Improved myocardial ischemic tolerance by contractile inhibition with 2,3-butanedione monoxime.
Contracture of the arrested myocardium during prolonged storage of the heart results in both systolic and diastolic dysfunction, and is a major limitation to extended preservation. We studied the effects of a reversible contractile inhibitor, 2,3-butanedione monoxime (BDM), on myocardial ischemic tolerance. Isolated rabbit hearts were flushed with University of Wisconsin (UW) solution with and without 30 mmol/L BDM and 1 mmol/L CaCl, stored at 4 degrees C for 24 hours, and subsequently reperfused for 60 minutes. Left ventricular pressure-volume relationships and adenine nucleotide content were determined before reperfusion. Left ventricular systolic pressure, diastolic volume, and adenine nucleotide content were measured after reperfusion. Hearts stored in UW solution underwent contracture and adenosine triphosphate (ATP) depletion during storage, and exhibited systolic dysfunction, impaired diastolic relaxation, and poor ATP regeneration upon reperfusion. The addition of calcium worsened contracture and ATP depletion (p < 0.005) and slightly improved function and ATP regeneration (p = not significant). Hearts stored in the presence of BDM experience no contracture during storage; ATP was preserved (10.7 versus 15.7 nmol/mg; p < 0.05), and left ventricular systolic pressure and ATP content recovered to 74% and 93% of control on reperfusion, respectively (p < 0.005). Left ventricular diastolic volume remained depressed, however, although less than with UW solution (0.87 versus 0.45 mL; p < 0.001). When both BDM and calcium were included in the UW solution, calcium-stimulated ATP hydrolysis and contracture were prevented, left ventricular systolic pressure returned to 87% of control, and left ventricular diastolic volume and ATP content returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Stringham
J C
JC
Department of Surgery, University of Wisconsin Hospitals and Clinics, Madison 53792-3236.
Paulsen
K L
KL
Southard
J H
JH
Fields
B L
BL
Belzer
F O
FO
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D003187:Compliance; D003326:Coronary Circulation; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D005978:Glutathione; D006339:Heart Rate; D006352:Heart Ventricles / Q000503:physiopathology; D066298:In Vitro Techniques; D007328:Insulin; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011817:Rabbits; D011887:Raffinose; D012996:Solutions
D000227:Adenine Nucleotides; D007328:Insulin; D019188:Organ Preservation Solutions; D012996:Solutions; C055206:University of Wisconsin-lactobionate solution; C004717:diacetylmonoxime; D000493:Allopurinol; D005978:Glutathione; D003931:Diacetyl; D000241:Adenosine; D002122:Calcium Chloride; D011887:Raffinose