Yonago Acta medica 1999;42:69–78

Serum Concentration of Myosin Light Chain I and Left Ventricular
Shortening Fraction in Neonates
Hiroshi Sawada, Ikuo Nagata and Kazuo Shiraki
Department of Pediatrics, Faculty of Medicine, Tottori University, Yonago 683-0826, Japan
We compared the serum concentrations of myosin light chain I (MLC-I) and left ventricular shortening fraction (LVSF) measured by echocardiography of 13 normal neonates with those of 38 neonates with fetal distress, neonatal asphyxia, or cardiovascular/
respiratory diseases not associated with structural abnormalities. The diseased group
included 9 neonates with elevated MLC-I concentrations and 18 with low LVSF. Elevated MLC-I concentrations were frequently noted in neonates with transient myocardialischemia and persistent pulmonary hypertension of the newborn, suggesting a highspecificity of MLC-I elevation in these diseases. Although echocardiographically determined LVSF identifies the affected sections of the myocardium, it did not allow ratingof the severity of the disorder. There was no correlation between MLC-I and LVSF
probably due to therapeutic interventions and pulmonary hypertension. Our results
suggest that MLC-I is a useful marker of neonatal myocardial diseases.
Key words: acute myocardial infarction; heart failure; persistent pulmonary hypertension of thenewborn; transient myocardial ischemia of the newborn infant

trations of MLC-I, as an index of myocardialischemia and myocyte necrosis, in neonateswith fetal distress, neonatal asphyxia, and thosewith circulatory/respiratory diseases not associated with cardiac structural abnormalities, andcompared these parameters with those of normal neonates.

Myocardial myosin light chain I (MLC-I), a
component of the myocardial structural protein,plays a key role in myocardial constriction as
well as echocardiographically left ventricular
shortening fraction (LVSF). Previous studies
showed increased blood levels of MLC-I in
myocyte disorders, and indicated that MLC-I isa good marker of myocardial necrosis and isuseful in the diagnosis and follow-up of myocardial infarction (Trahern et al., 1978; Yazaki
et al., 1980). In neonates, asphyxia and various
other pathologic conditions may cause heart
failure. In this regard, MLC-I may potentiallybe a useful marker for the assessment of theseverity of heart failure. To explore the usefulness of MLC-I for this purpose in the pediatricpopulation, we compared the LVSF, determined by echocardiography, with serum concen-

Subjects and Methods

Subjects
We studied 13 newborn children with no physical abnormalities weighing more than 2,500 g
who were delivered normally at full-term at our
hospital (normal neonates). The group consisted of 9 boys and 4 girls, with a mean gestational

Abbreviations: AMI, acute myocardial infarction; AST, aspartate aminotransferase; CK, creatine
phosphokinase; EFE, endocardial fibroelastosis; FD, fetal distress; MAS, meconium aspiration syndrome;
MLC-I, myosin light chain I; LVSF, left ventricular shortening fraction; NA, neonatal asphyxia; PPHN,
persistent pulmonary hypertension of the newborn; RDS, respiratory distress syndrome; TMI, transient
myocardial ischemia of the newborn infant; TTN, transient tachypnea of the newborn

69

H. Sawada et al.

period and mean birth weight of 38 weeks and 6
days (range: 37 weeks and 0 day–40 weeks and6 days) and 2,986 g (range: 2,500–3,392 g), respectively. We also examined 38 newborns at
our hospital or affiliated facilities, with a history of fetal distress (FD), neonatal asphyxia(NA), or circulatory/respiratory diseases not
associated with anatomical abnormalities. We
defined all cases using the biophysical profile
score (Manning et al., 1985) with less than 6
points as FD. The group consisted of 27 boys
and 11 girls, with a mean gestational period andmean birth weight of 34 weeks and 1 day (range:
27 weeks and 4 days–42 weeks and 2 days) and
2,107 g (range: 782–3,504 g), respectively. The
diseased group consisted of the following: i)
The FD group comprised 6 patients, including 5
with complications—2 with transient tachypneaof the newborn (TTN), 1 with meconium aspiration syndrome (MAS) and 2 with transient
myocardial ischemia of the newborn infant(TMI); ii) The FD + NA group consisted of 12
patients, including 7 with complications—2
with respiratory distress syndrome (RDS), 4
with TMI and 1 with MAS/persistent pulmonary hypertension of the newborn (PPHN); iii)
The NA group consisted of 9 patients, including
8 with complications—2 with TTN, 3 with RDS
and 3 with TMI; iv) The remaining newborns
had the following underlying diseases—TTN in
4 patients, PPHN with TTN in 1, RDS in 2, TMI
in 1, left ventricular dilation disease similar to
endocardial fibroelastosis (EFE-like disease) in
1, shock caused by anencephaly in 1, and latent
FD with reduced LVSF without heart failure in
1. Severe NA, defined by a 1-min Apgar scoreof 0 to 4 points, was noted in 13 patients. Of thecirculatory/respiratory diseases there was TTN
in 9 patients, RDS in 7, MAS in 2, PPHN in 2,
and TMI in 10. There were 3 infants in 2 pairs,
all with twin-to-twin transfusion syndrome(Table 1). Definite criteria are available for the
diagnosis of TMI and PPHN; these 2 are often
viewed together as one pathological condition(Riemenschneider et al., 1976; Levin et al.,1979). The diagnosis of PPHN was establishedin patients with marked pulmonary hypertension irrespective of the cause and the remaining

fetal circulation, and TMI in patients with heart
failure symptoms, and without underlying
respiratory diseases, congenital heart diseases
or metabolic diseases (Rowe, 1977; Daga et al.,1983).

Methods

Measurement of MLC-I
Serum concentrations of MLC-I were measured using the Yamaha EIA myosin L-1 kit(Yamasa Shoyu Co., Choshi, Japan). Briefly,
the inner walls of a tube were first coated withan anti-human ventricular myocardial MLC-I
mouse antibody (MLM-544; solid phase antibody, Yamasa Shoyu). To this tube, we added
200 µL of a peroxidase-labeled anti-humanventricular myocardial MLC-I mouse antibody(MLM-508; enzyme antibody, Yamasa Shoyu),
and a 50-µL sample (antigen), followed by incubation for 1 h. After triplicate washing with2,000 µL of 0.9% NaCl, we added 500 µL of acolor-developing substrate (liquid A: tetramethylbenzidine; liquid B: hydrogen peroxide),followed by incubation at 15 to 30˚C for 30
min. Finally, 1,000 µL of a reaction stopper (2N H2SO4) was added and mixed, followed bydetermination of absorbance at a 450 nm wavelength using a spectrophotometer. Serum concentrations of MLC-I were determined by aworking curve constructed using the kit component standard myosin solution.
Determination of LVSF
All ultrasonographic studies were performed by the same operator with an SSD-875(Aloka, Tokyo, Japan) with a 5.0 MHz transducer. Left ventricular internal dimensions at
end-diastole and -systole were measured by athoracic near-sternal procedure using the method of Sahn and coworkers (1978) , while thechild was in a supine position. Data from 3 runs
obtained on recording paper were averaged.
LVSF was then calculated using the following
equation:
LVSF = (LVIDd - LVIDs) / LVIDd

70

MLC-I and LVSF in neonates

where LVIDd = left ventricularinternal dimension at enddiastole, LVIDs = left ventricular internal dimension at endsystole.

NS
NS
NS

P < 0.05

MLC-I

Protocol(ng/mL)10

5
In the normal neonates, a 1-mL
blood sample was collected fromthe dorsal vein of the hand on
day 2 (3rd day of life) and used
for the determination of MLC-I.
In addition, we also determined
LVSF on day 0 (1st day of life).
Both procedures were repeated
NormalTMI* FD* NA* FD+NA*
on day 5. In the diseased group,
[13]
[10]
[18]
[21]
[12]
a 1-mL blood sample wasFig. 1. Comparison of MLC-I between normal and diseased
collected from the dorsal vein ofgroups. *Groups have duplicate cases. E, MLC-I < 1.0 ng/mL; J,
MLC-I ≥ 1.0 ng/mL. A significant difference is noted between thethe hand or radial artery andnormal and TMI groups. No significant difference in MLC-I is notassayed for MLC-I during
ed in the FD, NA and FD + NA groups compared with the normal
hospitalization (within 24 h after
group. [ ], patient number of the group. FD, fetal distress; MLC-I,
delivery). We also determined
myosin light chain I; NA, neonatal asphyxia; NS, not significant;
LVSF at the same time. In 25 of
TMI, transient myocardial ischemia of the newborn infant.
the 38 patients, MLC-I andLVSF were also determined ondays 2 through 10, more specifically in 6 pa- (< 1.0 ng/mL). However, in 1 neonate, a contients on days 0 and 2, in 3 on days 0 and 3, in 2 centration of 3.1 ng/mL was noted on day 2. Onon days 0 and 5, in 3 on days 0 and 6, in 7 on day 5, the concentrations were below thedays 0 and 10, in 2 on days 0, 2 and 6, and in 2 detection limit in all 13 neonates. There was no
on days 0, 5 and 8 (Table 1). In addition, pa- significant difference in MLC-I between days 2tients with reduced LVSF were also examined and 5.
over several days.

MLC-I in the diseased group
Statistical analysis

Of the 38 patients, nine had elevated MLC-I
concentrations, on day 0 in 8 and on day 2 in 1
(1.2–10 ng/mL). Of these, 8 had FD or NA,
including 7 with TMI and 1 with MAS and
PPHN. The remaining patient had shockcaused by anencephaly. Thus, MLC-I was notelevated in patients with FD or NA who did nothave associated TMI or PPHN. MLC-I was
also not elevated in patients with circulatory/
respiratory diseases not associated with FD or
NA. The mean concentration of MLC- I in the
TMI group was significantly higher than in thenormal group (P < 0.05). But the mean concentrations in FD, NA and FD + NA groups were

Data were expressed as the mean ± SD. Differences between groups were examined forstatistical significance by Mann-Whitney’s Utest. A P value of less than 0.05 denoted thepresence of a significant difference.

Results

MLC-I in normal neonates
In 12 of the 13 normal neonates, blood MLC-I
concentrations were below the detection limit
71

H. Sawada et al.

Table 1. Patient data
Pa- Sextient
number
1
2
3
4
5
6
7
8
9
10
11
12
13
14†
15
16
17
18

M
M
M
M
M
F
F
F
M
F
M
F
M
M
F
M
M
M

DiseaseFD
FD, TTN
FD, TTN
FD, MAS
FD, TMIFD, TMIFD, NA
FD, NA
FD, NA
FD, NA
FD, NA
FD, NA, RDS
FD, NA, RDS
FD, NA, TMI
FD, NA, TMI
FD, NA, TMI
FD, NA, TMI
FD, NA, MAS/
PPHN

Gestationalage(wk and d)

Body Apgar
weight score(g) (1/5 min)37 wk 6 d
35 wk 3 d
34 wk 0 d
40 wk 6 d
37 wk 0 d
32 wk 3 d
28 wk 3 d
40 wk 2 d
39 wk 1 d
38 wk 6 d
29 wk 3 d
31 wk 3 d
29 wk 4 d
40 wk 2 d
31 wk 4 d
39 wk 3 d
32 wk 0 d

2529
1241
1866
2308
2674
2144
995
3504
2928
2530
782
1942
1412
3176
1974
3330
1836

7/ 9
9/10
9/ 9
8/ 9
8/ 8
9/ 9
1/ 4
6/ 9
4/ 9
2/ 5
3/ 8
3/ 7
5/ 5
0/ 0
1/ 6
6/ 8
1/ 2

MLC-I
(ng/mL)[Age in d]

LVSF
(%)
[Age in d]<1 [0] → <1 [ 6]<1 [0]<1 [0]<1 [0]
5.0[0] → <1 [10]1.9[0] → <1 [10]<1 [0] → <1 [ 6]<1 [0] → <1 [ 3]<1 [0]<1 [0] → <1 [ 2]<1 [0]<1 [0] → <1 [ 5]
<1 [0] → <1 [ 2]
5.3[0]<1 [0] → <1 [10]3.1[0] → <1 [10]1.2[0] → <1 [10]38 [0] → 32 [6]38 [0]
30 [0]
33 [0]
15 [0] → 28 [10]11 [0] → 31 [10]30 [0] → 32 [ 6]33 [0] → 34 [ 3]
28 [0]
21 [0] → 38 [ 2]
27 [0]
24 [0] → 29 [ 5]
23 [0] → 30 [ 2]
20 [0]
6 [0] → 25 [10]20 [0] → 32 [10]24 [0] → 30 [10]<6.3[0] → 7.4[2]38 [0] → 32 [ 2]
→ 3.7[6]→ 34 [6]19FNA
39 wk 3 d2928
5/ 8
<1 [0]
30 [0]
20
M
NA, TTN
28 wk 0 d1144
6/ 8
<1 [0] → <1 [ 2]
25 [0] → 32 [ 2]21* M
NA, TTN
36 wk 6 d2194
6/ 9
<1 [0]
29 [0]
22
M
NA, RDS
30 wk 0 d1274
2/ 5
<1 [0]
29 [0]
23
F
NA, RDS
27 wk 4 d954
1/ 2
<1 [0] → <1 [ 5]30 [0] → 34 [ 5]
→ <1 [8]→ 35 [8]24* M
NA, RDS
36 wk 6 d2412
6/ 9
<1 [0]
36 [0]
25
M
NA, TMI
31 wk 6 d1840
2/ 4
<1 [0] → 1.2[2]24 [0] → 27 [ 2]
→ <1 [6]→ 31 [6]26M
NA, TMI
27 wk 4 d1042
3/ 6
3.0[0] → <1 [ 5]
20 [0] → 24 [ 5]
→ <1 [8]→ 29 [8]27F
NA, TMI
32 wk 5 d1654
3/ 7
<1 [0] → <1 [10]22 [0] → 29 [10]28MTTN
33 wk 5 d2299
9/ 9
<1 [0] → <1 [ 3]
29 [0] → 29 [ 3]
29* F
TTN
34 wk 2 d1742
9/10
<1 [0] → <1 [ 3]
22 [0] → 29 [ 3]30FTTN36 wk 3 d2494
8/ 9
<1 [0]
38 [0]
31
M
TTN
34 wk 4 d2374
9/ 9
<1 [0] → <1 [ 2]
33 [0] → 35 [ 2]32
M
TTN, PPHN
35 wk 5 d2300
9/ 9
<1 [0] → <1 [ 5]31 [0] → 31 [ 5]33MRDS34 wk 2 d2000
8/ 8
<1 [0] → <1 [ 2]
17 [0] → 27 [ 2]34MRDS
31 wk 6 d1599
9/10
<1 [0]
38 [0]
35
M
TMI
36 wk 1 d2862
8/ 9
<1 [0] → <1 [10]17 [0] → 27 [10]36MEFE-like
37 wk 3 d2402
8/10
<1 [0] → <1 [ 6]
16 [0] → 22 [ 6]37† M
Anencephaly
36 wk 0 d
3000
8/ 8
<1 [0]
25 [0]
38
M
Latent FD
31 wk 6 d1054
8/ 8
<1 [0] → <1 [ 2]
14 [0] → 35 [ 2]d, day(s); EFE, endocardial fibroelastosis; F, female; FD, fetal distress; M, male; MAS, meconium aspiration
syndrome; MLC-I, myosin light chain I; LVSF, left ventricular shortening fraction; NA, neonatal asphyxia;
PPHN, persistent pulmonary hypertension of the newborn; RDS, respiratory distress syndrome; TMI,transient myocardial ischemia of the newborn infant; TTN, transient tachypnea of the newborn; wk, week(s).
*TTTS, twin-to-twin transfusion syndrome: patient numbers 21, 24 and 29.
†dead.
42 wk 2 d

3312

5/ 3

72

MLC-I and LVSF in neonates

MLC-I(ng/mL)not significantly different
from the normal group (Fig.
10 (37)1). On days 2 through 10,
MLC-I was measured again in
25 patients. Regarding the8
population breakdown by(18)
disease, 12 patients had FD,
14 with NA, 9 with FD + NA,
6
5 with TTN, 4 with RDS, 1(14)(5)
with MAS, 2 with PPHN, 94
with TMI, 1 with EFE-like(26)
disease, and 1 with latent FD(16)with decreased LVSF without(6)
2
heart failure symptoms (over(17)lap cases included). One pa(25)tient with TMI and another0with shock caused by anen0246810 (day)
cephaly died on day 0. Of theAge
25 patients in whom MLC- I
Fig. 2. Nine cases with elevated MLC-I concentrations. Numbers in
re-measurements were perparentheses represent patient numbers from Table1. Patient Nos. 18
formed, 7 had elevated MLCand 25 showed a biphasic pattern of elevation followed by a fall in
I concentrations (1 with
MLC-I. In the other patients, frequent measurements were not
MAS/PPHN and 6 with TMI).
performed. MLC-I, myosin light chain I.
All these 7 had FD and/or
NA. Patients No.18 and 25
showed a biphasic pattern (arise followed by a fall) while in the other 5, and TMI groups were significantly lower than
MLC-I concentrations were high on day 0 and in normal neonates (P < 0.05). However, there
decreased below the detection limit on day 10. were no significant differences between the
In these 5 patients, changes of MLC-I could not normal group and the FD, RDS and TTN groups(Fig. 3). Of the 18 patients with reduced
be measured (Table 1 and Fig. 2).
LVSF, one patient with TMI died on day 0, but
we were able to measure LVSF again in the
LVSF in normal neonates
other 17 neonates on days 2 through 10. The
The mean LVSF in normal neonates was 30.9 ± data showed normalization in all but one neo3.6% on day 0 and 31.2 ± 3.0% on day 5, indi- nate with EFE-like disease. In addition, of thecating no significant difference between the 2 20 patients with normal LVSF on day 0, 8
days.
showed normal LVSF values when this parameter was determined again at the time of remeasurement of MLC-I (Table 1 ).
LVSF in diseased neonates

In the present study, a fall in LVSF was noted in
18 neonates (18.9 ± 5%). On day 0, 9 of 18 withFD, 11 of 21 with NA, 7 of 12 with FD + NA,
10 of 10 with TMI, 3 of 7 with RDS, 2 of 9 with
TTN, 1 of 1 with EFE-like disease, and 1 of 1
with latent FD with reduced LVSF without
heart failure symptoms, had reduced LVSF
(Table 1). LVSF values in the NA, FD + NA

Correlation between MLC-I and LVSF
Since MLC-I was not elevated, except in 1 normal neonate and neonates with diseases otherthan FD, NA, TMI and MAS/PPHN, it wasthought that the correlation of MLC-I andLVSF was unlikely. In 10 patients with TMI
and 9 with elevated MLC-I concentrations, the73

H. Sawada et al.

NS

(%)

NS
P < 0.001
P < 0.05
P < 0.05
NS

40

LVSF

30

20

10

NormalFD

NA FD+NA TMI

RDS

TTN

Fig. 3. LVSF in normal and different diseased groups. LVSF is significantly lower in neonates with NA, FD+ NA and TMI than in normal neonates. There is no significant difference in LVSF among the FD, RDS andTTN groups and the normal group. FD, fetal distress; LVSF, left ventricular shortening fraction; NA, neonatal
asphyxia; NS, not significant; RDS, respiratory distress syndrome; TMI, transient myocardial ischemia of thenewborn infant; TTN, transient tachypnea of the newborn.

correlation between MLC-I and LVSF was analyzed using the peak MLC-I concentration obtained during the period from days 0 to 10, andthe LVSF value measured on the day of peak
MLC-I concentration. Although similar analysis was conducted in patients with FD, NA and
FD + NA, no significant correlation was found(TMI; r = 0.36, 9 patients with elevated MLC-I
concentrations; r = 0.36, FD; r = 0.073, NA; r =0.055, FD + NA; r = 0.26). In the other patients,
statistical analysis could not be performed dueto the small sample size.

such information is useful for management of
the circulatory system. However, since creatine
phosphokinase (CK), aspartate aminotransferase (AST), myoglobin, which are intracellular soluble proteins, readily move extracellularly due to increased permeability of thecell membrane during myocardial muscle dysfunction, these proteins are inappropriate indexes of myocyte necrosis, although they arehighly sensitive in detecting ischemicassociated myocardial disorders. On the other
hand, MLC-I, a structural protein of myocardial
fiber, is very specific to myocardial muscle
necrosis because blood levels of this protein
become detectable only after necrosis of the
myocardium (Khaw et al.,1978; Trahern et al.,1978). In this regard, CK and CK-MB are also
non-specific for the myocardium in the neonate,
unlike in the adult (Cao et al., 1968; Omokhodion
et al., 1991; Primhak et al., 1985).
Concentrations under 1.0 ng/mL were considered normal, as shown in the study of
Murano and coworkers (1995) , who measured

Discussion
Assessment of heart function by echocardiography is very useful because it is practical andsimple. Unlike echocardiography, which only
provides visual assessment of heart function,
quantitative determination of serum proteinsthat originate from the myocardial muscles
provide information on myocardial damage and74

MLC-I and LVSF in neonatesand AMI. With respect to the single patientwith shock caused by anencephaly who wastransferred from a nearby clinic while in a
shock condition, it appears that the shock was
induced by the concomitant hypoxemia.
MLC-I is thought to begin to increase atabout 4 h after the onset of AMI, reaching apeak concentration at 2 to 4 days, followed by agradual decline, but remains elevated even at 10days (Yazaki et al., 1980). In those neonateswith unstable systemic conditions, such as
those with FD, NA or TMI, minimal handling is
an important component of overall management. In our patients investigated in the firsthalf of the study, MLC-I was remeasured at theage of 10 days, as was recommended by Yazaki
and coworkers (1980). However, in those withabnormalities, MLC-I was below the detection
limit on day 10, unlike in adults. Since frequent
measurements are very difficult in neonateswith poor systemic conditions, just as in adults,
MLC-I measurements were made as long as thesystemic condition was not affected (days 2, 3,
5 and 8). Of the patients showing elevated
MLC-I concentrations, 2 showed a single-peakchange, in agreement with Yazaki and coworkers (1980). Furthermore, with regard to
the time of the onset of changes in MLC-I, the
MLC-I flow-out curves suggest that MLC-I canbe elevated both in fetal life and after delivery;
high concentrations were already found justafter delivery in some patients, while theconcentration was elevated on day 2 in another.
In older infants, LVSF does not depend onage, body surface area, or heart rate but are
influenced by a variety of left ventricular loads.
Therefore, the accuracy of any assessment isaffected by abnormalities in left ventricularwall motion. Furthermore, in assessing LVSF,
special attention should be paid to the fact that
LVSF is elevated by an increased pre-load and areduced after-load (Johnson et al., 1976). Thisis more important in low birth weight infants,
who inevitably undergo therapeutic intervention; thus, it is substantially impossible toestablish normal values for these infants. However, Murase and coworkers (1997) determined
the mean value of LVSF in very low birthweight infants and demonstrated that this para-

MLC-I on day 0. MLC-I concentrations under
1.0 ng/mL were considered normal in normal
neonates, irrespective of age. Khaw and others(1978) reported a crossreaction rate of not morethan 3% for myocardial MLC-I and skeletal
muscle MLC-I. In our subject with a concentration of 3.1 ng/mL, the Apgar score, LVSF
and troponin T (Katus et al., 1992) were 9
points, 27% and not more than 0.1 ng/mL, respectively, suggesting a cross-reaction between
cardiac and skeletal muscles.
TMI is defined as a pathologic condition
associated with heart failure caused by transientischemia of the myocardium due to perinatal
hypoxia (Rowe, 1977). Several pathophysiological mechanisms have been proposed(Kimura et al., 1982), including that of Roweand Hoffman (1972), who attributed TMI to
myocardial ischemia due to asphyxia and concurrent pulmonary vasoconstriction. Morrowand coworkers (1982) showed that a hypoxiainduced rise in thromboxane A2 causes vasoconstriction of pulmonary and coronary arteries
in TMI. They also hypothesized the samemechanism for the onset of PPHN and earlyneonatal acute myocardial infarction (AMI).
On the other hand, PPHN is due to hypoxemia
and acidosis that develops soon after birth (Foxand Duara, 1993). With regard to the mechanism for the onset, pulmonary vasoconstriction
is induced by thromboxane A2, prostaglandin
F2α and leukotrienes, and pulmonary vasculardevelopmental abnormalities due to chronic
hypoxemia (Morrow et al., 1982; Stenmark etal., 1983). In other words, PPHN can be viewed
as a severe form of pulmonary vasoconstriction
and TMI as coronary vasoconstriction, while
AMI is a form of TMI resulting from the absence of re-perfusion due to thrombosis and/or
embolism associated with coronary arterial
constriction.
Of our 38 patients, none with FD, NA, or
circulatory/respiratory diseases who did nothave associated TMI or PPHN showed elevated
MLC-I concentrations. In addition, statisticalanalysis demonstrated no significant differences in MLC-I, except for TMI, in comparison
with normal neonates. These findings suggestthat MLC-I is highly specific for TMI, PPHN
75

H. Sawada et al.

meter is more useful when determined serially.
LVSF values reported by these investigators
are, in general, similar to those measured in thepresent study in normal neonates, suggestingthat LVSF serves as an index that is unlikely tobe affected by body weight and gestational age
in neonates born after 28 weeks of gestation.
We also examined the low LVSF values insome of our patients, using as a reference themean values reported by Murase and coworkers(1997). As pointed out previously (Walther etal., 1985; Gill and Weindling, 1993), LVSF was
significantly lower in the NA group than in normal neonates, with hypoxia as the likely cause.
Although no difference was noted in the FDgroup, a significant difference was present in
the FD + NA group, and the number of patientswith low LVSF was smaller in the FD group
without NA at delivery. These findings suggestthat LVSF depends mainly on hypoxia at delivery rather than in fetal life. We also reported acase with a low LVSF and very low birth weightwith no underlying disease and with a probablediagnosis of latent fetal distress, based on therise in CK and AST concentrations at delivery.
As reported previously (Finley et al ., 1979;
Oh et al., 1985; Mitomori et al., 1989), a significantly low LVSF was also noted in patientswith TMI alone. Several TMI patients had elevated MLC-I concentrations, indicating thepresence of some form of myocardial necrosis.
In these patients, we anticipated a delayed
recovery of LVSF, but we were unable to finddifferences compared with patients with NA.
Although no differences were found in LVSF,
left ventricular posterior wall motion wasmarkedly decreased in all patients with TMI or
PPHN in the present study, as pointed out previously (Rowe and Hoffman, 1972; Mitomori etal., 1989). This is in agreement with earlier
studies demonstrating the relative frequency of
myocardial infarction in the left ventricularposterior wall detected at autopsies of neonateswith AMI (Ravich and Rosenblatt, 1947;
Richart and Benirschke, 1959), supporting theabove mentioned hypothesis of Morrow andothers (1982). However, no similar finding
was noted in any other cases of asphyxia or
respiratory diseases, suggesting its usefulness

in differential diagnosis by echocardiography.
In addition, an index allowing quantitative
assessment of left ventricular posterior wallmotion would facilitate differential diagnosis.
In one patient with PPHN and elevated MLC-I
concentrations, the apparently normal LVSF
was attributed to increased pre-load associatedwith moderate mitral insufficiency (Johnson etal., 1976). As for our patient with EFE-like
disease, heart failure was attributed to longterm use in the mother of a high-dose of ritodrine throughout pregnancy (Katz and Seeds,1989).
In adult patients with AMI, there is a significant negative correlation between the left ventricular ejection fraction and MLC-I during theacute stage (Isobe et al., 1987). We anticipateda similar correlation between LVSF and MLC-I
in our patients with elevated MLC-I concentrations but unexpectedly failed to find such a
correlation. Differences between adult andneonates may be due to the following factors: i)Right ventricular pressure load and volume load
are accentuated by physiological pulmonary
hypertension during early neonatal life or bypulmonary vasoconstriction inducing pulmonary hypertension in hypoxic neonates, which
in turn adversely affects interventricular septal
wall motion and hence influences LVSF; ii)
Most patients with elevated MLC-I concentrations are in poor systemic condition necessitating therapeutic intervention that can influence LVSF, such as intubation, oxygen therapy
and administration of catecholamines; also
different patients receive different treatmentsthat also invariably influence LVSF.
In conclusion, our study demonstrated thatelevated MLC-I concentrations occur specifically in a series of pathologic conditions, i.e.,
TMI, PPHN and AMI in neonates, suggesting
the potential usefulness of MLC-I for estimating the onset and severity of myocardial
necrosis and as an index for the diagnosis andmanagement of circulatory disorders in these
conditions. In addition, echocardiographicallydetermined LVSF allowed estimation of theaffected sites, although the establishment of theseverity of this disorder remains elusive.

76MLC-I and LVSF in neonates

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(Received December 21, Accepted December 24, 1998)

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