The Effects of Mitochondrial Transplantation on Sepsis Depend on the Type of Cell from Which They Are Isolated.

Previously, we have shown that mitochondrial transplantation in the sepsis model has immune modulatory effects. The mitochondrial function could have different characteristics dependent on cell types. Here, we investigated whether the effects of mitochondrial transplantation on the sepsis model could be different depending on the cell type, from which mitochondria were isolated. We isolated mitochondria from L6 muscle cells, clone 9 liver cells and mesenchymal stem cells (MSC). We tested the effects of mitochondrial transplantation using in vitro and in vivo sepsis models. We used the LPS stimulation of THP-1 cell, a monocyte cell line, as an in vitro model. First, we observed changes in mitochondrial function in the mitochondria-transplanted cells. Second, we compared the anti-inflammatory effects of mitochondrial transplantation. Third, we investigated the immune-enhancing effects using the endotoxin tolerance model. In the in vivo polymicrobial fecal slurry sepsis model, we examined the survival and biochemical effects of each type of mitochondrial transplantation. In the in vitro LPS model, mitochondrial transplantation with each cell type improved mitochondrial function, as measured by oxygen consumption. Among the three cell types, L6-mitochondrial transplantation significantly enhanced mitochondrial function. Mitochondrial transplantation with each cell type reduced hyper-inflammation in the acute phase of in vitro LPS model. It also enhanced immune function during the late immune suppression phase, as shown by endotoxin tolerance. These functions were not significantly different between the three cell types of origin for mitochondrial transplantation. However, only L6-mitochondrial transplantation significantly improved survival compared to the control in the polymicrobial intraabdominal sepsis model. The effects of mitochondria transplantation on both in vitro and in vivo sepsis models differed depending on the cell types of origin for mitochondria. L6-mitochondrial transplantation might be more beneficial in the sepsis model.

The DEXA-SEPSIS study protocol: a phase II randomized double-blinded controlled trial of the effect of early dexamethasone in high-risk sepsis patients.

OBJECTIVE: Steroids are used in cases of sepsis, especially in patients experiencing septic shock. However, clinical trials to date have reported contradictory results. Different patient endotypes and variations in the type and dose of steroid may be at fault for this discrepancy, and further investigation is warranted. In this paper, we propose a new DEXA-SEPSIS study design. METHODS: We plan to conduct a multicenter, double-blinded randomized pilot study (DEXA-SEPSIS) investigating the feasibility and safety of early use of dexamethasone in sepsis. Participants will be high-risk septic patients presenting to the emergency department with a systolic blood pressure of <90 mmHg or serum lactate level of >2 mmol/L. Participants will be randomized to the following three groups: control, 0.1 mg/kg of dexamethasone, or 0.2 mg/kg of dexamethasone per day for 1 to 2 days. The primary outcome will be 28-day mortality. Secondary outcomes will include time to septic shock, shock reversal, additional steroid administration, number of ventilator-free days, use of continuous renal-replacement therapy, length of stay in the intensive care unit and/or hospital, delta Sequential Organ Failure Assessment score on days 3 and 7, superinfection, gastrointestinal bleeding, hypernatremia, and hyperglycemia. DISCUSSION: The DEXA-SEPSIS study will provide insight regarding the feasibility and safety of early use of dexamethasone in high-risk sepsis. The results could provide data to design a future phase III study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05136560.

Serial Change of Endotoxin Tolerance in a Polymicrobial Sepsis Model.

Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2',7'-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.

Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model.

Steroids are currently being used in sepsis, particularly in septic shock. However, clinical trials to date have shown contradictory results. This could be attributed to the different patient endotypes and steroid doses, which have also contributed to the inconclusive results. We investigated the effects of glucocorticoid therapy on sepsis in a polymicrobial sepsis model in a variety of settings, such as steroid dose, severity, and sepsis phase. We used a rat model of fecal slurry polymicrobial sepsis. First, we investigated the optimum dose of steroids in a sepsis model. We administered different doses of dexamethasone after sepsis induction (0.1DEX; 0.1 mg/kg, 0.2DEX; 0.2 mg/kg, 5DEX; 5 mg/kg). Second, we used two different severities of the fecal slurry polymicrobial sepsis rat model to examine the effects of the steroids. A moderate or severe model was defined as a survival rate of approximately 70% and 30%, respectively. Third, we administered steroids in an early (1 h after sepsis induction) or late phase (25 h after sepsis). In all the experiments, we investigated the survival rates. In the determined optimal model and settings, we measured serum lactate, alanine transferase (ALT), creatinine, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, and arterial blood gas. We evaluated the bacterial burden in the blood and spleen. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was also investigated to determine the level of immune suppression 24 h after sepsis by measuring TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. Early treatment of 0.2 mg/kg dexamethasone in a severe sepsis model showed the best beneficial effects. In moderate- or late-phase sepsis, there was no survival gain with steroid treatment. DEX0.2 group showed less acute kidney injury manifested by serum creatinine and blood urea nitrogen. DEX decreased the levels of cytokines, including IL-6, IL-10, and TNF-α. Colony-forming units were significantly decreased in the blood when administered with dexamethasone. Endotoxin tolerance was not significantly different between the DEX0.2 and control groups. In conclusion, early treatment of 0.2 mg/kg dexamethasone improved the outcomes of rats in a severe sepsis model.

A Unique Case of Inferior Vena Cava Aneurysm Complicated with Pulmonary Embolism and Cerebral Infarction.

Inferior vena cava (IVC) aneurysms rarely occur. They are commonly detected incidentally since they present with mild or no symptoms. This was the first study to report a fatal case of a saccular IVC aneurysm with pulmonary embolism and cerebral infarction. The patient developed cardiac arrest five minutes after arriving at the emergency department, and spontaneous circulation was restored after two minutes of cardiopulmonary resuscitation. Computed tomography scans of the brain, chest, and abdomen-pelvis were obtained. The patient was diagnosed with a saccular aneurysm of the IVC measuring 8 × 11 cm, massive embolism of both pulmonary arteries, and cerebral infarction. An electroencephalogram, taken on the third day of hospitalization, suggested brain death, and the patient died on the eleventh day of hospitalization. This case report highlights that an IVC aneurysm with pulmonary embolism can be associated with paradoxical emboli-induced cerebral infarction, which is fatal.

The Need of Enterococcal Coverage in Severe Intra-Abdominal Infection: Evidence from Animal Study.

Intra-abdominal infection (IAI) is a common and important cause of infectious mortality in intensive care units. Adequate source control and appropriate antimicrobial regimens are key in the management of IAI. In community-acquired IAI, guidelines recommend the use of different antimicrobial regimens according to severity. However, the evidence for this is weak. We investigated the effect of enterococcal coverage in antimicrobial regimens in a severe polymicrobial IAI model. We investigated the effects of imipenem/cilastatin (IMP) and ceftriaxone with metronidazole (CTX+M) in a rat model of severe IAI. We observed the survival rate and bacterial clearance rate. We identified the bacteria in blood culture. We measured lactate, alanine aminotransferase (ALT), creatinine, interleukin (IL)-6, IL-10, and reactive oxygen species (ROS) in the blood. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) was also estimated to determine the level of immune suppression. In the severe IAI model, IMP improved survival and bacterial clearance compared to CTX+M. Enterococcus spp. were more frequently isolated in the CTX+M group. IMP also decreased plasma lactate, cytokine, and ROS levels. ALT and creatinine levels were lower in IMP group. In the mild-to-moderate IAI model, however, there was no survival difference between the groups. Immune suppression of PBMCs was observed in IAI model, and it was more prominent in the severe IAI model. Compared to CTX+M, IMP improved the outcome of rats in severe IAI model.

Chest radiography for simplified evaluation of central venous catheter tip positioning for safe and accurate haemodynamic monitoring: a retrospective observational study.

OBJECTIVES: The tip-to-carina (TC) distance on a simple chest X-ray (CXR) has proven value in the determination of correct central venous catheter (CVC) positioning. However, previous studies have mostly focused on preventing the atrial insertion of the CVC tip, and not on appropriate positioning for accurate haemodynamic monitoring. We aimed to assess whether the TC distance could detect the passage of the CVC tip into the superior vena cava (SVC) and the right atrium (RA), and to accordingly suggest cut-off reference values for these two aspects. DESIGN: Retrospective observational cohort study. SETTING: Single urban tertiary level academic hospital. PARTICIPANTS: 479 patients who underwent CXR and chest CT scan after the insertion of a CVC with a 24-hour interval during the study period. INTERVENTION: The TC distance was measured on CXR, and the position of the CVC tip was assessed on the chest CT images. The TC distance was described as a negative or positive number if the CVC tip was above or below the carina, respectively. Receiver-operating characteristics curve analyses were conducted to ascertain the TC distance to detect SVC entrance and RA insertion of CVC tip. RESULTS: The TC distance could significantly detect both SVC entrance and RA insertion (p<0.001 for both; area under curve 0.987 and 0.965, respectively), with a reference range of -6.69 to 15.61 mm. CONCLUSION: The TC distance in CXR is a simple and precise method to confirm not only the safe placement of the CVC tip but also its optimal positioning for accurate haemodynamic monitoring.

MPG and NPRL3 Polymorphisms are Associated with Ischemic Stroke Susceptibility and Post-Stroke Mortality.

Ischemic stroke is a complicated disease which is affected by environmental factors and genetic factors. In this field, various studies using whole-exome sequencing (WES) have focused on novel and linkage variants in diverse diseases. Thus, we have investigated the various novel variants, which focused on their linkages to each other, in ischemic stroke. Specifically, we analyzed the N-methylpurine DNA glycosylase (MPG) gene, which plays an initiating role in DNA repair, and the nitrogen permease regulator-like 3 (NPRL3) gene, which is involved in regulating the mammalian target of rapamycin pathway. We took blood samples of 519 ischemic stroke patients and 417 controls. Genetic polymorphisms were detected by polymerase chain reaction (PCR), real-time PCR, and restriction fragment length polymorphism (RFLP) analysis. We found that two NPRL3 polymorphisms (rs2541618 C>T and rs75187722 G>A), as well as the MPG rs2562162 C>T polymorphism, were significantly associated with ischemic stroke. In Cox proportional hazard regression models, the MPG rs2562162 was associated with the survival of small-vessel disease patients in ischemic stroke. Our study showed that NPRL3 and MPG polymorphisms are associated with ischemic stroke prevalence and ischemic stroke survival. Taken together, these findings suggest that NPRL3 and MPG genotypes may be useful clinical biomarkers for ischemic stroke development and prognosis.

Effect of Pretreatment with the NADPH Oxidase Inhibitor Apocynin on the Therapeutic Efficacy of Human Placenta-Derived Mesenchymal Stem Cells in Intracerebral Hemorrhage.

Several studies have demonstrated the beneficial effect of mesenchymal stem cells (MSCs) on intracerebral hemorrhage (ICH). Enhancement of the therapeutic efficacy of MSCs in ICH is necessary, considering the diseases high association with mortality and morbidity. Various preconditioning methods to enhance the beneficial properties of MSCs have been introduced. We suggested apocynin, a well-known nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, as a novel preconditioning regimen to enhance the therapeutic efficacy of MSCs in ICH. Rat ICH models were made using bacterial collagenase. 24 h after ICH induction, the rats were randomly divided into apocynin-preconditioned MSC-treated (Apo-MSC), naïve MSC-treated and control groups. Hematoma volume, brain edema, and degenerating neuron count were compared at 48 h after the ICH induction. The expression of tight junction proteins (occludin, zona occludens [ZO]-1) were also compared. Hematoma size, hemispheric enlargement and degenerating neuron count were significantly lower in the Apo-MSC group than in the naïve MSC group (p = 0.004, 0.013 and 0.043, respectively), while the expression of occludin was higher (p = 0.024). Apocynin treatment enhances the therapeutic efficacy of MSCs in ICH in the acute stage, through the improvement of the beneficial properties of MSCs, such as neuroprotection and the reinforcement of endovascular integrity of cerebral vasculature.

Association of MicroRNA Biogenesis Genes Polymorphisms with Ischemic Stroke Susceptibility and Post-Stroke Mortality.

BACKGROUND AND PURPOSE: MicroRNA (miRNA) expression has been examined in multiple conditions, including various cancers, neurological diseases, and cerebrovascular diseases, particularly stroke. Existing evidence indicates that miRNA biosynthesis and function play crucial roles in ischemic stroke physiology and pathology. In this study, we selected six known polymorphisms in miRNA-biogenesis genes; DICER rs13078A>T, rs3742330A>G; DROSHA rs10719T>C, rs6877842G>C; Ran GTPase (RAN) rs14035C>T; exportin 5 (XPO5) rs11077A>C. METHODS: We analyzed the associations between these polymorphisms and disease status and clinical factors in 585 ischemic stroke patients and 403 controls. Genotyping was performed with the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The DICER rs3742330A>G (AA vs. AG+GG: adjusted odds ratio [AOR], 1.360; 95% confidence interval [CI], 1.024 to 1.807; P=0.034) and DROSHA rs10719T>C polymorphisms (TT vs. CC: AOR, 2.038; 95% CI, 1.113 to 3.730; P=0.021) were associated with ischemic stroke prevalence. During a mean follow-up of 4.80±2.11 years, 99 (5.91%) of the stroke patients died. In multivariate Cox proportional hazard regression models, a significant association was found between RAN rs14035 and survival of large artery disease patients with ischemic stroke (CC vs. TT: adjusted hazard ratio, 5.978; P=0.015). CONCLUSIONS: An association was identified between the DICER and DROSHA polymorphisms and ischemic stroke. Specifically, polymorphisms (rs3742330 and rs10719) were more common in stroke patients, suggesting that they may be associated with an increased risk of ischemic stroke.

25-hydroxyvitamin D Levels was not Associated with Blood Pressure and Arterial Stiffness in Patients with Chronic Kidney Disease.

BACKGROUND: We investigated the effect of vitamin D deficiency on cardiovascular risk profiles in an Asian population with chronic kidney disease (CKD). METHODS: A total of 210 participants (62 non-dialysis CKD patients and 148 hemodialysis [HD] patients) were enrolled between December 2009 and February 2010. Vitamin D deficiency was determined using the serum 25-hydroxyvitamin D [25(OH)D] concentration. Blood pressure and arterial stiffness were measured. Subjects were divided into groups according to 25(OH)D concentration based on a cut-off of 13.5 ng/mL in non-dialysis CKD patients and 11.3 ng/mL in HD patients. RESULTS: The mean age was 61.7±12.3 years in non-dialysis CKD patients and 57.0±12.7 years in HD patients. In the non-dialysis CKD group, mean estimated glomerular filtration rate (eGFR) was 29.7±15.4 mL/min/1.73 m2. Mean 25(OH)D concentration was 13.6±7.8 ng/mL in non-dialysis CKD patients and 11.3±6.7 ng/mL in HD patients. More than half of the subjects had vitamin D deficiency (67.6% in non-dialysis CKD patients and 80.4% in HD patients). There were no significant differences in systolic blood pressure, pulse pressure, and arterial stiffness between higher and lower 25(OH)D groups among non-dialysis CKD and HD patients. Multivariate analysis revealed that female sex (odds ratio [OR]: 5.890; 95% confidence interval [CI]: 2.597-13.387; p<0.001) and presence of diabetes (OR: 2.434; 95% CI: 1.103-5.370; p=0.028) were significantly associated with lower serum 25(OH)D levels in HD patients. CONCLUSION: The prevalence of vitamin D deficiency was high in both nondialysis CKD patients and HD patients. Serum 25(OH)D concentration was not a significant factor associated with blood pressure and arterial stiffness among non-dialysis CKD and HD patients.

Association of miR-34a, miR-130a, miR-150 and miR-155 polymorphisms with the risk of ischemic stroke.

MicroRNAs (miRNAs or miRs) are small (19-23 nt) non-coding RNA molecules that are endogenous regulators of gene expression. Previous studies have found that some miRNAs are related to the progression of ischemia in the cerebral artery. Furthermore, a recent study found a significant association between miRNA single nucleotide polymorphisms (SNPs) and the risk of ischemic stroke. Therefore, it may be valuable to investigate associations between megakaryocyte formation-related miRNA polymorphisms and the prevalence of ischemic stroke. We thus conducted a case-control study of 1,000 individuals who were screened for 4 miRNA polymorphisms (miR­34a rs6577555C>A, miR-130a rs731384C>T, miR-150 rs73056059G>A and miR­155 rs767649T>A) by PCR-RFLP analysis. The study population comprised 596 patients with ischemic stroke and 404 control subjects without any history of neurological disorders. We observed associations between miRNA polymorphisms and individual stroke subtypes. The miR­150 polymorphisms were significantly associated with ischemic stroke subgroups, such as left anterior descending artery (LAD) disease [GG vs. AA: adjusted odds ratio (AOR), 1.922; 95% confidence interval (CI), 1.003-3.681] and cardioembolism (GG vs. AA: AOR, 2.996; 95% CI, 1.293-6.939). Additionally, Cox proportional analysis indicated that the miR­150GA genotype was associated with survival in patients with ischemic stroke [adjusted hazard ratio (HR), 2.063; 95% CI, 1.142-3.727; P=0.017] and with the LAD subgroup [adjusted HR, 3.021; 95% CI, 1.345-6.785; P=0.008]. Our findings suggest that miR­150 polymorphisms may contribute to the development of ischemic stroke and may potentially act as biomarkers to predict the risk of ischemic stroke. To the best of our knowledge, this is the first study to evaluate the association between miRNA polymorphisms (miR-34aC>A, miR-130aC>T, miR-150G>A and miR-155T>A) and ischemic stroke.

Effect of the rate of chest compression familiarised in previous training on the depth of chest compression during metronome-guided cardiopulmonary resuscitation: a randomised crossover trial.

OBJECTIVES: To assess how the quality of metronome-guided cardiopulmonary resuscitation (CPR) was affected by the chest compression rate familiarised by training before the performance and to determine a possible mechanism for any effect shown. DESIGN: Prospective crossover trial of a simulated, one-person, chest-compression-only CPR. SETTING: Participants were recruited from a medical school and two paramedic schools of South Korea. PARTICIPANTS: 42 senior students of a medical school and two paramedic schools were enrolled but five dropped out due to physical restraints. INTERVENTION: Senior medical and paramedic students performed 1 min of metronome-guided CPR with chest compressions only at a speed of 120 compressions/min after training for chest compression with three different rates (100, 120 and 140 compressions/min). Friedman's test was used to compare average compression depths based on the different rates used during training. RESULTS: Average compression depths were significantly different according to the rate used in training (p<0.001). A post hoc analysis showed that average compression depths were significantly different between trials after training at a speed of 100 compressions/min and those at speeds of 120 and 140 compressions/min (both p<0.001). CONCLUSIONS: The depth of chest compression during metronome-guided CPR is affected by the relative difference between the rate of metronome guidance and the chest compression rate practised in previous training.

50% duty cycle may be inappropriate to achieve a sufficient chest compression depth when cardiopulmonary resuscitation is performed by female or light rescuers.

OBJECTIVE: Current guidelines for cardiopulmonary resuscitation recommend chest compressions (CC) during 50% of the duty cycle (DC) in part because of the ease with which individuals may learn to achieve it with practice. However, no consideration has been given to a possible interaction between DC and depth of CC, which has been the subject of recent study. Our aim was to determine if 50% DC is inappropriate to achieve sufficient chest compression depth for female and light rescuers. METHODS: Previously collected CC data, performed by senior medical students guided by metronome sounds with various down-stroke patterns and rates, were included in the analysis. Multiple linear regression analysis was performed to determine the association between average compression depth (ACD) with average compression rate (ACR), DC, and physical characteristics of the performers. Expected ACD was calculated for various settings. RESULTS: DC, ACR, body weight, male sex, and self-assessed physical strength were significantly associated with ACD in multivariate analysis. Based on our calculations, with 50% of DC, only men with ACR of 140/min or faster or body weight over 74 kg with ACR of 120/min can achieve sufficient ACD. CONCLUSION: A shorter DC is independently correlated with deeper CC during simulated cardiopulmonary resuscitation. The optimal DC recommended in current guidelines may be inappropriate for achieving sufficient CD, especially for female or lighter-weight rescuers.

Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.

Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke.

Induction of a shorter compression phase is correlated with a deeper chest compression during metronome-guided cardiopulmonary resuscitation: a manikin study.

OBJECTIVES: Recent studies have shown that there may be an interaction between duty cycle and other factors related to the quality of chest compression. Duty cycle represents the fraction of compression phase. We aimed to investigate the effect of shorter compression phase on average chest compression depth during metronome-guided cardiopulmonary resuscitation. METHODS: Senior medical students performed 12 sets of chest compressions following the guiding sounds, with three down-stroke patterns (normal, fast and very fast) and four rates (80, 100, 120 and 140 compressions/min) in random sequence. Repeated-measures analysis of variance was used to compare the average chest compression depth and duty cycle among the trials. RESULTS: The average chest compression depth increased and the duty cycle decreased in a linear fashion as the down-stroke pattern shifted from normal to very fast (p<0.001 for both). Linear increase of average chest compression depth following the increase of the rate of chest compression was observed only with normal down-stroke pattern (p=0.004). CONCLUSIONS: Induction of a shorter compression phase is correlated with a deeper chest compression during metronome-guided cardiopulmonary resuscitation.