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Creatine kinase is associated with bleeding after myocardial infarction.
Brewster, LM, Fernand, J
Open heart. 2020;(2)
Abstract
BACKGROUND The ADP-scavenging enzyme creatine kinase (CK) is reported to reduce ADP-dependent platelet activation. Therefore, we studied whether highly elevated CK after ST-elevation myocardial infarction (STEMI) is associated with bleeding. METHODS Data of the Thrombolysis in Myocardial Infarction Study Group phase II trial on the efficacy of angioplasty, following intravenous recombinant tissue-type plasminogen activator (rt-PA), are used to assess whether peak plasma CK (CKmax) is independently associated with adjudicated fatal or non-fatal bleeding (primary) and combined bleeding/all-cause mortality (secondary) in multivariable binomial logistic regression analysis, adjusting for baseline and treatment allocation covariates. RESULTS The included patients (n=3339, 82% men, 88% white, mean age 57 years, SE 0.2) had a history of angina pectoris (55%), hypertension (38%) and/or diabetes mellitus (13%). CKmax ranged from 16 to 55 890 IU/L (mean 2389 IU/L, SE 41), reached within 8 hours in 51% of the patients (93% within 24 hours). Adjudicated fatal/non-fatal bleeding occurred in 30% of the patients (respectively 26% in the low vs 34% in the high CK tertile), and bleeding/all-cause mortality in 35% (29% in the low vs 40% in the high CK tertile). In multivariable regression analysis, the adjusted OR for fatal/non-fatal bleeding (vs not bleeding and survival) was 2.6 (95% CI 1.8 to 3.7)/log CKmax increase, and 3.1 (2.2 to 4.4) for bleeding/all-cause mortality. CONCLUSION Highly elevated plasma CK after myocardial infarction might be an independent predictor of bleeding and haemorrhagic death. This biologically plausible association warrants further prospective study of the potential role of extracellular CK in ADP-dependent platelet activation and bleeding.
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Three-dimensional mapping of the creatine kinase enzyme reaction rate in muscles of the lower leg.
Parasoglou, P, Xia, D, Chang, G, Convit, A, Regatte, RR
NMR in biomedicine. 2013;(9):1142-51
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Abstract
Phosphorus ((31) P) magnetization transfer (MT) techniques enable the non-invasive measurement of metabolic turnover rates of important enzyme-catalyzed reactions, such as the creatine kinase reaction (CK), a major transducing reaction involving adenosine triphosphate and phosphocreatine. Alteration in the kinetics of the CK reaction rate appears to play a central role in many disease states. In this study, we developed and implemented at ultra-high field (7T) a novel three-dimensional (31) P-MT imaging sequence that maps the kinetics of CK in the entire volume of the lower leg at relatively high resolution (0.52 mL voxel size), and within acquisition times that can be tolerated by patients (below 60 min). We tested the sequence on five healthy and two clinically diagnosed type 2 diabetic subjects. Overall, we obtained measurements that are in close agreement with measurements reported previously using spectroscopic methods. Importantly, our spatially resolved method allowed us to measure local CK reaction rate constants and metabolic fluxes in individual muscles in a non-invasive manner. Furthermore, it allowed us to detect variations of the CK rates of different muscles, which would not have been possible using unlocalized MRS methods. The results of this work suggest that 3D mapping of the CK reaction rates and metabolic fluxes can be achieved in the skeletal muscle in vivo at relatively high spatial resolution and with acquisition times well tolerated by patients. The ability to measure bioenergetics simultaneously in large areas of muscles will bring new insights into possible heterogeneous patterns of muscle metabolism associated with several diseases and serve as a valuable tool for monitoring the efficacy of interventions.
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Effects of a hybrid exercise on the activities of myogenic enzymes in plasma.
Matsuse, H, Shiba, N, Umezu, Y, Nago, T, Maeda, T, Tagawa, Y, Matsuo, S, Nagata, K, Basford, JR
The Kurume medical journal. 2006;(3-4):47-51
Abstract
"Hybrid" exercise uses forces generated by an electrically stimulated muscle to resist the motion of a volitionally contracting agonist. This approach is effective in increasing muscle bulk and strength. Its safety, however, has not been studied and the purpose of this study was to address this lack by assessing the impact of a hybrid strengthening regimen on the serological markers of exercise associated muscle damage. Twelve healthy, sedentary men between the ages of 20 and 27 years were divided into two groups of 6. The members of each group completed an exercise session that consisted of 10 sets of 10 reciprocal elbow flexor and extensor contractions separated by 1-minute rest intervals. In one group, the subjects underwent a hybrid exercise protocol. Subjects in the second group underwent a conventional isometric electrical stimulation program with the same stimulation intensities. Plasma creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activities were determined immediately before and after the exercise session as well as at follow-up 1, 2, and 7 days later. Secondary variables included active and passive range of motion and the subjects' perceived levels of "soreness" . Evaluation revealed that neither enzymatic activities nor range of motion changed in a statistically significant manner with time within the groups or between the groups. In conclusion, the stimulation intensities involved in hybrid exercise programs of the upper extremity do not appear to be associated with either overt or covert signs of muscle injury.
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The creatine kinase system in human skin: protective effects of creatine against oxidative and UV damage in vitro and in vivo.
Lenz, H, Schmidt, M, Welge, V, Schlattner, U, Wallimann, T, Elsässer, HP, Wittern, KP, Wenck, H, Stäb, F, Blatt, T
The Journal of investigative dermatology. 2005;(2):443-52
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Abstract
Cutaneous aging is characterized by a decline in cellular energy metabolism, which is mainly caused by detrimental changes in mitochondrial function. The processes involved seem to be predominantly mediated by free radicals known to be generated by exogenous noxes, e.g., solar ultraviolet (UV) radiation. Basically, skin cells try to compensate any loss of mitochondrial energetic capacity by extra-mitochondrial pathways such as glycolysis or the creatine kinase (CK) system. Recent studies reported the presence of cytosolic and mitochondrial isoenzymes of CK, as well as a creatine transporter in human skin. In this study, we analyzed the cutaneous CK system, focusing on those cellular stressors known to play an important role in the process of skin aging. According to our results, a stress-induced decline in mitochondrial energy supply in human epidermal cells correlated with a decrease in mitochondrial CK activity. In addition, we investigated the effects of creatine supplementation on human epidermal cells as a potential mechanism to reinforce the endogenous energy supply in skin. Exogenous creatine was taken up by keratinocytes and increased CK activity, mitochondrial function and protected against free oxygen radical stress. Finally, our new data clearly indicate that human skin cells that are energetically recharged with the naturally occurring energy precursor, creatine, are markedly protected against a variety of cellular stress conditions, like oxidative and UV damage in vitro and in vivo. This may have further implications in modulating processes, which are involved in premature skin aging and skin damage.
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American ginseng supplementation attenuates creatine kinase level induced by submaximal exercise in human beings.
Hsu, CC, Ho, MC, Lin, LC, Su, B, Hsu, MC
World journal of gastroenterology. 2005;(34):5327-31
Abstract
AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance. METHODS Thirteen physically active male college students were divided into two groups (AG or placebo) and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk. They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover, the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise, immediately after exercise, and 20, 40, 60, and 120 min after exercise. RESULTS The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen. CONCLUSION Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.
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Relationship of irreversible myocardial injury to troponin I and creatine kinase-MB elevation after coronary artery bypass surgery: insights from cardiovascular magnetic resonance imaging.
Selvanayagam, JB, Pigott, D, Balacumaraswami, L, Petersen, SE, Neubauer, S, Taggart, DP
Journal of the American College of Cardiology. 2005;(4):629-31
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Functional coupling of adenine nucleotide translocase and mitochondrial creatine kinase is enhanced after exercise training in lung transplant skeletal muscle.
Guerrero, K, Wuyam, B, Mezin, P, Vivodtzev, I, Vendelin, M, Borel, JC, Hacini, R, Chavanon, O, Imbeaud, S, Saks, V, et al
American journal of physiology. Regulatory, integrative and comparative physiology. 2005;(4):R1144-54
Abstract
Mechanisms responsible for limitation of exercise capacity in lung transplant recipients (LR) and benefits gained by exercise training were studied. Mitochondrial respiration parameters, energy transfer, and cell structure were assessed in vastus lateralis biopsies using the permeabilized fiber technique with histochemical and morphometric measurements. Twelve male controls (C) and 12 LR performed exercise training over 12 wk. Before exercise training, there were strong correlations between exercise capacity (maximal O(2) consumption and endurance time at 70% maximal power output) and cellular events, as assessed by percentage of type I fibers and apparent K(m) for exogenous ADP. Anticalcineurins were not involved in LR exercise limitation, since there were no differences in maximal mitochondrial rate of respiration before exercise training and no abnormalities in respiratory chain complexes compared with C. Training resulted in a significant increase in physiological parameters both at the cellular (apparent K(m) for exogenous ADP and stimulating effect of creatine) and integrated (maximal O(2) consumption, power output at ventilatory threshold, maximal power output, and endurance time at 70% maximal power output) levels in LR and C. After the training period, improvements in maximal O(2) consumption and in maximal mitochondrial rate of respiration were noted, as well as changes in endurance time and percentage of type I fibers. Because there were no changes in diameters and fiber types, baseline alteration of apparent K(m) for exogenous ADP and its improvement after training might be related to changes within the intracellular energetic units. After the training period, intracellular energetic units exhibited a higher control of mitochondrial respiration by creatine linked to a more efficient functional coupling adenine nucleotide translocase-mitochondrial creatine kinase, resulting in better exercise performances in C and LR.
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Increased creatine kinase MB level predicts postoperative mortality after cardiac surgery independent of new Q waves.
Ramsay, J, Shernan, S, Fitch, J, Finnegan, P, Todaro, T, Filloon, T, Nussmeier, NA
The Journal of thoracic and cardiovascular surgery. 2005;(2):300-6
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Abstract
BACKGROUND Recent consensus statements recommend cardiac enzyme release as the essential criterion for diagnosing myocardial infarction. However, the outcome implications of cardiac enzyme release in patients undergoing coronary artery bypass grafting are controversial. METHODS Eight hundred patients were followed for 30 days after elective on-pump coronary artery bypass grafting in a multicenter, prospective, randomized trial of the anti-C5 complement antibody pexelizumab. Data from centralized electrocardiography and creatine kinase MB analyses were examined for any association with death or severe left ventricular dysfunction. RESULTS More than half of the 800 patients had peak creatine kinase MB levels of more than 5 times the upper limit of 5 ng/mL set by the core laboratory. The median peak value was 29 ng/mL. The incidence of the combined outcome (death or severe left ventricular dysfunction) was 1.7% if the peak creatine kinase MB level was less than 25 ng/mL and 18.0% if 100 ng/mL or greater (P < .01). Similarly, the incidence of new Q-wave myocardial infarction was 3.9% if the peak creatine kinase MB level was less than 25 ng/mL and 30.6% if 100 ng/mL or greater (P < .01). In a multivariate analysis that included preoperative and intraoperative factors, as well as peak enzyme release and Q-wave myocardial infarction, the strongest predictor of the combined outcome was a peak creatine kinase MB level of 100 ng/mL or greater. New Q-wave myocardial infarction did not significantly predict the combined outcome. CONCLUSIONS Increased postoperative peak creatine kinase MB level, especially when 20 times or more of the upper limit of normal, indicates increased risk of severe postoperative left ventricular dysfunction and mortality within 30 days of coronary artery bypass grafting. High peak enzyme level is a stronger predictor of adverse outcomes than is postoperative Q-wave myocardial infarction in this population.
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Differential mortality risk of postprocedural creatine kinase-MB elevation following successful versus unsuccessful stent procedures.
Jeremias, A, Baim, DS, Ho, KK, Chauhan, M, Carrozza, JP, Cohen, DJ, Popma, JJ, Kuntz, RE, Cutlip, DE
Journal of the American College of Cardiology. 2004;(6):1210-4
Abstract
OBJECTIVES This study was designed to evaluate the effect of periprocedural myocardial infarction (MI) on mortality according to success of the stent procedure. BACKGROUND The mortality effect of periprocedural MI relative to successful versus unsuccessful procedures has not been examined. METHODS All-cause mortality during the first year was evaluated prospectively among 5,850 patients from coronary stent clinical trials. Myocardial infarction was classified according to creatine kinase-MB level as type 1 (>1 but <3 times normal), type 2 (>or=3 but 8 times normal or Q-wave MI). Procedures were classified as successful unless there was a final diameter stenosis >50%; final Thrombolysis In Myocardial Infarction flow grade <3; final National Heart, Lung, and Blood Institute dissection grade >or=D; repeat revascularization within 24 h; or stent thrombosis within 24 h. RESULTS Myocardial infarction was more frequent after unsuccessful procedures (69.6% vs. 20.4%, p < 0.001). Mortality during the first year was higher in patients with MI (2.8% vs. 1.7%, p = 0.01), but the effect was significant only for type 3 MI (4.7% vs. 1.7%, p = 0.008). Moreover, the mortality difference for any MI was confined to patients with unsuccessful procedures (13.1% vs. 0%, p = 0.03), with no significant effect among patients with otherwise successful procedures (2.1% vs. 1.7%, p > 0.20). The independent predictors of mortality were unsuccessful procedure (p < 0.001), diabetes mellitus (p = 0.001), history of prior MI (p = 0.003), multivessel disease (p = 0.006), and advancing age (p < 0.001), but not periprocedural MI. CONCLUSIONS The association of periprocedural MI with increased mortality during the first year following stent placement was confined to patients with unsuccessful procedures.
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Creatine kinase-MB elevation after percutaneous coronary intervention predicts adverse outcomes in patients with acute coronary syndromes.
Roe, MT, Mahaffey, KW, Kilaru, R, Alexander, JH, Akkerhuis, KM, Simoons, ML, Harrington, RA, Tardiff, BE, Granger, CB, Ohman, EM, et al
European heart journal. 2004;(4):313-21
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Abstract
AIM: To study the relationship between outcomes and peak creatine kinase (CK)-MB levels after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). METHODS AND RESULTS Peak CK-MB ratios (peak CK-MB level/upper limit of normal [ULN]) after PCI were analysed in 6164 patients with NSTE ACS from four randomized trials who underwent in-hospital PCI. We excluded 696 patients with elevated CK or CK-MB levels <24h before PCI; the primary analysis included 2384 of the remaining 5468 patients (43.6%) with CK-MB levels measured <==24h after PCI. The incidence of in-hospital heart failure (0.1%, 0.8%, 3.4%, 4.1%, and 6.1%; P<0.001), arrhythmias (0.8%, 1.9%, 6.9%, 4.1%, and 7.9%; P<0.001), cardiogenic shock (0.1%, 1.3%, 2.0%, 2.3%, and 2.6%; P=0.004), and mortality through 6 months (2.1%, 2.4%, 4.9%, 4.1%, and 5.7%, P=0.005) was increased with peak CK-MB ratios of 0-1, 1-3, 3-5, 5-10, and >10xULN, respectively. The continuous peak CK-MB ratio after PCI significantly predicted adjusted 6-month mortality (risk ratio, 1.06 per unit increase above ULN; 95% confidence interval, 1.01-1.11; P=0.017). CONCLUSIONS Greater CK-MB elevation after PCI is independently associated with adverse outcomes in NSTE ACS. These results underscore the adverse implications of elevated CK-MB levels after PCI in this high-risk population.