Compromised right ventricular contractility in an ovine model of heart transplantation following 24 h donor brain stem death.

Background: Heart failure is an inexorably progressive disease with a high mortality, for which heart transplantation (HTx) remains the gold standard treatment. Currently, donor hearts are primarily derived from patients following brain stem death (BSD). BSD causes activation of the sympathetic nervous system, increases endothelin levels, and triggers significant inflammation that together with potential myocardial injury associated with the transplant procedure, may affect contractility of the donor heart.

Elevated Venous to Arterial Carbon Dioxide Gap and Anion Gap Are Associated with Poor Outcome in Cardiogenic Shock Requiring Extracorporeal Membrane Oxygenation Support.

Optimal management of cardiogenic shock requiring extracorporeal membrane oxygenation (ECMO) is still an evolving area in which assessment and optimization of the microcirculation may be critically important. We hypothesized that the venous arterial carbon dioxide gap (P(v-a)CO2 gap); the ratio of this gap to arterio-venous oxygen content (P(v-a)CO2/C(a-v)O2 ratio) and the anion gap would be early indicators of microcirculatory status and useful parameters for outcome prediction during ECMO support. We retrospectively reviewed 31 cardiogenic shock patients requiring veno-arterial ECMO, calculating P(v-a)CO2 gap and P(v-a)CO2/C(a-v)O2 ratios in the first 36 hours and the final 24 hours of ECMO support.

Current Understanding of Leukocyte Phenotypic and Functional Modulation During Extracorporeal Membrane Oxygenation: A Narrative Review.

A plethora of leukocyte modulations have been reported in critically ill patients. Critical illnesses such as acute respiratory distress syndrome and cardiogenic shock, which potentially require extracorporeal membrane oxygenation (ECMO) support, are associated with changes in leukocyte numbers, phenotype, and functions. The changes observed in these illnesses could be compounded by exposure of blood to the non-endothelialized surfaces and non-physiological conditions of ECMO.

The effect of hyperoxia on inflammation and platelet responses in an ex vivo extracorporeal membrane oxygenation circuit.

Use of extracorporeal membrane oxygenation (ECMO) is expanding, however, it is still associated with significant morbidity and mortality. Activation of inflammatory and innate immune responses and hemostatic alterations contribute to complications. Hyperoxia may play a role in exacerbating these responses.

Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation.

Background: Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO.

Objective: To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient.

Design, Participants And Intervention: An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours.

The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology.

Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened.

Protein-bound drugs are prone to sequestration in the extracorporeal membrane oxygenation circuit: results from an ex vivo study.

Introduction: Vital drugs may be degraded or sequestered in extracorporeal membrane oxygenation (ECMO) circuits, with lipophilic drugs considered to be particularly vulnerable. However, the circuit effects on protein-bound drugs have not been fully elucidated. The aim of this experimental study was to investigate the influence of plasma protein binding on drug disposition in ex vivo ECMO circuits.

The impact of acute lung injury, ECMO and transfusion on oxidative stress and plasma selenium levels in an ovine model.

The purpose of this study was to determine the effects of smoke induced acute lung injury (S-ALI), extracorporeal membrane oxygenation (ECMO) and transfusion on oxidative stress and plasma selenium levels. Forty ewes were divided into (i) healthy control (n=4), (ii) S-ALI control (n=7), (iii) ECMO control (n=7), (iv) S-ALI+ECMO (n=8) and (v) S-ALI+ECMO+packed red blood cell (PRBC) transfusion (n=14). Plasma thiobarbituric acid reactive substances (TBARS), selenium and glutathione peroxidase (GPx) activity were analysed at baseline, after smoke injury (or sham) and 0.

Oxidative stress during extracorporeal circulation.

There is an increased oxidative stress response in patients having cardiac surgery, haemodialysis or extracorporeal membrane oxygenation that is related to poorer outcomes and increased mortality. Exposure of the patients' blood to the artificial surfaces of these extracorporeal devices, coupled with inflammatory responses, hyperoxia and the pathophysiological aspects of the underlying illness itself, all contribute to this oxidative stress response. Oxidative stress occurs when there is a disruption of redox signalling and loss of control of redox balance.

Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation.

Introduction: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, with its success dependent on effective drug therapy that reverses the pathology and/or normalizes physiology. However, the circuit that sustains life can also sequester life-saving drugs, thereby compromising the role of ECMO as a temporary support device. This ex vivo study was designed to determine the degree of sequestration of commonly used antibiotics, sedatives and analgesics in ECMO circuits.

Development of simulated and ovine models of extracorporeal life support to improve understanding of circuit-host interactions.

Background: Extracorporeal life support (ECLS) is a lifesaving technology that is being increasingly used in patients with severe cardiorespiratory failure. However, ECLS is not without risks. The biosynthetic interface between the patient and the circuit can significantly alter inflammation, coagulation, pharmacokinetics and disposition of trace elements.

Antioxidant trace element reduction in an in vitro cardiopulmonary bypass circuit.

Many complications occurring after cardiac surgery are attributed to an acute increase in reactive oxygen and reactive nitrogen species, which under normal conditions are balanced by the antioxidant response. Two key enzymes of the antioxidant response, glutathione peroxidase (GPx) and superoxide dismutase (SOD), rely on trace elements for normal function. It was hypothesized that circulation of blood through the cardiopulmonary bypass (CPB) circuit would 1) reduce trace element levels and antioxidant function, 2) increase oxidative stress, and that 3) prepriming circuits with albumin would ameliorate trace element loss.