Search

Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6–9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial. [ABSTRACT FROM AUTHOR]

Introduction: Diving in SCUBA modality modifies human physiology in many ways. These modifications have been studied since Paul Bert in a seminal work. This area of research is very sensible to technological development. At now, it is possible to record heart rate (HR) continuously while diving. The study of HR changes in SCUBA diving at different depths in a constant temperature of thermal water is the objective of the present paper. Methods: 18 healthy subjects were enrolled and HR was recorded while SCUBA diving in thermal water at a constant temperature of 33.6°C in the deepest Italian pool at Montegrotto (Padova, Italy). Three depths were investigated: -20, -30 and -40 meters. The HR has been recorded with a Galileo SOL diving computer. The dive was subdivided into three phases: descent (DSC), steady on depth (STD), post-dive (RSF), and average HR was evaluated in each phase. Moreover, considering the DSC and STD time duration, a statistical linear regression of HR and relative parameters, intercept and slope, were here assessed. Results: In STD phase, HR slope obtained by regression decreased with depth. A significant difference was found between the slope during STD at -20 vs. -40 m (p = 0.05). Discussion: Present results emphasized different HR physiological adjustments among diving phases. Firstly, during the DSC, a rapid HR decrease is recognized as probably due to a vagal response; secondly, at STD, the inward blood redistribution requires another physiological adjustment. This latter is depth-dependent because of a reduction of cardiac variability. Present data highlight the important cardiac stress need to counteract the diving activity. [ABSTRACT FROM AUTHOR]

IntroductionDiving in SCUBA modality modifies human physiology in many ways. These modifications have been studied since Paul Bert in a seminal work. This area of research is very sensible to technological development. At now, it is possible to record heart rate (HR) continuously while diving. The study of HR changes in SCUBA diving at different depths in a constant temperature of thermal water is the objective of the present paper.Methods18 healthy subjects were enrolled and HR was recorded while SCUBA diving in thermal water at a constant temperature of 33.6∘ C in the deepest Italian pool at Montegrotto (Padova, Italy). Three depths were investigated: −20, −30 and −40 meters. The HR has been recorded with a Galileo SOL diving computer. The dive was subdivided into three phases: descent (DSC), steady on depth (STD), post–dive (RSF), and average HR was evaluated in each phase. Moreover, considering the DSC and STD time duration, a statistical linear regression of HR and relative parameters, intercept and slope, were here assessed.ResultsIn STD phase, HR slope obtained by regression decreased with depth. A significant difference was found between the slope during STD at −20 vs. −40 m (p ≤ 0.05).DiscussionPresent results emphasized different HR physiological adjustments among diving phases. Firstly, during the DSC, a rapid HR decrease is recognized as probably due to a vagal response; secondly, at STD, the inward blood redistribution requires another physiological adjustment. This latter is depth-dependent because of a reduction of cardiac variability. Present data highlight the important cardiac stress need to counteract the diving activity.

Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6–9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial.

Background: Mechanical circulatory support (MCS) devices may stabilize patients with severe cardiogenic shock (CS) following myocardial infarction (MI). However, the canonical understanding of hemodynamics related to the determination of the native cardiac output (CO) does not explain or support the understanding of combined left and right MCS. To ensure the most optimal therapy control, the current principles of hemodynamic measurements during biventricular support should be re-evaluated. Methods: Here we report a protocol of hemodynamic optimization strategy during biventricular MCS (VA-ECMO and left ventricular Impella) in a case series of 10 consecutive patients with severe cardiogenic shock complicating myocardial infarction. During the protocol, the flow rates of both devices were switched in opposing directions (+ / − 0.7 l/min) for specified times. To address the limitations of existing hemodynamic measurement strategies during biventricular support, different measurement techniques (thermodilution, Fick principle, mixed venous oxygen saturation) were performed by pulmonary artery catheterization. Additionally, Doppler ultrasound was performed to determine the renal resistive index (RRI) as an indicator of renal perfusion. Results: The comparison between condition 1 (ECMO flow > Impella flow) and condition 2 (Impella flow > VA-ECMO flow) revealed significant changes in hemodynamics. In detail, compared to condition 1, condition 2 results in a significant increase in cardiac output (3.86 ± 1.11 vs. 5.44 ± 1.13 l/min, p = 0.005) and cardiac index (2.04 ± 0.64 vs. 2.85 ± 0.69, p = 0.013), and mixed venous oxygen saturation (56.44 ± 6.97% vs. 62.02 ± 5.64% p = 0.049), whereas systemic vascular resistance decreased from 1618 ± 337 to 1086 ± 306 s*cm−5 (p = 0.002). Similarly, RRI decreased in condition 2 (0.662 ± 0.05 vs. 0.578 ± 0.06, p = 0.003). Conclusions: To monitor and optimize MCS in CS, PA catheterization for hemodynamic measurement is applicable. Higher Impella flow is superior to higher VA-ECMO flow resulting in a more profound increase in CO with subsequent improvement of organ perfusion. [ABSTRACT FROM AUTHOR]

Background: ModulHeart (Puzzle Medical Devices Inc) is a novel percutaneous flow entrainment pump anchored in the descending aorta. The current study evaluates the hemodynamic effect of ModulHeart support and its impact on cerebral, myocardial, and renal blood flow. Methods: ModulHeart was implanted in the descending aorta of four healthy calves. A ramp protocol (2000 RPM increments) was performed with the pump operating at five different speeds from 14 000 to 22 000 RPM. For each speed, pressures proximal and distal to the pump, and right heart catheterization measurements were recorded. Stable‐isotope labeled microspheres were injected in the left ventricle to evaluate organ perfusion. Results: Thermodilution cardiac output increased by 23% at 22 000 RPM. Greater pump speeds resulted in greater pump gradients, up to 10 mm Hg in mean arterial pressure at 22 000 RPM, without significant reduction of proximal perfusion pressures. Arterial pulse pressure remained stable at all speeds. ModulHeart was not associated with a reduction in cerebral or myocardial blood flow at any speed. Renal cortical and medullary blood flow increased by up to 50% and 40%, respectively. Conclusion: The ModulHeart device implanted in the descending aorta of healthy calves resulted in significant arterial pressure gradients and preserved pulse pressure. Greater pump speeds translated into greater increases in renal blood flow, with no decrease in cerebral or myocardial perfusion. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated. The variables relate to the engineering and function of the respective perfusion devices, such as the type of pump used, functional, like ventilation modes or physiological (e.g. perfusion solutions). This review reflects on the individual technical and fluid components relevant to EVLP and their respective impact on inflammatory response and outcome. We discuss key components of EVLP protocols and options for further improvement of EVLP in regard to PGD. This review offers an overview of available options for centers establishing an EVLP program and for researchers looking for ways to adapt existing protocols.

Abdominal normothermic regional perfusion (aNRP) is an in situ normothermic oxygenated donor perfusion technique before procurement during controlled donation after circulatory death (cDCD) procedures and allows for organ quality evaluation. There are few data on the effect of aNRP on pancreatic islet isolation and subsequent transplantation outcomes. We aim to evaluate the impact of aNRP on cDCD pancreatic islet isolation and transplantation. A retrospective analysis was performed on pancreatic islet isolation outcomes from aNRP, cDCD, and donation after brain death pancreases. Isolations were compared to previous donor age (60-75 years) matched isolations. Islet function was assessed by a dynamic glucose-stimulated insulin secretion. Donor baseline characteristics did not differ among groups. Isolations from aNRP pancreases (471 739 islet equivalents [IEQ] [655 435-244 851]) yielded more islets compared to cDCD (218 750 IEQ [375 951-112 364], P < .01) and to donation after brain death (206 522 IEQ [385 544-142 446], P = .03) pancreases. Dynamic glucose-stimulated insulin secretion tests in 7 aNRP islet preparations showed a mean stimulation index of 4.91, indicating good functionality. Bilirubin and alanine aminotransferase during aNRP correlated with islet yield (r 2 = 0.685, P = .002; r 2 = 0.491, P = .016, respectively). Islet isolation after aNRP in cDCD donors results in a high islet yield with viable functional islets. aNRP could increase the utilization of the pancreases for islet transplantation., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated. The variables relate to the engineering and function of the respective perfusion devices, such as the type of pump used, functional, like ventilation modes or physiological (e.g. perfusion solutions). This review reflects on the individual technical and fluid components relevant to EVLP and their respective impact on inflammatory response and outcome. We discuss key components of EVLP protocols and options for further improvement of EVLP in regard to PGD. This review offers an overview of available options for centers establishing an EVLP program and for researchers looking for ways to adapt existing protocols., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ponholzer, Dumfarth, Krapf, Pircher, Hautz, Wolf, Augustin and Schneeberger.)