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PubMed1983

Contribution of polycythaemia to pulmonary hypertension in simulated high altitude in rats.

A rat model was used to assess the viscosity factor in pulmonary hypertension of high altitude. Rats exposed to 10% O2 for three weeks developed increased pulmonary vascular resistance (p.v.r.) and polycythaemia; the haematocrit (Hct) was 50-60%, values similar to those in normal men at high altitudes. The contribution of high Hct to the increased p.v.r. was assessed in isolated perfused lungs of chronically hypoxic rats perfused with their own high Hct blood, or normal Hct blood from control rats. Pressure/flow relationships were measured over a wide range and the slope (P/Q) of this relationship and its extrapolated intercept on the pressure axis were increased by high Hct blood. A return to low Hct blood did not restore initial conditions although a second perfusion with high Hct blood again increased p.v.r. and intercept. Lack of reversibility was attributed to changes with time in blood or lung. In a second experiment designed to eliminate time changes, chronically hypoxic or litter-mate control rats were each perfused with only one blood, their own or each other's and P/Q relations were rapidly measured. The P/Q slope and pressure intercept increased progressively in the following groups: control rats perfused with their own blood (Hct 34%), control rats perfused with chronically hypoxic blood (Hct 56%), chronically hypoxic rats perfused with control blood (Hct 35%) and chronically hypoxic rats perfused with chronically hypoxic blood (Hct 53%). To exclude factors in chronically hypoxic blood other than high Hct which might increase p.v.r., control rats were perfused with blood of different Hct obtained by centrifugation. High Hct again increased p.v.r. There was a significant relationship in all rats between pulmonary artery pressure (Ppa), which takes into account both P/Q slope, intercept and Hct. There was substantial batch variation which may reflect sensitivity to hypoxia. In chronically hypoxic rats with high Hct blood, Ppa varied from 29-47 mmHg; with low Hct blood the range was 26-38 mmHg. Comparable values for control rats were 21-29 and 17-20 mmHg. We conclude that the polycythaemic blood of chronic hypoxia contributes substantially to pulmonary hypertension. Where it is excessive, it may prejudice tissue blood flow.

Altitude↗
PubMed1993

Effect of extravascular plasma protein on pressure-flow relations across synovium in anaesthetized rabbits.

1. The effect of extravascular plasma protein on fluid flux through interstitial matrix was investigated in vivo by studying the pressure-flow relation across synovium during intra-articular infusions of protein solutions (usually bovine serum albumin). Synovium is a sheet of non-epithelial cells separated by interstitium-filled gaps, beneath which are fenestrated capillaries: synovium regulates synovial fluid volume and composition. 2. Albumin solutions (10-150 g l-1) of measured oncotic pressure and viscosity were infused at known pressure into the synovial cavity of knees of anaesthetized rabbits. Flow across the synovial lining in the steady state (absorption rate Qs) was recorded at a series of joint pressures (Pj) to define the pressure-flow relation. Krebs solution was infused into the opposite knee as a control (26 animals). 3. Infusion of a low albumin concentration (10 g l-1, bovine or rabbit) or diluted rabbit serum revealed no specific effect of plasma protein on interstitial matrix permeability (cf. specific protein effect on capillary glycocalyx permeability). Physiological (22.5 g l-1) and higher concentrations reduced trans-synovial absorption rate. The slope of the pressure-flow relation was reduced and the pressure intercept displaced to the right (i.e. Pj at zero flow was raised). 4. Slope dQs/dPj correlated negatively with intra-articular viscosity (P = 0.001-0.04), in keeping with viscous interstitial flow. The reduction in normalized slope, however, did not equal the reduction in fluidity (1/viscosity) quantitatively. It is proposed that apparent fluidity within the interstitial matrix is higher than in the bulk phase due to steric exclusion of albumin (radius 3.55 nm) by the interstitial glycosaminoglycans. The latter form spaces of estimated mean hydraulic radius 14-18 nm in synovium. 5. The joint-pressure intercept at zero net trans-synovial flow was displaced 0.015 cmH2O per cmH2O intra-articular oncotic pressure (pi j; S.E.M. +/- 0.006). Thus large trans-synovial osmotic gradients were not maintained at physiological flow velocities. The 1.5% displacement of the Pj intercept by pi j was attributed principally to interstitial albumin exerting pericapillary oncotic pressure and enhancing net Starling filtration pressure. Indeed, net trans-synovial flow at low joint pressure sometimes reversed from absorption to filtration into the joint cavity at high intra-articular oncotic pressures. 6. The displacement of the trans-synovial flow intercept per unit change in intra-articular oncotic pressure, (dQs/d pi j)Pj = 0, was 18 +/- 3 nl min-1 cmH2O-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia↗
PubMed2003

Perception of airway narrowing during reduction of inhaled corticosteroids and asthma exacerbation.

BACKGROUND: The perception of airway narrowing is reduced in subjects with severe asthma and may be related to the severity of airway inflammation. A study was undertaken to determine if the perception of airway narrowing changes during the reduction of inhaled corticosteroid (ICS) dose or during an asthma exacerbation. METHODS: Forty two asthmatic subjects with well controlled asthma had their daily ICS dose halved every 2 months until they were weaned off ICS or they developed an exacerbation. Perception was measured at baseline and at monthly intervals during bronchial challenge with mannitol as the slope and intercept of the regression of the Borg score and percentage fall in forced expiratory volume in 1 second (FEV(1)), and as the Borg score at 20% fall in FEV(1) (PS(20)FEV(1)). Sputum was collected for measurement of inflammatory cell numbers. RESULTS: In 33 subjects who successfully halved their ICS dose without exacerbation there were significant reductions in slope (p = 0.01), intercept (p = 0.01), and PS(20)FEV(1) (p = 0.003). Sputum eosinophils and airway hyperresponsiveness increased significantly but, in 14 subjects from whom sputum was obtained, changes in eosinophils were not correlated with changes in perception. Change in airway hyperresponsiveness correlated with change in PS(20)FEV(1) (r = -0.40, p = 0.025). In 27 subjects who developed an exacerbation, slope decreased (p = 0.02) and intercept increased (p = 0.01) compared with the visit before the exacerbation. Changes in intercept correlated with changes in resting FEV(1) (r = -0.57, p = 0.002). CONCLUSIONS: Perception of airway narrowing decreases during ICS dose reduction and decreases further during a mild asthma exacerbation. These changes are related to concurrent changes in airway hyperresponsiveness and resting lung function. The effect of changes in airway inflammation on perception is unclear.

Administration, Inhalation↗
PubMed1980

Effect of shape on pressure-volume relationships of ellipsoidal shells.

Previous theoretical procedures for determining the slope and intercept of the stiffness-stress relationship of the passive myocardium from diastolic pressure-volume (P-V) data assume that the eccentricity of the left ventricle (LV) is invariant. In this study a mathematical model for an ellipsoidal membrane was developed that does not contain that constraint. The model predicts a small (less than 10%) but significant decrease in eccentricity as transmural pressure increases. This result was confirmed by the use of a thick-wall finite element model. The implications of this result are as follows. 1) The slope and intercept of the stiffness-stress relationship of unconstrained ellipsodial shells can be determined by fitting a spherical model to the P-V relationships exhibited by the shells. 2) An ellipsoidal model that assumes that the eccentricity of such shells is invariant for all pressures would predict erroneous intercepts. 3) If the eccentricity of the diastolic LV initially decreases relative to its value at zero transmural pressure, then a thick-wall spherical model may be adequate for determining the slope and intercept of the myocardial stiffness-stress relationship.

Compliance↗
PubMed1985

Multipoint pulmonary vascular pressure-cardiac output plots in conscious dogs.

To characterize quantitatively the relationships among pulmonary vascular pressures (P) and cardiac output (Q) in conscious dogs, multipoint plots of pulmonary arterial (PAP), pulmonary capillary wedge (PCWP), PAP - PCWP, and left atrial (LAP) pressure versus Q were generated by graded constriction of the thoracic inferior vena cava (IVC) to vary Q. Slopes and extrapolated pressure intercepts from linear regression fits to the P/Q plots were determined for three inspired oxygen tensions: normoxia, hyperoxia, and hypoxia. During normoxia (arterial Po2 87 +/- 1 Torr), the extrapolated pressure intercepts for PAP, PCWP, and PAP - PCWP were virtually 0 mmHg, and for LAP, substantially negative (-5.5 +/- 1.1 mmHg; P less than 0.01). Hyperoxia (Po2 365 +/- 28 Torr) had no effect on any of the P/Q plots. In contrast, hypoxia (Po2 51 +/- 1 Torr) significantly increased the intercepts (P less than 0.01) as well as the slopes (P less than 0.05) of PAP and PAP - PCWP versus Q, but produced only minor changes in PCWP and LAP versus Q. These hypoxia-induced changes in intercepts, perhaps related to changes in critical closing pressures, demonstrate the limitations of pulmonary vascular resistance calculations (quotient of pressure gradient and Q) in quantifying changes in pulmonary vasomotor tone. In this way, the IVC constriction technique provides a more complete description of P/Q relationships than that permitted by simple calculations of pulmonary vascular resistance. We conclude that this technique can be utilized to investigate the effects of other physiological and pharmacological interventions on pulmonary vasomotor tone in conscious dogs.

Animals↗
PubMed1988

Isochronal behavior in left ventricular systolic pressure-wall thickness relations.

Regional left ventricular systolic pressure-thickness relations have been used to assess regional load-insensitive contractility with the assumption that they possess linear isochrones that are fundamental to the time-varying elastance model of global pressure-volume relations. We examined the shape and time-varying behavior of pressure-thickness isochrones in six open-chest canine preparations. Transmural wall thickening (sonomicrometry) and ventricular pressure were altered by abrupt preload alterations during control, dobutamine, and propranolol. In all dogs and interventions, linear isochrones (r2 mean +/- SE = 0.91 +/- 0.11) were found at 5-ms intervals. During control, linear isochrone slope rose monotonically from onset to end of systole. Thickness-axis intercepts also varied continuously in time, but peak intercept and maximal slope were asynchronous. Dobutamine caused a steeper earlier maximum slope and increased slope-intercept asynchrony. Propranolol reduced maximum slope and slope-intercept asynchrony. Isochronal data during early systole were better fitted to a parabolic than to the linear model; however, fits to linear and parabolic models were equally good near end of systole. Linear isochronal behavior exists in systolic pressure-thickness relations especially near end systole and is maintained during modest inotropic alterations.

Animals↗
PubMed1989

Evaluation of long-term variance of left ventricular performance indexes in closed-chest dogs.

To assess the long-term variance of several parameters of left ventricular performance, we evaluated maximum rate of pressure development (dP/dtmax), ejection fraction, mean velocity of circumferential fiber shortening (VCF), the slope and volume-axis intercept of the end-systolic pressure-volume (PES-VES) relation, the stroke-work end-diastolic volume (SW-EDV) relation, and the dP/dtmax-EDV relation in six chronically instrumented dogs. Each dog was studied five times over a period of 3 wk in the conscious autonomically intact state, after autonomic blockade, and after administration of anesthesia. For each index under each set of testing conditions, a coefficient of variation was determined, defined as (SD/mean) x 100, and expressed as a percent. In conscious autonomically intact dogs, a low day-to-day variance was present in dP/dtmax (6.4%), ejection fraction (6.8%), mean VCF (6.5%), and the slope and volume intercept of the SW-EDV relation (7.2 and 6.2%), whereas higher variance was seen in the slope and intercept of the PES-VES relation (18.1 and 36.1%). The highest variance was present in parameters of the dP/dtmax-EDV relation. Thus dP/dtmax, ejection fraction, and the slope and volume intercept of the SW-EDV relation may be the most reliable indexes for long-term evaluation of left ventricular performance.

Animals↗
PubMed2004

New insights into the pathophysiology of the dysnatremias: a quantitative analysis.

Recent theoretical considerations have played an important role in advancing our understanding of the physiological mechanisms responsible for perturbing the plasma water sodium concentration ([Na(+)](pw)) in health and disease. Central to these considerations is the original empirical relationship between the [Na(+)](pw) and total exchangeable sodium (Na(e)), total exchangeable potassium (K(e)), and total body water (TBW) initially discovered by Edelman and colleagues (Edelman IS, Leibman J, O'Meara MP, and Birkenfeld LW. J Clin Invest 37: 1236-1256, 1958). The non-zero values of the slope and y-intercept in the Edelman equation are a consequence of the effects of the osmotic coefficient of Na(+) salts at physiological concentrations and Gibbs-Donnan and osmotic equilibrium. Moreover, in addition to Na(e), K(e), and TBW, the physiological components of the y-intercept in this equation play a role in modulating the [Na(+)](pw) and in the generation of the dysnatremias. In this review, the pathophysiological mechanisms underlying the generation and treatment of the dysnatremias are analyzed theoretically and quantitatively. Importantly, the non-zero values of both the slope and y-intercept in the Edelman equation result in several theoretical predictions that can be tested experimentally and have been mathematically incorporated into recently derived equations used to analyze both the generation and the optimal treatment of the dysnatremias. In addition, we review current concepts regarding 1) the role of Gibbs-Donnan and osmotic equilibrium in the determination of the [Na(+)](pw); 2) the modulating effect of osmotically inactive exchangeable Na(+) and K(+) on the [Na(+)](pw); 3) the effect of glucose on the [Na(+)](pw) as reflected by changes in Na(e), K(e), and TBW as well as changes in several components of the y-intercept resulting from the hyperglycemia; and 4) the complex role of K(+) in modulating the [Na(+)](pw).

Body Water↗
PubMed2004

Determinants of plasma water sodium concentration as reflected in the Edelman equation: role of osmotic and Gibbs-Donnan equilibrium.

Edelman et al. have empirically shown that plasma water sodium concentration ([Na(+)](pw)) is equal to 1.11(Na(e) + K(e))/TBW - 25.6 (Edelman IS, Leibman J, O'Meara MP, Birkenfeld LW. J Clin Invest 37: 1236-1256, 1958). However, the physiological significance of the slope and y-intercept in this equation has not been previously considered. Our analysis demonstrates that there are several clinically relevant parameters determining the magnitude of the y-intercept that independently alter [Na(+)](pw):1) osmotically inactive exchangeable Na(+) and K(+); 2) plasma water K(+) concentration; and 3) osmotically active non-Na(+) and non-K(+) osmoles. In addition, we demonstrate quantitatively the physiological significance of the slope in the Edelman equation and its role in modulating [Na(+)](pw). The slope of 1.11 in this equation which Edelman et al. determined empirically can be theoretically predicted by considering the combined effect of the osmotic coefficient of Na(+) salts at physiological concentrations and Gibbs-Donnan equilibrium. In addition, our results demonstrate that the slope has an independent quantitative impact on the magnitude of the y-intercept in the Edelman equation. From a physiological standpoint, the components of both the slope and the y-intercept need to be addressed when considering the factors that modulate [Na(+)](pw).

Animals↗
PubMed1983

Freeze-dissection analysis of 133Xe distribution to measure regional renal blood flow.

To verify the freeze-dissection technique for measuring renal blood flow (RBF) distribution in anesthetized dogs we compared the sum of all compartment flow rates with total RBF, compared compartment flow distribution with intercepts, and determined recirculated 133Xe. By dissection, we found that the cortex, delineated by its granular brownish red appearance, comprised 69%, whereas the outer medulla (the reddish portion) was 18% of the total kidney weight. Average cortical flow was 3.77 ml X g-1 X min-1 and the y-intercept for 133Xe washout was 85% of the initial radioactivity distribution. Outer medullary flow was 2.01 ml X g-1 X min-1 with a y-intercept of 13%. In a 100-g kidney, total cortical flow would be 259.8 ml/min (3.77 ml X g-1 X min-1 X 68.9 g) and total outer medullary flow would be 36.0 ml/min. These calculations indicate that 86% of the total flow is distributed to the cortex and 13% to the outer medulla, as the intercept-calculated percentages indicated. Summing whole cortical and medullary flows results in a flow that agrees with the electromagnetically measured flow of 292 ml/min for a 100-g kidney.

Animals↗
PubMed1985

Submaximal exercise responses of tetraplegics and paraplegics.

This study describes responses of 21 wheelchair users to a continuous, increasing work rate test to exhaustion on a wheelchair ergometer. Heart rate, ventilation, O2 uptake, respiratory exchange ratio, ventilation equivalent for O2, and O2 pulse were determined for each minute. Subjects were divided into tetraplegic (n = 8), high-lesion paraplegic (n = 6), and low-lesion paraplegic (n = 7) groups. Linear regression analyses, with O2 uptake as the independent variable, were used to determine the strength of relationships within each group and differences between groups in slopes and intercepts of regression equations. All variables were significantly (P less than 0.05) related to O2 uptake (r = 0.42-0.94). The only significant difference between the high- and low-lesion paraplegic groups was for heart rate intercept, as the heart rate for the low-lesion group tended to be lower at any given O2 uptake. Tetraplegics had a higher intercept and/or slope for ventilation equivalent, ventilation, and respiratory exchange ratio and lower intercepts for heart rate and O2 pulse. These differences in responses to a progressive exercise task are logically related to the differences in maximal O2 uptake, functional muscle mass, and vasomotor and cardiac control of the groups.

Exercise Test↗
PubMed1996

Effect of macroscopic deformation on lung microstructure.

Using an anisotropic theory of diffuse light scattering in lungs, we measured the fractional changes in geometric mean linear intercepts in orthogonal directions when freshly excised rabbit lungs were subjected to isovolume uniaxial strains. Results from the optical technique were compared with morphometric estimates of fractional changes in mean linear intercepts from the same strained and unstrained (control) lobes, with the conclusion that diffuse light scattering is adequate to estimate changes in mean free paths in different directions. We compared optical estimates of fractional changes in mean linear intercepts with the macroscopic strain field measured by displacements of pleural markers; this relationship did not significantly differ from the line of identity. We conclude that the microscopic strain field is closely matched to the macroscopic strain field during uniaxial distortion. This suggests that surface reorientation may not play a large role in the origin of the low shear modulus of the lung, but this cannot be definitively stated without comparison of these experimental results to specific model predictions of the changes in mean linear intercepts in shear deformation.

Animals↗
PubMed2003

Kinematic analysis of manual tracking in monkeys: characterization of movement intermittencies during a circular tracking task.

Segmentation of the velocity profiles into the submovements has been observed in reaching and tracking limb movements and even in isometric tasks. Submovements have been implicated in both feed-forward and feedback control. In this study, submovements were analyzed during manual tracking in the nonhuman primate with the focus on the amplitude-duration scaling of submovements and the error signals involved in their control. The task consisted of the interception and visually guided pursuit of a target moving in a circle. The submovements were quantified based on their duration and amplitude in the speed profile. Control experiments using passive movements demonstrated that these intermittencies were not instrumentation artifacts. Submovements were prominent in both the interception and tracking phases and their amplitude scaled linearly with duration. The scaling factors increased with tracking speed at the same rate for both interception and pursuit. A cross-correlation analysis between a variety of error signals and the speed profile revealed that direction and speed errors were temporally coupled to the submovements. The cross-correlation profiles suggest that submovements are initiated when speed error reaches a certain limit and when direction error is minimized. The scaling results show that in monkeys submovements characterize both the interception and pursuit portions of the task and that these submovements have similar scaling properties consistent with 1) the concept of stereotypy and 2) adding constant acceleration/force at a specific tracking speed. The correlation results show involvement of speed and direction error signals in controlling the submovements.

Animals↗
PubMed1987

The relationship of various measures of end-systole to left ventricular maximum time-varying elastance in man.

This investigation was designed to calculate left ventricular maximum time-varying elastance (Emax), to define the relationship between Emax and pressure-volume (P-V) relations at other, more easily defined measured of end-systole, and to determine whether these measures of left ventricular contractile function can be normalized in man. Accordingly, we studied 10 subjects with simultaneous high-fidelity micromanometer left ventricular and ascending aortic pressure recordings and biplane contrast cineangiograms at control conditions and during infusion of methoxamine and nitroprusside. Emax was defined as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. Left ventricular end-systole was also defined for each loading condition as: the time of the maximum P-V ratio (maxPV), minimum ventricular volume (minPV), (-)dP/dtmin [(-)dP/dtPV], and zero systolic flow approximated by the central aortic dicrotic notch (AodiPV). The mean heart rates and LV (+)dP/dtmax were insignificantly altered during the three loading conditions. Isochronal Emax ranged from 3.38 to 6.73 mm Hg/ml (mean 5.48 +/- 1.23 [SD] mm Hg/ml) and the volume-axis intercepts at zero pressure ranged from -2 to 51 ml (mean 18 +/- 16 ml). The isochronal slope calculations were reproducible (r = .97 to .99). The end-systolic P-V slope values for the maxPV, minPV, (-)dP/dtPV, and AodiPV relations correlated with isochronal Emax (r = .90, .88, .69, and .74, respectively). The average slope values for these end-systolic P-V relations, however, underestimated the mean Emax (p less than .01 to p less than .001). The mean extrapolated volume-axis intercepts for these end-systolic P-V relations also underestimated that for Emax. Finally, the isochronal Emax and other end-systolic P-V relation slope values demonstrated inverse linear relationships with left ventricular mass (r = -.68 to -.91, p less than .05 to p less than .001). Only the Emax volume-axis intercepts showed a linear relationship with left ventricular end-diastolic volume (r = .75). Thus we conclude that the time-varying elastic properties of the left ventricle can be calculated in man, that commonly used end-systolic P-V relations significantly underestimate isochronal Emax, and that normalization of isochronal Emax and other end-systolic P-V relation slope values might be performed in man with left ventricular mass; no obvious relationship between volume-axis intercepts and measures of left ventricular or body size was apparent.

Adult↗
PubMed1989

Comparison of measures of left ventricular contractile performance derived from pressure-volume loops in conscious dogs.

Three measures of left ventricular (LV) performance derived from pressure (P)-volume (V) loops have been proposed: the end-systolic P-V (PES-VES) relation, the stroke work-end-diastolic V (SW-VED) relation, and maximum dP/dt-VED (dP/dtmax-VED) relation. We evaluated the variability of repeated determinations, and inotropic and load sensitivity of these relations in conscious dogs. LVV was determined from three orthogonal LV diameters measured by sonomicrometry. Three to six sets of variably loaded P-V loops were generated by transient caval occlusions before and again after increasing inotropic state by infusing dobutamine (6 +/- 1 microgram/kg/min, mean +/- SD) and after increasing PES by 49 +/- 17 mm Hg with phenylephrine following autonomic blockade. The slope (MSW) of the SW-VED relation was the least variable at constant inotropic state (coefficient of variation, 4 +/- 3%) compared with the slope (EES) of the PES-VES relation (8 +/- 3%) or the slope (dE/dtmax) of the dP/dtmax-VED relation (11 +/- 6%, p less than 0.05). The extrapolated volume-axis intercept of the SW-VED relation was much less variable than the intercepts of the PES-VES or dP/dtmax-VED relations. MSW, EES, and dE/dtmax all increased (p less than 0.05) in response to dobutamine. The extrapolated volume-axis intercepts of the PES-VES and dP/dtmax-VED relations increased with dobutamine, whereas the volume intercept of the SW-VED relation was unchanged. MSW had the smallest increase in response to dobutamine (124 +/- 22% of control) compared to EES (178 +/- 67% of control) and dE/dtmax (211 +/- 68% of control, p less than 0.05). The position of the PES-VES relation, quantified as the VES at PES = 100 (V100), showed less variability (2 +/- 1%) than the slope of the PES-VES relation (8 +/- 3%, p less than 0.05). V100 decreased from 30.8 +/- 17.4 to 26.7 +/- 13.7 ml during dobutamine (p less than 0.05). After phenylephrine, EES, MSW, and dE/dtmax decreased by less than 10% (p = NS). The PES-VES relation shifted to the left with this increased afterload and V100 decreased by 3.2 +/- 1.5 ml (p less than 0.05), whereas the position of the SW-VED and dp/dtmax-VED relations were relatively unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty.

BACKGROUND: Severity of coronary artery stenosis has been defined in terms of geometric dimensions, pressure gradient-flow relations, resistance to flow and coronary flow reserve, or maximum flow capacity after maximum arteriolar vasodilation. A direct relation between coronary pressure and flow, however, may only be presumed if the resistances in the coronary circulation are constant (and minimal) as theoretically is the case during maximum arteriolar vasodilation. In that case, pressure measurements theoretically can be used to predict maximum flow and assess functional stenosis severity. METHODS AND RESULTS: A theoretical model was developed for the different components of the coronary circulation, and a set of equations was derived by which the relative maximum flow or fractional flow reserve in both the stenotic epicardial artery and the myocardial vascular bed and the proportional contribution of coronary arterial and collateral flow to myocardial blood flow are calculated from measurements of arterial, distal coronary, and central venous pressures during maximum arteriolar vasodilation. To test this model, five dogs were acutely instrumented with an epicardial, coronary Doppler flow velocity transducer. Distal coronary pressures were measured by an ultrathin pressure-monitoring guide wire (0.015 in.) with minimal influence on transstenotic pressure gradient. Fractional flow reserve was calculated from the pressure measurements and compared with relative maximum coronary artery flow measured directly by the Doppler flowmeter at three different levels of arterial pressure for each of 12 different severities of stenosis at each pressure level. Relative maximum blood flow through the stenotic artery (Qs) measured directly by the Doppler flowmeter showed an excellent correlation with the pressure-derived values of Qs (r = 0.98 +/- 0.01, intercept = 0.02 +/- 0.03, slope = 0.98 +/- 0.04), of the relative maximum myocardial flow (r = 0.98 +/- 0.02, intercept = 0.26 +/- 0.07, slope = 0.73 +/- 0.08), and of the collateral blood flow (r = 0.96 +/- 0.04, intercept = 0.24 +/- 0.07, slope = -0.24 +/- 0.06). Moreover, the theoretically predicted constant relation between mean arterial pressure and coronary wedge pressure, both corrected for venous pressure, was confirmed experimentally (r = 0.97 +/- 0.03, intercept = 9.5 +/- 13.3, slope = 4.4 +/- 1.2). CONCLUSIONS: These results provide the experimental basis for determining relative maximum flow or fractional flow reserve of both the epicardial coronary artery and the myocardium, including collateral flow, from pressure measurements during maximum arteriolar vasodilation. With a suitable guide wire for reliably measuring distal coronary pressure clinically, this method may have potential applications during percutaneous transluminal coronary angioplasty for assessing changes in the functional severity of coronary artery stenoses and for estimating collateral flow achievable during occlusion of the coronary artery.

Angioplasty, Balloon, Coronary↗
PubMed2003

Genome-wide linkage analysis of the tracking of systolic blood pressure using a mixed model.

BACKGROUND: Elevated blood pressure in middle age is a major risk factor for subsequent cardiovascular complications. An important longitudinal characteristic of blood pressure is the "tracking phenomenon". Tracking is defined as the persistence of the rank of a person's blood pressure level in a group over a long period of time. In this analysis, we used the Framingham data to investigate whether there are some genes responsible for this phenomenon. RESULTS: Both two-point and multipoint linkage analyses were applied to family members with complete data only and to all family data with missing values imputed by a Gaussian model. The results of two-point linkage analysis indicated that two loci for linkage with the intercept were on chromosomes 10 and 13, and two loci for linkage with both slope and intercept were on chromosomes 1 and 3. Multipoint linkage analysis indicated only one region, 200-240 cM on chromosome 1, to be linked with both intercept and slope. For the intercept of SBP, the highest LOD (4.43) was found at 214 cM when missing data were imputed, and the highest LOD (2.81) was at 231 cM for the complete case data. For the slope of SBP, the highest multipoint LODs were 3.63 at 227 cM and 2.02 at 234 cM for the complete case data and imputation data, respectively. CONCLUSION: One or more genes in the range of 200-240 cM on chromosome 1 may be related to the tracking phenomenon of SBP.

Adult↗
PubMed1987

Quantitative analysis of regional wall motion in dogs in situ--characteristics of end-systolic pressure-length relation.

Regional wall motion was analyzed to deduce the muscle property unique to regional contractile states. End-systolic pressure length relations were evaluated under global changes in a contractile state, under selective intracoronary administration of inotropic agents to produce regional hypo- or hyper-kinesis, and before and after extension of size of the ischemia. Linearity of the end-systolic pressure-length relation was confirmed in each perturbation; however, the behavior of this relation with regard to changes in the slope and X-axis intercept differed among the three situations. When the contractile state was altered globally by intravenous administration of inotropic agents such as dobutamine and propranolol, the slope of the end-systolic pressure-length relation changed in a manner similar to that seen with the pressure-volume relation or stress-strain relation, with no significant changes in the X-axis intercept. Namely, the level of global cardiac function determined the slope of the end-systolic pressure length relation. When regional hypokinesis was produced pharmacologically by selective intracoronary infusion of lidocaine, the X-axis intercept moved rightward, depending on the degree of regional hypokinesis. Expansion in the size of the ischemic area also shifted the X-axis intercept rightward. The latter two phenomena suggested that the hypokinetic segments were stretched by the surrounding intact myocardium. Accordingly, end-systolic pressure-length relations provide useful information concerning the functional state of regional myocardium. The systolic properties of the regional myocardium rendered hypokinetic have to be quantified so as to include the total geometry of the heart.

Animals↗