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Right arrow Myocardial protection

Ann Thorac Surg 2002;74:530-535
© 2002 The Society of Thoracic Surgeons

Original article: cardiovascular

Cold blood versus cold crystalloid cardioplegia for repair of ventricular septal defects in pediatric heart surgery: a randomized controlled trial

Massimo Caputo, MDa, Paul Modi, FRCSa, Hajime Imura, MDa, Ashwinikumar Pawade, FRCSa, Andrew J. Parry, FRCSa, M-Saadeh Suleiman, PhDa, Gianni D. Angelini, FRCS*a

a Bristol Heart Institute, University of Bristol, Bristol, United Kingdom

* Address reprint requests to Dr Angelini, Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom
e-mail: g.d.angelini{at}bristol.ac.uk

Presented at the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2002.


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 Discussion
 References
 
Background. There is little evidence in the literature on the benefits of cold blood cardioplegia in pediatric cardiac surgery. This study investigates the effects of cold crystalloid versus cold blood cardioplegia on myocardial metabolism, reperfusion injury, and clinical outcomes in patients undergoing ventricular septal defect (VSD) repair.

Methods. Patients were randomly assigned to receive antegrade cold (4 to 6°C) St Thomas’s I crystalloid (CCC) or blood (CBC) cardioplegia. Changes in myocardial adenine nucleotides and purine levels were monitored in right ventricular biopsies and postoperative serum troponin I (TnI) and lactate release were measured.

Results. Forty patients were randomly assigned to CCC (n = 21; age 21.1 ± 40.8 months) or to CBC (n = 19; age 27.4 ± 39.3 months). Patient characteristics were similar in the two groups and there was no mortality. After the ischemic period there was a significant drop in adenosine triphosphate levels compared with control values in the CCC (40.4 ± 9.9 versus 27.5 ± 12.5 nmol/mg protein, p = 0.01) but not in the CBC group (40.3 ± 23.2 versus 37.3 ± 18.9 nmol/mg protein). The fall was more marked in infants compared with children (40% versus 10%, respectively, p = 0.01). Mean total TnI release was 42% lower in the CBC than the CBC group (95% confidence interval 10% to 62%, p = 0.015). Total TnI release was significantly associated with age (p < 0.001) but as levels in infants in the CBC group were the same as for children, the reduction with age was seen almost entirely in the CCC group. There were no differences in the duration of inotropic support, ventilation time, intensive care unit, or hospital stay in the two groups.

Conclusions. The use of CBC is associated with less metabolic myocardial ischemic stress and reperfusion injury when compared with CCC in pediatric patients undergoing VSD repair.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 Discussion
 References
 
Current methods of myocardial protection during adult open heart surgery include a variety of cardioplegic techniques that have been shown to be effective in preserving myocardial function and metabolism during ischemia [1, 2]. In contrast myocardial protection during pediatric open heart surgery remains poor and is associated with relatively greater morbidity and mortality [3, 4]. This is because myocardial protection techniques used in adult hearts are often uncritically extended to pediatric hearts. Although many pediatric heart surgeons prefer crystalloid cardioplegia with its ease of use and less interference with visibility, the use of blood cardioplegia is gradually expanding [3, 5, 6]. This is because of its theoretical advantages over crystalloid cardioplegia, namely oxygen-carrying and buffering capacity and favorable oncotic properties [1, 2]. We have recently demonstrated [7] that cold crystalloid cardioplegia in pediatric cardiac surgery is associated with significant ischemic stress and myocardial injury and that the extent of myocardial protection is dependent on age and degree of cyanosis.

The aim of this study was to compare the effects of cold crystalloid and cold blood cardioplegia on myocardial metabolism, reperfusion injury and a variety of measures of clinical outcome in pediatric patients undergoing repairs of a ventricular septal defect (VSD).


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 Discussion
 References
 
Forty patients undergoing elective VSD repair between April 2000 and August 2001 at the Bristol Royal Hospital for Sick Children were randomly assigned to receive intermittent antegrade cold (4 to 6°C) crystalloid (CCC) or blood (CBC) cardioplegia for myocardial protection. All patients were noncyanotic (arterial blood oxygen saturation >90%) and in a stable condition without preoperative respiratory or inotropic support. Ethical approval from the local authority and informed consent for all patients were obtained. Random treatment allocations were generated in advance of starting the study and were concealed in sequentially number, sealed, opaque envelopes. After consent was obtained a patient was randomly assigned by opening the next numbered envelope.

Anesthetic and surgical technique
Anesthetic and surgical techniques were standardized for all patients. A slow induction with sevoflurane and 50% air-O2 followed by fentanyl (25 to 50 mg/kg-1) was used. Morphine (0.5 mg/kg) was infused during cardiopulmonary bypass (CPB) and neuromuscular blockade was achieved with pancuronium bromide (0.1 to 0.15 mg/kg). Alpha stat acid-base management was adopted. Heparin (3 mg/kg) was administered and supplemented as required to maintain an active clotting time of 480 sec or above.

CPB was established between ascending aortic and bicaval cannulation. Systemic hypothermic perfusion to 28°C was achieved in all patients. After the aorta was cross clamped, cold (4 to 6°C) St Thomas’ I crystalloid cardioplegia (16 mmol/L MgCl2, 2 mmol/L CaCl2, 20 mmol/L KCl, 147 mmol/L NaCl, 1.0 mmol/L procaine HCl; Martindale Pharmaceuticals, Romford, UK) or cold blood cardioplegia (4:1 dilution blood/St Thomas’ I crystalloid cardioplegia, KCl adjusted to 15 mmol/L) were administered in the CCC or CBC groups, respectively. Cardioplegic administration was as follows: a 25 mL/kg dose of cardioplegic solution was initially administered antegradely for 4 minutes, followed by a 2-minute repeated dose (15 mL/kg) at 20- to 30-minute intervals. Aortic root pressure was measured in every patient during cardioplegic delivery and was kept between 40 and 50 mm Hg. Topical cooling with cold saline solution was used in all patients. All VSDs (either perimembranous or muscular defects) were closed with a Dacron patch (C. R. Bard, Haverhill, PA) through the tricuspid valve.

Postoperative management and assessment of clinical outcome
All patients were admitted to the pediatric intensive care unit (ICU) after surgery and were managed by intensivists and pediatric cardiologists. Decisions regarding inotropic support and ventilation were based on unit protocols, hemodynamic status (eg, low mixed venous saturation, high lactic acidosis) and clinical judgment.

Intraoperative and postoperative clinical variables were measured to assess early clinical outcome. The former included the durations of CPB, aortic cross-clamp, and intraoperative use of inotropic agents to wean patients from CPB. Postoperative measurements included the level and duration of dopamine support, ventilation time, ICU and hospital stay. Dopamine (5 µg kg-1·min-1) was routinely infused to discontinue CPB and this dose was then titrated to the hemodynamic and clinical state of the patient according to unit protocol. Postoperative inotropic support was considered to be either minimal (dopamine <5 kg-1·min-1) or significant (dopamine >5 µg and <10 kg-1·min-1 with or without other inotropic agents such as adrenaline, noradrenaline, or milrinone).

Collection of ventricular biopsies
Myocardial biopsy specimens (5.3 ± 0.7 mg) were collected from the right ventricle using a true-cut needle immediately before cross-clamping the aorta (control biopsy), and just before releasing the cross-clamp (ischemic biopsy). Each specimen was immediately frozen in liquid nitrogen until processing for analysis of cellular metabolites. Adenine nucleotides and purine were measured in all biopsies collected, as previously reported [7].

Measurement of cardiac troponin I and serum lactate
Serum concentrations of troponin I (TnI) were determined before surgery and at 4, 12, 24, and 48 hours postoperatively, using the ACCESS Immunoassay System (Beckman Instruments, MN). Samples were stored at -80°C until the completion of the study when assays were performed by a laboratory technicain blinded to the clinical status of the patient or their inclusion in the study. The total TnI release in the first 48 hours postoperatively was calculated using the Trapezium rule (area under the curve).

Arterial oxygen saturation and blood lactate level measurements were recorded with a pediatric blood gas analyzer (Radiometer ABL 725; Radiometer A/S, Copenhagen, Denmark) before surgery, at the end of the ischemic time, at the end of surgery, and then 1 and 2 hours postoperatively. Total lactate up to 2 hours after the operation was calculated as for TnI.

Statistical analysis
The {chi}2 and Mann-Whitney rank sum tests were used to compare base line characteristics and clinical outcomes between groups. Changes in intracellular metabolites during ischemia were analyzed by repeated measures analysis of variance (ANOVA). The distributions of total TnI release and lactate levels were positively skewed and data were transformed into natural logarithms before carrying out regression analyses to investigate the effects of cardioplegia and age. All analyses were carried out using STATA software (v. 7.0, Stata Corp, College Station, TX).


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 Discussion
 References
 
Clinical outcome
A total of 40 patients were recruited to the study, of whom 21 were in the CCC group and 19 in the CBC group. The preoperative characteristics of the two groups are summarized in Table 1. No differences were found between CCC and CBC with regard to CPB and aortic cross clamping time (Table 1). There were no hospital deaths. Significant postoperative inotropic support was required more frequently in the CCC than in the CBC group (57% versus 36% respectively) and the overall postoperative inotropic duration was longer in the CCC (38 hours) than in the CBC group (29 hours, p = 0.5), without reaching statistical significance (Table 2). Three patients in the CCC group had supraventricular tachycardia, which included atrial fibrillation (1 patient) and junctional ectopic tachycardia (2 patients). No differences in ventilation time, ICU stay, and hospital stay were found between the two groups (Table 2).


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  		Table 1. Patient Characteristics

 

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  		Table 2. Clinical Outcomes

 
Changes in cellular metabolites during ischemia
Table 3 shows concentrations of intracellular myocardial metabolites before and after ischemia in the two groups. During ischemia a significant fall in ATP concentration was seen in the CCC but not in the CBC group (p = 0.01). Furthermore, the percentage drop in ATP levels during ischemia were significantly greater in infants using CCC compared with children (from 42.8 ± 10.3 to 25.0 ± 11.5 nmol/mg protein and from 36.8 ± 4.8 to 34.5 ± 13.6 nmol/mg protein, 40% versus 10%, respectively, p = 0.01), despite similar cross clamp time (38.5 ± 17.6 versus 41.8 ± 20.1 minutes, infants versus children, p = 0.7). Inosine and hypoxanthine levels increased significantly in both groups whereas adenosine levels increased only in the CCC group.


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  		Table 3. Myocardial Concentrations (nmol/mg Protein) of Metabolites Before and After Ischemia

 
Troponin I and lactate release
Figure 1 shows the time-related changes in TnI serum concentrations in both groups. There was a significant TnI increased to a peak at 4 hours postoperatively in both groups and the levels remained higher up to 48 hours postoperatively. Mean total TnI release up to 48 hours postoperatively was 42% lower in the CBC than the CBC group (95% confidence interval [CI] 10% to 62%, p = 0.015). Further analysis of total troponin I release showed that it was also significantly associated with age, and that the reduction with age occurred almost entirely in the CCC group (1.3% reduction [95% CI 0.1% to 1.9%] with each additional month of age) and hardly at all in the CBC group (0.2% reduction [95% CI 0.7% increase to 1.1% reduction] with each additional month of age, p for interaction = 0.01). This interaction is shown in Figure 2, classifying patients as infants (1 to 12 months) or children (>12 months).



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  		Fig 1. Time-related changes in mean troponin I serum concentrations in the cold blood cardioplegia (CBC) group (dotted bars) and cold crystalloid cardioplegia group (lined bars). Error bars represent 95% confidence intervals. p < 0.0001 versus control for all postoperative levels; *p = 0.01 versus CBC group.

 


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  		Fig 2. Total troponin I release in cold blood cardioplegia (CBC) group and cold crystalloid cardioplegia (CCC) group by age: infants (lined bars) and children (dotted bars). Error bars represent 95% confidence intervals. *p = 0.01 versus CBC and children in CCC group.

 
Figure 3 shows the time-related changes in serum lactate levels in both groups. Mean total lactate level up to 2 hours postoperatively was 29% lower in the CBC than the CCC group. There was no evidence that mean total lactate level was associated with age (p = 0.97).



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  		Fig 3. Time-related changes in mean lactate concentration in the cold blood cardioplegia (CBC) group (dotted bars) and cold crystalloid cardioplegia group (lined bars). Error bars represent 95% confidence intervals. *p = 0.05 versus control and CBC group.

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 Discussion
 References
 
We have recently shown that the use of CCC in pediatric open heart surgery is associated with significant ischemic stress and myocardial injury and that these effects are worse in infants than children [7]. The inadequacy of CCC in preserving postischemic adenosine triphosphate (ATP) levels and cardiac output has been associated with up to 50% of hospital deaths during pediatric open heart surgery [3, 8]. In recent years many surgeons, particularly in North America, have begun to use CBC for myocardial protection in pediatric heart surgery despite little clinical evidence suggesting its superiority compared with CCC [6, 9]. Laboratory data have given conflicting results possibly due to species differences and differing end points [10, 11]. In the normal neonatal lamb heart no beneficial effect of CBC compared with CCC was found [12] although Corno and colleagues demonstrated improved recovery in the neonatal piglet heart [13]. Others have demonstrated an advantage of CBC assessed by pressure-volume loops and myocardial edema in low risk noncyanotic patients [4]. Young and associates [9] found no clinical differences between CCP and CBC in a prospective randomized trial. Nevertheless the differences in age and cyanosis, and the varied pathologic entities involved in the study were important limitations and might have masked the effects of cardioplegia.

The present work shows that myocardial protection with CBC is associated with less myocardial ischemic stress and reperfusion injury compared with CCC in patients undergoing VSDs repair. However, when injury was assessed by total troponin I release the protection afforded by CBC seemed to be confined to infants. These results were obtained in an homogenous population with no differences in the distributions of age or preoperative saturation, CPB or cross clamp time between CCC and CBC groups. Blood cardioplegia was associated with better preservation of adenine nucleotides and decreased level of myocardial cell injury as shown by lower TnI release compared with CCC. Adenine nucleotides can be restored either by relatively slow de novo synthesis or by faster nucleotide salvage, which is possible only if adenosine is available as a precursor. In the CCC group there was a significant increase of adenosine during ischemia and a drop in ATP and ATP/adenosine diphosphate (ADP) ratio levels, which might indicate an inability of the mitochondria to phosphorylate precursors of ATP. The use of CBC could prevent the ATP and ATP/ADP ratio drop, probably by utilizing adenosine to replace the high energy phosphate stores. A reduction in the size of the adenine nucleotide pool (ATP+ADP+AMP) after ischemia was also seen in the CCC but not in the CBC group, further supporting the concept that nucleotide pool degradation is associated with reversible ischemic injury to the myocardium [14].

An interesting and novel finding of this study is the observation that in the CCC group infants had a significantly higher drop in intracellular ATP and greater postoperative TnI release compared with children. These differences were not observed in the CBC group. Available laboratory data have been inconclusive to explain vulnerability of immature myocardium to cardiac surgery. Most reports suggest that developing mammalian hearts are more resistant to damaging effects of cardiac insults than adult hearts [6, 15–17]. However, others [18, 19] have reported that immature myocardium is more vulnerable to injury than adult heart. This study seems to confirm our previous findings that infants undergoing cardiac surgery using CCC for myocardial preservation are less resistant to ischemia/reperfusion injury than children. The use of CBC seems to prevent these changes, indicating a protective effect of blood likely to be due to its buffering capacity, favorable oncotic properties, and free radical scavenging abilities [1, 2].

Despite these favorable effects of CBC on myocardial preservation there were no significant differences in clinical outcomes in the two groups, indicating that the metabolic derangement observed during ischemia/reperfusion were completely reversible.

Limitations of the study
The randomization was not stratified for age differences and the findings regarding the interaction of age and type of cardioplegia were found during posthoc analyses carried out on the basis of our continuing experience and literature reading.

It was not surprising that there were no major differences in clinical outcome between the two groups, as the study population included patients with VSD only and relatively short cross-clamp time. Nevertheless because only CCC was used before this trial we wanted to introduce CBC use only on low-risk patients to begin with. One might expect the benefits of CBC on clinical outcomes to be more evident on patients undergoing more complex procedures with longer cross-clamp times and preoperative cyanosis.

Conclusions
Our data have shown that CBC provides superior myocardial protection compared with CCC in acyanotic pediatric patients undergoing VSD repair. The use of CBC was associated with less metabolic derangement and myocardial cell damage compared with CCC. Infants seems more likely to gain the most benefits from the advantages of CBC compared with children.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
Discussion
 References
 
This work was supported by the Garfield Weston Trust, the National Heart Research Fund, and the British Heart Foundation. We would like to thank Dr Barnaby Reeves for the statistical analysis and for his help during the preparation of this manuscript, Mark Ginty and Svitlana Korolchuk for performing the biochemical analysis, and the ITU nursing staff for blood collection support.


   Discussion
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 Discussion
References
 
DR John E. MAYER (Boston, MA): First of all, how often is it that you’re repeating the cardioplegia?

DR CAPUTO: We repeat every 20 to 30 minutes in both groups, exactly the same protocol.

DR MAYER: So that with a mean cross-clamp time of about 38 or 39 minutes they were getting two doses?

DR CAPUTO: Yes.

DR MAYER: The second question is, do you make in your institution any interventions during reperfusion, whether that is vasodilator therapy or altering the oxygen being provided to the oxygenator? Are there any interventions during reperfusion that are directed at enhancing whatever it is that you did during the period of ischemia?

DR CAPUTO: No. In this trial, no specific measurements during perfusion time were adopted. There is an ongoing trial in which we are now testing the use of hot shot at the end of the cross-clamp time but no specific measurements were used in this series of patients.

DR Marshall L. JACOBS (Philadelphia, PA): Although I have been satisfied for many years with crystalloid cardioplegia in infants and children, I think your data are compelling and very nicely presented. I have a question really about the organization of the study and not the data. In your opening remarks you made reference to previous findings of disadvantages of crystalloid cardioplegia from your laboratory and your center. I am curious, with the preliminary data to which you made reference, does a clinical study such as this in the UK require an institutional review board approval before you undertake it and does it as well require parental consent for the biopsies and the randomization as it would in our practice?

DR CAPUTO: We have a large experience with biopsies in children and adults and we have never experienced any problems in biopsying these hearts. We use a Tru-Cut needle for the biopsy and, really, at the end of the procedure, we did not have any problems.

DR CONSTANTINE MAVROUDIS (Chicago, IL): Did you have IRB, an institutional review board, approval for this study? Or in other terms, did you have parental consent to do this study?

DR CAPUTO: Yes, there is an informed consent.

DR MAVROUDIS: You have informed consent for each?

DR CAPUTO: Yes, informed consent for each patient.

DR MAVROUDIS: And you also have an institutional review board that reviewed this study before you did it?

DR CAPUTO: Yes. We have to get approval from the hospital committee.

DR MAVROUDIS: Thank you for clarifying this important issue.

DR Jeffrey M. PEARL (Cincinnati, OH): I am obviously a big fan of blood cardioplegia having grown up in the UCLA system. My question is, do you know what the calcium concentration that you delivered to the heart was between the two solutions? The major finding that you presented was troponin-I degradation and that is clearly related, we think, to calcium levels within the myocardium with immature hearts being more susceptible to calcium concentrations. I was wondering if you had any information that might explain some of the difference between the crystalloid hearts and the blood cardioplegia hearts.

DR CAPUTO: The cardioplegia we use is the St. Thomas I for both techniques. I do not know if the concentrations were similar in both cardioplegia techniques. I will have to look into that. But I am aware that some investigators are saying that hypocalcemic solution might be beneficial. Some others are saying that normocalcemic solution might be beneficial.

DR MAVROUDIS: If I may interrupt with another question, I did not hear and maybe I missed it, that you controlled the administration of cardioplegia by a pressure. Did you have a pressure measurement?

DR CAPUTO: Yes, the pressure is constantly monitored on the aortic root.

DR MAVROUDIS: And so how did you measure it, in the aortic root or in the cardioplegia delivery system?

DR CAPUTO: In the cardioplegia delivery system

DR MAVROUDIS: And what were your limits on that?

DR CAPUTO: It is kept between the mean systolic and diastolic pressure.

DR MAVROUDIS: What was the number?

DR CAPUTO: It is around 40 to 50 mm Hg.

DR PEARL: If my memory serves me correctly, the St. Thomas solution has a fairly high calcium concentration. But when you mix it with blood at 4 to 1, you are going to have a vast difference in your electrolyte composition than just with the straight crystalloid, as well as your flow rates even at the same pressure may be different. So you may end up giving more cardioplegia in one heart than the other. So it is something that in future studies would be worth looking into.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 Discussion
 References
 

  1. Buckberg G.D. Update on current techniques of myocardial protection. Ann Thorac Surg 1995;60:805-814.[Abstract/Free Full Text]
  2. Caputo M., Ascione R., Angelini G.D., Suleiman M.S., Bryan A.J. The end of the cold era: from intermittent cold to intermittent warm blood cardioplegia. Eur J Cardiothorac Surg 1998;14:467-475.[Abstract/Free Full Text]
  3. Bull C., Cooper J., Stark J. Cardioplegic protection of the childs heart. J Thorac Cardiovasc Surg 1984;88:287-293.[Abstract]
  4. Chaturvedi R.R., Lincoln C., Gothard J.W., et al. Left ventricular dysfunction after repair of simple congenital heart defects in infants and children: quantitation with the use of conductance catheter immediately after bypass. J Thorac Cardiovasc Surg 1998;115:77-83.[Abstract/Free Full Text]
  5. Billingsley A., Laks H., Haas G. Myocardial protection in children. In: Baue A., Geha A., Hammond G., et al. , eds. Glenn’s thoracic and cardiovascular surgery. East Norwalk, CT: Appleton and Lange, 1991:915-924.
  6. Hammon J.W. Myocardial protection in the immature heart. Ann Thorac Surg 1995;60:839-842.[Abstract/Free Full Text]
  7. Imura H., Caputo M., Parry A., Pawade A., Angelini G.D., Suleiman M.-S. Age-dependent and hypoxia-related differences in myocardial protection during pediatric open heart surgery. Circulation 2001;103:1551-1556.[Abstract/Free Full Text]
  8. Hammon J.W., Graham T.P., Boucek R.J., Parrish M.D., Merrill W.H., Bender H.W. Myocardial adenosine-triphosphate content as a measure of metabolic and functional myocardial protection in children undergoing cardiac operation. Ann Thorac Surg 1987;44:467-470.[Abstract]
  9. Young J.N., Choy I.O., Silva N.K., Obayashi D.Y., Barkan H.E. Antegrade cold blood cardioplegia is not demonstrably advantageous over cold crystalloid cardioplegia in surgery for congenital heart disease. J Thorac Cardivasc Surg 1997;114:1002-1009.[Abstract/Free Full Text]
  10. Baker J.E., Boerboom L.E., Olinger G.N. Is protection of ischemic neonatal myocardium by cardioplegia species dependent?. J Thorac Cardiovasc Surg 1990;99:280-287.[Abstract]
  11. Bolling K., Kronon M., Allen B.S., Wang T., Ramon S., Feinberg H. Myocardial protection in normal and hypoxically stressed neonatal hearts: the superiority of blood versus crystalloid cardioplegia. J Thorac Cardiovasc Surg 1997;113:994-1003.[Abstract/Free Full Text]
  12. Fujiwara T., Heinle J., Britton L., Mayer J.E., Jr Myocardial preservation in neonatal lambs: comparison of hypothermia with crystalloid and blood cardioplegia. J Thorac Cardiovasc Surg 1991;80:703-712.
  13. Corno A.F., Bethencourt D.M., 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]
  14. Booker P.D. Myocardial stunning in the neonate. Br J Anaesth 1998;80:371-383.[Free Full Text]
  15. Riva E., Hearse D.J. The developing myocardium. New York: Futura, 1991.
  16. Starnes J.W., Bowles D.K., Seiler K.S. Myocardial injury and hypoxia in immature adult and aged rats. Aging Clin Exp Res 1997;9:268-276.
  17. Murashita T., Borgers M., Hearse D.J. Developmental changes in tolerance to ischaemia in the rabbit heart: disparity between interpratations of structural, enzymatic and functional indices of injury. J Mol Cell Cardiol 1992;24:1143-1154.[Medline]
  18. Pearl J.M., Laks H., Drinkwater D.C., et al. Normocalcemic blood or crystalloid cardioplegia provides better neonatal myocardial protection than does low-calcium cardioplegia. J Thorac Cardiovasc Surg 1993;105:201-206.[Abstract]
  19. Carr L.J., Vanderwerf Q.M., Anderson S.E., et al. Age-related response of rabbit heart to normothermic ischaemia: a 31P-MRS study. Am J Physiol 1992;262:H391-H398.[Abstract/Free Full Text]



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Massimo Caputo
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