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Influence of the pericardium on right and left ventricular filling in the dog.

We compared the influence of the pericardium on left and right ventricular (LV, RV) filling by measuring LV and RV pressures and segment lengths (SL, LV free wall, and RV inflow and outflow tracts) in six open-chest, pentobarbital sodium-anesthetized dogs before and after pericardiectomy. End-diastolic pressure (EDP) was varied by partial caval occlusion and dextran infusion. At each site the ln EDP-SL relation was fitted by linear regression and characterized by its slope and 1-Torr EDP intercept. The slope and 1-Torr intercept of the LV ln EDP-SL relation changed variably after pericardiectomy, but in each dog a change occurred that shifted this relation downward. In contrast, the RV inflow tract slope invariably decreased significantly after pericardiectomy, whereas its intercept was unchanged in all but one dog. The RV outflow tract results were similar to the inflow tract but less consistent. By the use of the raw EDP-SL data points, we calculated that the absolute contribution of the pericardium to EDP (i.e., the effective pericardial surface pressure) was similar at the three sites. However, as EDP values increased the proportional contribution of the pericardium to right ventricular end-diastolic pressure (RVEDP) increased, whereas that to left ventricular end-diastolic pressure (LVEDP) remained relatively constant. As a result, at the higher EDP values tested, the pericardium was responsible for a larger proportion of RVEDP than LVEDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rapid determination of glomerular filtration rate by single-bolus inulin: a comparison of estimation analyses.

Rapid measurement of glomerular filtration rate (GFR) by an inulin single-bolus technique would be useful, but its accuracy has been questioned. We hypothesized that reported inaccuracies reflect the use of inappropriate mathematical models. GFR was measured in 14 intact and 5 unilaterally nephrectomized conscious male Sprague-Dawley rats (mean weight 368 +/- 12 g) by both single-bolus (25 mg/kg) and constant-infusion techniques (0.693 mg . kg-1 . min-1). The temporal decline in plasma inulin concentration was analyzed through biexponential curve fitting, which accounted for renal inulin loss before complete vascular and interstitial mixing. We compared our mathematical model based on empirical rationale with those of other investigators whose studies suggest inaccuracy of single-bolus methods. Our mathematical model yielded GFR values by single bolus that agreed with those obtained by constant infusion [slope = 0.94 +/- 0.16 (SE); y intercept = 0.23 +/- 0.64; r = 0.82]. In comparison to the data obtained by constant inulin infusion, this method yielded a very small bias of -0.0041 +/- 0.19 ml/min. Two previously reported models yielded unsatisfactory values (slope = 1. 46 +/- 0.34, y intercept = 0.47 +/- 1.5, r = 0.72; and slope = 0.17 +/- 1.26, y intercept = 17.15 +/- 5.14, r = 0.03). The biases obtained by using these methods were -2.21 +/- 0.42 and -13.90 +/- 1. 44 ml/min, respectively. The data indicate that when appropriate mathematical models are used, inulin clearance after single-bolus delivery can be used to measure GFR equivalent to that obtained by constant infusion of inulin. Attempts to use methods of analysis for simplicity or expediency can result in unacceptable measurements relative to the clinical range of values seen.

Algorithms↗

Modeling the influence of body size on V(O2) peak: effects of model choice and body composition.

This study examined the bivariate relationship between peak oxygen uptake (V(O2) peak); l/min) and body size in adult men (n = 1,314, age 17-66 yr), using both "simple" and "full" iterative nonlinear allometric models. The simple model was described by V(O2) peak = M(b) (or FFM(b)) exp(c SR-PA) exp(a + d age) epsilon (where M is body mass in kg; FFM is fat-free mass in kg; SR-PA is self-reported physical activity; epsilon is a multiplicative error term; and exp indicates natural antilogarithms). The full model was described by V(O2) peak = M(b) (or FFM(b)) exp(c SR-PA) exp(a + d age) + e (epsilon), where e is a permitted Y-intercept term. The M exponent obtained from simple allometry was 0.65 [95% confidence interval (CI), 0.59-0.71], suggestive of a curvilinear relationship constrained to pass through the origin. This "zero Y-intercept" assumption was examined via the full allometric model, which revealed an M exponent of 1.00 (95% CI, 0.7-1.31), together with a positive Y-intercept term (e) of 1.13 (95% CI, 0.54-1.73). The FFM exponents were not significantly different from unity in either the simple or full allometric models. It appears that the curvilinearity of the simple allometric model (using total M) is fictitious and is due to the inappropriate forcing of the regression line through the origin. Utilizing FFM as the body-size variable revealed a linear relationship between body size and V(O2) peak, irrespective of model choice. We conclude that the population mass exponent for V(O2) peak is close to unity.

Adolescent↗

Validity of fluorescent microspheres method for bone blood flow measurement during intentional arterial hypotension.

In this study, we compared bone blood flow values obtained by simultaneously injected fluorescent (FM) and radiolabeled microspheres (RM) at stepwise reduced arterial blood pressure. Ten anesthetized female New Zealand White rabbits received simultaneous left ventricular injections of FM and RM at 90, 70, and 50 mmHg mean arterial blood pressure (MAP). After the experiments, both kidneys and long bones of all four limbs were removed and dissected in a standardized manner. Radioactivity (corrected for decay, background, and spillover) and fluorescence were determined, and blood flow values were calculated. Relative blood flow values estimated for each bone sample by RM and FM were significantly correlated (r = 0.98, slope = 0.99, and intercept = 0.04 for 90 mmHg; r = 0.98, slope = 0.94, and intercept = 0.09 for 70 mmHg; r = 0.98, slope = 0.96, and intercept = 0.07 for 50 mmHg). Blood flow values (ml x min-1 x 100 g-1) of right and left bone samples determined at the different arterial blood pressures were identical. During moderate hypotension (70 mmHg MAP), blood flow in all bone samples remained unchanged compared with 90 mmHg MAP, whereas a significant decrease of bone blood flow was observed at severe hypotension (50 mmHg MAP). Our results demonstrate that the FM technique is valid for measuring bone blood flow. Differences in bone blood flow during altered hemodynamic conditions can be detected reliably. In addition, changes in bone blood flow during hypotension indicate that vasomotor control mechanisms, as well as cardiac output, play a role in setting bone blood flow.

Algorithms↗

Quantitative characterization of airspace enlargement in emphysema.

The mean linear intercept (L(m)) can be used to estimate the surface area for gas exchange in the lung. However, in recent years, it is most commonly used as an index for characterizing the enlargement of airspaces in emphysema and the associated severity of structural destruction in the lung. Specifically, an increase in L(m) is thought to result from an increase in airspace sizes. In this paper, we examined how accurately L(m) measures the linear dimensions of airspaces from histological sections and a variety of computer-generated test images. To this end, we developed an automated method for measuring linear intercepts from digitized images of tissue sections and calculate L(m) as their mean. We examined how the shape of airspaces and the variability of their sizes influence L(m) as well as the distribution of linear intercepts. We found that, for a relatively homogeneous enlargement of airspaces, L(m) was a reliable index for detecting emphysema. However, in the presence of spatial heterogeneities with a large variability of airspace sizes, L(m) did not significantly increase and sometimes even decreased compared with its value in normal tissue. We also developed an automated method for measuring the area and computed an equivalent diameter of each individual airspace that is independent of shape. Finally, we introduced new indexes based on the moments of diameter that we found to be more reliable than L(m) to characterize airspace enlargement in the presence of heterogeneities.

Algorithms↗

Dynamics of squirrel monkey linear vestibuloocular reflex and interactions with fixation distance.

Horizontal, vertical, and torsional eye movements were recorded using the magnetic search-coil technique during linear accelerations along the interaural (IA) and dorsoventral (DV) head axes. Four squirrel monkeys were translated sinusoidally over a range of frequencies (0.5-4.0 Hz) and amplitudes (0.1-0.7 g peak acceleration). The linear vestibuloocular reflex (LVOR) was recorded in darkness after brief presentations of visual targets at various distances from the subject. With subjects positioned upright or nose-up relative to gravity, IA translations generated conjugate horizontal (IA horizontal) eye movements, whereas DV translations with the head nose-up or right-side down generated conjugate vertical (DV vertical) responses. Both were compensatory for linear head motion and are thus translational LVOR responses. In concert with geometric requirements, both IA-horizontal and DV-vertical response sensitivities (in deg eye rotation/cm head translation) were related linearly to reciprocal fixation distance as measured by vergence (in m-1, or meter-angles, MA). The relationship was characterized by linear regressions, yielding sensitivity slopes (in deg.cm-1.MA-1) and intercepts (sensitivity at 0 vergence). Sensitivity slopes were greatest at 4.0 Hz, but were only slightly more than half the ideal required to maintain fixation. Slopes declined with decreasing frequency, becoming negligible at 0.5 Hz. Small responses were observed when vergence was zero (intercept), although no response is required. Like sensitivity slope, the intercept was largest at 4.0 Hz and declined with decreasing frequency. Phase lead was near zero (compensatory) at 4.0 Hz, but increased as frequency declined. Changes in head orientation, motion axis (IA vs. DV), and acceleration amplitude produced slight and sporadic changes in LVOR parameters. Translational LVOR response characteristics are consistent with high-pass filtering within LVOR pathways. Along with horizontal eye movements, IA translation generated small torsional responses. In contrast to the translational LVORs, IA-torsional responses were not systematically modulated by vergence angle. The IA-torsional LVOR is not compensatory for translation because it cannot maintain image stability. Rather, it likely compensates for the effective head tilt simulated by translation. When analyzed in terms of effective head tilt, torsional responses were greatest at the lowest frequency and declined as frequency increased, consistent with low-pass filtering of otolith input. It is unlikely that IA-torsional responses compensate for actual head tilt, however, because they were similar for both upright and nose-up head orientations. The IA-torsional and -horizontal LVORs seem to respond only to linear acceleration along the IA head axis, and the DV-vertical LVOR to acceleration along the head's DV axis, regardless of gravity.

Animals↗

BAY 41-2272, a direct activator of soluble guanylate cyclase, reduces right ventricular hypertrophy and prevents pulmonary vascular remodeling during chronic hypoxia in neonatal rats.

Exposure to hypoxia during the first weeks of life in newborn rats decreases vascular growth and alveolarization and causes pulmonary hypertension (PH). BAY 41-2272 is a novel direct activator of soluble guanylate cyclase independent of nitric oxide, effective as an acute pulmonary vasodilator in an animal model of persistent pulmonary hypertension of the newborn, but whether prolonged BAY 41-2272 therapy is effective in the setting of chronic PH is unknown. We hypothesize that BAY 41-2272 would prevent PH induced by chronic exposure to neonatal hypoxia. At 2 days of age, newborn rats were randomly exposed to hypoxia (FiO2, 0.12) or room air, and received daily intramuscular treatment with BAY 41-2272 (1 mg/kg) or saline. After 2 weeks, rats were killed for assessment of right ventricular hypertrophy (RVH), wall thickness of small pulmonary arteries, vessels density, radial alveolar counts and mean linear intercepts. In comparison with control, hypoxia increased RVH and artery wall thickness, reduced vessels density, decreased radial alveolar counts and increased mean linear intercepts. In comparison with hypoxic controls, prolonged BAY 41-2272 treatment during chronic hypoxia reduced RVH (0.67 +/- 0.03 vs. 0.52 +/- 0.05; p < 0.05), and attenuated artery wall thickness (48.2 +/- 2.8% vs. 35.7 +/- 4.1 microm; p < 0.01). However, BAY 41-2272 did not change vessels density, radial alveolar counts or mean linear intercepts. We conclude that BAY 41-2272 prevents the vascular structural effects of PH and reduces RVH but does not protect from hypoxia-induced inhibition of alveolarization and vessel growth. We speculate that BAY 41-2272 may provide a new therapy for chronic PH.

Animals↗

Effects of amrinone and dobutamine on PGF2 alpha-induced pulmonary hypertension in dogs.

The hemodynamic benefits and pulmonary vascular selectivity of amrinone, dobutamine and amrinone + dobutamine were assessed in a canine model of vasoconstrictive pulmonary hypertension. Dogs were equipped with central and peripheral catheters and with an electromagnetic flow probe placed around the ascending aorta for the measurement of cardiac function. Through a laparotomy, an arteriovenous fistula was created between the abdominal aorta and the inferior vena cava. Gradual opening of this fistula, which permitted construction of pressure-flow curves (mean pulmonary artery pressure over the cardiac index, PAP/CI), was utilized to identify the pulmonary vascular effects of amrinone and dobutamine. PGF2 alpha, prostaglandin derivative, induced stable pulmonary hypertension along with significant reduction in CI. The resultant pulmonary hypertension translated into a significant increase in both the slope and pressure intercept of the PAP/CI curve. The bipyridine derivative, amrinone, did not reverse the CI reduction observed with PGF2 alpha: both mean arterial pressure and PAP were decreased as was the intercept of the PAP/CI curve. Dobutamine, a beta-agonist, reversed the CI decline elicited by PGF2 alpha but the elevated pulmonary pressure remained unaffected; dobutamine reduced the slope of the PAP/CI curve. When combined, amrinone and dobutamine demonstrated additive beneficial hemodynamic effects and improved lung perfusion. Their additive effects were also indicated by data on the PAP/CI curve: both the slope and the pressure intercept were significantly reduced. These results suggest that amrinone and dobutamine interact at different sites of the pulmonary vasculature and that their association might be beneficial in vasoconstrictive pulmonary hypertension although no significant pulmonary vascular selectivity could be observed.

Amrinone↗

Diminished metabolic responsiveness to beta-adrenergic stimulation in estradiol benzoate-treated rats.

Earlier studies have shown that chronic treatment with estradiol benzoate reduced the responsiveness of heart rate, drinking, and tail-skin temperature to administration of the beta-adrenergic agonist, isoproterenol. The objective of the present study was to assess the relationship between the isoproterenol-induced elevations in rate of oxygen consumption and tail-skin temperature in adult ovariectomized rats treated chronically with estradiol benzoate (28 micrograms/day) and untreated, ovariectomized controls. Isoproterenol (0, 10, 25, and 50 micrograms/kg, s.c.) elevated both rate of oxygen consumption and tail-skin temperature in ovariectomized and ovariectomized plus estradiol benzoate-treated rats in a dose-related fashion. However, in both cases the response of the estradiol-treated group was less than that of controls. A comparison of the regressions of rate of oxygen consumption versus dose of isoproterenol administered to each group revealed significant differences between the intercepts, but not the slopes. A similar comparison with respect to the regression of tail-skin temperature versus dose of isoproterenol administered to each group revealed significant differences between both the slopes and intercepts of the relationships. A comparison of the regressions of rate of oxygen consumption versus tail-skin temperature for control and estrogen-treated rats revealed significant differences between both slopes and intercepts of the relationships. The latter comparison suggests a reduced change in tail-skin temperature for a given change in rate of oxygen consumption in the estrogen-treated group. It is concluded from these results that the reduction in metabolic response to beta-adrenergic stimulation in estrogen-treated rats explains, in part at least, the attenuated response of tail-skin temperature. The tail of the rat is important in short-term temperature regulation. When threatened acutely with overheating, the rat uses its tail as a heat radiator, increasing its skin blood flow, temperature, and heat loss. Administration of isoproterenol to rats at doses of 50-100 micrograms/kg, subcutaneously can increase tail-skin temperature as much as 6 degrees C. This response is mediated by beta-adrenoceptors since it can be either attenuated or prevented by prior administration of propranolol. It serves as a simple and reliable test of beta-adrenergic responsiveness in rats. Chronic treatment with the oral contraceptive, Enovid (7.5 mg/kg food) attenuated this response. Chronic administration of the estrogenic component (ethinyl estradiol, 48-50 micrograms/kg/day) of Enovid also attenuated the response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Intracellular pH measurement with fluorescent dye in canine basilar arteries.

The intracellular pH (pHi) of basilar artery rings was determined with 2',7'-bis-(carboxyethyl)-5,(6)-carboxyfluorescein (BCECF) by measuring the ratio of emitted (540 nm) fluorescence intensities (FI) at excitation wavelengths of 500 and 440 nm. There was a dye loss from the rings in 90 min (39.3 +/- 3.6%, p less than 0.001). We found that the ratio of fluorescence intensities does not adequately correct for dye loss; hence, we derived a method to correct for dye loss during pHi determinations. Calibration curves of the ratio versus pHi were constructed for the artery rings. The slope and intercept of the calibration curves depended on FI440. Linear regression lines for the slope and intercept versus FI440 were: [formula; see text] In solutions with different pH and different concentrations of free BCECF, the slope of the ratio versus pH of the solution was steeper at high concentrations of BCECF. Thus, pHi was calculated from a calibration curve in which the slope and intercept were determined from FI440 with the above formula. The corrected pHi was 7.37 +/- 0.05 (n = 25) at pHo 7.4 and 37 degrees C.

Amiloride↗

Basal parathyroid activity and renal calcium handling during an intravenous calcium load.

Urinary excretion of calcium and urinary cyclic AMP (cAMP), plasma parathyroid hormone (PTH) and ionized serum calcium concentration, and creatinine clearance were measured in 15 healthy humans. In the same subjects, renal tubular reabsorption of calcium was evaluated by analyzing the regression line of urinary calcium excretion rate on rising the level of serum calcium during an intravenous calcium infusion. The regression line intercept on the y-axis, which has been proposed to depend on the calcium reabsorption in the renal distal tubule, was found to be significantly related to both urinary cAMP and PTH levels. The theoretical renal threshold for calcium excretion was directly related to the y-axis intercept and thus also to the index of parathyroid activity. No relationship was found between urinary cAMP or plasma PTH levels and the regression line slope of urinary calcium to serum calcium. In healthy subjects, parathyroid activity significantly affects the extrapolated regression line of urinary calcium to serum calcium by changing the intercept, but not the slope.

Adult↗

Human tissue valves in aortic position: determinants of reoperation and valve regurgitation.

BACKGROUND: Human tissue valves for aortic valve replacement have a limited durability that is influenced by interrelated determinants. Hierarchical linear modeling was used to analyze the relation between these determinants of durability and valve regurgitation measured by serial echocardiography. METHODS AND RESULTS: In adult patients, 218 cryopreserved aortic allografts were implanted with the subcoronary (85) or the root replacement technique (133), and 81 patients had root replacement with a pulmonary autograft. Mean follow-up was 4.2 years (SD 2.7; range, 0 to 10.5). Patient age, operator experience with subcoronary implantation, and allograft diameter were independent predictors for reoperation. With repeated color Doppler echocardiography, the severity of aortic regurgitation was assessed by the jet length method and the jet diameter ratio. Multilevel hierarchical linear modeling was used to estimate initial aortic regurgitation (intercept), its change over time (slope), and the effect of 11 potential determinants of durability on aortic regurgitation. With the jet length method, the intercept was 0.94 grade and the slope was 0.11 grade per year. With the jet diameter ratio, the intercept was 0.34 and the annual increase was 0.01. Subcoronary implanted valves had more initial aortic regurgitation, but progression of aortic valve regurgitation did not differ from root replacement. At midterm follow-up, recipient age <40 years was the only independent predictor of aortic regurgitation. CONCLUSIONS: Subcoronary implantation has a learning curve, resulting in more initial aortic regurgitation and early reoperation compared with root replacement. In both techniques, progression of aortic regurgitation over time is small but accelerated in young adults.

Adolescent↗

Effects of load alteration and coronary perfusion pressure on regional end-systolic relations.

Left ventricular end-systolic pressure-wall thickness and pressure-segment length relations have been used to assess regional myocardial contractility. The purpose of these studies was to determine whether the method of afterload alteration, coronary perfusion pressure, and the definition of end systole affected regional end-systolic relations. In paced open-chest pig hearts (n = 10), left ventricular pressure, wall thickness, and segment length were measured during vena caval occlusions. First, regional end-systolic relations were obtained before and after an increase in afterload with intravenous phenylephrine. This comparison was performed with the coronary circulation intact (closed loop) and with coronary perfusion pressure controlled extracorporeally (open loop). Second, with the open-loop preparation, the independent effect of a range of coronary perfusion pressures (45-155 mm Hg) on end-systolic relations was assessed. In both procedures, end systole was defined by the maximal isochronal slope, termed regional Emax, and by the maximal ratio of left ventricular pressure to regional dimension, termed Ees. In the first procedure, the slope and x-axis intercept of regional Emax were unchanged with phenylephrine. In contrast, the slope of Ees decreased with phenylephrine, consistent with a decrease in contractility. The extrapolated x-axis intercept of Ees shifted in a direction consistent with an increase in contractility. In the second procedure, increases in coronary perfusion pressure did not affect regional Emax but increased the slope of Ees. A decrease in the coronary perfusion pressure, particularly with ischemia, shifted the x-axis intercepts of both Emax and Ees in a direction consistent with a decrease in contractility. Thus, regional end-systolic relations in intact hearts are dependent on the method of afterload alteration and the coronary perfusion pressure. Furthermore, Emax differs from Ees, so the assessment of regional relations depends on how end systole is defined.

Animals↗

Relation between maximum time-varying elastance pressure-volume areas and myocardial oxygen consumption in dogs.

To establish whether pressure-volume areas (PVAs) calculated using the maximum time-varying elastance (Emax) have a relation with myocardial oxygen consumption (MVO2) that improves on other indexes of myocardial oxygen demand, we studied nine dogs of either sex weighing 19-39 kg, which were instrumented with a micromanometer left ventricular (LV) catheter and a Wilton-Webster coronary sinus flow catheter and had red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamics, coronary sinus flow determinations, and radionuclide angiograms were obtained under control conditions and during three to five steady-state loading conditions (mean +/- SD, 5.6 +/- 0.7). Isochronal pressure-volume data points from each pressure-volume loop were subjected to linear regression analysis to calculate Emax. The Emax relations, diastolic curves, and systolic portions of each pressure-volume loop were used to obtain calibrated PVAs. The Emax PVA (mm Hg.ml.beat-1.100 g-1) and MVO2 (ml O2.beat-1.100 g-1) values correlated in each animal (r = 0.77 to 0.99). Their slopes averaged (3.48 +/- 1.68) x 10(-5) ml O2.mm Hg-1.ml-1, and their y-axis intercepts averaged 0.07 +/- 0.04 ml O2.beat-1.100 g-1. When the MVO2 relations were compared with Emax PVA, LV systolic pressure-rate product, LV stroke work, and a modification of the LV pressure-work index, the Emax PVA, LV systolic pressure-rate product, and LV pressure-work index had similar relations with MVO2, whereas LV stroke work was a weaker index of MVO2 (p less than 0.05 versus Emax PVA). This occurred because the Emax PVA:MVO2 slopes and y-axis intercepts differed in each dog, which was due to differences in basal LV contractility. The Emax PVA:MVO2 slopes correlated with Emax (r = 0.73, p less than 0.05), and the y-axis intercepts were also weakly related to Emax (r = 0.48, p = 0.19). We conclude that the Emax PVAs calculated using data acquisition techniques that are clinically applicable have relations with MVO2 that in general do not improve on other indexes of myocardial oxygen demand in this animal preparation.

Animals↗

Comparative validation of quantitative coronary angiography systems. Results and implications from a multicenter study using a standardized approach.

BACKGROUND: Computerized quantitative coronary angiography (QCA) has fundamentally altered our approach to the assessment of coronary interventional techniques and strategies aimed at the prevention of recurrence and progression of stenosis. It is essential, therefore, that the performance of QCA systems, upon which much of our scientific understanding has become integrally dependent, is evaluated in an objective and uniform manner. METHODS AND RESULTS: We validated 10 QCA systems at core laboratories in North America and Europe. Cine films were made of phantom stenoses of known diameter (0.5 to 1.9 mm) under four experimental conditions: in vivo (coronary arteries of pigs) calibrated at the isocenter or by use of the catheter as a scaling device and in vitro with 50% contrast and 100% contrast. The cine films were analyzed by each automated QCA system without observer interaction. Accuracy and precision were taken as the mean and SD of the signed differences between the phantom stenoses, and the measured minimal luminal diameters and the correlation coefficient (r), the SEE, the y intercept, and the slope were derived by their linear regression. Performance of the 10 QCA systems ranged widely: accuracy, +0.07 to +0.31 mm; precision, +/- 0.14 to +/- 0.24 mm; correlation (r), .96 to .89; SEE, +/- 0.11 to +/- 0.16 mm; intercept, +0.08 to +0.31 mm; and slope, 0.86 to 0.64. CONCLUSIONS: There is a marked variability in performance between systems when assessed over the range of 0.5 to 1.9 mm. The range of accuracy, intercept, and slope values of this report indicates that absolute measurements of luminal diameter from different multicenter angiographic trials may not be directly comparable and additionally suggests that such absolute measurements may not be directly applicable to clinical practice using an on-line QCA system with a different edge detection algorithm. Power calculations and study design of angiographic trials should be adjusted for the precision of the QCA system used to avoid the risk of failing to detect small differences in patient populations. This study may guide the fine-tuning of algorithms incorporated within each system and facilitate the maintenance of high standards of QCA for scientific studies.

Algorithms↗

Coupling of hemodynamic measurements with oxygen consumption during exercise does not improve risk stratification in patients with heart failure.

BACKGROUND: Measurement of peak Vo2 has become an accepted method to select patients for cardiac transplantation. Some investigators have suggested that the addition of exercise hemodynamic measurements can further enhance risk stratification because these measurements may identify patients with a noncardiac limitation to exercise. METHODS AND RESULTS: Accordingly, we performed maximal bicycle exercise with respiratory gas analysis and hemodynamic measurements in 65 patients (47 men, 18 women) 53 +/- 10 years old (mean +/- SD) who underwent a transplant evaluation at Columbia Presbyterian Medical Center. Skeletal muscle oxygenation of the vastus lateralis during exercise was assessed with near-infrared spectroscopy. Exercise hemodynamic, ventilatory, and muscle oxygenation measurements were obtained in all patients. For each subject, a linear correlation was derived between Vo2 and pulmonary artery saturation (PA Sao2). The slope of this relationship and a theoretical Vo2max at a PA Sao2 of 0% (Vo2 intercept) was derived. Baseline measurements were left ventricular ejection fraction, 22 +/- 9%; pulmonary capillary wedge pressure (PCWP), 16 +/- 10 mm Hg; cardiac index (CI), 2.1 +/- 0.5 L. min-1. m-2; and PA Sao2, 53 +/- 8%. The cardiac output response to exercise was categorized as normal or abnormal by comparison to the linear equation of peak Vo2 versus peak cardiac output as described by Higginbotham. Exercise measurements were peak Vo2, 12.1 +/- 3.0 mL.kg-1.min-1; Vo2 intercept, 19.1 +/- 5.5 mL. kg-1.min-1; PCWP, 31 +/- 11 mm Hg; CI, 3.8 +/- 1.3 L.min-1.m-2; and PA Sao2, 27 +/- 9%. Only 6% of patients exhibited a normal cardiac output response to exercise. Multivariate analysis was performed with peak Vo2, Vo2 intercept, skeletal muscle oxygenation at end exercise, and peak exercise hemodynamic variables. Only left ventricular stroke work and left ventricular stroke work index were shown to be predictive of survival. CONCLUSIONS: Addition of exercise hemodynamic measurements to noninvasive metabolic stress testing minimally improves risk prognostication in patients with severe heart failure.

Adult↗

Effect of arterial impedance changes on the end-systolic pressure-volume relation.

To study the end-systolic pressure-volume relationship of left ventricle ejection against physiological afterload, we imposed seven simulated arterial impedances on excised canine left ventricles connected to a newly developed servo-pump system. We set each of the impedance parameters (resistance, capacitance, and characteristic impedance) to 50, 100, and 200% of normal value (resistance: 3 mm Hg sec/ml; capacitance: 0.4 ml/mm Hg; characteristic impedance: 0.2 mm Hg sec/ml), while leaving the other parameters normal. Under a given impedance, the end-systolic pressure-volume relationship was determined by preloading the ventricle at four different end-diastolic volumes. There was no significant change in the slope of the end-systolic pressure-volume relationship with changes in any of the afterloading impedance parameters. However, the volume intercept of the end-systolic pressure-volume relationship decreased significantly with resistance from 5.5 +/- 1.0 (SE) ml at resistance equal to 1.5 mm Hg sec/ml to 0.6 +/- 1.8 ml at resistance equal to 6 mm Hg sec/ml (P less than 0.01). The volume axis intercept also decreased with characteristic impedance, from 5.9 +/- 2.0 ml at a characteristic impedance of 0.1 mm Hg sec/ml to 5.4 +/- 2.1 ml at a characteristic impedance of 0.4 mm Hg sec/ml, (P less than 0.05). We conclude that the slope of the end-systolic pressure-volume relationship is insensitive to a wide range of changes in afterload impedance, but its volume intercept is dependent on resistance and characteristic impedance.

Animals↗

Pulmonary vascular pressure-flow plots in canine oleic acid pulmonary edema. Effects of prostaglandin E1 and nitroprusside.

We investigated the effects of prostaglandin E1 (PGE1) and of sodium nitroprusside (NP) on multipoint pulmonary arterial pressure (PAP)/cardiac index (Q) plots in 24 pentobarbital-anesthetized and ventilated dogs with pulmonary hypertension secondary to oleic acid lung injury. The PAP/Q plots were rectilinear in all experimental conditions. In control dogs (n = 8), PAP was increased over the entire range of Q studied, from 1 to 4 L/min.m2, 90 min after oleic acid 0.09 ml/kg, and remained so during 2 consecutive 5-point PAP/Q plots, each of them being constructed in about 30 min. Oleic acid increased the extrapolated pressure intercept (p less than 0.001) but not the slope of the PAP/Q plots. Infusion of PGE1 0.4 micrograms/kg.min intravenously (n = 8) reduced PAP at each level of Q, with a reduction of the extrapolated pressure intercept (p less than 0.01) and no change in slope of the PAP/Q plots. In contrast, NP 5 micrograms/kg.min intravenously (n = 8) slightly reduced PAP only at the highest Q studied, without any significant change in extrapolated pressure intercept or slope of PAP/Q plots. Systemic blood pressure was decreased by 21% after PGE1 and by 24% after NP. Neither drug affected Q nor blood gases after oleic acid. The results suggest that pulmonary hypertension secondary to oleic acid pulmonary edema may be due more to an increase in effective outflow pressure of the pulmonary circulation than to an increase in incremental vascular resistance, and that active vasoconstriction contributes to this type of pulmonary hypertension.

Alprostadil↗