bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of HSP70 in cultured rat neonatal cardiomyocytes by hypoxia and metabolic stress.
Authors: Iwaki K , Chi S H , Dillmann W H , Mestril R 
Published: June 2012

BACKGROUND
A cultured neonatal rat cardiomyocyte model is used to investigate the expression of the inducible heat shock protein 70 (HSP70i) during hypoxia/reoxygenation and metabolic stress.

METHODS AND RESULTS
The major HSP70i is increased in its expression at the mRNA and protein level in myocytes exposed to hypoxia/reoxygenation and metabolic stress by the addition of 2-deoxyglucose and sodium cyanide, which are inhibitors known to block ATP production. Surprisingly, the appearance of HSP70 mRNA precedes the intracellular ATP depletion caused by hypoxia, which is contrary to what we observe when the cardiomyocytes are subjected to metabolic stress.

CONCLUSIONS
It has been postulated recently that the decrease in intracellular ATP content in cells under stress may be the trigger that leads to the induction of HSP70i by reducing the pool of free HSP70, thus activating the stress response. Our results indicate that although this may be the case during metabolic stress, another route of activation must be used during the early stages of hypoxia in cardiomyocytes. The induction of HSP70i also appears to precede the onset of cellular damage as measured by the release of cytoplasmic enzymes and preincorporated arachidonic acid. This indicates that cardiomyocytes are able to respond to hypoxia/reoxygenation and metabolic stress with increased HSP70i production and points to a potential protective role of heat shock proteins during ischemia/reperfusion injury.
Survival after the onset of congestive heart failure in Framingham Heart Study subjects.
Authors: Ho K K , Anderson K M , Kannel W B , Grossman W , Levy D 
Published: June 2012

BACKGROUND
Relatively limited epidemiological data are available regarding the prognosis of congestive heart failure (CHF) and temporal changes in survival after its onset in a population-based setting.

METHODS AND RESULTS
Proportional hazards models were used to evaluate the effects of selected clinical variables on survival after the onset of CHF among 652 members of the Framingham Heart Study (51% men; mean age, 70.0 +/- 10.8 years) who developed CHF between 1948 and 1988. Subjects were older at the diagnosis of heart failure in the later decades of this study (mean age at heart failure diagnosis, 57.3 +/- 7.6 years in the 1950s, 65.9 +/- 7.9 years in the 1960s, 71.6 +/- 9.4 years in the 1970s, and 76.4 +/- 10.0 years in the 1980s; p < 0.001). Median survival after the onset of heart failure was 1.7 years in men and 3.2 years in women. Overall, 1-year and 5-year survival rates were 57% and 25% in men and 64% and 38% in women, respectively. Survival was better in women than in men (age-adjusted hazards ratio for mortality, 0.64; 95% CI, 0.54-0.77). Mortality increased with advancing age in both sexes (hazards ratio for men, 1.27 per decade of age; 95% CI, 1.09-1.47; hazards ratio for women, 1.61 per decade of age; 95% CI, 1.37-1.90). Adjusting for age, there was no significant temporal change in the prognosis of CHF during the 40 years of observation (hazards ratio for men for mortality, 1.08 per calendar decade; 95% CI, 0.92-1.27; hazards ratio for women for mortality, 1.02 per calendar decade; 95% CI, 0.83-1.26).

CONCLUSIONS
CHF remains highly lethal, with better prognosis in women and in younger individuals. Advances in the treatment of hypertension, myocardial ischemia, and valvular heart disease during the four decades of observation did not translate into appreciable improvements in overall survival after the onset of CHF in this large, unselected population.
Beneficial effects of colestipol-niacin therapy on the common carotid artery. Two- and four-year reduction of intima-media thickness measured by ultrasound.
Authors: Blankenhorn D H , Selzer R H , Crawford D W , Barth J D , Liu C R , Liu C H , Mack W J , Alaupovic P 
Published: June 2012

BACKGROUND
Controlled clinical trials have reported treatment effects evaluated with serial imaging in coronary and femoral but not cervical arteries. The Cholesterol Lowering Atherosclerosis Study, a coronary, cervical, and femoral angiographic trial of colestipol plus niacin, included a pilot study of standardized carotid ultrasound imaging.

METHODS AND RESULTS
Seventy-eight subjects had ultrasound studies at baseline, 2, and 4 years. Twenty-four drug and 22 placebo subjects had carotid ultrasound images at baseline, 2, and 4 years with matching cervical angiograms. Computer image processing was applied to ultrasound images of common carotid (far wall) and cervical angiograms. Computer operators were blind to treatment group. Carotid ultrasound measurements were tested for treatment effects and compared with measurements of atherosclerosis in coronary and cervical angiograms. Drug subjects showed significant progressive reduction in carotid thickness at 2 (P = .0001) and 4 years (P = .0001); placebo subjects significantly increased wall thickness at 2 and 4 years. Reduced levels of apolipoprotein B and increased levels of high density lipoprotein cholesterol and apolipoprotein C-III were significant predictors of carotid wall thinning. Ultrasound-measured carotid intima-media thickness was correlated at baseline with visually read coronary angiographic stenosis and at 2 years with a robust computer measurement of mild carotid atherosclerosis.

CONCLUSIONS
Common carotid intima-media thickening can be reduced by colestipol-niacin treatment. Two-year image-processed carotid ultrasound trials can provide adequate power with 50 subjects per group to test for this treatment effect.
Quantitative assessment of circulatory changes in the fetal aortic isthmus during progressive increase of resistance to umbilical blood flow.
Authors: Bonnin P , Fouron J C , Teyssier G , Sonesson S E , Skoll A 
Published: June 2012

BACKGROUND
This study investigated the effects of impairment to placental flow on flow patterns through the aortic isthmus because in the fetus, this vascular segment is the link between the parallel vascular systems perfused by the left and right ventricles.

METHODS AND RESULTS
A progressive increase in resistance to blood flow through the placenta was created in seven exteriorized fetal lambs by mechanical umbilical vein compression. Blood flows were measured in the ascending aorta, pulmonary artery, aortic isthmus, and umbilical artery at baseline and at each compression level. The severity of the levels of compression was determined by changes in the flow profile through the umbilical artery. An increase in placental resistance causing a fall in umbilical blood flow of approximately 50% was associated with a retrograde diastolic flow through the aortic isthmus even though the diastolic flow through the umbilical artery remained forward. Because of the systolic predominance, however, the net flow in the isthmus was forward. With a more severe increase in placental resistance corresponding to a decrease of 75% in umbilical blood flow, the net flow through the isthmus approached zero. A strong positive correlation was found between the umbilical blood flow and the net flow through the aortic isthmus (r = .89).

CONCLUSIONS
Variations in Doppler blood flow velocity waveforms and integrals of the aortic isthmus can be used as a sensitive indicator of the state of the umbilical circulation.
Preconditioning improves energy metabolism during reperfusion but does not attenuate myocardial stunning in porcine hearts.
Authors: Miyamae M , Fujiwara H , Kida M , Yokota R , Tanaka M , Katsuragawa M , Hasegawa K , Ohura M , Koga K , Yabuuchi Y 
Published: June 2012

BACKGROUND
It has been reported that a brief period of coronary occlusion and reperfusion slows the rate of ATP depletion during subsequent sustained ischemia as well as limiting infarct size. However, it has not yet been determined whether ischemic preconditioning also has an effect on the functional and metabolic recovery of stunned myocardium. Our study was designed to address this problem.

METHODS AND RESULTS
Farm pigs were anesthetized with fluothane and randomly assigned to either a control group or a preconditioned group. The control group (n = 15) underwent 15 minutes of coronary occlusion followed by 120 minutes of reperfusion. The preconditioned group (n = 14) underwent two episodes of 5-minute occlusion and 5-minute reperfusion followed by 15 minutes of occlusion and 120 minutes of reperfusion. This protocol was designed to exclude the stunning effect of the preconditioning procedure itself as much as possible besides preconditioning the heart. A pair of ultrasonic crystals was implanted in the area at risk perfused by the left anterior descending coronary artery. 31P-nuclear magnetic resonance spectroscopy and sonomicrometry were performed alternately. Regional myocardial blood flow (RMBF) was determined with colored microspheres. At 15 minutes of sustained ischemia, phosphocreatine (Pcr), ATP, and intracellular pH were significantly better preserved in the preconditioned group (Pcr: control/preconditioned, 1 +/- 1%/14 +/- 1%; ATP:control/preconditioned, 66 +/- 2%/74 +/- 2%; pH:control/preconditioned, 6.32 +/- 0.07/6.52 +/- 0.05; P < .05). After reperfusion, ATP increased progressively and was almost normalized at 120 minutes of reperfusion in the preconditioned group (control/preconditioned, 73 +/- 4%/95 +/- 3%; P < .05). Overshoot of Pcr (which indicates that the energy generating system is operating better than energy utilizing system) persisted in preconditioned hearts but disappeared rapidly in controls (control/preconditioned, 104 +/- 3%/130 +/- 3% after 120 minutes of reperfusion). There was no significant difference in percent segment shortening (%SS), RMBF, and hemodynamics between the two groups throughout the experiment (%SS: control/preconditioned, 29.8 +/- 5.9%/28.8 +/- 6.3% of baseline after 120 minutes of reperfusion).

CONCLUSIONS
Preconditioning improves energy metabolism during reperfusion, although it does not attenuate myocardial stunning for at least 2 hours after reperfusion.
Platelet membrane activation markers are predictive for increased risk of acute ischemic events after PTCA.
Authors: Tschoepe D , Schultheiss H P , Kolarov P , Schwippert B , Dannehl K , Nieuwenhuis H K , Kehrel B , Strauer B , Gries F A 
Published: June 2012

BACKGROUND
We wished to investigate whether platelet activation is related to the clinical outcome during the 24 hours immediately after elective percutaneous transluminal coronary angioplasty (PTCA).

METHODS AND RESULTS
In 102 patients with high-grade coronary stenosis admitted for elective PTCA, preprocedural platelet activation was characterized by flow cytometric measurement of the proteins CD62, CD63, and thrombospondin expressed on the platelet surface membrane. The prevalence of acute ischemic events during the 24 hours immediately after the procedure was then related to the pre-PTCA platelet activation status. Fifty-six patients were classified as "nonactivated," whereas 46 patients showed an increased percentage of activated platelets. Two patients developed acute occlusion (1.96%) and four patients high-grade restenosis (3.92%), as confirmed by second-look coronary angiography. All events occurred in patients classified as "activated" (six of 46, or 13%). None of these patients received beta-blocker medication, which was associated with lower expression of platelet membrane activation markers. In the nonactivated patient group, no clinical events were found (0 of 56, or 0%). This difference in prevalence is significant (p = 0.007).

CONCLUSIONS
We conclude that analysis of platelet membrane activation markers may help to predict an increased risk of acute ischemic events after angioplasty.
Influence of age and hemodynamics on myocardial blood flow and flow reserve.
Authors: Czernin J , Müller P , Chan S , Brunken R C , Porenta G , Krivokapich J , Chen K , Chan A , Phelps M E , Schelbert H R 
Published: June 2012

BACKGROUND
Aging is associated with changes of the systolic blood pressure that may increase cardiac work and myocardial blood flow at rest and reduce the myocardial flow reserve. This might be misinterpreted as age-related impairment of the coronary vasodilator capacity.

METHODS AND RESULTS
Myocardial blood flow was quantified at rest and after administration of intravenous dipyridamole in 40 healthy volunteers (12 women and 28 men) with 13N-ammonia and positron emission tomography. Eighteen of the normal subjects were less than and 22 were older than 50 years (31 +/- 9 versus 64 +/- 9 years). The resting rate-pressure product was lower in the younger than in the older subjects (6895 +/- 1070 versus 8634 +/- 1890; P < 0.01). Myocardial blood flow at rest averaged 0.76 +/- 0.17 mL.min-1.g-1 in the younger volunteers and 0.92 +/- 0.25 mL.min-1.g-1 in the older volunteers (P < 0.05). Hyperemic blood flows did not differ between younger and older subjects (3.0 +/- 0.8 versus 2.7 +/- 0.6 mL.min-1.g-1; P = NS); however, minimal coronary resistance was higher in the older subjects. Corrected for indexes of coronary driving pressure, hyperemic flow was lower in older than in younger normal subjects. The higher resting blood flows combined with similar hyperemic flows resulted in a lower myocardial flow reserve in the older than in the younger normal subjects (4.1 +/- 0.9 versus 3.0 +/- 0.70; P < 0.0001). The flow reserve was more closely correlated with resting than with hyperemic blood flows.

CONCLUSIONS
Aging does not alter significantly dipyridamole-induced hyperemic flows; although coronary vascular resistance after dipyridamole was somewhat increased in older subjects. The gradual decline of the myocardial blood flow reserve correlates with an age-related increase of baseline myocardial work and blood flow. These findings suggest that the reduced flow reserve with age is primarily due to increased cardiac work and blood flow at rest rather than to an abnormal vasodilator capacity.
Low doses of scopolamine increase cardiac vagal tone in the acute phase of myocardial infarction.
Authors: Casadei B , Pipilis A , Sessa F , Conway J , Sleight P 
Published: June 2012

BACKGROUND
Reduced cardiac vagal tone in patients with myocardial infarction (MI) is associated with a high risk of sudden death. Muscarinic blocking agents in small doses induce a paradoxical increase in cardiac vagal activity in normal subjects. We tested whether low doses of scopolamine delivered transdermally enhance tonic and reflex cardiac vagal activity in patients in the acute phase of MI.

METHODS AND RESULTS
Patients were randomized to a scopolamine (n = 17) or a placebo patch (n = 19) in a double-blind fashion 4.20 +/- 0.18 days after acute MI. Cardiac vagal activity was assessed by testing the arterial baroreflex sensitivity (BRS) using the phenylephrine method and by power spectral analysis of the RR interval variability. Twenty-four hours after scopolamine, we found a significant increase in BRS (from 7.05 +/- 1.21 to 13.99 +/- 2.33 ms/mm Hg, P < .05) and in RR variability, expressed as the mean standard deviation of 512 normal consecutive RR intervals (from 18.09 +/- 2.64 to 31.16 +/- 4.16 milliseconds, P < .05). The amplitude of respiratory sinus arrhythmia, measured by the absolute power of the high-frequency spectral component, was also enhanced (from 62.55 +/- 21.49 to 305.33 +/- 95.68 milliseconds squared, P < .05), whereas the power in the low-frequency spectral component of the RR variability, which results from the interaction between cardiac sympathetic and vagal activity, did not change significantly (from 73.12 +/- 24.44 to 126.46 +/- 44.29 milliseconds squared, P = .93).

CONCLUSIONS
In patients in the acute phase of MI, low doses of scopolamine cause a sustained increase in cardiac vagal tone and improve the autonomic indices associated with mortality.
Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease.
Authors: Mazzone A , De Servi S , Ricevuti G , Mazzucchelli I , Fossati G , Pasotti D , Bramucci E , Angoli L , Marsico F , Specchia G 
Published: June 2012

BACKGROUND
A rapid increase in leukocyte adhesion to endothelial cells is one of the first events in the acute inflammatory response and in the pathogenesis of vascular diseases. A subgroup of cell surface glycoproteins (the CD11/CD18 complex) play a major role in the leukocyte adhesion process; in particular, the CD11b/CD18 receptor can be upregulated severalfold in response to chemotactic factors. The purpose of this study was to assess whether upmodulation of granulocyte and monocyte CD11b/CD18 receptors takes place during the passage of blood through the coronary tree of patients with clinical manifestations of ischemic heart disease.

METHODS AND RESULTS
Thirty-nine patients who underwent diagnostic coronary arteriography were studied. Group 1 (15 patients) had a clinical diagnosis of unstable angina, group 2 (14 patients) had stable exertional angina, and group 3 (10 patients) had atypical chest pain. Simultaneous sampling from the coronary sinus and aorta was obtained before coronary arteriography. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytofluorimetry using monoclonal antibodies tagged with fluorescent markers. Leukocytes were stained in unseparated blood to avoid in vitro manipulation that could activate phagocytes. Group 1 and 2 patients had significant coronary artery disease (> 50% coronary narrowing in at least one major coronary vessel), whereas group 3 patients had normal coronary arteries. In group 1, granulocytes and monocytes showed a significantly higher expression of the CD11b/CD18 adhesion receptor in the coronary sinus than in the aorta (both P < .01), whereas no difference in CD11b/CD18 expression was seen in groups 2 and 3.

CONCLUSIONS
Patients with unstable angina have an increased expression of granulocyte and monocyte CD11b/CD18 adhesion receptors, indicating that an inflammatory reaction takes place within their coronary tree. Activation of these leukocytes may induce coronary vasoconstriction, favor thrombotic processes, and further activate platelets, thus having potential implications on the pathogenesis of unstable coronary artery disease.
Determinants of 6-month mortality in survivors of myocardial infarction after thrombolysis. Results of the GISSI-2 data base. The Ad hoc Working Group of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-2 Data Base.
Authors: Volpi A , De Vita C , Franzosi M G , Geraci E , Maggioni A P , Mauri F , Negri E , Santoro E , Tavazzi L , Tognoni G 
Published: June 2012

BACKGROUND
Current knowledge of risk assessment in survivors of myocardial infarction is largely based on data gathered before the advent of thrombolysis. It must be determined whether and to what extent available information and proposed criteria of prognostication are applicable in the thrombolytic era.

METHODS AND RESULTS
We reassessed risk prediction in the 10,219 survivors of myocardial infarction with follow-up data available (ie, 98% of the total) who had been enrolled in the GISSI-2 trial, relying on a set of prespecified variables. The 3.5% 6-month all-cause mortality rate of these patients compared with the higher value of 4.6% found in the corresponding GISSI-1 cohort, originally allocated to streptokinase therapy, indicates a 24% reduction in postdischarge 6-month mortality. On multivariate analysis (Cox model), the following variables were predictors of 6-month all-cause mortality: ineligibility for exercise test for both cardiac (relative risk [RR], 3.30; 95% confidence interval [CI], 2.36-4.62) and noncardiac reasons (RR, 3.28; 95% CI, 2.23-4.72), early left ventricular failure (RR, 2.41; 95% CI, 1.87-3.09), echocardiographic evidence of recovery phase left ventricular dysfunction (RR, 2.30; 95% CI, 1.78-2.98), advanced (more than 70 years) age (RR, 1.81; 95% CI, 1.43-2.30), electrical instability (ie, frequent and/or complex ventricular arrhythmias) (RR, 1.70; 95% CI, 1.32-2.19), late left ventricular failure (RR, 1.54; 95% CI, 1.17-2.03), previous myocardial infarction (RR, 1.47; 95% CI, 1.14-1.89), and a history of treated hypertension (RR, 1.32; 95% CI, 1.05-1.65). Early post-myocardial infarction angina, a positive exercise test, female sex, history of angina, history of insulin-dependent diabetes, and anterior site of myocardial infarction were not risk predictors. On further multivariate analysis, performed on 8315 patients with the echocardiographic indicator of left ventricular dysfunction available, only previous myocardial infarction was not retained as an independent risk predictor.

CONCLUSIONS
A decline in 6-month mortality of myocardial infarction survivors, seen within 6 hours of symptom onset, has been observed in recent years. Ineligibility for exercise test, early left ventricular failure, and recovery-phase left ventricular dysfunction are the most powerful (RR, > 2) predictors of 6-month mortality among patients recovering from myocardial infarction after thrombolysis. Qualitative variables reflecting residual myocardial ischemia do not appear to be risk predictors. The lack of an independent adverse influence of early post-myocardial infarction angina on 6-month survival represents a major difference between this study and those of the prethrombolytic era.
Does fish oil lower blood pressure? A meta-analysis of controlled trials.
Authors: Morris M C , Sacks F , Rosner B 
Published: June 2012

BACKGROUND
In a meta-analysis of 31 placebo-controlled trials on 1356 subjects, we examined the effect of omega-3 fatty acids in fish oil on blood pressure by grouping studies that were similar in fish oil dose, length of treatment, health of the subjects, or study design.

METHODS AND RESULTS
The mean reduction in blood pressure caused by fish oil for the 31 studies was -3.0/-1.5 mm Hg (95% confidence intervals: systolic blood pressure: -4.5, -1.5; diastolic blood pressure: -2.2, -0.8). There was a statistically significant dose-response effect when studies were grouped by omega-3 fatty acid dose: -1.3/-0.7 mm Hg at doses < or = 3 g/d, -2.9/-1.6 mm Hg at 3.3 to 7 g/d, and -8.1/-5.8 mm Hg at 15 g/d. Both eicosapentaenoic acid and docosahexaenoic acid were significantly related to blood pressure response. There was no effect on blood pressure in eight studies of "healthy" persons (mean reduction, -0.4/-0.7 mm Hg) at an overall mean dose of 4.2 g omega-3 fatty acids/d. By contrast, there was a significant effect of -3.4/-2.0 mm Hg in the group of hypertensive studies with a mean fish oil dose of 5.6 g/d and on systolic blood pressure only in six studies of hypercholesterolemic patients (-4.4/-1.1 mm Hg) with a mean dose of 4.0 g/d. A nonsignificant decrease in blood pressure was observed in four studies of patients with atherosclerotic cardiovascular disease (-6.3/-2.9 mm Hg). Variations in the length of treatment (from 3 to 24 weeks), type of placebo, and study design (crossover or parallel groups) did not appear to account for inconsistent findings among studies.

CONCLUSIONS
There is a dose-response effect of fish oil on blood pressure of -0.66/-0.35 mm Hg/g omega-3 fatty acids. The hypotensive effect may be strongest in hypertensive subjects and those with clinical atherosclerotic disease or hypercholesterolemia.