End Of Ejection Research Articles

Internal ballistic simulation and optimum design of gas-fired rodless cylinder ejection device

A kind of gas-fired rodless cylinder ejection device which is stoke and weight controlled and suitable for mobile launch was designed. The leakage test of the ejection device is carried out based on the principle prototype of rodless cylinder ejection device and the empirical formula between leakage rate and pressure and travel length was fitted. The mathematical model of gas-fired rodless cylinder ejector internal ballistic with considering the leakage rate is established based on the assumption of zero-dimensional internal ballistic. When comparing the results of internal ballistics considering and not considering the leakage rate, it can be seen that the influence of leakage rate on the results of internal ballistics can not be ignored. The internal ballistic model which coupled the leakage rate is optimized, taking the shortest design stroke and smallest ejection stability index as design target and the parameters of the grain are used as design variables. The results show that after the optimization, the mass flow rate of gas at the end of ejection is increased by 19%, the stroke required for piston speed reaching the design target is shortened by 13.1%, and the launch stability index is increased by 10.7%.

P5686Role of internal stretch fraction parameter in quantification of mechanical dyssynchrony and prediction of cardiac resynchronization therapy outcome

Abstract Background Dyssynchronous activation of the heart is a prerequisite for cardiac resynchronization (CRT) efficacy. Although the main goal of CRT is to resynchronize ventricular contraction, our abilities to quantify mechanical dyssynchrony are still limited. However, so called “internal stretch fraction” (ISF) might serve as a marker of global discoordination of ventricular contraction. Methods and aim of the study Thirty-six CRT candidates and 7 healthy controls underwent MRI scanning. Feature tracking data (in short axis) were analysed using Segment software and cicrumferential strain (S)/ strainrate (SR) was obtained for each of the 16 left-ventricular (LV) segments. ISF was calculated as an extent of stretch (product of number of stretched regions and their mean amount of stretch, integrated over given time period; ie. area under the positive part of the global SR curve) in relation to the extent of shortening (area under the negative part of the global SR curve) in 6 basal LV segments during the ejection time (ET). The onset and end of ejection for ISF calculation were set from the global S curve (obtained by the averaging of S curves in 6 basal LV segments). For flow-derived ISF (FISF) parameter, ET was defined from the MRI-flow through pulmonic and aortic valve (Fig-1). Higher ISF and FISF marks more ineffective ventricular contraction. Aim of our study was to assess the ability of ISF and FISF to distinguish healthy controls from CRT candidates and to predict CRT responders (↓LVESV>15% after 6 months of CRT). Results ISF and FISF were significantly higher in CRT candidates than in healthy controls, greater difference between the two groups exhibited FISF (Fig-2). There were 37% of nonresponders among CRT recipients. Both parameters (ISF and FISF) were higher in future CRT responders. Cut-off value discriminating CRT responders from CRT nonresponders was >0,045 for ISF and >0,174 for FISF, however FISF had higher sensitivity than ISF (Fig-3; sensitivity 71% (ISF) versus 79% (FISF) and specificity 70% for both ISF and FISF). Conclusion Internal stretch fraction might be a useful parameter for selection of patients with discoordinated ventricular contraction who might profit from CRT. Higher sensitivity of FISF compared to ISF may be explained by the fact that ET derived from global S curve reflects only part of the ejection phase whereas FISF describes presence of ventricular discoordination in the entire ejection phase. Acknowledgement/Funding Supported by Ministry of Health of the Czech Republic, grant nr. 15-31398A. All rights reserved.

Influence of the unloading conditions on capping and lamination: Study on a compaction simulator.

Capping and lamination are classical industrial issues that can be challenging during the scale up of solid dosage forms. Previous publications showed that changing the unloading conditions (triaxial decompression, loaded ejection) made it possible to mitigate capping. In the present study, a systematic study of the effect of the unloading conditions on capping and lamination was performed using a compaction simulator. One model formulation for capping and one for lamination were studied. When symmetrical decompression was performed, as on a rotary press, capping (on both side of the tablet) and lamination were obtained. Asymmetrical unloading (fixed lower punch during unloading) made it possible to suppress lamination and to limit capping to the upper face of the tablet. This unloading condition is similar to the unloading on an eccentric press with a stationary lower punch. Finally, loaded ejection (small pressure on both sides until the end of ejection) made it possible to eliminate both capping and lamination. By changing the unloading condition, it is possible to obtain defect free tablets even for formulations with a high capping or lamination tendency. Moreover, experiments performed on an eccentric press showed results similar to those obtained for asymmetrical unloading on a compaction simulator. Anticipation of tablets defects during the development on eccentric presses might thus be complicated especially in the case of lamination.

OP.4A.06] RELATIONSHIP BETWEEN CIRCADIAN PATTERNS OF BLOOD PRESSURE AND CAROTID ARTERY STIFFNESS AND WAVE INTENSITY IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: The aim of the study is to investigate the relationship between daytime and night-time mean blood pressure (BP) on carotid artery stiffness (CAS) and wave intensity (WI) in 1) hypertensive patients (pts) and in 2) the subgroups formed according to the circadian patterns of BP. Design and method: We investigated 148 hypertensive pts, mean age 58 years. The subgroups were created according to the circadian patterns (64 dippers, 56 non-dippers, 14 extreme dippers, 14 reverse dippers). Measurements of CAS and WI were performed on right common carotid artery (CCA) using ultrasound combined with echo-tracking. We analysed stiffness parameters: stiffness index (beta), pressure-strain elasticity modulus (Ep), arterial compliance (AC), augmentation index (AIx) and one-point pulse wave velocity (PWV). Parameters of WI: W1- correlates with the maximum rate of left ventricular pressure; W2 - occurs towards the end of ejection; negative area (NA) - indicates the effects of reflected waves, pre-ejection period (r-W1), ejection period (W1–2), provide the information about ventricular-arterial coupling. Results: Systolic daytime and night-time mean BP correlated with AIx (r = -0.32, p < 0.0001; r = -0.32, p < 0.0001), with mean CCA diameter (r = 0.30, p < 0.0001; r = 0.37, p < 0.0001) and with mean W1 (r = 0.31, p < 0.0001; r = 0.32, p < 0.0001). Daytime and night-time diastolic BP significantly correlated with AIx. Compared with dippers the stiffness values were higher in non-dippers, but highest in reverse dippers (PWVdipper = 7.2m/s, reverse dipper = 7.9m/s, p = 0.03). Similarly mean diameter was larger in non-dippers and largest in reverse dippers. On the other hand AIx was lower in non-dippers and lowest in reverse dippers. Value r-W1 was lowest in reverse group (r-W1 dipper = 98ms, reverse dipper = 80.5ms, p < 0.01). Differences between the stiffness values in dippers and extreme dippers were statistically not significant. Conclusions: Relationship between systolic daytime and night-time BP with AIx and W1 may provide information about the impact of BP on wave reflection and ventricular-arterial coupling. The stiffness values were significantly elevated in non-dippers and mainly in reverse dippers.

Intraventricular flow patterns and stasis in the LVAD-assisted heart

Left ventricular assist device (LVAD) support disrupts the natural blood flow path through the heart, introducing flow patterns associated with thrombosis, especially in the presence of medical devices. The aim of this study was to quantitatively evaluate the flow patterns in the left ventricle (LV) of the LVAD-assisted heart, with a focus on alterations in vortex development and stasis. Particle image velocimetry of a LVAD-supported LV model was performed in a mock circulatory loop. In the Pre-LVAD flow condition, a vortex ring initiating from the LV base migrated toward the apex during diastole and remained in the LV by the end of ejection. During LVAD support, vortex formation was relatively unchanged although vortex circulation and kinetic energy increased with LVAD speed, particularly in systole. However, as pulsatility decreased and aortic valve opening ceased, a region of fluid stasis formed near the left ventricular outflow tract. These findings suggest that LVAD support does not substantially alter vortex dynamics unless cardiac function is minimal. The altered blood flow introduced by the LVAD results in stasis adjacent to the LV outflow tract, which increases the risk of thrombus formation in the heart.

Intraventricular pressure gradients throughout the cardiac cycle: effects of ischaemia and modulation by afterload

The aim of the present study was to characterize the intraventricular pressure gradients (IVPGs) througout the cardiac cycle, to correlate them with myocardial segmental asynchrony and to evaluate the effects of ischaemia and modulation by afterload. Open-chest anaesthetized rabbits (n = 6) were instrumented with pressure-tip micromanometers placed in the apex and outflow tract of the left ventricular (LV) cavity and with sonomicrometer crystals placed in the apex and base of the LV free wall to measure IVPGs and myocardial segment length changes during basal, afterloaded (aortic cross-clamping) and ischaemic conditions (left anterior descending coronary artery ligation). During early diastole (rapid filling), we recorded an IVPG (4.6 ± 0.7 mmHg) from the cardiac base towards the apex followed by an apex-to-outflow pressure gradient (3.6 ± 0.2 mmHg). During systole, we recorded an IVPG (0.6 ± 0.1 mmHg) from apex to outflow during early rapid ejection, which inverted during late slow ejection. Interestingly, the maximal rate of LV pressure fall occurred earlier and relaxation rate was faster in the base than in the apex. While shortening of basal segments was complete at the end of ejection, apical segments always showed a significant amount of postsystolic shortening. The IVPGs were entirely lost during ischaemia and attenuated by afterload elevations. During ischaemia, systolic shortening of the apical segment decreased, while postsystolic shortening increased. The present study confirms the existence of diastolic and systolic IVPGs in the LV and demonstrates, for the first time, that this normal gradient pattern is related to physiological asynchrony between basal and apical myocardial segments. Moreover, we show that the IVPG, a marker of normal left ventricular function, can be attenuated, lost entirely or even reversed after regional acute ischaemia and afterload elevations.

Apex techniques, old and new, hold the key to estimated left ventricular end-diastolic and right ventricular systolic pressure

The clinical syndrome of heart failure is characterised by a raised venous pressure, dilated ventricular cavity, and exercise intolerance. Raised left ventricular (LV) end-diastolic pressure and high left atrial pressure suggest a poor prognosis [1, 2]. Detection of raised filling pressures are important not only in the progression of coronary artery disease and dilated cardiomyopathy, but also because recent evidence suggests that restrictive LV filling may predict non-responders [3] to the increasingly popular intervention of cardiac resynchronisation therapy. Measurements of ventricular long axis function rely on the fact that the cardiac apex is fixed with respect to the chest wall [4]. Atrio-ventricular coupling during systole and diastole is mediated by an anatomically distinct set of sub-endocardial and sub-epicardial fibres organised longitudinally from base to apex [5]. Systolic function is quantified by familiar measurements such as ejection fraction, fractional shortening or peak rate of pressure change (dp/ dt). Wiggers [6] defined diastole as the period in the cardiac cycle from the ‘‘end of aortic ejection until the onset of ventricular tension development’’. Diastole is a complex sequence involving mechanisms of restoring forces and ventricular compliance, changes in atrial and ventricular pressure, transmitral filling, ventricular interaction, and atrial mechanical activity [1]. Consequently, diastolic function has proved more elusive to quantify, accumulating a stable of surrogates indicative of left atrial (LA) pressure, left ventricular end-diastolic pressure (LVEDP), transmitral flow velocities or long axis function. Assessment is further complicated because abnormalities observed in diastole may arise during the isovolumic periods, as well as in systole. Diastolic function is far more age-dependent than systolic function because physiologically normal values in the young may indicate pathologies in the elderly [1]. Isovolumic relaxation time (from A2 [end of ejection] to mitral cusp separation on M-mode) shortens with raised left atrial pressure, but prolongs with age. Normal ranges for isovolumic relaxation time are 60 – 20 ms (M-mode) [1] or 85 – 15 ms (Doppler) [7]; values less than 40 ms indicate raised left atrial pressure, and zero isovolumic relaxation R. Chung AE M. Y. Henein (&) National Heart and Lung Institute, Department of Echocardiography, Royal Brompton Hospital, Sydney Street, SW3 6NP London, UK e-mail: m.henein@rbht.nhs.uk Int J Cardiovasc Imaging (2006) 22: 643–646 DOI 10.1007/s10554-006-9097-4

Effect of spermine and DNase on DNA release from bacteriophage T5

Bacterial viruses (bacteriophages) consist of nucleic acid protected by a protein envelope called capsid. At the start of infection, the phage genome is translocated into the bacterial cytoplasm. In vitro (and also in vivo), this DNA release can be triggered by binding a specific receptor protein to the phage tail. The force responsible for the release arises from energy stored in the capsid due to strong confinement of the DNA. We show that this force can be modified by adding molecules like spermine that affect DNA conformation. The tetravalent cation spermine can reduce the pressure inside the capsid and induce condensation of the released DNA. We examine the effect of spermine on DNA ejection from phage T5 by using light scattering and gel electrophoresis to measure the amount of DNA remaining in the capsid at the end of ejection. We discuss the results in terms of free energy minimization and we demonstrate that the presence of a DNA condensate outside the phage generates an additional force pulling passively on the DNA remaining inside the capsid.

531 Diagnosis of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy by tissue Doppler imaging

The presence of left ventricular outflow tract (LVOT) obstruction in hypertrophic obstructive cardiomyopathy (HOCM) has important therapeutic implications(surgical or catheter based treatment). LVOT obstruction in HOCM is diagnosed by asymmetric septal hypertrophy, mitral leaflet systolic anterior motion and a systolic LVOT gradient. We describe a new sign for LVOT obstruction obtained by colour-coded tissue Doppler imaging (TDI), which may help to identify affected patients (pts) and to monitor therapy. Methods: Septal longitudinal motion was studied by TDI (>100 frames/s) in 26 pts with suspected HOCM (septal wall thickness >15mm). We identified in 15/26 pts a characteristic biphasic systolic velocity pattern with an early (S1) and a late (S2) positive systolic peak velocity, interrupted by an abrupt mid-systolic septal deceleration (MSSD) notch (defined as >25% relative and >1 cm/s absolute decrease from S1). Isovolumic events were excluded from the analysis by identification of onset and end of ejection by aortic valve Doppler. The presence of an MSSD pattern identified severe LVOT obstruction (>30mmHg peak gradient at rest) with 92% sensitivity and 91% specificity. Doppler derived LVOT gradient was significantly higher in pts with MSSD compared to those without MSSD (71±27 vs. 17±10 mmHg, p<0.001). There was a close temporal relationship between invasive LVOT gradient development and the MSSD in the septal TDI trace as demonstrated by simultaneous recordings(Figure, post-extrasystolic beat).

Myocardial time intervals preceding left ventricular filling in chronic coronary artery disease: value of a decreased septal ejection time

The aim was to assess the capabilities of a two-segment myocardial recording to recognize patients with an underlying chronic ischemic process as a fast screening from controls, prior to the usual segment-to-segment tissue Doppler echocardiographic assessment of ischemia. Ischemia generates systolic and relaxation abnormalities. A flow Doppler index of global systolic and diastolic myocardial performance was recently drawn from time durations studied by coupling isovolumic relaxation (IR) to preejection (PEP)/ejection (ET) ratio (PEP/ET). We derived a similar tissue Doppler approach to the period preceding the left ventricular filling: PEP′, the ejectional inward wall motion representing ET′ and the prefilling (PreFg) period ranging from the end of ET′ to the onset of the outward wall motion approximating IR, were measured and ratios calculated between variables. Spectral tissue Doppler was applied to septal and posterior walls of 28 patients with proven chronic coronary artery disease and preserved left ventricular function and of 12 age-matched controls. Data were compared with global flow data. Global information did not differentiate both groups, save for IR (sensitivity 32%, specificity 57%). In patients, tissue Doppler mean values of single variables ( P=0.004–0.0006) and ratios ( P=0.03–0.002) significantly differed from controls. Moreover, septal ET′ differentiated 13 patients with one-vessel (219±34 ms) from 10 with two-vessel disease (158±70 ms, P=0.01). Sensitivity and specificity of a septal ET′<190 ms for a two-vessel disease were 80%. The two-segment tissue Doppler echocardiographic study provided a rapid screening of patients versus controls and helped to predict the number of diseased vessels.

The effects of cross-fiber deformation on axial fiber stress in myocardium.

We incorporated a three-dimensional generalization of the Huxley cross-bridge theory in a finite element model of ventricular mechanics to examine the effect of nonaxial deformations on active stress in myocardium. According to this new theory, which assumes that macroscopic tissue deformations are transmitted to the myofilament lattice, lateral myofilament spacing affects the axial fiber stress. We calculated stresses and deformations at end-systole under the assumption of strictly isometric conditions. Our results suggest that at the end of ejection, nonaxial deformations may significantly reduce active axial fiber stress in the inner half of the wall of the normal left ventricle (18-35 percent at endocardium, depending on location with respect to apex and base). Moreover, this effect is greater in the case of a compliant ischemic region produced by occlusion of the left anterior descending or circumflex coronary artery (26-54 percent at endocardium). On the other hand, stiffening of the remote and ischemic regions (in the case of a two-week-old infarct) lessens the effect of nonaxial deformation on active stress at all locations (9-32 percent endocardial reductions). These calculated effects are sufficiently large to suggest that the influence of nonaxial deformation on active fiber stress may be important, and should be considered in future studies of cardiac mechanics.

Matching dicrotic notch and mean pulmonary artery pressures: implications for effective arterial elastance.

It has been suggested that pulmonary artery pressure at the end of ejection is close to mean pulmonary artery pressure, thus contributing to the optimization of external power from the right ventricle. We tested the hypothesis that dicrotic notch and mean pulmonary artery pressures could be of similar magnitude in 15 men (50 +/- 12 yr) referred to our laboratory for diagnostic right and left heart catheterization. Beat-to-beat relationships between dicrotic notch and mean pulmonary artery pressures were studied 1) at rest over 10 consecutive beats and 2) in 5 patients during the Valsalva maneuver (178 beats studied). At rest, there was no difference between dicrotic notch and mean pulmonary artery pressures (21.8 +/- 12.0 vs. 21.9 +/- 11.1 mmHg). There was a strong linear relationship between dicrotic notch and mean pressures 1) over the 10 consecutive beats studied in each patient (mean r = 0.93), 2) over the 150 resting beats (r = 0.99), and 3) during the Valsalva maneuver in each patient (r = 0.98-0.99) and in the overall beats (r = 0.99). The difference between dicrotic notch and mean pressures was -0.1 +/- 1.7 mmHg at rest and -1.5 +/- 2.3 mmHg during the Valsalva maneuver. Substitution of the mean pulmonary artery pressure by the dicrotic notch pressure in the standard formula of the pulmonary vascular resistance (PVR) resulted in an equation relating linearly end-systolic pressure and stroke volume. The slope of this relation had the dimension of a volume elastance (in mmHg/ml), a simple estimate of volume elastance being obtained as 1.06(PVR/T), where T is duration of the cardiac cycle. In conclusion, dicrotic notch pressure was of similar magnitude as mean pulmonary artery pressure. These results confirmed our primary hypothesis and indicated that human pulmonary artery can be treated as if it is an elastic chamber with a volume elastance of 1.06(PVR/T).

975-79 The Effects of Pressure Recovery and Subvalvular Acceleration May Explain the Discrepancy Between Catheterlsation and Echocardlographlc Pressure Gradients in Children with Aortic Valve Disease

The echocardiographic (E) aortic valve pressure gradient (ΔP) is useful to assess the severity of aortic stenosis. However, E ▵P using the modified Bernoulli equation (Pi) often exceeds that measured by catheter (Pc). Subvalvular acceleration and pressure recovery (Rp) need to be calculated to get E ▵P that more closely reflects Pc. To determine the contribution of each of these components. a more complete descriptor of the ▵P was developed using the complete Bernoulli equation and a formula for pressure recovery developed by Clark. This equation was applied to a published pediatric data set. The pressure data (mmHg) are presented below (Pr = ▵P corrected only for Rp and Pa = ▵P corrected for both Rp and subvalvular acceleration) (mean ± SO):Empty CellPeakMeanPc42.6 ± 24.332.1 ± 16.1Pi64.0 ± 26.7*38.4 ± 16.9*Pr47.9 ± 22.9*29.9 ± 15.3Pa43.5 ± 23.727.7 ± 15.7†*p &lt; 0.001†p &lt; 0.01 vs Pc p &lt; 0.001 p &lt; 0.01 vs Pc Peak E ΔP corrected for both subvalvular acceleration and Rp reduced the difference between E and cath ΔP from –21.2 ± 14.5 to 0.6 ± 12.3 mmHg (p &lt; 0.001). The R-value increased from 0.84 to 0.87. and SEE decreased from 13.3 to 12.1 mmHg. Mean E AP corrected only for Rp reduced the difference between echo and cath ΔP from 6.3 ± 9.8 to -2.2 ± 8.3 mmHg (p &lt; 0.001). The R-value increased from 0.83 to 0.86, and SEE decreased from 9.2 to 8.2 mmHg. We conclude: Rp and subvalvular acceleration contribute to overestimation of E ▵P seen in pediatric patients. Correction for both results in a peak ▵P more closely related to cath. Correcting only for Rp realized the best correlation of mean E ▵P with cath. This may be due to the subvalvular acceleration having little effect on ▵P at the beginning and end of ejection.

Effects of arterial distensibility on left ventricular ejection in the depressed contractile state.

The aim was to evaluate the effects of arterial distensibility on ventricular ejection in various ventricular contractile states: (1) control; (2) a regionally depressed contractile state due to left circumflex coronary artery occlusion (ligation); (3) a globally depressed contractile state induced by lignocaine (lignocaine); and (4) a globally augmented contractile state due to dobutamine infusion (dobutamine). Arterial compliance was decreased from 2.3 x 10(-4) dyne-1.cm5 (C2.3) to 0.4 x 10(-4) dyne-1.cm5 (C0.4), maintaining other afterload components and left ventricular end diastolic pressure constant. Nine excised perfused and paced canine hearts, supported from donor dogs, were used. In control, ligation, lignocaine, and dobutamine groups, the difference in cardiac output between the compliance values of C0.4 and C2.3 was 124(SEM 32), 204(36), 163(33), and 130(24) ml, respectively. Thus cardiac output at C0.4, as a percentage of that at C2.3, was 88(2.8)% (control), 75(2.9)% (ligation), 82(2.9)% (lignocaine), and 88(2.4)% (dobutamine), respectively: control v ligation, and lignocaine v ligation, p < 0.001; control v lignocaine, and dobutamine v ligation, p < 0.01. Stroke work at C0.4 decreased in the ligation group (63%, p < 0.001) and in the lignocaine group (70%, p < 0.001). When cardiac dysfunction is already present, decreased arterial distensibility has a further deleterious effect on cardiac output. This may be due to the fact that the pressure at the end of ejection is higher and as a result the change in dimension during ejection is considerably reduced, especially in cases with depressed cardiac function caused by afterload dependency.

Factors influencing late right ventricular ejection.

Forward flow from the right ventricle into the pulmonary artery continues longer than contraction in the right ventricular free wall. The momentum of blood flow, contraction of other areas of the right ventricular free wall, and movement of the interventricular septum are possible mechanisms regulating late right ventricular ejection. In this study the changes in shortening in right ventricular free wall and in free wall to septum distance were measured using sonomicrometry. Right ventricular free wall shortening was studied in both outflow and inflow regions in hoop and apex to base axes. Pulmonary artery flow was simultaneously measured using an electromagnetic flowmeter. Right ventricular free wall in the hoop axis was motionless during late ejection. The inflow segment in the hoop axis stopped shortening before all other segments (p less than 0.01). Both outflow and inflow segments in the hoop axis lengthened after the end of shortening. Both shortening of the right ventricular free wall in the apex to base axis and decrease in free wall to septum distance were continued until the end of ejection (p less than 0.01). Compared with the right ventricular outflow segment, the inflow segment shortened for a longer duration. It is concluded that forward flow during late right ventricular ejection is associated with continued shortening of the free wall in the apex to base axis. However, the results of this study do not exclude the role of septal bulge into the right ventricle during late ejection.

Relaxation time constant of isolated rabbit left ventricle.

Experiments were performed on isolated rabbit left ventricles. Controlled ejections during otherwise isovolumic contractions were studied. The time constant of relaxation was defined as the slope of the linear approximation of the ln(P)-t relation over a 40-ms period starting 20 ms after the minimum of the first time derivative of left ventricular pressure (dP/dt) of the isovolumic contraction. Variations in time of ejection, its amplitude, and velocity are applied independently. No direct effect of the variations in time and velocity of the ejection on the time constant of relaxation was found. This is in conflict with the findings of Hori et al. (Circ. Res. 55: 31-38, 1984). The difference is due to the influence of the recovery of pressure directly after the end of ejection in their study. This effect is present especially when ejection was timed to take place late in the contraction phase. The effect of the variation of the amplitude of the ejection on the time constant was similar to the effect of the end-diastolic pressure on the end-diastolic volume. It is concluded that the time constant of relaxation depends linearly on the same processes that are responsible for the height of the end-diastolic pressure.

Angiotensin II excites neurones in cat solitary tract nuclei which are involved in respiration and related reflex activities

In anaesthetized cats, effects of iontophoretic application of angiotensin II were studied in the nuclei of the tractus solitarius. Specifically, its effects were tested on single respiratory neurones, having rhythmic activity related temporally with the phrenic nerve discharge, and on presumed reflex interneurones, which lacked rhythmic activity but responded to stimulation of vagus nerve or superior laryngeal nerve. Angiotensin II (30–100 nA positive current for 30–60 s) excited 8/27 respiratory neurones; 19 were unaffected. Five of 8 reflex interneurones were excited; 3 were unaffected. Excitation consisted of a delayed, slow increase in the rate of firing which continued for about 60–120 s following the end of ejection. These results provide physiological evidence to support the possibility that angiotensin II may be a chemical mediator of synaptic transmission in the nuclei of the tractus solitarii, in pathways related to respiratory control.

Effects of reduced resistive afterload on left ventricular pressure-volume relationship

In seven anesthetized, beta-blocked dogs, we investigated the effects of a reduction in systemic vascular resistance (SVR) on left ventricular (LV) systolic mechanics. LV pressure and volumes (scintigraphic techniques) were measured in base-line condition, after opening one and then two arteriovenous fistulas (AVF). Volume was infused to maintain LV end-systolic pressure (LVESP). Despite a constant ESP, the mean end-systolic volume (LVESV) fell from 42 to 31 ml (P less than 0.025) when the SVR fell from 81 to 48 units (P less than 0.0025), and the LVESV fell further to 24 ml (P less than 0.0025) when the SVR was decreased to 30 units (P less than 0.025). In six similarly prepared dogs, aortic flow was measured, and when resistive afterload decreased, instantaneous flow increased. Since end-diastolic volume was not significantly changed when resistive afterload decreased, instantaneous LV volume decreased despite constant systolic LV pressure. In two of these dogs, LV pressure-volume (PV) trajectories were drawn for the ejection period. When SVR decreased there was a marked leftward shift of the PV trajectory as the end of ejection was approached. It is concluded that at a given contractile state and ventricular pressure, alterations in resistive load directly affect rate and extent of ventricular shortening.

Ejection timing as a major determinant of left ventricular relaxation rate in isolated perfused canine heart.

In the present study, we attempted to test the hypothesis that ejection timing rather than peak left ventricular pressure is a primary determinant of ventricular relaxation rate. In cross-circulated isolated canine hearts instantaneous left ventricular volume was controlled by a servo-pump system. To eliminate the effects of end-systolic and end-diastolic volumes and ejection velocity on left ventricular relaxation rate, these parameters were clamped, and only the ejection timing (onset and end of ejection) was altered, keeping the duration of ejection unchanged. Left ventricular relaxation rate was assessed by time constants of left ventricular pressure decline during the isovolumic relaxation phase calculated by both a semilogarithmic method, assuming that the asymptote is zero, and a best exponential fitting method. In 25 runs, a pair of contractions with ejection timings which differed by 53.1 +/- 2.1 (SE) msec were imposed, while end-systolic and end-diastolic left ventricular volumes and ejection duration were unchanged. All pairs of contractions demonstrated early ejection resulted in significantly (P less than 0.001) slowed relaxation as indicated by a prolongation of the time constants of isovolumic left ventricular pressure decay (delta 4.2 +/- 0.7, sec and delta 15.4 +/- 2.1 msec by semilogarithmic plot and the best exponential fit respectively), although peak left ventricular pressures (104.6 +/- 2.4 mm Hg) were even lower than those (116.6 +/- 2.8 mm Hg) in contractions with later ejection timing. Furthermore, in seven experiments, the heart was allowed to eject at five different timings; onset and end of ejection were progressively delayed in steps of 20 or 30 msec.(ABSTRACT TRUNCATED AT 250 WORDS)

Beat-by-beat control of cardiac output in awake dogs with atrioventricular block.

In dogs with atrioventricular block and implanted ascending aortic flow probes, cardiac output can be controlled on each beta. The procedure is implemented through on-line use of a digital computer. The algorithm has three steps: 1) aortic flow is measured and integrated to give stroke volume; 2) at the end of ejection, the program computes how long the current beat must be to keep cardiac output at a target level; and 3) the ventricle is stimulated at the proper time. Cardiac output can be controlled over a range of 60-110% of normal in a resting dog. This range can be expanded by combining hemorrhage or volume infusion with the control procedure.