Prevalence of hypophosphatemia in the ICU - Results of an international one-day point prevalence survey.

BACKGROUND & AIMS: Hypophosphatemia (HypoP) is associated with organ dysfunction and mortality. Despite its potential severe consequences, HypoP remains poorly characterized in terms of real prevalence and timing of onset. The primary objective was to determine the prevalence of HypoP defined as blood phosphate <0.8 and < 0.65 mmol/l on one particular day at international level. METHODS: One-day point prevalence survey conducted by the Section of Metabolism, Endocrinology and Nutrition (MEN) of the European Society of Intensive Care Medicine (ESICM) during week 11-2020. RESULTS: In total, 56 adult and 4 paediatric ICUs, from 22 countries participated: 41 ICUs were mixed medico surgical, the 19 others being cardiac, medical or surgical. Phosphate measurements were performed daily in 21 ICUs, and 1-3 times per week in 39 ICUs. On D-Day 909 patients (883 adults) were present and 668/883 (75.7%) had serum/plasma phosphate determined, revealing a HypoP in 103 (15.4%) patients aged 62 [18 to 85] years. Of those, 49 patients presented phosphate <0.65 mmol/l: cases of hypophosphatemia were detected at any time of patient's ICU stay. No HypoP was observed in children. A treatment protocol existed only in 41.1% of adult ICUs, independently of ICU type, or size. Only 41/98 of the HypoP patients (29/41 of patients with phosphate <0.65 mmol/l) were receiving phosphate. CONCLUSION: HypoP is present at least in 15.4% of ICU patients, and may occur at any time during the ICU stay. The absence of phosphate repletion protocols in 60% of participating ICUs is an unexpected finding, and confirms the necessity for the development of ICU phosphate protocols and guidelines. CLINICALTRIALS IDENTIFIER: NCT04201899.

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines

PURPOSE: To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. METHODS: We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. RESULTS: We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. CONCLUSIONS: We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.

Evolution of severe trauma in Estonia comparing early versus established independence of the state.

PURPOSE: Trauma mechanisms and patterns of severe injuries during the Estonian independence have not been evaluated. The aim of the study was to compare the incidence and outcomes of severe injuries between time periods of early independence from the Soviet Union and the present time. METHODS: After the ethics review board approval, all adult trauma admissions to major trauma facilities in 1993-1994 and 2013-2014 with Injury Severity Score >15 were identified. Data collection included demographics, injury severity variables, interventions, and in-hospital outcomes. Primary outcome was in-hospital mortality. Secondary outcomes included incidence of penetrating trauma, hospital length of stay (HLOS), and in-hospital complications. Primary outcome difference comparing the two time segments was determined using logistic regression analysis. RESULTS: A total of 1064 patients were included, 593 and 471 from 1993-1994 to 2013-2014, respectively. Incidence of penetrating trauma during 1993-1994 was 11.1 % and in 2013-2014 at 6.4 % (p = 0.007). Gunshot injuries constituted 62.1 and 23.3 % of all penetrating trauma in 1993-1994 and 2013-2014, respectively (p < 0.001). The overall mean HLOS was 15.5 ± 19.8 days and did not differ between the periods. The rate of adjusted complications showed a trend for a decreased incidence (adj. p = 0.064). Adjusted mortality rate was 50.3 and 16.4 % during 1993-1994 and 2013-2014, respectively (adj. OR 7.01; 95 % CI 4.69-10.47; p < 0.001). CONCLUSIONS: Effective law enforcement, gun control, evolution of trauma system, and reduction of interpersonal violence have all contributed to a significant decrease in penetrating trauma incidence and all-cause adjusted mortality during the 20 years of Estonian independence.

Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam during high volume haemodiafiltration in patients with septic shock.

BACKGROUND: The purpose of the study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of piperacillin and tazobactam during high-volume haemodiafiltration (HVHDF). METHODS: A single dose of piperacillin/tazobactam (4/0.5 g) was administered as 30 minute infusion during HVHDF to 10 patients with acute kidney injury due to septic shock. Arterial blood samples were collected before and at 30 or 60 min intervals over 8 h (12 samples) after study drug administration. Concentrations of piperacillin and tazobactam were determined by HPLC-MS/MS. R software was used for population PK analysis and Monte Carlo Simulation of probability of PK/PD target attainment (PTA) in 1000 subjects. RESULTS: A total of 101 samples were collected during HVHDF. The median (IQR) estimated glomerular filtration rate of the patients was 16 (11.25-27.5) ml/min/1.73 m(2) and HVHDF effluent rate was 208 (146.3-298.3) ml/kg/h. A final two-compartment population PK model predicted mean (%SE) total piperacillin clearance on HVHDF was 6.9 (6.4) l/h, volume of distribution of central compartment 9.0 (10.1) l and of peripheral compartment 11.2 (12.2) l. The PTA of 50% fT>MIC for piperacillin 4 g/tazobactam 0.5 g dosed every 8 h as 0.5-h and 4-h infusion was 84.3% and 100% for MIC of 16 mg/l respectively. Aiming 100% fT>MIC of 16 mg/l, the PTA values were 88.6% and 61.0%, for piperacillin 4 g/tazobactam 0.5 g 4-h infusion every 6 and 8 h respectively. CONCLUSIONS: For bactericidal PK/PD target attainment piperacillin/tazobactam doses of 4/0.5 g every 8 h appear appropriate in septic shock patients with minimal residual renal function during HVHDF.

Severe Trauma in Estonia: 256 consecutive cases analysed and the impact on outcomes comparing two regions.

PURPOSE: The purpose of this study was to investigate epidemiology of severe injuries in Estonia while comparing outcomes at regional trauma facilities. METHODS: After the ethics review board approval, all consecutive trauma admissions with Injury Severity Score (ISS) > 15 to North Estonia Medical Center/Tallinn Children's Hospital (NEMC + TCH) and Tartu University Hospital (TUH) were identified between 1/1/2013 and 31/12/2013. Data collection included demographics, admission data, injury severity variables, interventions, and in-hospital outcomes. Primary outcome was in-hospital mortality. Secondary outcomes were complications per Clavien-Dindo and hospital length of stay (HLOS). Logistic regression analysis was used to compare adjusted mortality between the two regional hospitals. RESULTS: A total of 256 patients met inclusion criteria. The mean ISS for the cohort was 23.6 ± 7.8, 13.3 % were hypotensive on admission, and 44.1 % had a Glasgow Coma Scale < 9. Overall rate of complications was 40.2 % that did not differ between the facilities. The mean HLOS at the NEMC + TCH and the TUH were 20.1 ± 25.1 and 10.5 ± 11.2 days (p < 0.001), respectively. Overall mortality was 20.7 % (n = 53). Mortality was 25.4 and 14.9 % for the NEMC + TCH and the TUH, respectively (p = 0.04). Logistic regression analysis resulted in comparable mortality at the regional trauma facilities (adj. OR 1.38; 95 % CI 0.66-2.92; p value 0.39). CONCLUSIONS: The annual incidence of injuries with ISS > 15 was 256 cases with overall mortality at 20.7 % in Estonia. We observed comparable adjusted outcomes at the major regional trauma facilities. This study contains benchmarking data on severely injured patients in Estonia providing potential for future trauma care evaluation and regional outcome comparisons.

Exposure to sixty minutes of hyperoxia upregulates myocardial humanins in patients with coronary artery disease - a pilot study.

In experimental setting the concept of myocardial preconditioning by hyperoxia has been introduced and different intracellular protective mechanisms and their effects have been described. To study whether similar protective phenotype can be induced by hyperoxia also in humans, gene expression profile after hyperoxic exposure was analyzed. Adult patients were randomized to be ventilated with either FiO2 0.4 (n = 14) or 1.0 (n = 10) for 60 minutes before coronary artery bypass grafting. A tissue sample from the right atrial appendage was taken for gene analysis and expression profile analysis on genome wide level by RNA-seq analysis was applied. Exposure to > 96% oxygen for 60 minutes significantly changed the expression of 20 different genes, including upregulation of two different humanins - MTRNR2L2 and MTRNR2L8, and activated a "cell survival" network as detected by Ingenuity Pathway Analyses. We concluded that administration of > 96% oxygen for 1 hour changes gene expression in the myocardium of the patients with coronary artery disease and may enhance cell survival capability.

Definition, prevalence, and outcome of feeding intolerance in intensive care: a systematic review and meta-analysis.

Clinicians and researchers frequently use the phrase 'feeding intolerance' (FI) as a descriptive term in enterally fed critically ill patients. We aimed to: (1) determine what is the most accepted definition of FI; (2) estimate the prevalence of FI; and (3) evaluate whether FI is associated with important outcomes. Systematic searches of peer-reviewed publications using PubMed, MEDLINE, and Web of Science were performed with studies reporting FI extracted. We identified 72 studies defining FI. In 33 studies, the definition was based on large gastric residual volumes (GRVs) together with other gastrointestinal symptoms, while 30 studies relied solely on large GRVs, six studies used inadequate delivery of enteral nutrition (EN) as a threshold, and three studies gastrointestinal symptoms without reference to GRV. The median volume used to define a 'large' GRV was 250 ml (ranges from 75 to 500 ml). The pooled proportion (n = 31 studies) of FI was 38.3% (95% CI 30.7-46.2). Five studies reported outcomes, all of them observed adverse outcome in FI patients. In three studies, respectively, FI was associated with increased mortality and ICU length-of-stay. In summary, FI is inconsistently defined but appears to occur frequently. There are preliminary data indicating that FI is associated with adverse outcomes. A standard definition of FI is required to determine the accuracy of these preliminary data.

A systematic review and individual patient data meta-analysis on intra-abdominal hypertension in critically ill patients: the wake-up project. World initiative on Abdominal Hypertension Epidemiology, a Unifying Project (WAKE-Up!).

Intra-abdominal hypertension (IAH), defined as a pathologically increase in intraabdominal pressure, is commonly found in critically ill patients. While IAH has been associated with several abdominal as well as extra-abdominal conditions, few studies have examined the occurrence of IAH in relation to mortality. The aim of this paper was to evaluate the prognostic role of IAH and its risk factors at admission in critically ill patients across a wide range of settings and countries. An individual patient meta-analysis of all available data and a systematic review of published (in full or as abstract) medical databases and studies between 1996 and June 2012 were performed. The search was limited to "clinical trials" and "randomized controlled trials", "adults", using the terms "intra-abdominal pressure", "intraabdominal hypertension" combined with any of the terms "outcome" and "mortality". All together data on 2707 patients, representing 21 centers from 11 countries was obtained. Data on 1038 patients were not analysed because of the following exclusion criteria: no IAP value on admission (N.=712), absence of information on ICU outcome (N.=195), age <18 or >95 years (N.=131). Data from 1669 individual patients (19 centers from 9 countries) were analyzed in the meta-analysis. Presence of IAH was defined as a sustained increase in IAP equal to or above 12 mmHg. At admission the mean overall IAP was 9.9±5.0 mmHg, with 463 patients (27.7%) presenting IAH with a mean IAP of 16.3±3.4 mmHg. The only independent predictors for IAH were SOFA score and fluid balance on the day of admission. Five hundred thirteen patients (30.8%) died in intensive care. The independent predictors for intensive care mortality were IAH, SAPS II score, SOFA score and admission category. This systematic review and individual patient data meta-analysis shows that IAH is frequently present in critically ill patients and it is an independent predictor for mortality.

Clinical evaluation of the intestinal microcirculation using sidestream dark field imaging--recommendations of a round table meeting.

INTRODUCTION: In clinical setting, Sidestream Dark Field (SDF) imaging has provided unprecedented insights into the gut microcirculation mainly by studying the intestinal mucosa of patients with ileostomies. Visualizing microvascular structure and function of ileal mucosa at the bedside brings unique opportunity for clinical research, particularly in critically ill patients. Several papers that were focused on intestinal microcirculation, used different methods of assessment because an accepted scoring systems does not exist so far and it is no surprise that it is rather difficult to compare the results from these studies. The present paper presents recommendations concerning specific aspects of image acquisition and proposes some parameters for the description of the intestinal microcirculation in human studies, as suggested by the participants of a round table meeting. METHODS: The round table meeting participants reviewed all relevant literature, discussed various aspects of image acquisition by SDF technology in patients with ileostomy and parameters for the description of intestinal mucosa microcirculation. Selected key conditions for high quality and reproducible image recordings were identified. To evaluate quality of intestinal microcirculation, selected parameters and scoring system were suggested and described. RESULTS: For image acquisition in ileostomies, five key points were proposed: optimal timing, optimal SDF device probe positioning, optimal stabilization, optimal number and length of acquired video recordings, and optimal avoidance of pressure artefacts. With regard to image analysis, simplified set of quantitative and qualitative parameters for the description of the intestinal mucosa microcirculation for the clinical studies has been proposed: vessels per villus, microvascular flow index, proportion of perfused villi, and borders of villi. The proposed parameters can be included in a semi-quantitative scoring system; however, this scoring system needs further validation. This simplified analysis does not require sophisticated software and can be performed manually on the video screen. CONCLUSION: We propose a simple methodology for image acquisition and suggest specific microvascular parameters to analyze SDF imaging studies of the intestinal mucosa microcirculation in patients with ileostomy. Proposed scoring system needs to be validated in further clinical studies.

A Systematic Review And Individual Patient Data Meta-Analysis On Intraabdominal Hypertension In Critically Ill Patients: The Wake-Up Project World Initiative on Abdominal Hypertension Epidemiology, a Unifying Project (WAKE-Up!).

Background: Intraabdominal hypertension (IAH), defined as a pathologically increase in intraabdominal pressure, is commonly found in critically ill patients. While IAH has been associated with several abdominal as well as extra-abdominal conditions, few studies have examined the occurrence of IAH in relation to mortality. Objective: To evaluate the prognostic role of IAH and its risk factors at admission in critically ill patients across a wide range of settings and countries. Data sources: An individual patient meta-analysis of all available data and a systematic review of published (in full or as abstract) medical databases and studies between 1996 and June 2012 were performed. The search was limited to "clinical trials" and "randomized controlled trials", "adults", using the terms "intraabdominal pressure", "intraabdominal hypertension" combined with any of the terms "outcome" and "mortality". All together data on 2707 patients, representing 21 centers from 11 countries was obtained. Data on 1038 patients were not analysed because of the following exclusion criteria: no IAP value on admission (n=712), absence of information on ICU outcome (n=195), age <18 or > 95 years (n=131). Results: Data from 1669 individual patients (19 centers from 9 countries) were analyzed in the meta-analysis. Presence of IAH was defined as a sustained increase in IAP equal to or above 12 mmHg. At admission the mean overall IAP was 9.9±5.0 mmHg, with 463 patients (27.7%) presenting IAH with a mean IAP of 16.3±3.4 mmHg. The only independent predictors for IAH were SOFA score and fluid balance on the day of admission. Five hundred thirteen patients (30.8%) died in intensive care. The independent predictors for intensive care mortality were IAH, SAPS II score, SOFA score and admission category. Conclusions: This systematic review and individual patient data meta-analysis shows that IAH is frequently present in critically ill patients and it is an independent predictor for mortality.

Risk factors for intra-abdominal hypertension in mechanically ventilated patients.

BACKGROUND: Intra-abdominal hypertension (IAH) in intensive care patients is associated with an adverse outcome, but the risk factors for development of IAH have not been extensively studied. We aimed to identify independent risk factors for IAH in mechanically ventilated (MV) patients. METHODS: In this prospective observational study, 563 MV patients staying in the general intensive care unit (ICU) of a university hospital for more than 24 h were observed during their ICU stay. Repeated intermittent measurements of intra-abdominal pressure (IAP) via the urinary bladder were performed. RESULTS: IAH (sustained or repeated IAP≥12 mmHg) developed in 182 patients (32.3%). From all the study patients, 44.4% had a primary pathology in the abdomino-pelvic region. Two thirds of all IAH cases developed in this group. Obesity [body mass index (BMI)>30], high positive end-expiratory pressure (PEEP>10), respiratory failure (PaO(2)/FiO(2) <300), use of vasopressors/inotropes, pancreatitis, hepatic failure/cirrhosis with ascites, gastrointestinal bleeding and laparotomy on admission day were identified as independent risk factors for IAH. None of the patients without any of these risk factors (26 patients) developed IAH. CONCLUSION: The precise prediction of development IAH in mixed ICU population remains difficult. In the absence of BMI>30, PEEP>10 cmH(2)O, PaO(2)/FiO(2) <300, use of vasopressors/inotropes, pancreatitis, hepatic failure/cirrhosis with ascites, gastrointestinal bleeding and laparotomy on admission day, the risk for development of IAH in MV ICU patients is minimal.

Gastrointestinal symptoms in intensive care patients.

BACKGROUND: Gastrointestinal (GI) problems are not uniformly assessed in intensive care unit (ICU) patients and respective data in available literature are insufficient. We aimed to describe the prevalence, risk factors and importance of different GI symptoms. METHODS: We prospectively studied all patients hospitalized to the General ICU of Tartu University Hospital in 2004-2007. RESULTS: Of 1374 patients, 62 were excluded due to missing data. Seven hundred and seventy-five (59.1%) patients had at least one GI symptom at least during 1 day of their stay, while 475 (36.2%) suffered from more than one symptom. Absent or abnormal bowel sounds were documented in 542 patients (41.3%), vomiting/regurgitation in 501 (38.2%), high gastric aspirate volume in 298 (22.7%), diarrhoea in 184 (14.0%), bowel distension in 139 (10.6%) and GI bleeding in 97 (7.4%) patients during their ICU stay. Absent or abnormal bowel sounds and GI bleeding were associated with significantly higher mortality. The number of simultaneous GI symptoms was an independent risk factor for ICU mortality. The ICU length of stay and mortality of patients who had two or more GI symptoms simultaneously were significantly higher than in patients with a maximum of one GI symptom. CONCLUSION: GI symptoms occur frequently in ICU patients. Absence of bowel sounds and GI bleeding are associated with impaired outcome. Prevalence of GI symptoms at the first day in ICU predicts the mortality of the patients.

Pharmacokinetics of meropenem determined by microdialysis in the peritoneal fluid of patients with severe peritonitis associated with septic shock.

Our objective was to describe the pharmacokinetics of meropenem in the peritoneal fluid (PF) of six patients with severe peritonitis and septic shock and to relate measured concentrations to the minimum inhibitory concentration of bacteria. Microdialysis catheters were placed into the peritoneal space during surgery. Meropenem concentrations in plasma and in PF were analyzed using compartmental modeling. Meropenem areas under the concentration-time curve were lower in PF than in plasma (average ratio, 73.8+/-15%) because of degradation confirmed ex vivo. Compartment modeling with elimination from a peripheral compartment described the data adequately, and was used to simulate steady-state concentration profiles in plasma and PF during various dosing regimens. At the currently recommended dosing regimen of 1 g infused over 20 min every 8 h, PF concentrations of meropenem in patients with severe peritonitis associated with septic shock reach values sufficient for antibacterial effects against susceptible, but not always against intermediately susceptible, bacteria.

Pre-treatment with hyperoxia before coronary artery bypass grafting - effects on myocardial injury and inflammatory response.

BACKGROUND: In experimental studies, exposure to hyperoxia for a limited time before ischaemia induces a low-grade systemic oxidative stress and evokes an (ischaemic) preconditioning-like effect of the myocardium. We hypothesised that hyperoxia before cardioplegia could protect the myocardium against necrosis and stunning caused by ischaemia-reperfusion. METHODS: Forty patients undergoing coronary artery bypass grafting were randomly exposed to an oxygen fraction of 0.4 or > 0.96 in inspired air on an average of 120 min before cardioplegia. Blood for troponin I, creatine kinase-MB, lactate, glutathione and interleukin-6 was sampled from arterial and coronary sinus cannulae during 20 min of reperfusion. Additional arterial samples were drawn 60 min after declamping and in the first post-operative morning. The cardiac index and right and left ventricular stroke work indices were measured before sternotomy and up to 12 h post-operatively. RESULTS: Troponin I, creatine kinase-MB and lactate did not differ between the groups. Hyperoxic pre-treatment had no impact on the post-operative haemodynamic indices measured with the thermodilution pulmonary artery catheter. More oxidised glutathione was released in the hyperoxia group in the first minute of reperfusion (P = 0.015). Hyperoxic pre-treatment abolished the myocardial release of interleukin-6 during 20 min of reperfusion (P = 0.021 vs. controls). In the first post-operative morning, interleukin-6 was higher in the hyperoxia group [127.0 (86.0-140.0) vs. 85.2 pg/ml (66.6-94.5 pg/ml); P = 0.016]. CONCLUSIONS: Exposure to >96% oxygen before cardioplegia did not attenuate ischaemia-reperfusion injury of the heart in patients undergoing coronary artery bypass grafting. The only potentially beneficial effect observed was the decreased transmyocardial release of interleukin-6.

Defining gastrointestinal failure.

INTRODUCTION: Gastrointestinal failure (GIF) has been postulated as the motor of multiple organ dysfunction syndrome (MODS) but is not commonly included among other organ failures in scoring systems identifying MODS. MATERIALS AND METHODS: Relevant articles and published reviews were identified and analyzed through a PubMed search of English language literature on gastrointestinal problems. RESULTS AND DISCUSSION: Wide variability in terms and definitions was observed. Data on the incidence of GIF and its impact on mortality in critically ill patients are controversial. Very few objectively measurable variables of GI function are available. Most of the definitions of GIF are diagnosis-, but not function-based. Diagnosis-based approach to GIF differs significantly from the function-based assessment of other organ failures and has not justified itself over time. CONCLUSIONS: There is no consensus on definition of GIF and different medical specialties have different approaches. Development of a proper definition of GIF is warranted.

Defining gastrointestinal failure.

INTRODUCTION: Gastrointestinal failure (GIF) has been postulated as the motor of multiple organ dysfunction syndrome (MODS) but is not commonly included among other organ failures in scoring systems identifying MODS. MATERIALS AND METHODS: Relevant articles and published reviews were identified and analyzed through a PubMed search of English language literature on gastrointestinal problems. RESULTS AND DISCUSSION: Wide variability in terms and definitions was observed. Data on the incidence of GIF and its impact on mortality in critically ill patients are controversial. Very few objectively measurable variables of GI function are available. Most of the definitions of GIF are diagnosis-, but not function-based. Diagnosis-based approach to GIF differs significantly from the function-based assessment of other organ failures and has not justified itself over time. CONCLUSIONS: There is no consensus on definition of GIF and different medical specialties have different approaches. Development of a proper definition of GIF is warranted.

An antioxidant tetrapeptide UPF1 in rats has a neuroprotective effect in transient global brain ischemia.

Different glutathione analogues have potential to maintain or increase tissue glutathione level and to scavenge the reactive oxygen species. We designed and synthesized a novel non-toxic glutathione analogue, named UPF1, which possessed 60-fold higher hydroxyl radical scavenger efficiency in vitro, compared with glutathione itself, and investigated the effects of UPF1 on a four-vessel occlusion model of rats. The UPF1 was administered via the jugular vein in two separate experiments at two time points: 20 min before global brain ischemia and immediately before reperfusion. In both cases the number of pyramidal cells surviving in the subfield of CA1 at the dorsal hippocampus in the UPF1-treated groups of rats was twice as high as in the vehicle group.

Exposure of rats to hyperoxia enhances relaxation of isolated aortic rings and reduces infarct size of isolated hearts.

Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia-reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose-response to phenylephrine (PHE), prostaglandin F2alpha (PGF2alpha) and endothelin-1 (ET-1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer-perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 +/- 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 +/- 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application.

Cardioprotection by breathing hyperoxic gas-relation to oxygen concentration and exposure time in rats and mice.

OBJECTIVES: Breathing a hyperoxic gas (> or =95% O(2)) protects against ischaemia-reperfusion injury in rat and mouse hearts. The present study investigated how oxygen concentration and duration of hyperoxic exposure influenced cardioprotection, and whether hyperoxia might induce delayed cardioprotection (after 24 h). METHODS: Animals were kept in normal air or in a hyperoxic environment, and their hearts were isolated and Langendorff-perfused immediately or 24 h thereafter. Global ischaemia was induced for 25 min in rats and 40 min in mice, followed by 60 min of reperfusion. Infarct size was determined by triphenyl tetrazolium chloride staining. RESULTS: In rats exposure to > or =95, 80, and 60%, but not to 40% of oxygen immediately before heart isolation and perfusion improved postischaemic functional recovery. Eighty or more percent of oxygen also reduced infarct size. A preconditioning-like effect could be evoked by 60 or 180 min of hyperoxia, giving both immediate and delayed protection. In the mouse heart protection could be induced by pretreatment for 15 or 30, but not by 60 min with > or =95% oxygen. The protective effect of hyperoxia in mice could be evoked in the immediate model only. CONCLUSIONS: Hyperoxia protects the isolated rat and mouse heart against ischaemia-reperfusion injury, but some species-different responses exist. The protection depends on both oxygen concentration in inspired air, and duration of hyperoxic exposure.