Ann Thorac Surg 1995;59:1439-1440
© 1995 The Society of Thoracic Surgeons
INVITED COMMENTARY
Franklin L. Rosenfeldt, FRACS,
Stephen M. Richards, PhD
Baker Medical Research Institute, PO Box 348, Commercial Rd, Prahran, Victoria 3181, Australia
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Introduction
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See also page 1435.
This report describes the effect of inotropic stimulation with milrinone or dobutamine of neonatal hearts that had been stunned by 60 minutes of normothermic ischemia. It was not surprising that at the end of 30 minutes of reperfusion with the inotropic agents milrinone and dobutamine, these hearts exhibited greater contractile function (still in the presence of the inotropes) than if they were perfused with unmodified buffer. What was surprising, however, was that in the hearts that had been stimulated with milrinone—a phosphodiesterase inhibitor—analysis of the myocardium at the end of the reperfusion period failed to show a rise in cyclic AMP level. This finding was hard to reconcile with the known mechanism of action of this drug.
More surprising still was the difference in the levels of total adenine nucleotides between 10 and 40 minutes of reperfusion, implying that during working reperfusion, ATP demand exceeded the rate of ATP synthesis. This is in stark contrast to the situation in adult hearts, in which total adenine nucleotide levels generally do not change from the end of ischemia to the end of a 30-minute reperfusion period, and ATP level increases over the same period [1].
In the present study Pridjian and co-workers found that dobutamine and milrinone opposed the decline in total adenine nucleotide levels during reperfusion, presumably by correcting the ATP supply/demand imbalance. This finding is difficult to explain and seems counterintuitive. One possible explanation is that neonatal hearts behave differently than adult hearts in this respect. It is known that neonatal hearts are more reliant on glycolysis for energy production. ß-Adrenergic agents stimulate glycolysis and hence, conceivably, could increase ATP production during reperfusion to a level greater than the degradation rate.
The failure of cyclic AMP levels to rise in this model in the presence of a phosphodiesterase inhibitor needs to be explained or confirmed in further studies. Furthermore, the fall in high-energy phosphate levels during unstimulated reperfusion and the paradoxic prevention or reversal of this fall by inotropic stimulation during reperfusion also need to be confirmed in further studies. In the meantime, caution should be applied before interpreting these studies to indicate that there is a metabolic benefit in the use of phosphodiesterase inhibitors or ß-adrenergic agents to stimulate neonatal hearts during the recovery period after cardioplegic arrest.
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Reference
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- Bilsen MV, et al. Am J Physiol 1989;257(Heart Circ Physiol 26):H47–54.[Abstract/Free Full Text]
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