LUCAS - Lund University Cardiopulmonary Assist System

Lund University Cardiopulmonary Assist System (LUCAS) is a mechanical device providing automatic 5 cm deep chest compressions and active decompressions back to normal anatomical position with a frequency of 100 per minute, and a duty cycle of 50%, i.e., LUCAS is constructed to give chest compressions according to the latest international guidelines in cardiopulmonary resuscitation (CPR). The aim of the thesis was to study cardiac arrest using different porcine models of ventricular fibrillation. Four hypotheses were formulated: 1. LUCAS-CPR is superior to manual CPR regarding coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC). 2. Hypothermic LUCAS-CPR is superior to normothermic LUCAS-CPR in treating prolonged ventricular fibrillation. 3. The rate of ROSC after prolonged ventricular fibrillation will increase if LUCAS-CPR is given before defibrillation, and if defibrillation is given during on-going chest compressions. 4. LUCAS-CPR will cause fewer rib fractures than manual CPR. LUCAS-CPR gave significantly higher rates of ROSC and significantly higher CPP than manual CPR. LUCAS-CPR combined with surface cooling to 34°C was superior to normothermic LUCAS-CPR during 1 hour of CPR for ventricular fibrillation. Defibrillation was more effective to obtain ROSC after prolonged ventricular fibrillation if chest compressions were done before the shock, and if the shock was given during on-going LUCAS-CPR. LUCAS-CPR caused significantly fewer rib fractures during 20 minutes of CPR compared to manual CPR

A novel nonlinear afterload for ex vivo heart evaluation: Porcine experimental results

Background: Existing working heart models for ex vivo functional evaluation of donor hearts often use cardiac afterloads made up of discrete resistive and compliant elements. This approach limits the practicality of independently controlling systolic and diastolic aortic pressure to safely test the heart under multiple loading conditions. We present and investigate a novel afterload concept designed to enable such control. Methods: Six ∼70 kg pig hearts were evaluated in vivo, then ex vivo in left-ventricular working mode using the presented afterload. Both in vivo and ex vivo, the hearts were evaluated at two exertion levels: at rest and following a 20 μg adrenaline bolus, while measuring aortic pressure and flow, left ventricular pressure and volume, and left atrial pressure. Results: The afterload gave aortic pressure waveforms that matched the general shape of the in vivo measurements. A wide range of physiological systolic pressures (93 to 160 mm Hg) and diastolic pressures (73 to 113 mm Hg) were generated by the afterload. Conclusions: With the presented afterload concept, multiple physiological loading conditions could be tested ex vivo, and compared with the corresponding in vivo data. An additional control loop from the set pressure limits to the measured systolic and diastolic aortic pressure is proposed to address discrepancies observed between the set limits and the measured pressures

Prevention of ischemic myocardial contracture through hemodynamically controlled DCD

Purpose—Ischemic myocardial contracture (IMC) or ‘‘stoneheart’’ is a condition with rapid onset following circulatory death. It inhibits transplantability of hearts donated uponcirculatory death (DCD). We investigate the effectiveness of hemodynamic normalization upon withdrawal of life-sustaining therapy (WLST) in a large-animal controlled DCD model, with the hypothesis that reduction in cardiac work delays the onset of IMC. Methods—A large-animal study was conducted comprising of a control group (n = 6) receiving no therapy upon WLST, and a test group (n = 6) subjected to a protocol for fully automated computer-controlled hemodynamic drug administration. Onset of IMC within 1 h following circulatory death defined the primary end-point. Cardiac work estimates based on pressure-volume loop concepts were developed and used to provide insight into the effectiveness of the proposed computer-controlled therapy. Results—No test group individual developed IMC within 1 h, whereas all control group individuals did (4/6 within30 min). Conclusion—Automatic dosing of hemodynamic drugs in the controlled DCD context has the potential to prevent onset of IMC up to 1 h, enabling ethical and medically safe organ procurement. This has the potential to increase the use of DCD heart transplantation, which has been widely recognized as a means of meeting the growing demand for donor hearts

Identification of cardiac afterload dynamics from data

The prospect of ex vivo functional evaluation of donor hearts is considered. Particularly, the dynamics of a synthetic cardiac afterload model are compared to those of normal physiology. A method for identification of continuous-time transfer functions from sampled data is developed and verified against results from the literature. The method relies on exact gradients and Hessians obtained through automatic differentiation. This also enables straightforward sensitivity analyses. Such analyses reveal that the 4-element Windkessel model is not practically identifiable from representative data while the 3-element model underfits the data. Pressure–volume (PV) loops are therefore suggested as an alternative for comparing afterload dynamics

Closed-loop Prevention of Hypotension in the Heartbeating Brain-dead Porcine Model

Objective: The purpose of this paper is to demonstrate feasibility of a novel closed-loop controlled therapy for prevention of hypertension in the heartbeating brain-dead porcine model. Methods: Dynamic modeling and system identification were based on in-vivo data. A robust controller design was obtained for the identified models. Disturbance attenuation properties, and reliability of operation of the resulting control system, were evaluated in vivo. Results: The control system responded both predictably and consistently to external disturbances. It was possible to prevent mean arterial pressure to fall below a user-specified reference throughout 24 h of completely autonomous operation.Conclusion: Parameter variability in the identified models confirmed the benefit of closed-loop controlled administration of the proposed therapy. The evaluated robust controller was able to mitigate both process uncertainty and external disturbances. Significance: Prevention of hypertension is critical to the care of heartbeating brain-dead organ donors. Its automation would likely increase the fraction of organs suitable for transplantation from this patient group

The effects of epinephrine/norepinephrine on end-tidal carbon dioxide concentration, coronary perfusion pressure and pulmonary arterial blood flow during cardiopulmonary resuscitation

End-tidal CO2 concentration correlates with pulmonary blood flow during cardiopulmonary resuscitation and has been claimed to be a useful tool to judge the effectiveness of chest compression. A high concentration of end-tidal CO2 has been related to a better outcome. However, most authors have noticed a decrease in end-tidal CO2 concentration after administration of epinephrine, concomitant with an increase in coronary perfusion pressure and an increased incidence of return of spontaneous circulation. This study was performed to evaluate changes in end-tidal CO2 concentration after injection of vasopressors during cardiopulmonary resuscitation and to investigate the time-course of the response and possible explanations for it. After 1 min of electrically induced cardiac arrest and 5 min of chest compressions, 18 pigs were randomly assigned to receive 0.045 mg kg(-1) epinephrine, 0.045 mg kg(-1) norepinephrine or no drug. After another 4 min of chest compressions the pigs were defibrillated. End-tidal CO2, pulmonary blood flow and coronary perfusion pressure decreased immediately after the induction of cardiac arrest, increased slightly during chest compressions and increased initially to supernormal levels after the return of spontaneous circulation. Injection of epinephrine or norepinephrine during chest compressions decreased end-tidal CO2 51 +/- 2%, (mean +/- S.E.M.), and 43 +/- 1%, respectively, and pulmonary blood flow by 134 +/- 13 and 125 +/- 16%, respectively, within 1 min, simultaneously increasing coronary perfusion pressure from 10 +/- 2 to 45 +/- 5 mm Hg and from 11 +/- 1 to 38 +/- 5 mm Hg, respectively. The coronary perfusion pressure slowly fell, but the effects on end-tidal CO2 and pulmonary blood flow were prolonged. In conclusion, vasopressors increased coronary perfusion pressure and the likelihood of a return of spontaneous circulation, but decreased end-tidal CO2 concentration and induced a critical deterioration in cardiac output and thus oxygen delivery in this model of cardiopulmonary resuscitation

Safe Orthotopic Transplantation of Hearts Harvested 24 Hours after Brain Death and Preserved for 24 Hours.

The aim of this study was to demonstrate safe orthotopic transplantation of porcine donor hearts harvested 24 hours after brain death and preserved for 24 hours before transplantation

Levosimendan cardioprotection reduces the metabolic response during temporary regional coronary occlusion in an open chest pig model.

Background: Inotropic and myocardial anti-ischemic effects have been demonstrated with levosimendan. The comparison of levosimendan started before an ischemia-reperfusion event as compared with levosimendan started during ischemia has not been studied. Methods: In anesthetized pigs, a major branch of the circumflex artery was completely occluded for 30 min and then reperfused. The metabolism in the ischemic myocardium and in non-ischemic control myocardium was studied with microdialysis concomitantly with monitoring of global hemodynamics and coronary artery flow in the chosen artery. In the protection group (PRO, n = 6), a levosimendan infusion was started 30 min before coronary artery occlusion, and in the treatment group (TRE, n = 6), a levosimendan infusion was started 10 min after the coronary artery occlusion with a loading dose of 13.3 mu g/kg followed by an infusion of 0.67 mu g/kg/min. A two-way repeated measures ANOVA completed with Bonferroni's multiple comparison procedure was applied to the data. A P < 0.05 was considered significant. Results: During the ischemic period, the cardiac output and contractility (dp/dt(max)) were higher in the PRO as compared with the TRE and the systemic vascular resistance was lower. The myocardial microdialysate glucose concentration in the ischemic area during ischemia was higher in the PRO as compared with the TRE, and the lactate/pyruvate ratio and the lactate concentration were lower. The differences in the metabolites persisted into the first 10 min of reperfusion. No differences were found for the non-ischemic areas. Conclusions: Levosimendan used throughout myocardial ischemia-reperfusion might have a cardioprotective affect on the response to myocardial ischemia as compared with levosimendan started during the ischemia

Detection of Bronchial Function of NHBD Lung Following One-h Warm Ischemia by Organ Bath Model

This study investigated the feasibility and effects of organ bath to be used for detection of bronchial function of non-heart-beating donor (NHBD) lung after 1-h warm ischemia. Sixteen Swedish pigs were divided into two groups randomly: heart-beating donor (HBD) group and NHBD with 1-h warm ischemia (NHBD-1 h) group. The bronchial rings whose lengths and inner diameters were both 1.5 mm were obtained from isolated left lungs of all the pigs. Acetylcholine, arachidonic acid natrium and papaverine were used to test and compare the contractile and relaxant function of bronchial smooth muscles and epithelium-dependent relaxation (EpiDR) response between HBD and NHBD-1 h groups. The results showed that there was no significant difference in the values of bronchial precontraction between HBD and NHBD-1 h groups (5.18 +/- 0.07 vs 5.10 +/- 0.11 mN, P > 0.05). No significant difference in the values of EpiDR responses between HBD and NHBD-1 h groups (1.26 +/- 0.05 vs 1.23 +/- 0.07 mN, P > 0.05) was observed either. During the process of EpiDR induction, the rings had no spontaneous relaxation in two groups. In addition, papaverine solution completely relaxed the bronchial smooth muscles of all bronchial rings. It was concluded that after warm ischemia for 1 h, the contractile and relaxant abilities of bronchial smooth muscles, and the epithelium-dependent adjustment both kept intact. Organ bath model could be a liable and scientific way to evaluate the bronchial function of NHBD lung