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A Recombinant Human Neuregulin-1 Peptide Improves Preservation of the Transplanted Rat Heart After Prolonged Hypothermic Storage
S168
Heart, Lung and Circulation 2009;18S:S1–S286
Abstracts
ABSTRACTS
Conclusions: We demonstrate favourable outcomes in patients with PPCM in this small series. More data is required to determine if this is a true reflection of current outcomes.
381 ACETAZOLAMIDE: OBSOLETE OR OVERLOOKED AS A DIURETIC IN HEART FAILURE?
doi:10.1016/j.hlc.2009.05.381
The Prince Charles Hospital, Brisbane, Australia
380 A RECOMBINANT HUMAN NEUREGULIN-1 PEPTIDE IMPROVES PRESERVATION OF THE TRANSPLANTED RAT HEART AFTER PROLONGED HYPOTHERMIC STORAGE
Background: Refractory oedema in chronic congestive cardiac failure (CCF) is often difficult to treat with unsatisfactory results both for patient and physician. Acetazolamide, a carbonic anhydrase inhibitor causing diuresis via the proximal tubule, is often overlooked and rarely used in favour of other diuretics. Method: We treated three patients experiencing refractory oedema predominantly from Right Heart Failure (RHF), despite increasing doses of multiple diuretics, with addition of acetazolamide 250 mg bd, every 2 of 3 days. CCF hospital admissions, length of stay (LOS) and renal function were measured pre- and post-treatment. Results: Two of the three patients were end stage CCF and all three had existing renal impairment with average eGFR 33, 35 and 45, respectively. Addition of acetazolamide did not increase electrolyte or renal dysfunction. Total LOS was halved in the two palliative patients (35–18 days, 56–28 days) with CCF LOS reductions (35–10 days, 45–28 days) over 6 and 3 months, respectively. The third patient had total LOS reduction from 53 to 2 days (CCF LOS; 46 days to 2 days) in the 12 months preand post-addition of acetazolamide. There was subjective improvement in all three patients. Conclusion: In CCF patients with refractory oedema, addition of acetazolamide improved oedema control, significantly reduced CCF hospital admissions, LOS and improved quality of life, subjectively. In selected cases acetazolamide may offer significant improvement of refractory oedema, bringing important benefits to patients and the healthcare system.
A. Jabbour 1 , L. Gao 1 , J. Kwan 1 , A. Watson 1 , L. Sun 1 , X. Liu 2 , M. Zhou 2 , R.M. Graham 1 , M. Hicks 1 , P. Macdonald 1 1 St Vincent’s Hospital and Victor Chang Cardiac Research Institute, Sydney, Australia 2 Zensun (Shanghai) Sci & Tech Co., Ltd., Shanghai, China
Aims: Neuregulin-1 promotes cell survival via activation of ErbB2/4 receptors. We hypothesised that supplementing the cardiac storage solution (Celsior; C) with a recombinant human neuregulin-12a peptide (rhNRG-1) alone and with GTN and Cariporide (Car) would improve cardiac preservation. Methods: Pre-arrest cardiac function was measured in 77 isolated working rat hearts, which were then stored for 6 h at 4 ◦ C in C ± rhNRG-1 (14 M) or for 10 h in C ± rhNRG-1 (14 M) ± GTN (0.1 mg/ml) ± Car (10 M). Hearts were subsequently reperfused, cardiac function remeasured and tissue collected for protein analysis and histology. Optimal timing of administration of rhNRG-1 was also assessed. Results: These graphs represent post-storage recovery as a percentage of pre-arrest function (mean ± SEM).
Margaret Lucas
doi:10.1016/j.hlc.2009.05.383
Functional improvements were accompanied by increased Akt and ERK1/2 activation, GSK-3 inactivation (western blotting) and cleaved caspase-3 reduction (immunohistochemistry) (p < 0.05), effects abrogated by the PI3K inhibitor wortmannin. Conclusions: rh-NRG1 given together with other activators of pro-survival pathways improves preservation of the rat heart and shows promise for increasing the cold ischemic shelf life of donor hearts in transplantation. doi:10.1016/j.hlc.2009.05.382
Heart, Lung and Circulation 2009;18S:S1–S286
Abstracts
ABSTRACTS
Conclusions: We demonstrate favourable outcomes in patients with PPCM in this small series. More data is required to determine if this is a true reflection of current outcomes.
381 ACETAZOLAMIDE: OBSOLETE OR OVERLOOKED AS A DIURETIC IN HEART FAILURE?
doi:10.1016/j.hlc.2009.05.381
The Prince Charles Hospital, Brisbane, Australia
380 A RECOMBINANT HUMAN NEUREGULIN-1 PEPTIDE IMPROVES PRESERVATION OF THE TRANSPLANTED RAT HEART AFTER PROLONGED HYPOTHERMIC STORAGE
Background: Refractory oedema in chronic congestive cardiac failure (CCF) is often difficult to treat with unsatisfactory results both for patient and physician. Acetazolamide, a carbonic anhydrase inhibitor causing diuresis via the proximal tubule, is often overlooked and rarely used in favour of other diuretics. Method: We treated three patients experiencing refractory oedema predominantly from Right Heart Failure (RHF), despite increasing doses of multiple diuretics, with addition of acetazolamide 250 mg bd, every 2 of 3 days. CCF hospital admissions, length of stay (LOS) and renal function were measured pre- and post-treatment. Results: Two of the three patients were end stage CCF and all three had existing renal impairment with average eGFR 33, 35 and 45, respectively. Addition of acetazolamide did not increase electrolyte or renal dysfunction. Total LOS was halved in the two palliative patients (35–18 days, 56–28 days) with CCF LOS reductions (35–10 days, 45–28 days) over 6 and 3 months, respectively. The third patient had total LOS reduction from 53 to 2 days (CCF LOS; 46 days to 2 days) in the 12 months preand post-addition of acetazolamide. There was subjective improvement in all three patients. Conclusion: In CCF patients with refractory oedema, addition of acetazolamide improved oedema control, significantly reduced CCF hospital admissions, LOS and improved quality of life, subjectively. In selected cases acetazolamide may offer significant improvement of refractory oedema, bringing important benefits to patients and the healthcare system.
A. Jabbour 1 , L. Gao 1 , J. Kwan 1 , A. Watson 1 , L. Sun 1 , X. Liu 2 , M. Zhou 2 , R.M. Graham 1 , M. Hicks 1 , P. Macdonald 1 1 St Vincent’s Hospital and Victor Chang Cardiac Research Institute, Sydney, Australia 2 Zensun (Shanghai) Sci & Tech Co., Ltd., Shanghai, China
Aims: Neuregulin-1 promotes cell survival via activation of ErbB2/4 receptors. We hypothesised that supplementing the cardiac storage solution (Celsior; C) with a recombinant human neuregulin-12a peptide (rhNRG-1) alone and with GTN and Cariporide (Car) would improve cardiac preservation. Methods: Pre-arrest cardiac function was measured in 77 isolated working rat hearts, which were then stored for 6 h at 4 ◦ C in C ± rhNRG-1 (14 M) or for 10 h in C ± rhNRG-1 (14 M) ± GTN (0.1 mg/ml) ± Car (10 M). Hearts were subsequently reperfused, cardiac function remeasured and tissue collected for protein analysis and histology. Optimal timing of administration of rhNRG-1 was also assessed. Results: These graphs represent post-storage recovery as a percentage of pre-arrest function (mean ± SEM).
Margaret Lucas
doi:10.1016/j.hlc.2009.05.383
Functional improvements were accompanied by increased Akt and ERK1/2 activation, GSK-3 inactivation (western blotting) and cleaved caspase-3 reduction (immunohistochemistry) (p < 0.05), effects abrogated by the PI3K inhibitor wortmannin. Conclusions: rh-NRG1 given together with other activators of pro-survival pathways improves preservation of the rat heart and shows promise for increasing the cold ischemic shelf life of donor hearts in transplantation. doi:10.1016/j.hlc.2009.05.382