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303: Oxygenated perfusion of donor hearts reduces ischemic damage during preservation
S168
Abstracts
sion. Extended transportation times also appear possible without impact on clinical outcomes. 302 FEMALE GENDER IS ASSOCIATED WITH CARDIAC DYSFUNCTION IN BRAIN DEAD ORGAN DONORS K.K. Khush,1 R.L. Menza,2 W.D. Babcock,2 C.W. Hoopes,3 J.G. Zaroff,1 1Medicine/Cardiology, University of California, San Francisco, CA; 2California Transplant Donor Network, Oakland, CA; 3Surgery, University of California, San Francisco, CA Purpose: In the setting of acute subarachnoid hemorrhage, female gender is associated with left ventricular (LV) systolic dysfunction and regional wall motion abnormalities (RWMA). This form of neurocardiogenic injury, which is often reversible, is likely due to excessive myocardial catecholamine release. We studied the association between female gender and LV dysfunction in a diverse population brain dead patients evaluated for organ donation. Methods and Materials: All potential cardiac organ donors managed by the California Transplant Donor Network between 2002-03, aged 14-60 years and without coronary artery disease, were included in this analysis. Univariate predictors of LV dysfunction were identified and multiple regression analysis was used to assess the relative independent contribution of each predictor. Results: 197 potential donors (122 male, 75 female, mean age 38 ⫾ 14 years) were studied. The cause of brain death was trauma in 64 potential organ donors, and non-traumatic (cerebrovascular death, anoxia, or other) in 133 potential donors. 12% had LV systolic dysfunction (LV ejection fraction⬍50%) and 15% had RWMA by echocardiography. Univariate analyses revealed that female gender, smaller donor size (weight, height, and body-mass index), and higher heart rate were independent predictors of LV systolic dysfunction and RWMA. Donor cause of death, cardiopulmonary resuscitation, and history of cocaine or methamphetamine use, smoking, and hypertension did not predict LV dysfunction or RWMA. In a multivariable model, after adjusting for donor age, size, and heart rate, female gender remained a strong independent predictor of LV systolic dysfunction (OR 5.75, 95% CI 1.76-18.76, p⫽0.004) and RWMA (OR 5.73, 95% CI 2.02-16.20, p⫽0.001). Conclusions: Female gender is associated with the presence of LV systolic dysfunction and RWMA in brain dead organ donors. Further studies assessing the reversibility of LV dysfunction and suitability of these organs for transplantation are required. 303 OXYGENATED PERFUSION OF DONOR HEARTS REDUCES ISCHEMIC DAMAGE DURING PRESERVATION A. Halldorsson,1 H.A. Goolsby,2 M.D. Tomison,2 S.D. Prien,2 1 Surgery, Texas Tech University Health Sciences Center, Lubbock, TX; 2Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Lubbock, TX Purpose: It is well documented that ischemic cold storage of hearts during transplantation procedures can cause damage to the organ at the cellular level. The damage manifests itself as structural changes in both the tissue and subcellular organelles, and limits the time the heart can be stored to a few short hours. Recently, a number of groups have proposed perfusion of the hearts during storage to supply oxygen and other nutrient during the storage process as a means of combating ischemic damage. However, concerns have been raised that the use of crystalloid solutions will lead to edema of the organ and further damage to tissue and cells. The objective of the present study was to compare heart tissue at the cellular and subcellular levels from cadaver hearts that had been stored using a
The Journal of Heart and Lung Transplantation February 2007
traditional cold, static method verses a new organ preservation system (LifeCradle™, Organ Transport Systems; Frisco, TX) which perfuses an oxygenated solution through the organ while maintaining the temperature at 5° C. Methods and Materials: Twenty-six cadaver hearts were extracted from swine donors within 5 minutes of euthanasia in a slaughter facility. The hearts were flushed with heparinized cardioplegic solution and weighed prior to storage. The hearts were then stored in using either the standard ice-slurry methodology (n⫽9; SIS) for 4-8 hrs or in the new preservation device (n⫽17; LC) for times of 4-14 hrs. At the end of the storage time the hearts were weighed again to establish weight gain and tissue samples collected for ultrastructural analysis using TEM. Results: Results indicated no significant increased weight gain in the LC as compared to SIS (12.9 gm vs. 12.3 gm respectively; p⫽.954) even after 3X longer is storage. Further, ultrastructural damage was minimal in hearts from the LC as compared to the control as assessed by a pathologist blinded to tissue source. Conclusions: These data suggest the LC may be a superior storage environment over SIS and suggest further transplant studies are warranted. Grant support and supply of experimental instrument; Organ Transplant Systems. 304 INTERMITTENT ANTEGRADE CARDIOPLEGIA: IMPLICATIONS FOR DONOR HEART PRESERVATION A.L. Rivard,1,3 C.M. Swingen,4 F.D. Kamdar,5 Z. Demorest,5 E.J. Cordova,5 J.E. Foker,2 M. Jerosch-Herold,,6 R.W. Bianco,3 R. John,3 1Radiology, University of Florida, Gainesville, FL; 2 Surgery, Division of Cardiovascular and Thoracic, University of Minnesota, Minneapolis, MN; 3Surgery, University of Minnesota, Minneapolis, MN; 4Radiology, University of Minnesota, Minneapolis, MN; 5Medical School, University of Minnesota, Minneapolis, MN; 6Radiology, Oregon Health Sciences Center, Portland, OR Purpose: The scarcity of donor hearts limits the growth of heart transplantation. Currently, donor heart preservation techniques allow for only 4-6 hours of ischemia. Prolongation of this time would allow procurement at greater distances, thus reducing wastage. Because pH is directly related to the degree of ischemia, we hypothesized that administration of cardioplegia to the isolated heart would improve microvascular perfusion. Methods and Materials: Porcine hearts were excised, flushed with a ribose based cardioplegic solution and stored at 9.2 °C for 6.1 ⫾ 0.6 hours. Control hearts (Group 1, n ⫽ 9) were stored without receiving any additional perfusion, whereas experimental hearts (Group 2, n ⫽ 8) received an intermittent antegrade bolus (150 ml, q30 min, 150 ml/min). Ph probes were placed into the LV and RV myocardium for continuous measurement. At the end of the preservation, contrast enhanced, T-1 weighted MR imaging was performed in the short axis view. Peak contrast enhancement was used as a measurement of viable microvasculature. Wet/dry weight was then measured. Results: In both groups, myocardial LV pH decreased exponentially in all hearts immediately following flushing. In Group 1 hearts, pH decreased to 6.2 ⫾0.2. As opposed to Group 2 hearts; pH at the end of 6 hours was 6.7 ⫾0.3. The mean pH difference was of 0.55 (p ⬍ .005). Ph measurements of the RV had a similar response to perfusion (p ⫽ .02). MR contrast imaging showed no differences in peak contrast enhancement in the 2 groups, Group 1 ⫽ 62%, Group 2 ⫽ 40% (p ⫽ .08). There was also no difference of the wet/dry weights. Conclusions: Although microvascular perfusion was not significantly different between the two groups in this study; we demonstrated that intermittent perfusion maintains a significantly higher
Abstracts
sion. Extended transportation times also appear possible without impact on clinical outcomes. 302 FEMALE GENDER IS ASSOCIATED WITH CARDIAC DYSFUNCTION IN BRAIN DEAD ORGAN DONORS K.K. Khush,1 R.L. Menza,2 W.D. Babcock,2 C.W. Hoopes,3 J.G. Zaroff,1 1Medicine/Cardiology, University of California, San Francisco, CA; 2California Transplant Donor Network, Oakland, CA; 3Surgery, University of California, San Francisco, CA Purpose: In the setting of acute subarachnoid hemorrhage, female gender is associated with left ventricular (LV) systolic dysfunction and regional wall motion abnormalities (RWMA). This form of neurocardiogenic injury, which is often reversible, is likely due to excessive myocardial catecholamine release. We studied the association between female gender and LV dysfunction in a diverse population brain dead patients evaluated for organ donation. Methods and Materials: All potential cardiac organ donors managed by the California Transplant Donor Network between 2002-03, aged 14-60 years and without coronary artery disease, were included in this analysis. Univariate predictors of LV dysfunction were identified and multiple regression analysis was used to assess the relative independent contribution of each predictor. Results: 197 potential donors (122 male, 75 female, mean age 38 ⫾ 14 years) were studied. The cause of brain death was trauma in 64 potential organ donors, and non-traumatic (cerebrovascular death, anoxia, or other) in 133 potential donors. 12% had LV systolic dysfunction (LV ejection fraction⬍50%) and 15% had RWMA by echocardiography. Univariate analyses revealed that female gender, smaller donor size (weight, height, and body-mass index), and higher heart rate were independent predictors of LV systolic dysfunction and RWMA. Donor cause of death, cardiopulmonary resuscitation, and history of cocaine or methamphetamine use, smoking, and hypertension did not predict LV dysfunction or RWMA. In a multivariable model, after adjusting for donor age, size, and heart rate, female gender remained a strong independent predictor of LV systolic dysfunction (OR 5.75, 95% CI 1.76-18.76, p⫽0.004) and RWMA (OR 5.73, 95% CI 2.02-16.20, p⫽0.001). Conclusions: Female gender is associated with the presence of LV systolic dysfunction and RWMA in brain dead organ donors. Further studies assessing the reversibility of LV dysfunction and suitability of these organs for transplantation are required. 303 OXYGENATED PERFUSION OF DONOR HEARTS REDUCES ISCHEMIC DAMAGE DURING PRESERVATION A. Halldorsson,1 H.A. Goolsby,2 M.D. Tomison,2 S.D. Prien,2 1 Surgery, Texas Tech University Health Sciences Center, Lubbock, TX; 2Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Lubbock, TX Purpose: It is well documented that ischemic cold storage of hearts during transplantation procedures can cause damage to the organ at the cellular level. The damage manifests itself as structural changes in both the tissue and subcellular organelles, and limits the time the heart can be stored to a few short hours. Recently, a number of groups have proposed perfusion of the hearts during storage to supply oxygen and other nutrient during the storage process as a means of combating ischemic damage. However, concerns have been raised that the use of crystalloid solutions will lead to edema of the organ and further damage to tissue and cells. The objective of the present study was to compare heart tissue at the cellular and subcellular levels from cadaver hearts that had been stored using a
The Journal of Heart and Lung Transplantation February 2007
traditional cold, static method verses a new organ preservation system (LifeCradle™, Organ Transport Systems; Frisco, TX) which perfuses an oxygenated solution through the organ while maintaining the temperature at 5° C. Methods and Materials: Twenty-six cadaver hearts were extracted from swine donors within 5 minutes of euthanasia in a slaughter facility. The hearts were flushed with heparinized cardioplegic solution and weighed prior to storage. The hearts were then stored in using either the standard ice-slurry methodology (n⫽9; SIS) for 4-8 hrs or in the new preservation device (n⫽17; LC) for times of 4-14 hrs. At the end of the storage time the hearts were weighed again to establish weight gain and tissue samples collected for ultrastructural analysis using TEM. Results: Results indicated no significant increased weight gain in the LC as compared to SIS (12.9 gm vs. 12.3 gm respectively; p⫽.954) even after 3X longer is storage. Further, ultrastructural damage was minimal in hearts from the LC as compared to the control as assessed by a pathologist blinded to tissue source. Conclusions: These data suggest the LC may be a superior storage environment over SIS and suggest further transplant studies are warranted. Grant support and supply of experimental instrument; Organ Transplant Systems. 304 INTERMITTENT ANTEGRADE CARDIOPLEGIA: IMPLICATIONS FOR DONOR HEART PRESERVATION A.L. Rivard,1,3 C.M. Swingen,4 F.D. Kamdar,5 Z. Demorest,5 E.J. Cordova,5 J.E. Foker,2 M. Jerosch-Herold,,6 R.W. Bianco,3 R. John,3 1Radiology, University of Florida, Gainesville, FL; 2 Surgery, Division of Cardiovascular and Thoracic, University of Minnesota, Minneapolis, MN; 3Surgery, University of Minnesota, Minneapolis, MN; 4Radiology, University of Minnesota, Minneapolis, MN; 5Medical School, University of Minnesota, Minneapolis, MN; 6Radiology, Oregon Health Sciences Center, Portland, OR Purpose: The scarcity of donor hearts limits the growth of heart transplantation. Currently, donor heart preservation techniques allow for only 4-6 hours of ischemia. Prolongation of this time would allow procurement at greater distances, thus reducing wastage. Because pH is directly related to the degree of ischemia, we hypothesized that administration of cardioplegia to the isolated heart would improve microvascular perfusion. Methods and Materials: Porcine hearts were excised, flushed with a ribose based cardioplegic solution and stored at 9.2 °C for 6.1 ⫾ 0.6 hours. Control hearts (Group 1, n ⫽ 9) were stored without receiving any additional perfusion, whereas experimental hearts (Group 2, n ⫽ 8) received an intermittent antegrade bolus (150 ml, q30 min, 150 ml/min). Ph probes were placed into the LV and RV myocardium for continuous measurement. At the end of the preservation, contrast enhanced, T-1 weighted MR imaging was performed in the short axis view. Peak contrast enhancement was used as a measurement of viable microvasculature. Wet/dry weight was then measured. Results: In both groups, myocardial LV pH decreased exponentially in all hearts immediately following flushing. In Group 1 hearts, pH decreased to 6.2 ⫾0.2. As opposed to Group 2 hearts; pH at the end of 6 hours was 6.7 ⫾0.3. The mean pH difference was of 0.55 (p ⬍ .005). Ph measurements of the RV had a similar response to perfusion (p ⫽ .02). MR contrast imaging showed no differences in peak contrast enhancement in the 2 groups, Group 1 ⫽ 62%, Group 2 ⫽ 40% (p ⫽ .08). There was also no difference of the wet/dry weights. Conclusions: Although microvascular perfusion was not significantly different between the two groups in this study; we demonstrated that intermittent perfusion maintains a significantly higher