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Biomedical subjects

P Eliasen

Publications and source records attributed to P Eliasen.

At least 19 recordsLinked to original sources

Changes in absolute and relative importance in the prognostic value of left ventricular systolic function and congestive heart failure after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation.

Changes in the importance of left ventricular (LV) systolic dysfunction and congestive heart failure (CHF) with time after an acute myocardial infarction (AMI) after the introduction of thrombolytic therapy have not been studied. LV systolic function, measured as wall motion index (WMI) by echocardiography, was assessed in 6,676 consecutive patients with an enzyme-confirmed AMI. So that changes in the prognostic value of WMI or CHF could be studied, separate analyses were performed at selected time periods. Average monthly mortality (deaths per 100 patients per month) was determined from life-table analyses, with groups divided by WMI above and below 1.2 (a WMI > 1.2 corresponds to an ejection fraction > 0.35) or by presence and/or absence of CHF. Relative risk (95% confidence intervals [CI]) was determined by proportional hazard models, including baseline characteristics. In patients with LV dysfunction or CHF, monthly mortality was high during the first month (18.3 +/- 1.6% and 20.2 +/- 1.6%, respectively), decreased during the first year, and was stable thereafter (0.8 +/- 0.1% and 1.0 +/- 0.1%, respectively, average monthly mortality after year 3). The relative risk of LV dysfunction decreased from 2.4 (CI 2.0 to 2.9) to 1.3 (CI 1.0 to 1.6) in the same period. The relative risk of CHF decreased from 2.9 (CI 2.3 to 3.8) to 1.6 (CI 1.3 to 2.0). In patients without LV dysfunction or CHF, monthly mortality was relatively high during the first month (5.2% +/- 0.7% and 3.4% +/- 0.6%, respectively) but decreased within the first year to low, stable values (0.6% +/- 0.1% and 0.4% +/- 0.1%, respectively, average monthly mortality after year 3). In patients who received thrombolytic therapy, the relative risk associated with a WMI < or = 1.2 decreased from 3.0 (CI 2.0 to 4.4) to 1.3 (CI 0.9 to 1.6) and from 3.2 (CI 2.0 to 5.1) to 1.7 (CI 1.2 to 2.4) in patients with CHF. The risk of dying decreases steeply with time after an AMI with or without LV dysfunction or CHF and stabilizes at low values after 1 year. This is in contrast to the relative importance of these risk factors, which is maintained for > or = 5 years but decreases with time.

Aged

[Aminoglycoside treatment I. Administration of gentamicin once versus three times daily].

Gentamicin is the most commonly used aminoglycoside in Danish hospitals. The aim of this study was to compare two dosage regimens, thrice-a-day (TID) and once-a-day (OD) with regard to efficacy, safety and tissue toxicity. Twenty-three patients were allocated to TID and 26 were allocated to OD gentamicin. Data from patients treated for more than 72 hours were evaluated. Efficacy was assessed by the rate at which body temperature fell to normal. Renal toxicity was judged by an increase in serum creatinine of more than 50 mumol/l and inner ear toxicity was clinically estimated daily during treatment, followed up by audiometry if positive signs occurred. Serum gentamicin was determined daily to estimate the size of next dose. A low frequency of dose adjustments was considered to reflect safety, as well as the absence of renal and inner ear affection. Results showed no significant differences between the two groups regarding efficacy, safety or tissue toxicity. Renal toxicity developed in two patients on TID regime and in one patient on OD regime. No inner ear toxicity was seen. The renal toxicity appeared unpredictably, both early and late in the treatment period and preceded by low or high values serum gentamicin. It is recommended that gentamicin be administered OD for reasons of economy and convenience and that kidney function be monitored daily throughout the treatment period.

Adult

[Aminoglycoside treatment II: Dosage regimes at the departments of internal medicine in Denmark].

The aim of this study was to get a general view of the habitual practice of the usage of aminoglycosides in Danish medical departments, regarding choice of drug, dosage regimen and monitoring of drug-related toxicity, as this antimicrobial agent is commonly used in Danish hospitals against severe infections in spite of the potential for nephro- and ototoxicity. The survey, taking place in 1991 and in 1994, showed that gentamicin and netfilmicin were preferred as first choice with an equal frequency in university and county hospital department, whereas in departments in small hospitals gentamicin was preferred twice as often. From 1991 to 1994 the dosage regimen most commonly used had altered from thrice-a-day to once-a-day. Monitoring of serum levels of the drug was performed on all treated patients in fifty-two of the seventy-nine departments questioned. Most of the departments also monitored the kidney function.

Anti-Bacterial Agents

[The significance of trandelapril for mortality after AMI in patients with reduced left ventricular function. TRACE Study Group].

Angiotensin converting-enzyme (ACE) inhibition reduces mortality among patients surviving an acute myocardial infarction, but whether to give ACE-inhibitors to all patients or target their use to selected patients is unclear. Seven thousand and one consecutive enzyme-confirmed myocardial infarctions were screened. One thousand seven hundred and forty-nine patients with echocardiographic signs of left ventricular dysfunction were randomized to oral trandolapril (876 patients) or placebo (873 patients) starting from days three to seven following the infarction. Average follow-up was 27 months. There were 304 deaths (34.7 percent) among patients on trandolapril vs. 369 deaths (42.3 percent) among patients on placebo (p = 0.0013). Relative risk (RR) of death in the trandolapril group was 0.78 (95% confidence interval (CD 0.67-0.91). Trandolapril reduced cardiovascular death (RR 0.75, CI 0.63-0.89) and sudden death (RR 0.76, CI 0.59-0.98). Progression to severe/resistant heart failure was reduced (RR 0.71, CI 0.56-0.90). Recurrent myocardial infarction (fatal or non-fatal) was not significantly reduced (RR 0.86, CI 0.66-1.13). It is concluded that long-term treatment with trandolapril in patients with reduced left ventricular function shortly after myocardial infarction significantly reduced total mortality. The substantial mortality risk reduction was obtained in 25% of consecutive patients screened for entry encouraging a selective use of ACE inhibition following myocardial infarction.

Adult

A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group.

BACKGROUND: Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces mortality among survivors of acute myocardial infarction, but whether to use ACE inhibitors in all patients or only in selected patients is uncertain. METHODS: We screened 6676 consecutive patients with 7001 myocardial infarctions confirmed by enzyme studies. A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction (ejection fraction, < or = 35 percent). On days 3 to 7 after infarction, 1749 patients were randomly assigned to receive oral trandolapril (876 patients) or placebo (873 patients). The duration of follow-up was 24 to 50 months. RESULTS: During the study period, 304 patients (34.7 percent) in the trandolapril group died, as compared with 369 (42.3 percent) in the placebo group (P = 0.001). The relative risk of death in the trandolapril group, as compared with the placebo group, was 0.78 (95 percent confidence interval, 0.67 to 0.91). Trandolapril also reduced the risk of death from cardiovascular causes (relative risk, 0.75; 95 percent confidence interval, 0.63 to 0.89; P = 0.001) and sudden death (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98; P = 0.03). Progression to severe heart failure was less frequent in the trandolapril group (relative risk, 0.71; 95 percent confidence interval, 0.56 to 0.89; P = 0.003). In contrast, the risk of recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk, 0.86; 95 percent confidence interval, 0.66 to 1.13; P = 0.29). CONCLUSIONS: Long-term treatment with trandolapril in patients with reduced left ventricular function soon after myocardial infarction significantly reduced the risk of overall mortality, mortality from cardiovascular causes, sudden death, and the development of severe heart failure. That mortality was reduced in a randomized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infarction.

Adult

[Early discharge after acute myocardial infarction. Cost-effectiveness of early echocardiographic risk evaluation].

A total of 195 consecutive patients with acute myocardial infarction were examined and risk classified (low or middle/high risk) on the fifth day by two physicians. These two physicians employed two different sets of criteria: conventional clinical examination compared with 2-D echocardiographic assessment of the wall motion of the left ventricle (wall motion index, WMI). Both physicians concluded their examination by determination of a theoretical time for discharge. By design this was on the 5th-7th days for low risk patients by echocardiography, while low risk patients by clinical criteria are normally discharged on the 7th to 8th days. The most sensitive method of identifying the low risk patients was achieved by combining the clinical examination with echocardiographic WMI determination. In this manner, a total of 104 (53%) low risk patients could be identified. A potential saving of 18% of the total duration of hospitalization could be calculated from the two theoretical times of discharge for the total population. All of the patients in this study could be assessed by echocardiography which provided valuable information and thus may be implemented in the routine treatment of acute myocardial infarction.

Adult

[Relation between 1-year mortality after acute myocardial infarction and left ventricular ejection function estimated by echocardiography].

The pump function of the left ventricle was characterized by means of early echocardiographic determination of the motion of the ventricular walls (wall motion index, WMI) in a consecutive unselected series of 195 patients with acute myocardial infarction. The pump function, WMI, was related to one-year mortality after infarction. The patients were subdivided prospectively into three risk groups (low, middle and high) depending on WMI. One-year mortality in the three groups were 2%, 34% and 37%, respectively (p less than 0.0001). Patients with previous infarcts had significantly lower WMI and greater one-year mortality than patients with first infarct (p less than 0.001 and less than 0.05, respectively). Among patients with first infarct with inferior localization, significantly higher WMI and lower one-year mortality were found than with anterior localization (p less than 0.001 and = 0.15, respectively, (NS)). Women had significantly higher one-year mortality than men (30.2% compared with 16.9% (p less than 0.04)) although this was reflected by a corresponding difference in WMI. Regardless of sex, age, localization of the infarct and signs of residual ischaemia, patients who were allocated to the low risk group solely on the basis of WMI, had particularly good prognoses. Among patients with more extensive myocardial damage, WMI less than or equal to 1.3, other risk factors probably played a greater role.

Adult

Risk stratification after acute myocardial infarction by means of echocardiographic wall motion scoring and Killip classification.

In order to perform risk stratification, 195 consecutive, unselected patients with acute myocardial infarction (AMI) underwent independent echocardiographic and clinical evaluation of their left ventricular function by means of the wall motion index (WMI) and Killip classification 5 days after AMI. The patients were prospectively allocated to a low, medium or high risk class depending on WMI alone, and the 1-year mortality in these classes was 2, 34 and 37%, respectively (p < 0.0001). The 1-year mortality of the patients in Killip class I, II, or III and IV was 6, 26 and 48%, respectively (p < 0.00001). The number of patients allocated to the low risk group by means of WMI was 87, and the number of patients in Killip class I was 86. Since these groups were not identical, a total of 103 patients, i.e. 53% of the study population, could be identified as low risk patients regarding 1-year mortality 5 days after AMI, when WMI and Killip classification were used in combination. We conclude that the combination of echocardiographic and clinical evaluation of left ventricular function after AMI provides a strong and yet very simple procedure to identify low risk patients, which could be easily implemented in the routine work of coronary care units.

Adult

The microvascular haematocrit as a determinant of myocardial oxygenation.

Ischaemia of the left ventricular myocardium preferentially threatens the subendocardial layers. The microvascular haematocrit is a main factor for oxygen delivery to the left ventricular wall together with coronary blood flow and perfused capillary area. The influence of coronary perfusion, precapillary flow, haematocrit, the viscosity of the blood, and the viscoelastic properties of red cells are considered with emphasis on their influence on oxygen delivery to the myocardium. The microvascular haematocrit is decreased distal to a coronary artery stenosis, and especially in subendocardial layers, so the oxygenation of the deep layers within the left ventricle is reduced more than could be expected from a decrease in coronary blood flow alone.

Coronary Circulation

[Hypertension in Borrelia infections].

A patient with severe hypertension caused by Borrelia burgdorferi-encephalitis is reported. The patient recovered from all symptoms following treatment with high dose cefuroxime. The diagnosis was not established until lumbar puncture was performed.

Adult

Subcutaneous and muscle blood flow during dopamine infusion in man.

Subcutaneous fat tissue and skeletal-muscle blood flow was measured in six male volunteers using the local 133Xe-washout method. Measurements were obtained before and during intravenous dopamine infusion in non-pressor (1 microgram kg-1 min-1) and pressor infusion rates (3-6 micrograms kg-1 min-1). During non-pressor infusion rate the systolic and diastolic arterial pressure and heart rate remained unchanged. When pressor dose dopamine was infused the systolic and mean arterial pressures increased significantly, whereas the diastolic pressure and the heart rate were left unchanged. The blood flow increased progressively from control values in both subcutis (control: 2.9 +/- 0.2, non-pressor: 5.0 +/- 1.6, pressor: 9.1 +/- 0.4 ml min-1 100 g-1, mean +/- SEM) and in skeletal muscle (control: 1.2 +/- 0.2, non-pressor: 1.5 +/- 0.2, pressor: 1.9 +/- 0.4 ml min-1 100 g-1, mean +/- SEM) and was significantly different from baseline values at any dopamine infusion rate. Side-effects were observed only at pressor dose infusion. It is concluded that dopamine in humans seems to possess vasodilatoric properties in subcutaneous fat tissue, and in skeletal muscles.

Adult

The effect of isosorbide dinitrate on the arterial vascular bed: a dose response study in dogs.

Isosorbide dinitrate (ISDN) was infused stepwise intraarterially into the left hindlimb (5.7-364.8 micrograms/kg/min.) into six dogs. The mean local vascular resistance was decreased by 32% in the left hindlimb after a dose of up to 91.2 micrograms/kg/min. corresponding to a 1.6-fold increase in the left femoral artery blood flow, without significant changes in the control limb or central haemodynamics. The muscular blood flow in the adductor magnus muscle obtained by the Xenon washout technique remained unchanged in 6 of 7 other dogs at ISDN infusion rates of 91.2 micrograms/kg/min., indicating that the increase in femoral artery blood flow was not a consequence of increased muscular blood flow. The arterio-venous extraction fraction of radioactive microspheres was lower in the experimental leg during ISDN infusion when compared with the control leg, suggesting that AV-shunts are opened during ISDN infusion. In addition to the well-known effect on preload, the present results confirm that ISDN also acts on afterload. Thus, ISDN may be classified as a mixed agent acting on both pre- and afterload which is in agreement with some previous studies.

Animals

Determinants of regional myocardial oxygen supply in the left ventricle. An experimental study in the in situ working canine heart.

The main factors that regulate myocardial oxygen supply include the 1. coronary blood flow controlling the volume flow fraction of red cells, 2. the oxygen carrying capacity of capillary blood dependent on the red cell volume fraction occupying the capillaries, and 3. the density of perfused capillaries affecting the capillary diffusion capacity and the diffusion distance in the tissue. Differences exist between the inner and outer layers of the left ventricle that include differences of systolic and possibly diastolic tissue stresses and oxygen consumption. The highest values were observed in the vicinity of the left ventricular cavity. The regional differences of myocardial oxygenation were studied in anaesthetized open-chest dogs by measuring the myocardial perfusion rate, the microvascular hematocrit, the PS-product of 51Cr-EDTA, and the microvascular blood volume across the left ventricular wall in the heart working in situ. Gradients of blood flow rates were present with the highest flow in deep myocardial layers. Maximally increasing the coronary blood flow at normal perfusion pressure and metabolic load did not change the distribution of blood flow between subendocardial and subepicardial layers. Distal to a coronary stenosis, blood flow was markedly reduced and redistributed away from the subendocardial layers, indicating a relatively severe decrease of fractional red cell flow to the left ventricular myocardium. The microvascular dynamic hematocrit, i.e. the volume fraction of red cells, was evenly distributed across the left ventricular wall, but consistently reduced to 75 per cent of great vessel hematocrit. The maximal increase of coronary blood flow provoked a further reduction of microvascular hematocrit due to a decrease of the red cell volume, possibly by shunt flow of red cells through low resistance vessels of capillary size. At restricted coronary inflow, the microvascular hematocrit was decreased with a redistribution of red cells away from deep myocardial layers. Extern compression of microvessels by the tissue pressure, phase-separation between red cells and plasma at microvascular bifurcations, or decrease of the red cell fluidity may all contribute to this change. Reduction both of microvascular red cell flow fraction and the hematocrit diminishes the red cell flux within capillaries and decreases the ability of blood to deliver oxygen to the tissue, and more so in the subendocardial layers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Absence of capillary recruitment during increased coronary blood flow in the working dog heart.

Myocardial plasma flow (MPF) and capillary permeability--surface area product (PS) were determined simultaneously on a regional basis in subendocardial and subepicardial layers of the left ventricular free wall in the working dog heart at control flow rate and during coronary vasodilation. The value for MPF was determined by the radioactive microsphere method and PS was assessed by an integral tissue-uptake method using [51Cr]-EDTA as test molecule. During coronary vasodilation achieved by intra-coronary infusion of adenosine, MPF increased markedly from 101.5 +/- 14.2 to 778.1 +/- 135.2 ml X min-1 X 100 g-1 in subendocardial layers and from 77.7 +/- 10.3 to 635.3 +/- 85.9 ml X min-1 X 100 g-1 in subepicardial layers of the left ventricular wall. Raising MPF by 800% was accompanied by a modest but statistically significant increase in PS[51Cr]-EDTA. In subendocardial layers PS increased from 49.3 +/- 5.0 to 60.0 +/- 3.3 ml X min-1 X 100 g-1 and in subepicardial layers from 43.8 +/- 4.1 to 52.1 +/- 2.4 ml X min-1 X 100 g-1, respectively. Taking into account back-diffusion of the tracer from the tissue to capillary blood which was higher at low flows than at high flows, PS[51Cr]-EDTA showed no increase with an eight-fold increment in flow. This observation rebuts the concept of additional perfusion of capillaries which are devoid of plasma flow under resting conditions during coronary vasodilation.

Adenosine

Oxygen transport to the canine left ventricle distal to a flow-limiting coronary artery stenosis.

Myocardial blood flow, microvascular blood volume and red cell volume fraction (hematocrit) were investigated on a regional basis distal to the site of a coronary artery constriction in the left ventricular myocardium of anaesthetized open-chest dogs. Myocardial oxygen consumption was computed with the Fick equation. After application of the coronary artery stenosis myocardial blood flow decreased from 76.6 +/- 8.4 to 36.6 +/- 6.6 ml X min-1 X 100 g-1 in subepicardial layers and from 90 +/- 6.9 to 24.1 +/- 6.5 ml X min-1 X 100 g-1 in subendocardial layers of the left ventricular wall with a significant redistribution of blood flow away from the subendocardium. The red cell volume decreased significantly from 1.27 +/- 0.07 to 0.95 +/- 0.07 ml X 100 g-1 in subepicardial layers and from 1.52 +/- 0.09 to 1.01 +/- 0.11 ml X 100 g-1 in subendocardial layers of the left ventricle, whereas the plasma volume increased slightly but not significantly. In the subepicardial layers the plasma volume increased from 2.84 +/- 0.11 to 3.40 +/- 0.21 ml X 100 g-1 and in the subendocardial layers from 3.24 +/- 0.09 to 3.76 +/- 0.22 ml X 100 g-1. Coronary capillary density as reflected in measurements of microvascular blood volume (red cell volume + plasma volume) did not change significantly. The microvascular hematocrit (red cell volume/red cell volume + plasma volume) was uniformly distributed in both myocardial layers. The average hematocrit of the microcirculation during control flow rate (31 +/- 1%) was consistently lower than hematocrit drawn from large arteries. Expressed relatively to the hematocrit in arterial blood, the microvascular hematocrit was found to be in the order of 0.75. Distal to the flow-limiting coronary artery constriction, mean microvascular hematocrit fell significantly to 23 +/- 1%. During impeded coronary inflow, the myocardial oxygen consumption fell significantly from 3.3 +/- 0.6 to 2.0 +/- 0.4 ml X min-1. These results indicate that during ischemia, the myocardium is not only suffering from a diminished blood supply, but also is perfused by blood with a diminished oxygen delivery capacity.

Animals

Distribution of myocardial blood flow and capillary diffusion capacity across the canine heart wall.

Myocardial capillary permeability was determined in 20 dogs by applying a new method which resembles the tissue-uptake technique. The method consisted of a bolus injection of 51Cr-EDTA into the left atrium, determination of the average arterial tracer concentration and subsequent assay of myocardial tissue activity 10, 20 and 30 s after injection. Under the fundamental assumption of no back-diffusion of tracer to capillary blood, uptake of 51Cr-EDTA into myocardium allowed calculation of the transfer constant, Kin, independent of blood flow. Regional plasma flow, fpl, was simultaneously determined from tissue content and average arterial concentration of radioactive microspheres and haematocrit. From estimates of Kin and fpl the fractional extraction, E, of 51Cr-EDTA was calculated as E = Kin/fpl. The capillary permeability-surface area product, PS, was calculated as PS = -fpl X k X 1n (1 - E). Constant fractional extraction of 51Cr-EDTA indicates that the method can be employed 10 to 20 s after injection without risk of back-diffusion. From tissue samples taken from subendocardial and subepicardial layers of the left and right ventricular walls and from left and right side parts of the septal region we measured similar PS values. Letting capillary surface area, S, equal 500 cm2 X -1 the permeability coefficient for 51Cr-EDTA was 1.39 X 10(-5) cm X s-1.

Animals

Effect of intracoronary adenosine upon regional blood flow, microvascular blood volume and hematocrit in canine myocardium.

Microvascular blood volume and red cell volume fraction (hematocrit) and their relation to increased coronary blood flow were investigated in the dog heart. In response to intracoronary adenosine infusion into the anterior descending branch (LAD) of the left coronary artery, myocardial blood flow increased markedly in the perfusion zone compared with a region of the left ventricular free wall as supplied with blood from the circumflex branch (Cx) of the left coronary artery. Raising the LAD blood flow by 800% significantly reduced microvascular blood volume in the dilated vascular bed compared with the undilated vascular bed of the Cx. Control microvascular hematocrit averaged 29 +/- 2%. Hematocrit was not only low at control flow but decreased with increased blood flow, average 20 +/- 2%. The volume of red cells contained within microvessels decreased significantly in the adenosine-dilated vascular bed whereas the volume of plasma remained unchanged compared with the control vascular bed. The present data favor the view that such alterations in microvascular blood volume and red cell volume fraction may be due to reduction of the density of red blood cell perfused capillaries and unchanged density of plasma perfused capillaries.

Adenosine

Regional blood flow, microvascular blood content and tissue haematocrit in canine myocardium.

Regional myocardial blood flow, myocardial microvascular blood content and tissue haematocrit were determined in mongrel dogs. In nine dogs the intramyocardial distribution volumes of 99Tcm-albumin and 125I-fibrinogen were examined. Tracer equilibration times of 5, 10 and 30 min were used. The 125I-fibrinogen distribution volume was significantly lower than the distribution volume of 99Tcm-albumin. The 125I-fibrinogen distribution volume was not found to change with time and was thus taken to be a measure of the plasma volume. In 10 dogs intramyocardial distribution of 51Cr-labelled red cells and 125I-fibrinogen was estimated and regional myocardial blood flow was measured by 15 microns 99Tcm-albumin spheres. Plasma and red cell volumes, interpreted as myocardial microvascular blood content, ranged from 3.66 to 4.93 cm3-100 g-1. The distribution volumes indicated gradients with higher endocardial and longitudinal microvascular blood content in the left ventricular free wall and the septum. The intramyocardial haematocrits calculated from the plasma and red cell volumes were uniformly 0.3 all over the heart and amounted to 0.75 of arterial haematocrit. The mean right ventricular blood flow of 46.80 cm3 . min-1 . 100 g-1 amounted to 0.6 of a mean left ventricular blood flow of 86.65 cm3 . min-1 . 100 g-1. Transmural and longitudinal gradients of regional myocardial blood flow within the ventricular wall were observed. The patterns of transmural and longitudinal gradients of regional blood flow and microvascular blood content implies higher flow rates through more or larger vessels indicating a greater endocardial and apical vascular conductance in the vicinity of the left ventricular cavity.

Animals