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Poststorage diastolic abnormalities of heart transplants: is vascular dysfunction or myocardial contracture the
E Kevelaitis1, C Mouas, P Menasché
1Department of Physiology, Medical Academy, Kaunas, Lithuania.
Insights
Myocardial contracture significantly impacts heart transplant diastolic function. Supplementing preservation solutions with 2,3-butanedione monoxime improved diastolic function and coronary vasodilation.
Area of Science:
- Cardiology
- Transplantation Medicine
- Biochemistry
Background:
- Vascular dysfunction and myocardial contracture contribute to post-transplant diastolic abnormalities in heart allografts.
- The relative importance of these factors in diastolic dysfunction remains unclear.
- This study investigates novel preservation solutions to mitigate these issues.
Purpose of the Study:
- To evaluate the efficacy of Celsior preservation solution supplemented with L-arginine and 2,3-butanedione monoxime in preserving cardiac function post-transplantation.
- To elucidate the roles of myocardial contracture and vascular dysfunction in post-transplant diastolic abnormalities.
Main Methods:
- Fifty isolated rat hearts were divided into four groups, receiving different preservation solutions (St. Thomas' No. 2 or Celsior, with or without L-arginine and 2,3-butanedione monoxime).
- Hearts underwent 10 hours of cold storage followed by 1 hour of reperfusion.
- Left ventricular pressure-volume curves were analyzed, and coronary vascular responses to 5-hydroxytryptamine and papaverine were assessed.
Main Results:
- Group 4, treated with Celsior supplemented with L-arginine and 2,3-butanedione monoxime, exhibited the best preserved left ventricular diastolic function.
- A major postischemic contracture was observed in the control group (group 1).
- Endothelium-independent vasodilation to papaverine was preserved in hearts treated with 2,3-butanedione monoxime, unlike other groups.
Conclusions:
- Myocardial contracture is a primary contributor to diastolic abnormalities in cardiac allografts.
- Alleviating contracture with 2,3-butanedione monoxime improves coronary smooth muscle responsiveness.
- Separate interventions are necessary to address vascular endothelium dysfunction.
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.