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At least 235 records · Page 13Linked to original sources
PubMed2004

Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results.

BACKGROUND: Successful antitachycardia pacing (ATP) terminates ventricular tachycardia (VT) up to 250 bpm without the need for painful shocks in implantable cardioverter-defibrillator (ICD) patients. Fast VT (FVT) >200 bpm is often treated by shock because of safety concerns, however. This prospective, randomized, multicenter trial compares the safety and utility of empirical ATP with shocks for FVT in a broad ICD population. METHODS AND RESULTS: We randomized 634 ICD patients to 2 arms-standardized empirical ATP (n=313) or shock (n=321)-for initial therapy of spontaneous FVT. ICDs were programmed to detect FVT when 18 of 24 intervals were 188 to 250 bpm and 0 of the last 8 intervals were >250 bpm. Initial FVT therapy was ATP (8 pulses, 88% of FVT cycle length) or shock at 10 J above the defibrillation threshold. Syncope and arrhythmic symptoms were collected through patient diaries and interviews. In 11+/-3 months of follow-up, 431 episodes of FVT occurred in 98 patients, representing 32% of ventricular tachyarrhythmias and 76% of those that would be detected as ventricular fibrillation and shocked with traditional ICD programming. ATP was effective in 229 of 284 episodes in the ATP arm (81%, 72% adjusted). Acceleration, episode duration, syncope, and sudden death were similar between arms. Quality of life, measured with the SF-36, improved in patients with FVT in both arms but more so in the ATP arm. CONCLUSIONS: Compared with shocks, empirical ATP for FVT is highly effective, is equally safe, and improves quality of life. ATP may be the preferred FVT therapy in most ICD patients.

Aged↗
PubMed1994

Relation between shock-related myocardial injury and defibrillation efficacy of monophasic and biphasic shocks in a canine model.

BACKGROUND: Certain biphasic waveforms with specific time ratios of positive and negative components require less energy for successful defibrillation of the fibrillating ventricles than monophasic waveforms. However, if more efficient waveforms were also to be associated with more injurious effects on myocardial function, they might not provide a true biological advantage. This study investigates the relation between defibrillation efficacy and potential toxicity of monophasic and asymmetric, single capacitor, biphasic waveforms with equal durations of positive and negative components. METHODS AND RESULTS: The myocardial lactate extraction rate (LER) was used to measure the injurious effects on myocardial oxidative metabolism of two synchronized 35-J shocks in sinus rhythm. LER, mean arterial pressure (MAP) and, in a subset of experiments, cardiac output (CO) and coronary blood flow (CBF) were measured at baseline, 30 seconds, 60 seconds, 90 seconds, 150 seconds, 300 seconds, and 600 seconds after the shocks. In 12 dogs, three different waveforms (M 10: monophasic 10 milliseconds; BI 10: biphasic 10 milliseconds; BI 20: biphasic 20 milliseconds) were tested as series of two consecutive shocks (60 seconds apart) resulting in a total of 36 sets of data. At baseline, LER was 25 +/- 11%. After monophasic shocks, LER decreased significantly more than after biphasic shocks (LER at 150 seconds: M 10: -6 +/- 31% versus BI 10: 21 +/- 15% versus BI 20: 21 +/- 16%; M 10 versus BI 10 and M 10 versus BI 20, P < .05) and showed also a slower recovery (LER at 300 seconds: M 10: 1 +/- 24% versus BI 10: 20 +/- 11% versus BI 20: 20 +/- 15%; M 10 versus BI 10 and M 10 versus BI 20, P < .05). The maximal decrease in LER was 41 +/- 27% for M 10 compared with 18 +/- 15% for BI 10 and 15 +/- 11% for BI 20 (both, M 10 versus BI 10 and M 10 versus BI 20, P < .05). There was a similar decrease in CO and MAP, with the lowest MAP after monophasic shocks. The maximal decrease in MAP was significantly greater after M 10 compared with BI 20 (-29 +/- 15 mm Hg versus -13 +/- 11 mm Hg, P < .05). The defibrillation threshold was 18.6 +/- 8 J for M 10 compared with 11.5 +/- 4.0 J for BI 10 (P < .05) and 15.0 +/- 6.1 J for BI 20, respectively (P = NS). CONCLUSIONS: Our results suggest that these specific biphasic waveforms are associated with less injurious effects on myocardial oxidative metabolism and hemodynamic performance. Given their higher defibrillation efficacy as well, biphasic waveforms may provide important long-term benefits in patients receiving frequent shocks from implantable cardioverter-defibrillators.

Animals↗
PubMed1996

Multicenter comparison of truncated biphasic shocks and standard damped sine wave monophasic shocks for transthoracic ventricular defibrillation. Transthoracic Investigators.

BACKGROUND: The most important factor for improving out-of-hospital ventricular fibrillation survival rates is early defibrillation. This can be achieved if small, lightweight, inexpensive automatic external defibrillators are widely disseminated. Because automatic external defibrillator size and cost are directly affected by defibrillation waveform shape and because of the favorable experience with truncated biphasic waveforms in implantable cardioverter-defibrillators, we compared the efficacy of a truncated biphasic waveform with that of a standard damped sine monophasic waveform for transthoracic defibrillation. METHODS AND RESULTS: The principal goal of this multicenter, prospective, randomized, blinded study was to compare the first-shock transthoracic defibrillation efficacy of a 130-J truncated biphasic waveform with that of a standard 200-J monophasic damped sine wave pulse using anterior thoracic pads in the course of implantable cardioverter-defibrillator testing. Pad-pad ECGs were also examined after transthoracic defibrillation. After the elimination of data for 24 patients who did not meet all protocol criteria, the results from 294 patients were analyzed. The 130-J truncated biphasic pulse and the 200-J damped sine wave monophasic pulse resulted in first-shock efficacy rates of 86% and 86%, respectively (P = .97). ST-segment levels measured 10 seconds after the shock in 151 patients in sinus rhythm were -0.26 +/- 1.58 and -1.86 +/- 1.93 mm for the 130- and 200-J shocks, respectively (P < .0001). CONCLUSIONS: We found that 130-J biphasic truncated transthoracic shocks defibrillate as well as the 200-J monophasic damped sine wave shocks that are traditionally used in standard transthoracic defibrillators and result in fewer ECG abnormalities after the shock.

Adolescent↗
PubMed1995

Biphasic defibrillation waveforms reduce shock-induced response duration dispersion between low and high shock intensities.

Mechanisms underlying defibrillation threshold reduction with biphasic waveforms remain unclear. The interaction of local shock-induced voltage gradients, which change with distance from the shocking electrode, and the state of membrane repolarization results in different cellular responses that may influence the success of defibrillation. We used intracellular microelectrodes and S1S2 pacing protocols in myocardial cell aggregates to determine the effects of shock intensity and waveform on refractory period responses during simulated fibrillation (3 s of S1 pacing at 180-ms cycle length). We simulated defibrillation by electric field stimulation S2 using 8-ms monophasic (MS2) and 4/4 biphasic (BS2) waveforms (65% total tilt) delivered at intensities of 1.5, 3, and 5 times S1 diastolic threshold, or approximately 2 to 7 V/cm. Responses following MS2 varied with S2 intensity and coupling interval (P < .001). When averaged over the last 10 ms of the refractory period, MS2 produced a negligible response (8.8 +/- 1.4 ms) at 1.5 times diastolic threshold and a prolonged response (53.0 +/- 3.1 ms) at 5 times diastolic threshold (P < .01). In contrast, BS2 response duration did not change significantly (P - NS) between 1.5 times diastolic threshold (35.1 +/- 12.6 ms) and 5 times diastolic threshold (46.2 +/- 2.7 ms). Our results suggest that biphasic waveforms not only prolong response duration at low shock intensity but reduce dispersion of refractoriness produced by differing local potential gradients generated by defibrillation shocks compared with monophasic waveforms. Preventing dispersion of refractoriness and prolonging shock-induced responses may improve biphasic waveform efficacy at low shock intensity.

Action Potentials↗
PubMed1975

Choice for signalled over unsignalled shock as a function of shock intensity.

Choice between a signalled shock schedule and an unsignalled one was examined at various shock intensities. Three rats were given the opportunity to change from the unsignalled schedule to the signalled one at intensity values between 0.15 mA and 1.0 mA. Steps were usually 0.15 mA and both ascending and descending series were given. For two other rats, shock intensity increased from 0.20 mA to 1.0 mA in 0.20-mA increments; for two additional rats, shock intensity was first 3.0 mA and was then reduced to 1.0 mA. Subjects tended to remain in the unsignalled schedule at the lower shock intensities, but spent most of each session under the signalled schedule at the higher intensities (1.0 mA and 3.0 mA). In addition, the time spent in the signalled schedule tended to vary systematically with shock intensity over at least part of the range of intensity values. It was concluded that the relationship between shock intensity and choice behavior is similar to the relationship between intensity and behavior in procedures involving avoidance, escape, and punishment.

Journal Article↗
PubMed1981

Effects of d-amphetamine on responding of squirrel monkeys maintained under second-order schedules of food presentation, electric shock presentation or stimulus-shock termination.

The effects of d-amphetamine (0.01-5.6 mg/kg i.m.) were studied on lever pressing of squirrel monkeys maintained under various second-order schedules by a visual stimulus (S) that, with separate monkeys, was occasionally paired with the presentation of either food, electric shock or with the termination of a stimulus in the presence of which shocks occurred. Under one condition, the first response after 5 min produced a 3-sec stimulus change and the fourth stimulus change was followed immediately by food delivery, electric shock presentation or by the termination of a stimulus in the presence of which shocks occurred [fixed-ratio (FR); fixed-interval (FI) [FR 4 (FI 5-min:S)]. The effects of d-amphetamine were also studied under the food- and shock-presentation schedules when food or shock occurred only once, at the end of each session, after completion of 53n 3-min fixed-intervals all of which ended with a brief stimulus change [FR 10 (FI 3-min : S)]. Under a third condition, each thirtieth response produced the 3-sec brief stimulus (FR 30 : S) and the first FR 30 completed after 5 min elapsed produced the stimulus followed by food or, with separate monkeys, electric shock [FI 5-min (FR 30:S)]. Low to intermediate doses of d-amphetamine (0.03-0.3 mg/kg) generally increased and higher doses (0.56-5.6 mg/kg) decreased responding under all conditions. The effects of d-amphetamine on responding maintained by brief stimuli under different types of second-order schedules are generally similar, regardless of the type of reinforcing event or particular second-order schedule.

Animals↗
PubMed2001

Mutation of amino acids 566-572 (KKKVLDK) inhibits nuclear accumulation of heat shock protein 72 after heat shock.

Heat shock protein (HSP) 72 translocates from the cytoplasm to the nucleus in response to a wide variety of stresses, including heat shock and tissue ischemia. It is thought that this concentration of HSP72 in the nucleus with stress is part of the protein's protective response. Therefore, further understanding of the regulation of this response would be of interest. The signals regulating HSP72's nuclear localization have not been completely defined. Previously, we observed that mutation of amino acids 246-251 (KRKHKK) reduced nuclear accumulation of HSP72 and that a KRKHKK-EGFP (enhanced green fluorescent protein) fusion protein concentrated in the nucleoli. In examining HSP72 for other potential nuclear localization signals, we identified an additional sequence, KKKVLDK, amino acids 566-572, that might effect nuclear accumulation. We now report that mutation of KKKVLDK inhibited nuclear concentration of HSP72 following heat shock, and the fusion protein KKKVLDK-EGFP concentrated in the nucleus. Cells overexpressing the KKKVLDK mutant showed reduced resistance to heat shock. Mutation of KKKVLDK and KRKHKK abolished nuclear accumulation of HSP72 and reduced cell viability following heat shock to a greater extent than mutation of either site alone. These findings suggest that these two sequences, KRKHKK and KKKVLDK, have complementary function(s) in cellular protection after heat shock.

Adenosine Triphosphate↗
PubMed2001

Absence of gender differences in clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction. A report from the SHOCK Trial Registry.

OBJECTIVES: The aim of this study was to assess the impact of gender on clinical course and in-hospital mortality in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). BACKGROUND: Previous studies have demonstrated higher mortality for women compared with men with ST elevation myocardial infarctions and higher rates of CS after AMI. The influence of gender and its interaction with various treatment strategies on clinical outcomes once CS develops is unclear. METHODS: Using the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? (SHOCK) Registry database of 1,190 patients with suspected CS in the setting of AMI, we examined shock etiologies by gender. Among the 884 patients with predominant left ventricular (LV) failure, we compared the patient demographics, angiographic and hemodynamic findings, treatment approaches as well as the clinical outcomes of women versus men. This study had a 97% power to detect a 10% absolute difference in mortality by gender. RESULTS: Left ventricular failure was the most frequent cause of CS for both gender groups. Women in the SHOCK Registry had a significantly higher incidence of mechanical complications including ventricular septal rupture and acute severe mitral regurgitation. Among patients with predominant LV failure, women were, on average, 4.6 years older, had a higher incidence of hypertension, diabetes and a lower cardiac index. The overall mortality rate for the entire cohort was high (61%). After adjustment for differences in patient demographics and treatment approaches, there was no significant difference in in-hospital mortality between the two gender groups (odds ratio = 1.03, 95% confidence interval of 0.73 to 1.43, p = 0.88). Mortality was also similar for women and men who were selected for revascularization (44% vs. 38%, p = 0.244). CONCLUSIONS: Women with CS complicating AMI had more frequent adverse clinical characteristics and mechanical complications. Women derived the same benefit as men from revascularization, and gender was not independently associated with in-hospital mortality in the SHOCK Registry.

Aged↗
PubMed2003

Percutaneous coronary intervention for cardiogenic shock in the SHOCK trial.

OBJECTIVES: We examined the clinical, angiographic, and procedural characteristics determining survival after percutaneous coronary intervention (PCI) for cardiogenic shock. BACKGROUND: The SHOCK (SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK?) trial prospectively enrolled patients with shock complicating acute myocardial infarction (MI). Patients were randomized to a strategy of early revascularization or initial medical stabilization. METHODS: Patients randomized to early revascularization underwent PCI or bypass surgery on the basis of predefined clinical criteria. Patients randomized to early revascularization who underwent PCI and had angiographic films available for analysis are the subject of this report (n = 82). RESULTS: The median time from MI to PCI was 11 h. The majority of patients had occluded culprit arteries (Thrombolysis In Myocardial Infarction [TIMI] grade 0 or 1 flow in 62%) and multivessel disease (81%). One-year mortality in PCI patients was 50%. Mortality was 39% if PCI was successful but 85% if unsuccessful (p < 0.001). Mortality was 38% if TIMI flow grade 3 was achieved, 55% with TIMI grade 2 flow, and 100% with TIMI grade 0 or 1 flow (p < 0.001). Mortality was 67% if severe mitral regurgitation was documented. Independent correlates of mortality were as follows: increasing age (p < 0.001), lower systolic blood pressure (p = 0.009), increasing time from randomization to PCI (p = 0.019), lower post-PCI TIMI flow (0/1 vs. 2/3) (p < 0.001), and multivessel PCI (p = 0.040). CONCLUSIONS: Restoration of coronary blood flow is a major predictor of survival in cardiogenic shock. Benefit appears to extend beyond the generally accepted 12-h post-infarction window. Surgery should be considered in shock patients with severe mitral insufficiency or multivessel disease not amenable to relatively complete percutaneous revascularization.

Aged↗
PubMed2001

Percutaneous coronary intervention for cardiogenic shock in the SHOCK Trial Registry.

BACKGROUND: The SHOCK Registry prospectively enrolled patients with cardiogenic shock complicating acute myocardial infarction in 36 multinational centers. METHODS: Cardiogenic shock was predominantly attributable to left ventricular pump failure in 884 patients. Of these, 276 underwent percutaneous coronary intervention (PCI) after shock onset and are the subject of this report. RESULTS: The majority (78%) of patients undergoing angiography had multivessel disease. As the number of diseased arteries rose from 1 to 3, mortality rates rose from 34.2% to 51.2%. Patients who underwent PCI had lower in-hospital mortality rates than did patients treated medically (46.4% vs 78.0%, P < .001), even after adjustment for patient differences and survival bias (P = .037). Before PCI, the culprit artery was occluded (Thrombolysis In Myocardial Infarction grade 0 or 1 flow) in 76.3%. After PCI, the in-hospital mortality rate was 33.3% if reperfusion was complete (grade 3 flow), 50.0% with incomplete reperfusion (grade 2 flow), and 85.7% with absent reperfusion (grade 0 or 1 flow) (P < .001). CONCLUSIONS: This prospective, multicenter registry of patients with acute myocardial infarction complicated by cardiogenic shock is consistent with a reduction in mortality rates as the result of percutaneous coronary revascularization. Coronary artery patency was an important predictor of outcome. Measures to promote early and rapid reperfusion appear critically important in improving the otherwise poor outcome associated with cardiogenic shock.

Aged↗
PubMed2002

Gene expression of 70 kDa heat shock protein of Candida albicans: transcriptional activation and response to heat shock.

CaHSP70 (70 kDa heat shock protein) is a highly immunogenic protein of Candida albicans. We have studied heat shock-induced expression of the CaHSP70 gene under germ tube-inductive and non-inductive conditions. The CaHSP70 upstream regulatory region was cloned and sequenced. It contains at least three heat shock elements (HSEs), specific DNA sequences that are bound by the heat shock transcription factor (HSF), and one stress response element (STRE), which is an upstream activator sequence (UAS) that causes transcription activation under stress. The binding of HSF to HSE in the CaHSP70 promoter region is constitutive, although the mobility of protein/DNA complexes is altered after heat shock. The CaHSP70 promoter was cloned into a lacZ reporter plasmid, and was able to respond to heat shock in C. albicans as well as in Saccharomyces cerevisiae.

Amino Acid Sequence↗
PubMed2002

Circulating heat shock protein and heat shock protein antibody levels in established hypertension.

OBJECTIVE: Serum Hsp60 and anti-Hsp65 antibody levels are raised in subjects with borderline hypertension, and there is an association between circulating Hsp60 levels and early atherosclerosis. Given the recognized relationship between hypertension and atherosclerosis, this study determined heat shock protein and heat shock protein antibody levels in subjects with established hypertension. METHODS: Samples from 111 men with hypertension were obtained from the European Lacidipine study on Atherosclerosis and samples from 75 normotensive controls were taken from a population-screening programme (diastolic pressure, 95 and 80 mmHg, respectively). Hsp60, Hsp70 and anti-human Hsp60, anti-human Hsp70 and anti-mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. Intima-media thickness (I-M) and the presence of carotid atherosclerosis were determined by ultrasonography. RESULTS: Hsp60, Hsp70 and anti-Hsp60 antibody levels in hypertension were similar to those in normotensive controls, whereas anti-Hsp70 and anti-Hsp65 antibody levels were elevated ( 0.001). Hsp60 levels and atherosclerosis were not associated. Anti-Hsp70 and anti-Hsp65 antibody levels were both associated with hypertension, independently of age, smoking habits and blood lipids. CONCLUSIONS: This study demonstrates elevated levels of selected heat shock protein antibodies in subjects with hypertension. Although the association between heat shock protein antibody levels and human cardiovascular stress/disease appears to be robust, the relationship of the latter with heat shock protein levels is more complex. Further studies are required before the factors inducing, and the clinical significance of, circulating heat shock proteins can be evaluated.

Antibodies↗
PubMed2002

A comparative study of localization of heat shock protein 27 and heat shock protein 72 in the developmental and degenerative intervertebral discs.

STUDY DESIGN: The lumbar intervertebral discs of 135 subjects after autopsy were immunostained with antihuman heat shock protein 27 (HSP27) monoclonal antibody and antihuman heat shock protein 72 (HSP72) polyclonal antibody. OBJECTIVES: To present the data on metabolic changes that occurred in the chondrocytes of intervertebral discs during development and aging. SUMMARY OF BACKGROUND DATA: Heat shock proteins have been implicated in the progressive degeneration of articular cartilage in joint disease, such as rheumatoid arthritis and osteoarthritis. However, the role and expression of heat shock proteins in human intervertebral discs have received little study. METHODS: One hundred thirty-five specimens of human intervertebral discs were stained with hematoxylin and eosin, alcian blue, and Masson's trichrome and were immunostained with HSP27 and HSP72 by an indirect immunoperoxidase method. The relative amounts of HSP27 and HSP72 deposition were graded according to a semiquantitative scoring system. RESULTS: Heat shock protein 72 accumulated in the cytoplasm of the chondrocytes of both endplate cartilage and nucleus pulposus during gestation and thereafter decreased with aging (age, </=60 years), and HSP72 immunoreactivity increased in the chondrocytes of degenerative discs. In addition, HSP72 was located in the nuclei of certain chondrocytes of the degenerated nucleus pulposus and anulus fibrosus, was highly expressed in the chondrocytes of endplate cartilage during gestation and childhood, and thereafter decreased with aging. Furthermore, with the progressive degeneration of the endplate cartilage, HSP27 immunoreactivity increased. The degree of HSP27 immunoreactivity did not change significantly according to age in either the nucleus pulposus or the anulus fibrosus. CONCLUSIONS: Heat shock protein 27 and HSP72 are thus considered to be useful molecular indicators for degenerative change in intervertebral discs. Both HSP27 and HSP72 are presumed to play a role in cell protection from stress that is induced by mechanical and biologic factors causing intervertebral disc degeneration.

Adult↗
PubMed2002

The modulation of hepatic injury and heat shock expression by inhibition of inducible nitric oxide synthase after hemorrhagic shock.

The role of nitric oxide (NO) in maintaining homeostasis and regulating organ function during hemorrhagic shock is complex. The inducible NO synthase (iNOS) has been hypothesized to play a critical role in the pathophysiologic consequences of severe hemorrhage. Heat shock protein (HSP) expression is increased by hemorrhage and is a marker of the magnitude of ischemic injury in the liver. HSP induction is protective against injury in animal models of inflammation and is regulated by NO in hepatocytes. To clarify the role of iNOS in hepatic injury and its relationship to HSP expression in hemorrhagic shock, NOS was inhibited with L-N-6-(1-iminoethyl) lysine (L-NIL), which is reported to be a selective inhibitor of the inducible NOS isoform. Doses of 50 microg/kg or 150 microg/kg were infused over 1 h at the end of compensated shock. Plasma ornithine carbamoyltransferase (OCT), a specific marker of liver injury, was significantly reduced after hemorrhage with low-dose L-NIL (7.1+/-1.5 IU/L) compared to saline-treated control rats (13.0+/-1.5 IU/L, P < 0.005), while high-dose L-NIL significantly increased OCT release (35.9+/-7.2 IU/L, P< 0.05 versus shock alone) despite a greater MAP after resuscitation. HSP expression (HSP-72 and HSP-32) after hemorrhage was increased by L-NIL treatment at the highest dose. We conclude that excessive NO production from iNOS contributes to shock-induced hepatic injury. Our data suggest HSP expression may reflect the degree of ischemic injury after hemorrhage.

Animals↗
PubMed1997

Stress dose-dependent suppression of heat shock protein gene expression by inhibiting protein synthesis during heat shock treatment.

When a clone of Chinese hamster ovary (CHO) cells transfected with a plasmid containing a luciferase reporter gene under the control of the human heat shock protein (hsp) 70 gene promoter was treated with cycloheximide during heat exposure at 42 and 43 degrees C for 15 to 100 minutes and then incubated at 37 degrees C after removal of cycloheximide, reporter gene expression was suppressed by the protein synthesis inhibitor only at small heat shock doses (i.e., heat shock of less than 40 minutes at 42 degrees C and 15 minutes at 43 degrees C). A similar stress dose-dependent suppression of reporter gene expression by cycloheximide was also demonstrated by treatment with sodium arsenite at 37 degrees C. However, dexamethasone-dependent reporter gene expression in a different CHO clone was not inhibited after the inducer treatment for different times in the presence of cycloheximide. In addition, synthesis of most cellular proteins (except for hsp) was not affected after heat shock treatment with cycloheximide. The results suggested that the cycloheximide inhibition of gene expression is specific to hsp gene expression induced by limited stress doses. Furthermore, a prior 42 degrees C heat shock treatment for 30 minutes induced a decreased responsiveness (tolerance) to a second 42 degrees C heat treatment for hsp gene expression, but tolerance did not develop in cells exposed to the first heat shock in the presence of cycloheximide. These results confirm previous findings that induction of hsp gene expression by stress is balanced by the severity of stress and rate of protein synthesis. They also support the proposed model of autoregulation of hsp gene expression by levels of free hsp70.

Animals↗
PubMed2006

Induction of the 72-kilodalton heat shock protein and protection from ultraviolet B-induced cell death in human keratinocytes by repetitive exposure to heat shock or 15-deoxy-delta(12,14)-prostaglandin J2.

It has been demonstrated that hyperthermia protects keratinocytes from ultraviolet B (UVB)-induced cell death in culture and in vivo. This effect is mediated by the antiapoptotic effect of heat shock proteins that are transiently induced after exposure to heat at sublethal temperatures. Consequently, induction of Hsp has been proposed as a novel means of photoprotection. However, in the face of daily UVB exposure of human skin in vivo, this approach would not be useful if keratinocytes become less sensitive to Hsp induction with repeated exposure to the inducing agent. The aim of this study was to investigate whether repeated exposure to hyperthermia or to the stress protein activating cyclopentenone prostaglandin 15-deoxy-delta(12,14)-prostaglandin J2 (15dPGJ2) leads to adaptation of the cells, attenuation of the heat shock response, and abrogation of the protective effect. Normal human epidermal keratinocytes (NHEK) and the carcinoma-derived cell line A431 were exposed to either 42 degrees C or to 15dPGJ2 for 4 hours at 24-hour intervals for 4 consecutive days. The intracellular level of the 72-kDa heat shock protein (Hsp72) was determined by enzyme-linked immunosorbent assay (ELISA). Cells were exposed to UVB from a metal halide source after the last heat or 15dPGJ2 treatment, and survival was determined 24 hours after exposure by a MTT assay. Our results demonstrate that (1) heat shock and 15dPGJ2 are potent inducers of Hsp72 expression and lead to increased resistance to UVB-induced cell death in human keratinocytes; (2) re-exposure to heat shock leads to a superinduction without attenuation of the absolute increase in Hsp72 and of its UVB-protective effect; (3) the UVB tolerance induced by 15dPGJ2 is enhanced by repeated exposure without a further increase of Hsp72; (4) repeated heat shock and 15dPGJ2 up to a concentration of 1 microg/mL have no influence on cell growth over a period of 4 days. We conclude that through repeated exposure to Hsp-inducing factors, stress tolerance can be maintained without additional toxicity in human keratinocytes. These results provide a basis for the development of nontoxic Hsp inducers that can be repeatedly applied without loss of effect.

Cell Death↗
PubMed1992

Heat-shock gene expression excludes hepatic acute-phase gene expression after resuscitation from hemorrhagic shock.

BACKGROUND: To determine whether the gene expression of both acute-phase reactants (APR) and the major heat-shock protein (hsp-72) can occur simultaneously, transcriptional rates were measured during shock and resuscitation. METHODS: A nuclear runoff technique was applied to hepatic biopsy specimens obtained from pigs before shock, during 40% blood volume hemorrhagic shock (1 and 2 hours), and after resuscitation (4 and 6 hours). RESULTS: Shock-induced transcription of hsp-72 was elevated elevenfold over sham operation at 2 hours (p less than 0.02, Mann-Whitney rank test). Individually shocked animals did not transcribe both classes of stress genes but segregated into two groups: (1) strong APR transcriptional responders and (2) hsp-72 transcriptional responders. In group 2, APR transcription was significantly suppressed. Antichymotrypsin transcription was an average of eighteenfold lower in group 2 versus group 1 (p less than 0.05 at 1,2, and 6 hours). CONCLUSIONS: Different classes of stress protein genes are not transcribed simultaneously. We infer that their increased accumulation at the mRNA level is the result of sequential transcription. Hsp-72 transcription excludes that of the APR genes that may be critical to survival after stress.

Acute-Phase Proteins↗
PubMed2005

[Changes in glucocorticoid receptor and heat shock protein 70 in liver tissue after trauma with hemorrhagic shock in rats].

OBJECTIVE: To investigate changes and functions of glucocorticoid (GR) and heat shock protein 70 (HSP70) at the level of cellular receptor in liver in hemorrhagic shock after trauma. METHODS: Adult Wistar rats were used and a rat model of shock was reproduced by hemorrhaging accompanied by bilateral femur fracture. Changes in hepatic tissue GR, HSP70, pathology of liver, hepatic function markers in serum were dynamically observed. The expression of GR and HSP70 in hepatic tissue was assayed by Western blot and then analyzed with computer imaging system. RESULTS: Protein content of GR gradually decreased in hepatic tissue after trauma, reduced to the nadir at 6 hours after trauma, and it was decreased even more when trauma was added to bleeding. Protein content of HSP70 was gradually increased in hepatic tissue after severe trauma, peaking at 6 hours after trauma, and it maintained at a rather high level at 8 hours after trauma. It was even more increased in when hemorrhagic shock was followed by trauma. Alterations in hepatic function markers and pathology were not obvious after simple trauma. But after trauma was added to hemorrhagic shock, significant increase in alanine aminotransferase (ALT) and total bilirubin (TB) in serum was noted at 4 and 2 hours after trauma respectively (all P<0.01), and albumin content was obviously decreased (P<0.01). There were more inflammatory cell infiltrations in hepatic sinusoids at 6 hours after trauma. CONCLUSION: GR may play an important role in anti-injury mechanism of hepatic tissue cell after trauma with hemorrhagic shock. HSP70 may participate in initiating anti-injury mechanism of hepatic cells.

Animals↗