Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

Early patency of the infarct-related artery after myocardial infarction preserves diastolic filling.

A patent infarct-related artery (IRA) following myocardial infarction has been associated with lower mortality, increased systolic function, decreased left ventricular remodeling, and electrical stability. The purpose of this study was to determine whether coronary artery patency early after myocardial infarction is associated with greater early diastolic filling than a closed artery. Radionuclide ventriculograms were performed at a central laboratory on 167 patients who received alteplase for an acute myocardial infarction and had infarct artery patency determined by cardiac catheterization. The peak early filling rate (PEFR) was assessed by 4 different methods: (1) PEFR (EDV/s)--normalized to the end-diastolic volume; (2) PEFR (SV/s)--normalized to the stroke volume; (3) PEFR (ml/s/m(2))--an absolute diastolic filling rate; and (4) PEFR (PER)--normalized to the peak ejection rate. Patients with a closed IRA (n = 16, Thrombolysis In Myocardial Infarction [TIMI] 0 or 1 flow) and patients with an open IRA (n = 151, TIMI 2 or 3 flow) had similar ages, ejection fractions, and cardiac volumes. However, among patients with an occluded IRA, the PEFR was decreased by 12% to 18% by the 4 measures of diastolic filling (3 of 4 methods, p <0.05). PEFR (EDV/s) was 1.69 +/- 0.9 in the occluded group versus 2.06 +/- 0.4 EDV/s in the open artery group (p = 0.005). By multivariate analysis, IRA patency was an independent predictor of the PEFR by all 4 methods. Early coronary artery patency after an acute myocardial infarction preserves diastolic filling. Improved diastolic function may in part explain part of the long-term benefits of a patent IRA after thrombolytic therapy when there is no documented improvement in the ejection fraction.

Norepinephrine alters exercise oxygen consumption in heart failure patients.

PURPOSE: The primary aim of this research was to evaluate the effect of acute norepinephrine (NE) infusion on the exercise oxygen utilization in heart failure patients as compared with healthy adults. METHODS: Eleven healthy adults and 10 patients with NYHA class II-III heart failure (ejection fraction <40%) who were not on beta-blocker therapy underwent steady state exercise under placebo or NE infusion conditions, followed by maximal ramp exercise testing. Oxygen utilization, hemodynamic responses, and serum lactate NE levels were evaluated. RESULTS: The hemodynamic effects of NE were evident in both groups with statistically significant increases in blood pressure and concomitant decreases in heart rates. Lactate levels were higher in heart failure subjects under all conditions and steady state exercise increased levels by 24% (P = 0.04). NE infusion increased lactate levels by a nonsignificant 24% (P = 0.19). NE infusion tended to increase oxygen consumption (VO2) at the end of steady state exercise in CHF subjects (4% change; P = 0.06). Compared with healthy adults, NE infusion significantly impaired (increased) the gross VO2/W relationship in heart failure subjects (P = 0.037). There was also a modest trend for a worsening (decrease) in net efficiency after NE infusion in CHF subjects. There were no significant adverse effects of low-dose NE infusion in either group. CONCLUSIONS: We conclude that 1) acute low-dose NE infusion impairs the oxygen utilization in stable heart failure patients but not in healthy adults. This may help to explain the exercise intolerance that accompanies congestive heart failure. 2) Acute infusion of low-dose NE infusion is safe and well tolerated in both healthy adults and compensated heart failure patients.

Effect of endurance exercise training on heart rate variability at rest in healthy young and older men.

Heart rate variability (HRV) (SD of the RR interval), an index of parasympathetic tone, was measured at rest and during exercise in 13 healthy older men (age 60 to 82 years) and 11 healthy young men (age 24 to 32 years) before and after 6 months of aerobic exercise training. Before exercise training, the older subjects had a 47% lower HRV at rest compared with the young subjects (31 +/- 5 ms vs 58 +/- 4 ms, p = 0.0002). During peak exercise, the older subjects had less parasympathetic withdrawal than the young subjects (-45% vs -84%, p = 0.0001). Six months of intensive aerobic exercise training increased maximum oxygen consumption by 21% in the older group and 17% in the young group (analysis of variance: overall training effect, p = 0.0001; training effect in young vs old, p = NS). Training decreased the heart rate at rest in both the older (-9 beats/min) and the young groups (-5 beats/min, before vs after, p = 0.0001). Exercise training increased HRV at rest (p = 0.009) by 68% in the older subjects (31 +/- 5 ms to 52 +/- 8 ms) and by 17% in the young subjects (58 +/- 4 ms to 68 +/- 6 ms). Exercise training increases parasympathetic tone at rest in both the healthy older and young men, which may contribute to the reduction in mortality associated with regular exercise.

Donor left ventricular hypertrophy increases risk for early graft failure.

A review of factors contributing to early mortality after cardiac transplantation revealed that up to 25% of deaths were due to primary graft dysfunction unrelated to rejection or infection. In light of this finding, evaluation of a donor heart with regard to its suitability for transplantation takes on added importance. In an effort to screen the suitability of donor hearts in the region covered by the Northwest Organ Procurement Agency (USA), all donors are evaluated by two-dimensional transthoracic echocardiography as part of the initial evaluation. A total of 110 donor echocardiograms were reviewed and an attempt was made to correlate the 30-day outcome with the parameters measured. An unexpected finding was that the presence of left ventricular hypertrophy in the donor heart was associated with an increase in the incidence of donor heart dysfunction compared with donors with normal echocardiographic profiles (33% vs 3%, P = 0.007).

The circulatory regulation of TPA and UPA secretion, clearance, and inhibition during exercise and during the infusion of isoproterenol and phenylephrine.

BACKGROUND: Exercise to exhaustion and infusions of isoproterenol and phenylephrine were used to study interactions between plasminogen activator regulation and the control of regional blood flow in 10 healthy males. METHODS AND RESULTS: Experimental measurements of cardiac output, heart rate, tissue plasminogen activator (TPA), urokinase plasminogen activator (UPA), plasminogen activator inhibitor (PAI-1), C1-inhibitor, and TPA/C1-inhibitor complex during the infusions and exercise were used to develop a comprehensive fluid-phase model of the circulatory regulation of fibrinolysis. alpha- and beta-adrenergic agonists increased TPA and UPA in plasma by different mechanisms: Phenylephrine decreased hepatic blood flow and thus clearance while isoproterenol stimulated increased secretion of TPA and UPA. Exercise to exhaustion increased TPA and UPA through a combination of increased secretion and decreased clearance. The time course of UPA and TPA release were similar, but the magnitude of their secretion responses differed. In vivo, C1-inhibitor bound to TPA at a rate of 553 mol-1.s-1. C1-inhibitor contributed equally with PAI-1 to TPA inhibition when active PAI-1 levels were low (20 to 50 pmol/L) but was less important when active PAI-1 levels were high. CONCLUSIONS: We conclude that secretion, inhibition, clearance, and regional blood flow effects must all be taken into account when evaluating changes in plasminogen activator levels.

Beta-adrenergic effects on left ventricular filling: influence of aging and exercise training.

Reduced heart rate and contractile responses to beta-agonist stimulation characterize normal cardiac aging, but whether diastolic responses also decline with aging has not been determined in humans. Diastolic filling responses to isoproterenol were determined in 13 older (60-82 yr) and 11 young (24-32 yr) healthy men before and after endurance training. Filling rates were expressed in three ways: 1) normalized to end-diastolic volume per second, 2) normalized to stroke volume per second, and 3) as absolute milliliters of blood (ml.s-1.m-2). Peak early filling rates by all methods were reduced at rest and all isoproterenol doses with aging (all P < 0.0001 for old vs. young), whereas peak atrial filling rates were increased with aging. During isoproterenol, both peak early and peak atrial filling rates increased significantly (all P < 0.01); the increase in filling rates with isoproterenol was not different with aging (all NS for old vs. young x dose). Endurance training did not augment diastolic filling responses to isoproterenol. Although diastolic filling rates at rest are markedly altered by aging, diastolic filling responses to isoproterenol are not reduced with aging. Thus the age-associated declines in heart rate, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol do not extend to diastolic filling responses.

Cardiovascular responses to exercise. Effects of aging and exercise training in healthy men.

BACKGROUND: Cardiac aging alters many of the acute responses to exercise stress, but the extent to which chronic exercise (ie, training) can alter or improve the effects of aging in humans is largely unknown. METHODS AND RESULTS: Cardiovascular responses to graded supine exercise stress (beginning at 200 kpm and increasing by 200 kpm every 3 minutes till exhaustion) were assessed using radionuclide ventriculography in 13 older (age, 60 to 82 years) and 11 young (age, 24 to 32 years) rigorously screened healthy men before and after 6 months of endurance training. Repeated-measures ANOVA was used to test significance. During exercise, the old group had a lesser increase in heart rate (+105% old versus +166% young), a greater increase in mean blood pressure (+35% old versus +22% young), lesser increases in ejection fraction (+3 ejection fraction units old versus +11 units young) and peak ejection rate (+62% old versus +119% young), a greater increase in end-diastolic volume index (+8% old versus -10% young), a lesser fall in end-systolic volume index (-0% old versus -32% young), and a lesser increase in cardiac index (+135% old versus +189% young) (all P < .01 young/old versus exercise stage). Stroke volume index response to exercise was not different with aging (+14% old versus +6% young, P = NS). Exercise training increased maximal oxygen intake by 21% in the older group (28.9 +/- 4.6 to 35.1 +/- 3.8 mL.kg-1.min-1, P < .001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/- 6.3 mL.kg-1.min-1, P < .001) and increased peak workload by 24% in the old and 28% in the young. Exercise training had no differential effects on old versus young men. Among all subjects, training significantly reduced the resting heart rate by 12% (-8 beats per minute) and increased resting end-diastolic volume index by 13% (+9 mL/M2) and resting stroke volume index by 18% (+7 mL/M2) (all P < .01). At peak exercise, cardiac index increased by 16% (+1.07 L.M-2.min-1) compared with before training, which was the result of an increase in stroke volume of 18% (+7 mL/M2) (P < .001); peak heart rate was unchanged. The increase in stroke volume index at peak exercise was the result of both a 12% increase in end-diastolic volume index (+8 mL/M2) (P < .01) and an increase in ejection fraction (+3 ejection fraction units) (P < .05) at peak exercise. The increased ejection fraction at peak exercise occurred despite a 9% increase in systolic blood pressure (+18 mm Hg) (P < .01), suggesting an increase in contractility. Thus, both the young and old increased peak exercise cardiac output by use of the Frank-Starling mechanism (ie, cardiac dilatation) as well as an increase in ejection fraction. CONCLUSIONS: We conclude that there is an age-associated decline in heart rate, ejection fraction, and cardiac output responses to supine exercise in healthy men. Although the stroke volume responses of the young and old are similar, the old tend to augment stroke volume during exercise more through cardiac dilatation, with an increase in end-diastolic volume (+8%) but without much change in ejection fraction (+3 ejection fraction units), whereas the young rely more on an increase in the ejection fraction (+11 ejection fraction units) with no cardiac dilatation (-10%). Despite the significant cardiovascular changes that occur in the response to a single bout of exercise with aging, adaptations to chronic exercise training were not different with aging and included improvements in maximal workload and increases in ejection fraction, stroke volume index, and cardiac index at peak exercise.

Endurance exercise training augments diastolic filling at rest and during exercise in healthy young and older men.

BACKGROUND: Diastolic filling at rest is altered markedly with advancing age. Whether exercise training can improve diastolic filling at rest or during exercise in either healthy older or healthy young men has not been determined. The purpose of this study was to determine if 6 months of aerobic exercise training improves diastolic filling. METHODS AND RESULTS: Radionuclide diastolic filling parameters were measured at rest and during exercise in 14 older (age, 60 to 82 years) and 17 young (age, 24 to 32 years) rigorously screened healthy males before exercise training and in 13 older and 11 young men after 6 months of endurance exercise training. Diastolic filling rates were expressed in two ways, as absolute milliliters of blood (mL.s-1.m-2) and normalized to the end-diastolic volume. At baseline, the peak early filling rates were lower in the older group compared with the young group as expressed in absolute milliliters of blood (older, 85 +/- 7 mL.s-1.m-2; young, 173 +/- 10 mL.s-1.m-2; P < or = .0001) and in end-diastolic volume per second (1.66 +/- 0.11 versus 2.55 +/- 0.08, P < .0001), whereas the peak atrial filling rates were greater in absolute milliliters of blood (85 +/- 5 versus 56 +/- 7 mL.s-1.m-2, P = .003) and in end-diastolic volume per second (1.70 +/- 0.12 versus 0.80 +/- 0.06, P < .0001). During exercise, at any given heart rate, the older group had a lower peak filling rate than the young group. Also, at peak exercise, the single peak filling rate was decreased in the older group in mL.s-1.m-2 (384 +/- 19 versus 565 +/- 36 mL.s-1.m-2, P = .0002) and in end-diastolic volume per second (6.01 +/- 0.25 versus 7.91 +/- 0.28 end-diastolic volume per second, P < .0001). Six months of intensive aerobic exercise training had similar effects in the old and young groups overall. Maximal oxygen consumption increased 19% (ANOVA training effect, P < or = .0001) and echocardiographic left ventricular mass increased 8% (ANOVA training effect, P = .002). Training increased the resting peak early filling rate in absolute milliliters of blood by +14% (ANOVA training effect, P = .02). During exercise, the peak early or single peak filling rate at any given heart rate was increased. At peak exercise, the single peak filling rate was increased by 14% in mL.s-1.m-2 (ANOVA training effect, P = .0004). The only age-related differential effect of training was on the peak atrial filling rate in end-diastolic volume per second, which decreased by 27% in the older group but was unchanged in the young (+5%) (ANOVA young versus older, P = .001). The independent predictors of a greater maximal oxygen consumption by multivariate analysis were a higher peak exercise heart rate, a greater resting peak early filling rate, the exercise trained state, and a younger age. CONCLUSIONS: Healthy older men have reduced early diastolic filling at rest and during exercise compared with young men. Endurance exercise training enhances early diastolic filling at rest and during exercise in both the old and the young. Training reduces the elevated resting atrial filling rate in the old, whereas the young were unchanged. The training-induced augmentation of early diastolic filling at rest and during exercise may be an important adaptation to allow an increase in stroke volume at rest and an increase in stroke volume, cardiac output, and maximal oxygen consumption during exercise.

A kinetic model of the circulatory regulation of tissue plasminogen activator during exercise, epinephrine infusion, and endurance training.

A computer simulation of the circulatory system was used to kinetically model secretion, inhibition, and clearance of tissue plasminogen activator (t-PA) during three different processes that increase active t-PA levels: epinephrine infusion, exercise, and endurance training. Infusion of epinephrine stimulated an increase in t-PA secretion that was proportional to the plasma epinephrine concentration. In addition, epinephrine infusion increased hepatic blood flow and t-PA clearance, thus slowing the increase of plasma t-PA levels. During exercise, t-PA levels increased due both to increased t-PA secretion and to decreased clearance secondary to reduced hepatic blood flow. The increase in t-PA secretion during exercise was directly proportional to the epinephrine concentration in blood with the same ratio of t-PA secretion to epinephrine as found during epinephrine infusion, suggesting that increased plasma epinephrine during exercise was the primary stimulus for t-PA secretion. Lastly, the simulation predicted that 6 months of endurance training produced a decrease in resting plasminogen activator inhibitor type 1 (PAI-1) secretion, resulting in less t-PA inhibition and an overall increase in active t-PA after training. Accurate analysis of the regulation of active t-PA levels in blood required simultaneous modeling of t-PA and PAI-1 secretion, hepatic clearance, and inhibition of t-PA by PAI-1.

Radionuclide cardiac volumes: effects of region of interest selection and correction for Compton scatter using a buildup factor.

The effects of region of interest (ROI) selection and correction for Compton-scattered photons using a buildup factor on radionuclide left ventricular volumes calculated by the Links method were compared in 19 humans with contrast ventriculography and in phantoms. Three different methods of ROI selection were compared: a manual ROI, a second derivative ROI and a 50% count-threshold ROI. In phantoms without Compton scatter correction, volumes were overestimated by 30% (manual ROI), 20% (derivative ROI) and 1% (count threshold ROI). In subjects, results without Compton scatter correction were similar with overestimates of 50% (manual ROI) and 20% (derivative ROI) and an underestimate by 3% (count threshold method). Correction for Compton-scattered photons with the use of a phantom-derived buildup factor resulted in improved accuracy for the manual ROI (+15%) and the derivative ROI (0%). A 50% count threshold ROI following interpolative background subtraction allows the accurate calculation of cardiac volumes without the need for scatter correction, while a second derivative ROI method requires a correction for Compton scatter with the use of a buildup factor.

Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men.

BACKGROUND: Cardiac aging is characterized by a reduced heart rate response to beta-agonist stimulation with isoproterenol, but whether the ejection fraction and other cardiovascular responses are reduced in humans is largely unknown. In addition, whether reduced beta-agonist responses can be improved with exercise training has not been determined in humans. METHODS AND RESULTS: Cardiovascular responses to graded isoproterenol infusions (3.5, 7, 14, and 35 ng/kg/min for 14 minutes each) were assessed in 15 older (age, 60-82 years) and 17 young (age, 24-32 years) rigorously screened healthy men. Thirteen older and 11 young subjects completed 6 months of endurance training and were retested. At baseline, the older group had reduced responses to isoproterenol for heart rate (+65% older versus +92% young, p less than 0.001), systolic blood pressure (+9% versus +24%, p less than 0.001), diastolic blood pressure (-12% versus -24%, p less than 0.05), ejection fraction (+12 versus +20 ejection fraction units, p less than 0.001), and cardiac output (+70% versus +100%, p less than 0.001). The mean plasma isoproterenol concentrations achieved during the infusions were marginally higher (p = 0.07) in the older group (128 +/- 58, 227 +/- 64, 354 +/- 114, and 700 +/- 125 pg/ml) than in the young (79 +/- 20, 178 +/- 49, 273 +/- 79, and 571 +/- 139 pg/ml). Intensive training increased maximal oxygen consumption by 21% in the older group (28.9 +/- 4.6 to 35.1 +/- 3.8 ml/kg/min, p less than 0.001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/- 6.3 ml/kg/min, p less than 0.001), but training did not augment any of the cardiovascular responses to isoproterenol in either group. The mean plasma isoproterenol concentrations at the four infusion doses were unchanged after training in both groups. CONCLUSIONS: We conclude that there is an age-associated decline in heart rate, blood pressure, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol in healthy men. Altered beta-adrenergic responses probably contribute to the reduced cardiac responses to maximal exercise that also occur with aging. Furthermore, intensive exercise training does not increase cardiac responses to beta-adrenergic stimulation with isoproterenol in either young or older men. The reduced beta-adrenergic response appears to be a primary age-associated change that is not caused by disease or inactivity.

Factors influencing serial measurements of cardiac volumes by count-based methods: effects of elevated catecholamines, position, and exercise on technetium-99m-blood radioactivity concentration.

Most radionuclide methods for measuring cardiac volume require a determination of the blood radioactivity concentration. Thus, changes in blood radioactivity over time or during interventions might lead to spurious volume estimates unless blood radioactivity is serially measured. The effects of elevated epinephrine, posture and exercise on 99mTc-labeled blood radioactivity concentration were studied in 15 young (mean age = 28 yr) and 14 older (mean age = 68 yr) healthy males. An epinephrine infusion of 50 ng/kg/min resulted in a 4.1% +/- 1.0% increase in 99mTc-blood radioactivity (p less than or equal to 0.001) compared to baseline. Sitting increased blood radioactivity concentration by 12.3% +/- 3.0% (p less than 0.0002) compared to the supine position and peak supine bicycle exercise caused an 11.0% +/- 1.7% increase (p less than or equal to 0.0001) compared to supine rest. There was a significantly greater increase during peak supine exercise in the young compared to the older subjects (15.0% +/- 2.3% versus 6.3% +/- 2.0%, p less than or equal to 0.01). The mechanism of the increase in blood radioactivity concentration is uncertain, but presumably reflects the addition of hemoconcentrated red blood cells from the spleen and/or the loss of plasma volume. Failure to correct for the increased blood radioactivity concentration during exercise or pharmacological interventions will result in a significant error in serial measurements of cardiac volumes by methods requiring RBC radioactivity measurements.

Fibrinolytic response during exercise and epinephrine infusion in the same subjects.

To determine whether exercise-induced increases in tissue plasminogen activator (t-PA) were related to plasma epinephrine concentration during exercise, 14 healthy men (aged 24 to 62 years) were studied during epinephrine infusions (10, 25 and 50 ng/kg per min) and graded supine bicycle exercise, beginning at 33 W and increasing in 33-W increments until exhaustion. Plasma epinephrine, active and total t-PA, active plasminogen activator inhibitor type 1 (PAI-1) and t-PA/PAI-1 complex concentrations were measured at each exercise and infusion level. During epinephrine infusion, active and total t-PA levels increased linearly with the plasma epinephrine concentration (respective slopes [+/- SEM] of 0.062 +/- 0.003 and 0.076 +/- 0.003 pmol/ng epinephrine). During exercise, t-PA levels did not increase until plasma epinephrine levels increased, after which both active and total t-PA levels again increased linearly with the plasma epinephrine concentration, but at twice the rate observed with epinephrine infusion (0.131 +/- 0.005 and 0.147 +/- 0.005 pmol/ng, respectively). The t-PA level in blood was directly proportional to the plasma epinephrine concentration during both exercise and epinephrine infusion, suggesting that epinephrine release during exercise stimulates t-PA secretion. In these healthy subjects, active plasminogen activator inhibitor type 1 and t-PA/PAI-1 complex levels were low (41 +/- 11 and 21 +/- 5 pmol/liter, respectively) and did not change significantly during exercise or epinephrine infusion. It is concluded that approximately 50% of the increase in t-PA during exercise is due to stimulated release of t-PA by epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Four radionuclide methods for left ventricular volume determination: comparison of a manual and an automated technique.

This study compared the accuracy and reproducibility of three previously described and one new radionuclide method of measuring left ventricular volumes in 19 subjects using contrast ventriculographic volumes (n = 38, mean volume = 126.6 ml) as the gold standard. The four methods were compared using both manual and automated ROIs. For manual ROIs, the Links (189.7 ml, r = 0.85), Starling (183.2 ml, r = 0.77) and the new count ratio method (141.4 ml, r = 0.90) overestimated contrast volumes, while the Massardo method (122.5 ml, r = 0.91) provided accurate volumes. For the automated ROIs, we performed an interpolative background subtraction and used a 50% threshold of the highest count pixel to define the ventricular regions. The automated Massardo method severely underestimated the contrast volume (59.5 ml, r = 0.90), while the other automated methods yielded accurate volumes: Links (122.4 ml, r = 0.89), Starling (118.1 ml, r = 0.81) and the new count ratio method (125.0 ml, r = 0.90). The interobserver reproducibility of the automated methods was excellent (mean difference = 1%-4%) compared to the manual methods (2%-8%). Because no additional images, blood counting, attenuation, or decay correction were necessary, the manual Massardo method and the automated count ratio method are the simplest to perform. We conclude that automated determination of left ventricular volumes using the new count ratio method is rapid, accurate, reproducible and could readily be incorporated into routine clinical use.

Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults.

BACKGROUND: The effects of 6 months of intensive endurance exercise training on resting tissue-type plasminogen activator (t-PA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, t-PA antigen, and fibrinogen were studied in 10 young (24-30 years) and in 13 old male subjects (60-82 years). METHODS AND RESULTS: After training, maximum oxygen consumption was increased in the young group by 18% (44.9 +/- 5.0 to 52.9 +/- 6.6 ml/kg/min, p less than 0.001), whereas it was increased in the old group by 22% (29.0 +/- 4.2 to 35.5 +/- 3.6 ml/kg/min, p less than 0.001). The young group had no significant changes in any of the measured variables, whereas the old group had a 39% increase in t-PA activity (0.82 +/- 0.47 to 1.14 +/- 0.42 IU/ml, p less than 0.03), a 141% increase in the percentage of t-PA in the active form (11.1 +/- 7.7 to 26.8 +/- 15.1%, p less than 0.01), a 58% decrease in PAI-1 activity (8.4 +/- 4.9 to 3.5 +/- 1.7 AU/ml, p less than 0.01), and a 13% decrease in fibrinogen (3.57 +/- 0.79 to 3.11 +/- 0.52 g/l, p less than 0.01). CONCLUSIONS: We conclude that intensive exercise training enhances resting t-PA activity and reduces fibrinogen and PAI-1 activity in older men. These effects are potential mechanisms by which habitual physical activity might reduce the risk of cardiovascular disease.

Ranking of laboratory tests by consensus analysis.

A new analytical technique (consensus analysis) was devised to assess the performance of laboratory tests that are commonly used to monitor the acute and chronic phases of inflammatory disease. On thirty-one tests carried out monthly for 7 months in seventeen patients with rheumatoid arthritis, the consensus analysis procedure ranked plasma viscosity and erythrocyte sedimentation rate in a tie for first place. Measurement of the acute-phase serum protein orosomucoid ranked third. Consensus analysis has the potential to reduce laboratory costs by identifying the most useful tests; it also promises to be helpful in the design of new laboratory tests that are more sensitive and specific.

The incorporation of red blood cell index mean data into quality control programs.

Patient red blood cell (RBC) index means, when used in quality control, form an independent standard that is as accurate and precise as preserved blood controls. If such patient data are routinely incorporated in intralaboratory and interlaboratory quality control programs, a substantial improvement in the present state-of-the-art is possible. Within the laboratory, each method serves to confirm the adequacy of the other. In interlaboratory control trials the combination makes it possible to specify the cause of most misanalyses. For similar reasons, the combination of both methods enables the manufacturer of quality control material to assess the adequacy of the manufacturing and value assignation process.