Novel Porcine Model of Acute Severe Cardiogenic Shock Developed by Upper-Body Hypoxia

Abstract

Despite the urgent need for experimental research in the field of acute heart failure and, particularly cardiogenic shock, currently there are only limited options in large animal models enabling research using devices applied to human subjects. The majority of available models are either associated with an unacceptably high rate of acute mortality or are incapable of developing sufficient severity of acute heart failure. The objective of our research was to develop a novel large animal model of acute severe cardiogenic shock. Advanced left ventricular dysfunction was induced by global myocardial hypoxia by perfusing the upper body (including coronary arteries) with deoxygenated venous blood. The model was tested in 12 pigs: cardiogenic shock with signs of tissue hypoxia developed in all animals with no acute mortality. Cardiac output decreased from a mean (± SD) of 6.61±1.14 l/min to 2.75±0.63 l/min, stroke volume from 79.7±9.8 ml to 25.3±7.8 ml and left ventricular ejection fraction from 61.2±4.3 % to 17.7±4.8 % (P≤0.001 for all comparisons). In conclusion, the porcine model of acute cardiogenic shock developed in the present study may provide a basis for studying severe left ventricular dysfunction, low cardiac output and hypotension in large animals. The global myocardial hypoxia responsible for the decrease in cardiac contractility was not associated with acute death in this model.

Increasing venoarterial extracorporeal membrane oxygenation flow puts higher demands on left ventricular work in a porcine model of chronic heart failure

“…A recent study by our group described hemodynamic effects of VA ECMO on an innovative animal model of acute HF induced by hypoxic coronary perfusion [8,20], and these findings were later confirmed by computer modeling [9]. Similar to our current design, the effects of increasing EBF on LV were reported.…”

“…Especially in this context of LV overload, evaluation of VA ECMO in experiments with heart failure (HF) models have become important before translations to clinical practice. LV performance has been studied on models with intact or acutely decompensated hearts [6,8,[19][20][21][22], but to our knowledge, there have been no experimental studies on hemodynamic effects of VA ECMO in conditions of chronic HF and its decompensation. Even though a significant part of VA ECMO clinical applications is for circulatory decompensation developed on grounds of previously present chronic heart disease, we still lack evidence from corresponding experiments.…”

Electrocardiogram-synchronized pulsatile extracorporeal life support preserves left ventricular function and coronary flow in a porcine model of cardiogenic shock

“…Sixteen female swine ( Sus scrofa domestica , Large White × Landrace crossbreed), four to five months of age and a mean body weight of 45 kg were used. Full details of the animal model used in the present study can be found in previous publications [ 13 , 23 ].…”

“…An initial rapid IV infusion of 1000 mL normal saline was administered after anesthesia induction, followed by a continuous IV drip at a rate of 100 mL/h to 500 mL/h to reach and maintain a mean right atrial pressure of 5 mmHg to 7 mmHg. An unfractionated heparin IV bolus (100 U/kg) was administered after sheath placement, followed by a continuous IV infusion of 50 U/kg/h to maintain an activated clotting time of 200 s to 250 s. Values were monitored every hour using the Hemochron Jr Signature Plus Microcoagulation System (ITC, Piscataway, NJ, USA)” [ 13 ][ 23 ].…”

Technical Feasibility and Physiological Relevance of Hypoxic Cell Culture Models

“…Similarly, a systemic response of the entire body to high altitude is triggered by hypoxia (7,8). Hypoxia is an integral part of the pathophysiology of many diseases, including chronic obstructive pulmonary disease (9), heart failure (10,11), sleep apnea syndrome (12), anemia (13), and cancer, and its basic research can reveal mechanisms that may 1 day be exploited in therapy development (14).…”