- Email: [email protected]
Nitric oxide-superoxide interaction after ischemia-reperfusion in long-term heart preservation
The Journal of Heart and Lung Transplantation Volume 21, Number 1
Abstracts
at less than 90 days. Group II early deaths had donor risk factor combinations of CAD, left ventricle hypertrophy, and long distance. Freedom from rejection ⬎ ISHLT grade 3A was 100% in group I and 84.6% in group II. Freedom from GCAD was 100% at 2-years in group I and 87.5% in group II excluding pre-existing disease. Conclusions: Use of certain donor hearts with CAD, possibly requiring revascularization, is acceptable in selected recipients. Early deaths are related to recipient factors as well as associated donor risk factors. 239 RESULTS OF A PROSPECTIVE STUDY USING HIGHFREQUENCY CHEST WALL OSCILLATION FOR ORGAN DONORS W.D. Babcock,1 R.L. Menza,1 S. Riznyk,2 P. Prince,2 T.J. Kern,3 1 California Transplant Donor Network, Oakland, CA; 2Pacific Northwest Transplant Bank, Portland, Oregon; 3Golden State Donor Services, Sacramento, CA Purpose: To assess the effect of high-frequency chest wall oscillation (HFCWO) in the management of organ donors. Methods: Three organ procurement organizations (OPO)participated in a prospective study to evaluate effects of HFCWO in donor management. Data from 100 eligible donors was analyzed. Effectiveness of HFCWO was measured by evaluating four study end-points monitored from the onset of OPO clinical management to organ procurement. End-points included; a) change in P:F ratios of ABG on 100% FiO2, b) change in CXR densities of any type, c) change in prevalence of organisms present by sputum gram stain, and d) rate of lung procurement. Results: 55 donors received HFCWO therapy (HFCWO), and 45 donors did not (Control). No significant differences were shown between groups with respect to demographics, known major factors influencing lung donor acceptance, or related clinical parameters. The change in mean P:F ratio was greater in the HFCWO group compared with control group, but did not reach statistical significance. CXR densities demonstrated significant improvement in the HCFWO group versus the control group. Significantly fewer organisms were detected by sputum gram stain in the HFCWO group than in the control group. The rate of lung procurement in the HCFWO group was notably greater than in the control group, but did not reach statistical significance (Table 1).
Mean Change in P:F Ratio of Challenge Gas (torr) Improvement in CXR Density Decreased Degree of Organisms Lung Procurement Rate
HFCWO (n ⴝ 55)
Control (n ⴝ 45)
P Value
⫹124.0
⫹37.6
0.059
74.0% 73.9% 40.0%
50.0% 38.9% 24.4%
0.026 0.031 0.135
Conclusion: HFCWO during clinical management of organ donors improved chest radiograph densities and gram stain results. These results suggest that HFCWO may significantly improve the quantity and quality of lungs available for transplantation. 240 NITRIC OXIDE-SUPEROXIDE INTERACTION AFTER ISCHEMIA-REPERFUSION IN LONG-TERM HEART PRESERVATION S. Morita, Y. Tanoue, Y. Ochiai, N. Haraguchi, M. Masuda, H. Yasui, Cardiovascular Surgery, Kyushu University, Fukuoka, Japan
141
Purpose: Nitric oxide (NO) donors are well recognized cardioprotective agents. However, their role in ischemia-reperfusion is controvertial, because NO react with superoxide to produce peroxynitrate, a highly toxic substance. With the presence of excessive NO, the antioxidant inhibiting the reaction from superoxide to hydroxyl radical (Fenton reaction) might exaggerate reperfusion injury, because inhibition of Fenton reaction increases the amount of superoxide. Using a canine orthotopic heart transplantation model, we aimed to elucidate the NOsuperoxide interaction by examining the cardioprotective effect of combining nitroglycerine (an NO donor) and Lazaroid U74500A (a Fenton reaction inhibitor). Experimental Procedures and Results: Canine hearts were preserved for 24 hours in UW solution containing, nitroglycerine (Grp-N, n⫽9), Lazaroid (Grp-L, n⫽8), or both nitroglycerine and Lazaroid (Grp-N&L, n⫽8). The hearts preserved without nitroglycerine or Lazaroid served as a control (Grp-C, n⫽10). After orthotopic heart transplantation (120 minutes after reperfusion), ventricular function determined with Emax (mmHg/ml) was significantly better in Grp-L(9.87⫾4.01) and GrpN(9.56⫾3.26) than in Grp-C(6.20⫾2.75) but no further improvement was seen in Grp-N&L(10.23⫾4.26). Increased serum lipid peroxide(LPO) level(nmol/ml) in Grp-N&L(3.97⫾1.23) compared to Grp-N(2.45⫾1.33) and Grp-L(0.27⫾0.53) indicated high oxidative stress in Grp-N&L (LPO levels in Grp-C was 1.33⫾0.74). Serum nitrate and nitrite (NOx) level (mmol/L) in Grp-N&L(17.8⫾8.1) was lower than in Grp-N (29.9⫾ 13.3), and NOx level in Grp-L(11.3⫾7.5) was lower than control(14.2⫾9.3). The finding of lower NOx levels seen in the groups with Lazaroid was suggestive that NO was consumed as a scavenger of superoxide, then converted to peroxynitrite, which resulted in the increase in LPO. Conclusion: Nitroglycerine and Lazaroid exerted superb cardioprotective effect. Combining these two agents, however, did not improve protection, synergistically. Increased LPO level observed in Grp-N&L indicated that NO-superoxide interaction worked unfavorably in the setting of ischemia-reperfusion. 241 VASOPRESSOR DOSE PREDICTS INTRINSIC RIGHT VENTRICULAR DYSFUNCTION IN THE HUMAN DONOR D.K. Satchithananda,1 S.C. Stoica,1 P.A. White,1 L. Sharples,1 M. Petrou,1 P.M. Schofield,1 J. Wallwork,1 J. Parameshwar,1 A. Redington,2 S.R. Large,1 1Transplant Unit, Papworth Hospital, Cambridge, United Kingdom; 2Great Ormond Street Hospital, London, United Kingdom Introduction: Associations between higher dose pressor support and intrinsic donor cardiac dysfunction are assumed, but have never been demonstrated. Hypothesis: Vasopressor dose correlates with donor heart dysfunction independently of cardiac loading conditions. Method: 27 unselected human donors had right ventricular (RV) function prospectively assessed by our unit using the conductance catheter technique. These assessments were made following haemodynamic optimisation and minimisation of norepinephrine (NOR) support with vasopressin (ADH) replacement. Groups were determined by the dose of NOR initiated in response to donor hypotension at the referring hospital: Group 1 (no NOR initiated n⫽ 13), Group 2 (⬍0.05mcg/kg/min NOR initiated n⫽ 8), Group 3 (⬎0.05mcg/kg/min NOR initiated n⫽ 8). Load
Abstracts
at less than 90 days. Group II early deaths had donor risk factor combinations of CAD, left ventricle hypertrophy, and long distance. Freedom from rejection ⬎ ISHLT grade 3A was 100% in group I and 84.6% in group II. Freedom from GCAD was 100% at 2-years in group I and 87.5% in group II excluding pre-existing disease. Conclusions: Use of certain donor hearts with CAD, possibly requiring revascularization, is acceptable in selected recipients. Early deaths are related to recipient factors as well as associated donor risk factors. 239 RESULTS OF A PROSPECTIVE STUDY USING HIGHFREQUENCY CHEST WALL OSCILLATION FOR ORGAN DONORS W.D. Babcock,1 R.L. Menza,1 S. Riznyk,2 P. Prince,2 T.J. Kern,3 1 California Transplant Donor Network, Oakland, CA; 2Pacific Northwest Transplant Bank, Portland, Oregon; 3Golden State Donor Services, Sacramento, CA Purpose: To assess the effect of high-frequency chest wall oscillation (HFCWO) in the management of organ donors. Methods: Three organ procurement organizations (OPO)participated in a prospective study to evaluate effects of HFCWO in donor management. Data from 100 eligible donors was analyzed. Effectiveness of HFCWO was measured by evaluating four study end-points monitored from the onset of OPO clinical management to organ procurement. End-points included; a) change in P:F ratios of ABG on 100% FiO2, b) change in CXR densities of any type, c) change in prevalence of organisms present by sputum gram stain, and d) rate of lung procurement. Results: 55 donors received HFCWO therapy (HFCWO), and 45 donors did not (Control). No significant differences were shown between groups with respect to demographics, known major factors influencing lung donor acceptance, or related clinical parameters. The change in mean P:F ratio was greater in the HFCWO group compared with control group, but did not reach statistical significance. CXR densities demonstrated significant improvement in the HCFWO group versus the control group. Significantly fewer organisms were detected by sputum gram stain in the HFCWO group than in the control group. The rate of lung procurement in the HCFWO group was notably greater than in the control group, but did not reach statistical significance (Table 1).
Mean Change in P:F Ratio of Challenge Gas (torr) Improvement in CXR Density Decreased Degree of Organisms Lung Procurement Rate
HFCWO (n ⴝ 55)
Control (n ⴝ 45)
P Value
⫹124.0
⫹37.6
0.059
74.0% 73.9% 40.0%
50.0% 38.9% 24.4%
0.026 0.031 0.135
Conclusion: HFCWO during clinical management of organ donors improved chest radiograph densities and gram stain results. These results suggest that HFCWO may significantly improve the quantity and quality of lungs available for transplantation. 240 NITRIC OXIDE-SUPEROXIDE INTERACTION AFTER ISCHEMIA-REPERFUSION IN LONG-TERM HEART PRESERVATION S. Morita, Y. Tanoue, Y. Ochiai, N. Haraguchi, M. Masuda, H. Yasui, Cardiovascular Surgery, Kyushu University, Fukuoka, Japan
141
Purpose: Nitric oxide (NO) donors are well recognized cardioprotective agents. However, their role in ischemia-reperfusion is controvertial, because NO react with superoxide to produce peroxynitrate, a highly toxic substance. With the presence of excessive NO, the antioxidant inhibiting the reaction from superoxide to hydroxyl radical (Fenton reaction) might exaggerate reperfusion injury, because inhibition of Fenton reaction increases the amount of superoxide. Using a canine orthotopic heart transplantation model, we aimed to elucidate the NOsuperoxide interaction by examining the cardioprotective effect of combining nitroglycerine (an NO donor) and Lazaroid U74500A (a Fenton reaction inhibitor). Experimental Procedures and Results: Canine hearts were preserved for 24 hours in UW solution containing, nitroglycerine (Grp-N, n⫽9), Lazaroid (Grp-L, n⫽8), or both nitroglycerine and Lazaroid (Grp-N&L, n⫽8). The hearts preserved without nitroglycerine or Lazaroid served as a control (Grp-C, n⫽10). After orthotopic heart transplantation (120 minutes after reperfusion), ventricular function determined with Emax (mmHg/ml) was significantly better in Grp-L(9.87⫾4.01) and GrpN(9.56⫾3.26) than in Grp-C(6.20⫾2.75) but no further improvement was seen in Grp-N&L(10.23⫾4.26). Increased serum lipid peroxide(LPO) level(nmol/ml) in Grp-N&L(3.97⫾1.23) compared to Grp-N(2.45⫾1.33) and Grp-L(0.27⫾0.53) indicated high oxidative stress in Grp-N&L (LPO levels in Grp-C was 1.33⫾0.74). Serum nitrate and nitrite (NOx) level (mmol/L) in Grp-N&L(17.8⫾8.1) was lower than in Grp-N (29.9⫾ 13.3), and NOx level in Grp-L(11.3⫾7.5) was lower than control(14.2⫾9.3). The finding of lower NOx levels seen in the groups with Lazaroid was suggestive that NO was consumed as a scavenger of superoxide, then converted to peroxynitrite, which resulted in the increase in LPO. Conclusion: Nitroglycerine and Lazaroid exerted superb cardioprotective effect. Combining these two agents, however, did not improve protection, synergistically. Increased LPO level observed in Grp-N&L indicated that NO-superoxide interaction worked unfavorably in the setting of ischemia-reperfusion. 241 VASOPRESSOR DOSE PREDICTS INTRINSIC RIGHT VENTRICULAR DYSFUNCTION IN THE HUMAN DONOR D.K. Satchithananda,1 S.C. Stoica,1 P.A. White,1 L. Sharples,1 M. Petrou,1 P.M. Schofield,1 J. Wallwork,1 J. Parameshwar,1 A. Redington,2 S.R. Large,1 1Transplant Unit, Papworth Hospital, Cambridge, United Kingdom; 2Great Ormond Street Hospital, London, United Kingdom Introduction: Associations between higher dose pressor support and intrinsic donor cardiac dysfunction are assumed, but have never been demonstrated. Hypothesis: Vasopressor dose correlates with donor heart dysfunction independently of cardiac loading conditions. Method: 27 unselected human donors had right ventricular (RV) function prospectively assessed by our unit using the conductance catheter technique. These assessments were made following haemodynamic optimisation and minimisation of norepinephrine (NOR) support with vasopressin (ADH) replacement. Groups were determined by the dose of NOR initiated in response to donor hypotension at the referring hospital: Group 1 (no NOR initiated n⫽ 13), Group 2 (⬍0.05mcg/kg/min NOR initiated n⫽ 8), Group 3 (⬎0.05mcg/kg/min NOR initiated n⫽ 8). Load