Intrinsic Heart Rate Research Articles

Endurance exercise training has a minimal effect on resting heart rate: the HERITAGE study

This study determined the effects of a 20-wk endurance training program (The HERITAGE Family Study) on resting heart rate (HRrest). HRrest was obtained on a sample of 26 men and 21 women during sleep; during resting metabolic rate and resting blood pressure measurement periods in the early morning following a 12-h fast and 24-h post-exercise; and at rest prior to a maximal bout of exercise. Following training, the subjects exhibited a 16.0 +/- 9.4% (mean +/- SD) increase in VO2max (P < 0.05), but the HRrest for each of the resting conditions was decreased by only 1.9 to 3.4 bpm (P < 0.05), or an average across the three conditions of 2.7 bpm. In a larger sample of 253 HERITAGE subjects, HRrest obtained only at the time of the resting blood pressure measurement decreased by only 2.6 bpm, while VO2max increased 17.7 +/- 10.0%. It is concluded that there is a significant, but small, decrease in resting heart rate as a result of 20 wk of moderate- to high-intensity endurance training; which suggests a minimal alteration in either, or both, intrinsic heart rate and autonomic control of HRrest.

Intravenous instrumentation alters the autonomic state in humans.

Intravascular instrumentation may induce syncope or presyncope. It is not known whether asymptomatic subjects also have autonomic reactions, albeit concealed. We addressed this issue by studying 44 healthy young male subjects of various levels of fitness, ranging from inactivity to athletic [mean maximal oxygen uptake was 49.1 (SD 10.7) ml*kg(-1)*min(-1), range 28.7-71.9 ml*kg(-1)*min(-1)]. The autonomic response to venous cannulation was quantified by measuring heart rate before cannulation (HR(1)), after cannulation (HR(2)), and after complete pharmacological autonomic blockade (HR(0) = the intrinsic heart rate). The sympathovagal balance before and after cannulation was computed as HR(1)/HR(0) and HR(2)/HR(0), respectively. The group means of heart rate and sympathovagal balance decreased significantly (paired Student's t-test P <0.01) from 62.5 to 59.9 beats*min(-1), and from 0.71 to 0.68, respectively. The maximal decrease in heart rate was 8.8 beats*min(-1), and in the sympathovagal balance was 0.11. Our study demonstrated that the asymptomatic subjects responded to intravenous instrumentation with a concealed autonomic reaction. Thus, from our findings it would seem that intravenous instrumentation interferes with measurements relating to autonomic nervous system activity.

Heart rate variability during repeated incremental head-up tilt discloses time dependence of individual autonomic dynamics.

According to the Rosenblueth-Simeone model, the heart rate (HR) is proportional to the sympathovagal balance. The individual proportionality constant is the intrinsic HR, which can be determined only invasively. The percentage low-frequency spectral HR variability power, relative to the low- plus high-frequency spectral power (%LF) has been raised as a noninvasive alternative. We previously studied young healthy male subjects, in whom gradual autonomic changes were induced by incremental head-up tilt (0-10-20-30-40-45-50-55-60-65-70-75-80 degrees). At each tilt angle we computed HR and %LF. Linear regressions of %LF on HR, characterizing individual autonomic dynamics, confirmed that, within a subject, changes in %LF were proportional to changes in HR. For the current study, we made repeated measurements in 19 subjects after 1 to 8 months. In six subjects, the session 1 and session 2 regression lines differed significantly (t-test, p < 0.05), demonstrating the time dependence of the autonomic dynamics. In such cases, similar HR values on different days are to be associated with different %LF values. We also determined the reproducibility of the supine HR and %LF values. For all 19 subjects, the coefficients of variation were 7 and 22%, respectively: HR reproduces better than %LF. Hence, time-dependent autonomic dynamics contribute systematically to the inferior reproducibility of %LF.

Radiofrequency catheter modification of sinus pacemaker function guided by intracardiac echocardiography.

The sinus P wave arises from a pacemaker complex distributed along the crista terminalis. We investigated the feasibility of modification of sinus pacemaker function using graded applications of radiofrequency energy along the crista terminalis in dogs to achieve sinus rate control. Modification of sinus pacemaker function (30 +/- 5% reduction in intrinsic heart rate with retention of a normal P-wave axis) was performed in 11 dogs (group 1). Total sinus pacemaker ablation (> 50% reduction in intrinsic heart rate with development of a low ectopic atrial or a junctional rhythm) was performed in 4 dogs (group 2). Intracardiac echocardiography was used to identify the crista terminalis as an anatomic marker of sinus node location. Sinus pacemaker modification caused a significant decrease in intrinsic heart rate (31% reduction, P < .001), heart rate responsiveness to isoproterenol (30% reduction, P < .0001), and average (20% reduction, P = .0002) and maximal (22% reduction, P = .0007) heart rates during 24-hour Holter monitoring. In 6 of the 11 animals, the targeted rate reduction of 30 +/- 5% was accurately achieved (mean, 31.6 +/- 4.3%; P < .001), and in the other 5, significant reduction of intrinsic heart rate was achieved but with greater variation (28.0 +/- 17.3%, P < .005). Corrected sinus node recovery time was not prolonged. After modification, earliest activation was mapped to the crista terminalis inferior to the lesion in all animals. In long-term follow-up (3.7 +/- 1.0 months), effects were maintained. After total sinus pacemaker ablation, junctional and low atrial escape pacemakers were unstable. This study demonstrates the feasibility of modification of sinus pacemaker function for sinus rate control using catheter-based radiofrequency ablation guided by intracardiac echocardiography. This can be done while pacemaker stability and attenuated responsiveness to autonomic influences are preserved. Intracardiac echocardiography accurately defined the crista terminalis and provided a reliable means to anatomically localize catheter position in relation to the sinus node.

Cholinergic and adrenergic regulation of heart rate and ventral aortic pressure in two species of tropical tunas,Katsuwonus pelamisandThunnus albacares

Tonic cholinergic and adrenergic control of heart rate and ventral aorta pressure was examined in two species of tropical tunas, the skipjack tuna (Katsuwonus pelamis) and the yellowfin tuna (Thunnus albacares). Unlike that of many other teleosts, the basal heart rate in spinally blocked tunas (at 25 °C) was dominated by a cholinergic rather than an adrenergic tonus. Infusion of atropine increased the heart rate by 143 and 58% in skipjack and yellowfin tunas, respectively. Ventral aortic pulse pressure was significantly decreased and mean ventral aortic pressure was slightly increased. Blockade of β-adrenergic receptors with propranolol produced small (&lt;6%) decreases in both heart rate and mean ventral aortic pressure, indicating a low level of tonic β-adrenergic stimulation. The small magnitude of the drop, however, suggests that tonic adrenergic regulation of heart rate and pressure is of less importance in tunas than in other teleosts, despite comparable circulating levels of adrenaline and noradrenaline. The α-adrenergic blocker phentolamine did not affect either heart rate or pressure. The intrinsic heart rate (i.e., the heart rate in the absence of cholinergic or adrenergic stimulation) was 180 beats/min in skipjack tuna and 119 beats/min in yellowfin tuna; these are the highest reported values for any teleost to date.

Effects of age on intrinsic heart rate, heart rate variability, and AV conduction in healthy humans

Heart rate, heart rate variability, and atrioventricular (AV) conduction were studied in 20 young (30 +/- 5 yr) and 19 older (69 +/- 7 yr) healthy men and women before and after single and double autonomic blockade (randomized order: atropine, 0.04 mg/kg i.v.; propranolol, 0.2 mg/kg i.v.). Basal R-R intervals did not differ, but older age increased P-R intervals (177 +/- 24 vs. 149 +/- 17 ms, P < 0.001) and decreased SD of R-R (43 +/- 17 vs. 70 +/- 18 ms, P = 0.001) and heart rate spectral content (area under the power vs. frequency curve from 0.04 to 0.32 Hz: 3.01 +/- 2.1 vs. 7.82 +/- 4.8 beats/min2, P < 0.009), as well as postural responses (R-R decreases of 107 +/- 80 vs. 250 +/- 72 ms, P < 0.002). Atropine decreased R-R intervals, SD of R-R, and high-frequency (0.24-0.32 Hz) spectral content less in elderly subjects compared with younger subjects. Propranolol increased R-R and P-R intervals equally in old and young and abolished low-frequency (0.04-0.12 Hz) increases with standing (P < 0.0008). After double blockade, R-R, P-R, and paced AV intervals were longer in old subjects. Mean values were as follows: R-R intervals, 859 +/- 176 vs. 677 +/- 106 ms, P < 0.001; P-R intervals, 179 +/- 23 vs. 149 +/- 17 ms, P = 0.0002; paced P-R intervals (500 ms), 251 +/- 39 vs. 215 +/- 47 ms; and AV block cycle length, 413 +/- 51 vs. 385 +/- 69 ms (multivariate analysis of variance, P < 0.03). After double autonomic blockade, heart rate variability was nearly eliminated in young and old (reduced > 98%, P < 0.0001). We conclude that age differences in heart rate variability can be explained by autonomic influences, but heart rate and AV conduction differences exist independently of beta-adrenergic and/or parasympathetic influences.

Intrinsic Heart Rate Response as a Predictor of Rate-Adaptive Pacing Benefit

More than half of the pacemaker systems now being implanted can be rate adaptively paced. Our objective was to determine which patients benefit from rate-adaptive pacing in terms of improvement in maximum performance and aerobic capacity. Thirty patients with implanted accelerometer-driven, rate-adaptive pacemakers underwent a standardized, ergospirometrically and maximally symptoms = limited cardiopulmonary exercise (CPX) stress test with both rate-adaptive and fixed-rate stimulation in a randomized order. The patients were divided into three groups depending on the intrinsic heart rate achieved during maximum workload: group 1 achieved < or = 90 beats per minute (bpm), group 2 achieved 90 to < or = 110 bpm, and group 3 achieved > 110 bpm. Group 1 demonstrated a significant increase (p < or = 0.01) in maximum oxygen uptake from 16.4 +/- 5.6 mL/kg/min with fixed-rate pacing to 23.2 +/- 11.1 mL/kg/min (+ 41.5%) with rate-adaptive pacing. At the anaerobic threshold, oxygen uptake significantly increased (p < or = 0.01) from 11.8 +/- 2.7 mL/kg/min to 15.7 +/- 5 mL/kg/min (+33.1%). Group 2 patients showed an increase in maximum oxygen uptake from 23.3 +/- 5.4 mL/kg/min to 25.3 +/- 4.9 mL/kg/min (+8.5%, p < or = 0.05) as well as an increase in oxygen uptake at the anaerobic threshold from 15.9 +/- 2.6 mL/kg/min to 18.1 +/- 2.9 mL/kg/min (+13.8%, p < or = 0.05) with rate-adaptive pacing. Group 3 demonstrated no significant difference between the two pacing methods (from 25.6 +/- 9.4 mL/kg/min to 25.9 +/- 9.3 mL/kg/min and from 15.8 +/- 5.5 mL/kg/min to 16.3 +/- 6 mL/kg/min). No difference in maximum oxygen uptake and in oxygen uptake at the anaerobic threshold was evident among the three groups when paced rate adaptively (not significant). The second-generation, accelerometer controlled rate-adaptive pacemakers used in testing enabled a stress-oriented heart rate increase and an age- and gender-dependent adequate matching of maximum performance. The benefit from a rate-adaptive system to the patient increases as his or her chronotropic reserve limitation became more pronounced.

733-1 Improved Early Myocardial Function with Bicaval Versus Standard Orthotopic Heart Transplantation

The technique of standard orthotopic heart transplantation (SOHT) has changed little since it was first described by Shumway and Lower. SOHT requires anastomoses between the posterior remnants of the recipient left and right atria and the donor heart. Although many transplants have been performed with excellent results. echocardiographic studies have shown that the large capacitance chambers created by combining the recipient and donor atria prevent the augmentation of myocardial function by properly timed atrial contraction. If the recipient and donor atria are synchronized. mitral valve flow velocity and hemodynamics are improved. Bicaval OHT (BOHT) involves complete excision of the right atrium and near total excision of the left atrium in recipients. The donor right atrium is left intact and bicaval anastomoses performed; the left atrium is anastomosed back to the pulmonary veins. We studied the effect of both techniques on immediate post-transplantation myocardial function. Twenty four transplants between 9/93 to 3/94 were studied; twelve patients received SOHT (group A) and twelve consecutive subsequent patients received BOHT (group B). Inotropes were adjusted to maintain HR &gt; 100 bpm, CI &gt; 2.5 I/min/m 2 and mean BP &gt; 75 mmHg. All patients received standard triple immunosuppression. The two groups were similar with regard to 1) recipient weight. sex. age, pretransplant hemodynamics; 2) donor ischemic times, preharvest donor inotropes. donor 1recipient weight ratios; 3) post transplantation hemodynamics and dopamine requirements. Significant differences at p &lt; 0.05 include (group A vs. group B): time for implantation (38.6 ± 10.6 vs. 50.2 ± 12.2 minutes), isuprel requirements at POD 1 (1.2 ± 0.2 vs. 0.2 ± 0.1 μg/min), epinephrine requirements at POD 1 (2.2 ± 0.3 vs. 0.4 ± 0 1 μg/min), need for temporary external pacing before POD 7 (67% vs. 4%). intrinsic heart rate at one week (67.4 ± 10.2 vs. 85.4 ± 12.1 bpm) and incidence of echocardiographic tricuspid regurgitation at one week (50% vs. 0%). All patients survived. This study demonstrates similar hemodynamics with significantly less inotropic requirements. especially of epinephrine and isupre!. Furthermore. chronotropy is improved and tricuspid regurgitation is eliminated. Although BOHT adds an anastomosis and requires longer for completion. the improved myocardial and sinus node function suggest that it can be considered a superior alternative to SOHT.

Myocardial Energy Metabolism in the Newborn Lamb In Vivo during Pacing-Induced Changes in Oxygen Consumption

Myocardial energy metabolism was studied in newborn sheep to determine whether the metabolic responses to pacing-induced increases in heart rate were similar to those previously found during catecholamine stimulation. Open-chest newborn sheep, 3 to 9 d old (n = 11), underwent atrial pacing at a respiratory rate harmonic just above the intrinsic heart rate. Pacing rate was increased by 30 beats/min every 5 min until conduction block or a drop in systemic arterial pressure occurred. Phosphorous metabolites were monitored simultaneously (n = 7) using a 31P magnetic resonance surface coil over the heart within a magnet operating at 4.7 tesla. Myocardial oxygen consumption was monitoring via an extracorporeal shunt from the coronary sinus. Rate pressure product increased with heart rate and was found to relate to myocardial oxygen consumption (r = 0.75), which increased maximally by 47 +/- 9% due to increases in coronary blood flow. Phosphocreatine/ATP ratio decreased significantly, and calculated ADP increased between baseline and peak performance but returned to near baseline levels during recovery at the initial pacing rate. These findings indicate that intracellular high-energy phosphate concentrations do change with alterations in myocardial oxygen consumption induced by cardiac pacing in the newborn. These changes are similar to those found during epinephrine infusion. Furthermore, the ATP hydrolysis products probably participate in myocardial respiratory regulation in the newborn in vivo.

Vagal and adrenergic tone on the heart of Xenopus laevis at different temperatures

1. 1. The heart rate of normal Xenopus laevis increased with acclimated temperature (5, 15 and 25°C) with a Q 10 of about 1.4. 2. 2. The injection of atropine abolishing a cholinergic vagal tone and raised heart rate. The proportional increase in heart rate (atropinized h.r./normal h.r.) increased with temperature so that the Q 10 increased to about 2.5. 3. 3. Injection of propranolol decreased heart rate, indicating that there was a β-adrenergic tone on the heart. 4. 4. Propranolol injection followed by atropine resulted in a heart rate higher than control but below the atropinised rate. This is likely to be the intrinsic heart rate, which also varied with temperature, having a Q 10 of about 2. 5. 5. Temperature related changes in heart rate are determined centrally and controlled chiefly by variations in cardiac vagal tone.

912-43 Sick Sinus Syndrome. A Cardiac or a Neurocardiogenic Disorder?

The commonly proposed mechanism of syncope in patients (pts) with sick sinus syndrome (SSS) is a long sinus pause without an effective escape rhythm. Nevertheless, the probability of a coexistent neurally mediated syncope (NMS) component has not been adequatelly investigated in these pts. We studied 3 groups: Gl: 12 syncopal pts (age: 58 ± 12 years, M/F: 9/3) with SSS (unexplained sinus bradycardia with inadequate chronotropic response to exercise or atropine, long sinus node recovery or sinoatrial conduction times and low intrinsic heart rate), G2; 52 pts (37 ± 17 years, M/F; 18/12) with syncope of unknown etiology and G3: 20 healthy controls (HC) (34 ± 9 years, M/F: 16/4). The same tilt table test (TTT) protocol was used (20 min in 80° upright followed by three 10 min stages in the same position under graded isoproterenol intravenous infusion at 1 – 3μg/min). TTT was considered positive (pos) if induced pre or syncope due to hypotension with or without bradycardia. A pos TTT was observed in 7 Gl pts (58.3%) and 30 G2 pts (57.7%) (p: NS). In contrast, only 4 of the G3 HC (20%) developed syncope (p &lt; 0.005). The mean pos TTT duration was similar in both pts with SSS and pts with NMS (57 ± 18 vs 55 ± 17 min, p: NS). The mean posm duration was longer in the 4 HC with an induced vagotonic reaction when compared to the 30 NMS pts of G2168 ± 10 vs 55 ± 17 min, p &lt; 0.05). We conclude that syncopal SSS pts commonly demonstrate a pos TTT. This might explain the occasional failure to avoid recurrence of syncope in SSS pts treated with cardiac pacing.

Haemodynamic actions of a novel sino‐atrial node function modulator, ZENECA ZD7288, in the anaesthetized dog: a comparison with zatebradine, atenolol and nitrendipine

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows sinus node rate. Its effects on haemodynamic function have been studied in pentobarbitone anaesthetized dogs, in comparison with zatebradine, atenolol and nitrendipine. 2. ZD7288 lowered heart rate in the dose-range 0.02 to 1.0 mg kg-1 i.v. from 152 to 77 beats min-1. Myocardial contractile function (measured as both dPLV/dtmax and right ventricular free wall developed force) decreased along with rate. Stroke volume increased as rate decreased. Cardiac output decreased at doses in excess of 0.2 mg kg-1, i.v. 3. These haemodynamic changes were reversed when heart rate reduction was reversed by atrial pacing and are, therefore, considered to be indirect consequences of heart rate changes induced by ZD7288. 4. The effects of zatebradine paralleled those of ZD7288 (heart rate reduced from 149 to 60.5 beats min-1 over the dose-range 0.02 to 1.0 mg kg-1, i.v.), except that dPLV/dtmax did not decrease with heart rate and increased during arial pacing. 5. Neither ZD7288 nor zatebradine had significant effects on atrio-ventricular conduction at intrinsic heart rates, but both significantly and dose-dependently prolonged the atrio-ventricular conduction interval during atrial pacing at 180 beats min-1. 6. The observed effects of atenolol were commensurate with removal of beta-sympathetic cardiac drive. Atrial pacing was found not to restore the pre-atenolol heamodynamic state completely. 7. Nitrendipine up to 0.2 mg kg- i.v. induced changes indicative of direct vasodilatation accompanied by reflex compensation, followed by cardiac depression at higher doses. Atrial pacing failed to compensate for the effects of vasodilatation, but caused atrio-ventricular conduction block at doses above 0.5mgkg-1, i.v.8.data show ZD7288 has marked heart rate slowing properties and that accompanying haemodynamic changes appear to be secondary to the rate changes, being reversed by atrial pacing even in the continued presence of the drug. Heart rate slowing without depression of contractile function should prove to be of benefit in the treatment of myocardial ischaemia, particularly in the presence of myocardial dysfunction.

Mechanism of 'inappropriate' sinus tachycardia. Role of sympathovagal balance.

"Inappropriate" sinus tachycardia (IST) is an uncommon and poorly defined atrial tachycardia characterized by inappropriate tachycardia and exaggerated acceleration of heart rate with "normal" P wave. The mechanism of this tachycardia is unknown. The purpose of the present study was to determine the role of autonomic balance in the genesis of IST. Six female patients aged 23 to 38 years with IST and 10 age- and sex-matched control subjects were assessed with the following autonomic function tests: (1) sympathovagal balance to the sinus node assessed by calculating the LF/HF (low frequency/high frequency) ratio using power spectral analysis both in the supine position and after 10 minutes of head-up tilt to 60 degrees, (2) cardiovagal reflex assessed by cold face test (CFT), (3) beta-adrenergic sensitivity as determined by calculating isoproterenol dose-response curves and isoproterenol chronotropic dose 25 (CD25), and (4) intrinsic heart rate (IHR) assessed after autonomic blockade with atropine 0.04 mg/kg and propranolol 0.2 mg/kg administered as an intravenous bolus. No significant differences in the LF/HF ratio both in the supine position (2.8 +/- 0.3 versus 2.6 +/- 0.4) and during upright tilt (8.7 +/- 1.3 versus 8.5 +/- 0.5) were observed between control subjects and IST patients. Cardiovagal response to CFT was markedly depressed in all patients (6.3% IST patients versus 24.2% control subjects, P < .001). beta-Adrenergic hypersensitivity to isoproterenol was noted in all patients (mean CD25, 0.29 +/- 0.10 microgram IST patients versus 1.27 +/- 0.4 microgram control subjects; P < .001), and high IHR was noted in all cases. The patients were treated with high doses of beta-blockers with adequate short-term control. Radiofrequency catheter ablation of the sinus node area was performed in one drug-refractory patient. These findings suggest that the mechanism leading to IST is related to a primary sinus node abnormality characterized by a high IHR, depressed efferent cardiovagal reflex, and beta-adrenergic hypersensitivity.

Heart rate and heart rate variability as indexes of sympathovagal balance.

According to the Rosenblueth-Simeone model, the heart rate (HR) is proportional to the sympathovagal balance. The individual proportionality constant is the intrinsic heart rate, which can only be determined invasively. The normalized low-frequency heart rate variability power (LF) has been raised as a calibrated noninvasive alternative. To concrete this assumption, we studied the individual LF-HR relation during incremental head-up tilt (0, 10, 20, 30, 40, 45, 50, 55, 60, 65, 70, 75, and 80 degrees) in 21 young, healthy males. HR (means +/- SD) increased from 61.0 +/- 9.1 beats/min at 0 degree to 85.9 +/- 18.3 beats/min at 80 degrees. LF increased from 45.8 +/- 16.7 nu at 0 degrees to 79.8 +/- 13.8 nu at 80 degrees (nu meaning normalized units). Individual regressions of LF on HR yielded correlation coefficients of 0.80 +/- 0.13 (means +/- SD). The demonstrated linear relation between LF and HR confirms the potential significance of heart rate variability as a noninvasive means of assessing the sympathovagal balance.

Recovery of attenuated baroreflex sensitivity in conscious dogs after reversal of pacing induced heart failure

Rapid ventricular pacing reliably induces severe congestive heart failure in dogs, with an associated attenuation of baroreflex sensitivity. Unique to this model is the capacity for rapid recovery of haemodynamics and plasma noradrenaline following the cessation of pacing; however, whether baroreflex sensitivity will similarly recover is unknown. The aims of this study were (1) to assess baroreflex control of heart rate in response to acute hypertensive and hypotensive stimuli during the development of and recovery from severe heart failure, and (2) to correlate baroreflex sensitivity with haemodynamic and echocardiographic indices and with noradrenaline concentrations. Serial assessments were performed on six dogs paced to severe heart failure and then allow to recover for four weeks. R-R interval and systolic blood pressure were monitored during administrations of phenylephrine and nitroprusside and the slope (ms.mm Hg-1) of the resultant R-R interval-systolic blood pressure relationship was used to define baroreflex sensitivity. Control phenylephrine and nitroprusside derived slopes were 27.05(SD 7.88) and 17.1(11.03) ms.mm Hg-1 respectively. After one week of pacing the phenylephrine derived slope was unchanged while the nitroprusside slope tended to be attenuated. In severe heart failure, both slopes were severely attenuated, at 1.88(6.45) ms.mm Hg-1 (phenylephrine) and 4.21(3.28) ms.mm Hg-1 (nitroprusside) (both p < 0.05). Intrinsic heart rate, noradrenaline concentrations and cardiac filling pressures were raised at severe heart failure while cardiac output and systolic blood pressure were significantly reduced. Recovery of baroreflex control of heart rate was evident as early as 48 h following pacing cessation and was maintained after four weeks recovery. Haemodynamics, cardiac output, and noradrenaline also returned to control while cardiac dilatation persisted. Nitroprusside and phenylephrine derived slopes were inversely correlated with intrinsic heart rate and pulmonary arterial/capillary wedge pressures respectively. Despite marked attenuation of baroreflex control of heart rate at severe heart failure, rapid recovery was seen in response to both hypotensive and hypertensive stimuli. The speed with which recovery occurs suggests that attenuation of baroreflex sensitivity at severe heart failure is likely to be mediated by functional alterations rather than morphological damage.

THE INTRINSIC PROPERTIES OF AN IN SITU PERFUSED CROCODILE HEART

An in situ perfused crocodile (Crocodylus porosus) heart preparation was developed to investigate the effects of input and output pressure on cardiac dynamics and to determine the conditions that lead to a right-to-left cardiac shunt. The pericardium was kept intact, both the left and right atria were perfused and all three outflow tracts (right aortic, left aortic and pulmonary) were cannulated, enabling pressures and flows to be monitored. The perfused heart preparation had an intrinsic heart rate of 34 beats min-1 and generated a physiological power output. Both the left and right sides of the heart were sensitive to filling pressure. Increasing the filling pressure to both atria resulted in an increase in stroke volume and cardiac output (Frank&shy;Starling effect). Increasing the filling pressure to the right atrium also had a positive chronotropic effect. Large right ventricular stroke volumes initiated a right-to-left shunt, despite the left aorta having a pressure 1.5 kPa higher than the pulmonary output pressure. The left ventricle was able to maintain its output and stroke volume up to an output pressure of approximately 8 kPa. However, the right ventricle was significantly weaker. Right ventricular output and stroke volume showed a marked decrease when the output pressure was increased above 5 kPa. A right-to-left shunt occurred when pulmonary output pressure was increased. Surprisingly, a shunt occurred into the left aorta before the pressure in the pulmonary artery became greater than that in the left aorta. Once the pressure in the pulmonary artery exceeded the left aortic pressure, pulmonary artery flow ceased and right ventricular output was solely via the left aorta. A right-to-left shunt could also be initiated by increasing the filling pressure to the left atrium.

End-systolic pressure length relations of stunned right and left ventricles after inotropic stimulation

Regional end-systolic pressure-segment length relationships (ESPSLR) were used to compare the degree of right and left ventricular stunning induced by a 10-min occlusion of the left anterior descending coronary artery and the response to subsequent atrial pacing (50 beats/min above intrinsic heart rate) without and with dobutamine (2 micrograms.kg-1.min-1) in nine anesthetized open-chest pigs. From the ESPSLR, the slope (Ees) (at 100 mmHg for the left and 25 mmHg for the right ventricle) and the total area of the pressure-length relationship (PLA) were determined. From the latter, the distribution into external work (EW) and potential energy (PE) as well as the efficiency of energy transfer (EET = EW/PLA) were calculated. In both the stunned left and right ventricular myocardium Ees and EW were reduced according to the same linear regression equations (delta Ees = 0.7 Ees,baseline - 11.4, r2 = 0.86 and delta EW = 0.4 EWbaseline + 2.3, r2 = 0.67), where Ees,baseline and EWbaseline are Ees and EW at baseline, respectively. EET of the stunned left and right ventricular segments decreased as PLA remained unchanged, due to an increase in PE. EET decreased from 0.84 +/- 0.02 to 0.71 +/- 0.03 (P < 0.05) in the stunned right ventricular segment and from 0.71 +/- 0.02 to 0.44 +/- 0.03 (P < 0.05) in the stunned left ventricular segment. Atrial pacing did not affect EET with respect to stunning levels, whereas the additional infusion of dobutamine restored Ees, EW, and PE and consequently EET to baseline values. In conclusion, the right ventricle is susceptible to stunning. During atrial pacing the EET was lower than expected from the Ees, which could, in agreement with the time-varying elastance concept, be explained by an increase in afterload (a consequence of the decrease in stroke volume). Dobutamine not only increased Ees, EW, and EET but also restored the relationship between Ees and EET in both ventricular stunned segments.

An abnormal neural reflex plays a role in causing syncope in sinus bradycardia

Objectives. This study Investigates the rote of an abnormal neural reflex in causing syncope in patients with sinus bradycardia.Background. Syncope is commonly considered an indication of severity in sinus bradycardia. However, the occurrence of syncope is unpredictable, and the prognosis appears to be similar in patients with and without syncope.Methods. Head-up tilt testing (60 ° for 60 min), carotid sinus massage in the supine and standing positions, 24-h Bolter ambulatory electrocardiographic (ECG) recording and etectrophysiologic study before and after pharmacologic autonomic blockade were performed in 25 patients with sinus bradycardia and syncope (group I, sinus rate <50 beats/min, age 71 ± 12 years) and 25 patients with sinus bradycardia and no neurologic symptoms (group II, sinus rate <50 beats/min, age 67 ± 16 years).Results. Clinical characteristics and ambulatory ECG monitoring data were similar in the two study groups. A positive response (induction of syncope or presyncope with hypotension and/or bradycardia) was obtained by head-up tilt testing in 15 group I (60%) and in 3 group II (12%) patients (p < 0.001) and by carotid sinus massage in 11 group I (44%) and 6 group II (24%) patients (p = NS). Results of at least one test (head-up tilt testing or carotid sinus massage, or both) were positive in 19 group I (76%) and 9 group II (36%) patients (p < 0.01). Basal and intrinsic corrected sinus node recovery time did not differ significantly between the two groups. An abnormal intrinsic heart rate was present in 66% of group I and 26% of group II patients (p < 0.01). The different percentage of positive findings on head-up tilt testing and carotid sinus massage in the two groups was independent of the presence of intrinsic sinus node dysfunction.Conclusions. These results indicate that an abnormal neural reflex plays a role in causing syncope in patients with sinus bradycardia. This reflex seems to be unrelated to the severity of sinus node dysfunction, even if the latter could enhance the cardioinhibitory response.

Impaired subsidiary pacemaker function in patients with a right bundle branch block created prior to complete catheter ablation of the AV junction.

The impact of a right bundle branch block (RBBB), inadvertently created prior to complete ablation of the atrioventricular (AV) junction, on the intrinsic subsidiary pacemaker function was investigated. In 31 patients suffering from intractable supraventricular tachyarrhythmia, catheter ablation of the AV junction was performed using direct current (n = 13) or radiofrequency (n = 18) energy. In 16/31 patients a RBBB was created prior to complete AV ablation. Subsidiary pacemaker function was evaluated after a mean period of 5 months. Following 5 min of ventricular pacing (70 beats.min-1) escape interval and spontaneous heart rate were measured. In patients with a RBBB there was a trend towards a longer escape interval (2979 +/- 2559 vs 1867 +/- 1254 ms, P = ns) and a significantly lower intrinsic heart rate (38 +/- 14 vs 47 +/- 8 beats.min-1, P < 0.05). Pacemaker dependency was only observed among patients with a RBBB (4/16 vs 0/15, P < 0.05). HV intervals were shorter in those energy discharges resulting in a RBBB as compared to those inducing a complete heart block (52 +/- 8 vs 66 +/- 6 ms, P < 0.05). Creation of a RBBB prior to complete ablation of the AV junction results in impaired intrinsic subsidiary pacemaker function; the most proximal catheter position should be carefully sought to minimize the risk of pacemaker dependency.

Mechanism of heat acclimation induced bradycardia in the sand rat.

The effect of heat acclimation on chronotropic response of the heart under normothermic and hyperthermic conditions was studied in the sand rat, Psammomys obesus, a diurnal desert species. All animals were acclimated at 34 degrees C for 0, 5, 14, 30 or 60 days; heat stress was achieved by exposure at 38 degrees C. Continuous measurements of heart rate (HR) were carried out on conscious animals, using chronic subcutaneous electrodes. Atropine (0.1 mg/100 g) and propranolol (1 mg/100 g) were administered to evaluate the para-sympathetic (V) and sympathetic (S) influences on HR. Intrinsic HR (HRi) was measured following administration of both drugs simultaneously. P. obesus developed bradycardia from day 5 of the acclimation. This bradycardia was induced solely by decreased HRi, overriding partial vagal withdrawal. During hyperthermia apparent thermal insensitivity of HR was observed. This was attained by partial sympathetic withdrawal compensating for the increase in HRi due to body temperature rise. It can be concluded that in P. obesus, heat acclimation induced bradycardia is attained by intrinsic changes in the pacing cells. It also emerges that the hyperthermic response is independent of and is not affected by heat acclimation.