Pharmacological normalization of circulation after acute brain death

Steen, Stig; Sjöberg, Trygve; Liao, Qiuming; Božović, Gracijela; Wohlfart, Björn

doi:10.1111/j.1399-6576.2012.02721.x

Cited by 28 publications

(52 citation statements)

References 13 publications

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“…This led Steen et al to propose a collection of hormones which promoted hemodynamic stability in decapitated animals, including epinephrine, thyroxine, desmopressin, and cortisol; similar results were obtained by Hing et al. 22,23 Keeping with these principles, the OCS includes constant infusion of TransMedics Maintenance Solution, which includes insulin, glucocorticoids, bicarbonate, adenosine, and low dose epinephrine. 9,10,24 However, given that preservation time appears to remain limited, the current list of OCS perfusate ingredients must lack essential components.…”

Section: Discussionmentioning

confidence: 76%

“…6,18,20 Blood perfusion alone is inadequate, however, as the isolated perfused heart tends to emulate the loss of viability and vascular tone seen in the cardiovascular collapse of brain-dead humans and animals. 11,21,22 It is likely that circulating metabolic substrates and hormones are necessary to maintain organ integrity. This led Steen et al to propose a collection of hormones which promoted hemodynamic stability in decapitated animals, including epinephrine, thyroxine, desmopressin, and cortisol; similar results were obtained by Hing et al.…”

Section: Discussionmentioning

confidence: 99%

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Normothermic Ex Vivo Heart Perfusion: Effects of Live Animal Blood and Plasma Cross Circulation

et al. 2017

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Prolonged normothermic ex-vivo heart perfusion (NEVHP) could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via NEVHP. Standard perfusion (n=40) utilized red blood cell/plasma perfusate and Langendorf technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-Blood; n=6) or cross-circulated filtered plasma (XC-Plasma; n=7) between a live paracorporeal pig under anesthesia and the perfusate reservoir. Data included oxygen metabolism, vascular resistance, lactate production, left ventricular function, myocardial electrical impedance, and histopathologic injury score. All cross-circulation hearts were successfully perfused for 12 hours, compared to 22 of 40 standard perfusion hearts (55%; p=0.002). Both cross-circulation groups demonstrated higher oxygen consumption and vascular resistance than standard hearts from hours 3–12. No significant differences were seen between XC-Blood and XC-Plasma hearts in any variable, including left ventricular dP/dT after 12 hours (1478±700mmHg/s vs. 872±500; p=0.17). We conclude that cross circulation of whole blood or plasma from a live animal improves preservation of function of perfused hearts, and cross-circulated plasma performs similarly to cross-circulated whole blood.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Normothermic Ex Vivo Heart Perfusion: Effects of Live Animal Blood and Plasma Cross Circulation

et al. 2017

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“…6 This theory is supported by clinical observation and experimental paradigms suggesting that neurologic regulation may be important for organ viability and vascular tone. 18,19 Dr. Steen’s group has proposed a cocktail of hormones that may be important in regulating vascular tone, and were able to use this cocktail to promote hemodynamic stability in decapitated animal experiments. Others have shown that hormone therapies can improve myocardial function after brain death in similar animal experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Others have shown that hormone therapies can improve myocardial function after brain death in similar animal experiments. 19,20 …”

Section: Discussionmentioning

confidence: 99%

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts

Trahanas¹,

Witer

Alghanem

et al. 2016

ASAIO Journal

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Although total body perfusion with extracorporeal life support (ECLS) can be maintained for weeks, individual organ perfusion beyond 12 hours has yet to be achieved clinically. Normothermic ex situ heart perfusion (ESHP) offers the potential for prolonged cardiac preservation. We developed an ESHP system to study the effect of perfusate variables on organ preservation, with the ultimate goal of extending organ perfusion for ≥ 24 hours. Forty porcine hearts were perfused for a target of 12 hours. Hearts that maintained electromechanical activity and had a <3× increase in vascular resistance were considered successful preservations. Perfusion variables, metabolic byproducts, and histopathology were monitored and sampled to identify factors associated with preservation failure. Twenty-two of 40 hearts were successfully preserved at 12 hours. Successful 12-hour experiments demonstrated lower potassium (4.3±0.8 vs. 5.0±1.2 mmol/L, p=0.018) and lactate (3.5±2.8 vs. 4.5±2.9 mmol/L, p=0.139) levels, and histopathology revealed less tissue damage (p=0.003) and less weight gain (p=0.072). Results of these early experiments suggest prolonged ESHP is feasible, and that elevated lactate and potassium levels are associated with organ failure. Further studies are necessary to identify the ideal perfusate for normothermic ESHP.

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“…A comprehensive summary of the pathophysiological evolution of the BD patient is found in [4]. An in vivo porcine study presented in [5], shows promising results of a novel pharmacological therapy aimed at achieving hemodynamic stability in BD patients. The therapy consists of intravenous infusion of a drug cocktail, consisting of noradrenaline (0.02 mg/ml), adrenaline (0.02 mg/ml), cocaine (0.02 mg/ml), thyroid hormones T3 (0.006 mg/ml) and T4 (0.006 mg/ml), anti-diuretic hormone (desmopressin) (0.72 µg/ml 1 ), and cortisol (6 mg/ml).…”

Section: Introductionmentioning

confidence: 99%

Closed-Loop Prevention of Hypotension in the Heartbeating Brain-Dead Porcine Model

Soltesz

Sturk

Paskevicius

et al. 2017

IEEE Trans. Biomed. Eng.

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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.

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Pharmacological normalization of circulation after acute brain death

Cited by 28 publications

References 13 publications

Normothermic Ex Vivo Heart Perfusion: Effects of Live Animal Blood and Plasma Cross Circulation

Normothermic Ex Vivo Heart Perfusion: Effects of Live Animal Blood and Plasma Cross Circulation

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts

Closed-Loop Prevention of Hypotension in the Heartbeating Brain-Dead Porcine Model

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