Extended Ex-Vivo Myocardial Preservation in the Beating State Using a Novel Peg-Hemoglobin Based Solution

Jones, Bianding U.; Connolly, Peter J.; Smulowitz, Peter; Sema, Dan; Beckham, Gerry; Kahwaji, Chad; Shrivastata, Vini; Perez, Yannelly; Farber, Adam; West, J. B.; Steward, Earl; Parker, Lane; Ages, Berend; Purdy, Ralph E.; Milliken, Jeffrey C.

doi:10.1097/00002480-200203000-00174

Cited by 4 publications

(6 citation statements)

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“…Although mechanisms for this finding were not investigated, it was hypothesized that there may have been less preservation injury with the addition of PEG. Extended periods of myocardial preservation have been achieved using a novel polyethylene glycolated hemoglobin perfusate-based solution in experimental studies (11). Rabbit hearts were harvested after cold cardioplegic arrest and then underwent cold ischemic storage or continuous warm perfusion with a PEG-hemoglobin solution.…”

Section: Discussionmentioning

confidence: 99%

High-molecular-weight polyethylene glycol protects cardiac myocytes from hypoxia- and reoxygenation-induced cell death and preserves ventricular function

Malhotra

Valuckaite

Staron

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Apoptosis plays a significant role in maladaptive remodeling and ventricular dysfunction following ischemia-reperfusion injury. There is a critical need for novel approaches to inhibit apoptotic cell death following reperfusion, as this loss of cardiac myocytes can progressively lead to heart failure. We investigated the ability and signaling mechanisms of a high-molecular-weight polyethylene glycol-based copolymer, PEG 15-20, to protect cardiac myocytes from hypoxia-reoxygenation (H-R)-induced cell death and its efficacy in preserving ventricular function following extended hypothermic ischemia and warm reperfusion as relevant to cardiac transplantation. Pretreatment of neonatal rat ventricular myocytes with a 5% PEG solution led to a threefold decline in apoptosis after H-R relative to untreated controls. There was a similar decline in caspase-3 activity in conjunction with inhibition of cytochrome c release from the inner mitochondrial membrane. Treatment with PEG also reduced reactive oxygen species production after H-R, and sarcolemmal lipid-raft architecture was preserved, consistent with membrane stabilization. Cell survival signaling was upregulated after H-R with PEG, as demonstrated by increased phosphorylation of Akt, GSK-3β, and ERK1/2. There was also maintenance of cardiac myocyte β-adrenergic signaling, which is critical for myocardial function. PEG 15-20 was very effective in preserving left ventricular function following prolonged hypothermic ischemia and warm reperfusion. PEG 15-20 has a potent protective antiapoptotic effect in cardiac myocytes exposed to H-R injury and may represent a novel therapeutic strategy to decrease myocardial cell death and ventricular dysfunction at the time of reperfusion during acute coronary syndrome or following prolonged donor heart preservation.

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Section: Discussionmentioning

confidence: 99%

High-molecular-weight polyethylene glycol protects cardiac myocytes from hypoxia- and reoxygenation-induced cell death and preserves ventricular function

Malhotra

Valuckaite

Staron

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Jones et al. [4] experimented on perfusion with a PEG‐Hb solution at 20 °C and 30 mmHg for 24 h in the rabbit model. A coronary perfusion pressure that is too low (15 mmHg) may result in inhomogeneous tissue perfusion and oxygen delivery [16].…”

Section: Discussionmentioning

confidence: 99%

“…Two major drawbacks with CS are hypothermia‐induced injury (at 0–4 °C) and myocardial ischemia and hypoxia. It has been reported that continuous perfusion (CP) of harvested hearts with oxygen and metabolic substrates provides better support in preservation, by maintaining myocardial integrity during organ transport [1–5]. However, in most previous studies, subjects were small animals, which do not have a very similar anatomy and physiology to the human.…”

Section: Introductionmentioning

confidence: 99%

“…However, in most previous studies, subjects were small animals, which do not have a very similar anatomy and physiology to the human. Moreover, these studies used ex vivo nonworking Langendorff heart models for functional evaluation, instead of orthotopic transplanted hearts [1–8]. To assess whether CP preservation is superior to CS preservation, swine models were chosen for our study because of the similarities between human and swine in terms of anatomic and physiologic characteristics [9].…”

Section: Introductionmentioning

confidence: 99%

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Continuous perfusion of donor hearts with oxygenated blood cardioplegia improves graft function

Zhang

Wen

et al. 2010

Transplant International

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Summary Donor hearts cannot be preserved beyond 6 h using cold storage (CS). Improving preservation methods may permit prolonged storage of donor heart. We compared graft function in large animal model after prolonged preservation (8 h) using continuous perfusion (CP) and CS method. Twenty‐four miniature pigs were used as donors and recipients. Donor hearts were either stored in University of Wisconsin solution (UW solution) for 8 h at 0–4 °C (CS group, n = 6) or were continuously perfused with oxygenated blood cardioplegia at 26 °C for 8 h (CP group, n = 6). After preservation, hearts were transplanted into recipients and reperfused for 3 h. Left ventricular (LV) function, cardiac output (CO), malondialdehyde (MDA) and adenosine triphosphate (ATP) levels, and water content were measured. Although water content of CP hearts was higher than that of CS, LV contractility and diastolic function of CP hearts were superior to those of CS. In addition, CP hearts performed better than CS hearts on CO in working heart state. ATP was better preserved and MDA levels were lower in CP hearts compared with those of CS (P < 0.0001). Donor hearts can be preserved longer using continuous perfusion with oxygenated blood cardioplegia and this method prevents time‐dependent ischemic injury.

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“…Rabbit model studies have demonstrated that HMP supplemented with oxygen-carrying hemoglobin or polyethylene-glycolated bovine hemoglobin (bHb-PEG) could extend preservation times and decrease ischemic injury [19]. Furthermore, conjugation with PEG chains effectively increases the circulation time of Hb and avoids its nephrotoxicity.…”

Section: Oxygen Carriersmentioning

confidence: 99%

In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

Giraud

Thuillier

Cau

et al. 2020

IJMS

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Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve kidney preservation. This review highlights the most promising avenues of in kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.

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Extended Ex-Vivo Myocardial Preservation in the Beating State Using a Novel Peg-Hemoglobin Based Solution

Cited by 4 publications

References 0 publications

High-molecular-weight polyethylene glycol protects cardiac myocytes from hypoxia- and reoxygenation-induced cell death and preserves ventricular function

High-molecular-weight polyethylene glycol protects cardiac myocytes from hypoxia- and reoxygenation-induced cell death and preserves ventricular function

Continuous perfusion of donor hearts with oxygenated blood cardioplegia improves graft function

In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

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