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Quantitative determination of aortic regurgitant volumes in dogs by ultrafast computed tomography.

Current imaging modalities can provide only a qualitative or semiquantitative measure of the severity of aortic regurgitation. Ultrafast computed tomography (CT) has the capability of rapid imaging (17 frames/sec) coupled with high spatial resolution (1.5 mm2). Eight millimeter thick images can be acquired to interrogate simultaneously the right and left ventricles. End-diastolic and end-systolic tomograms can be reconstructed serially from apex to base by Simpson's rule to provide end-diastolic and end-systolic volumes from which the right and left ventricular stroke volumes can be derived. To determine whether the difference between left and right ventricular stroke volume measured with ultrafast CT could be used to estimate the volume of experimentally induced aortic regurgitation, we studied six dogs in which proximal aortic electromagnetic flow probes had been implanted. Varying degrees of aortic regurgitation were induced by manipulation of a basket catheter through the aortic valve. During suspended respiration in the control state in the absence of aortic regurgitation, right and left ventricular stroke volumes measured with ultrafast CT were nearly identical (mean difference 1.0 +/- 1.2 ml [mean +/- SE]). In the presence of varying degrees of aortic regurgitation, regurgitant volume derived by ultrafast CT as the difference between right and left ventricular stroke volumes correlated closely to the regurgitant volume measured by the electromagnetic flow probe (r = .99, slope = .92, y intercept = 0.98 ml, SEE = 1.02 ml, n = 16). Regurgitant fraction also correlated closely to the regurgitant fraction measured by the electromagnetic flow probe (r = .94, slope = .98, y intercept = 0.66%, SEE = 4.73%, n = 16).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Response of the left ventricular end-systolic pressure-volume relation in conscious dogs to a wide range of contractile states.

We assessed the linearity and slope of the left ventricular end-systolic pressure (PES)-volume (VES) relation over a wide range of contractile states in conscious dogs. The animals were instrumented to determine left ventricular volume from ultrasonic left ventricular internal dimensions and measure left ventricular pressure with a micromanometer. Studies were performed 1-2 weeks after instrumentation while the animals were conscious. Contractile state was increased by incremental infusion of dobutamine (0, 2, 4, 6, and 8 micrograms/kg/min i.v.) and decreased by verapamil (10 mg i.v.) given after autonomic blockade. The 44 +/- 11 mm Hg (mean +/- SD) portion of the PES-VES relation generated by bicaval occlusion demonstrated a slight but consistent nonlinearity, apparent as a concavity toward the volume axis. This nonlinearity, present at all inotropic states, did not prevent the PES-VES relation from being well approximated by a straight line (r = 0.984 +/- 0.020, SEE = 2.1 +/- 1.4 mm Hg); furthermore, the slope of the PES-VES line provided a sensitive index of contractile state, progressively increasing with incremental doses of dobutamine and decreasing in response to verapamil. The volume-axis intercept of the linear approximation of the PES-VES relation was 2.9 +/- 3.3 ml less (p less than 0.05) than the volume-axis intercept of the nonlinear quadratic fit. Thus, the linear PES-VES relation, whose slope is sensitive to a wide variety of inotropic states, is a reasonable and useful description of the left ventricle in the range of PES-VES points that can be produced by bicaval occlusion in the conscious dog. However, linear extrapolation of the relation beyond the range of data points may not be accurate.

Animals↗

Influence of contractile state on curvilinearity of in situ end-systolic pressure-volume relations.

Although in situ end-systolic pressure-volume relations (ESPVRs) are approximately linear throughout a limited load range, they often yield seemingly "negative" volume axis intercepts (V0) and V0 shifts with inotropic interventions. We tested whether or not these findings could stem from in situ ESPVR nonlinearity, and we examined the physiologic meaning and limitations of linearized ESPVR variables frequently used for assessing contractile state. Continuous left ventricular pressures and volumes were obtained by micromanometer and conductance (volume) catheters in six open-chest dogs. Left ventricular loading was varied throughout a wide range by rapid left atrial hemorrhage into a reservoir. Propranolol and verapamil were administered to reduce inotropic state, with heart rate maintained by atrioventricular sequential pacing. ESPVRs were fit to nonlinear [Pes = a(Ves-V'0)2 + b(Ves-V'0)] and linear (Pes = Ees (Ves-V0)] models. Contractile state was assessed by the slope of the ESPVR at V'0 (b, of nonlinear model) and by two other ESPVR model-independent measures: the slope of the dP/dtmax and end-diastolic volume relation, and the slope of the stroke work and end-diastolic volume relation. ESPVR was frequently curvilinear, and a significant correlation existed between the extent of nonlinearity (a) and contractile state. Volume intercepts derived from linear fits to the high load ESPVR range were mostly negative and were dependent on changes in Ees. V0 estimates derived from the low load portion were positive and relatively insensitive to Ees. Thus, in situ ESPVR displays contractility-dependent curvilinearity. The contractility range throughout which ESPVRs are essentially linear is typical for isolated hearts, but the range represents low values for in situ ventricles. Despite curvilinearity, Ees determined in situ throughout limited load ranges can accurately assess inotropic state; however, comparisons between ESPVRs should consider potential nonlinearity, and if possible, they should be made within similar end-systolic pressure ranges.

Animals↗

Preload-induced curvilinearity of left ventricular end-systolic pressure-volume relations. Effects on derived indexes in closed-chest dogs.

End-systolic pressure-volume relations (ESPVRs) were analyzed in 10 closed-chest autonomically blocked dogs before and after volume loading that restored end-diastolic volume to its value measured in the control conscious state. Dogs had been previously instrumented with a left ventricular pressure micromanometer and ultrasonic crystals for measurements of major, anteroposterior, and septum-free wall diameters. Left ventricular volume was calculated with an ellipsoidal model in the left ventricular cavity. ESPVRs obtained during caval occlusion after volume loading were curvilinear as shown by the division of the relation into two parts. The initial part of the relation had a significantly smaller ESPVR slope (Ees, 12.0 +/- 1.8 mm Hg/ml) and ESPVR volume-axis intercept (Vd, - 3.5 +/- 0.8 ml) than the final part of the relation (19.5 +/- 3.1 mm Hg/ml and 0.0 +/- 0.6 ml, respectively, p less than 0.01). The end-diastolic volume-peak dP/dt relation showed a similar curvilinearity when end-diastolic volumes were larger than 1.5-1.7 times the minimal end-diastolic volume reached during caval occlusion. ESPVRs were not different during aortic constriction and caval occlusion when end-diastolic volume was small. In contrast, with large end-diastolic volumes, Ees and Vd were significantly smaller during caval occlusion than during aortic constriction. The final part of ESPVR (with small end-diastolic volume) had the same slope and intercept as that during aortic constriction. We conclude that preload produces a curvilinearity of ESPVR that significantly modifies derived indexes when the range of preload changes is large.

Animals↗

Nonlinearity and load sensitivity of end-systolic pressure-volume relation of canine left ventricle in vivo.

The effects of mechanical changes in loading conditions on the left ventricular end-systolic pressure-volume relation (ESPVR) were studied in nine open-chest dogs, including three dogs studied before and after beta-adrenergic blockade. Left ventricular pressure was measured with a micromanometer, and left ventricular volume was measured with a conductance catheter. ESPVRs were obtained by increasing left atrial inflow over wide volume ranges (as much as threefold) under three different conditions: control or high or low aortic impedance. High impedance was obtained by occlusion of the descending aorta, and low impedance was obtained by a shunt between the subclavian artery and the left atrium. In the unblocked animals in 21 of 28 runs, a second-order polynomial equation gave a better fit for the ESPVR than a linear relation. To quantify the effects of the changes in aortic impedance on the ESPVR, we calculated from the quadratic equation its volume intercept (V18) and its local slope (E18) at an end-systolic pressure (Pes) of 18 kPa. In the unblocked animals, a statistically significant difference was found in V18 between low impedance (21.50 +/- 6.27 ml) and high impedance (14.10 +/- 8.98 ml; p less than 0.005) and between control (19.14 +/- 9.58 ml) and high impedance (p less than 0.05). In most dogs, E18 was increased at high and decreased at low impedance, but not significantly. In the additional experiments with beta-blockade, the nonlinearity diminished somewhat, but the load dependency of the ESPVR remained present after beta-blockade because the same leftward shift of the ESPVR with high aortic impedance was found. Two other relations, namely, of dP/dtmax and of stroke work versus end-diastolic volume, were also investigated, which on the whole showed the same behavior as the ESPVR. These results indicate that the ESPVR and dP/dtmax-Ved and stroke work-end-diastolic volume relations, when studied over a wide volume range, are nonlinear and that changes in loading conditions influence indexes of contractility derived from these relations, especially the volume intercepts, in such a way that an increase in aortic impedance may be interpreted as an increase in contractility. Blocking the beta-adrenergic receptors did not influence the load dependency of the ESPVR but, in some cases, tended to decrease the nonlinearity in concordance with the relation between contractility and nonlinearity in isolated hearts.

Adrenergic beta-Antagonists↗

Relation between left ventricular oxygen consumption and pressure-volume area in conscious dogs.

BACKGROUND: The relation between left ventricular (LV) oxygen consumption (MVO2) and pressure-volume area (PVA) developed in isolated hearts provides a powerful method to understand cardiac energetics. We investigated application of this relation to the intact circulation, determining its response to steady-state and transient load alterations and enhanced contractility in conscious animals. METHODS AND RESULTS: Eight dogs were instrumented to measure LV pressure (micromanometer), LV volume (three sonomicrometers), and left circumflex and anterior descending coronary artery flows (ultrasonic flowmeter). Data were acquired after recovery from the surgery with the animals awake and unsedated. After administration of hexamethonium and atropine, steady-state loading conditions were changed with phenylephrine or nitroprusside in four to five steps before and during the infusion of dobutamine (6 to 10 micrograms.-1kg.-1min). MVO2 and PVA obtained under steady-state conditions were linearly correlated both before and during dobutamine. The MVO2-PVA relation obtained on a beat-to-beat basis during transient caval occlusion was less linear and not coincident with the steady-state relation. Dobutamine shifted the steady-state MVO2-PVA relation upward in all hearts, increasing the MVO2 axis intercept of the MVO2-PVA relation (P < .01). This intercept correlated with ventricular contractility assessed by the slope (Ees) of the LV end-systolic pressure-volume relation determined by caval occlusion (r = .76, P < .05). The slope of the MVO2-PVA relation increased with dobutamine in seven of eight animals, with the inverse of the slope (representing contractile efficiency) being 31 +/- 6% during control and 24 +/- 6% after dobutamine (P = .06). CONCLUSIONS: MVO2 and PVA are linearly related during steady-state alterations in loading conditions in conscious dogs but not on a beat-by-beat basis during transient caval occlusion. Increase in contractility by dobutamine produces an upward shift of the MVO2-PVA relation.

Animals↗

In vivo assessment of left atrial contractile performance in normal and pathological conditions using a time-varying elastance model.

BACKGROUND: Contractile function of the ex vivo, isolated left atrium (LA) has been described by a time-varying elastance, but this atrial chamber property has not been shown in vivo. METHODS AND RESULTS: Instantaneous LA pressure-volume (P-V) relations were studied in 12 anesthetized, autonomically blocked, atrially paced dogs. LA volume was calculated from orthogonal sonomicrometer pairs using a cast-validated formula. Data were collected during increases in LA pressure produced by a phenylephrine bolus (200 to 400 micrograms IV). Isochronal P-V points from 5 beats, representing a wide range of atrial pressures, were fitted by linear regression analysis (range of R2, .92 to .99). There were significant time-dependent increases in the slopes [E(t)] and small but statistically insignificant decreases in the volume axis intercepts [VO(t)] of the instantaneous LA P-V relations during atrial contraction; maximal elastance (Emax) occurred 29 +/- 16 milliseconds before atrial end systole (minimal LA volume). Emax was not significantly different than the slopes of either the nonisochronal end-systolic P-V relation (Ees) or the nonisochronal maximal P-to-V relation (EmaxPV): 5.5 +/- 2.8, 4.3 +/- 1.5, and 5.4 +/- 4.2 mm Hg/mL, respectively. In 7 dogs, data were collected both before and after a rapid infusion of calcium gluconate (1 to 2 g IV). Emax increased significantly with a calcium-induced increase in inotropic state (4.5 +/- 1.6 to 5.7 +/- 1.8 mm Hg/mL, P < .01), but the volume axis intercept was unchanged (3.6 +/- 0.7 versus 3.4 +/- 1.9, P = NS). In 4 additional dogs with heart failure (mean LA pressure, 26 +/- 6 mm Hg) produced by 3 weeks of rapid right ventricular pacing, LA stroke volume was significantly greater than and elastance determinations were similar to those of normal dogs. However, the effects of calcium infusion on LA function were attenuated in these animals. CONCLUSIONS: We conclude that (1) in the intact heart, LA contraction may be approximated by time-varying elastance with time-dependent changes in E(t) and that (2) LA systolic P-V relations using either the nonisochronal maximum P-to-V ratio or end systole may be useful as an estimate of Emax, are highly linear and sensitive to calcium-induced changes in inotropic state, and may be useful in identifying LA chamber adaptation to chronic hemodynamic loads.

Animals↗

Slope of the instantaneous hyperemic diastolic coronary flow velocity-pressure relation. A new index for assessment of the physiological significance of coronary stenosis in humans.

BACKGROUND: Coronary flow reserve (CFR), the functional index of stenosis severity more frequently used in the catheterization laboratory, is greatly affected by the hemodynamic conditions at the time of measurement and cannot be applied in the immediate assessment of the outcome of coronary interventions. The aim of the present study was to establish the feasibility and reproducibility of the assessment of the slope of the instantaneous diastolic relation between coronary flow velocity and aortic pressure during maximal hyperemia (IHDVPS) using a spectral analysis of the intracoronary Doppler signal, to assess the sensitivity and specificity of this index in the detection of flow-limiting coronary stenoses in comparison with CFR, and to study the possibility of determining the zero-flow pressure from the intercept of the velocity-pressure relation on the pressure axis during a controlled cardiac arrest. METHODS AND RESULTS: The instantaneous peak coronary flow velocity measured after intracoronary papaverine with a Doppler guidewire was plotted against the simultaneously measured aortic pressure, and the slope of the velocity-pressure relation in the phase of progressive diastolic velocity decrease was calculated during four consecutive beats. In nine normal arteries, a controlled diastolic cardiac arrest was induced by an intracoronary bolus injection of 3 mg adenosine. The IHDVPS could be assessed in 79 of 95 patients (83%), with a moderate intraobserver variability (0.4 +/- 11% after independent selection of different beats during maximal hyperemia). The IHDVPS showed no significant correlation with heart rate, mean diastolic aortic pressure, type of vessel studied, and cross-sectional area at the site of the velocity recording. The IHDVPS was significantly lower in arteries with > or = 30% diameter stenosis than in normal or near-normal arteries (0.71 +/- 0.48 versus 1.73 +/- 0.80 cm.s-1.mm Hg-1, P < .0000002). In the stenosis group, both IHDVPS and CFR were significantly correlated with the minimal luminal cross-sectional area (r = .46, P < .05 and r = .62, P < .002, respectively). The study of the velocity-pressure relation during long diastolic pauses showed a curvilinear relation between velocity and pressure in the lower pressure range, with an upward concavity to the velocity axis and no intercept with the pressure axis in most cases. CONCLUSIONS: The IHDVPS can distinguish between arteries with and without coronary stenoses and has a significant inverse correlation with the severity of the stenosis. Under the stable hemodynamic conditions of this study, the IHDVPS and CFR had similar sensitivities and specificities in distinguishing normal and stenotic vessels and demonstrated similar correlation with minimal luminal cross-sectional area. The curvilinearity of the velocity-pressure relation during long diastolic pauses, possibly due to a significant reduction of luminal cross-sectional area at low pressures, complicates the use of the flow velocity-pressure relation for the assessment of the zero-flow pressure.

Adult↗

Effects of load manipulations, heart rate, and contractility on left ventricular apical rotation. An experimental study in anesthetized dogs.

BACKGROUND: Left ventricular twist or torsion has been defined as the counterclockwise rotation of the ventricular apex with respect to the base during systole. We have recently shown that since base rotation is minimal, measurement of apex rotation reflects the dynamics of left ventricular (LV) twist. Since the mechanisms by which load and contractility affect twist are controversial, we aimed to determine the relation between apex rotation and volume, contractility, and heart rate under conditions in which dimensions and pressures were accurately measured. METHODS AND RESULTS: Using our optical device coupled to the LV apex, apex rotation was recorded simultaneously with LV pressure, ECG, LV segment length, and minor-axis diameters (sonomicrometry) in 12 open-chest dogs. Using vena caval occlusion and volume loading, a linear end-diastolic (ED) relation between apex rotation and LV area index was obtained (slope, 0.61 +/- 0.06 degrees/percent change; intercept, -60.1 +/- 6.2 degrees; n = 10) that differed from the end-systolic (ES) relation (slope, 1.36 +/- 0.27 degree/percent change; intercept, -132.5 +/- 24.9 degrees; P < .005). With changes in contractility, afterload, or heart rate, for both ED and ES the apex rotation-volume points fell within the range of the relations established by changing preload, suggesting that volume is the major determinant of twist. Vena caval occlusion (preload and afterload decrease) caused an increase in amplitude of apex rotation, with maximal apex rotation occurring earlier in ejection. In contrast, acute volume loading (predominant preload increase) caused a small decrease in the amplitude of apex rotation, and twist relaxation was delayed into the isovolumic relaxation period. Likewise, with single-beat aortic occlusion (increased afterload), there was a slight decrease in the amplitude of apex rotation, and maximal apex rotation was delayed into the isovolumic relaxation period. Paired pacing (increased contractility) increased the total amplitude of apex rotation by 42% and caused a delay in untwisting until the end of the isovolumic relaxation period. An increase in heart rate over 150 beats per minute resulted in a significant decrease in the amplitude of apex rotation with a similar delay of twist relaxation into the isovolumic relaxation period. CONCLUSIONS: The effects of load, contractility, and heart rate manipulations on LV twist as measured throughout the cardiac cycle by the optical apex rotation method are manifested by changes in both the amplitude and dynamics of torsion. LV twist at ED and ES is primarily a function of volume; this relation appears to be unaltered by heart rate, afterload, and contractility. Whereas decreased load caused early untwisting, increases in preload, afterload, heart rate, and contractility caused a consistent pattern of delay in twist relaxation.

Anesthesia↗

Single-beat estimation of end-systolic pressure-volume relation in humans. A new method with the potential for noninvasive application.

BACKGROUND: The end-systolic pressure-volume relation (ESPVR) provides a useful measure of contractile function. However, the need to acquire multiple cardiac cycles at varying loads limits its applicability. We therefore developed and tested a novel single-beat estimation method that is based on normalized human time-varying elastance curves [EN(tN)]. METHODS AND RESULTS: Pressure-volume (PV) data were measured by conductance catheter in 87 patients with normal or myopathic hearts. Time-varying elastance curves were generated from 72 PV loops (52 patients) and normalized both by amplitude and time to peak amplitude. The resulting EN(tN) curves were remarkably consistent despite variations in underlying cardiac disease, contractility, loading, and heart rate, with minimal interloop variance during the first 25% to 35% of contraction. On the basis of this finding and assuming ESPVR linearity and constant volume-intercept, ESPVRs were estimated from one beat with the use of PV data measured at normalized time (tN) and end systole (tmax) to predict intercept: Vo(SB) = [EN(tN) x P(tmax) x V(tN)-P(tN)x V(tmax)]/[EN(tN) x P(tmax)-P(tN)] and slope Emax(SB) = Pes/[Ves-Vo(SB)]. Single-beat estimates were highly correlated with measured ESPVR values obtained by standard multiple-beat analysis (including data from 35 additional patients). Emax(SB) accurately reflected acute inotropic change and was influenced little by loading. The new estimation method also predicted measured ESPVRs better than prior techniques and was applicable to noninvasive analysis. CONCLUSIONS: ESPVRs can be reliably estimated in humans from single cardiac cycles by a new method that has a potential for noninvasive application.

Adult↗

Effects of the Dietary Approaches to Stop Hypertension (DASH) diet on the pressure-natriuresis relationship.

Blood pressure-lowering mechanisms of the Dietary Approaches to Stop Hypertension (DASH) diet, rich in fruits, vegetables, and low-fat dairy foods, were analyzed based on the pressure-natriuresis relationship. Participants (n=375) were randomly assigned to control or DASH diet groups by using a parallel-group design. They then ate their assigned diet for 3 consecutive 30-day intervention feeding periods, during which sodium intake varied among 3 levels by a randomly assigned sequence. Urinary sodium excretion rate and mean arterial pressure were measured at the end of each sodium intake level. Mean arterial pressure and urinary sodium excretion were plotted on x and y axes, respectively, for participants eating control and DASH diets and were modeled as linear relationships for simplicity to allow the estimation of the extrapolated x-intercept and slope of the relationships. The DASH diet steepened the slope of the relationship (29.5+/-3.4 vs 64.9+/-13.1 [mmol/d]/mm Hg, P=0.0002) without significantly shifting the x-intercept (94.1+/-0.5 vs 93.2+/-0.6 mm Hg, NS) of the relationship. These data suggest a natriuretic action of the DASH diet.

Adult↗

The role of angiotensin in the control of blood pressure during sodium depletion.

Sodium depletion was induced in dogs to raise plasma renin activity (PRA) from 1.11 to 26.48 ng/ml/hr. Little overall change in blood pressure (BP) occurred, but cardiac output (CO) and central venous pressure fell, while total peripheral resistance and heart rate (HR) increased. A nonapeptide converting enzyme inhibitor (CEI) produced a fall in BP which was linearly related to log. PRA; the intercept with PRA was at 1.05 ng/ml/hr, close to the average value for dogs on a normal diet. The fall in BP with this agent was not accompanied by an increase in HR or CO. When Sar1-Ala8 angiotensin II was used to antagonize the action of angiotensin, the fall in BP was also linearly related to log. PRA. However, for a given level of PRA this fall in BP was less than that achieved with CEI and the intercept of BP fall with PRA was 2.6 ng/ml/hr. Again with this agent there was little change in HR or CO as BP was reduced. Thus, both antagonists lowered peripheral resistance without exciting the homeostatic reflexes indicating that, as PRA rose above the normal resting level, the angiotensin generated had both a direct and indirect effect in maintaining BP.

Angiotensin II↗

Plasma norepinephrine and dihydroxyphenylglycol in essential hypertension.

The aim of the present study was to examine whether essential hypertension is associated with altered plasma concentrations of dihydroxyphenylglycol, the principal presynaptic metabolite of norepinephrine. Forearm venous plasma dihydroxyphenylglycol and norepinephrine were determined at rest and during graded orthostasis in 47 normotensive control subjects and 58 outpatients with essential hypertension. There was no group difference in age. At supine rest as well as during sitting and standing, hypertensive subjects had plasma norepinephrine concentrations similar to those in normotensive control subjects, but plasma dihydroxyphenylglycol concentrations were higher than those in normotensive control subjects. Both groups showed a linear relation between plasma dihydroxyphenylglycol (ordinate) and plasma norepinephrine (abscissa). The resulting regression line was steeper (p less than 0.02) and its ordinate intercept higher (p less than 0.01) in hypertensive than in control subjects. Eleven normotensive and 14 hypertensive subjects were also tested 3 hours after desipramine (1.5 mg/kg orally) was administered to inhibit neuronal norepinephrine reuptake. The drug did not alter plasma norepinephrine, but did reduce plasma dihydroxyphenylglycol and did abolish plasma dihydroxyphenylglycol responses to upright posture in both groups of subjects. The mean plasma dihydroxyphenylglycol concentration observed in the presence of desipramine again was higher in the hypertensive than in the control group (p less than 0.01) and closely agreed, in both groups, with the dihydroxyphenylglycol concentration given by the ordinate intercept of the dihydroxyphenylglycol versus norepinephrine regression line in the absence of desipramine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hydrochlorothiazide improves ventricular compliance and thus performance without reducing hypertrophy in renal artery stenosis in rats.

The effect of hydrochlorothiazide (1 mg/kg per day) on left ventricular (LV) mass and systolic and diastolic function was investigated in two-kidney, one clip (2K1C) renovascular hypertensive rats. Hydrochlorothiazide was administered from 8 weeks, and LV mass and function were measured at 16 weeks after surgery to induce hypertension. Cardiac performance was determined from cardiac output, stroke volume (per 100 g of body weight), and stroke work (per gram of LV weight) versus LV end-diastolic pressure (LVEDP) and versus LV strain relations in anesthetized open-chest, ventilated rats. LV compliance was determined from the LVEDP versus strain relation. Strain was calculated from LV end-diastolic short-axis diameter values. Hydrochlorothiazide reduced systolic blood pressure in 2K1C rats to levels similar to those in sham-operated controls (sham) at 12 weeks after surgery. A reduced afterload failed to influence LV mass, as left LV hypertrophy developed to the same extent in treated 2K1C rats. 2K1C hypertension produced abnormal cardiac performance with altered cardiac output, stroke volume, and stroke work versus LVEDP relations (stroke work versus LVEDP, intercept of 2K1C versus sham, p < 0.001). This was attributed to a decreased ventricular compliance (strain versus LVEDP, slope of 2K1C versus sham, p < 0.001). In contrast, hydrochlorothiazide improved ventricular compliance (strain versus LVEDP, slope of 2K1C versus 2K1C hydrochlorothiazide, p < 0.01) and thus returned the stroke work versus LVEDP relation to sham values (intercept of 2K1C versus 2K1C hydrochlorothiazide, p < 0.001). We conclude that hydrochlorothiazide reduces blood pressure but not the development of ventricular hypertrophy in 2K1C rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A fresh approach to the evaluation of antihypertensive agents.

Clinical studies on the use and activity of drugs often rely on data generated from a relatively small number of patients, and definitive conclusions are drawn that are assumed to represent the population at large. Similarly, interpretation and comparison of studies are made difficult when end points of effectiveness, particularly with antihypertensive agents, are arbitrarily chosen. The results from a clinical study of more than 1400 hypertensive patients after indapamide therapy for 3 months, alone or in combination with a beta blocker, are presented using a different graphic approach. This is based on the assumption that the magnitude of the fall in blood pressure after hypertensive therapy is dependent on initial blood pressure. Diastolic and systolic pressures were plotted as a scattergram against the change in blood pressure. Predetermined response lines were drawn with a slope of 1 and intercepts on the initial blood pressure axis of 90 mm Hg for diastolic and 140 mm Hg for systolic pressures with tolerance limits of +/- 10 mm Hg drawn about it. Subdivisions of response can be achieved by counting the number of patients above and below these lines. This allows a drug to be "finger-printed" in terms of its pattern of activity in all degrees of severity of hypertension and, more relevant, direct comparisons with other drugs can be made. Similarly, the potential activity of the drug can be determined by computing the slope and intercept of the actual regression line through the data points.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Static pressure-flow relation in the total systemic vascular bed of the dog and its modification by the baroreceptor reflex.

To evaluate arterial baroreceptor reflex control of total systemic vascular resistance, we studied the relation between mean arterial blood pressure (P) and mean aortic flow (Q) before and after the reflex was abrogated. In 12 dogs with a perfusion pump interposed at the vena-caval-right atrial junction, Q was kept at 60, 80, 100, 120, and 140 ml/min kg-1 for up to 20 minutes. There was little time-dependent change in P at any of these flows. When the reflex was intact, the mean P-Q curve was only slightly convex to the pressure axis; its linearized slope was 0.55 mm Hg-min-kg/ml and its pressure axis intercept was 44 mm Hg. After section of the sinovagal nerves, administration of hexamethonium (30 mg/kg, iv) and norepinephrine (3-5 mug/kg min-1, iv), or both, the slope became 0.96 mm Hg-min-kg/ml and the pressure axis intercept was about 3 mm Hg. Similar findings were obtained in 3 closed-chest dogs in which P was servocontrolled and Q was measured. Therefore, we think that the conventional practice of calculating total peripheral resistance as P/Q and evaluating reflex control of it in terms of the changes in that value involves only a small error in the moderately sub -and supranormal flow range.

Animals↗

Diastolic coronary artery pressure-flow relations in the dog.

Conscious dogs were used to investigate the relations between aortic (Pa) pressure and coronary flow (F) during individual diastoles. When the dogs were in a semibasal state, coronary pressure-flow relations were described by a family of lines, and diastolic flow was a linear function of aortic pressure. For a given perfusion pressure, higher flows were associated with lines of progressively greater slope and lower zero flow pressure intercept (Pf=0). Zero flow pressure intercepts were estimated by extrapolation and found to vary between 20 and 50 mm Hg, depending on the magnitude of flow. The zero flow pressure may represent the height of a vascular waterfall caused by vasomotor tone with the resistance-controlling coronary flow being (P-Pf=0).F-1. Interventions that decrease vasomotor tone increase coronary flow by both decreasing vascular resistance and increasing the perfusion pressure gradient. The gradient increases because the effective coronary back pressure is the height of the vascular waterfall and the latter is reduced when vasomotor tone falls. Passive changes in vessel dimensions, arterial recruitment, and autoregulation appear to be of little importance during individual diastoles.

Animals↗

Effect of atrial systole on canine and porcine coronary blood flow.

A feature of phasic coronary flow patterns recorded in conscious chronically instrumented dogs is the atrial cove--a transient depression of arterial flow that occurs during atrial systole. The association between the hemodynamic effects of atrial systole and the atrial cove was studied in anesthetized dogs and pigs with complete heart block. Many atrial coves are available for study in these preparations because atrial activity continues unabated during the diastolic ventricular arrest that follows cessation of electrical pacing. The effect of atrial systole is to translate the pressure-flow relation found during diastole to a higher intercept pressure without change in slope. The increase in the intercept pressure equals the increase in intramyocardial pressure measured with microtransducers embedded in the left ventricular wall. The decrement in flow during the atrial cove is a direct function of the change in intramyocardial pressure and an inverse function of coronary vascular resistance. Each atrial systole is associated with a forward flow transient in the coronary veins, the peak of which occurs at the same instant as does the nadir of atrial flow. These data suggest that the coronary vessels are acting as collapsible tubes and that the waterfall model of the coronary circulation is applicable. The following sequence is proposed to account for the atrial cove. Atrial systole ejects a bolus of blood into the left ventricle increasing both ventricular cavity and intramyocardial pressures. The increase in intramyocardial pressure raises the back pressure opposing coronary flow, reducing the arterial perfusion pressure gradient and causing flow to fall.

Animals↗