Creatine kinase and lactate dehydrogenase isoenzymes in stage D prostatic carcinoma.

Serum creatine kinase (CK) and lactate dehydrogenase (LD) isoenzymes were determined electrophoretically, along with various other biochemical markers of malignancy, in 19 patients with metastatic carcinoma of the prostate. Mitochondrial CK appeared in 15 patients, the CK-BB isoenzyme in 6. As a result, CK activity not inhibited by anti-M-subunit antibodies, CK non-M, was above the reference value in altogether 17 patients. There was a cathodic shift among the LD isoenzymes, significantly more prominent with increasing total LD, and a positive correlation between elevations of CK non-M and LD-5, suggesting a relation to tumour burden for both. An LD 'flip' (LD-1 greater than LD-2) was present in 10/15 patients. The frequency of CK non-M elevations was similar to--but not quantitatively correlated with--elevations of prostatic acid phosphatase and alkaline phosphatase. Thus, changes in CK and LD patterns are frequent in patients with prostatic cancer and must be taken into consideration when acute cardiac symptoms are evaluated in such patients.

Influence of various irrigation fluids on serum enzyme patterns following transurethral resection of the prostate.

Serum levels of a variety of enzymes were determined preoperatively and repeatedly postoperatively in a comprehensive biochemical study of 60 patients undergoing transurethral resection of the prostate (TURP). These patients were divided into four groups depending on the type of fluid used for irrigation during TURP. Prostatic acid phosphatase (PAP, analysed by radio-immunoassay) in serum showed a marked postoperative increase but wide inter-individual variation in all groups. It returned to normal within 24 to 48 hours. When water was used for irrigation, similar but less pronounced increases were observed for serum lactate dehydrogenase (LD, LD-1) and aminotransferases (ASAT, ALAT). This is interpreted as being due to an influx of irrigating fluid into the general circulation from the bladder through opened veins, by absorption from a perivesical accumulation or, in the case of PAP, also from the prostatic wound. The enzyme increases (other than PAP) may be due to their release from haemolysed red cells in the bladder or in a perivesical fluid accumulation, which conjecture is supported by the marked increase also seen in plasma haemoglobin. When iso-osmolar fluids were used for irrigation signs of haemodilution, such as a postoperative decrease in serum sodium, were observed. Several of the variables studied may be used as markers to indicate the quantity of irrigating fluid absorbed during resection. Plasma haemoglobin, serum LD (or LD-1) in connection with water irrigation, serum sodium in connection with iso-osmolar fluid irrigation and serum PAP, regardless of the type of irrigating fluid used, are some practical suggestions for such markers.

Serum creatine kinase (CK) activity after M-subunit inhibition in patients with atypical CK isoenzymes--a comparison to findings in acute myocardial infarction.

The serum levels of total creatine kinase (CK), and of CK-B, as estimated by the enzymatic anti-M-subunit immunoinhibition method, were studied in 14 patients with CK-B elevation associated with advanced malignant disease, in nine subjects with electrophoretically verified, immunoglobulin-bound CK-BB (macro CK) and in 28 patients with acute myocardial infarction (AMI). The range of CK-B activity was similar in all three groups. In AMI, the ratio CK-B/total CK at peak CK-B was less than 13% (mean 7%). In both the groups with atypical CK, the ratios varied from about 30% to nearly 100%, with a mean amounting to 2/3 of total CK activity. CK-B elevations in patients with untreated malignant tumours tended to increase with time, but occasionally remained fairly constant for months, like those in subjects with macro CK. Complementary CK isoenzyme separation, e.g. by electrophoresis, is needed to differentiate conditions with atypical CK activity, detected by routine use of CK-B determinations in the diagnosis of AMI.

Serum creatine kinase isoenzymes in patients with advanced malignant disease.

Serum creatine kinase (CK) B subunit (CK-B) activity, as estimated by the enzymatic anti-M immunoinhibition method, and the CK isoenzyme pattern after agarose gel electrophoresis, were studied in 28 patients with advanced, untreated malignant disease. CK-B was above the decision limit, i.e. the discrimination limit used in the diagnosis of acute myocardial infarction (AMI), in 14 patients (50%). Electrophoresis demonstrated, besides CK-MM, an atypical, cathodically migrating CK band in 10 of these patients. This band may represent mitochondrial CK. The CK-BB isoenzyme was detected in 9 and CK-MB in 3 subjects. Histopathologic findings indicated that the occurrence of these isoenzymes was related to tumour burden and the overall severity of the disease. Survival among patients with CK-B elevation was shorter than among other patients. The present findings are relevant to the enzyme diagnosis of AMI and of potential significance for the evaluation of patients with known or suspected malignant tumours.

Myocardial injury and CK-MB release during aortic valve surgery with selective coronary perfusion.

The postoperative serum activity of creatine kinase MB isoenzyme (CK-MB) was studied in 25 patients undergoing isolated aortic valve replacement (Björk-Shiley prosthesis). Hypothermia at 30 degrees C and selective coronary perfusion (CP) were used for myocardial protection. Repeated electrocardiograms revealed no signs of perioperative myocardial infarction. In all patients, CK-MB was detected in the serum. The CK-MB as a percentage of total CK at peak CK-MB [12 +/- 1 (mean +/- SEM)] was of the same magnitude as that found in acute myocardial infarction (AMI). Peak CK-MB occurred 2 +/- 0 h after the end of surgery. Peak total CK occurred after 17 +/- 3 h, and the plasma half-life for total CK was three times that of CK-MB. Thus, the kinetics of serum CK differed from those in AMI, but were similar to those reported after coronary bypass operations. The release of CK-MB, as well as of asparatate aminotransferase and thermostable lactate dehydrogenase, was related to the duration of aortic cross-clamping (AC), with a marked increase after 90 min. In two subgroups with similar AC time, postoperative CK-MB activity was higher in the subgroup with longer CP, indicating that CP as a method of myocardial protection may be entirely beneficial.

Myocardial protection during aortic valve replacement. Comparison between sanguineous and Asanguineous Cardioplegic Solutions.

Myocardial substrate metabolism and enzyme release following hypothermic potassium cardioplegia were studied in two series of patients undergoing isolated aortic valve replacement. In 15 patients blood was used as cardioplegia vehicle (blood cardioplegia group) and a plain electrolyte solution was used in a control group of 17 patients. Simultaneous blood samples were drawn from arterial and coronary sinus blood before and during the first 60 min after release of aortic cross-clamping. Blood samples were analyzed for PO2. O2-saturation and content, PCO2, pH, lactate, pyruvate, glucose, potassium, myoglobin, creatine kinase (CK), its isoenzyme MB and aspartate aminotransferase (ASAT). In addition, myoglobin and enzymes were followed in peripheral venous blood for 48 hours. The pattern of metabolic changes after cardioplegia was similar in both groups, but some differences were encountered in the degree of the changes in potassium, myoglobin and CK-MB between the groups. The differences were nevertheless small and cell damage was probably of reversible nature in all patients, but the myocardial protection afforded by single dose blood cardioplegia was not unquestionably better than that of the control group.

Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following continuous blood cardioplegia.

Cardiac metabolism following hypothermic potassium cardioplegia with blood as cardioplegia vehicle was studied in two groups of patients undergoing aortic valve replacement. In 15 patients, blood was given as single dose infusion (single dose group) and in 18 patients the same initial bolus was followed by a continuous perfusion (25-30 ml/min) with modified blood from the heart-lung machine (continuous blood group). Simultaneous samples were drawn from arterial and coronary sinus blood before and during the first 60 min after cardioplegia. In the continuous blood group, samples were also drawn during the period of cardioplegic perfusion. The samples were analyzed for PO 2, O2-saturation and content, PCO2, pH, lactate, pyruvate, glucose, potassium, myoglobin, creatine kinase (CK), its isoenzyme MB, and aspartate aminotransferase (ASAT). In addition myoglobin and enzymes were followed in peripheral venous blood for 24 hours. Myocardial biopsies were taken from the left ventricle at the beginning and end of cardioplegia and analyzed for adenosine triphosphate (ATP), creatine (C) and creatinephosphate (CP). The pattern of metabolic changes after cardioplegia was similar in both groups with decreased myocardial oxygen extraction, marked lactate and potassium release, increased glucose uptake and significant enzyme and myoglobin release. However, the degree of changes was significantly smaller in the continuous blood group. The myocardial biopsies also showed significantly less ATP and CP decrease in the continuous blood group, suggesting, together with the other metabolic results, that the myocardial protection afforded by continuous blood cardioplegia was superior to that of the single dose group. Furthermore, continuous perfusion permitted easy control of myocardial temperature during the period of aortic cross-clamping.

Diagnostic significance of serum CK-MB elevations following surgical damage to skeletal muscles.

Total creatine kinase (CK) and its isoenzyme MB (CK-MB) were studied in the serum of 14 patients following thoracotomy, mostly for pulmonary surgery, and in various thoracic muscles from another 9 patients subjected to the same procedure. CK-MB consistently appeared in the serum and was present in all muscle samples examined. CK-MB as a percentage of total CK (the CK-MB/CK ratio) was of similar order in serum and muscle, approximately 1.5%. Compared with previous findings after cardiopulmonary bypass surgery, maximum serum CK-MB activity occurred later, and the CK-MB levels as well as the CK-MB/CK ratio were considerably lower after non-cardiac thoracic surgery. It is suggested that the CK-MB/CK ratio 24 hours after operation may be used in the diagnosis of peri-operative myocardial infarction, particularly in non-cardiac surgery. After thoracotomy, this ratio was below 2.2%. In a series of patients with acute myocardial infarction, reported previously, the ratio was above 5.4%. Secondary rises of serum CK-MB following cardiac surgery should, apparently also be analysed in relation to the simultaneous total CK level.

Myocardial protection during aortic valve replacement. effects of mannitol in the cardioplegic solution on cardiac metabolism and enzyme release.

Myocardial substrate metabolism and enzyme release following hypothermic potassium cardioplegia with and without the addition of mannitol in the cardioplegic solution were studied in two series of patients undergoing isolated aortic valve replacement. Measurements were made of PO2. O2-saturation and content, PCO2, pH, glucose, lactate, pyruvate, potassium, myoglobin, creatine kinase (CK), its isoenzyme MB and aspartate aminotransferase (ASAT) simultaneously in arterial and coronary sinus blood before cardioplegia and during the first 60 min after the release of aortic cross-clamping. In addition, myoglobin and enzymes were followed in peripheral venous blood for 72 hours after cardioplegia. Analysis of the results revealed no striking difference between the groups. Nevertheless, with the addition of mannitol, there was a slightly lower release of lactate and myoglobin probably indicating a more rapid metabolic recovery of the myocardium.

The effect of fasting on plasma cyclic adenosine-3', 5'-monophosphate in rheumatoid arthritis.

Cyclic adenosine-3', 5'-monophosphate (cAMP) may influence important mechanisms in the inflammatory process, and fasting has been claimed to be clinically beneficial in rheumatoid arthritis (RA). A study was therefore designed to measure the concentrations of plasma cAMP in RA patients not undergoing drug treatment during a control and a fasting period. Twelve female RA patients were hospitalized for two 14-day periods and investigated in a crossover study. Clinical and laboratory variables of inflammatory activity were assessed during both periods. During the control period the concentrations of cAMP in plasma were slightly below the lower normal limit, with no significant change throughout the period. The clinical and laboratory variables of inflammatory activity were unchanged during the same period. In the fasting period, the prefasting level of plasma cAMP was significantly higher than on the corresponding day in the control period. During 7 days of total fasting the plasma cAMP concentrations decreased significantly. The clinical and laboratory variables of inflammatory activity decreased significantly from the start to the end of fasting. High prefasting plasma cAMP concentrations were associated with improvement in clinical inflammatory activity. A decrease in plasma cAMP concentrations during fasting in RA patients is in contrast to the findings in obese and healthy subjects previously reported.

CK-MB in serum and in heart and skeletal muscles in patients subjected to mitral valve replacement.

Serum catalytic concentrations of total creatine kinase (CK) and its more heart-specific isoenzyme CK-MB were studied in 25 consecutive patients subjected to isolated mitral valve replacement (Björk--Shiley prosthesis). Heart and skeletal muscle CK and CK-MB content was determined in 10 cases. The postoperative serum levels did not reflect differences in myocardial CK-MB content between patients. CK-MB as a percentage of total CK at peak serum CK-MB (16 +/- 1%) (mean +/- SEM) was of similar order as the percentage of CK-MB in the myocardium (papillary muscle 20.9 +/- 1.3%, right auricle 18.2 +/- 0.5%). A small proportion of CK-MB was present in all skeletal muscle samples examined (diaphragm 4.2 +/- 0.6%, rectus abdominis 0.4 +/- 0.1%), indicating that the total CK level should also be taken into account in attempts to determine the origin of a raised postoperative serum CK-MB activity. The degree of postoperative CK-MB elevation was related to the duration of operation and of aortic cross-clamping. Perioperative myocardial infarction occurred in one patient, and serum CK-MB kinetics in this patient, with a biphasic enzyme curve, differed from those in the other patients.

Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following hypothermic cardioplegia.

Cardiac metabolism following hypothermic potassium cardioplegia was studied in 23 patients undergoing isolated aortic valve replacement. All had normal coronary arteries. Cardioplegia was induced by infusing 700-1 000 ml of cold Ringer's acetate containing 20 mekv K+ selectively into the left coronary artery. Simultaneous blood samples were taken from the radial artery, a central vein and from the coronary sinus before and after cardioplegia. The PO2, O2-saturation and content, PCO2, pH, lactate, glucose, potassium, myoglobin, total creatine kinase (CK), its isoenzyme CK-MB, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were assessed. Before bypass lactate was extracted by the heart. During the initial 10 to 20 min after cardioplegia there was a marked release of lactate in the coronary sinus. Myoglobin concentration and CK-MB serum activity peaked during the first 4 hours after the release of the aortic cross-clamping. In order to determine the best indicator of myocardial damage after cardioplegia, duration of extracorporeal circulation (ECC-time), aortic occlusion time (AOT), mean myocardial temperature (MMT) and the product of AOT and MMT, referred to as time-temperature area (TTA), were related to possible indicators of myocardial injury, such as enzyme and myoglobin release. The TTA was the best way of expressing the degree of exposure of the heart to ischaemia. The CK-MB to peak area (CK-MB max area) was the best indicator of the degree of ischaemic injury sustained by the heart during operation.

Serum enzymes with special reference to CK-MB following coronary bypass surgery.

In a consecutive series of 25 coronary bypass operations, the postoperative serum activity levels of total creatine kinase (CK) and its more heart-specific isoenzyme CK-MB were examined and related to the levels of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and thermostable lactate dehydrogenase (LD-T), to electrocardiographic (ECG) findings and to surgical characteristics. Detectable CK-MB activity was found in all patients, usually appearing while the operation was still in progress. Peak CK-MB occurred earlier than peak total CK. There was no ECG evidence of myocardial infarction in any patient. The degree of postoperative CK-MB elevation, however, correlated to the duration of extracorporeal circulation (ECC) and aortic cross-clamping (AC). After 120 min of ECC and 70 min of AC, release of CK-MB, as well as of the other enzymes studied, increased considerably. There was a significant correlation between high CK-MB activity and high early postoperative activities of total CK, ASAT and LD-T. When CK-MB determinations are not available, ASAT is preferable to total CK or LD-T in the early evaluation of operative myocardial injury. From the fourth postoperative day, only LD-T is informative in this respect; a second rise of ASAT and ALAT is probably of hepatic origin.

Serum CK-MB kinetics in acute myocardial infarction and after coronary bypass operations.

Serum creatine kinase (CK) isoenzyme MB and total CK activity concentrations in 11 patients with acute myocardial infarction (AMI) were compared with the corresponding enzyme activities in 25 patients after coronary bypass surgery, not complicated clinically by AMI. Peak CK-MB occurred 2 +/- 0 (mean +/- SEM) hours after the end of surgery (mean duration of operation 6 hours), but 17 +/- 1 hours from the onset of symptoms in AMI. The plasma half"life for CK-MB was 11 +/- 1 hours under both conditions. Peak total CK was found after about 20 hours in both series of patients. Total CK half-life was 17 +/- 2 hours in AMI, but 30 +/- 3 hours following surgery. CK kinetics were thus different in these two situations, indicating different mechanisms for the elevations of serum CK-MB activity. In conclusion, the time course for the transient CK-MB elevation following bypass surgery should be considered in the diagnosis of peri operative infarction.

Myoglobin, creatine kinase and its isoenzyme MB in serum after acute myocardial infarction.

Serum creatine kinase, creatine kinase MB and myoglobin were determined in patients suffering from acute myocardial infarction (AMI) with shorter duration of symptoms than 6 h. At admission 83% had increased concentrations of myoglobin while 28% had creatine-kinase value above the reference limit. After onset of symptoms peak levels were found after 9.4 h (myoglobin) and 23.0 h (creatine kinase). Maximal levels of myoglobin and creatine kinase divided by upper reference limits correlated and were approximately of the same sensitivity. Compared to myoglobin, there was no difference in behavior between creatine kinase and its isoenzyme. In conclusion the study demonstrates myoglobin to be an early and sensitive indication of AMI.