Improved right heart function after myocardial preservation with 2,3-butanedione 2-monoxime in a porcine model of allogenic heart transplantation.
BACKGROUND
Right heart dysfunction is a major cause for early morbidity and mortality after heart transplantation. Experiments were designed to evaluate the influence of the calcium-desensitizing drug 2,3-butanedione 2-monoxime (BDM) on right heart function in a porcine model of heart transplantation.


METHODS
Donor hearts of domestic pigs were arrested with BDM in Krebs solution (n = 7) and with BDM in Bretschneider's histidine-tryptophan-ketoglutarate (HTK) solution (n = 6). There were 2 control groups: University of Wisconsin (UW, n = 6) and HTK (n = 6). An isovolumic model was used in which the right ventricular volume was precisely controlled in vivo with an intracavitary high-compliance balloon. After 4 hours of ischemia, hearts were transplanted into recipients. After 1 and 2 hours of reperfusion, the right ventricular balloon volume was increased in 10-mL increments until right ventricular failure occurred and the developed pressures were recorded.


RESULTS
Maximal right ventricular developed pressures were significantly different after 2 hours of reperfusion (UW: 35 +/- 13 mm Hg; HTK: 47 +/- 8 mm Hg; Krebs+BDM: 49 +/- 9 mm Hg; HTK+BDM: 50 +/- 6 mm Hg; P =.04). Hearts subjected to BDM could be loaded with a significantly increased volume after 1 hour and after 2 hours (UW: 57 +/- 10 mL vs HTK: 43 +/- 8 mL vs Krebs+BDM: 70 +/- 10 mL vs HTK+BDM: 67 +/- 15 mL; P =.002). Postischemic right ventricular enddiastolic compliance was significantly increased in groups treated with BDM after 1 hour (P =.02) and after 2 hours (P =.039).


CONCLUSIONS
The drug BDM significantly improves right ventricular function in a heart transplantation model. The increase in volume load and developed right ventricular pressure achieved by BDM application would translate into a decreased risk of right ventricular failure after clinical transplantation.
Warnecke
Gregor
G
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany.
Schulze
Benjamin
B
Hagl
Christian
C
Haverich
Axel
A
Klima
Uwe
U
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D003931:Diacetyl / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005947:Glucose; D005978:Glutathione; D016027:Heart Transplantation / Q000009:adverse effects / Q000502:physiology*; D007328:Insulin; D007527:Isoenzymes / Q000097:blood; D007552:Isotonic Solutions; D019344:Lactic Acid / Q000097:blood; D008353:Mannitol; D009206:Myocardium / Q000378:metabolism; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011189:Potassium Chloride; D011343:Procaine; D011887:Raffinose; D013552:Swine; D018497:Ventricular Dysfunction, Right / Q000209:etiology / Q000517:prevention & control; D016278:Ventricular Function, Right / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
C039984:Bretschneider cardioplegic solution; D007328:Insulin; D007527:Isoenzymes; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; C004717:diacetylmonoxime; D019344:Lactic Acid; D008353:Mannitol; D011343:Procaine; D000493:Allopurinol; D011189:Potassium Chloride; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D005978:Glutathione; D005947:Glucose; D003931:Diacetyl; D000241:Adenosine; D011887:Raffinose; D002118:Calcium