Dynamic right and left ventricular interactions in the rabbit: simultaneous measurement of ventricular pressure-volume loops.

PURPOSE: This study was performed to characterize the dynamic factors determining ventricular interdependence in an open-pericardium intact animal model. MATERIALS AND METHODS: Simultaneous measures of right ventricular (RV) and left ventricular (LV) pressures and volumes in 6 urethane-anesthetized open-chested, open-pericardium rabbits. RV and LV V were calculated every 2 milliseconds. Measurements were made at initial baseline blood volume, and again after two infusions of 20 mL/kg isoconductive colloid solution. At each blood volume level, partial aortic (AO), pulmonary artery (PAO), and inferior vena caval (IVC) occlusions were performed. Biventricular diastolic compliance and end-systolic elastance were calculated from these data. RESULTS: Baseline end-diastolic (ED) and end-systolic (ES) V were 3.29 +/- 0.55 and 2.43 +/- 0.33 mL (mean +/- SD) for the LV, and 3.38 +/- 1.56 and 2.84 +/- 1.36 mL for the RV, respectively. AO increased all LV pressure and volume (P < .05) but did not alter RV ED volume (2.85 +/- 1.20 mL) or ED pressure (3.3 +/- 2.0 to 3.6 +/- 2.1 mm Hg). PAO increased RV ES pressure (P < .05) but did not alter RV ED volume, ED pressure, or ES volume, although it decreased LV ED volume (2.82 +/- 0.59, P < .05). AO also immediately increased end-systolic RV elastance to a value greater than that defined by IVC (7.9 +/- 4.4 to 10.9 +/- 6.6 mm Hg/mL, P < .05). Intravascular volume expansion though increasing baseline pressure and volume, did not alter qualitatively biventricular responses to AO, PA, or IVC. CONCLUSION: Ventricular interdependence has both systolic and diastolic components that have differing directional effects. In the pericardectomized rabbit, increases in RV ED volume decrease LV ED volume by decreasing LV diastolic compliance, but do not alter LV systolic function. Whereas, increases in LV ED volume decrease RV ES volume resulting in an increase in RV maximal elastance, but minimally alter RV diastolic function.

Autonomic control of skin microvessels: assessment by power spectrum of photoplethysmographic waves.

1. Although it is well known that the microvessels of the skin constantly undergo spontaneous variations in volume, the significance of these rhythmic changes remains uncertain. 2. In 10 healthy males and in 15 patients in intensive care, we assessed the origin of the autonomic influences on spontaneous fluctuations in the microcirculation of the skin, obtained by an infra-red photoplethysmographic device; we used spectral analysis techniques to compare these fluctuations (which were recorded simultaneously in two sites) with those of blood pressure, in order to test the presence of autonomic control of any synchronous fluctuations in these different measurements from the cardiovascular system. In order to minimize mechanical fluctuations caused by occasional slow breaths, rather than nervously mediated fluctuations in skin blood flow, respiration was controlled at 15 breaths/min (0.25 Hz). 3. Spontaneous infra-red photoplethysmographic fluctuations were observed in different body areas (left index finger and left ear lobe, right and left index finger), and all were evident at 0.1 Hz, as well as respiration-related components at 0.25 Hz. Active standing increased the power of the 0.1 Hz fluctuations (sympathetic activity) in both blood pressure (from 62.7 +/- 7.1 to 79.2 +/- 3.7 normalized units, P < 0.05) and IRP (finger: from 68.5 +/- 6.4 to 86.9 +/- 3.4 normalized units, P < 0.05; ear: from 59.0 +/- 5.9 to 88.1 +/- 2.0, P < 0.01). There was a high (> 0.5) coherence between the fluctuations obtained in blood pressure, in IRP signals obtained simultaneously at the finger and at the ear, and in R-R interval. This synchronization between the oscillations in all these signals, which were unrelated to the respiratory frequency or to the pulse rate, suggests a common neural, non-local origin. The phase between IRP and blood pressure was positive in the 0.1 Hz region (+1.65 +/- 0.41 radians, i.e. IRP was leading blood pressure, showing that 0.1 Hz fluctuations were not passively transmitted to the skin microvessels from large arteries) and negative in the 0.25 Hz region (-0.74 +/- 0.19 radians, P < 0.01 compared with phase in the 0.1 Hz region, i.e. IRP was lagging behind blood pressure, suggesting possible passive transmission to the skin microvessels of blood pressure fluctuations caused by respiration). Fluctuations at lower frequency were observed in all IRP recordings, suggesting a local origin for these. Intra-arterial and IRP fluctuations were compared in the 15 intensive care patients and gave similar results. 4. The skin microcirculation is thus not only under local control, but also reflects changes in sympathetic activity; the effect of these changes on the skin microcirculation can be easily evaluated by the spectral analysis of the IRP signal obtained simultaneously in multiple areas, in conjunction with the spectra of R-R interval and blood pressure.

Autonomic and ventilatory components of heart rate and blood pressure variability in freely behaving rats.

The relative role of parasympathetic, sympathetic, and ventilatory influences in the genesis of blood pressure and R-R interval variability is controversial. In 13 freely behaving WKY rats instrumented with venous and arterial catheters and chest electrodes, mean arterial pressure (MAP, mmHg), R-R interval (ms), and respiratory fluctuations were monitored for 90 min in the control condition and after intravenous atropine (0.75 mg/kg) and/or propranolol (1 mg/kg). Spectral power (pw) in the 0.25- to 0.75-Hz (midfrequency, MF) and the 0.75- to 3.0-Hz (high-frequency, HF, respiratory-synchronous) bands was computed in sequences of 400 heartbeats by use of a combined autoregressive analysis. Atropine reduced but did not abolish HF R-R interval pw (from 1.73 +/- 0.50 to 0.39 +/- 0.27 ms2, P < 0.01) and halved HF MAP pw (from 0.41 +/- 0.30 to 0.21 +/- 0.12 mmHg2, P < 0.05), whereas propranolol did not affect HF pw of the R-R interval or MAP. Propranolol also failed to significantly modify MF R-R interval pw (from 0.48 +/- 0.44 to 0.40 +/- 0.34 ms2, P = NS) or MF MAP pw (from 0.54 +/- 0.39 to 0.42 +/- 0.20 mmHg2, P = NS), whereas atropine virtually abolished MF R-R interval pw (from 0.48 +/- 0.44 to 0.01 +/- 0.01 ms2, P < 0.01) and also significantly reduced MF MAP pw (from 0.54 +/- 0.39 to 0.33 +/- 0.24 mmHg2, P < 0.01). The effects of combined blockade were similar to those of atropine alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of respiratory sinus arrhythmia in the vagotomized rabbit.

After cardiac denervation, a small-amplitude respiratory sinus arrhythmia (RSA) has been described in animals and humans. Its mechanical and chemical determinants were investigated in 19 urethan-anesthetized, vagotomized, and mechanically ventilated rabbits. We measured the influence on RSA of arterial blood gases, beta-adrenergic blockade, and phasic and steady changes in right atrial pressure (RAP) induced by changes in tidal volume (VT, 20, 40, 60 ml), respiratory frequency (RF, 10, 20, 30 cycles/min), and dextran-induced RAP increases. Phasic changes in RAP during each recording were quantified as standard deviation of the first derivative of the RAP signal (dRAP) as a measure of magnitude of variations of the rate of change due to respiration. RSA was assessed by combined autoregressive power spectral analysis of R-R interval and respiration on sequences of 256 heart-beats. Despite vagotomy, RSA was present in all recordings in all animals. During room air breathing, RSA changes were dependent on RF and VT (P < 0.025 and P < 0.001, respectively) and correlated with dRAP (P < 0.001) and arterial PO2 (P < 0.001). beta-Adrenergic blockade did not change the amplitude of this residual RSA or its dependence on ventilatory mechanics. Dextran-induced increase in mean RAP from 2.9 to 11.9 mmHg did not modify RSA or dRAP. During 100% O2 inhalation, RSA changes were no longer significantly linked to RF and VT, and also the correlation of RSA with dRAP was reduced (P < 0.05). Changing the arterial PCO2 from 28 to 79 mmHg (induced by increasing dead space at fixed ventilation) did not modify RSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous monitoring of right ventricular volume changes using a conductance catheter in the rabbit.

To assess the reliability of conductance (G) catheter for evaluating right ventricular (RV) volume changes, a miniature (3.5F) six-electrode catheter was developed and tested in 11 New Zealand rabbit hearts. In five animals the heart was excised; in six it was left in the thorax. RV conductance was recorded while the RV was filled with blood in 0.25-ml steps at different left ventricular (LV) volumes. Linear correlation of measured conductance vs. reference volumes was computed. RV conductance was highly correlated with reference volume [correlation coefficient (r) ranging from 0.991 to 0.999]. Slope of regression lines was not significantly affected by LV volume variations in 1-ml steps or by acute conductance changes of structures surrounding the heart, whereas the intercept was affected only by the 0- to 1-ml LV volume change. In four rabbits, RV conductance changes during a cardiac cycle [stroke volume- (SV) G] were compared in vivo with electromagnetic flow probe-derived estimates of SV (SVem) as stroke volume was varied by graded inferior vena caval occlusion. SV-G correlated well with SVem (r ranging from 0.92 to 0.96). This correlation persisted after the thorax was filled with saline; however, significant differences were found in individual slopes (P < 0.001). These results show that the conductance catheter has a potential to reliably monitor in vivo relative RV volume changes in small-animal hearts.

[The evaluation of the end-ejection pressure-length relation as an index of regional contractility]. / Validazione della relazione pressione-lunghezza a fine eiezione quale indice di contrattilità regionale.

Although end-systolic pressure-length relationship (ESPLR) is now widely used as a regional substitute for the end-systolic pressure-volume relationship, there are some reservations about its use as an index of systolic performance. This study aimed at assessing whether by using end-ejection (zero aortic flow) as a definition of end-systole, ESPLR can be used to characterize myocardial performance independent of load, and if the choice of the region where to implant the sonomicrometers is critical. Ten anaesthetized dogs (16 +/- 2 kg) were instrumented with a left ventricular (LV) pressure micromanometer and an aortic flow probe. Sonomicrometers were implanted in the apical (L1) and the mid-ventricular (L2) regions of the anterior LV wall, and in the basal region of the lateral wall (L3). End-systolic pressure-length relationships were obtained during acute preload reduction induced by the inflation of a vena caval balloon. This evaluation was repeated after increasing end-diastolic pressure to 14-18 mmHg (delta PL), after increasing systolic pressure by 15 (delta P-I) and 25 mmHg (delta P-II) with graded descending aorta occlusion, and during dobutamine infusions at 2.5 (Db 2.5) and 5 micrograms/kg/min (Db5). End-systolic pressure-length relationships (r > 0.97; pressure range: 70-100 mmHg) were characterized by their slopes (Ees), the extrapolated intercept at zero pressure (L0) and the values of segment length at a pressure of 75 (L75) and 100 mmHg (L100). In all the myocardial regions studied by sonomicrometry, the increments in preload and afterload did not significantly shift ESPLR.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function.

BACKGROUND: Many secondary abnormalities in chronic heart failure (CHF) may reflect physical deconditioning. There has been no prospective, controlled study of the effects of physical training on hemodynamics and autonomic function in CHF. METHODS AND RESULTS: In a controlled crossover trial of 8 weeks of exercise training, 17 men with stable moderate to severe CHF (age, 61.8 +/- 1.5 years; left ventricular ejection fraction, 19.6 +/- 2.3%), increased exercise tolerance (13.9 +/- 1.0 to 16.5 +/- 1.0 minutes, p less than 0.001), and peak oxygen uptake (13.2 +/- 0.9 to 15.6 +/- 1.0 ml/kg/min, p less than 0.01) significantly compared with controls. Training increased cardiac output at submaximal (5.9-6.7 l/min, p less than 0.05) and peak exercise (6.3-7.1 l/min, p less than 0.05), with a significant reduction in systemic vascular resistance. Training reduced minute ventilation and the slope relating minute ventilation to carbon dioxide production (-10.5%, p less than 0.05). Sympathovagal balance was altered by physical training when assessed by three methods: 1) RR variability (+19.2%, p less than 0.05); 2) autoregressive power spectral analysis of the resting ECG divided into low-frequency (-21.2%, p less than 0.01) and high-frequency (+51.3%, p less than 0.05) components; and 3) whole-body radiolabeled norepinephrine spillover (-16%, p less than 0.05). These measurements all showed a significant shift away from sympathetic toward enhanced vagal activity after training. CONCLUSIONS: Carefully selected patients with moderate to severe CHF can achieve significant, worthwhile improvements with exercise training. Physical deconditioning may be partly responsible for some of the associated abnormalities and exercise limitation of CHF, including abnormalities in autonomic balance.

[The variability of the heart rate, arterial pressure and peripheral circulation as the indices of autonomic control in essential hypertension]. / Variabilità della frequenza cardiaca, della pressione arteriosa e del circolo periferico quale indice del controllo autonomico nell'ipertensione essenziale.

In recent years the influence of autonomic nervous system on cardiac rhythm and blood pressure has been increasingly studied by analysis of cardiovascular fluctuations, particularly in diabetic and normal persons under various physiologic conditions, while still few data exist on essential hypertension. To characterize the autonomic cardiovascular control in essential hypertension we studied 22 untreated hypertensives, diagnosed within 1 year (mean age 43 +/- 2 years, mean +/- SEM) and 16 age-matched normotensives. Recordings of RR interval, breathing activity, noninvasive blood pressure (Finapres) and skin arteriolar flow (infrared photoplethysmogram) were obtained while in supine position and after sympathetic activation induced by passive transition to upright posture (tilting table). Autoregressive power spectral analysis was then carried out, and low- (0.03-0.15 Hz, LF) and high-frequency fluctuations (0.15-0.35 Hz, HF) were measured. LF and HF have been considered as markers of sympathetic and parasympathetic activity on the heart, respectively, and as markers of sympathetic and mechanic chest activity on the circulation, respectively. In supine position both cardiac and vascular variability were similar in both hypertensive and normotensive groups. After tilting however the increase in the sympathetic component of cardiac variability was blunted in hypertensives with respect to normotensives (hypertensives LFnu from 43.6 +/- 4.7 nu to 59.4 +/- 5.1 nu, p less than 0.005; normotensives LFnu from 36.9 +/- 3.3 nu to 83.4 +/- 2.6 nu, p less than 0.001), the increase in LFnu being statistically (p less than 0.001) reduced in the hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Time course of pressure and flow in ascending aorta during ejection.

To analyze aortic flow and pressure relationships, 10 closed-chest anaesthetised dogs were instrumented with electromagnetic aortic flow probes and micromanometers in the left ventricle and ascending aorta. Left ventricular ejection time was divided into: time to peak flow (T1) (both pressure and flow rising), peak flow to peak pressure time (T2) (pressure rising, flow decreasing), and peak pressure to dicrotic notch time (T3) (pressure and flow both decreasing). These time intervals were expressed as percent of total ejection time. Load-active interventions rose markedly T2 (from 4.2 +/- 5.5 to 19.4 +/- 3.5 after phenylephrine (p less than 0.02); from 4.2 +/- 6.5 to 21.2 +/- 5.3 after dextran (p less than 0.02)). Conversely, dobutamine reduced T2 from 4.4 +/- 5.9 to -2.5 +/- 6.5 (p less than 0.05). Thus, during load-active interventions aortic pressure increases for a longer T2 time although forward flow is decreasing, as a result of higher aortic elastic recoil during ejection. Conversely, beta 1-adrenergic stimulation significantly shortens T2. Dynamic pressure-flow relationship is thus continuously changing during ejection. T2 seems to be inversely related to the efficiency of left ventricular ejection dynamics.

Evidence for an intrinsic mechanism regulating heart rate variability in the transplanted and the intact heart during submaximal dynamic exercise?

STUDY OBJECTIVE: The aim was to assess the changes in sympatho-vagal balance which occur with exercise. DESIGN: The power spectrum of RR interval fluctuations (low frequency [LF] and high frequency components [HF]) was determined before, during, and after graded work load exercise on a cycle ergometer. The power spectrum of the respiratory signal, oxygen consumption, and respiratory volumes were also evaluated. In all subjects HF was considered to be an index of respiratory sinus arrhythmia. In normal subjects HF and LF were considered to be indices of relative vagal and sympathetic activity, respectively, whereas in heart transplant subjects HF was considered as a respiratory modulation of the intrinsic heart rate, and not dependent on autonomic tone. Heart rate variability was evaluated as RR interval variance. SUBJECTS: 15 normal subjects (six trained cyclists and nine healthy sedentary subjects) and six orthotopic heart transplant recipients took part in the study. MEASUREMENTS AND MAIN RESULTS: During the first part of exercise, heart rate increased, RR interval variance decreased, HF decreased, and the relative amount of LF increased both in sedentary and athletic subjects, suggesting a relative increase in sympathetic tone. However, when approaching peak exercise, while heart rate further increased and the variance slightly decreased, the relative proportion of LF decreased and HF proportionally increased. At peak exercise HF accounted for 99.9% of heart rate variability in athletic subjects and for 88.9% in sedentary subjects (p less than 0.001 v baseline and v LF in both groups). In heart transplant subjects both the variance and the HF increased from the beginning of exercise (p less than 0.05), and showed a direct correlation with ventilatory variables and an inverse correlation with heart rate (r = 0.794, p less than 0.001, multiple regression analysis). No measurable LF components could be obtained in these subjects. During recovery, while the heart rate decreased and the RR interval variance increased, there was a relative increase in LF and a relative decrease in HF in normal subjects (either sedentary or athletic). Similarly, in heart transplant subjects, there was a decrease in HF during recovery. Thus the increase in HF at peak exercise in normal subjects contrasts with all the other data which suggest a prevalence in sympathetic tone during the entire exercise and the early recovery period, but appears similar to the increase in HF observed in heart transplant subjects due to the effect of increased ventilation during exercise. CONCLUSIONS: These findings suggest that at peak exercise a non-autonomic mechanism, possibly intrinsic to the heart muscle, may determine heart rate fluctuations in synchrony with ventilation in the intact as well as in the denervated human heart.

Measuring left ventricular dimensions by conductance catheter in the rabbit.

A miniaturized (3.5 F), six-electrode conductance catheter was tested in 18 anaesthetized adult rabbits (weight 3.8-4.6 kg, ethylurethane 2.5 g kg-1). In eight animals, the reference stroke volume (ref-SV) was obtained by an electromagnetic flow probe, while reference end-diastolic volume (ref-LVEDV) was computed by dividing ref-SV by undamped thermal dilution ejection fraction (ref-EF) estimates. Comparisons with conductance indexes (z-SV, z-LVEDV and z-EF) were made at baseline, subsequent levels of graded haemorrhage and reinfusion state. In 10 animals intraventricular segmental conductance was compared with echocardiographic left ventricular cross-section (5 MHz short-focus probe), in the basal state and during acute left ventricular volume changes generated by inferior vena cava balloon occlusion. In each experiment, parallel conductance due to the tissues surrounding the left ventricle (Gp) was determined by infusing a 5M NaCl solution bolus into the right ventricle. Linear regression analysis showed fairly good correlations between z-SV, z-LVEDV and z-EF and reference indexes (r = 0.84, r = 0.83, and r = 0.72, respectively; P less than 0.001 in all cases). A linear regression analysis from 17 interventions (inferior vena cava balloon occlusion) showed a good correlation between left ventricular echocardiographic cross-sectional area and conductance, and higher correlation coefficients, r ranging from 0.870 to 0.986 were obtained from continuously sampled conductance and echographic measurements. Parallel conductance Gp was correlated (r = 0.807, P less than 0.01) with the intercept of the regression line of echographic vs conductance data. The determination of Gp thus improved the accuracy of the left ventricular dimension estimate. These results add further evidence for the possibility of continuous monitoring of left ventricular dimension by means of a conductance catheter, and demonstrate the feasibility of such studies on small experimental animals.

[Factors influencing left ventricular function in arterial hypertension]. / Fattori che influenzano la funzione ventricolare sinistra nella ipertensione arteriosa.

Using digitized M-mode echograms we evaluated the role of preload, afterload, inotropic state and left ventricular (LV) mass on LV systolic and diastolic function in 2 groups of hypertensive patients: Group 1: 25 subjects (18 men, mean age 48 +/- 6 years) with normal LV mass (less than 230 g); Group 2: 25 subjects (20 men, mean age 50 +/- 8 years) with LV hypertrophy (wall hypertrophy with normal LV diameter). As control group, we evaluated 50 normal subjects, matched for age, sex and body surface area with hypertensives. LV mass was significantly (p less than 0.001) higher as respect to normals also in hypertensives with normal LV mass; indexes of LV systolic and diastolic function were similar in normals and in hypertensives with normal LV mass and significantly lower in subjects with LV hypertrophy. The end-systolic wall stress was not significantly different in the 2 groups of hypertensives. We evaluated the relative role of preload (end-diastolic LV diameter), afterload (end-systolic wall stress) inotropic state (systolic arterial pressure/end-systolic LV diameter) and LV mass on LV systolic and diastolic function using multiple regression analysis. As regards LV systolic function, the major determinant was the systolic pressure/end-systolic diameter ratio in normals, the end-systolic stress in hypertensives. As regards LV diastolic function, the major determinant was end-systolic stress in normals and hypertensives with normal LV mass, LV mass in hypertensives with myocardial hypertrophy. Preload seems not to influence LV function in normals and in hypertensives with normal LV diastolic diameter. The major determinant of LV systolic function is the inotropic state in normals and the afterload in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute haemodynamic effects of ibopamine and dopamine on isovolumic relaxation.

The effects of intraduodenal ibopamine (a new orally active inotropic agent claimed to have haemodynamic effects similar to dopamine) on isovolumic relaxation were monitored for 90 min in eight closed-chest anaesthetized dogs. Dopamine and epinine (ibopamine active metabolite) were also infused at graded doses. After 15 min, ibopamine (12 mg/kg) shortened the time constant of isovolumic relaxation, and increased stroke volume and mean aortic pressure. Peak positive dP/dt increased significantly only 10 min later. Heart rate did not change. Dopamine (10 micrograms/kg per min) similarly reduced the time constant, and increased stroke volume, mean aortic pressure, peak positive dP/dt and heart rate. Epinine (10 micrograms/kg per min) caused similar changes in peak positive dP/dt, stroke volume, mean aortic pressure, and accelerated time constant without raising the heart rate. Ibopamine and epinine therefore significantly improved the isovolumic relaxation phase, like dopamine, without however affecting the heart rate.

Fast microcomputer-based multipurpose filtering routine.

In order to perform high-speed digital signal filtering or differentiating at reduced costs, we developed a 68000 assembler routine which runs on a 68000 coprocessor card in an Apple II computer. It achieves a remarkable saving of computational time and may also be used directly with any 68000-based microcomputer.