Poststorage diastolic abnormalities of heart transplants: is vascular dysfunction or myocardial contracture the culprit?
BACKGROUND
Vascular dysfunction and myocardial contracture can both contribute to posttransplantation diastolic abnormalities commonly exhibited by heart transplants, but their respective importance remains incompletely elucidated. To address this issue, we assessed the effects of supplementing a new heart preservation solution, Celsior, with a nitric oxide precursor (L-arginine) and a compound known to uncouple excitation from contraction (2, 3-butanedione monoxime).


METHODS
Fifty isolated buffer-perfused rat hearts were divided into four groups. In group 1, hearts were arrested with St. Thomas' Hospital solution No. 2 (Plegisol) and stored in normal saline solution. In group 2, Celsior solution was used for cardiac arrest and storage. Group 3 hearts were arrested with and stored in Celsior solution supplemented with 2 mmol/L of L-arginine. In group 4, Celsior solution used for arrest and storage was supplemented with both 2 mmol/L of L-arginine and 30 mmol/L of 2, 3-butanedione monoxime. All hearts were stored for 10 hours, subsequently reperfused for 1 hour on a Langendorff column, and left ventricular pressure-volume curves were constructed. 5-Hydroxytryptamine (10(-7) mol/L) and papaverine (5 x 10(-6) mol/L) were used to test changes in endothelium-dependent and endothelium-independent coronary vascular responses, respectively, and compared with those obtained during the preischemic period.


RESULTS
After 10 hours of cold storage, a major postischemic contracture was found in group 1. Left ventricular diastolic function was best preserved in group 4 at the end of storage and over the entire period of reperfusion. Coronary vasodilatory response to 5-hydroxytryptamine was completely lost in all groups after cold storage and reperfusion. Endothelium-independent vasodilatory response to papaverine was preserved in 2, 3-butanedione monoxime-treated hearts, whereas it was reduced in other groups.


CONCLUSIONS
Our results suggest that myocardial contracture plays a major role in posttransplantation diastolic abnormalities shown by cardiac allografts. Alleviation of contracture significantly improves the responsiveness of coronary smooth muscles but does not affect that of the vascular endothelium which needs to be handled by separate interventions.
Kevelaitis
E
E
Department of Physiology, Medical Academy, Kaunas, Lithuania.
Mouas
C
C
Menasché
P
P
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use; D001639:Bicarbonates / Q000627:therapeutic use; D002122:Calcium Chloride / Q000627:therapeutic use; D002306:Cardiac Volume / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects; D003931:Diacetyl / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D003971:Diastole / Q000187:drug effects; D004187:Disaccharides / Q000008:administration & dosage / Q000627:therapeutic use; D004573:Electrolytes / Q000008:administration & dosage / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects; D005971:Glutamates / Q000008:administration & dosage / Q000627:therapeutic use; D005978:Glutathione / Q000008:administration & dosage / Q000627:therapeutic use; D016027:Heart Transplantation / Q000502:physiology*; D006639:Histidine / Q000008:administration & dosage / Q000627:therapeutic use; D008274:Magnesium / Q000627:therapeutic use; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000187:drug effects; D009926:Organ Preservation; D010208:Papaverine / Q000494:pharmacology; D011189:Potassium Chloride / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012965:Sodium Chloride / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D001639:Bicarbonates; D002314:Cardioplegic Solutions; C088453:Celsior; D002801:Cholinesterase Reactivators; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D017366:Serotonin Receptor Agonists; C041711:St. Thomas' Hospital cardioplegic solution; D014665:Vasodilator Agents; C004717:diacetylmonoxime; D012701:Serotonin; D008353:Mannitol; D012965:Sodium Chloride; D006639:Histidine; D011189:Potassium Chloride; D001120:Arginine; D010208:Papaverine; D005978:Glutathione; D008274:Magnesium; D003931:Diacetyl; D002122:Calcium Chloride