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Enhanced 24-hour in vitro heart preservation with adenosine and adenosine monophosphate
D Petsikas1, M A Ricci, R Baffour
1Cardiovascular Research Unit, Royal Victoria Hospital, Montreal, Quebec, Canada.
Insights
Adding adenosine or adenosine monophosphate to hypothermic perfusion solutions significantly improved canine cardiac allograft preservation. These precursors enhanced coronary blood flow and myocardial function, offering a promising strategy for organ transplantation.
Area of Science:
- Cardiology
- Transplantation Immunology
- Biochemistry
Background:
- Continuous hypothermic perfusion is a standard method for preserving cardiac allografts.
- Enhancing the protective effects of perfusion is crucial for improving organ viability.
Purpose of the Study:
- To evaluate the efficacy of high-energy phosphate precursors, adenosine and adenosine monophosphate (AMP), in augmenting hypothermic preservation of canine cardiac allografts.
- To assess the impact of these precursors on myocardial function and metabolic markers.
Main Methods:
- Canine hearts were subjected to 24-hour continuous hypothermic perfusion.
- Control group received standard Krebs-Henseleit solution.
- Experimental groups received perfusate supplemented with adenosine (20 µmol/L) or adenosine monophosphate (0.1 mmol/L).
- Evaluated heart weight, coronary vascular resistance, developed pressures, pressure development rate, myocardial ATP, and lactate levels.
Main Results:
- Adenosine and AMP supplementation decreased coronary vascular resistance compared to controls.
- Both adenosine and AMP groups showed significantly improved developed pressures and rate of pressure development.
- Myocardial adenosine triphosphate levels were significantly higher in the AMP group.
- Lactate levels were significantly lower in the adenosine and AMP groups compared to controls.
Conclusions:
- Adenosine and adenosine monophosphate enhance the protective effects of continuous hypothermic perfusion for cardiac allografts.
- These precursors improve coronary hemodynamics and preserve myocardial energy metabolism.
- Supplementation with these high-energy phosphate precursors represents a promising strategy to improve cardiac allograft outcomes.
Abstract:
Continuous hypothermic perfusion is an effective means of preserving ex vivo cardiac allografts. Using canine hearts, we assessed the ability of the high-energy phosphate precursors adenosine and adenosine monophosphate to enhance the protective effect of continuous hypothermic perfusion. Group 1 hearts (controls) were perfused for 24 hours with a modified Krebs-Henseleit solution. Group 2 hearts were perfused with control perfusate to which adenosine was added (20 mumol/L). Group 3 hearts were perfused with control perfusate with adenosine monophosphate (0.1 mmol/L). After perfusion heart weights increased similarly in all groups. Coronary vascular resistance increased during the preservation period in group 1 hearts, but decreased in groups 2 and 3 hearts. Developed pressures were 103 +/- 22 mm Hg in group 1, 163 +/- 27 mm Hg in group 2 (p less than 0.01), and 141 +/- 34 mm Hg (p less than 0.05) in group 3. The rate of pressure development in group 2 (2143 +/- 249 mm Hg) and group 3 (2059 +/- 395 mm Hg) hearts was significantly greater than in group 1 hearts (1434 +/- 363 mm Hg, p less than 0.01). Only group 3 myocardial adenosine triphosphate levels were significantly greater than controls (3.18 +/- 0.52 mumol/gm vs 2.12 +/- 0.74 mumol/gm, p less than 0.05) on completion of perfusion. Myocardial lactate levels at this time were significantly higher in group 1 hearts (7.48 +/- 3.96 mumol/gm) compared with groups 2 and 3 (0.34 +/- 0.58 mumol/gm and 1.50 +/- 0.91 mumol/gm, respectively, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)