Reducing postischemic reperfusion damage in neonates using a terminal warm substrate-enriched blood cardioplegic reperfusate.
BACKGROUND
In adult cardiac operations, a warm cardioplegic reperfusate ("hot shot") before removing the aortic cross-clamp improves postbypass myocardial function and metabolic recovery. This modality, however, is rarely used in infants, despite the fact that postbypass cardiac dysfunction remains problematic, especially in cyanotic ("stressed") patients.


METHODS
To produce stress, 15 neonatal piglets underwent 60 minutes of ventilator hypoxia (fraction of inspired oxygen, 8% to 10%). All piglets then received similar protection with multidose cold blood cardioplegic solution during 70 minutes of arrest and were separated into three groups to examine the role of a warm reperfusate as well as possible augmentation by aspartate and glutamate enrichment. In 5 piglets (group 1), the cross-clamp was simply removed; in 5 (group 2), an unsupplemented warm blood cardioplegic reperfusate was given; and in 5 (group 3), the warm reperfusate was enriched with aspartate and glutamate. Myocardial function was assessed using pressure-volume loops and expressed as a percentage of control.


RESULTS
Compared with hearts receiving reperfusion with unmodified blood (group 1), a warm unsupplemented cardioplegic reperfusate (group 2) slightly improved systolic contractility (end-systolic elastance, 41% versus 50%; p < 0.05 versus group 1) and preload recruitable stroke work (41% versus 52%; p < 0.05 versus group 1), reduced diastolic stiffness (263% versus 245%; p < 0.05 versus group 1), and increased adenosine triphosphate (10.7 versus 11.9 microg/g tissue, p < 0.05 versus group 1). However, if aspartate and glutamate was included in the warm reperfusate (group 3), there was complete recovery of systolic function (end-systolic elastance, 105%+/-3%; p < 0.001 versus all groups) and preload recruitable stroke work (103%+/-2%; p < 0.001 versus all groups), a minimal rise in diastolic stiffness (154%+/-7%; p < 0.001 versus all groups), and preservation of adenosine triphosphate (15.5+/-0.5 microg/g; p < 0.001 versus all groups).


CONCLUSIONS
A warm cardioplegic reperfusate helps reduce the reperfusion injury, resulting in improved myocardial function and metabolic recovery in hypoxic (stressed) neonatal hearts, and this effect is maximized if the reperfusate is enriched with aspartate and glutamate, which completely preserves myocardial function.
Kronon
M T
MT
Division of Pediatric Cardiovascular Surgery, The Heart Institute for Children, Hope Children's Hospital, Oak Lawn, Illinois 60453, USA.
Allen
B S
BS
Rahman
S
S
Wang
T
T
Tayyab
N A
NA
Bolling
K S
KS
Ilbawi
M N
MN
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000494:pharmacology; D001769:Blood; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D006321:Heart / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption; D013552:Swine; D013696:Temperature
D002314:Cardioplegic Solutions; D001224:Aspartic Acid; D018698:Glutamic Acid; D000255:Adenosine Triphosphate