Korean Circ J.  2011 Mar;41(3):130-136. 10.4070/kcj.2011.41.3.130.

Effect of Hyperkalemia and Hemolysis Caused by Hyperacute Rejection on Cardiac Function in Pig to Human Ex Vivo Xenogeneic Cardiac Perfusion Model

• Kim JS
• Lee HM
• Oh BC
• Lim HG
• Lee JR

• KMID: 2225126
• DOI: http://doi.org/10.4070/kcj.2011.41.3.130

Abstract

BACKGROUND AND OBJECTIVES
Hyperacute rejection (HAR) is a major obstacle to successful xenotransplantation of vascularized organs. This study was conducted to observe the effect of hemolysis of perfused human whole blood on pig heart function, and determine the major risk factors for preservation of xenoperfused cardiac function using ex-vivo pig to human xenogeneic cardiac perfusion model.
MATERIALS AND METHODS
Harvested pig hearts were perfused with normal human whole blood (group 1), two different types of pre-treated human whole blood (group 2: immunoglobulins were depleted by plasmapheresis, group 3: pre-treated with plasmapheresis, GAS914, cobra venom factor (CVF) and steroid), and normal porcine whole blood as control (group 4) for 3 hours.
RESULTS
Duration of heart beat was significantly prolonged in group 2 and group 3. Histological examination showed widespread HAR features but was gradually delayed in groups 2 and 3 compared to group 1. The absolute levels of serum creatine kinase-MB and Troponin I increased gradually, and was lower in group 3. Serum hemoglobin levels were rapidly increased in groups 3 and 4, compared to group 1. Extracellular potassium level increased sharply from the beginning of blood perfusion in groups 1, 2 and 3, compared to group 4.
CONCLUSION
Pretreatment of human whole blood, including immunoglobulin depletion, CVF and steroid reduced and delayed the destruction of pig myocardium by HAR. However, the increased extracellular potassium levels in groups 1, 2 and 3 reflected that these treatments could not prohibit myocardial injury by HAR.

Keyword

Transplantation, heterologous; Hyperkalemia; Hemolysis; Extracorporeal circulation

MeSH Terms

Cobra Venoms
Creatine
Diphtheria Toxoid
Extracorporeal Circulation
Haemophilus Vaccines
Heart
Hemoglobins
Hemolysis
Humans
Hyperkalemia
Immunoglobulins
Myocardium
Perfusion
Plasmapheresis
Potassium
Rejection (Psychology)
Risk Factors
Transplantation, Heterologous
Trisaccharides
Troponin I
Cobra Venoms
Creatine
Diphtheria Toxoid
Haemophilus Vaccines
Hemoglobins
Immunoglobulins
Potassium
Trisaccharides
Troponin I

Figure

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  Fig. 1 Diagram of the isolated, non-working heart perfusion circuit. Ao: aorta, RA: right atrium, RV: right ventricle, PA: pulmonary artery, LA: left atrium, LV: left ventricle.

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  Fig. 2 Histologic findings of xenoperfused porcine myocardium following perfusion in group 1 (A: 10 minutes, B: 60 minutes) and group 2 (C: 10 minutes, D: 60 minutes). Typical features of HAR were noted and myocardial destruction began within 10 minutes of perfusion (A), and almost all cells were destroyed within 60 minutes in group 1 (B). Morphological changes and congestion were noted in group 2 also (C and D), but delayed and milder than in group 1 (A and B) (H&E, Magnification ×400).

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  Fig. 3 Histologic findings of xenoperfused porcine myocardium after perfusion in group 3 (A: 60 minutes, B: 180 minutes) and group 4 (C: 60 minutes, D: 180 minutes). The degree of destruction was less and delayed in group 3, compared to groups 1 and 2 (Fig. 2B and D). The myocardial cell contour was maintained relatively well in group 4, and the changes in myocytes in group 3 was similar to that in group 4 (H&E, Magnification ×400).

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  Fig. 4 The levels of Troponin I (A) and CK-MB (B). They increased gradually in all groups, including group 4, especially after perfusion began in group 1, and were lowest in group 3.

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  Fig. 5 The levels of serum hemoglobin (A) and potassium (B). Serum hemoglobin levels were higher in group 3 than in groups 1 and 2 (p=0.018). Hemolysis also occurred similarly in group 4. Extracellular potassium levels were increased sharply from the beginning of perfusion in xenograft groups. Notice that the potassium level of the group 4 was increased mildly (p=0.043).

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