0 and CA‐FIO 2 0.3 when compared with sham‐FIO 2 0.3 in minutes 5 to 40 after resuscitation (CA‐FIO 2 1.0: 16.7±2.2, P<0.01; CA‐FIO 2 0.3: 17.4±1.4, P<0.01; versus sham‐FIO 2 0.3: 13.6±1.1 mL/kg per minute), and then returned to normal. VO 2 in CA‐FIO 2 1.0 and CA‐FIO 2 0.3 increased gradually and was significantly higher than sham‐FIO 2 0.3 2 hours after resuscitation (CA‐FIO 2 1.0: 28.7±6.7, P<0.01; CA‐FIO 2 0.3: 24.4±2.3, P<0.01; versus sham‐FIO 2 0.3: 15.8±2.4 mL/kg per minute). The RQ of CA animals persistently decreased (CA‐FIO 2 1.0: 0.54±0.12 versus CA‐FIO 2 0.3: 0.68±0.05 versus sham‐FIO 2 0.3: 0.93±0.11, P<0.01 overall).Conclusions CA altered cellular metabolism resulting in increased VO 2 with normal VCO 2. Normal VCO 2 suggests that the postresuscitation Krebs cycle is operating at a presumably healthy rate. Increased VO 2 in the face of normal VCO 2 suggests a significant alteration in O2 utilization in postresuscitation. Several RQ values fell well outside the normally cited range of 0.7 to 1.0. Higher FIO 2 may increase VO 2, leading to even lower RQ values.

Looking for CO 2 : Exploring the Novel Finding of Low Respiratory Quotient After Cardiac Arrest

“…The primary finding of Shinozaki and colleagues7 was that VO 2 increased out of proportion to the observed increase in VCO 2 , leading to lower‐than‐expected RQs in the post‐cardiac arrest animals. The RQ in rats and all mammals depends on the fuels being consumed during metabolism, and normally ranges from 0.7 (with chiefly lipid fuel) to 1.0 (with predominantly carbohydrate fuel).…”

“…These parameters are both potential prognostic indicators and targets of treatment. The work by Shinozaki and colleagues7 is painstakingly done and well thought out. The investigators have done everything possible to minimize the chance of measurement error and they present a truly novel finding.…”

“…In the current issue of the Journal of the American Heart Association (JAHA) , Shinozaki and colleagues present a rat model used to compare VO 2 , carbon dioxide production (VCO 2 ) and the respiratory quotient (RQ) after asphyxial cardiac arrest and resuscitation with the same calculations made in rats undergoing a sham surgery 7. This model has been used widely since the 1980s 8.…”

“…The study by Shinozaki and colleagues7 required precise accounting for gas exchange to estimate components of global metabolism, and the investigators meticulously describe the techniques for ensuring that measurements were accurate. For many reasons, it is challenging to obtain accurate measurements of VO 2 and VCO 2 in critically ill patients with devices that use breath‐by‐breath measurements (as most clinically available devices do).…”

“…Shinozaki and colleagues7 considered all these factors in designing their device. Gases were sampled from the ventilator circuit.…”