Incomplete cardiac vagal blockade with atropine in the anesthetized dog

Summary In dogs in neurolept-anesthesia the successive administration of - and -adrenergic blocking agents and atropine, which should cause the functional equivalent of surgical denervation of the heart, always results in a marked tachycardia. The same is observed in conscious dogs, but not during methoxyflurane anesthesia. Bilateral vagotomy and administration of hexamethonium abolish the tachycardia. These observations demonstrate the presence of a vagally mediated chronotropic effect which becomes manifest when the inhibitory vagal effect is eliminated through blockade of the muscarinic receptors with atropine.     

Characteristics of cardiac period responses to prolonged vagal stimulation in dogs

In 13 dogs anaesthetised with a-chloralose and urethane, and β-blocked with propranolol, the sensitivity of both the left and right cervical vagi was tested with constant-current electrical stimulation at 10 Hz. All 17 active vagi were stimulated for 60 s with supramaximal constant-current pulses at frequencies between 2·5 and 12·5 Hz. In all 17 vagi tested, statistically significant (p<0·0001) linear relationships were found between the vagal stimulus frequency and (i) the steady-state bradycardia, (ii) postvagal tachycardia and (iii) the slope of the response at the onset and termination of stimulation. Postvagal tachycardia was also correlated to the preceding bradycardia and to the slope of the response at the end of stimulation. In all 13 experiments and over 70 responses the steady-state bradycardia was highly correlated (r=0·9382) to the slope at the onset of stimulation. A simple model describing the release, hydrolysis and effect of ACh at the SA node is presented, which predicts the experimental results obtained and gives the average time constant for the hydrolysis of ACh at the cardiac pacemaker as 1·76±0·14 s (p<0·01).     

Influence of body position and pre-exercise activity on cardiac output and oxygen uptake following step changes in exercise intensity

Summary Parallel measurements of breath-by-breath oxygen uptake, cardiac output (Doppler technique), blood pressure (Finapres technique) and heart rate were performed in nine subjects during cycle ergometer exercise in the upright and supine positions. Transients were monitored during power steps starting from and leading to either rest or lower levels of exercise intensity. Oxygen uptake ( ) and cardiac output kinetics were markedly faster than in all other conditions when exercise was started from rest. In contrast to exercise-exercise on steps, the computed arteriovenous difference in O₂ content increased almost immediately in this situation, indicating that not only the additional energy expenditure due to the acceleration of the flywheel but also an increased venous admixture from non-exercising parts of the body contributed to the early kinetics. The off kinetics generally showed a more uniform pattern and did not simply mirror the on transients. The present findings indicate that transitions from rest should be avoided when muscle kinetics are to be assessed on the basis of ₂ measurements at the mouth.     

Revised one-step method for determination of cardiac output

Cardiac output (Q) is a determinant of blood pressure and O(2) delivery and is critical in the maintenance of homeostasis, particularly during environmental stress and exercise. Cardiac output can be determined invasively in patients; however, indirect methods are required for other situations. Soluble gas techniques are widely used to determine (Q). Historically, measurements during a breathhold, prolonged expiration and rebreathing to CO(2) equilibrium have been used; however, with limitations, especially during stress. Farhi and co-workers developed a single-step CO(2) rebreathing method, which was subsequently revised by his group, and has been shown to be reliable and compared closely to direct, invasive measures. V(CO2), P(ACO2), and P(VCO2) are determined during a 12-25s rebreathing, using the appropriate tidal volume, and (Q) is calculated. This method can provide accurate data in laboratory and field experiments during exercise, increased or decreased gravity, water immersion, lower body pressure, head-down tilt, altered ambient pressure or changes in inspired gas composition.     

Continuous determination of cardiac output during exercise by the use of impedance plethysmography

A computer-based system has been developed that enables the continuous measurement of cardiac output at rest as well as during exercise. The respiratory and motion artefacts appearing in the first derivative of the transthoracic impedance change (dZ/dt) were eliminated by adopting an ensemble averaging technique. A sufficiently high correlation was observed between cardiac outputs determined by the impedance and CO₂ rebreathing methods. The system may facilitate the physiological investigation of cardiac function during exercise.     

Postural effect on cardiac output,oxygen uptake and lactate during cycle exercise of varying intensity

Owing to changes in cardiac output, blood volume distribution and the efficacy of the muscle pump, oxygen supply may differ during upright and supine cycle exercise. In the present study we measured, in parallel, circulatory (heart rate, stroke volume, blood pressure) and metabolic parameters (oxygen uptake, lactic acid concentration [1a]) during incremental-exercise tests and at constant power levels ranging from mild to severe exercise. In supine position, cardiac output exceeded the upright values by 1.0-1.5 1 · min^–1 during rest, light ([la] < 2 mmol · 1^–1) and moderate ([la] =2–4 mmol · 1^–1) exercise. At higher exercise intensities the cardiac output in an upright subject approached and eventually slightly exceeded the supine values. For both rest-exercise transitions and large-amplitude steps (W 140 W) the cardiac output kinetics was significantly faster in upright cycling. The metabolic parameters (VO₂ and [la]) showed no simple relationship to the circulatory data. In light to moderate exercise they were unaffected by body position. Only in severe exercise, when cardiac output differences became minimal, could significant influences be observed: with supine body posture, [la] started to rise earlier and maximal power (W=23 W) and exercise duration (64 s) were significantly reduced. However, the maximal [la] value after exercise was identical in both positions. The present findings generally show advantages of upright cycling only for severe exercise. With lower workloads the less effective muscle pump in the supine position appears to be compensated for by the improved central circulatory conditions and local vasodilatation.     

Dynamics of cardiac period responses after prolonged vagal stimulation in the dog

In 12 dogs anesthetised with α-chloralose and urethane, and β-adrenergic blocked with propranolol, the cervical vagi were stimulated for 60 seconds with supramaximal constant current pulses at frequencies between 2.0 and 10 Hz. The time course of the recovery of the cardiac period response, after cessation of vagal stimulation, was analyzed using nonlinear curve fitting techniques. It was found that the recovery phase could be reliably fitted with a function consisting of the sum of up to three exponential terms. The first term has a moderate rate constant of 0.2260±0.0112 S⁻¹ (SE) and is independent of vagal stimulus frequency and the preceding bradycardia. We propose that this term is associated with a recovery from the bradycardia with a rate constant indicative of the reduction of acetylchloline at the pacemaker caused by hydrolysis and washout. The second term has a small rate constant of 0.0499±0.0014 s⁻¹ (SE) and a negative gain. This term describes the time course of the post vagal tachycardia observed at cessation of stimulation. It is also independent of stimulus frequency and the preceding bradycardia. The third term has a large and variable rate constant (range: 0.247–8.01 s⁻¹) and becomes increasingly dominant when the preceding bradycardia is large. We propose that this third component arises from a rapid return of the pacemaker focus to the dominant location prior to vagal stimulation. The mathematical characterisation of this component is important to permit the accurate derivation of the time courses of the remaining two components. Curvilinear relationships exist between the gain parameters for each of the exponential terms and the preceding bradycardia.     

Reliability of echocardiography in assessing cardiac output

Summary Because of the potential benefits from a noninvasive technique in assessing cardiac output, we compared cardiac output estimates from left ventricular echocardiograms with results obtained simultaneously by a standard technique, dye dilution in 10 healthy normal volunteers. During rest, cardiac outputs by echocardiographic and dye dilution techniques were reproducible and not significantly different. Increases in cardiac output produced by intravenous infusion of isoproterenol (15 ng/kg/min for 4 min) were accurately estimated by echocardiography in subjects whose stroke volume increased less than 40%, but were significantly underestimated when stroke volume increased more than 40%. Decreased cardiac output produced by intravenous propranolol (0.2 mg/kg) was comparable by both methods. Although echocardiography accurately estimated mean cardiac output for the group it over- or underestimated cardiac output in individual subjects. We propose that echocardiography can reliably estimate cardiac output in groups at rest and when stroke volume changes less than 40%.This study was supported in part by grants from the Michigan Heart Association     

Non-invasive assessment of cardiac output and stroke volume in patients during exercise

Summary A one-step CO₂ rebreathing method for the determination of cardiac output and stroke volume (SV) has been evaluated by comparison with the direct Fick technique during recumbent exercise (10–90 W) in 13 patients. In an initial analysis, the influence of different rebreathing times and of correction for haemoglobin concentration was studied. The best correlation with the direct Fick technique was obtained with the longest analysis time, i. e. 21 s, and correction for variations in haemoglobin concentration further improved the correlation. Consequently, an analysis time of 21 s and correction for haemoglobin have been used. At low cardiac outputs, the CO₂-rebreathing method overestimated the flow compared to the Fick technique. The correlation between the methods, however, was so good that a valid estimate of cardiac output could be obtained from the CO₂ rebreathing method with appropriate corrections (Cardiac output, CO₂ method=2.7+0.77. Cardiac output, Fick; r=0.91; Residual Standard deviation (SD res) =0.77 l · min⁻¹). Stroke volumes measured with the CO₂ rebreathing method did not differ significantly from those obtained with the direct Fick technique, although there was a tendency to overestimate stroke volume with the CO₂ rebreathing method (SV, CO₂ method=12+0.89 · SV, Fick; r=0.82; SD res=11 ml).     

Reliability of the cardiac output measurement with the indirect Fick-principle for CO2 during exercise

Cardiac output measurements were performed during 50 exercise tests in 16 normal subjects employing the indirect Fick principle for CO₂. During sub-maximal steady state exercise the plateau CO₂ tension ( ) was estimated with a rebreathing procedure. The mixed venous CO₂ tension ( ) was calculated by subtracting the alveolocapillary CO₂ tension difference from the . Compared with data from the literature the most valid calculation of the cardiac output was obtained by using the . Cardiac output values, calculated via the turned out to be too low.The reproducibility was tested by repitition of 18 exercise tests at least after 5 days. The relative standard error of a single observation was 4.1% for the cardiac output, which was found to be as good as that of invasive measurements.     

Influence of different respiratory maneuvers on exercise-induced cardiac vagal inhibition

Physical exercise inhibits cardiac vagal activity. To study the relationship between heart rate (HR) and respiratory pattern, we applied the 4-s exercise test (4sET) and measured cardiac vagal index (CVI) in 30 healthy subjects who served as their own controls, using the standard plus three additional variations, essentially respiratory, of the original protocol: (a) a maximum inspiratory apnea of 16 s, of which 8 s were in the pre-exercise phase (4sET_insp); (b) free respiratory pattern (4sET_unc); and (c) maximum expiratory apnea of 12 s (4sET_exp). The respective results were expressed by the following CVIs: CVI_insp, CVI_unc and CVI_exp. CVI was determined in a continuous digital ECG recording through a specific ratio of two RR interval durations. The results [(mean ± SEM)] for the four different maneuvers were as follows: CVI (1.56 ± 0.05), CVI_insp (1.55 ± 0.05), CVI_unc (1.63 ± 0.05) and CVI_exp (1.37 ± 0.02). ANOVA-Bonferroni significant differences were only found between CVI_exp and CVI_insp (P = 0.009), CVI_unc (P < 0.001) and CVI (P = 0.003). Dividing our sample in terciles according to CVI values, those with lower CVI, showed an attenuation of biphasic HR response after a 15 s maximum inspiratory apnea. We conclude that cardiac vagal reflex seems to be influencing the biphasic HR response modulation after a 12 s inspiratory apnea as described in the original protocol of 4sET, and this appears to be the option that best discriminates the cardiac vagal reflex, with less variability in the maneuvers when subjects are divided in terciles.     

Effects of local nerve cooling on conduction in vagal fibres shed light upon respiratory reflexes in the rabbit

In ten vagus nerves the effect of local cooling on the compound action potential was studied in the temperature range of 34 to 0 °C in spontaneously breathing, anaesthetized rabbits. The mean temperature at which the myelinated (A) fibres were completely blocked, was 10.2±2.4 °C (mean ± S.D.). In nine nerves, local vagus cooling to 0 °C failed to block all non-myelinated (C) fibres. In one nerve, total blocking occurred at 2.0 °C. We conclude that in the rabbit, the earlier found increase in tonic activity of the diaphragm following lung inflation or deflation during bilateral local vagus cooling to a temperature between 8 and 0 °C is due to afferent impulses in vagal C fibres.     

Psychiatric disorders and cardiac anxiety in exercising and sedentary coronary artery disease patients: a case-control study

Regular physical exercise has been shown to favorably influence mood and anxiety; however, there are few studies regarding psychiatric aspects of physically active patients with coronary artery disease (CAD). The objective of the present study was to compare the prevalence of psychiatric disorders and cardiac anxiety in sedentary and exercising CAD patients. A total sample of 119 CAD patients (74 men) were enrolled in a case-control study. The subjects were interviewed to identify psychiatric disorders and responded to the Cardiac Anxiety Questionnaire. In the exercise group (N = 60), there was a lower prevalence (45 vs 81%; P < 0.001) of at least one psychiatric diagnosis, as well as multiple comorbidities, when compared to the sedentary group (N = 59). Considering the Cardiac Anxiety Questionnaire, sedentary patients presented higher scores compared to exercisers (mean ± SEM = 55.8 ± 1.9 vs 37.3 ± 1.6; P < 0.001). In a regression model, to be attending a medically supervised exercise program presented a relevant potential for a 35% reduction in cardiac anxiety. CAD patients regularly attending an exercise program presented less current psychiatric diagnoses and multiple mental-related comorbidities and lower scores of cardiac anxiety. These salutary mental effects add to the already known health benefits of exercise for CAD patients.     

Influence of combined exercise and gravity transients and apnea on hemodynamics

Hemodynamic responses to combined heavy dynamic leg exercise (hiP), breath holding (BH) and gravity-induced blood volume shifts direction were studied. Thirteen subjects were studied at normal gravity and 12 during parabolic flight, performing 20 s hiP or combined hiP&BH (stimulus period) from a baseline of 30 W at normal gravity (1 G_z+). Heart rate and mean arterial pressure responses to BH were similar between gravity conditions, but stroke volume (SV) differed markedly between gravity conditions: at 1 G_z+ SV was higher [112 ± 16 ml (mean ± SD)] during BH, than during eupnea [101 ± 17 ml (P < 0.05, N = 13)]. In weightlessness the corresponding SV values were 105 ± 16 and 127 ± 20 ml, respectively (P < 0.05, N = 6). Transthoracic electrical conductance (TTC) was used as index for intrathoracic volume. TTC fell significantly during BH. This decrease was attenuated in weightlessness. It is concluded that the transient microgravity temporarily reduces the efficiency of the muscle pump so that the deep inspiration at the onset of the high-intensity exercise and breath-hold period cannot augment venous return as it could during identical manoeuvres at normal gravity.     

Relationship between cardiac output and oxygen uptake at the onset of exercise

Summary The purpose of the present study was to assess the relationship between the rapidity of increased gas exchange (i.e. oxygen uptake ) and increased cardiac output ( ) during the transient phase following the onset of exercise. Five healthy male subjects performed multiple rest-exercise or light exercise (25 W)-exercise transitions on an electrically braked ergometer at exercise intensities of 50, 75, or 100 W for 6 min, respectively. Each transition was performed at least eight times for each load in random order. The was obtained by a breath-by-breath method, and was measured by an impedance method during normal breathing, using an ensemble average. On transitions from rest to exercise, rapidly increased during phase I with time constants of 6.8–7.3 s. The also showed a similar rapid increment with time constants of 6.0–6.8 s with an apparent increase in stroke volume (SV). In this phase I, increased to about 29.7%–34.1% of the steady-state value and increased to about 58.3%–87.0%. Thereafter, some 20 s after the onset of exercise a mono-exponential increase to steady-state occurred both in and with time constants of 26.7–32.3 and 23.7–34.4 s, respectively. The insignificant difference between and time constants in phase I and the abrupt increase in both and SV at the onset of exercise from rest provided further evidence for a cardiodynamic contribution to following the onset of exercise from rest.     

Selective brain cooling in resting and exercising Norwegian reindeer (Rangifer tarandus tarandus)

The threshold body core temperature for selective brain cooling (SBC) as well as the slope of brain cooling were determined in three Norwegian reindeer (Rangifer tarandus tarandus) during rest and during exercise. Brain temperature was measured in the hypothalamus (T_hypo) and blood temperature (T_blood) was measured either in the right carotid artery or in a few cases in the right atrium of the heart. During rest the animals were subjected to ramp-like increases of T_blood by means of a thermostatically controlled water circulated heat exchanger (HE) introduced into the rumen via a chronically implanted rumen cannula. During exercise the animals ran on a treadmill at a speed of between 5.5–8.0 km hr^-1 and a slope of 13.5° for periods of 30–60 min. The elevation of T_blood during both rest and exercise resulted in significant amounts of SBC. The mean threshold for SBC (T_hypo= T_blood) during rest was 38.7°C. The threshold for SBC was elevated significantly to 39.5°C during exercise. The mean slope of SBC (increase of SBC per degree increase of T_blood) was 0.82 both during rest and exercise.     

The importance of blood resistivity in the measurement of cardiac output by the thoracic impedance method

Twenty simultaneous pairs of cardiac output values from patients who did not have valvular abnormalities were obtained by the radioisotope method and the electrical-impedance method of Kubicek et al. (1966). If a standard value of 150Ω-cm was assumed for the resistivity of each patient's blood, the mean value for the impedance cardiac output was 14·5% high compared with the mean radioisotope value. In this study the patient's haematocrits ranged from 20 to 48%. Inserting the appropriate value of the resistivity for each patient into the stroke volume equation of Kubicek from the data of Geddes and Sadler (1973) made the mean impedance value 10·3% low compared with the mean isotope value. The use of our measured resistivity data made the mean impedance cardiac output value 21·5% lower than the mean isotope value. The correlation coefficient between the impedance and isotope techniques was 0·61 for the standard value of resistivity of 150Ω-cm. Using the resistivity data of Geddes and Sadler (1973) the correlation became 0·87, and with our data it was 0·88.