losartan-potassium and Heart-Arrest

Many efforts have been made in the last decades to improve outcome in patients who are successfully resuscitated from sudden cardiac arrest. Despite some advances, postanoxic encephalopathy remains the most common cause of death among those patients and several investigations have focused on early neuroprotection in this setting.. Therapeutic hypothermia is the only strategy able to provide effective neuroprotection in clinical practice. Experimental studies showed that therapeutic hypothermia was even more effective when it was started immediately after the ischemic event. In human studies, the use of prehospital hypothermia was able to reduce the time to target temperature but did not result in higher survival rate or neurological recovery in patients with out-of-hospital cardiac arrest, when compared with standard in-hospital therapeutic hypothermia. Thus, intra-arrest hypothermia (i.e., initiated during cardiopulmonary resuscitation) may be a valid alternative to improve the effectiveness of therapeutic hypothermia in this setting; however, more clinical data are needed to demonstrate any potential benefit of such intervention on neurological outcome. Together with cooling, early hemodynamic optimization should be considered to improve cerebral perfusion in cardiac arrest patients and minimize any secondary brain injury. Nevertheless, only scarce data are available on the impact of early hemodynamic optimization on the development of organ dysfunction and neurological recovery in such patients. Some new protective strategies, including inhaled gases (i.e., xenon, argon, nitric oxide) and intravenous drugs (i.e., erythropoietin) are emerging in experimental studies as promising tools to improve neuroprotection, especially when combined with therapeutic hypothermia.. Early cooling may contribute to enhance neuroprotection after cardiac arrest. Hemodynamic optimization is mandatory to avoid cerebral hypoperfusion in this setting. The combination of such interventions with other promising neuroprotective strategies should be evaluated in future large clinical studies.

Topics: Administration, Inhalation; Cardiopulmonary Resuscitation; Erythropoietin; Female; Heart Arrest; Humans; Hypothermia, Induced; Hypoxia, Brain; Male; Neuroprotective Agents; Recovery of Function; Xenon

Topics: Adenosine Triphosphate; Animals; Cardiopulmonary Resuscitation; Energy Metabolism; Erythropoietin; Heart Arrest; Humans; Mitochondria; Mitochondria, Heart; Protein Isoforms; Sodium-Hydrogen Exchangers; Treatment Outcome

Sudden cardiac arrest is a leading cause of death worldwide with survival rates still remaining suboptimal. Unfortunately, most cardiac arrest patients, who achieve return of spontaneous circulation (ROSC), develop a multi-faceted post-cardiac arrest syndrome, including post-cardiac arrest brain injury, myocardial dysfunction, and systemic ischemia/reperfusion response. Erythropoietin (EPO), the principal hematopoietic hormone regulating erythropoiesis, exhibits diverse cellular effects in nonhematopoietic tissues. Due to its anti-apoptotic, anti-inflammatory, and anti-oxidant properties, as well as its angiogenic action, EPO plays a role in neuroprotection and cardioprotection. In this regard, EPO represents a promising agent in the cardiac arrest setting, based on a therapeutic strategy that focuses on the post-resuscitation phase. This review aims to provide a comprehensive account of EPO's role in the treatment of each individual component of post-cardiac arrest syndrome.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Brain Diseases; Cardiomyopathies; Cardiotonic Agents; Erythropoietin; Heart Arrest; Humans; Reperfusion Injury; Syndrome

To test the possible neuroprotective effect of early high-dose erythropoietin-alpha (Epo-alpha) after out-of-hospital cardiac arrest (OHCA).. A matched control study. Following resuscitation with mild hypothermia after OHCA, participants received a first dose of Epo-alpha followed by four additional injections within 48 h (40,000 IU intravenously each injection). Plasma Epo-alpha levels were measured at different time points. Outcome and adverse events were assessed up to day 28 and were compared with those of matched-paired controls.. In all 18 participants received Epo-alpha and were compared with 40 matched controls. Pharmacokinetic variables were similar to those previously reported for healthy people or for persons treated with usual dosages of Epo. At day 28, survival rates among the Epo-treated group and the controls (55% versus 47.5%, p=0.17) and rates of full neurological recovery (55% versus 37.5%) did not differ significantly. Incidences of thrombocytosis in the Epo-treated group and controls were 15% and 5%, respectively; an arterial vascular thrombosis was observed in one case (5%) from the Epo-treated cohort.. Among victims of OHCA treated with Epo-alpha and hypothermia, we observed a high survival rate, with no minor cerebral sequels but potential haematological side effects. Future studies of Epo should pay particular attention to these findings.

Topics: Aged; Cardiopulmonary Resuscitation; Erythropoietin; Female; Heart Arrest; Hemoglobins; Humans; Hypothermia, Induced; Leukocyte Count; Male; Middle Aged; Neuroprotective Agents; Pilot Projects; Prospective Studies; Recovery of Function; Survival Analysis; Thrombocytosis

Activation of renin-angiotensin system (RAS) is one of the pathological mechanisms associated with myocardial ischemia-reperfusion injury following resuscitation. The present study aimed to determine whether erythropoietin (EPO) improves post‑resuscitation myocardial dysfunction and how it affects the renin‑angiotensin system. Sprague‑Dawley rats were randomly divided into sham, vehicle, epinephrine (EP), EPO and EP + EPO groups. Excluding the sham group, all groups underwent cardiopulmonary resuscitation (CPR) 4 min after asphyxia‑induced cardiac arrest (CA). EP and/or EPO was administrated by intravenous injection when CPR began. The results demonstrated that the vehicle group exhibited lower mean arterial pressure, left ventricular systolic pressure, maximal ascending rate of left ventricular pressure during left ventricular isovolumic contraction and maximal descending rate of left ventricular pressure during left ventricular isovolumic relaxation (+LVdP/dt max and ‑LVdP/dt max, respectively), and higher left ventricular end‑diastolic pressure, compared with the sham group following return of spontaneous circulation (ROSC). Few significant differences were observed concerning the myocardial function between the vehicle and EP groups; however, compared with the vehicle group, EPO reversed myocardial function indices following ROSC, excluding‑LVdP/dt max. Serum renin and angiotensin (Ang) II levels were measured by ELISA. The serum levels of renin and Ang II were significantly increased in the vehicle group compared with the sham group, which was also observed for the myocardial expression of renin and Ang II receptor type 1 (AT1R), as determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. EPO alone did not significantly reduce the high serum levels of renin and Ang II post-resuscitation, but changed the protein levels of renin and AT1R expression in myocardial tissues. However, EPO enhanced the myocardial expression of Ang II receptor type 2 (AT2R) following ROSC. In conclusion, the present study confirmed that CA resuscitation activated the renin‑Ang II‑AT1R signaling pathway, which may contribute to myocardial dysfunction in rats. The present study confirmed that EPO treatment is beneficial for protecting cardiac function post‑resuscitation, and the roles of EPO in alleviating post‑resuscitation myocardial dysfunction may potentially be associated with enhanced myocardial expression of AT2R.

Topics: Angiotensin II; Animals; Biomarkers; Cardiomyopathies; Cardiopulmonary Resuscitation; Erythropoietin; Female; Gene Expression Regulation; Heart Arrest; Male; Myocardium; Rats; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin

To study the protective effect of erythropoietin (EPO) on brain tissue with cardiac arrest-cardiopulmonary resuscitation (CA-CPR) and its mechanism.. 120 male Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 40), namely: sham group, routine chest compression group, and conventional chest compression + EPO group (EPO group). The rats in each group were subdivided into CA and 6, 12, 24, 48 hours after restoration of spontaneous circulation (ROSC) five subgroups (each n = 8). The model of CA was reproduced according to the Hendrickx classical asphyxia method followed by routine chest compression, and the rats in sham group only underwent anesthesia, tracheostomy intubation and venous-puncture without asphyxia and CPR. The rats in EPO group were given the routine chest compression + EPO 5 kU/kg (2 mL/kg) after CA. Blood sample was collected at different time points of intervention for the determination the content of serum S100 β protein by enzyme linked immunosorbent assay (ELISA). All the rats were sacrificed at the corresponding time points, and the hippocampus was harvested for the calculation of the number of S100 β protein positive cells, and to examine the pathological changes and their scores at 24 hours after ROSC by light microscopy.. With prolongation of ROSC time, the serum levels of S100 β protein (µg/L) in the routine chose compression group and the EPO group were significantly elevated, peaking at 24 hours (compared with CA: 305.7 ± 29.2 vs. 44.4 ± 6.2 in routine chest compression group, and 276.7 ± 28.9 vs. 44.7 ± 5.6 in the EPO group, both P < 0.05), followed by a fall. The levels of S100 β protein at each time point after ROSC in EPO group were significanthy lower than those of the routine chest compression group (83.2 ± 7.5 vs. 114.3 ± 15.3 at 6 hours, 123.9 ± 20.2 vs. 184.9 ± 22.2 at 12 hours, 276.7 ± 28.9 vs. 305.7 ± 29.2 at 24 hours, 256.3 ± 26.6 vs. 283.2 ± 23.6 at 48 hours, all P < 0.05). With the prolongation of ROSC time, the S100 β protein positive cell number in brain (cells/HP) in the routine chest compression group and the EPO group was significantly increased, peaking at 24 hours (compared with CA: 14.3 ± 2.2 vs. 6.7 ± 0.7 in the routine chest compression group, 11.3 ± 1.3 vs. 6.8 ± 0.9 in the EPO group, both P < 0.05), then it began to fall. The S100 β protein positive cell number in brain at each time point after ROSC in the EPO group was significantly lower than that of the routine chest compression group (7.0 ± 0.9 vs. 7.9 ± 1.9 at 6 hours, 8.4 ± 1.1 vs. 10.2 ± 2.2 at 12 hours, 11.3 ± 1.3 vs. 14.3 ± 2.2 at 24 hours, 8.3 ± 0.8 vs. 10.8 ± 2.0 at 48 hours, all P < 0.05). Under the light microscope, a serious brain cortex injury was found after reproduction of the model, and the degree of injury was reduced after EPO intervention. The pathological score at 24 hours after ROSC in EPO group was lower than that of routine chest compression group (3.83 ± 0.73 vs. 4.17 ± 0.75, P < 0.05).. The S100 β protein level in serum and brain tissue was increased early in asphyxia CA-CPR rats. EPO intervention can reduce the expression of S100 protein and reduce the degree of brain injury.

Topics: Animals; Asphyxia; Brain; Brain Injuries; Cardiopulmonary Resuscitation; Erythropoietin; Heart Arrest; Male; Random Allocation; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein beta Subunit

In addition to its role in the endogenous control of erythropoiesis, recombinant human erythropoietin (rh-EPO) has been shown to exert tissue protective properties in various experimental models. However, its role in the cardiac arrest (CA) setting has not yet been adequately investigated.. The aim of this study is to examine the effect of rh-EPO in a pig model of ventricular fibrillation (VF)-induced CA.. Ventricular fibrillation was electrically induced in 20 piglets and maintained untreated for 8 minutes before attempting resuscitation. Animals were randomized to receive rh-EPO (5000 IU/kg, erythropoietin [EPO] group, n = 10) immediately before the initiation of chest compressions or to receive 0.9% Sodium chloride solution instead (control group, n = 10).. Compared with the control, the EPO group had higher rates of return of spontaneous circulation (ROSC) (100% vs 60%, P = .011) and higher 48-hour survival (100% vs 40%, P = .001). Diastolic aortic pressure and coronary perfusion pressure during cardiopulmonary resuscitation were significantly higher in the EPO group compared with the control group. Erythropoietin-treated animals required fewer number of shocks in comparison with animals that received normal saline (P = .04). Furthermore, the neurologic alertness score was higher in the EPO group compared with that of the control group at 24 (P = .004) and 48 hours (P = .021).. Administration of rh-EPO in a pig model of VF-induced CA just before reperfusion facilitates ROSC and improves survival rates as well as hemodynamic variables.

Topics: Animals; Blood Circulation; Blood Pressure; Cardiopulmonary Resuscitation; Disease Models, Animal; Erythropoietin; Female; Heart Arrest; Swine; Treatment Outcome; Ventricular Fibrillation

To examine the effects of EPO administration on the integrity of myocardium in a rat model of asphyxia-induced cardiac arrest/CPR.. 24 male Sprague-Dawley (SD) rats were randomly divided into three groups (8 each) to receive (1) cardiac arrest (induced by tracheal catheter clamping for 8 minutes)/CPR (by chest compressions and mechanical ventilation 8 minutes after cardiac arrest), (2) cardiac arrest/CPR +EPO (5 kU/kg, i.v, 3 minutes after restoration of spontaneous circulation (ROSC), and (3) no-treatment (control). The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal positive/negative filling pressure change versus time (±dp/dt max) in the animals were recorded 30, 60, 90, and 120 minutes after ROSC. Blood and heart tissue samples were collected 120 minutes after ROSC for the examination of serum troponin I (cTnI) level, myocardium pathological change (by light/electronic microscopy), and myocardium apoptosis [by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) staining].. The LVSP, +dp/dt max and - dp/dt max absolute value in CPR group and EPO group were significantly lower than those of baseline at 30, 60, 90, 120 minutes after ROCS. In comparison with the control group, the LVSP( mm Hg, 1 mm Hg = 0.133 kPa: 119.52±12.68, 134.32±15.78 vs. 165.82±7.05), +dp/dt max (mm Hg/sec: 4457.14±826.22, 6019.85±1192.19 vs. 10325.93±773.09), and - dp/dt max ( mm Hg/sec: - 3956.04±952.37, - 4957.22±838.60 vs. - 8421.33±886.65) were significant lower (all P < 0.01) in the CPR and EPO group 30 minutes after ROSC, and such tendency remained till 120 minutes after ROSC: (LVSP: 124.62±8.07, 145.61±16.70 vs. 162.34±7.63; +dp/dt max: 4977.67±350.40, 7471.62±998.32 vs. 9999.39±727.96; - dp/dt max: - 4145.51±729.77, - 5895.64±787.30 vs. - 8089.75±981.52). Compared to the CPR group, the value of LVSP, + dp/dt max and - dp/dt max at all time points were significantly higher in EPO group (all P < 0.05). The LVEDP value was significantly higher ( P < 0.01) in both CPR and EPO group in comparison with the control (mm Hg/sec: 22.94±3.94, 11.18±2.58 vs. 2.89±0.70) 120 minutes after ROSC, and it was significantly lower in EPO group in comparison with CPR group ( P < 0.05). Light/electronic microscopy revealed myocardial necrosis, inflammatory cell infiltration, myocardial cell membrane integrity loss, mitochondrial swelling, and increased number of apoptotic cardiomyocyte (314.1±30.7 vs. 165.2±45.9 as in control) in CPR group samples. In contrast, the cardiomyocyte morphologic damages were significantly fewer in EPO group, so is the numbers of apoptotic cardiomyocyte (242.1±20.0 vs. 314.1±30.7, P < 0.05). In comparison with the control, the serum cTnI 120 minutes after ROSC was significantly higher (all P < 0.01) in CPR and EPO group (μg/L: 20.70±5.96,16.98±3.81 vs. 2.60±0.86), but no such difference was found between these two groups.. EPO can attenuate the post resuscitation myocardial injury probably through its mitochondrial protective, anti-apoptotic effect.

Topics: Animals; Asphyxia; Cardiopulmonary Resuscitation; Erythropoietin; Heart Arrest; Male; Myocardium; Rats; Rats, Sprague-Dawley; Troponin I

Erythropoietin activates potent protective mechanisms in non-hematopoietic tissues including the myocardium. In a rat model of ventricular fibrillation, erythropoietin preserved myocardial compliance enabling hemodynamically more effective CPR.. To investigate whether intravenous erythropoietin given within 2 min of physician-led CPR improves outcome from out-of-hospital cardiac arrest.. Erythropoietin (90,000 IU of beta-epoetin, n=24) was compared prospectively with 0.9% NaCl (concurrent controls=30) and retrospectively with a preceding group treated with similar protocol (matched controls=48).. Compared with concurrent controls, the erythropoietin group had higher rates of ICU admission (92% vs 50%, p=0.004), return of spontaneous circulation (ROSC) (92% vs 53%, p=0.006), 24-h survival (83% vs 47%, p=0.008), and hospital survival (54% vs 20%, p=0.011). However, after adjusting for pretreatment covariates only ICU admission and ROSC remained statistically significant. Compared with matched controls, the erythropoietin group had higher rates of ICU admission (92% vs 65%, p=0.024) and 24-h survival (83% vs 52%, p=0.014) with statistically insignificant higher ROSC (92% vs 71%, p=0.060) and hospital survival (54% vs 31%, p=0.063). However, after adjusting for pretreatment covariates all four outcomes were statistically significant. End-tidal PCO(2) (an estimate of blood flow during chest compression) was higher in the erythropoietin group.. Erythropoietin given during CPR facilitates ROSC, ICU admission, 24-h survival, and hospital survival. This effect was consistent with myocardial protection leading to hemodynamically more effective CPR (Trial registration: http://isrctn.org. Identifier: ISRCTN67856342).

Topics: Aged; Cardiopulmonary Resuscitation; Cardiovascular Agents; Coronary Circulation; Erythropoietin; Female; Heart; Heart Arrest; Humans; Infusions, Intravenous; Male; Middle Aged; Retrospective Studies; Sodium Chloride; Survival Analysis; Treatment Outcome

Recent data have demonstrated potent cardioprotective and neuroprotective effects of the application of growth hormones like erythropoietin (EPO) after focal cardiac or cerebral ischemia. In order to assess possible benefits regarding survival and resuscitation conditions, EPO was tested against placebo in a model of cardiac arrest in the rat.. Thirty-four male Wistar rats were randomized into two groups (EPO versus control; n=17 per group). Under anesthesia, cardiac arrest was induced by asphyxia after neuromuscular blockade. After 6 min of global ischemia, animals were resuscitated by external chest compression combined with epinephrine administration. An intravenous bolus of recombinant human EPO (rhEPO, 3000 UIkg(-1) body weight, i.v.) or saline (in control group) was performed 15 min before cardiac arrest, by a blinded investigator. Restoration of spontaneous circulation (ROSC), survival at 1, 24, 48 and 72 h and hemodynamic changes after cardiac arrest were studied.. Survival to 72 h was significantly improved in the EPO group (n=15/17) compared to the control group (n=7/17). All the EPO-treated rats were successfully resuscitated whereas only 13 of 17 control animals resuscitated. EPO-treated animals required a significantly smaller dose of epinephrine before resuscitation, compared to control rats. Time course of systolic arterial blood pressure after resuscitation revealed no significant differences between both groups.. EPO, when administrated before cardiac arrest, improved initial resuscitation and increased the duration of post-resuscitation survival.

Topics: Advanced Cardiac Life Support; Animals; Cardiovascular Agents; Disease Models, Animal; Erythropoietin; Heart Arrest; Male; Rats; Rats, Wistar

Topics: Cardiopulmonary Resuscitation; Cardiovascular Agents; Erythropoietin; Heart Arrest; Humans

Erythropoietin has been noted for its cardioprotective effects. The objective of the study is to investigate its effects on postresuscitation myocardial dysfunction and therapeutic windows.. Randomized animal study.. Animal research laboratory.. Adult male adult Wistar rats.. Cardiopulmonary resuscitation was started after 6.5 or 9.5 mins of asphyxia-induced cardiac arrest. The resuscitated animals received either erythropoietin (1000, 3000, or 5000 U/kg) or placebo intravenously 3 mins after return of spontaneous circulation.. Erythropoietin treatment improved the 3-day survival and left ventricular dP/dt40 and peak negative dP/dt after 6.5 mins asphyxia-induced cardiac arrest. The cardioprotective effects of erythropoietin decreased after 9.5 mins asphyxia-induced cardiac arrest with worse postresuscitation left ventricular dP/dt40 and peak negative dP/dt (p < .01 for both). The erythropoietin showed a dose-dependent response for its cardioprotective effects. The 3-day survival rates were higher in the group treated with erythropoietin 5000 U/kg than with 3000 and 1000 U/kg groups (p = .045 and .003, respectively). Postresuscitation left ventricular dP/dt40 and peak negative dP/dt were more preserved in the group treated with erythropoietin 5000 U/kg than the groups with lower doses (p < .05 for both).. Erythropoietin has the potential to improve postresuscitation myocardial dysfunction and short-term survival in appropriate therapeutic windows.

Topics: Animals; Cardiotonic Agents; Coronary Circulation; Dose-Response Relationship, Drug; Erythropoietin; Heart Arrest; Hemodynamics; Male; Myocardial Reperfusion Injury; Random Allocation; Rats; Rats, Wistar; Respiration, Artificial; Time Factors

Topics: Animals; Brain; Brain Ischemia; Erythropoietin; Heart Arrest; Injections, Intravenous; Rats; Recovery of Function; Treatment Outcome

After transient global cerebral ischaemia, selectively vulnerable areas of the brain show delayed neuronal degeneration. Recent data have demonstrated potent neuroprotective effects of the application of growth hormones like erythropoietin (EPO) after focal cerebral ischaemia. In order to assess possible effects of the application of EPO on cerebral recovery after cardiac arrest in rats, the vulnerable hippocampal CA-1 sector was investigated.. Thirty male Wistar rats were randomised into two groups (EPO versus placebo; n=15 per group). Cardiac arrest was induced by ventricular fibrillation during general anaesthesia. After 6 min of global cerebral ischaemia, animals were resuscitated by external chest compressions combined with defibrillation. Investigator blinded bolus application of EPO (5000 IE/kg bodyweight) and placebo was performed at three different time points, respectively: 5 min before cardiac arrest (i.v.; intravenously), 24h (i.p.; intraperitoneally) and 72 h (i.p.) after ischaemia. At 24h, 72 h and 7 days, animals were tested according to a neurological deficit score. After of reperfusion, coronal brain sections were analysed by TUNEL- and Nissl-staining. A caspase activity assay was done to determine antiapoptotic properties of EPO. Statistical analyses were done using ANOVA.. Neurological deficit scoring did not show differences between the groups. However, in all groups typical delayed neuronal degeneration could be found in the CA-1 sector. There was no difference in neuronal survival between the groups (viable neurons EPO (median [interquartile range]): 15.5 [10.1-21.3]; placebo: 16.8 [7.7-26.3]). Results from TUNEL-staining revealed no differences in the amount of apoptotic cell death between the groups (EPO: 71.2 [58.1-81.8]; placebo: 73.4 [67.8-78.2]). Caspase activity assays demonstrated a strong expression of general caspase activity as well as caspase-3 activity in the CA-1 sector and the nucleus reticularis thalami, without any differences between both groups.. Despite the well known neuroprotective properties of EPO in ischaemia induced neuronal degeneration, this study could not reveal any beneficial effects of EPO after global cerebral ischaemia due to cardiac arrest in rats.

Topics: Analysis of Variance; Animals; Brain Ischemia; Caspases; Erythropoietin; Heart Arrest; In Situ Nick-End Labeling; Injections, Intravenous; Male; Random Allocation; Rats; Rats, Wistar; Statistics, Nonparametric

To investigate the effect of erythropoietin for the management of postresuscitation myocardial dysfunction following asphyxia-induced cardiac arrest. Male adult Wistar rats were used for the prospective controlled animal study. Asphyxia-induced cardiac arrest was performed by turning-off the ventilator and clamping the endotracheal tube. Cardiopulmonary resuscitation with an intravenous injection of 0.01 mg/kg epinephrine and mechanical ventilation were started after 6.5 minutes of asphyxia. The resuscitated animals received either erythropoietin (5000 U/kg) or equivalent volume of 0.9% saline as placebo intravenously 3 minutes after return of spontaneous circulation. The erythropoietin treatment produced better left ventricular dP/dt40 and -dP/dt in the invasive hemodynamic measurements, and left ventricular fraction shortening by echocardiography. Administration of erythropoietin also improved three days survival among those successfully resuscitated. The molecular effects of erythropoietin were shown by activation of its down streaming Akt and ERK 42/44 signaling pathways. EPO has the potential to improve postresuscitation myocardial dysfunction and short term survival in rats after asphyxia-induced cardiac arrest.

Topics: Animals; Asphyxia; Cardiopulmonary Resuscitation; Cardiotonic Agents; Disease Models, Animal; Erythropoietin; Heart; Heart Arrest; Male; Rats; Rats, Wistar; Recombinant Proteins; Signal Transduction; Ventricular Dysfunction, Left

Inflammation and hypoxia are frequently associated, but their interaction is poorly understood. In vitro studies have shown that hypoxia stimulates the genes of acute phase proteins (APP) and cytokines known to induce APP. We decided to determine kinetics and potential determinants of an acute phase response after cardiac arrest and to assess whether isolated moderate hypoxia can induce APP in humans in vivo.. Prospective, observational study in patients and human experiment.. Tertiary care university hospital.. 22 patients after primarily successful cardiopulmonary resuscitation (CPR) and 7 healthy volunteers.. None in patients; exposure of volunteers to simulated altitude (460 torr/6 h).. Following CPR, type-1 APP (C-reactive protein, alpha 1-acidglycoprotein, serum amyloid A) and type-2 APP (haptoglobin, alpha 1-antitrypsin) increased consistently within 1-2 days and the 'negative' APP transferrin was downregulated. This APP response occurred irrespective of the cause of arrest, the estimated time of anoxia, clinical course or patient outcome and was not different in patients with and without infectious complications. Exposure of healthy volunteers to less severe but more prolonged hypoxia did not induce APP, although a time dependent increase of serum erythropoietin (EPO) was measurable under these conditions, indicating the activation of oxygen dependent gene expression.. (i) A marked acute phase response occurs regularly after cardiac arrest, but within the complexity of this situation the severity of hypoxia is not a predominant determinant of this response. (ii) Despite in vitro evidence for similarities in the oxygen dependent regulation of APP and EPO production, the oxygen sensitivity of these proteins in vivo is different. (iii) Measurements of APP are not revealing regarding infectious complications in the early phase after CPR.

Topics: Acute-Phase Proteins; Acute-Phase Reaction; Adolescent; Adult; Aged; Cardiopulmonary Resuscitation; Erythropoietin; Female; Heart Arrest; Hemoglobins; Humans; Hypoxia; Inflammation; Kinetics; Male; Middle Aged; Prospective Studies