Slowly Progressive Rhabdomyolysis Post COVID-19: Insights for Acute Kidney Injury Prediction With Discordant Creatine Kinase and Myoglobin Elevations.

Rhabdomyolysis can lead to acute kidney injury (AKI), primarily due to myoglobin-induced tubular damage. We present a case of slowly progressive rhabdomyolysis following SARS-CoV-2 infection in a 28-year-old male who was monitored through serial serum creatine kinase (CK) and myoglobin levels. Despite prominent CK elevations, the patient did not develop AKI, probably due to disproportionately mild serum myoglobin elevation with distinctive cyclic spikes. This case underscores the informative value of frequent monitoring of both CK and myoglobin to assess muscle damage severity and AKI risk in rhabdomyolysis, particularly with viral infections like COVID-19 that can cause delayed-onset muscle injury.

Asymptomatic COVID-19 Infection-Induced Rhabdomyolysis in the Backdrop of Statin-Cyclosporine Drug Interaction.

Rhabdomyolysis involves skeletal muscle breakdown leading to high serum creatine kinase (CK) levels and myoglobinuria. Here, we report the case of a middle-aged man who developed rhabdomyolysis, resulting in acute kidney injury (AKI) over pre-existing chronic kidney disease (stage 3a) secondary to focal segmental glomerulosclerosis (primary FSGS), during an asymptomatic COVID-19 infection. The patient had been on treatment with cyclosporine and statin, among other drugs, for his comorbidities. He had initially presented to the hospital after a fall due to difficulty walking in the setting of increasing edema. Lab workup revealed elevated CK and AKI. Urinalysis showed "large" blood on a dipstick with only two RBCs per high-power field on microscopy, suggesting myoglobinuria. A standard respiratory pathogen polymerase chain reaction panel revealed positive SARS-CoV-2. The chest X-ray and oxygenation were normal, and he had no respiratory symptoms. He was treated with intravenous fluids and albumin, with a steady improvement in renal function. Our case underlines that rhabdomyolysis can occur in asymptomatic COVID-19 infection. Therefore, it may be worth monitoring CK levels in COVID-19-positive patients with risk factors for rhabdomyolysis, such as the concurrent usage of statins and cyclosporine, even if they are otherwise asymptomatic.

Comparison of Different Animal Models in Hindlimb Functional Recovery after Acute Limb Ischemia-Reperfusion Injury.

Acute limb ischemia (ALI) is a sudden lack of blood flow to a limb, primarily caused by arterial embolism and thrombosis. Various experimental animal models, including non-invasive and invasive methods, have been developed and successfully used to induce limb ischemia-reperfusion injuries (L-IRI). However, there is no consensus on the methodologies used in animal models for L-IRI, particularly regarding the assessment of functional recovery. The present study aims to compare different approaches that induce L-IRI and determine the optimal animal model to study functional limb recovery. In this study, we applied a pneumatic cuff as a non-invasive method and ligated the aorta, iliac, or femoral artery as invasive methods to induce L-IRI. We have measured grip strength, motor function, creatine kinase level, inflammatory markers such as nuclear factor NF-κB, interleukin-6 (IL-6), hypoxia markers such as hypoxia-induced factor-1α (HIF-1α), and evaluated the muscle injury with hematoxylin and eosin (H&E) staining in Sprague Dawley rats after inducing L-IRI. The pneumatic pressure cuff method significantly decreased the muscle strength of the rats, causing the loss of ability to hold the grid and inducing significant limb function impairment, while artery ligations did not. We conclude from this study that the tourniquet cuff method could be ideal for studying functional recovery after L-IRI in the rat model.

Assessment of the role of N-terminal pro-B-type natriuretic peptide as a predictive biomarker of mortality in acute aluminum phosphide poisoning.

BACKGROUND: In Egypt, aluminum phosphide (ALP) is a known lethal poison due to its cardiotoxicity. This study aimed to evaluate the predictive ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality in ALP-poisoned patients. METHODS: This prospective study was conducted on patients with ALP poisoning admitted to the Poison Control Center Ain Shams University Hospitals between July and December 2022. Upon admission, all patients were followed up and had their levels of NT-proBNP, troponin I (cTnI), and creatine kinase myocardial band (CK-MB) analyzed. RESULTS: Thirty patients were enrolled in the study and were divided into survivors and non-survivors. The initial NT-proBNP levels were significantly higher among non-survivors in contrast to the initial cTnI and CK-MB levels. The study identified that the best cutoff point of NT-proBNP for predicting mortality was ≥72 pg/ml, with AUC (0.869). CONCLUSION: It can be concluded that NT-proBNP can serve as an early predictor of mortality in ALP poisoning.

Effect of creatine administration on locomotor activity and stress response in olive flounder (Paralichthys olivaceus).

The creatine kinase system is crucial for maintaining cellular energy homeostasis and plays a role in regulating locomotor behavior in organisms, but its significance in the regulating the motionless behavior in olive flounder is limited. In the first experiment of this study, elevated levels of creatine kinase (CK) activity in the spinal cord were detected in the juvenile group (JG) flounder compared to the adult group (AG) flounder. In the second experiment, to further confirm the involvement of CK in the locomotor behavior, the adult flounder was given an intraperitoneal injection of creatine (150 mg/kg), while the flounder in the control group received a saline solution. After one week post-injection, the behavioral analysis revealed that the flounder in the creatine-treated group displayed higher levels of locomotor activity and a greater number of escape attempts in response to external stimuli when compared to the control group. However, the acute stress response, induced by intraperitoneal injection and characterized by tail beating, was significantly alleviated in the flounder in the creatine-treated group. Additionally, there was an upregulation of the UII and AchR genes in the spinal cord, as well as increased levels of UII and AchR in the muscle tissues of the creatine-treated flounder. However, a reduction in UI mRNA levels was observed in the brain of the flounder. Collectively, our data provide the evidence that the elevated enzyme activity and gene expression of creatine kinase play important roles in off-bottom swimming behavior in the JG flounder. Furthermore, administration of creatine improved the locomotor activity and alleviated the stress response in flounder, which is associated with regulation of the locomotor- and stress-related gene in the brain, spinal cord, and muscle.

Rare skin color changes in an acute pancreatitis patient undergoing maintenance hemodialysis.

BACKGROUND: Skin conditions are common in patients on maintenance hemodialysis and those with pancreatitis. However, there is a lack of research on dermatological issues in patients who have both hemodialysis and pancreatitis concurrently. CASE PRESENTATION: A 62-year-old male patient with a 4-year history of maintenance hemodialysis (MHD) presented with pain and was diagnosed with acute pancreatitis and gallbladder stones. Markedly elevated blood amylase, creatine kinase, and myoglobin were noted, alongside a purplish-red skin discoloration. Treatment included inhibition of digestive fluid secretion, anti-infection measures, blood purification, fasting, rehydration, and symptomatic care. Notably, continuous renal replacement therapy (CRRT) combined with hemoperfusion (HP) was employed. The patient's dialysis effluent initially appeared red. Upon examination of the patient's peripheral blood smear, red blood cell debris was not observed. The dialysis effluent (on Day 0) was analyzed, revealing no hemoglobin (0 g/L) but an elevated myoglobin concentration of 80.4 U/L. After the therapeutic intervention, the indicators, including the blood amylase, C-reactive protein, total bilirubin, creatine kinase, and myoglobin were improved. The patient experienced resolution of sternal and upper abdominal pain within two days. After four consecutive days of CRRT and HP treatment, the skin color returned to normal, alongside improved clarity of the dialysis effluent. Subsequently, the patient's method of blood purification was reverted to conventional hemodialysis. On the eighth day of hospitalization, the patient resumed normal diet and was discharged. CONCLUSIONS: In the case of the current patient with acute pancreatitis undergoing MHD, it is noteworthy to report the observation of a unique purplish-red skin discoloration. This phenomenon may be attributable to inflammation resulting from acute pancreatitis, and the retention of myoglobin within the body.

Contribution of medical resonance imaging in the return to physical activity after exertional rhabdomyolysis a case report.

INTRODUCTION: Exertional rhabdomyolysis (ER) is the breakdown of muscle cells that occurs after intensive physical activity. Although a cautious and gradual return to physical activity (RTPA) is recommended after an episode of ER, physical sequelae are reported long afterwards. CASE REPORT: We present the case of a 31-year-old untrained amateur runner with no prior medical history who developed heat stroke, ER, and acute kidney failure on the occasion of a half-marathon. Three months later, whereas the patient was symptom-free and CK levels were normal, an MRI revealed typical signs of rhabdomyolysis, which normalized thereafter. DISCUSSION: Given that clinical and biological data inform RTPA decisions, the delay between clinical biological and MRI normalization may cause an RTPA to be initiated prior to full muscle recovery, which could account for the symptoms' prolonged persistence. In sportspeople who have recovered and their CK blood levels are returned to normal, MRI data could defer the RTPA if MRI abnormalities persist or, conversely, give it the green light.

In the event of exertional rhabdomyolysis following a race, the presence of muscular lesions on MRI, even if the patient feels healed and creatine kinase levels have returned to normal, should postpone the return to physical activity.

MDMA("Ecstasy") abuse leading to delayed onset rhabdomyolysis: A case report and literature review.

MDMA and cocaine can result in acute onset rhabdomyolysis. However, delayed onset rhabdomyolysis and its pathophysiology is of concern Early therapeutic intervention improves prognosis. Such cases should be promptly referred and managed in centers equipped with critical care and renal replacement therapy.

Cardiac function and energetics in mice with combined genetic augmentation of creatine and creatine kinase activity.

Improving energy provision in the failing heart by augmenting the creatine kinase (CK) system is a desirable therapeutic target. However, over-expression of the creatine transporter (CrT-OE) has shown that very high creatine levels result in cardiac hypertrophy and dysfunction. We hypothesise this is due to insufficient endogenous CK activity to maintain thermodynamically favourable metabolite ratios. If correct, then double transgenic mice (dTg) overexpressing both CrT and the muscle isoform of CK (CKM-OE) would rescue the adverse phenotype. In Study 1, overexpressing lines were crossed and cardiac function assessed by invasive haemodynamics and echocardiography. This demonstrated that CKM-OE was safe, but too few hearts had creatine in the toxic range. In Study 2, a novel CrT-OE line was generated with higher, homogeneous, creatine levels and phenotyped as before. Myocardial creatine was 4-fold higher in CrT-OE and dTg hearts compared to wildtype and was associated with hypertrophy and contractile dysfunction. The inability of dTg hearts to rescue this phenotype was attributed to downregulation of CK activity, as occurs in the failing heart. Nevertheless, combining both studies in a linear regression analysis suggests a modest positive effect of CKM over a range of creatine concentrations. In conclusion, we confirm that moderate elevation of creatine is well tolerated, but very high levels are detrimental. Correlation analysis lends support to the theory that this may be a consequence of limited CK activity. Future studies should focus on preventing CKM downregulation to unlock the potential synergy of augmenting both creatine and CK in the heart.

Rhabdomyolysis-related acute kidney injury in patients with COVID-19.

BACKGROUND: Viral and bacterial infections may be complicated by rhabdomyolysis, which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnormalities to life-threatening conditions such as renal failure. Direct viral injury as well as inflammatory responses may cause rhabdomyolysis in the course of coronavirus disease 2019 (COVID-19). When presented with acute kidney injury (AKI), rhabdomyolysis may be related to higher morbidity and mortality. AIM: To compare rhabdomyolysis-related AKI with other AKIs during COVID-19. METHODS: A total of 115 patients with COVID-19 who had AKI were evaluated retrospectively. Fifteen patients had a definite diagnosis of rhabdomyolysis (i.e., creatine kinase levels increased to > 5 times the upper normal range with a concomitant increase in transaminases and lactate dehydrogenase). These patients were aged 61.0 ± 19.1 years and their baseline creatinine levels were 0.87 ± 0.13 mg/dL. Patients were treated according to national COVID-19 treatment guidelines. They were compared with patients with COVID-19 who had AKI due to other reasons. RESULTS: For patients with rhabdomyolysis, creatinine reached 2.47 ± 1.17 mg/dL during follow-up in hospital. Of these patients, 13.3% had AKI upon hospital admission, and 86.4% developed AKI during hospital follow-up. Their peak C-reactive protein reached as high as 253.2 ± 80.6 mg/L and was higher than in patients with AKI due to other reasons (P < 0.01). Peak ferritin and procalcitonin levels were also higher for patients with rhabdomyolysis (P = 0.02 and P = 0.002, respectively). The mortality of patients with rhabdomyolysis was calculated as 73.3%, which was higher than in other patients with AKI (18.1%) (P = 0.001). CONCLUSION: Rhabdomyolysis was present in 13.0% of the patients who had AKI during COVID-19 infection. Rhabdomyolysis-related AKI is more proinflammatory and has a more mortal clinical course.

Significance of detecting cardiac troponin I and creatine kinase MB in critically Ill children without primary cardiac illness.

Objective: To investigate the incidence of myocardial injury in children with critically ill children without primary cardiac disease and the association between elevated cardiac troponin I (cTnl) and creatine kinase MB (CK-MB) concentrations and disease progression and prognosis to guide early treatment. Methods: The serum cTnI and CK-MB concentrations of 292 children with critically ill children without primary cardiac disease in Yantai Yuhuangding Hospital between January 2021 and January 2024 were retrospectively analyzed within 24 h after entering the Pediatric Intensive Care Unit (PICU). The children were divided into normal and abnormal groups according to the myocardial marker results. The abnormal group was further divided into the cTnI-elevated, CK-MB-elevated, single-elevated (cTnI- or CK-MB-elevated) and double-elevated (cTnI- and CK-MB-elevated) groups. The differences in the clinical indicators and their relationships with prognosis for the groups were compared. Results: The incidence of myocardial injury among the critically ill children without primary cardiac disease was 55.1%. The incidence of myocardial injury in children with infectious diarrhea combined with moderate and severe dehydration reached 85.19%. The pediatric critical illness score; frequency of use of vasoactive drugs; hypotension, shock, heart failure, respiratory failure, and multiple organ dysfunction syndrome; and mortality indexes differed significantly for the normal and abnormal myocardial marker groups (P < 0.05). The single-elevated and normal groups only showed a difference in mortality (P < 0.017). The cTnI and CK-MB concentrations were negatively correlated with prognosis (P < 0.01). Conclusion: Myocardial injury, as evidenced by elevated cardiac biomarkers, is common in critically ill children without primary cardiac illness. cTnI and CK-MB are associated with outcomes. Shock, heart failure, and multiple organ dysfunction syndromes are independently associated with simultaneous elevations of CK-MB and cTnI concentrations. Further prospective studies are needed to elucidate the clinical utility of these biomarkers.

Almond Consumption Modestly Improves Pain Ratings, Muscle Force Production, and Biochemical Markers of Muscle Damage Following Downhill Running in Mildly Overweight, Middle-Aged Adults: A Randomized, Crossover Trial.

Background: Almonds promote cardiometabolic health benefits; however, the ergogenic effect of almond supplementation on exercise recovery is less explored. Objectives: We evaluated the impacts of raw, shelled, almonds on pain, muscle force production, and biochemical indices of muscle damage and inflammation during recovery from eccentrically biased exercise. Methods: Using a randomized, crossover design, 26 healthy adults (37 ± 6 y) ran downhill (-10%) for 30 min at a heart rate corresponding to 65%-70% of maximal oxygen consumption followed by 3-d recovery periods after 8-wk adaptations to either ALMOND (2 oz/d) or isocaloric pretzel (CONTROL) feedings. Volunteers consumed the study food immediately following the run and each day during recovery. Fasted blood samples were collected, and pain and muscle function were tested before the downhill run and over 72 h of recovery. Results: Downhill running elicited moderate muscle damage (Time: P < 0.001; η2 = 0.395) with creatine kinase (CK) peaking after 24 h (CONTROL: Δ + 180% from baseline compared with ALMOND: Δ + 171% from baseline). CK was reduced after 72 h in ALMOND (Δ - 50% from peak; P < 0.05) but not CONTROL (Δ - 33% from peak; P > 0.05). Maximal torque at 120°/s of flexion was greater (Trial: P = 0.004; η2 = 0.315) in ALMOND compared with CONTROL at 24 h (Δ + 12% between trials; P < 0.05) and 72 h (Δ + 9% between trials; P < 0.05) timepoints. Pain during maximal contraction was lower (Trial: P < 0.026; η2 = 0.225) in ALMOND compared with CONTROL after 24 h (Δ - 37% between trials; P < 0.05) and 48 h (Δ - 33% between trials; P < 0.05). No differences (P > 0.05) in vertical jump force, C-reactive protein concentrations, myoglobin concentrations, and total antioxidant capacity were observed between trials. Conclusions: This study demonstrates that 2.0 oz/d of almonds modestly reduces pain, better maintains muscle strength, and reduces the CK response to eccentric-based exercise. This apparent effect of almond ingestion on exercise recovery has the potential to promote increased exercise adherence, which should be investigated in future studies.This trial was registered at the clinicaltrials.gov as NCT04787718.

Creatine Kinase Surge: Levetiracetam-Induced Rhabdomyolysis.

Rhabdomyolysis is the breakdown of muscle cells secondary to both traumatic and non-traumatic causes. The lysing of the muscle cells can lead to the release of cell contents that can lead to acute injury and other life-threatening conditions. Levetiracetam is an anticonvulsant commonly used in generalized and partial tonic-clonic seizures. Well-known side effects include agitation, depression, anxiety, irritability, rash, and somnolence; however, there are an increasing number of case reports that report rhabdomyolysis secondary to antiepileptic use. We present a case of a 27-year-old male with new-onset seizures who was started on levetiracetam therapy and found to have elevated creatine kinase (CK), which decreased only with tapering of the drug. Our case displays the importance of considering levetiracetam as a cause of rhabdomyolysis, supporting this rare side effect of the antiseizure medication. Rhabdomyolysis is a potentially life-threatening condition that can lead to irreversible renal damage if not managed properly.

Assessing risk factors for elevated creatine kinase levels as an indicator of compartment syndrome following laparoscopic or robot-assisted colorectal cancer surgery in the lithotomy-trendelenburg position.

BACKGROUND: Well-leg compartment syndrome (WLCS) can occur due to compression and lower limb circulation disturbances caused by the surgical position during the procedure. Although rare, with an incidence of 1 in 3500 surgeries performed in the lithotomy position, it can lead to serious complications. Therefore, prevention and early diagnosis are critical. Symptoms of WLCS, such as leg pain, swelling, paresthesia, and serum creatine kinase (CK) levels are useful for diagnosis. This study aimed to investigate the risk factors for postoperative CK elevation in laparoscopic or robot-assisted colorectal cancer surgery performed in the lithotomy-Trendelenburg position. METHODS: Postoperative CK levels were measured in 178 patients who underwent laparoscopic or robot-assisted colorectal cancer surgery between February 2022 and March 2023. We compared patient backgrounds, short-term outcomes, and thigh/calf circumferences between patients with CK levels ≥ 250 (n = 62) and those with CK levels < 250 (n = 116). We investigated risk factors for elevated CK levels using both univariate and multivariate analyses. RESULTS: Four patients with CK levels of 22405 U/L, 4685 U/L, 4050 U/L, and 3824 U/L reported symptoms, which improved with conservative treatment. The following independent prognostic factors were identified by multivariate analysis: male sex (odds ratio [OR], 4.403; 95% CI, 1.960 to 9.892), rectal surgery (OR, 2.779; 95% CI, 1.249 to 6.184), continuous head-down position duration ≥ 180 min (OR, 3.523; 95% CI, 1.552 to 7.997), and preoperative calf circumference ≥ 33 cm (OR, 2.482; 95% CI, 1.154 to 5.339). CONCLUSIONS: Risk factors for CK elevation after colorectal cancer surgery in the lithotomy position include male sex, rectal surgery, an extended continuous head-down position without position changes, and a larger preoperative calf circumference. This study highlights the potential importance of intraoperative position changes every 3 h for preventing elevated CK levels, although the preventive effect was not specifically examined.

Modeling creatine-kinase MB concentrations following coronary artery bypass grafting.

BACKGROUND: An increase in cardiac biomarkers is a prerequisite for diagnosing periprocedural myocardial infarction (PMI) after coronary artery bypass grafting (CABG). Early-phase risk detection may be aided by modeling time-dependent serum creatine kinase-MB (CK-MB) concentrations. This study aimed to model the kinetics of CK-MB while identifying its influencing factors. METHODS: Patients who underwent elective CABG and had CK-MB measurements within 72 hours postoperatively were included. The primary outcome was the modeled post hoc kinetics of CK-MB in patients without potential PMI. These patients were defined as having no potential PMI based on the absence of ischemic electrocardiographic abnormalities, imaging abnormalities, in-hospital cardiac arrest, mortality, or postoperative unplanned catheterization. A web-based application was created using mixed-effect modeling to provide an interactive and individualized result. RESULTS: A total of 1589 CK-MB measurements from 635 patients who underwent elective isolated CABG were available for analysis. Of these, 609 patients (96%) had no potential PMI and 26 (4%) had potential PMI. Male sex, aortic cross-clamp time, and cardioplegia type significantly impacted CK-MB concentrations. The diagnostic accuracy of the model had an area under the receiver operating characteristic curve of 82.8% (95% confidence interval, 72.6%-90.2%). A threshold of 7 µg/L yielded a sensitivity of 94% and a specificity of 80% (positive predictive value, 17%; negative predictive value, 99%) for excluding potential PMI in our study population. CONCLUSIONS: CK-MB release after CABG depends on the timing of measurement, patient sex, aortic cross-clamp time, and cardioplegia type. The model (available at https://www.cardiomarker.com/ckmb) can be validated, reproduced, refined, and applied to other biomarkers.

A Case of Legionella Pneumonia with Rhabdomyolysis, with Extremely high Creatinine Kinase without Acute Kidney Injury in an Adult.

Legionella pneumophila is a bacterium that usually causes pulmonary disease but can rarely present with extrapulmonary manifestations, such as rhabdomyolysis. This is a case of Legionella infection with significant rhabdomyolysis but a lack of acute kidney injury. A 38-year-old male with a history of epilepsy presented to the emergency department after a seizure episode with confusion, fever, emesis and bruises. He also complained of a productive cough and scant haemoptysis for the past two months. Chest X-ray showed retrocardiac and left upper lobe opacities; urine was positive for Legionella antigen and myoglobinuria. Creatinine phosphokinase was 242,488 U/l and creatinine was 0.5 mg/dl. The patient was managed with oxygen therapy, aggressive IV hydration and IV azithromycin, and later IV levofloxacin until his symptoms resolved. Rhabdomyolysis may be a sign of Legionella infection. Rapid testing of Legionella antigen, especially in populations at risk, may be crucial for timely diagnosis and treatment. Kidney function may be preserved in the early stages of disease, but early treatment with antibiotics and aggressive hydration are an effective way to prevent deterioration in kidney function. LEARNING POINTS: Legionella pneumonia is difficult to distinguish from bacterial pneumonia, therefore rapid Legionella testing, particularly in areas with high rates of incidence, is important for targeted therapy.Legionella pneumonia with rhabdomyolysis with extremely high CPK levels is usually associated with AKI but preserved kidney function is possible and early diagnosis and treatment can lead to decreased mortality and morbidity in severe cases.

Prognostic significance of preoperative creatine kinase in resected thymic epithelial tumors.

Background: The preoperative serum creatine kinase (CK) concentration is a prognostic factor for malignant diseases. We investigated the significance of CK in surgically resected thymic epithelial tumors and the relationship between CK and clinicopathological factors. Methods: We retrospectively evaluated the relationship between preoperative CK levels and prognosis in 120 patients with thymic epithelial tumors who underwent surgical resection at two centers. The cutoff for CK was determined by the standard value in our institution (<62 IU/L for men and <45 IU/L for women). The paravertebral muscle at the Th12 level was used to assess skeletal muscle area to investigate sarcopenia. Results: Eighteen patients (15.0%) were categorized into the low CK group. The CK level was not associated with age, sex, performance status, myasthenia gravis, and pathological findings. Preoperative serum albumin and total cholesterol concentrations were significantly lower in the low CK group than in the normal CK group (both P<0.001). Moreover, the Th12 muscle index was lower in the low CK group (P=0.03), indicating that low CK was related to sarcopenia. Kaplan-Meier curve analysis illustrated that patients in the low CK group had significantly shorter disease-free survival (DFS) and overall survival (OS) than those in the normal CK group (P=0.03 and P=0.002, respectively). Multivariate analysis identified low CK as an independent prognostic factor for DFS (P=0.03) and OS (P=0.005). Conclusions: Preoperative serum CK might reflect the host nutritional status in patients with resected thymic epithelial tumors; therefore, CK could be a biomarker of postoperative prognosis.

Compartmentalization in cardiomyocytes modulates creatine kinase and adenylate kinase activities.

Intracellular molecules are transported by motor proteins or move by diffusion resulting from random molecular motion. Cardiomyocytes are packed with structures that are crucial for function, but also confine the diffusional spaces, providing cells with a means to control diffusion. They form compartments in which local concentrations are different from the overall, average concentrations. For example, calcium and cyclic AMP are highly compartmentalized, allowing these versatile second messengers to send different signals depending on their location. In energetic compartmentalization, the ratios of AMP and ADP to ATP are different from the average ratios. This is important for the performance of ATPases fuelling cardiac excitation-contraction coupling and mechanical work. A recent study suggested that compartmentalization modulates the activity of creatine kinase and adenylate kinase in situ. This could have implications for energetic signaling through, for example, AMP-activated kinase. It highlights the importance of taking compartmentalization into account in our interpretation of cellular physiology and developing methods to assess local concentrations of AMP and ADP to enhance our understanding of compartmentalization in different cell types.

Protective effects of fructose-1,6-bisphosphate postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing valve replacement: a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVES: Pharmacological postconditioning can protect against myocardial ischaemia-reperfusion injury during cardiac surgery with extracorporeal circulation. The aim of this study was to observe the protective effects of fructose-1,6-bisphosphate (FDP) postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing cardiac valve replacement with extracorporeal circulation. METHODS: Patients undergoing elective mitral valve replacement and/or aortic valve replacement were divided into normal saline postconditioning group (NS group) and FDP postconditioning group (FDP group). The primary outcome was the plasma concentration of creatine kinase-MB (CK-MB). The secondary outcomes were the plasma concentrations of lactate dehydrogenase, CK, high-sensitivity C-reactive protein, alpha-hydroxybutyrate dehydrogenase and cardiac troponin I, the spontaneous cardiac rhythm recovery profile, the extracorporeal circulation time and duration of surgery, intensive care unit and postoperative hospitalization. RESULTS: Forty patients were randomly assigned to receive intervention and included in the analysis. The serum concentrations of CK-MB, lactate dehydrogenase, CK, cardiac troponin I, alpha-hydroxybutyrate dehydrogenase and high-sensitivity C-reactive protein at T1∼4 were lower in the FDP group than in the NS group (P < 0.001). Compared with the NS group, the dosage of dopamine administered 1-90 min after cardiac resuscitation, the spontaneous cardiac rhythm recovery time and the incidence of ventricular fibrillation were lower in the FDP group (P < 0.001, P < 0.001 and P = 0.040, respectively). The values of ST- changes were increased more significantly in the NS group than in the FDP group (median [standard deviation] 1.3 [0.3] mm vs 0.7 [0.2] mm; P < 0.001). Compared with the NS group, the time of recovery of ST-segment deviations was shorter in the FDP group (50.3 [12.3] min vs 34.6 [6.9] min; P < 0.001). CONCLUSIONS: The FDP postconditioning could improve both myocardial ischaemia-reperfusion injury and the spontaneous cardiac rhythm recovery during cardiac valve surgery with extracorporeal circulation.