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Transpulmonary pressure can be estimated using esophageal balloon (EB) catheters, which come in a variety of manufacturing configurations. We assessed the performance of novel polyurethane EB designs, Aspisafe NG and NG+, against existing alternatives. We created a biomechanical model of the chest cavity using a plastic chamber and an ex-vivo porcine esophagus. The chamber was pressurized (− 20 and + 20 cmH2O) to simulate pleural pressures. We conducted tests with various EB inflation volumes and measured transesophageal pressure (TEP). TEP measurement was defined as accurate when the difference between pressure within the EB and chamber was 0 ± 1 cmH2O. We computed the minimal (Vaccuracy-min) and maximal (Vaccuracy-max) EB inflation volumes of accuracy. Inflation volumes were further validated using a surrogate method derived by the clinically validated positive pressure occlusion test (PPOT). When the esophageal balloons were filled with inflation volumes within the range provided by the manufacturers, the accuracy of TEP measurements was marginal. Our tests found median Vaccuracy-min across EB of 0.00–0.50 mL (p = 0.130), whereas Vaccuracy-max ranged 0.50–2.25 mL (p = 0.002). Post PPOT validation, median TEP was − 0.4 cmH2O (− 1.5 to 0.3) (p < 0.001 among catheters). The Aspisafe NG and NG+ were accurate in 81.7% and 77.8% of the measurements, respectively. We characterized two new EBs, which demonstrated good benchtop accuracy in TEP measurements. However, accuracy was notably influenced by the precise selection of EB inflation volumes. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Left ventricular stroke work index (LVSWI) and cardiac power index (CPI) account for the haemodynamic load of the left ventricle and are promising prognostic values in cardiogenic shock. However, accurately and non‐invasively measuring these parameters during veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) is challenging and potentially biased by the extracorporeal circulation. This study aimed to investigate, in an ovine model of cardiogenic shock, whether Pressure‐Strain Product (PSP), a novel speckle‐tracking echocardiography parameter, (1) can correlate with pressure‐volume catheter‐based LVSWI and CPI, and (2) can be load‐independent during the flow modification of V‐A ECMO.Nine Dorset‐cross ewes (51 ± 4 kg) were included. After cardiogenic shock was induced, full support V‐A ECMO (X L/min based on 60 mL/kg/min) commenced. At seven time points during 24‐h observation, echocardiographic parameters as well as pressure‐volume catheter‐based LVSWI and CPI were simultaneously measured with X and following X‐1 L/min of ECMO flow. PSP was calculated by multiplying global circumferential strain or global radial strain, and mean arterial pressure, for PSPcirc or PSPrad, respectively.PSPcirc showed a stronger correlation with LVSWI (correlation coefficient, CC = .360, p < .001) and CPI (CC = .283, p < .001) than other echocardiographic parameters. The predictability of PSPcirc for pressure‐volume catheter‐based LVSWI (AUC .82) and CPI (AUC .80) was also higher than other echocardiographic parameters. No statistically significant differences were identified between the two ECMO flow variations in PSPcirc (p = .558).A novel echocardiographic parameter, PSP, may non‐invasively predict pressure‐volume catheter‐based LVSWI and CPI in a load‐independent manner in a cardiogenic shock supported by V‐A ECMO. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The commonest echocardiographic measurement, left ventricular ejection fraction, can not necessarily predict mortality of recipients following heart transplantation potentially due to afterload dependency. Afterload‐independent left ventricular stroke work index (LVSWI) is alternatively recommended by the current guideline; however, pulmonary artery catheters are rarely inserted in organ donors in most jurisdictions. We propose a novel non‐invasive echocardiographic parameter, Pressure‐Strain Product (PSP), as a potential surrogate of catheter‐based LVSWI. This study aimed to investigate if PSP could correlate with catheter‐based LVSWI in an ovine model of brain stem death (BSD) donors. The association between PSP and myocardial mitochondrial function in the post‐transplant hearts was also evaluated.Thirty‐one female sheep (weight 47 ± 5 kg) were divided into two groups; BSD (n = 15), and sham neurologic injury (n = 16). Echocardiographic parameters including global circumferential strain (GCS) and global radial strain (GRS) and pulmonary artery catheter‐based LVSWI were simultaneously measured at 8‐timepoints during 24‐h observation. PSP was calculated as a product of GCS or GRS, and mean arterial pressure for PSPcirc or PSPrad, respectively. Myocardial mitochondrial function was evaluated following 6‐h observation after heart transplantation.In BSD donor hearts, PSPcirc (n = 96, rho = .547, p < .001) showed the best correlation with LVSWI among other echocardiographic parameters. PSPcirc returned AUC of .825 to distinguish higher values of cardiomyocyte mitochondrial function (cut‐off point; mean value of complex 1,2 O2 Flux) in post‐transplant hearts, which was greater than other echocardiographic parameters.PSPcirc could be used as a surrogate of catheter‐based LVSWI reflecting mitochondrial function. [ABSTRACT FROM AUTHOR]

Background: Left ventricular stroke work index (LVSWI) and afterload‐related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle‐tracking echocardiography parameter, Pressure‐Strain Product (PSP), can non‐invasively predict catheter‐based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub‐phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis‐like conditions. Methods: Sixteen sheep with ARDS were randomly assigned to either (1) sepsis‐like (n = 8) or (2) non‐sepsis‐like (n = 8) group. Each ARDS and sepsis‐like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter‐based LVSWI (the product of stroke work index, mean arterial pressure and.0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). Results: PSPcirc showed a significant correlation with LVSWI (r2 =.66, p <.001) and ACP (r2 =.82, p <.001) in the sepsis‐like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC.86) and ACP (AUC.88), and PSPrad predicted serum lactate (AUC.75) better than LV ejection fraction, global circumferential and radial strain. Conclusions: A novel PSP has the potential to non‐invasively predict catheter‐based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Whilst the presence of 2 subphenotypes among the heterogenous Acute Respiratory Distress Syndrome (ARDS) population is becoming clinically accepted, subphenotype-specific treatment efficacy has yet to be prospectively tested. We investigated anti-inflammatory treatment in different ARDS models in sheep, previously shown similarities to human ARDS subphenotypes, in a preclinical, randomized, blinded study. Thirty anesthetized sheep were studied up to 48 h and randomized into: (a) OA: oleic acid (n = 15) and (b) OA-LPS: oleic acid and subsequent lipopolysaccharide (n = 15) to achieve a PaO2/FiO2 ratio of < 150 mmHg. Then, animals were randomly allocated to receive treatment with methylprednisolone or erythromycin or none. Assessed outcomes were oxygenation, pulmonary mechanics, hemodynamics and survival. All animals reached ARDS. Treatment with methylprednisolone, but not erythromycin, provided the highest therapeutic benefit in Ph2 animals, leading to a significant increase in PaO2/FiO2 ratio by reducing pulmonary edema, dead space ventilation and shunt fraction. Animals treated with methylprednisolone displayed a higher survival up to 48 h than all others. In animals treated with erythromycin, there was no treatment benefit regarding assessed physiological parameters and survival in both phenotypes. Treatment with methylprednisolone improves oxygenation and survival, more so in ovine phenotype 2 which resembles the human hyperinflammatory subphenotype. [ABSTRACT FROM AUTHOR]

Whilst the presence of 2 subphenotypes among the heterogenous Acute Respiratory Distress Syndrome (ARDS) population is becoming clinically accepted, subphenotype-specific treatment efficacy has yet to be prospectively tested. We investigated anti-inflammatory treatment in different ARDS models in sheep, previously shown similarities to human ARDS subphenotypes, in a preclinical, randomized, blinded study. Thirty anesthetized sheep were studied up to 48 h and randomized into: (a) OA: oleic acid (n = 15) and (b) OA-LPS: oleic acid and subsequent lipopolysaccharide (n = 15) to achieve a PaO2/FiO2 ratio of < 150 mmHg. Then, animals were randomly allocated to receive treatment with methylprednisolone or erythromycin or none. Assessed outcomes were oxygenation, pulmonary mechanics, hemodynamics and survival. All animals reached ARDS. Treatment with methylprednisolone, but not erythromycin, provided the highest therapeutic benefit in Ph2 animals, leading to a significant increase in PaO2/FiO2 ratio by reducing pulmonary edema, dead space ventilation and shunt fraction. Animals treated with methylprednisolone displayed a higher survival up to 48 h than all others. In animals treated with erythromycin, there was no treatment benefit regarding assessed physiological parameters and survival in both phenotypes. Treatment with methylprednisolone improves oxygenation and survival, more so in ovine phenotype 2 which resembles the human hyperinflammatory subphenotype. [ABSTRACT FROM AUTHOR]

Differential hypoxaemia (DH) is common in patients supported by femoral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and can cause cerebral hypoxaemia. To date, no models have studied the direct impact of flow on cerebral damage. We investigated the impact of V-A ECMO flow on brain injury in an ovine model of DH. After inducing severe cardiorespiratory failure and providing ECMO support, we randomised six sheep into two groups: low flow (LF) in which ECMO was set at 2.5 L min−1 ensuring that the brain was entirely perfused by the native heart and lungs, and high flow (HF) in which ECMO was set at 4.5 L min−1 ensuring that the brain was at least partially perfused by ECMO. We used invasive (oxygenation tension—PbTO2, and cerebral microdialysis) and non-invasive (near infrared spectroscopy—NIRS) neuromonitoring, and euthanised animals after five hours for histological analysis. Cerebral oxygenation was significantly improved in the HF group as shown by higher PbTO2 levels (+ 215% vs − 58%, p = 0.043) and NIRS (67 ± 5% vs 49 ± 4%, p = 0.003). The HF group showed significantly less severe brain injury than the LF group in terms of neuronal shrinkage, congestion and perivascular oedema (p < 0.0001). Cerebral microdialysis values in the LF group all reached the pathological thresholds, even though no statistical difference was found between the two groups. Differential hypoxaemia can lead to cerebral damage after only a few hours and mandates a thorough neuromonitoring of patients. An increase in ECMO flow was an effective strategy to reduce such damages. [ABSTRACT FROM AUTHOR]

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments. [ABSTRACT FROM AUTHOR]

R3270 --> 701.5 --> Introduction: Heart transplantation (HTx) is the primary therapy for end‐stage heart failure. For HTx, donor hearts are typically preserved on ice in a cooler (devoid of oxygen), termed cold static storage (CSS). CSS beyond 4 hrs increases the risk of primary graft dysfunction (PGD), the leading cause of early death post‐HTx. Hypothermic ex vivo perfusion (HEVP) of donor hearts allows oxygen delivery during preservation, and we hypothesise, may safely extend donor heart preservation time without increasing PGD risk. We sought to compare post‐HTx recipient survival, cardiac contractility, mitochondrial function, and injury following donor heart preservation by CSS (2 hrs) or HEVP (2 and 8 hrs). Methods: Brain death was induced in donor sheep for 24 hrs, hearts were then preserved by a) CSS for 2 hrs (n=8), b) HEVP for 2 hrs (n=6), or c) HEVP for 8 hrs (n=7). Orthotopic HTx was performed in matched recipients, with progressive hemodynamic management and monitoring for 6 hrs post‐HTx. Recipient cardiac function was assessed by echocardiography, and troponin I levels were measured in plasma. Mitochondrial function, in vitro contractile responses to noradrenaline (trabeculae), and histopathological changes were determined in cardiac tissue collected at end‐study. Results: All HEVP recipients survived to 6 hrs post‐HTx, compared to 6/8 CSS recipients. HEVP (2 and 8 hrs) recipients required less vasoactive support for adequate hemodynamic function, and exhibited reduced blood lactate levels compared to CSS. Post‐HTx cardiac function and troponin I levels were comparable between groups over time, however improved contractile responses to noradrenaline were observed in isolated trabeculae from 2 and 8 hr HEVP hearts. Cardiac mitochondrial function was similar between all groups, except for the 2 hrs HEVP left ventricle, where greater improvements in mitochondrial membrane potential generation were observed. Regardless of preservation technique, histological scores revealed widespread cardiac injury (e.g. myocytolysis and neutrophil infiltration). Conclusion: Donor heart preservation by HEVP shows promising post‐HTx outcomes in comparison to CSS in a sheep HTx model. HEVP can be safely extended up to 8 hrs, without compromising post‐HTx recipient survival, cardiac contractile or mitochondrial function. HEVP may assist in overcoming limitations in preservation time associated with HTx, without increasing PGD risk. The Australian Non‐Ischemic Heart Preservation (NIHP) trial is currently assessing extended HEVP in clinical HTx (ACTRN12620000595910p). [ABSTRACT FROM AUTHOR]