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Ann Thorac Surg 2009;87:1517-1523. doi:10.1016/j.athoracsur.2009.02.067
© 2009 The Society of Thoracic Surgeons
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Original Articles: Pediatric Cardiac

Pediatric Cardioplegia Strategy Results in Enhanced Calcium Metabolism and Lower Serum Troponin T

J. Darcy O'Brien, MSa, Susan E. Howlett, PhDa, Hayley J. Burton, RNb, Stacey B. O'Blenes, MDb, D. Sharon Litz, MDc, Camille L. Hancock Friesen, MDb,*

a Department of Pharmacology, Izaak Walton Killam Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada
b Department of Surgery/Division of Pediatric Cardiac Surgery, Izaak Walton Killam Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada
c Department of Pediatric Anaesthesia, Izaak Walton Killam Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada

Accepted for publication February 23, 2009.

* Address correspondence to Dr Friesen, The Maritime Heart Center, 1796 Summer St, No. 2269, Halifax, Nova Scotia, B3H 3A7, Canada (Email: camillehf{at}hotmail.com).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background: Pediatric myocardium is unique from mature myocardium; thus, the use of adult cardioplegia for pediatric cardiac operations may provide suboptimal myocardial protection. We evaluated our standard adult cardioplegia (AC; modified Buckberg) and a pediatric cardioplegia (PC) solution (del Nido solution, Baxter) in vitro in rat cardiomyocytes and compared short-term outcomes in pediatric cardiac surgical patients.

Methods: Contractions, intracellular calcium, and action potentials were recorded from isolated rat cardiomyocytes exposed to PC or AC, followed by reperfusion. Pediatric patients (n = 118) undergoing cardiac operations using PC (group PC, n = 59) or AC (group AC, n = 59) were matched 1:1 for age, diagnosis, and duration of cardiopulmonary bypass.

Results: PC-perfused rat ventricular cardiomyocytes had lower diastolic calcium during cardioplegia and early reperfusion than AC-perfused cardiomyocytes. Cardiomyocytes remained excitable despite introduction of AC but not PC. The mean age in each pediatric group was 3.7 years (range, 3 days to 17 years; p = 0.95). Median serum troponin T levels at intensive care admission were significantly lower in group PC (0.83 ± 0.25 µg/L) than in group AC (13.8 ± 12.7 µg/L, p = 0.0001), which persisted at 24 hours postoperatively. There were no significant differences in duration of intubation or length of stay in intensive care or the hospital.

Conclusions: Pediatric cardioplegia is associated with reduced intracellular diastolic calcium during arrest and reperfusion and more complete arrest during exposure in rat cardiomyocytes. Pediatric patients receiving pediatric cardioplegia had reduced troponin T release compared with those receiving adult cardioplegia.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Immature myocardium has unique structural and functional characteristics compared with mature myocardium. These characteristics influence responses of pediatric myocardium to ischemia during cardiac surgical procedures. There is conflicting evidence regarding the tolerance of pediatric myocardium to ischemia. Although some studies report that pediatric myocardium is more tolerant of ischemia than adult myocardium [1–3], others suggest the converse is true [4, 5]. Even if pediatric myocardium is ischemia-resistant, cardiac surgical intervention in these patients almost always occurs under conditions of cyanosis, volume load, and pressure load, or a combination of these stressors that reduce resting adenosine triphosphate (ATP) and nucleotide availability and increase intracellular calcium (Ca2+) levels [6, 7]. Therefore, the enhanced tolerance to ischemia observed experimentally in normal pediatric hearts may not be generalizable to pediatric cardiac surgical patients.

Pediatric hearts, particularly those exposed to hypoxia, are more sensitive to Ca2+-induced injury during ischemia and reperfusion than adult hearts [8, 9]. In pediatric myocardium, intracellular calcium regulatory elements, including the sarcoplasmic reticulum, Ca2+-ATPase, and ryanodine receptor 2, function at reduced levels compared with mature myocardium [10–12]. Until these calcium regulatory elements mature, pediatric myocardium is more sensitive to extracellular calcium levels than mature myocardium. Compared with mature heart, pediatric myocardium relies more on Ca2+ influx and efflux for excitation-contraction coupling and is poorly equipped to deal with postischemic Ca2+ overload [13]. Thus, particular attention to Ca2+ management is critical in any myocardial preservation strategy for children's hearts. There is growing interest in the effect of cardioplegia on pediatric myocardium [14, 15] and in optimizing techniques for myocardial preservation in pediatric myocardium [16–21].

Our standard cardioplegia strategy used for pediatric cardiac surgical cases is antegrade delivery of adult (modified Buckberg) cardioplegia (Table 1). However, a myocardial preservation strategy tailored to the unique metabolic requirements of pediatric myocardium has been developed using a pediatric-formulated cardioplegia (del Nido, Table 1), the major unique additives of which are lidocaine and magnesium.


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  		Table 1 Composition of Cardioplegia Solutions
 
We evaluated the pediatric (PC) and adult cardioplegia (AC) solutions on isolated rat ventricular cardiomyocytes using an in vitro model to determine effects of cardioplegia on myocyte contractile activity, intracellular Ca2+ homeostasis, and membrane potential. We also compared short-term outcomes in pediatric patients treated with a pediatric (group PC) or adult cardioplegia (group AC) strategy.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Acknowledgments
 References
 
In Vitro
Animal procedures were approved by the Dalhousie University Committee on Animal Care and conformed to Canadian Council on Animal Care Guidelines (Vol 1, 1980, and Vol 2, 1984, Ottawa, Ontario). Ventricular cardiomyocytes (myocytes) were obtained by enzymatic dissociation as described previously [22]. Briefly, young adult male Fisher 344 rats (3 months, Charles River, St. Constant, QC) were anesthetized with pentobarbital sodium (220 mg/kg intraperitoneal). The aorta was cannulated and perfused for 5 minutes (18 to 20 mL/min, 37°C, oxygen) with buffer consisting of 135 mM NaCl, 4 mM KCl, 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), 1.2 mM MgSO4, 1.2 mM KH2PO4, 50 µM CaCl2, and 12mM glucose (pH, 7.4). Hearts were digested for 15 to 20 minutes with buffer plus protease Dispase II (0.1 mg/mL) (Roche Diagnostics, Lowal, QC) and collagenase type 2 (0.3 mg/mL). Ventricles were minced in high-potassium buffer: 80 mM KOH, 30 mM KCl, 3 mM MgSO4 . 7 mM H2O, 30 mM KH2PO4, 50 mM L-glutamic acid, 20 mM taurine, 0.5 mM ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA), 10 mM HEPES, and 10 mM glucose (pH, 7.4), and filtered through 225-µm polyethylene mesh. No more than two ventricular myocytes per heart were included in any data set.

Myocytes were incubated with Ca2+-sensitive dye (fura 2 AM, 5 µM for 15 to 20 minutes, light-protected) and then equilibrated in Tyrode's solution (37°C, 3 mL/min) containing 129 mM NaCl, 20 mM NaHCO3, 0.9 mM NaH2PO4, 4 mM KCl, 0.5 mM MgSO4, 1.8 mM CaCl2, and 5.5 mM glucose (pH 7.2) in 95% O2x 5% CO2. Myocytes were field-stimulated (4 Hz, 3-msec pulses) with platinum electrodes. After equilibration, myocytes were superfused with pediatric cardioplegia (group PC, mixed 4 parts cardioplegia to 1 part Tyrode's) or adult cardioplegia (group AC, mixed 1 part cardioplegia to 4 parts Tyrode's, Table 1).

Cardioplegia was delivered for 30 minutes at room temperature to mimic cooling during in vivo cardioplegia. Myocytes were not field-stimulated during cardioplegia, except briefly at 12.5 and 22.5 minutes of cardioplegia to check for excitability. Cardioplegic solutions were bubbled with 90% NO2 and 10% CO2, and this gas was directed over the chamber to simulate hypoxia during cardioplegia. Myocytes were reperfused with Tyrode's solution. Recordings of contractions and Ca2+ transients were made for 65 minutes; and responses remained stable for this time, as shown previously [22].

Cell shortening and intracellular Ca2+ were measured simultaneously with a video edge detector (Crescent Electronics, Sandy, UT) and whole-cell photometry (Felix 32 software, Photon Technology Int, Birmingham, NJ) as described previously [22]. Fura-2 was excited alternately at 340 nm and 380 nm, and fluorescence emission was collected at 510 nm (background subtracted). Ten-second recordings were repeated every 5 minutes, with additional recordings at 12.5 and 22.5 minutes of cardioplegia and at 1 and 2 minutes of reperfusion. Contractions and Ca2+ transients (5- to 10-second recordings) were averaged and measured with Clampfit 8.2 software (Molecular Devices, Sunnyvale, CA). Contraction and Ca2+ transient amplitudes were the difference between diastolic and systolic values. Data were normalized to values at the beginning of the experiment.

In some experiments, myocytes were impaled with high-resistance microelectrodes (15 to 25 M{Omega}, filled with 2.7M KCl) to measure membrane potential. Action potentials were recorded with an Axon Instruments amplifier (Union City, CA) and Clampex 8.1 software (Molecular Devices). In these experiments, cardioplegia was delivered at 37°C because cooling to room temperature made electrical recordings unstable.

Mean values are presented with standard error, and medians with interquartile ranges (IQR 25 and 75). The t test was used to compare averages of normally distributed continuous variables and medians of skewed populations were compared with a Mann-Whitney test. A one-way repeated measures analysis of variance (ANOVA) was used to compare within in vitro groups and a two-way repeated measures ANOVA was used to compare between in vitro groups.

In Vivo
Ethics approval (IWK Health Care Centre) was obtained for a review of congenital cardiac patients undergoing cardiac procedures requiring cardiac arrest between January 1, 2003, and August 31, 2006. All operations were performed by two surgeons (C. H. F., S. O.). Patients treated with PC (group PC, Table 1) were matched 1:1 with a recent historic cohort (group AC) based on pathologic diagnosis, age at operation, operation performed, cross-clamp duration, and cardiopulmonary bypass duration (Table 2). Group PC represents a consecutive cohort except for 13 patients excluded from analysis because no matching case was found in group AC. All operations were performed in the same 3-year period. Group AC cases were performed slightly earlier in the study period, July 2003 to November 2005, and group PC cases were performed March 2005 to August 2006.


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  		Table 2 Surgical Cases
 
Group PC was treated using the pediatric myocardial management strategy, which included a single cold (7° to 10°C) antegrade dose (20 mL/kg) of del Nido cardioplegia, mixed 4:1 ratio of cardioplegia to blood (Table 1). Cardioplegia was not renewed in group PC patients regardless of the cross-clamp time (protocol from Boston Children's Hospital, Dr P.J. del Nido, personal communication). Group AC patients were treated with our standard myocardial protection strategy of modified Buckberg solution mixed in a 1:4 ratio of cardioplegia to blood administered as a cold (7° to 10°C) antegrade 60-mL/kg induction dose, followed by additional 20-mL/kg doses every 20 minutes for the cross-clamp duration.

The primary outcome was 30-day mortality. Secondary outcomes included serum troponin T on admission to the intensive care unit (ICU, time 1) and 24 hours after ICU admission (time 2), inotrope requirement (inotrope scores were calculated at time 1 and then at 6-hour intervals throughout the ICU stay) [23], maximum temperature and white blood cell count, minimum platelet count in ICU, and length of stay on the ventilator, in the ICU, and in the hospital.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Acknowledgments
 References
 
In Vitro Data
Myocyte shortening and CA2+ homeostasis
Representative recordings are presented in Figure 1A. Mean data are shown in Figure 1B. Contractions were absent in PC- and AC-exposed myocytes during cardioplegia when myocytes were not field-stimulated. When myocytes were briefly stimulated at 12.5 and 22.5 minutes of cardioplegia, contractions were elicited in AC but not in PC myocytes. In early reperfusion, AC myocytes exhibited an overshoot in contraction before recovery, whereas PC myocytes recovered more slowly.


Figure 1
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  		Fig 1. Contractions in myocytes exposed to pediatric cardioplegia (group PC) or adult cardioplegia (group AC). (A) Representative examples of contraction recordings throughout an experiment in group PC and group AC myocytes. (CP = cardioplegia; RF = reperfusion.) (B) Group AC (white circles) but not group PC myocytes (black circles) were contractile when stimulated. There was an overshoot in contraction upon reperfusion in group AC but not in group PC. Arrows indicate field-stimulation during cardioplegia. (Data are presented with the standard error; 7 to 9 myocytes/group; *p < 0.05.)

 
CA2+ transients in myocytes
Representative recordings are presented in Figure 2A. Mean data are shown in Figure 2B and C. At 5 minutes of cardioplegia, myocytes were not field-stimulated and Ca2+ transients were absent in both groups (Fig 2B). Diastolic Ca2+ declined below control levels in PC but not in AC myocytes (Fig 2C). When myocytes were briefly stimulated, no Ca2+ transients were elicited in PC and diastolic Ca2+ remained low. In contrast, stimulation elicited Ca2+ transients in AC myocytes, and diastolic Ca2+ levels were elevated with respect to control values. Ca2+ transients and diastolic Ca2+ recovered gradually in early reperfusion in PC myocytes. In contrast, Ca2+ transients and diastolic Ca2+ exhibited a rapid overshoot in early reperfusion in AC myocytes and then recovered to near control levels later in reperfusion.


Figure 2
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  		Fig 2. Changes in Ca2+ levels in myocytes exposed to pediatric (group PC) or adult cardioplegia (group AC). (A) Examples of intracellular Ca2+ levels in group PC and group AC myocytes. (B) Ca2+ transients were elicited by stimulation in group AC (white circles) but not group PC (black circles) myocytes. An overshoot in Ca2+ transients occurred in group AC, but Ca2+ transients recovered slowly in group PC. (C) Throughout cardioplegia, diastolic Ca2+ was lower in group PC (black circles) than in group AC (white circles). Diastolic Ca2+ rose during stimulation in group AC but not in group PC. Diastolic Ca2+ levels recovered rapidly in early reperfusion in group AC but recovered slowly in group PC. Arrows indicate stimulation during cardioplegia. (Data are presented with the standard error; n = 7 to 9 myocytes/group, *p < 0.05).

 
Resting and action potentials
In separate experiments, membrane potential was recorded before and during exposure to PC and AC. Figure 3A shows representative recordings of action potentials before cardioplegia in both groups. Resting membrane potential was near –80 mV under control conditions. During cardioplegia, myocytes in both groups depolarized. Resting membrane potential depolarized to near –45 mV in PC myocytes and near –55 mV in AC myocytes (p = 0.09, ANOVA). Mean data are presented in Figure 3B.


Figure 3
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  		Fig 3. Changes in resting membrane potential in myocytes exposed to pediatric (group PC) or adult cardioplegia (group AC). (A) Cardioplegia caused depolarization of the resting membrane potential in both groups. (B) Resting membrane potential was near –80 mV before cardioplegia. Myocytes depolarized to similar levels during cardioplegia in group PC (black bars) and in group AC (white bars). Dashed line represents –50 mV. Recordings were made from 3 to 4 myocytes in each group. (Data are presented with the standard error; *p < 0.05 vs control values).

 
In Vivo Data
Demographics
There were 118 patients, 59 in each group. There were 4 neonates in group PC (aged 3, 4, 5, and 11 days at operation) and 3 in group AC (aged 6, 11, and 16 days at operation). There were 32 infants (aged < 2 years at the time of operation) in group PC and 36 in group AC. Single ventricle operations (stage I, II, or III) comprised four of 59 operations in group PC and three of 59 in group AC (Table 2). Each group had 12 patients with cyanotic diagnoses. Of 19 patients with tetralogy of Fallot, 7 of 9 in group PC underwent right ventricle muscle resection or transannular patches were used vs 9 of 10 in group AC. The mean age, weight, and body surface area at operation were similar between groups (Table 3).


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  		Table 3 Perioperative Variables
 
Operative variables
The average duration of cross-clamp and cardiopulmonary bypass were slightly longer in group AC, a difference that reflects the time required for the administration of multiple doses of cardioplegia (Table 3).

Mortality
There were no early deaths in either group.

Serum troponin T
Serum troponin T levels were assayed on admission to the ICU (time 1) and at 24 hours after ICU admission (time 2) and were significantly different between the groups. The median serum level of troponin T at time 1 was 0.83 ± 0.25 µg/L in group PC and 13.8 ± 12.7 µg/L in group AC (p < 0.0001. The median serum level of troponin T at time 2 was 0.71 ± 0.2 µg/L in group PC vs 16 ± 8.7 µg/L in group AC (p = 0.0001). We analyzed serum troponin T levels in three subpopulations (Fig 4). In all but the tetralogy subgroup, group PC had lower serum troponin T levels than group AC.


Figure 4
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  		Fig 4. Subgroup serum troponin T after cardiotomy. (A) In both infants and noninfants, pediatric cardioplegia (group PC) resulted in significantly lower serum troponin T levels at time 1 and time 2 (data not shown) than adult cardioplegia (group AC). (B) In both cyanotic and acyanotic cohorts, group PC had lower serum troponin T levels than group AC at time 1, whereas only the acyanotic group was significantly different between groups at time 1 (data not shown). (C) Serum troponin T levels were similar between groups for tetralogy patients (p = 0.12), but levels in group PC were significantly lower than group AC in the nontetralogy patients, indicating that when muscle incision is excluded as a source of troponin T, the difference in serum troponin T correlates with the cardioplegia strategy used.

 
Inotrope scores
Inotrope requirement was similar between groups. The average inotrope score for group PC at time 1 was 8.7 ± 0.78 compared with 7.4 ± 1.2 for group AC. At time 2, the average inotrope score for group PC was 4.3 ± 0.7 vs 5.8 ± 1.0 for group AC (ANOVA, p = 0.78).

There were no significant differences in platelet count or white blood cell count between groups (data not shown). Duration of intubation tended to be shorter in group PC than in group AC, but lengths of stay in the ICU and hospital were comparable (Table 3).


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Acknowledgments
 References
 
PC-Treated Myocytes had More Complete Electromechanical Quiescence and Lower Diastolic Calcium Levels
This study showed that Ca2+ transients and contractions could be elicited by field-stimulation in myocytes exposed to AC. In contrast, Ca2+ transients and contractions could not be induced when myocytes were field-stimulated during exposure to PC. This illustrates a marked difference in cell excitability between AC and PC. This effect may be due to blockade of Na+ channels by lidocaine in the PC. Blockade of Na+ channels by lidocaine is enhanced at more depolarized membrane potentials [24], and myocytes exposed to both cardioplegic solutions exhibited membrane depolarization as a result of high K+ concentrations (Table 1). The combination of lidocaine plus depolarization in the PC acts to prevent action potential development and reduce excitability. Higher levels of Mg2+ in the PC also may contribute to the lower excitability observed with PC [25]. The reduction of excitability in myocytes exposed to PC may provide clinical benefit by reducing cellular metabolism and ATP utilization.

Myocytes exposed to AC exhibited a marked overshoot in contraction amplitude, an increase in Ca2+ transient amplitude in early reperfusion, and increased diastolic Ca2+ levels. In contrast, contractions and Ca2+ transients recovered gradually in early reperfusion in myocytes superfused with PC, and diastolic Ca2+ levels were lower. Much of the damage associated with ischemia and reperfusion is due to increased levels of Ca2+ [26]. Hypercontractility during early reperfusion has been described in isolated myocytes after exposure to simulated ischemia [22]. Excessive force generation during early reperfusion is thought to result from Ca2+ overload and can lead to cytoskeletal damage and contraction band necrosis [27]. Thus, the absence of hypercontractility in myocytes reperfused after PC may be physiologically advantageous. In the present study, blockade of Na+ channels with lidocaine in the PC may have inhibited the overshoot in contractions and Ca2+ transients in early reperfusion and also reduced diastolic Ca2+ levels. Lidocaine has been shown to reduce Na+ accumulation in ischemia and limit Ca2+ overload by reverse-mode Na+/Ca2+ exchange [28, 29]. PC also has less Ca2+ and more Mg2+ than AC, and both of these factors may reduce cytosolic Ca2+ and contractility [25].

Previous studies have demonstrated that hyperpolarizing cardioplegic solutions supplemented with lidocaine provide superior protection compared with traditional hyperkalemic depolarizing cardioplegic solutions [30, 31]. Preservation of resting membrane potential near resting levels is thought to attenuate Ca2+ overload by inhibiting Na+ and Ca2+ window currents that are activated at depolarized membrane potentials [31]. This report documents intracellular calcium homeostasis in a hyperkalemic depolarizing cardioplegic solution supplemented with lidocaine. The results of this study clearly demonstrate that supplementation with lidocaine reduces accumulation of Ca2+ during cardioplegia, even at depolarized membrane potentials where window currents would be active.

Pediatric Cardioplegia is Associated With Reduced Troponin T Release
We observed a significant reduction in serum troponin T levels in patients treated with a PC strategy compared with patients treated with an AC strategy. Troponin T is a sensitive and specific marker of ischemic myocardial injury and an independent predictor of early death in pediatric cardiac surgical patients [32]. Although no early deaths occurred in either group, there was a trend to reduced duration of intubation in patients with lower postoperative troponin T levels.

In addition to the cellular mechanisms that have been discussed, there are a number of possible reasons why the PC strategy may provide superior myocardial protection. First, under conditions of moderate hypothermia, microvascular distribution of cardioplegia may be enhanced in the lower-viscosity PC. Second, a single dose of cardioplegia (group PC) may be associated with a reduction in the amount of unintentional air introduced into the coronary arteries, leading to improved reperfusion at the time of aortic cross-clamp removal. Third, laboratory [33, 34] and clinical trials [35] have shown that multidose cardioplegia as used in the AC strategy is associated with worse postischemic ventricular function, possibly as a result of myocardial edema.

We did not witness any difference in clinical outcome as documented by early death, inotrope score, and ICU and hospital length of stay, but these relatively insensitive outcomes may not be sufficiently sensitive to reflect outcome differences between the groups.

Study Limitations
Because this is a retrospective review with a historic control, there may have been systematic differences in the way perfusion, anesthesia, and surgery were performed more recently that have created a bias for better protection irrespective of the cardioplegia that was used.

Conclusions
A strategy that uses pediatric cardioplegia is associated with significantly reduced troponin T release. The calcium handling of cardiomyocytes exposed to pediatric cardioplegia appeared to be superior. Further studies are indicated to determine how the myocardial protection is mediated and whether there may be a role for this type of pediatric cardioplegia in the myocardial protection strategy for myocardium that is fragile as a result of any number of stressors.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
References
 
Funding was provided by Dalhousie Department of Surgery Seed Funding (C.H.F./S.B.O.), Faculty of Medicine Clinical Research Scholar (C.H.F./S.B.O.), and Heart and Stroke Foundation (S.E.H.).


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Yee E, Ebert P. Effect of ischemia on ventricular function, compliance and edema in immature and adult canine hearts Surg Forum 1979;30:250-252.[Medline]
  2. Hiramatsu T, Zund G, Schermerhorn ML, Shinóka T, Miura T, Mayer Jr JE. Age differences in effects of hypothermic ischemia on endothelial and ventricular function Ann Thorac Surg 1995;60:S501-S504.[Medline]
  3. Yano Y, Braimbridge MV, Hearse DJ. Protection of the pediatric myocardium. Differential susceptibility to ischemic injury of the neonatal rat heart. J Thorac Cardiovasc Surg 1987;94:887-896.[Abstract]
  4. Wittnich C, Peniston C, Ianuzzo D, Abel JG, Salerno TA. Relative vulnerability of neonatal and adult hearts to ischemic injury Circulation 1987;76:V156-V160.[Medline]
  5. Parrish MD, Payne A, Fixler DE. Global myocardial ischemia in the newborn, juvenile, and adult isolated isovolumic rabbit heart. Age-related differences in systolic function, diastolic stiffness, coronary resistance, myocardial oxygen consumption, and extracellular pH. Circ Res 1987;61:609-615.[Abstract/Free Full Text]
  6. Allen BS. Pediatric myocardial protection: where do we stand? J Thorac Cardiovasc Surg 2004;128:11-13.[Free Full Text]
  7. Modi P, Suleiman MS, Reeves BC, et al. Basal metabolic state of hearts of patients with congenital heart disease: the effects of cyanosis, age, and pathology Ann Thorac Surg 2004;78:1710-1716.[Abstract/Free Full Text]
  8. Bolling K, Kronon M, Allen BS, et al. Myocardial protection in normal and hypoxically stressed neonatal hearts: the superiority of hypocalcemic versus normocalcemic blood cardioplegia J Thorac Cardiovasc Surg 1996;112:1193-1200.[Abstract/Free Full Text]
  9. Corno AF, Bethencourt DM, Laks H, et al. Myocardial protection in the neonatal heart. A comparison of topical hypothermia and crystalloid and blood cardioplegic solutions. J Thorac Cardiovasc Surg 1987;93:163-172.[Abstract]
  10. Gombovosa I, Boknik P, Kirchhefer U, et al. Postnatal changes in contractile time parameters and calcium regulatory proteins and phosphatases Am J Physiol Heart Circ Physiol 1998;274:H2123-H2132.[Abstract/Free Full Text]
  11. Pavlovic M, Schaller A, Pfammatter JP, Carrel T, Berdat P, Gallati S. Age-dependent suppression of SERCA2a mRNA in pediatric atrial myocardium Biochem Biophys Res Commun 2005;326:344-348.[Medline]
  12. Harrell MD, Harbi S, Hoffman JF, Zavadil J, Coetzee WA. Large-scale analysis of ion channel gene expression in the mouse heart during perinatal development Physiol Genomics 2007;28:273-283.[Abstract/Free Full Text]
  13. Aoki M, Nomura F, Kawata H, Mayer Jr JE. Effect of calcium and preischemic hypothermia on recovery of myocardial function after cardioplegic ischemia in neonatal lambs J Thorac Cardiovasc Surg 1993;105:207-212.[Abstract]
  14. del Nido PJ. Myocardial protection and cardiopulmonary bypass in neonates and infants Ann Thorac Surg 1997;64:878-879.[Free Full Text]
  15. Allen BS. Pediatric myocardial protection: a cardioplegic strategy is the "solution." Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2004;7:141-154.[Medline]
  16. Amark K, Berggren H, Björk K, et al. Blood cardioplegia provides superior protection in infant cardiac surgery Ann Thorac Surg 2005;80:989-994.[Abstract/Free Full Text]
  17. Caputo M, Modi P, Imura H, et al. Cold blood versus cold crystalloid cardioplegia for repair of ventricular septal defects in pediatric heart surgery: a randomized controlled trial Ann Thorac Surg 2002;74:530-534.[Abstract/Free Full Text]
  18. Kohman LJ, Veit LJ. Single-dose versus multidose cardioplegia in neonatal hearts J Thorac Cardiovasc Surg 1994;107:1512-1518.[Abstract/Free Full Text]
  19. Magovern JA, Pae Jr WE, Miller CA, Waldhausen JA. The immature and the mature myocardium. Responses to multidose crystalloid cardioplegia. J Thorac Cardiovasc Surg 1988;95:618-624.[Abstract]
  20. Modi P, Suleiman MS, Reeves B, et al. Myocardial metabolic changes during pediatric cardiac surgery: a randomized study of 3 cardioplegic techniques J Thorac Cardiovasc Surg 2004;128:67-75.[Abstract/Free Full Text]
  21. Takeuchi K, Maida K, Tanaka S, Yoshida S, McGowan Jr X, del Nido PJ. Superior myocardial protection with a new histidine-buffered crystalloid cardioplegic solution in clinical trial Thorac Cardiovasc Surg 1999;47:148-152.[Medline]
  22. O'Brien JD, Ferguson JH, Howlett SE. Effects of ischemia and reperfusion on isolated ventricular myocytes from young adult and aged Fischer 344 rat hearts Am J Physiol Heart Circ Physiol 2008;294:H2174-H2183.[Abstract/Free Full Text]
  23. Wernovsky G, Wypij D, Jonas RA, et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardioplumonary bypass and circulatory arrest. Circulation 1992;92:2226-2235.
  24. Hondeghem LM, Katzung BG. Time- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels Biochim Biophys Acta 1977;472:373-398.[Medline]
  25. Hall SK, Fry CH. Magnesium affects excitation, conduction, and contraction of isolated mammalian cardiac muscle Am J Physiol Heart Circ Physiol 1992;263:H622-H633.[Abstract/Free Full Text]
  26. Piper HM, Abdallah Y, Schäfer C. The first minutes of reperfusion: a window of opportunity for cardioprotection Cardiovasc Res 2004;61:365-371.[Abstract/Free Full Text]
  27. Van Emous JG, Nederhoff MG, Ruigrok TJ, van Echteld CJ. The role of the Na+ channel in the accumulation of intracellular Na+ during myocardial ischemia: consequences for post-ischemic recovery J Mol Cell Cardiol 1997;29:85-96.[Medline]
  28. Ten Hove MT, Jansen MA, Nederhoff MG, Van Echteld CJ. Combined blockade of the Na+ channel and the Na+/H+ exchanger virtually prevents ischemic Na+ overload in rat hearts Mol Cell Biochem 2007;297:101-110.[Medline]
  29. Lee JA, Allen DG. Mechanisms of acute ischemic contractile failure of the heart. Role of intracellular calcium. J Clin Invest 1991;88:361-367.[Medline]
  30. Dobson GP, Jones MW. Adenosine and lidocaine: a new concept in nondepolarizing surgical myocardial arrest, protection, and preservation J Thorac Cardiovasc Surg 2004;127:794-805.[Abstract/Free Full Text]
  31. Chambers DJ. Polarization and myocardial protection Curr Opin Cardiol 1999;14:495-500.[Medline]
  32. Mildh LH, Pettilä V, Sairanen HI, Rautiainen PH. Cardiac troponin T levels for risk stratification in pediatric open heart surgery Ann Thorac Surg 2006;82:1643-1648.[Abstract/Free Full Text]
  33. Murashita T, Avkiran M, Hearse DJ. Detrimental effects of multidose hypothermic cardioplegia in the neonatal heart: the role of frequency of cardioplegia infusions Eur J Cardiothorac Surg 1991;5:183-190.[Abstract/Free Full Text]
  34. Kohman LJ, Veit LJ. Single-dose versus multidose cardioplegia in neonatal hearts J Thorac Cardiovasc Surg 1994;107:1512-1518.[Abstract/Free Full Text]
  35. DeLeon SY, Idriss FS, Ilbawi MN, Duffy CE, Benson Jr DW, Backer CL. Comparison of single versus multidose blood cardioplegia in arterial switch procedures Ann Thorac Surg 1988;45:548-553.[Abstract/Free Full Text]

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