Biomedical subjects

J Oliveras

Publications and source records attributed to J Oliveras.

18 recordsLinked to original sources

PubMed1999

Attenuated severity of new acute ischemic events in patients with previous coronary heart disease receiving long-acting nitrates.

BACKGROUND: Platelet aggregation and secondary vasoconstriction are key events in the genesis of acute coronary syndromes. HYPOTHESIS: Since nitrates have vasodilatory and antiaggregant effects, treatment with long-acting nitrates at the time of onset of acute coronary syndromes could be associated with attenuation of their severity. METHODS: A consecutive series of 533 patients with acute coronary syndrome and past history of coronary artery disease admitted to the Cardiology Service of a general hospital was studied. A specific questionnaire assessed the use of nitrates and other relevant drugs, as well as other clinical variables. The diagnosis of unstable angina or acute myocardial infarction (MI) was established according to clinical, electrocardiographic, and enzymatic criteria. RESULTS: In the whole cohort, 169 patients had MI and 364 had unstable angina. Previous use of long-acting nitrates was significantly more common in patients with unstable angina (56%) than in those with MI (37%) (p < 0.0001). Multivariate analysis identified being a nonsmoker [odds ratio: 95%, confidence limits (CL) 0.37, 0.23-0.59], previous unstable angina (CL 0.62, 0.41-0.92), use of aspirin (CL 0.58, 0.41-0.92), and use of long-acting nitrates (CL 0.61, 0.40-0.93) as the independent predictors of the development of unstable angina rather than MI; of these the combination of nitrates and aspirin was the strongest predictor. CONCLUSIONS: Long-acting nitrates as well as aspirin are suggested to have a protective or modifying effect on the development of acute coronary syndromes, favoring unstable angina rather than acute MI.

Adrenergic beta-Antagonists↗

PubMed1997

Dose of non-heat-treated factor VIII concentrate and HIV-1 RNA levels.

Explore the source record for details and available documents.

Disease Progression↗

PubMed1996

Myocardial segment shrinkage during coronary reperfusion in situ. Relation to hypercontracture and myocardial necrosis.

We have investigated the changes in myocardial segment length induced by reperfusion, and their relation to myocyte hypercontracture and contraction band necrosis. Regional wall function was monitored by ultrasonic gauges in 39 pigs submitted to 48-min occlusion of the left anterior descending coronary artery (LAD) and 6h of reperfusion. Infarct size (triphenyltetrazolium reaction), the extent of contraction band necrosis (quantitative histology) and myocardial water content (desiccation) were measured. Reperfusion induced a marked reduction in end-diastolic length of the LAD segment in all animals, maximal within 15 min after reflow. After 30 min of reperfusion, end-diastolic length of the LAD segment remained below the basal value in 15 animals. The 15 animals that showed shrinkage of the reperfused segment did not differ from the remaining animals in heart rate, aortic pressure, or control segment variables, but had larger infarcts (mean +/- SEM: 32.1 +/- 5.4 vs 12.1 +/- 3.2% of the area at risk, P = 0.003). There was an inverse correlation between end-diastolic length of the LAD segment after 30 min of reperfusion and infarct percentage (r = -0.72) or the extent of contraction band necrosis (r = -0.71). End-diastolic length reduction was more pronounced in larger infarcts despite a more severe myocardial oedema. Neither systolic shortening of the LAD segment nor end-diastolic length or systolic shortening of the control segment, or haemodynamic variables after 30 min of reperfusion correlated to infarct percentage or to the extent of contraction band necrosis. It is concluded that myocardial segment shrinkage during reperfusion reflects myocyte hypercontracture leading to contraction band necrosis.

Animals↗

PubMed1996

Intimal injury in a transiently occluded coronary artery increases myocardial necrosis. Effect of aspirin.

This study tested the hypothesis that intimal injury in a transiently occluded coronary artery limits myocardial salvage. The effect of intimal injury on reactive hyperaemia was investigated in 17 pigs submitted to a 30-min occlusion of the left anterior descending coronary artery (LAD), not resulting in myocardial infarction. Catheter-induced intimal damage increased local platelet deposition (99mTc) and reduced hyperaemia, but did not modify myocardial platelet or polymorphonuclear leucocyte content (myeloperoxidase activity) after 6 h reperfusion. To investigate the influence of intimal injury on the extent of myocardial necrosis secondary to a more prolonged coronary occlusion, and the role of platelets on this influence, 52 pigs were submitted to a double randomization (2x2 factorial design) to 250 mg i.v. aspirin vs. placebo and to coronary intimal injury vs. no coronary damage before a 48-min occlusion of the LAD and 6 h of reperfusion. After excluding 12 animals with reocclusion, coronary intimal injury was associated with larger infarcts (triphenyltetrazolium reaction) in animals receiving placebo (36.2+/-7.0% of the area at risk in animals with intimal injury vs. 10.8+/-3.9% in animals without coronary injury, P=0.006) but not in those receiving aspirin (20.3+/-6.5 vs. 21.7+/-6.5% of the area at risk in animals with and without intimal injury respectively). These results suggest that coronary intimal injury in the reperfused artery may have adverse effects on myocardial salvage by mechanisms other than reocclusion or embolization of platelet aggregates.

Animals↗

PubMed1995

Previous aspirin use may attenuate the severity of the manifestation of acute ischemic syndromes.

BACKGROUND: The present study was designed to investigate whether the prior use of aspirin could influence the severity of the manifestation of acute coronary artery syndromes, given the well-documented observations that aspirin can prevent myocardial infarction, stroke, and death in cardiovascular disease. METHODS AND RESULTS: A series of 539 consecutive patients admitted to the Coronary Care Unit of a General Hospital was carefully characterized in a study with an ambidirectional design, with regard to previous medical history, aspirin use, and subsequent hospital diagnosis. Among the 214 patients previously taking aspirin, the hospital diagnosis was myocardial infarction in 24% and unstable angina in 76% compared with 54% and 46%, respectively, among the 325 not taking aspirin (P < .0001), for a reduction in the odds ratio of myocardial infarction with aspirin of 72% (95% CI, 59% to 90%). The decrease in odds was homogeneous in all subsets studied and independent of age, sex, previous angina, or previous myocardial infarction. The myocardial infarction was of a Q-wave type in 62% of aspirin users compared with 76% of nonusers (P < .05). By multivariate analysis, previous aspirin use was a strong predictor of unstable angina versus myocardial infarction and the only independent predictor of non-Q-wave versus Q-wave myocardial infarction. CONCLUSIONS: This study, thus, suggests a shift to less severe manifestation of acute coronary syndromes with aspirin use, implying that the failure of the drug in many patients with an acute coronary syndrome is only partial and that aspirin has the potential of attenuating the severity of the underlying acute thrombotic disease process.

Angina, Unstable↗

PubMed1995

An association between clotting factor concentrates use and mortality in human immunodeficiency virus-infected hemophilic patients.

There is much evidence that clotting factor concentrates (CFC), especially the so-called intermediate-purity preparations, exert an immunomodulating effect in vitro. The impact of this effect on the outcome of human immunodeficiency virus (HIV) infection in hemophiliacs is still controversial. In this retrospective cohort study, the effects of treatment with CFC on mortality and progression to acquired immunodeficiency syndrome (AIDS) were estimated while controlling for individual risk factors. Logistic regression and survival analysis, including the Cox proportional-hazards regression model, were performed with data from a 11-year follow-up of 225 hemophilic patients seropositive for HIV type 1 (HIV-1) of two hemophilia centers. Mortality and progression to AIDS rates were strongly associated with lower administration of CFC. After adjusting for age, a statistically significant and robust association was observed. The use of CFC was negatively associated with progression to AIDS (P = .0252) and mortality (P = .0033). The adjusted relative hazards of mortality and progression to AIDS rate between the most treated patients (> 700 IU/kg/yr) versus the least treated (< or = 700 IU/kg/yr) were 0.53 (confidence limits, 0.33 to 0.86) and 0.57 (0.39 to 0.84), respectively. Although the effects of other unmeasured risk factors cannot be excluded with certainty, these results suggest that there is a negative association between treatment with CFC and progression to AIDS and mortality.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Contraction band necrosis at the lateral borders of the area at risk in reperfused infarcts. Observations in a pig model of in situ coronary occlusion.

The aim of this study was to test the hypothesis that increased mechanical stress at the lateral borders of the area at risk may render this area more susceptible to ischaemia/reperfusion injury in the absence of collateral flow. The spatial distribution of myocardial necrosis within the territory of a transiently occluded left anterior descending coronary artery was investigated in 31 porcine hearts submitted to 48 min of coronary occlusion and 6 h of reperfusion. Immediately before excising the heart, the left anterior descending coronary artery was re-occluded and 10% fluorescein was injected in the left atrium. The area at risk was imaged by ultraviolet illumination of the myocardial slices, and the area of necrosis by incubation in triphenyltetrazolium chloride. The area at risk was divided in four sectors and an index of eccentricity was calculated as the percent of the area of necrosis located in the two lateral sectors of the area at risk. The area of contraction band necrosis was measured in whole heart histological sections. Infarcts were generally small, and were composed almost exclusively of contraction band necrosis. There was a good correlation between the extent of the area of contraction band necrosis and infarct size (r = 0.831, P < 0.0005). The area of necrosis had a patchy appearance and was predominantly distributed along the lateral borders of the area at risk. This eccentric distribution was more prominent in smaller infarcts, and the eccentricity index was inversely correlated with infarct size (r = -0.471, P = 0.007), suggesting that contraction band necrosis occurs first at the interface between control and reperfused myocardium in this model. These results are in agreement with a prominent role of mechanical factors in the genesis of myocardial necrosis during transient coronary occlusion.

Animals↗

PubMed1995

Dissociation between anti-infarct effect and anti-edema effect of ischemic preconditioning.

This study tested the hypothesis that preconditioning, by reducing catabolite accumulation during ischemia, reduces osmotic swelling and myocardial necrosis during subsequent reperfusion. Farm pigs were randomly allocated to one of three groups of treatment: a control group undergoing a 48-min coronary occlusion (CO) of the middle left anterior descending artery, a preconditioned group (2 cycles of 5-min CO and 5-min reperfusion before the 48-min CO), or an intracoronary perfusion group receiving a substrate-free anoxic buffer perfusion into the area at risk between minutes 5 and 10 of the prolonged CO. Animals were killed after 30 min (n = 23) or 6 h (n = 31) of reperfusion. Compared with the control group, both ischemic preconditioning and washout of ischemic by-products by transient anoxic perfusion reduced myocardial edema after 30 min of reperfusion (P < 0.002) by 35 and 32%, respectively, but only ischemic preconditioning reduced final infarct size (by 55%, P < 0.006). Myocardial lactate content before reperfusion, measured in an additional series of 12 experiments, was reduced by 35% in animals receiving preconditioning or intracoronary perfusion. Thus ischemic preconditioning has a marked protective effect against reperfusion edema, and this effect can be explained by reduced catabolite accumulation during ischemia. However, there is no evidence from this study indicating that reduced catabolite accumulation and limited reperfusion edema explain the important anti-infarct effect of ischemic preconditioning.

Animals↗

PubMed1995

Administration of lipid-emulsion versus conventional amphotericin B in patients with neutropenia.

OBJECTIVE: To evaluate the usefulness of a 20% lipid emulsion as a delivery system for amphotericin B (1 mg/mL) administered over 1 hour to patients with neutropenia with hematologic malignancies compared with amphotericin B (0.1 mg/mL) administered in dextrose 5% solution over the same time. DESIGN: A prospective, comparative, randomized, labeled study. SETTING: Hematology unit, pharmacy service, university general hospital. PARTICIPANTS: Twenty patients with neutropenia with hematologic malignancies and proven or suspected fungal infections, 10 in the fat emulsion group (group 1) and 10 in the dextrose 5% group (group 2). MAIN OUTCOME MEASURES: Clinical tolerance (i.e., fever, shaking chills, nausea, blood pressure, pulse rate) and biologic tolerance (i.e., urea, creatinine, sodium, potassium). RESULTS: Clinical tolerance was comparable in both groups although amphotericin B in fat emulsion was better tolerated. Medication for symptoms related to the administration of amphotericin B was given in 6 cases in group 1 and in 8 cases in group 2. There was a statistically significant difference in the urea concentrations between the 2 groups (p = 0.023); there was an observed increase between the initial and the final serum urea (56.8 mg/d in group 1, 79.8 mg/dL in group 2). Statistically significant differences in creatinine serum concentrations (84.9 mumol/L in group 1, 123.8 mumol/L in group 2) (p = 0.047) were found. No differences were found in the antifungal efficacy of the treatment. However, as amphotericin B was started in the majority of cases (75%) as empiric treatment for fever unresponsive to antibiotic therapy, it is difficult to compare the efficacy of both preparations. CONCLUSIONS: The clinical tolerance of lipid-emulsion infusions is similar to that of conventionally administered amphotericin B therapy. Renal toxicity appears to be decreased when the drug is administered in a fat emulsion. This type of preparation permits the reduction of the volume and the time of administration for amphotericin B therapy.

Adolescent↗

PubMed1995

[Effects of reoxygenation-induced osmotic edema on cell viability. Study using isolated myocytes].

OBJECTIVE: To investigate the hypothesis that reperfusion edema may kill myocytes. METHODS: Adult Sprague-Dawley rat hearts were perfused with a calcium free dissociation buffer containing collagenase 0.03% in a Langedorff system. Intact cells were selected and myocytes were cultured in adherent pretreated dishes. After 3 hours, 80% of cells were rod-shaped. Anoxia was simulated by means of metabolic inhibition by adding NaCN 2 mM to the control media, and reoxygenation by substituting this media with one of the following media non containing NaCN: 1) normo-osmotic (312 mOsm); 2) hypoosmotic (80 mOsm); 3) normo-osmotic with low Na+ (312 mOsm). A group of cells was kept with control media without metabolic inhibition and then submitted to simulated reoxygenation with hypoosmotic media (control group). The number of rod, square and round-shaped cells was monitored, and cell viability was assessed after 5 min of reoxygenation by the Trypan blue test. RESULTS: After 60 min of metabolic inhibition there were no differences in the % of cells without hypercontracture among groups reoxygenated with normo-osmotic, hypoosmotic, low Na+ normo-osmotic and control media (84 +/- 16, 74 +/- 10, 76 +/- 14 and 90 +/- 6% respectively (p = NS). After 5 min of reoxygenation, these values decreased (p < 0.001) to 19 +/- 6, 11 +/- 9 and 13 +/- 3% (p = NS), respectively, in groups with normo-osmotic, hypoosmotic, and low Na+ normo-osmotic reoxygenation, but were not modified in the control group (78 +/- 4). The % of viable cells (Trypan negative) preserved after 5 min of reoxygenation was 67 +/- 29% in the group with normo-osmotic reoxygenation, 31 +/- 23% in the group with hypoosmotic reoxygenation, and 85 +/- 12% in the group with low Na+ normo-osmotic reoxygenation (p < 0.001). Exposing cells without metabolic inhibition to hypoosmotic media resulted in no significative reduction of cell viability. CONCLUSION: Hypoosmotic reoxygenation following prolonged metabolic inhibition may kill viable myocytes. This effect is not due to the low Na+ concentration in the hypoosmotic medium.

Animals↗

PubMed1993

Analysis of myocardial oedema by magnetic resonance imaging early after coronary artery occlusion with or without reperfusion.

OBJECTIVE: The aim was to analyse the relationship between magnetic resonance (MR) imaging parameters and myocardial water content early after coronary occlusion with or without reperfusion. METHODS: 21 pigs were used. After 78 min of coronary occlusion (n = 7) or 48 min of coronary occlusion and 30 min of reperfusion (n = 14) the heart was excised. In seven animals in the reperfusion protocol the area at risk was perfused for 5 min with an anoxic buffer, starting 5 min after coronary occlusion. Serial T2 weighted and density weighted images of the heart were obtained from apex to base, by using a 1.5 tesla magnetic resonance imager. Water content was measured in samples from control and at-risk myocardium and relaxation parameters were measured in corresponding areas of the magnetic resonance images. RESULTS: Water content was 399(SEM 2) ml x 100 g-1 dry tissue in control myocardium, 427(8) in ischaemic myocardium, and 511(8) in reperfused myocardium (p < 0.001). Reperfused myocardium that had received intracoronary infusion contained less water than myocardium that did not: 498(9) v 534(4) ml x 100 g-1 (p = 0.003). T2 relaxation time and T2 weighted signal intensity in the different sampling sites of magnetic resonance images correlated well with water content in the corresponding myocardial samples (r = 0.76 and r = 0.83) and with the relative volume of extracellular space, as calculated by quantitative histology (r = 0.58 and r = 0.59, p < 0.001). The increase in T2 weighted signal intensity in the area at risk with respect to control myocardium allowed differentiation between ischaemic and reperfused myocardium [9(8)% v 63(3)% respectively]. The area at risk measured by MR imaging correlated very well with that determined at pathology by the fluorescein method (r = 0.92). CONCLUSIONS: Magnetic resonance imaging allows evaluation of myocardial oedema associated with acute coronary occlusion and reperfusion, and analysis of its spatial distribution. Changes in myocardial water content occurring early during acute myocardial infarction allow quantification of the area at risk and detection of reperfusion by magnetic resonance imaging.

Animals↗

PubMed1993

Myocardial oedema: a preventable cause of reperfusion injury?

Myocardial ischaemia increases cellular and extracellular osmolarity, alters membrane permeability to ions and causes moderate cell swelling and interstitial oedema. Ischaemia also reduces the mechanical resistance of the sarcolemma of myocytes, probably as a result of proteolytic digestion of the connections between cell membrane and the cellular scaffold. During reperfusion, the abrupt normalisation of extracellular osmotic pressure results in marked osmotic cell swelling. In the clinical situation, the ability of mechanical stress imposed by cell swelling to disrupt the weakened sarcolemma of viable myocytes during reperfusion has not been definitively established. Observations demonstrating the important role of mechanical stress caused by contraction and cell to cell interaction in myocyte necrosis support the hypothesis that osmotic cell swelling may actually produce lethal reperfusion injury. This hypothesis has been investigated by analysing the effect of hyperosmotic reperfusion with mannitol on final infarct size after coronary occlusion. Studies using highly hyperosmotic reperfusion after relatively short periods of ischaemia have yielded positive results, while studies using intravenous mannitol at the time of reperfusion, and more closely resembling clinical situations, have failed to detect any beneficial effect. Myocardial oedema could also contribute to postischaemic functional derangements, such as reperfusion arrhythmias and stunning, and could modify the passive mechanical properties of the infarcts and alter ventricular remodelling. Interventions aimed to limit myocardial oedema will probably not play a role as a co-adjuvant therapy in patients with acute myocardial infarction receiving thrombolytic treatment. However, they should probably form part of controlled reperfusion strategies to be evaluated in patients with acute myocardial infarction in whom reperfusion is accomplished by percutaneous transcoronary angioplasty or surgery.

Cardiomyopathies↗

PubMed1974