Extracorporeal resuscitation with carbon monoxide improves renal function by targeting inflammatory pathways in cardiac arrest in pigs.

Deleterious consequences like acute kidney injury frequently occur upon successful resuscitation from cardiac arrest. Extracorporeal life support is increasingly used to overcome high cardiac arrest mortality. Carbon monoxide (CO) is an endogenous gasotransmitter, capable of reducing renal injury. In our study, we hypothesized that addition of CO to extracorporeal resuscitation hampers severity of renal injury in a porcine model of cardiac arrest. Hypoxic cardiac arrest was induced in pigs. Animals were resuscitated using a conventional [cardiopulmonary resuscitation (CPR)], an extracorporeal (E-CPR), or a CO-assisted extracorporeal (CO-E-CPR) protocol. CO was applied using a membrane-controlled releasing system. Markers of renal injury were measured, and histopathological analyses were carried out. We investigated renal pathways involving inflammation as well as apoptotic cell death. No differences in serum neutrophil gelatinase-associated lipocalin (NGAL) were detected after CO treatment compared with Sham animals (Sham 71 ± 7 and CO-E-CPR 95 ± 6 ng/mL), while NGAL was increased in CPR and E-CPR groups (CPR 135 ± 11 and E-CPR 124 ± 5 ng/mL; P < 0.05). Evidence for histopathological damage was abrogated after CO application. CO increased renal heat shock protein 70 expression and reduced inducible cyclooxygenase 2 (CPR: 60 ± 8; E-CPR 56 ± 8; CO-E-CPR 31 ± 3 µg/mL; P < 0.05). Caspase 3 activity was decreased (CPR 1,469 ± 276; E-CPR 1,670 ± 225; CO-E-CPR 755 ± 83 pg/mL; P < 0.05). Furthermore, we found a reduction in renal inflammatory signaling upon CO treatment. Our data demonstrate improved renal function by extracorporeal CO treatment in a porcine model of cardiac arrest. CO reduced proinflammatory and proapoptotic signaling, characterizing beneficial aspects of a novel treatment option to overcome high mortality.

Standardized model of porcine resuscitation using a custom-made resuscitation board results in optimal hemodynamic management.

AIM: Standardized modeling of cardiac arrest and cardiopulmonary resuscitation (CPR) is crucial to evaluate new treatment options. Experimental porcine models are ideal, closely mimicking human-like physiology. However, anteroposterior chest diameter differs significantly, being larger in pigs and thus poses a challenge to achieve adequate perfusion pressures and consequently hemodynamics during CPR, which are commonly achieved during human resuscitation. The aim was to prove that standardized resuscitation is feasible and renders adequate hemodynamics and perfusion in pigs, using a specifically designed resuscitation board for a pneumatic chest compression device. METHODS AND RESULTS: A "porcine-fit" resuscitation board was designed for our experiments to optimally use a pneumatic compression device (LUCAS® II, Physio-Control Inc.), which is widely employed in emergency medicine and ideal in an experimental setting due to its high standardization. Asphyxial cardiac arrest was induced in 10 German hybrid landrace pigs and cardiopulmonary resuscitation was performed according to ERC/AHA 2015 guidelines with mechanical chest compressions. Hemodynamics were measured in the carotid and pulmonary artery. Furthermore, arterial blood gas was drawn to assess oxygenation and tissue perfusion. The custom-designed resuscitation board in combination with the LUCAS® device demonstrated highly sufficient performance regarding hemodynamics during CPR (mean arterial blood pressure, MAP 46 ±â€¯1 mmHg and mean pulmonary artery pressure, mPAP of 36 ±â€¯1 mmHg over the course of CPR). MAP returned to baseline values at 2 h after ROSC (80 ±â€¯4 mmHg), requiring moderate doses of vasopressors. Furthermore, stroke volume and contractility were analyzed using pulse contour analysis (106 ±â€¯3 ml and 1097 ±â€¯22 mmHg/s during CPR). Blood gas analysis revealed CPR-typical changes, normalizing in the due course. Thermodilution parameters did not show persistent intravascular volume shift. CONCLUSION: Standardized cardiopulmonary resuscitation is feasible in a porcine model, achieving adequate hemodynamics and consecutive tissue perfusion of consistent quality.