acetazolamide: obsolete or overlooked as a diuretic in heart failure?

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ABSTRACTS S168 Heart, Lung and Circulation Abstracts 2009;18S:S1–S286 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. doi:10.1016/j.hlc.2009.05.381 380 A RECOMBINANT HUMAN NEUREGULIN-1 PEPTIDE IMPROVES PRESERVATION OF THE TRANSPLANTED RAT HEART AFTER PROLONGED HYPOTHERMIC STORAGE 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 Insti- tute, 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 supplement- ing the cardiac storage solution (Celsior; C) with a recombinant human neuregulin-1 2a 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 6h 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). Functional improvements were accompanied by increased Akt and ERK1/2 activation, GSK-3 inactiva- tion (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 acti- vators 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.2009.05.382 381 ACETAZOLAMIDE: OBSOLETE OR OVERLOOKED AS A DIURETIC IN HEART FAILURE? Margaret Lucas The Prince Charles Hospital, Brisbane, Australia Background: Refractory oedema in chronic conges- tive 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 refrac- tory 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 acetazo- lamide 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 pre- and 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, sig- nificantly 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. doi:10.1016/j.hlc.2009.05.383

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Page 1: Acetazolamide: Obsolete or Overlooked as a Diuretic in Heart Failure?

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S168 Heart, Lung and CirculationAbstracts 2009;18S:S1–S286

Conclusions: We demonstrate favourable outcomes inpatients with PPCM in this small series. More data isrequired to determine if this is a true reflection of currentoutcomes.

doi:10.1016/j.hlc.2009.05.381

380A RECOMBINANT HUMAN NEUREGULIN-1PEPTIDE IMPROVES PRESERVATION OF THETRANSPLANTED RAT HEART AFTER PROLONGEDHYPOTHERMIC STORAGE

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 Insti-tute, Sydney, Australia2 Zensun (Shanghai) Sci & Tech Co., Ltd., Shanghai, China

Aims: Neuregulin-1 promotes cell survival via activationof ErbB2/4 receptors. We hypothesised that supplement-ing the cardiac storage solution (Celsior; C) with arecombinant human neuregulin-1�2a peptide (rhNRG-1)alone and with GTN and Cariporide (Car) would improvecardiac preservation.

Methods: Pre-arrest cardiac function was measured in77 isolated working rat hearts, which were then storedfor 6 h at 4 ◦C in C ± rhNRG-1 (14 �M) or for 10 h inC ± rhNRG-1 (14 �M) ± GTN (0.1 mg/ml) ± Car (10 �M).Hearts were subsequently reperfused, cardiac functionremeasured and tissue collected for protein analysis andhistology. Optimal timing of administration of rhNRG-1was also assessed.

Results: These graphs represent post-storage recoveryas a percentage of pre-arrest function (mean ± SEM).

Functional improvements were accompanied byincreased Akt and ERK1/2 activation, GSK-3� inactiva-tion (western blotting) and cleaved caspase-3 reduction(immunohistochemistry) (p < 0.05), effects abrogated bythe PI3K inhibitor wortmannin.

Conclusions: rh-NRG1 given together with other acti-vators of pro-survival pathways improves preservation ofthe rat heart and shows promise for increasing the coldischemic shelf life of donor hearts in transplantation.

doi:10.1016/j.hlc.2009.05.382

381ACETAZOLAMIDE: OBSOLETE OR OVERLOOKED ASA DIURETIC IN HEART FAILURE?

Margaret Lucas

The Prince Charles Hospital, Brisbane, Australia

Background: Refractory oedema in chronic conges-tive cardiac failure (CCF) is often difficult to treat withunsatisfactory results both for patient and physician.Acetazolamide, a carbonic anhydrase inhibitor causingdiuresis via the proximal tubule, is often overlooked andrarely used in favour of other diuretics.

Method: We treated three patients experiencing refrac-tory oedema predominantly from Right Heart Failure(RHF), despite increasing doses of multiple diuretics, withaddition of acetazolamide 250 mg bd, every 2 of 3 days.CCF hospital admissions, length of stay (LOS) and renalfunction were measured pre- and post-treatment.

Results: Two of the three patients were end stage CCFand all three had existing renal impairment with averageeGFR 33, 35 and 45, respectively. Addition of acetazo-lamide 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 (35–10days, 45–28 days) over 6 and 3 months, respectively. Thethird patient had total LOS reduction from 53 to 2 days(CCF LOS; 46 days to 2 days) in the 12 months pre-and post-addition of acetazolamide. There was subjectiveimprovement in all three patients.

Conclusion: In CCF patients with refractory oedema,addition of acetazolamide improved oedema control, sig-nificantly reduced CCF hospital admissions, LOS andimproved quality of life, subjectively. In selected casesacetazolamide may offer significant improvement ofrefractory oedema, bringing important benefits to patientsand the healthcare system.

doi:10.1016/j.hlc.2009.05.383