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PubMed1990

Coronary oscillatory flow amplitude is more affected by perfusion pressure than ventricular pressure.

In this study on the isolated, maximally vasodilated, blood-perfused cat heart we investigated the relation between left ventricular developed pressure (delta Piv) and coronary oscillatory flow amplitude (diastolic minus systolic flow, delta F) at different levels of constant perfusion pressure (Pp). We hypothesized that the effect of cardiac contraction on the phasic flow results from the changing elastic properties of cardiac muscle. The coronary vessel compartment can, as can the left ventricular lumen compartment, be described by a time-varying elastance. This concept predicts that the effect of left ventricular pressure on delta F is small, whereas the effect of Pp is considerable. Both the waterfall model and the intramyocardial pump model predict the inverse. The relation between delta Piv and delta F at a Pp of 10 kPa is delta F = (4.71 +/- 3.08).delta Piv + 337 +/- 75 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 7); the relation between (constant levels of) Pp and delta F at a constant delta Piv of 10 kPa is delta F = 51.Pp + 211 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 6). The differences in slope are best predicted by the time-varying elastance concept.

Animals↗
PubMed1990

Relationship between diastolic shape (eccentricity) and passive elastic properties in canine left ventricle.

This study was designed to investigate the relationship between left ventricular (LV) eccentricity, volume, and passive elastic properties. Eight open-chest fentanyl-anesthetized dogs were instrumented with an LV micromanometer, a remote-controlled mitral valve occluder, and two pairs of ultrasonic crystals to measure anterior-posterior and base-apex dimensions. We identified the presence of elastic recoil forces with negative LV diastolic pressure in nonfilling diastoles (end-systolic volume clamp). Using linear regression analysis we related midwall eccentricity to volume in nonfilling diastoles at the time of LVPmin and at end diastole, and in normal beats at end systole at LVPmin and at end-diastole. Intersection of the end-systolic and end-diastolic lines (transitional volume, Vt = 38.0 + 6.4 ml) divides cycles with and without the presence of elastic recoil forces. Vt is analogous to the equilibrium volume (V0), determined as the volume intercept of the logarithmic passive pressure-volume (P-V) relationship using LV volume estimated from LV weights (V0 nl = 37.6 + 4.4 ml), or the volume intercept of the linearized P-V relationship calculated from a prolate spheroidal model using measured minor and major diameters (V0 l = 44.5 + 3.5 ml). Linear regression analysis was also used to relate the square of peak mitral flow (MF2) with the corresponding atrioventricular pressure gradient (delta P); the slope represents a dissipative constant for the cycles without, P = 0.00058(MF)2 + 0.35 (n = 48, r = 0.73), and with elastic recoil P = 0.00035(MF)2 + 0.21 (n = 24, r = 0.81).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Slope of human left ventricular end-systolic force-length relation is independent of myocardial length.

We have introduced a new contractility index (Ec), i.e., the slope of the left ventricular (LV) end-systolic force-length (Fes-Les) relation. To examine whether Ec was dependent on the LV wall myocardial length, 16 normal hearts of human subjects were evaluated to determine the LV end-systolic force-dimension (Fes-Des) and pressure-dimension (Pes-Des) relations (dimension denotes the distance between the LV septum and posterior wall). LV end-systolic pressures and dimensions were estimated simultaneously by intra-arterial cannulation and LV echocardiography. In seven subjects, the effect of a dobutamine infusion was also assessed. The Fes-Des relation was found to be nearly linear. Slopes and extrapolated dimension intercepts were obtained for the LV Fes-Des and Pes-Des relations [Ec, slope of LV Pes-Des relation (Es), and extrapolated dimension intercept of LV Fes-Des (Do), and of Pes-Des relation (D'o), respectively]. Es showed a hyperbolic relation to the baseline LV Des, whereas Ec was unrelated to it. The average variation for Ec (9.5%) was smaller than that for Es (22.5%). Dobutamine infusion increased Ec, Es, and D'o, whereas Do was not changed. Thus the assumption of linearity of the LV Fes-Les relation was found to be reasonable in normal human hearts. Do appears to provide a more accurate parameter than D'o for estimating the actual unstressed myocardial length, whereas Ec could possibly serve as an index of LV wall performance in the normal human heart that is independent of myocardial length and nearly constant between individuals.

Adult↗
PubMed1991

Effects of oxidant stress on steady-state background currents in isolated ventricular myocytes.

Free radicals and oxidant stress have previously been shown to induce depolarization, transient action potential prolongation, and automaticity. We have investigated the ionic basis of these electrophysiological changes in isolated rabbit ventricular cells. Oxidant stress was generated by the photoactivation of rose bengal, and, in current-clamp experiments, the effects of oxidant stress on the action potential were confirmed. In voltage-clamp studies, oxidant stress decreased both inward and outward current through the inward-rectifier potassium channel, and the slope conductance (measured at the voltage-axis intercept near the resting membrane potential) was decreased from 40 +/- 8 to 25 +/- 6 nS (n = 6). Transient inward currents were induced on repolarization after a depolarizing clamp step, suggesting that the cells were calcium overloaded. In addition, oxidant stress activated a steady-state membrane conductance that showed a slight outward-going rectification and a reversal potential of approximately 0 mV. Evidence is presented to indicate that this reflects an increase in the conductance of the calcium-activated nonselective cation channel. The slope conductance of this calcium-activated channel (measured at the voltage-axis intercept) increased with prolonged exposure to oxidant stress (from 0.5 to 12 nS after 7 min), indicating that the intracellular free calcium increased gradually during the maintained application of rose bengal. These results suggest that oxidant stress depolarizes the cell membrane by reducing the inward-rectifier potassium current and by activating a calcium-activated membrane conductance. Both factors may contribute to the oxidant stress-induced changes in action potential duration and automaticity.

Action Potentials↗
PubMed1991

Stability of myocardial O2 consumption-pressure-volume area relation in red cell-perfused rabbit heart.

We evaluated the mechanical and energetic stability of the isolated rabbit heart perfused with a suspension of bovine red cells in Krebs-Henseleit buffer in terms of the pressure-volume area (PVA) concept. PVA, the area surrounded by the end-systolic and end-diastolic pressure-volume (P-V) relations and the systolic P-V trajectory of the P-V diagram, represents the total mechanical energy generated by each cardiac contraction. Myocardial O2 consumption (VO2) per beat has been reported to be highly linearly correlated with PVA. We used the slope and VO2-axis intercept of the VO2-PVA relation as energetic parameters and the maximum P-V ratio (Emax) as a contractility index of the left ventricle (LV) and compared them every 30 min for 120 min. Emax, the slope, and VO2 intercept of the VO2-PVA relation did not change significantly over 120 min compared with their control values [7.3 +/- 2.9 mmHg.ml-1.100 g LV, (1.67 +/- 0.40) x 10(-5) ml O2.mmHg-1.ml-1, and (3.26 +/- 1.01) x 10(-2) ml O2.beat-1.100 g LV-1, respectively]. However, the goodness of the linear fit of the VO2-PVA relation decreased after 90 min (r = 0.94 control, 0.62 at 90 min, and 0.64 at 120 min). Therefore, we conclude that the isolated bovine red cell-perfused rabbit heart preparation is stable for mechanical and energetic studies for at least 60 min.

Animals↗
PubMed1993

Use of 2,3-butanedione monoxime to estimate nonmechanical VO2 in rabbit hearts.

The purpose of the present study was to evaluate the feasibility of partitioning myocardial O2 consumption (VO2) into mechanical and nonmechanical components in the whole heart preparation using a negative inotrope, 2,3-butanedione monoxime (BDM), which has been reported to have a selective effect on the contractile proteins in a low concentration range (< 6 mM). In six isolated bovine red blood cell-perfused rabbit hearts, VO2 and force-time integral (FTI) were measured during infusion of varying concentrations of BDM at a constant left ventricular volume chosen such that control left ventricular peak isovolumic pressure was approximately 100 mmHg. The VO2-FTI relation with BDM concentrations < or = 5 mM was highly linear (median r = 0.98). Its VO2-axis intercept at zero FTI had a positive value (mean 23% of control, 0.014 ml O2.beat-1 x 100 g-1). To confirm the selective effect of BDM on the contractile proteins, the intracellular free Ca2+ transient was measured with the fluorescent indicator indo 1 in three isolated buffer-perfused rabbit hearts. The amplitude of the Ca2+ transient was not altered by BDM at concentrations < or = 10 mM, although left ventricular developed pressure was markedly depressed. This finding indicates that BDM < or = 10 mM does not affect excitation-contraction coupling. We conclude that the VO2-axis intercept value of the VO2-FTI relation during BDM infusion in a low concentration range represents VO2 for nonmechanical energy utilization. The BDM method to partition VO2 into mechanical and nonmechanical components is thus feasible in the whole rabbit heart.

Animals↗
PubMed1994

Effect of adenosine on contractile state and oxygen consumption in isolated rat hearts.

We studied the effects of adenosine on oxygen consumption and contractile state in 17 isolated, crystalloid-perfused, isovolumically contracting rat heart preparations at constant coronary flow. In 10 experiments we determined adenosine-contractile state dose-response relationships in three groups of hearts using two different perfusates and in the presence and absence of adrenergic blockade. Adenosine consistently reduced contractile state in a dose-dependent fashion, reducing the ventricular pressure developed at a constant ventricular volume by 24% on average at its maximal effect. An adenosine concentration of 111 microM on average produced 50% of the maximal effect. In seven experiments we determined the end-systolic pressure-volume and oxygen consumption-pressure-volume area (MVO2-PVA) relationships at two calcium concentrations (1.5 and 0.75 mM) and with adenosine 400 microM (1.5 mM Ca2+). Contractile state was indexed by the developed pressure at a ventricular volume of 0.3 ml (P0.3). Compared with 1.5 mM Ca2+, mean P0.3 was reduced by 38% with 0.75 mM Ca2+ and by 18% with adenosine. Whereas the MVO2-PVA slopes did not change, the mean MVO2 intercept was reduced by 22% with 0.75 mM Ca2+ and by 13% with adenosine. The MVO2 intercept, which represents the oxygen consumed by the unloaded heart, was directly related to P0.3. This relationship, which represents the oxygen cost of contractility, was not affected by adenosine. We conclude that at constant coronary flow and perfusion pressure adenosine reduces myocardial contractility and the oxygen consumed for excitation-contraction coupling. However, adenosine does not affect the slope of the MVO2-PVA relation or the oxygen cost of contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1997

Characterizing ventricular mechanics and energetics following repeated coronary microembolization.

Myocardial mechanics and energetics were investigated in an animal model of moderate chronic heart failure (CHF) created by repeated coronary microembolizations in six dogs. The final fractional area change was 34 +/- 4%. Hearts of these animals were isolated and cross-perfused, and balloons were placed in the left ventricle (LV). Chamber contractile state was markedly depressed in embolized hearts as assessed by the slope (Ees 2.74 +/- 0.49 vs. 4.00 +/- 1.18 mmHg/ml, P < 0.01) and volume axis intercept (V: 8.7 +/- 5.9 vs. 1.0 +/- 3.2 ml, P < 0.01) of end-systolic pressure-volume relation compared with a group of six normal dogs. The end-diastolic pressure-volume relation of embolized hearts was shifted to the right, indicating a dilation of the LV. However, systolic and diastolic stress strain relationships were similar in the two groups, suggesting that the average myocardial properties of the embolized hearts are similar to those of normal hearts. The relationship between oxygen consumption and pressure-volume area in embolized hearts had smaller intercept (2.98 +/- 0.44 vs 3.92 +/- 0.39 x 10(-2) ml O2.beat-1.100 g LV-1, P < 0.01) compared with the control group, with no change in the slope. These results contrast with previous findings in pacing CHF and serve as an important characterization of ventricular properties in this model of CHF from different etiology.

Adrenergic beta-Agonists↗
PubMed1998

ESPVR of in situ rat left ventricle shows contractility-dependent curvilinearity.

We developed a miniaturized conductance catheter for in situ rat left ventricular (LV) volumetry. After the validation study of the conductance volumetry in 11 rats, we characterized the end-systolic pressure-volume relationship (ESPVR) in 24 sinoaortic-denervated, vagotomized and urethan-anesthetized rats. Stroke volume (SV) measured with the conductance catheter correlated closely with that measured by electromagnetic flowmetry (r > 0.95). No significant difference was found between the in situ LV end-diastolic volumes measured by conductance volumetry and postmortem morphometry; a linear regression analysis indicated that the correlation coefficient was 0.934, that the slope was not significantly different from 1, and that the intercept was not significantly different from 0. During cardiac sympathotonic conditions, the ESPVR was curvilinear. The estimated slope of ESPVR (end-systolic elastance, Ees) by quadratic curve fitting at end-systolic pressure of 100 mmHg was 2,647 +/- 846 mmHg/ml. Bilateral cervical and stellate ganglionectomy depressed contractility and made the ESPVR linear; a quadratic equation did not improve the fit. Ees was 946 +/- 55 mmHg/ml with the volume-axis (V0) intercept of 0.076 +/- 0.007 ml. Administration of propranolol (1 mg/kg) further reduced Ees (573 +/- 61 mmHg/ml, P < 0.001) and increased V0 slightly (0.091 +/- 0.011 ml). We conclude that the conductance catheter method is useful for the assessment of the ESPVR of the in situ rat left ventricle and that the ESPVR displays contractility-dependent curvilinearity.

Animals↗
PubMed1998

End-systolic stress-velocity and pressure-dimension relationships by transthoracic echocardiography in mice.

The purposes of this study were to assess load-independent, end-systolic relationships in mice and compare these relationships to ejection phase indexes in assessing contractility. In 13 mice, ejection phase indexes (shortening fraction and velocity of fiber shortening) and end-systolic relationships [pressure-dimension relationship (ESPDR) and stress-velocity relationship (ESSVR)] were determined using M-mode echocardiography and simultaneous left ventricular pressure. Load was altered with phenylephrine and nitroprusside. Contractility was increased with dobutamine and decreased by induction of hypothyroidism. Ejection phase indexes increased with dobutamine infusion but were not significantly decreased with hypothyroidism. However, end-systolic relationships changed significantly with both dobutamine (gamma-intercepts: ESPDR from 22 to 48 mmHg, ESSVR from 3.7 to 6.6 circ/s, P < 0.05) and hypothyroidism (gamma-intercepts: ESPDR from 22 to 11 mmHg, ESSVR from 3.7 to 3.2 circ/s, P < 0.05). We conclude that end-systolic indexes can be accurately measured in the intact mouse by echocardiography with simultaneous left ventricular pressure recording and appear to be more sensitive to inotropic state than ejection phase indexes.

Animals↗
PubMed2001

Microvascular pressure measurement reveals a coronary vascular waterfall in arterioles larger than 110 microm.

Pressure-flow relationships at the entrance of the coronary circulation in the diastolic myocardium exhibit a zero-flow pressure intercept (P(int)). We tested whether this intercept is the same throughout the vascular bed. Microvascular pressure-flow relationships were therefore measured in vessels of various sizes of the maximally dilated vasculature of perfused unstimulated papillary muscle using the servo-null technique. From these relationships, P(int) were calculated with nonlinear regression. The P(int) at the level of the septal artery (diameter, 150-250 microm) was 23.2 +/- 4.4 cmH2O (n = 12). In arterioles with a diameter range between 24 and 110 microm, P(int) was 1.7 +/- 0.5 cmH2O (n = 6, P < 0.01), significantly lower than in the septal artery but significantly higher than zero, and not dependent on vessel size. In venules with the same diameters, P(int) was 1.1 +/- 1.1 cmH2O (n = 4), which was not different from zero. We conclude that, in the dilated vascular bed of the papillary muscle, two vascular waterfalls are found. The first waterfall is located in arterioles between 150 and 110 microm. The second waterfall is probably located in the small postcapillary venules.

Animals↗
PubMed1976

Independent secretion of different digestive enzymes by the pancreas.

Pancreatic secretion was collected from the cannulated duct of anesthetized rabbits during the perfusion of the upper duodenum with a balanced salt solution with or without 5 mM glucose. The secretion of amylase, chymotrypsinogen, trypsinogen, and total protein was measured. While glucose did not increase overall digestive enzyme secretion, it did change the proportions of the enzymes in secretion. In addition, the following was observed: 1) non-0,0 intercepts when the output of one enzyme was plotted against that of another (an enzyme-pair plot), 2) changes in the variance of the slope and intercept of enzyme-pair plots, and 3) an increase in the variance around the slope of an enzyme-pair plot, concurrent with a decrease in the variance around the slope of a plot for another enzyme pair that contained a common member. These observations suggest that different digestive enzymes can be secreted independently of each other.

Amylases↗
PubMed2006

Three-dimensional imaging and morphometric analysis of alveolar tissue from microfocal X-ray-computed tomography.

We evaluated microfocal X-ray-computed tomography (micro-CT) as a method to visualize lung architecture two and three dimensionally and to obtain morphometric data. Inflated porcine lungs were fixed by formaldehyde ventilation. Tissue samples (8-mm diameter, 10-mm height) were stained with osmium tetroxide, and 400 projection images (1,024 x 1,024 pixel) were obtained. Continuous isometric micro-CT scans (voxel size 9 microm) were acquired to reconstruct two- and three-dimensional images. Tissue samples were sectioned (8-microm thickness) for histological analysis. Alveolar surface density and mean linear intercept were assessed by stereology-based morphometry in micro-CT scans and corresponding histological sections. Furthermore, stereology-based morphometry was compared with morphometric semi-automated micro-CT analysis within the same micro-CT scan. Agreement of methods was assessed by regression and Bland-Altman analysis. Comparing histology with micro-CT, alveolar surface densities (35.4 +/- 2.4 vs. 33.4 +/- 1.9/mm, P < 0.05) showed a correlation (r = 0.72; P = 0.018) with an agreement of 2 +/- 1.6/mm; the mean linear intercept (135.7 +/- 14.5 vs. 135.8 +/- 15 microm) correlated well (r = 0.97; P < 0.0001) with an agreement of -0.1 +/- 3.4 microm. Semi-automated micro-CT analysis resulted in smaller alveolar surface densities (33.4 +/- 1.9 vs. 30.5 +/- 1/mm; P < 0.01) with a correlation (r = 0.70; P = 0.023) and agreement of 2.9 +/- 1.4/mm. Non-destructive micro-CT scanning offers the advantage to visualize the spatial tissue architecture of small lung samples two and three dimensionally.

Animals↗
PubMed2003

Progressive adult-onset emphysema in transgenic mice expressing human MMP-1 in the lung.

Mice with lung-specific expression of human matrix metalloproteinase-1 (MMP-1) develop emphysematous changes similar to those seen in smoking-induced emphysema in humans. Morphometric analyses of three transgenic lines [homozygous colony (Col) 34, Col 50, and Col 64] with varying temporal expression of MMP-1 were undertaken to determine the validity of this animal as a model of adult-onset emphysema. Line 50 mice, which have early expression of MMP-1 (14 days postconception), exhibited morphometric changes by 5 days of age. In contrast, homozygous line 34 and 64 with delayed expression (birth and 2 wk of age) were normal up until 4 wk of age when progressive changes in their mean linear intercept were first noted. In contrast, heterozygous mice from line 34 with lower transgene expression did not develop emphysema until 1 yr of age. The changes in mean linear intercept coincided with an increase in lung compliance. Emphysema in these mice was associated with decreased immunostaining for type III collagen within the alveolar septa. This study provides evidence that MMP-1 induces progressive adult-onset emphysema by the selective degradation of type III collagen within the alveolar wall.

Acute Disease↗
PubMed1977

Fitting straight lines to experimental data.

The problem associated with use of statistical methods for determining a best linear relationship of the form Y = AX +B have been examined for a condition quite prevalent with experimental research, i.e., when the values of both variables are subject to essentially unknown errors. Under this condition standard least-squares regression analysis underestimates the value of the slope A. A very simple method for determining the best value of the slope and intercept has been introduced which can be used when errors are present in both variables. With this proposed method, the calculated slope is equal to the standard error of Y divided by the standard error of X (with the appropriate sign) and the intercept is found from the mean values of X and Y, i.e., B = Y - AX. The best estimate of the slope is also equal to the slope found with the conventional regression method divided by the absolute value of the correlation coefficient. The line determined with the suggested method can be considered to be a line of symmetry through the data.

Regression Analysis↗
PubMed1982

Chloride secretion and conductance of teleost opercular membrane: effects of prolactin.

Effects of prolactin on transport properties of opercular membranes from seawater-adapted tilapia, Sarotherodon mossambicus, have been examined. These membranes are high conductance (average Gt approximately 4 mS.cm-2) tissues with short-circuit currents (I) equal to net chloride secretion. Despite high Gt, nonlinear current-voltage relationships suggest that opercular membranes cannot be classified as "leaky" tissues. Variability among membranes is reflected in a linear relationship between I and Gt with a slope equal to 26 mV and the zero-current Gt intercept equal to 0.45 mS.cm-2. Prolactin injections decrease I and Gt in a dose-dependent manner. Phosphodiesterase inhibition, without effect on I in untreated fish, often partially reverses these prolactin effects. Gt-I data from prolactin-treated fish yield a slope of 18 mV and a Gt intercept of 0.10 mS.cm-2. The effects of prolactin are discussed in terms of conventional equivalent circuit analysis. Discrepancies between predictions based on this model and the actual data indicate that an alternative interpretation, based on a heterogeneous cell population, is more accurate. Analysis of this circuit suggests that the ratio of paracellular to active transport pathway conductances associated with chloride cells is constant and that differences in Gt and I are due to parallel changes in these conductances. Prolactin may effectively "remove" chloride cells from these membranes as well as inhibit (reversible by elevated cellular cAMP levels) active transport pathway conductance of remaining cells.

Animals↗
PubMed1991

Excitatory pathways in smooth muscle investigated by phase-plot analysis of isometric force development.

Excitatory pathways in the smooth muscle of the pig urinary bladder were investigated using phase-plot analysis of isometric contractions. The phase plots, plots of the rate of change of the force as a function of the force itself, were dominated by a straight line described by the horizontal intercept (Fiso) and the vertical intercept (U). The quotient Fiso/U is a time constant that characterizes the rate-limiting step in isometric force development in the muscle. Bladder strips of 1 mm diameter were activated by electrical field stimuli, acetylcholine, potassium, and ATP in combination with selective pathway inhibitors such as verapamil, atropine, or a calcium-free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. When pathways that depended significantly on depolarization or intracellular calcium release were selected, the time constant was significantly smaller, indicating a faster process. The results indicated that the rate-limiting step in force development was determined by the influx of extracellular calcium.

Animals↗
PubMed1994

A gradient-layer calorimeter for measurement of energy expenditure of infants.

We have developed and validated a gradient-layer calorimeter for direct measurement of energy expenditure of preterm infants. Infant calorimeters must be operated and tested differently from adult calorimeters, because the calorimeter must be warmed during operation to limit heat loss from the infant, the calorimeter wall temperature (which is selected on the basis of the infant's maturity) must be precisely controlled, and energy expenditure (heat output) is typically < 10 W. We calibrated our calorimeter by varying the heat produced by a dry source (manikin or light bulb) with airflow (n = 42) and without airflow (n = 8) at various water jacket temperatures (n = 7) and by a wet source (combustion of ethyl alcohol) with airflow (n = 9). With no air moving, qc = 0.740 Vc + 0.029 Twj-0.697, where qc (W) is the estimated output of the heat source measured by the calorimeter, Vc (mV) is the gradient-layer voltage of the calorimeter, and Twj (degree C) is the temperature of the water jacket surrounding the walls of the device. From this equation and enthalpy calculations, the slope and intercept of the regression line relating the estimated heat production to the actual heat produced from alcohol combustion are 1.029 +/- 0.046 and -0.549 +/- 0.484 (SE), respectively. The slope is not significantly different from unity, and the intercept is not significantly different from zero. Thus we can accurately estimate the energy expenditure of preterm infants from the equations describing our calorimeter, and we can accurately resolve the total heat output into a dry (nonevaporative) component and a wet (evaporative) component.

Calibration↗