Dear Editor

Simon J. Clark is asking some interesting questions from the paper “Resuscitation with 100% O2 does not protect the myocardium in hypoxic newborn piglets”,[1] whether cardiac troponin T (cTnT) is preferable to cardiac troponin I (cTnI) in neonates. He is referring to Trevisanuto et al.[2] that found cTnI undetectable in neonates.

Other investigators have proven cTnI to be a reliable marker of myocardial injury in neonatal population,[3,5] and have risen the question whether cTnI is a new “gold standard” of cardiac injury in children (6). Others have compared cTnI and cTnT,[5,7] and found both cTnI and cTnT to be sensitive and specific markers of myocardial injury.

Comparing measured cTnI values between different studies are difficult because of variations in sensitivity and specificity of various commercially available cTnI diagnostic immunoassay kits (8;9). These differences are due to: i) lack of mass standardisation (10;11),
ii) the presence of post- translationally modified cTnI in serum, and
iii) variations in antibody reactivities to different detectable forms of cTnI.(11,12)

Regarding cTnT it does not yet have these problems, since only one manufacturer has patented and marketed a diagnostic cTnT assay.

The Beckman Coulter Access cTnI method has shown to identify adult cardiac patients with poor prognosis not detectable by the cTnT method.[13] In human neonates, we believe it is proven that both cTnI and cTnT are reliable markers of myocardial injury.[3,6] However, regarding assessment of cTnI, one has to choose among the most sensitive and specific assays.[8]

In our study [1] care was taken to include only healthy piglets. We excluded seventeen piglets mainly due to common ailments such as diarrhoea. CTnI was measured by a human kit. No commercial porcine cardiac troponin kit was available, and we do not know if there are any crossreactions with other porcine cTnI isoforms.

References

(1) Borke WB, Munkeby BH, Morkrid L, Thaulow E, Saugstad OD. Resuscitation with 100% O2 does not protect the myocardium in hypoxic newborn piglets. Arch Dis Child Fetal Neonatal Ed 2004; 89(2):F156-F160.

(2) Trevisanuto D, Pitton M, Altinier S, Zaninotto M, Plebani M, Zanardo V. Cardiac troponin I, cardiac troponin T and creatinin kinase MB concentrations in umbilical cord blood of healthy term neonates. Acta Paediatr 2003; 92:1463-1467.

(3) Hirsch R, Landt Y, Porter S, Canter CE, Jaffe AS, Ladenson JH et al. Cardiac troponin I in pediatrics: normal values and potential use in the assessment of cardiac injury. [see comments.]. J Pediatr 1997; 130(6):872-877.

(4) Soldin SJ, Murthy JN, Agarwalla PK, Ojeifo O, Chea J. Pediatric reference ranges for creatine kinase, CKMB, troponin I, iron, and cortisol 9. Clin Biochem 1999; 32(1):77-80.

(5) Taggart DP, Hadjinikolas L, Hooper J, Albert J, Kemp M, Hue D et al. Effects of age and ischemic times on biochemical evidence of myocardial injury after pediatric cardiac operations. Journal of Thoracic & Cardiovascular Surgery 1997; 113(4):728-735.

(6) Towbin JA, Gajarski RJ. Cardiac troponin I: a new diagnostic gold standard of cardiac injury in children? [letter; comment.]. J Pediatr 1997; 130(6):853-855.

(7) Adamcova M. Troponines in children and neonates. Acta Paediatr 3 A.D.; 92:1373-1375.

(8) Christenson RH, Duh SH, Apple FS, Bodor GS, Bunk DM, Dalluge J et al. Standardization of Cardiac Troponin I Assays: Round Robin of Ten Candidate Reference Materials. Clin Chem 2001; 47(3):431-437.

(9) Labugger R, Organ L, Collier C, Atar D, Van Eyk JE. Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction. [see comments.]. Circulation 2000; 102(11):1221- 1226.

(10) Newman DJ, Olabiran Y, Bedzyk WD, Chance S, Gorman EG, Price CP. Impact of antibody specificity and calibration material on the measure of agreement between methods for cardiac troponin I. Clinical Chemistry 1999; 45(6:Pt 1):t-8.

(11) Shi Q, Ling M, Zhang X, Zhang M, Kadijevic L, Liu S et al. Degradation of cardiac troponin I in serum complicates comparisons of cardiac troponin I assays. Clinical Chemistry 1999; 45(7):1018-1025.

(12) Wu AH, Feng YJ, Moore R, Apple FS, McPherson PH, Buechler KF et al. Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. American Association for Clinical Chemistry Subcommittee on cTnI Standardization. Clinical Chemistry 1998; 44(6:Pt 1):t-208.

(13) Venge P, Lagerqvist B, Diderholm E, Lindahl B, Wallentin L. Clinical performance of three cardiac troponin assays in patients with unstable coronary artery disease (a FRISC II substudy). Am J Cardiol 2002; 89(9):1035-1041.

Dear Editor

Børke et al.[1] in their paper "Resuscitation with 100% O₂ does not protect the myocardium in hypoxic newborn piglets" showed a significant rise in cardiac troponin I following an asphyxial event in newborn piglets with a pleasing suggestion that normocarbia may be better for the myocardium.

I note that the baseline levels of cardiac troponin I were also measurable. Trevisanuto et al. [2] found that in human neonates cardiac troponin I was undetecable. This is different from cardiac troponin T where studies [2-4] have found detectable levels in human neonates. Although, Trevisanuto et al acknowledged that the failure to detect cardiac troponin I could be due to the assay, which has a higher lower limit of detection than the assay for cardiac troponin T.

Sasse et al. [5] suggested another reason for cardiac troponin I to be undetectable in human neonates. They showed that up to 75% of the troponin I in the human myocardium may be skeletal slow twitch troponin I. This allows better myocardial performance in the acidotic conditions during the perinatal period. It can take up to 9 months following delivery for all of the troponin I in the myocardium to be converted to the cardiac isoform. I am not familiar with the ontogeny and expression of porcine cardiac troponins, but I wonder whether there is a similar under-expression of cardiac troponin I in the piglet myocardium. If there is then it is even more surprising that there were detectable levels of cardiac troponin I at baseline.

I note that 19 piglets were excluded from the study due to various perinatal features including a skull fracture. I wonder whether it is possible that the elevated cardiac troponin I seen by Børke et al is due to worse perinatal conditions in piglets than in humans.

Another possible explanation for the raised baseline cardiac troponin I could be cross reactivity with other contractile components. If the cardiac troponin I assay was a human specific assay, it is possible that there could be marked cross reactivity with porcine skeletal troponins or other porcine cardiac contractile proteins.

In human neonates, because of the under expression of cardiac troponin I and the lower limit of detection for the third generation human cardiac troponin T assays our research group has preferred measurement of cardiac troponin T to I. It may be that in newborn piglets cardiac troponin I is the troponin of choice. However, in human neonates it is not yet clear which is best.

References

1. W B Børke, B H Munkeby, L Mørkrid, E Thaulow, and O D Saugstad. Resuscitation with 100% O2 does not protect the myocardium in hypoxic newborn piglets. Arch Dis Child Fetal Neonatal Ed 2004;89:F156-F160

2. Trevisanuto D, Pitton M, Altinier S, Zaninotto M, Plebani M, Zanardo V. Cardiac troponin I, cardiac troponin T and creatine kinase MB concentrations in umbilical cord blood of healthy term neonates. Acta Paediatr 2003;92(12):1463-1467

3. Clark SJ, Newland P, Yoxall CW, Subhedar NV. Cardiac troponin T in cord blood. Arch Dis Child 2000;84:F34-F37

4. Clark SJ, Newland P, Yoxall CW, Subhedar NV. Neonatal levels of cardiac troponin T with and without respiratory distress Arch Dis Child In press

5. Sasse S, Brand NJ, Kyprianou P, Dhoot GK, Wade R, Arai M, Periasamy M, Yacoub MH, Barton PJR. Troponin I gene expression during human cardiac development and in end-stage heart failure. Circ Res 1993;72:932-938

Potential conflict of interest: All my troponin research has been conducted using cardiac troponin T.