OBJECTIVE

To determine the frequency of increase of serum values, not of cardiac origin, of creatine kinase-MB (CK-MB) in trauma patients.

METHODS

Prospective.

METHODS

University Hospital, Groningen, the Netherlands.

METHODS

51 trauma patients without chest injury (without myocardial contusion) but with (among others) soft tissue injuries, were included. At admission (time point t1) an ECG and chest X-ray were made and blood was collected for measurement of CK total, CK-MB activity and CK-MB mass. If the CK-MB activity/CK total fraction exceeded 3%, CK electrophoresis was performed. Blood analysis was repeated after 24 hours (t2).

RESULTS

CK-MB activity was elevated in 27 patients (53%) at t1 and in 3 (6%) at t2. The fraction CK-MB activity/CK total exceeded 3% in 96% and 33% of these patients at t1 and t2, respectively. In all these cases a CK-BB band was detected by electrophoresis (CK-BB interferes with the CK-MB activity measurement). CK-MB mass was elevated in 11 patients (22%) at t1 and in 19 (37%) at t2.

CONCLUSIONS

CK-MB was frequently elevated in trauma patients owing to skeletal muscle damage and to interference with CK-MB activity measurements. For the detection of myocardial damage in trauma patients, CK-MB measurements are of little use.

Several physical properties of creatine kinase (EC 2.7.3.2) isozymes MM (CK-MM, muscle-type) and BB (CK-BB, brain-type), both homodimers, and isozyme MB (CK-MB), a heterodimer, were compared to determine how formation of the hybrid modifies subunit conformation and dynamics. Circular dichroic spectra revealed additional alpha-helical content for the hybrid isozyme. Double-beam absorption difference spectra between CK-MB and a stoichiometric mixture of CK-MM and CK-BB revealed decreased exposure of intrinsic chromophores in the hybrid. The relative intensity of the intrinsic fluorescence of CK-MB was between the two homodimers, but was 16% closer to the less fluorescent CK-MM. Steady state anisotropy spectra and decay of the anisotropy of CK derivatized on a single subunit with the fluorescent sulfhydryl reagent 5-[2-(iodoacetyl)amino-ethyl]aminonaphthalene-1-sulfonate indicated that the derivatized sites are more flexible in the heterodimer. The slow component in the anisotropy decay suggests that hybridization results in a small increase in the packing density or contraction of overall conformation of the B-subunit. The KM for MgATP with singly derivatized CK-MB was the same as the KM for the native enzyme. However, derivatization of a single subunit caused the Vmax to decrease by greater than 50%, which indicates that subunit-subunit interactions may modulate the activity of CK. A model for assembly of CK-MB is proposed which includes subunit characteristics more similar to those found in the muscle-type homodimer than in the brain-type homodimer and increased flexibility of the active site domain of both subunits.

The ectopic expression in peripheral blood cells of the brain-type creatine kinase (CKB) is an autosomal dominant inherited anomaly named CKBE (MIM ID 123270). Here, we characterized the CK activity in serum, platelets (PLT) and leukocytes (WBC) of 22 probands (from 8 unrelated families) and 10 controls. CK activity was measured by standard UV-photometry. Expression of the CKB gene was analyzed by real-time PCR and Western blotting. DNA sequencing including bisulfite treatment was used for molecular analysis of the CKB gene. Serum CK levels were comparable between probands and controls. CKBE probands revealed significantly higher CK activity in PLT (3.7 ± 2.7 versus 179.2 ± 83.0 U/10(12) PLT; p<0.001) and WBC (0.4 ± 0.3 versus 2.6 ± 2.1 U/10(9) WBC; p=0.004). Inhibitory anti-CKM antibodies did not affect CK activity indicating that the CK activity is generated exclusively by the CK-BB isoenzyme. CKB mRNA and protein levels were significantly higher in PLT and WBC from probands compared to controls. Re-sequencing of the entire CKB gene and methylation analysis of a CpG island revealed no alteration in CKBE probands. The genetic basis of CKBE remains unclear, however, we propose that a de-methylated CKB gene is inherited that leads to high CKB expression levels in myeloic precursor cells in the bone marrow.

BACKGROUND

Serum creatine kinase-MB isoenzyme (CK-MB) is widely used as a marker of myocardial injury. We prepared recombinant human CK (r-hCK) MB isoenzyme and examined its potential for use as a control material for assay of CK-MB in serum.

METHODS

cDNAs encoding CK-M and CK-B subunits were inserted into the same plasmid vector, followed by transformation of Escherichia coli. The resulting three types of CK isoenzymes were purified by conventional chromatography.

RESULTS

The ratio of MB to MM to BB was 50:40:10 on the basis of CK activity. Highly purified CK-MB with a specific activity of 533 U/mg was produced in a yield of 5.7 mg/g of packed cells. Purified r-hCK-MB had the isoelectric point (pI 5.3) and molecular size (46 kDa for the subunit) of native CK-MB. Its immunoreactivity in an ELISA using antibody against native heart enzyme was similar to that of cardiac CK-MB. The r-hCK-MB retained >90% activity for at least 4 months at 11 degrees C in a delipidated serum matrix in a liquid form at a concentration of 118 U/L.

CONCLUSIONS

r-hCK-MB shows key properties of the native cardiac isoenzyme and may be useful as a control and calibrator for serum assays of CK-MB.

A novel immunochemical technique for a specific enzymic determination of the myocardial isoenzyme of creatine kinase, CK-MB, involves determination of B-subunit activity of a specimen in which the M-subunit activity has been inhibited by specific antibodies to the M-subunit. Interfering activities from CK-BB isoenzyme, atypical forms of creatine kinase, and adenylate kinase are eliminated by using a blank tube in which all the M-subunit-containing isoenzymes have been removed by a specific immunoprecipitation step. The assay is convenient, linear, and reproducible, and results compare well with those by agarose electrophoresis.

Total CK and CK isoenzyme activity in serum was investigated during pregnancy, labor and after delivery as well as in cord blood. Total CK was decreased in the second trimester of pregnancy but increased in late pregnancy. Low CK-MB activity in serum was found in patients with early labor pains. CK-BB activity could never be detected during pregnancy. Total CK and isoenzyme activity increased after delivery. The rise of total CK and CK-MB in maternal serum is directly correlated with the following: type of delivery, duration of labor, parity of the mother, and birth weight. From this it can be deduced that postpartum CK levels depend on skeletal muscle activity as well as on the activity of uterine muscle. Prematures and infants "small for date" have significantly lower total CK and slightly more elevated CK-BB activity in cord blood than children of normal maturity. CK-BB activity is much more pronounced in high risk patients with low Apgar score.

Biochemical analyses of the brain of cichlid fish larvae, exposed for 7 days to increased acceleration of 3g (hyper-g), revealed an increase in energy availability (succinate dehydrogenase activity, SDH), and in mitochondrial energy transformation (creatine kinase, Mia-CK), but no changes in an energy consumptive process (high-affinity Ca(2+)-ATPase). Brain glucose-6-phosphate dehydrogenase (G6PDH) of developing fish was previously found to be increased after hyper-g exposure. Three respectively 5 hours thereafter dramatic fluctuations in enzyme activity were registered. Analysing the cytosolic or plasma membrane-located brain creatine kinase (BB-CK) of clawed toad larvae after long-term hyper-g exposure a significant increase in enzyme activity was demonstrated, whereas the activity of a high affinity Ca(2+)-ATPase remained unaffected.

In the present study, the cause of suspected false-positive (anomalous) values for CK-MB activity, in Indian patients investigated for ACS. Total serum CK and CK-MB activity, serum Troponin I were measured and CK-MB as a percentage of the total CK activity (%CK-MB) calculated. CK-MB was also estimated using densitometry and CK-MB mass assay. Anomalous specimens were tested for the presence of CK isoenzymes. In 22 healthy subjects, 11 male and female, the %CK-MB ranged from 3.6 to 30.2. In 11 male patients, with proven ACS, the %CK-MB was from 4.0 to 17.5. The cut off for anomalous CK-MB activity values was set as >33.0%. In 35 patients with anomalies, total CK values ranged from 39 to 231 U/L, CK-MB from 30 to 161 U/L. Investigation of CK isoenzymes, showed 10 patients had a CK-BB band, 14 an intermediate band between CK-MM and CK-MB (macro-CK type 1), 7 had a cathodal band (macro-CK type 2), and 3 had a band intermediate between CK-MB and CK-BB. This later band does not seem to have been previously reported. Against the CK-MB mass assay, the activity assay showed no correlation, in 43 patients (19 M, 24 F), Pearson coefficient (R(2)) was 0.006. The CK-MB immunoinhibition assay is better described as measuring "non-CK-MM activity." A %CK-MB activity >6% as a marker of ACS is not valid in our patient population. Laboratories should not use only CK-MB activity as a biochemical marker of ACS.

The relative diagnostic usefulness of total serum acid phosphatase, tartrate-inhibited fraction of acid phosphatase, immunoreactive prostatic acid phosphatase, and creatine kinase-BB isoenzyme was evaluated in 30 patients with biopsy-proven adenocarcinoma of prostate. The total and tartrate-inhibited acid phosphatase, measured by standard chemical methods, were elevated in 8 patients with stage D disease. The radioimmunoassay (RIA) method confirmed these abnormal values and also indicated the presence of elevated prostatic serum acid phosphatase in 3 additional patients. The electrophoretic fractionation of total serum creatine kinase (CK) into its various isoenzyme components showed the presence of CK-BB isoenzyme in 8 patients. In 5 of these patients with detectable CK-BB isoenzyme, RIA values for prostatic acid phosphatase were also elevated. Histologic studies of the prostatic tissues revealed that the presence of serum CK-BB was invariably associated with poorly differentiated adenocarcinoma of prostate. The results of the present studies indicate that 1) with simultaneous measurements of serum CK-BB and immunoreactive prostatic acid phosphatase laboratory confirmation of prostatic cancer can be obtained in 50 per cent of patients; 2) determination of total and tartrate-inhibited acid phosphatase along with CK-BB and immunoreactive prostatic acid phosphatase does not increase the frequency of correct diagnosis; and 3) the presence of serum CL-BB isoenzyme is suggestive of poorly differentiated adenocarcinoma of prostate.

Pregnant mice were exposed to 100 mg/kg 2,4,5-T, IG, on gestation days 6 through 17, and sacrificed on postpartum day 1 or 21. Toxicologic evaluation showed no changes in body weight, heart weight, heart to body weight ratio, or cardiac supernate protein between corn oil control and 2,4,5-T treated mice on days 1 or 21 postpartum (pp). There were no effects of 2,4,5-T treatment on the total LDH enzyme activity of cardiac supernate on day 1 or 21pp. Serum LDH total activity was depressed on day 1pp and comparable to control values on day 21pp. Cardiac CK total activity was elevated on day 1pp, but not on day 21pp. Serum CK total activity on day 1 was comparable to control values; however, on day 21, a significant decrease in activity was observed. Cardiac LDH and CK isozyme profiles were normal on days 1 and 21pp. The serum LDH isozyme profile was normal at both times. The serum CK isozyme profile on Day 1 was markedly altered by athe appearance of two aberrant isozyme bands while on day 21, there was a profile shift with an increase in the BB band and a compensatory decrease in the MM band. These changes in creatine kinase suggest metabolic or pathologic changes in the cardiac muscle.

The novel natural product DT56a (Secure Pharmaceuticals, Yavne, Israel), derived from soybean, has been shown to relieve menopausal vasomotor symptoms and increase in bone mineral density with no effect on sex steroid hormone levels or endometrial thickness. In single injection, like 17beta-estradiol (E2), DT56a stimulated bone, cartilage and uterus in immature or ovariectomized female rats, by measuring the changes in the specific activity of the BB isozyme of creatine kinase (CK). When administered in multiple oral doses, DT56a stimulated skeletal tissues similarly to E2 but not uterine CK. The selective estrogen receptor modulator raloxifene blocked the stimulation of CK by either DT56a or by E2 in all tissues tested. In the present study we measured the effects of DT56a on vascular tissues i.e. aorta (Ao) and the left ventricle of the heart (Lv). Both types of animals responded to either single or multiple administration of DT56a like to E2. In the Ao from both animals and in the Lv from ovariectomized rats, raloxifene completely blocked CK activity induced by DT56a, whereas in the Lv of immature female rats the inhibition was partial. Our experimental findings suggest that DT56a acts as estrogen; it has beneficial effects not only on skeletal tissues, but also on vascular tissues, however contrary to estrogen DT56a, did not affect the uterus. These findings suggest that DT56a--which has similar beneficial effects on vascular tissues like that of E2--is probably mediated via common receptor(s).

Total serum creatine kinase (CK) and its isozyme activities were determined in dogs with dirofilariasis. Before heartworm removal, total CK and isozyme activities in dogs of the mild group were not different from those in dogs of the heartworm-free group. BB activity was higher in dogs of the hemoptysis group. Dogs of the ascites group displayed a mild increase in MM activity. In dogs of the caval syndrome (CS) group, total CK and MM activities were highest among the heartworm-free and heartworm-infected dogs, and MM isozyme accounted for most (75%) of total CK activity. MB and BB activities were also higher. However, there were no significant differences in CK activities between the surviving and non-surviving cases. In dogs with pulmonary heartworm disease (mild and ascites groups), MM activity correlated significantly with the number of heartworms (r = 0.45), hematocrit value (Ht, r = -0.40), serum alanine aminotransferase (ALT, r = 0.42) and lactate dehydrogenase (LDH, r = 0.46) activities, mean pulmonary arterial pressure (r = 0.64) and total pulmonary resistance (r = 0.50). In dogs with CS, MM activity did not correlate with any parameter, but BB activity correlated with the number of heartworms at the right atrium (r = 0.61), Ht (r = -0.53), ALT (r = 0.80), LDH (r = 0.73) and serum urea nitrogen (r = 0.47). At 1 week after heartworm removal, BB and MM activity decreased in dogs of the hemoptysis and ascites groups, respectively. In dogs of the CS group, total CK and MM isozyme activities decreased markedly (P less than 0.01) regardless of their prognosis.

The purpose of this study is to find, besides the determination of lactate in blood, a suitable and specific indicator of brain damage in newborn. Accordingly, we studied the total creatine kinase (CK) activity, by the method of Rosalki, and its subunit isoenzymes BB (CK BB) by fluorescence following electrophoresis on cellulose acetate. A first group (thirty newborns) without any disease represents our taest group. We havae found that the normal ranges for CK total were elevated (about 7 200 nkat/l). Electrophoresis of sera from these patients showed in addition to the normally migration isoenzyme (CK BB) was present in very small amounts, no sufficient for quantification. A second group was constituted to thirty ill newborns, with perinatal brain damage. In twenty-eight to thirty children, we find a significant correlation between the level of CK BB and brain insult. But, we have showed that it was necessary to take in consideration the time passed between the hypoxic insult and the blood puncture. Otherwise, we showed by immuno inhibition with specific antibody and by chromatography with gradient elution that identification of CK BB by electrophoresis cannot be misinterpreted. Furthermore, we demonstrated by this method, that position of CK 1 BB in blood is exactly the same that an purified human extract. This study concluded that a high level CK 1 BB in blood of newborn infants with perinatal brain damage has an accurately diagnosis value, if the blood puncture is done immediately during the severe CNS damage.

Freshwater (FW) teleosts are capable of acclimating to seawater (SW) following such a transfer from FW. However, their osmoregulating mechanisms are still unclear, particularly those in the brain. The present study was conducted to examine acute changes that occur in brain Na(+)-K(+)-ATPase activity, creatine kinase (CK) activity, creatine, creatinine contents, and ATP levels of tilapia (Oreochromis mossambicus) in response to this transition. After transfer to SW (25 ppt), the Na(+)-K(+)-ATPase activity was maintained for 8 hr at higher levels than that in FW. In contrast, in 35 ppt SW, Na(+)-K(+)-ATPase was maintained at a even higher level than in FW for the first 2 hr. Brain Na(+)-K(+)-ATPase contents in both the 25 and 35 ppt SW groups were significantly elevated within 1 and 0.5 hr after transfer from FW, respectively. Interestingly, brain CK activities and content (homodimer of the B subunit [BB] form) in both the 25 and 35 ppt SW groups were significantly elevated within 1 hr after transfer from FW. The ATP contents in 35 ppt SW increased abruptly within 0.5 hr, and then gradually decreased during the next 2 hr. Unlike the 35 ppt group that declined in ATP contents, the 25 ppt group leveled off within 24 hr. The elevations in CK activity and creatine levels after transfer from FW to SW imply that abrupt salinity changes alter phosphocreatine/CK ratio. Such changes are needed to satisfy the increases in the energetic requirement of the cotransport mechanisms mediating osmoregulation.

BACKGROUND

Information about the electrophoretic distribution of <em>CK</em>-MM, <em>CK</em>-MB, and <em>CK</em>-<em>BB</em>, serum creatine kinase (<em>CK</em>) isoenzymes that are indicators of skeletal muscle, cardiac muscle, and brain lesions, respectively, and <em>CK</em> macroenzymes (macro-<em>CK</em>1 and macro-<em>CK</em>2) in dogs and cats with and without central neurologic disease is scant and equivocal.

OBJECTIVE

The objectives of this study were to describe the electrophoretic distribution of CK isoenzymes and macroenzymes in healthy dogs and cats and to provide a preliminary assessment of the utility of CK enzymatic electrophoresis in dogs and cats with central neurologic disease.

METHODS

Electrophoretic separation of serum CK isoenzymes and macroenzymes was performed on freeze-thawed serum samples from 20 healthy dogs and 3 dogs with central neurologic disease and from 14 healthy cats and 6 cats with neurologic feline infectious peritonitis (FIP). Electrophoretic separation was also performed on supernatants of homogenized brain, skeletal muscle, and cardiac muscle from both species, to assess the tissue distribution of isoenyzmes in dogs and cats.

RESULTS

CK-MM was the predominant isoenzyme in the serum of healthy dogs and cats, followed by macro-CKCK-BB in dogs and by both macroenzymes in cats. In dogs, CK-MB was essentially absent from both serum and homogenized hearts. CK-BB increased in dogs with neurologic disease. In cats, CK-BB was essentially absent from serum, but was present in brain homogenates. Two of 6 cats with FIP had increased macro-CKCK-BB activity.

CONCLUSIONS

This study identified the electophoretic distribution of CK isoenzymes and macroenzymes of dogs and cats and provided encouraging data about the possible use of CK-BB as a biomarker for canine neurologic disorders, but not for FIP.

We surveyed the sera of 100 regularly hemodialyzed patients for creatine kinase (CK) and isoenzyme activity (MM, MB, BB) in order to determine the meaning of persistently elevated CK fortuitously noted in a porportion of these patients in the absence of clinical events to account for this finding. Nineteen patients (19 percent) had sustained CK elevation over the period of investigation with the skeletal muscle isoenzyme (MM) predominating. BB was within the normal range in these patients and MB exceeded 3.0% of total CK in only 2 patients. The pre-dialysis blood urea nitrogen mean for ths group was significantly higher (P < 0.02) as was the serum creatine per kilogram of dry body weight (P < 0.05) than for the group with normal CK totals. There was no significant difference in peroneal nerve conduction velocity of serum bicarbonate between these groups. CK activity also correlated significantly with predialysis blood urea nitrogen values (r = 0.52, P < .001). The deranged nitrogen metabolism previously noted in uremia leads us to conclude that the excess skeletal muscle CK may be related to the muscle wasting noted in some uremic patients.

We studied the effect of Zn(2+) on the folding and aggregation of brain creatine kinase (CK-BB). We developed a method to purify CK-BB from rabbit brain and conducted inhibition kinetics and unfolding studies of CK-BB. Zn(2+) conspicuously aggregated and osmolytes, such as glycine and proline, were able to suppress the formation of aggregates and protect the enzymatic activity against Zn(2+). These results suggest that Zn(2+) might act as a risk factor for CK-BB in the brain under certain conditions, and some osmolytes may help CK-BB to sustain the active state when Zn(2+) is present. Our study provides useful information regarding the effect of Zn(2+) on brain-derived metabolic enzymes, especially those that are putatively related to brain disease. Furthermore, our study suggests that although Zn(2+) may induce CK-BB inactivation and misfolding, the ability of some abundant proteins and osmolytes to chelate Zn(2+) nonspecifically may protect CK-BB and allow it to exist in the active form.

The occurrence of acrylamide is frequently observed in processed foods. Therefore, the harmful effects of acrylamide on metabolic enzymes are important to understand. We studied the inhibitory effects of acrylamide on the brain creatine kinase (CK-BB). We found that CK-BB was kinetically inactivated by acrylamide accompanied by the disruption of the hydrophobic surface. Acrylamide mainly interacted with the thiol (-SH) residue of CK-BB and resulted in alkylation. A computational docking simulation supported that acrylamide directly bound to the active site of CK-BB where cysteine and glycine residues interacted mainly. The inhibition kinetics combined with computational prediction can be useful in order to have insights into the mechanisms regarding environmentally hazardous factors at the molecular level.

In 2.9% of sera from 1253 unselected patients we detected two different types of macromolecular creatine kinases (CK; EC 2.7.3.2). One macro type was represented by immunoglobulin-linked CK: in sera containing macro CK-BB isoenzyme, 125I-labeled CK-BB was bound with high affinity to the immunoglobulin fraction. Furthermore, during electrophoresis, macro CK-BB mostly migrated between CK-MB and CK-MM, and was fixed to Protein A from Staphylococcus aureus. We therefore propose radioelectrophoresis as a specific, highly sensitive, and simple method for detecting this type of macro CK. This form occurs predominantly in elderly women, is not correlated to any specific disease, and persists in blood over a long period of time. In contrast, a second type (macro-CK type 2) never bound radiolabeled CK isoenzymes, and was not adsorbed to Protein A. Electrophoretic migration of this macro-CK type 2 was generally cathodic to CK-MM. We observed this type in severely ill patients, frequently those suffering from malignant tumors. Clinical observations and biochemical data suggest that macro-CK type 2 is of mitochondrial origin.

Creatine kinase (CK EC 2.7.3.2) and CK-BB activity was analyzed in 41 malignant tumors of 6 different sites and different histological structures. The same analyses were done on 150 sera of patients with malignant diseases of various localizations. The rate of CK activity was determined kinetically, whereas tissue and serum CK-BB were separated chromatographically (Mercer). Insofar as malignant tumor tissues are concerned, the highest average rate of CK-BB activity was detected in tumors of the prostate (mean 1450 IU/g), and the lowest in tumors of the parotid gland (mean 5.2 IU/g). CK-BB was detected by the Mercer technique in 56 (37.3%) of 150 analyzed sera of patients with malignant diseases. The rate of CK activity in sera of patients with malignant diseases was 8 to 74 IU/I. In comparison with the site of the malignant process no significant CK serum activity differences were observed. T2-T3 tumors did not significantly influence the activity of either CK or CK-BB in the case of either tissues or sera (T1-T3). Enzyme activity was found to be much higher--both in tumoral tissue and in sera--with T4 tumors. The highest rate of CK-BB activity was found in sera of patients with malignant tumors of the stomach (mean 8.1 IU/I), and the lowest in malignant tumors of the rectum (mean 1.8 IU/l).

The case of a patient with bronchial neoplasm is described. A non-typical form of creatine kinase found in the plasma gave rise to a false positive CK MB test by the immunoinhibition procedure. Electrophoresis on agarose gels beside a normal MM band showed an additional band between the MB and the MM band of a standard mixture. It could be shown by an immunoprecipitation test using precipitating antibodies against CK-MM and CK-BB that the creatine kinase of the abnormal band consists entirely of the MM-type, which after treatment with polyethylene glycol not only became susceptible to inhibiting anti-M antibodies, but also showed the electrophoretic motility of CK-MM. Gel filtration chromatography clearly demonstrated the macromolecular nature of this abnormal creatine kinase.

Total creatine kinase (CK) activity and isoenzyme distribution were determined in normal and tumour of gastrointestinal (GI) tract. Total CK activity per gram wet tissue appeared to be markedly reduced in malignant tumour tissue, yet it was raised in benign tumour tissue. CK-BB was the predominant isoenzyme in both normal and tumour tissue of GI tract. Alteration of isoenzyme pattern was noted between the normal and tumour tissue. In one patient, macro-CK was found in tissue homogenate.

OBJECTIVE

To observe the changes of endothelin-1 (ET-1), nitrogen oxide (NO) and creatine phosphokinase BB isozyme (CK-BB) in blood and cerebrospinal fluid (CSF) in patients of infantile hypoxic-ishemic encephalopathy (HIE), and explore the efficacy of compound Salvia injection (CSI) in treating mid-severe HIE.

METHODS

Sixty mid-severe infantile HIE patients were divided randomly into the treated and the control group. To the treated group CSI was added on the basis of conventional treatment, and to the control group the conventional treatment was given alone. The blood and CSF content of ET-1, NO and CK-BB at acute and convalescent stage in the two groups were determined and the therapeutic effects were compared between the two groups.

RESULTS

The markedly effective rate and effective rate of the treated group was 80.0% and 93.3% respectively, while that of the control group was 66.7% and 83.3% respectively, the therapeutic effect in the treated group were obviously superior to that in the control group, the difference was significant (P < 0.05).

CONCLUSIONS

ET-1, NO and CK-BB participated the pathological process of HIE. CSI was markedly effective in treating mid and severe HIE infants.