X-Message-Number: 13248
Date: Sat, 12 Feb 2000 14:10:43 -0800 (PST)
From: Doug Skrecky <>
Subject: cardiac preservation with polyethylene glycol (long)

<1-4>
<1>
Authors
  Gutierrez-Carretero E.  Bello-Puentes R.  Borrego-Dominguez JM. 
  Hernandez-Fernandez A.  Munoz-Garcia J.  Ordonez-Fernandez A.
Institution
  Virgen del Rocio Hospital, Seville, Spain.
Title
  Alteration in diastolic function following cardiac
  cryopreservation at subzero temperatures.
Source
  Journal of Heart & Lung Transplantation.  18(4):372-5, 1999 Apr.
Abstract
  BACKGROUND: We have studied the alterations produced in the diastolic
  function of the left ventricle after applying a protocol of
  cryopreservation at subzero temperatures. METHODS: Isolated
  rabbit hearts and 5% polyethylene glycol
  (PM 4000) as the cryoprotective agent were used for the study.
  RESULTS-CONCLUSIONS: Following cryopreservation we found a
  statistically significant increase in systolic function. However, the
  diastolic function shows worsening, with a statistically significant increase
  (p < 0.05) in mean stiffness, decrease in differential stiffness, (p < 0.05)
  and upward and leftward displacement of the diastolic pressure-volume curve.

<2>
Authors
  Wicomb WN.  Hill DJ.  Collins GM.
Institution
  Research Institute, California Pacific Medical Center, San Francisco 94115.
Title
  Twenty-four-hour ice storage of rabbit heart.
Source
  Journal of Heart & Lung Transplantation.  13(5):891-4, 1994 Sep-Oct.
Abstract
  Although cardioplegia is limited to 4 hours of ice storage, University of
  Wisconsin solution has successfully extended this period to approximately 12
  hours. In this study we have substituted polyethylene
  glycol for hydroxyethyl starch in a simplified University of
  Wisconsin solution (Cardiosol). Rabbit hearts were ice stored for 24 hours at
  0 degrees C in either University of Wisconsin solution or Cardiosol
  (containing either 5% or 10% polyethylene
  glycol). Fresh control hearts were tested immediately after
  cardiectomy. Function was evaluated in an in vitro working heart model for 1
  hour with aortic afterload at 100 cm H2O. Total cardiac output or the
  proportion of hearts reaching 100 cm H2O were compared. Hearts stored in
  University of Wisconsin solution for 24 hours functioned at 6% of control
  levels at 15 minutes of observation. None reached 100 cm H2O or deteriorated
  further with time (p < 0.05). By contrast, hearts stored in 5% Cardiosol
  showed progressive recovery during the 1-hour observation. Of the 13 hearts,
  11 reached 100 cm H2O with a mean cardiac output of 51% of the control value.
  Increasing the concentration of polyethylene
  glycol to 10% improved cardiac output at all observation
  times, reaching 80% of control heart performance at 1 hour (control > 10% >
  5% > University of Wisconsin solution [p < 0.05]). We concluded that 10%
  polyethylene glycol significantly improved
  24-hour ice storage and, hence, viability to a functional level that matched
  our previously reported microperfusion results.

<3>
Authors
  Banker MC.  Layne JR Jr.  Hicks GL Jr.  Wang T.
Institution
  Department of Surgery, University of Rochester, N.Y. 14642.
Title
  Freezing preservation of the mammalian heart explant. III. Tissue dehydration
  and cryoprotection by polyethylene glycol.
Source
  Journal of Heart & Lung Transplantation.  11(4 Pt 1):619-23, 1992 Jul-Aug.
Abstract
  Isolated rat hearts perfused with hyperosmotic Krebs-Henseleit buffer
  containing 60 mmol/L NaCl lose 10% of their tissue water. Perfusion of the
  rat hearts with Krebs-Henseleit buffer containing
  polyethylene glycol 8000 caused a
  concentration-dependent reduction in tissue water. In a study of the effect
  of different cryoprotectants on cardiac preservation, isolated rat hearts
  were flushed with a cardioplegic solution (CP-14), or CP-14 with either 50
  mmol/L glycerol (CP-15), or 5% polyethylene
  glycol (CP-16) and frozen at -1.4 degrees C for 5 hours.
  Thawed hearts were reperfused in working mode to assess function. There was
  no recovery in CP-14 hearts. Hearts treated with CP-15 recovered 39.3% +/-
  2.9% (mean +/- SEM) of control cardiac output. CP-16 boosted the recovery of
  cardiac output to 54.4% +/- 5.7% (p less than 0.05 vs CP-15). Glycerol
  significantly reduced tissue ice content; PEG further decreased the ice
  content to 31.7% +/- 0.6%, which was distinctively lower than that in CP-14
  (44.7% +/- 1.1%) and in CP-15 hearts (34.6% +/- 1.1%). Tissue water content
  of CP-14 and CP-15 hearts was similar (3.83 and 3.87 gm H2O/gm dry weight).
  Polyethylene glycol reduced the tissue
  water content to 3.24 +/- 0.04 gm H2O/gm dry (p less than 0.01 vs CP-14 and
  CP-15 by ANOVA). Thus both glycerol and polyethylene
  glycol offered cryoprotection to the heart explant by
  reducing tissue ice formation. Polyethylene
  glycol was superior to glycerol by dehydrating myocardial
  tissue and further minimizing freezing damage.

<4>
Authors
  Banker MC.  Layne JR Jr.  Hicks GL Jr.  Wang TC.
Institution
  Department of Surgery, University of Rochester, New York 14642.
Title
  Freezing preservation of the mammalian cardiac explant. II. Comparing the
  protective effect of glycerol and polyethylene
  glycol.
Source
  Cryobiology.  29(1):87-94, 1992 Feb.
Abstract
  We compared the cryoprotective ability of glycerol and
  polyethylene glycol (PEG) during freezing.
  Isolated rat hearts were flushed with one of three cardioplegic solutions
  (CP-14, CP-15, and CP-16), frozen at -1.4 degrees C, and reperfused after
  thawing to assess function. After 3 h freezing, cardiac output (CO) in
  CP-14-flushed hearts recovered to 58.1% of control. CP-16 (CP-14 with 5% PEG)
  improved CO to 77.5%. Five hours of freezing abolished recovery in CP-14
  hearts, but CP-15 (CP-14 with 50 mM glycerol) and CP-16 hearts produced 40.0
  and 49.0% CO, respectively. With 6 h freezing, CP-15 hearts did not recover,
  whereas CP-16 hearts recovered 37.5% CO. In CP-14 hearts frozen for 3 h,
  37.4% of the tissue water was ice that increased to 44.7% with 5 h freezing.
  CP-15 and CP-16 hearts had 34.4 and 30.9% tissue ice, respectively, after 5 h
  freezing. Tissue water contents in CP-14 and CP-15 hearts (3.83 to 3.96 g
  H2O/g dry) were 14 to 24% higher than that in CP-16 hearts. Six hours of
  freezing elevated AMP and ADP contents and reduced ATP levels in CP-15 and
  CP-16 hearts. Total adenine nucleotide (TAN) content of CP-15 hearts was 72%
  of control, while that of CP-16 hearts was normal. In conclusion, both
  glycerol and PEG offered cryoprotection by reducing tissue ice formation. PEG
  was superior by reducing tissue ice content further via dehydration and by
  better preserving TAN content.

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