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.atropine alone. It is concluded that, in the unanesthetized rat, efferent vagal influences are responsible for a large fraction of HF R-R interval power, but a sizable amount of such fluctuations persists after atropine and has a ventilatory, rather than an efferent vagal, origin. Vagal influences also contribute to HF MAP power. Vagal (but not sympathetic) influences are important determinants of MF R-R interval fluctuations and also contribute significantly to MF MAP fluctuations

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. Thus, after urethan anesthesia and vagotomy, RSA persists and seems to be proportional to changes in ventilation through phasic (rather than steady) changes in RAP, presumably by the increase in mechanical stretch imposed on the sinoatrial node by inspiratory increases in venous return. One hundred percent 02, but not raised arterial PCO2, consistently reduced these mechanically induced changes in RSA by an unknown mechanism

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

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

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

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

Experience from controlled trials of physical training in chronic heart failure. Protocol and patient factors in effectiveness in the improvement in exercise tolerance. European Heart Failure Training Group

BACKGROUND: Beneficial effects of physical training on exercise tolerance, autonomic and skeletal muscle function and limb blood flow have been demonstrated in chronic heart failure. Because this rehabilitation is expensive, may involve risk, and has unknown effects on prognosis, the possibility of predicting benefit on the basis of individual patient data is intriguing. The most suitable exercise training programme has not yet been established. METHODS AND RESULTS: We reviewed the progress of 134 stable heart failure patients studied in randomized controlled trials of physical training. A significant training effect (+13% peak oxygen consumption, +17% exercise duration) was associated with improved autonomic indices (resting catecholamines and hormones, heart rate variability), without significant side-effects. No ventilatory, haemodynamic, autonomic or clinical factor at baseline was a predictor of outcome. Similar beneficial effects were observed in both male and female patients. The improvement in oxygen consumption after 16 weeks training was higher than after 6 weeks (+2.6 +/- 3.0 vs +0.3 +/- 3.1 ml.kg.min-1, P < 0.05). The combination of cycle ergometer with calisthenic exercises was more beneficial than cycle ergometer alone (+2.7 +/- 4.2 vs 1.2 +/- 2.0 ml.kg.min-1, P < 0.01). The presence of nonsustained ventricular tachycardia did not preclude a training effect. Patients older than 70 years were able to train, although less effectively than the younger ones. No difference in exercise gain was observed whether the patients trained in the hospital or at home. CONCLUSION: The positive effects of physical rehabilitation in chronic stable heart failure patients are confirmed. No baseline patient factor was significantly correlated with outcome. A tailored, moderate, home-based, combined cycle ergometer, plus calisthenic exercise training seems safe and beneficial in a large cohort of heart failure patients, with similar benefits in a variety of conditions and different hospital settings