Blunted arterial baroreflex causes "pathological" heart rate turbulence

Sudden cardiac death is the leading cause of cardiovascular mortality in developed countries. Recently, two post-myocardial-infarction risk predictors were introduced that are superior to all other presently available indicators: turbulence onset (TO) and turbulence slope (TS). These parameters characterize the behavior of instantaneous heart rate after a ventricular premature beat, i.e., they describe the reestablishing of heart rate control after an acute perturbation. We propose that the dysfunction of an important cardiovascular control mechanism, the arterial baroreflex, is the mechanism behind these new potent markers. The hypothesis is tested by means of a physiological model involving the excitation generation in the heart, the hemodynamic situation in the aorta, and baroreceptor feedback mechanisms. The data show that a blunted baroreceptor response of the heart resembles patterns of heart rate turbulence that correspond to pathological values of TO and TS. The results of the model suggest that the recently established risk parameters TO and TS characterize baroreflex function, a known risk stratifier in patients.     

Regular physical exercise, heart rate variability and turbulence in a 6-year randomized controlled trial in middle-aged men: the DNASCO study

HRV and HRT are independent predictors of cardiovascular mortality. Aging reduces HRV, but results from the physical exercise trials are controversial. The primary aim was to study changes in heart rate variability (HRV) and heart rate turbulence (HRT) in a six-year controlled randomized trial at regular low to moderate intensity physical exercise. One hundred forty men aged 53--63 years were randomized in to an exercise or a control groups. The participants underwent a maximal bicycle ergometer exercise test with respiratory gas analyses annually for six years. At baseline and after intervention, 24-h ambulatory ECG registrations were performed to assess HRV (n=100). HRT was determined among subjects with single ventricular premature complexes (VPC) (n=73). In the exercise group, ventilatory aerobic threshold (VAT) increased by 16% indicating enhanced submaximal cardiorespiratory fitness. No significant differences were found in any of the HRV or HRT parameters between the groups. However, the observed increase in VAT correlated significantly with the improvement in HRV parameters. The change in turbulence slope (TS) correlated with the changes in most HRV variables and the change in turbulence onset (TO) correlated with the changes in three frequency domain parameters. Our results suggest that in addition to improvement in submaximal cardiorespiratory fitness, regular low to moderate intensity physical exercise seems to have beneficial effects also on cardiac autonomic nervous function, a clinically relevant predictor of cardiovascular morbidity and mortality.     

The effects of changes in heart rate and aortic systolic pressure on left ventricular myocardial oxygen consumption in lambs

To determine whether changes in heart rate and aortic systolic pressure contribute equally to the determination of left ventricular myocardial oxygen consumption, we independently varied heart rate and pressure and compared the resultant oxygen consumption for similar rate-pressure products. In 6 young lambs which underwent atrioventricular node ablation, we varied heart rate by ventricular pacing at 250 beats/min, 300 beats/min, and 120 beats/min while aortic pressure remained stable and varied aortic systolic pressure by infusion of phenylephrine (to 132 +/- 15 mm Hg and 155 +/- 14 mm Hg) and by infusion of sodium nitroprusside (to 79 +/- 6 mm Hg) while heart rate was maintained stable at 200 beats/min. The 3 levels of change in aortic systolic pressure were chosen so that the ratepressure product during the pressure changes matched the rate-pressure product during the heart rate changes. We found that left ventricular myocardial oxygen consumption was the same at all 3 levels of the rate-pressure product whether heart rate was changed and pressure remained stable or pressure was changed and heart rate remained stable. Also, the correlation between oxygen consumption and the rate-pressure product was similar for both heart rate and pressure changes. During nitroprusside infusion at a fixed heart rate, oxygen extraction was significantly lower than during pacing at a heart rate of 120 beats/min when the rate-pressure product was comparable because of the direct vasodilatory effects of nitroprusside. We conclude that heart rate and aortic systolic pressure contribute equally to left ventricular myocardial oxygen consumption at the same rate-pressure product, even though there may be differences in myocardial blood flow and oxygen extraction.     

Antiarrhythmic properties of acetaminophen in the dog

Mongrel dogs bred for research and weighing 25 +/- 3 kg were used to test the hypothesis that acetaminophen has antiar-rhythmic properties. Only ventricular arrhythmias defined by the Lambeth Conventions were investigated. Dogs were exposed either to 60 mins of regional myocardial ischemia followed by 180 mins of reperfusion (n = 14) or were administered a high dose of ouabain (n = 14). Both groups of 14 dogs were further divided into vehicle and acetaminophen treatment groups (n = 7 in each). During selected 10-min intervals, we recorded the numbers of ventricular premature beats, ventricular salvos, ventricular bigeminy, ventricular tachycardia (nonsustained and sustained), and we recorded the heart rate, systemic arterial blood pressure, and left ventricular function. Neither heart rate nor the number of ventricular arrhythmias differed significantly under baseline conditions. Conversely, the combined average number of ventricular ectopic beats during ischemia and reperfusion was significantly less in the presence of acetaminophen (28 +/- 4 vs. 6 +/- 1; P < 0.05). Similarly, percent ectopy during reperfusion in vehicle- and acetaminophen-treated dogs was 1.4 +/- 0.4 and 0.4 +/- 0.2, respectively (P < 0.05). The number of all ventricular ectopic beats except ventricular salvos was also significantly reduced in the presence of acetaminophen. Similar results were obtained with ouabain. Our results reveal that systemic administration of a therapeutic dose of acetaminophen has previously unreported antiarrhythmic effects in the dog.     

Differences between heart rate and blood pressure variability in schizophrenia.

Heart rate and blood pressure variability parameters were assessed to determine the risk of cardiac mortality in schizophrenia. We investigated 21 acute, unmedicated patients with paranoid schizophrenia and 21 matched controls. Cardiovascular parameters obtained included heart rate variability, blood pressure variability, cardiac output and left ventricular work index. All parameters investigated were analyzed using linear and non-linear techniques. These investigations revealed increased left ventricular work index and reduced heart rate variability. Furthermore, blood pressure was significantly higher compared to controls, whereas its variability was unchanged. We conclude that our results reflect autonomic cardiovascular dysregulation in acute schizophrenia.     

Chlorpromazine: cardiac arrhythmogenicity in the cat

To determine the effect of chlorpromazine on ouabain-induced arrhythmia and death, dial-urethane anesthetized cats were pretreated with chlorpromazine (5, 10, 20, 30, 40, or 60 mg/kg, i.v.) and then administered ouabain (2 microgram/kg/min, i.v.). Blood pressure, heart rate and lead II electrocardiogram (ECG) were monitored. The dosages of ouabain necessary to induce premature ventricular contractions, ventricular tachycardia and death were determined. No significant correlation between the dose of chlorpromazine given and the dose of ouabain required to produce arrhythmia or death was found. These doses of chlorpromazine could, therefore, be considered neither arrhythmogenic nor antiarrhythmic in the ouabain model. To determine whether chlorpromazine produced arrhythmia in the dial-urethane anesthetized cat model, the drug was infused at a rate of 1 mg/kg/min, i.v. Chlorpromazine produced arrhythmia at 185 +/- 4.3 minutes and death via cardiovascular collapse at 128 +/- 4.7 minutes. Bilateral adrenal vein ligation, employed to eliminate the influence of adrenal catecholamines, decreased the dosage of chlorpromazine necessary to produce arrhythmia and death to 67.8 +/- 17.7 and 84.7 +/- 15.7 mg/kg, respectively. Thus, adrenal catecholamines did not appear to contribute to chlorpromazine-induced arrhythmia, although the procedure of bilateral adrenal vein ligation appeared to be deleterious in combination with chlorpromazine. In all experiments, chlorpromazine depressed blood pressure without producing the reflex tachycardia normally seen with hypotension. This suggests that the drug may be interfering with the baroreceptor reflex arc. As chlorpromazine modifies the autonomic parameters of blood pressure, heart rate, and cardiac electrophysiology, sudden unexplained death in patients managed with this agent may be due to drug-induced arrhythmia.     

Respiratory-related heart rate variability in progressive experimental heart failure

Heart failure is associated with autonomic imbalance, and this can be evaluated by a spectral analysis of heart rate variability. However, the time course of low-frequency (LF) and high-frequency (HF) heart rate variability changes, and their functional correlates during progression of the disease are not exactly known. Progressive heart failure was induced in 16 beagle dogs over a 7-wk period by rapid ventricular pacing. Spectral analysis of heart rate variability and respiration, echocardiography, hemodynamic measurements, plasma atrial natriuretic factor, and norepinephrine was obtained at baseline and every week, 30 min after pacing interruption. Progressive heart failure increased heart rate (from 91 +/- 4 to 136 +/- 5 beats/min; P < 0.001) and decreased absolute and normalized (percentage of total power) HF variability from week 1 and 2, respectively (P < 0.01). Absolute LF variability did not change during the study until it disappeared in two dogs at week 7 (P < 0.05). Normalized LF variability increased in moderate heart failure (P < 0.01), leading to an increased LF-to-HF ratio (P < 0.05), but decreased in severe heart failure (P < 0.044; week 7 vs. week 5). Stepwise regression analysis revealed that among heart rate variables, absolute HF variability was closely associated with wedge pressure, right atrial and pulmonary arterial pressure, left ventricular ejection fraction and volume, ratio of maximal velocity of early (E) and atrial (A) mitral flow waves, left atrial diameter, plasma norepinephrine, and atrial natriuretic peptide (0.45 < r < 0.65, all P < 0.001). In tachycardia-induced heart failure, absolute HF heart rate variability is a more reliable indicator of cardiac dysfunction and neurohumoral activation than LF heart rate variability.     

Pregnancy increases baroreflex-independent GABAergic inhibition of the RVLM in rats

During baroreceptor unloading, sympathoexcitation is attenuated in near-term pregnant compared with nonpregnant rats. Alterations in balance among different excitatory and inhibitory inputs within central autonomic pathways likely contribute to changes in regulation of sympathetic outflow in pregnancy. Both baroreflex-dependent and baroreflex-independent GABAergic inputs inhibit sympathoexcitatory neurons within rostral ventrolateral medulla (RVLM). The present experiments tested the hypothesis that influence of baroreflex-independent GABAergic inhibition of RVLM is greater in pregnant compared with nonpregnant rats. Afferent baroreceptor inputs were eliminated by bilateral sinoaortic denervation in inactin-anesthetized rats. In pregnant compared with nonpregnant rats, baseline mean arterial pressure (MAP) was lower (pregnant = 75 +/- 6 mmHg, nonpregnant = 115 +/- 7 mmHg) and heart rate was higher (pregnant = 381 +/- 10 beats/min, nonpregnant = 308 +/- 10 beats/min). Pressor and sympathoexcitatory [renal sympathetic nerve activity, (RSNA)] responses due to bilateral GABA(A) receptor blockade (bicuculline, 4 mM, 100 nl) of the RVLM were greater in pregnant rats (delta MAP: pregnant = 101 +/- 4 mmHg, nonpregnant = 80 +/- 6 mmHg; delta RSNA: pregnant = 182 +/- 23% control, nonpregnant = 133 +/- 10% control). Unexpected transient sympathoexcitatory effects of angiotensin AT(1) receptor blockade in the RVLM were greater in pregnant rats. Although excitatory responses to bicuculline were attenuated by prior RVLM AT1 receptor blockade in both groups, pressor responses to disinhibition of the RVLM remained augmented in pregnant rats. Increased influence of baroreflex-independent GABAergic inhibition in RVLM could contribute to suppressed sympathoexcitation during withdrawal of arterial baroreceptor input in pregnant animals.     

Atrial natriuretic peptide inhibits compensatory responses when cardiac performance is depressed.

We tested the hypothesis that the atrial natriuretic peptide (ANP) mediated decrease in baroreceptor sensitivity that is seen in normal rats is more pronounced in a state of depressed cardiac performance. Holtzman rats (n = 15) were injected with Adriamycin (1 mg/kg i.p. 3 times/week for 8-10 weeks). Control rats (n = 17) were injected with 0.9% saline. Experiments were done in conscious animals that had been catheterized for i.v. infusions and for measurement of arterial blood pressure (ABP) and heart rate (HR). ANP (250 ng.kg-1.min-1) or saline vehicle was infused i.v. Graded periodic bolus injections of phenylephrine or sodium nitroprusside were given to assess baroreceptor sensitivity (beats.min-1.mmHg-1) up to 60 mmHg (1 mmHg = 133.3 Pa) above and below resting ABP. The following day the experiment was repeated with the ANP-vehicle regimen reversed. Finally, the rats were anesthetized and the rate of left ventricular pressure increase (dP/dt) was measured. Data evaluation included calculation of least squares linear regression slopes of peak delta HR vs. peak delta ABP, applying corrections for experimental errors in both the dependent and independent variables. Adriamycin rats (A) did not differ significantly from control rats (C) with respect to either initial ABP (A = 105 +/- 5; C = 100 +/- 3; mean mmHg +/- SEM) or initial HR (335 +/- 9 vs. 312 +/- 13 beats.min-1). However, their indices of cardiac performance were significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate

Systemic corticosterone (Cort) modulates arterial baroreflex control of both heart rate and renal sympathetic nerve activity. Because baroreceptor afferents terminate in the dorsal hindbrain (DHB), an area with dense corticosteroid receptor expression, we tested the hypothesis that prolonged activation of DHB Cort receptors increases the midpoint and reduces the gain of arterial baroreflex control of heart rate in conscious rats. Small (3-4 mg) pellets of Cort (DHB Cort) or Silastic (DHB Sham) were placed on the surface of the DHB, or Cort was administered systemically by placing a Cort pellet on the surface of the dura (Dura Cort). Baroreflex control of heart rate was determined in conscious male Sprague Dawley rats on each of 4 days after initiation of treatment. Plots of arterial pressure vs. heart rate were analyzed using a four-parameter logistic function. After 3 days of treatment, the arterial pressure midpoint for baroreflex control of heart rate was increased in DHB Cort rats (123 +/- 2 mmHg) relative to both DHB Sham (108 +/- 3 mmHg) and Dura Cort rats (109 +/- 2 mmHg, P < 0.05). On day 4, baseline arterial pressure was greater in DHB Cort (112 +/- 2 mmHg) compared with DHB Sham (105 +/- 2 mmHg) and Dura Cort animals (106 +/- 2 mmHg, P < 0.05), and the arterial pressure midpoint was significantly greater than mean arterial pressure in the DHB Cort group only. Also on day 4, maximum baroreflex gain was reduced in DHB Cort (2.72 +/- 0.12 beats x min(-1) x mmHg(-1)) relative to DHB Sham and Dura Cort rats (3.51 +/- 0.28 and 3.37 +/- 0.27 beats x min(-1) x mmHg(-1), P < 0.05). We conclude that Cort acts in the DHB to increase the midpoint and reduce the gain of the heart rate baroreflex function.     

Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety.

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) without hypotension during orthostasis. The relationship between the tachycardia and anxiety is uncertain. Therefore, we tested whether the HR response to orthostatic stress in POTS is primarily related to psychological factors. POTS patients (n = 14) and healthy controls (n = 10) underwent graded venous pooling with lower body negative pressure (LBNP) to -40 mmHg while wearing deflated antishock trousers. "Sham" venous pooling was performed by 1) trouser inflation to 5 mmHg during LBNP and 2) vacuum pump activation without LBNP. HR responses to mental stress were also measured in both groups, and a questionnaire was used to measure psychological parameters. During LBNP, HR in POTS patients increased 39 +/- 5 beats/min vs. 19 +/- 3 beats/min in control subjects at -40 mmHg (P < 0.01). LBNP with trouser inflation markedly blunted the HR responses in the patients (9 +/- 2 beats/min) and controls (2 +/- 1 beats/min), and there was no HR increase during vacuum application without LBNP in either group. HR responses during mental stress were not different in the patients and controls (18 +/- 2 vs. 19 +/- 1 beats/min; P > 0.6). Anxiety, somatic vigilance, and catastrophic cognitions were significantly higher in the patients (P < 0.05), but they were not related to the HR responses during LBNP or mental stress (P > 0.1). These results suggest that the HR response to orthostatic stress in POTS patients is not caused by anxiety but that it is a physiological response that maintains arterial pressure during venous pooling.     

Aortic baroreceptor deafferentation in the baboon

Previous animal studies have indicated that removal of the aortic baroreceptors causes a moderate increase in arterial pressure that is not fully buffered by receptors in the carotid sinus. However, the role of these separate baroreceptors in the conscious nonhuman primate has not been examined. To address this question, adult male baboons were chronically maintained on a tether system that permitted them to move freely about their cage. With this system, arterial pressure and heart rate could be monitored continuously over 24-h periods with periodic drug administration to test cardiovascular function. Control values of arterial pressure and heart rate were 85.6 +/- 4.0 mmHg and 77.5 +/- 2.9 beats/min, respectively. Following removal of the aortic baroreceptors, arterial pressure rose to 104.6 +/- 5.5 mmHg and heart rate increased to 117.9 +/- 3.1 beats/min. The variability of these parameters did not change following denervation. There was, however, a suppression of the arterial pressure-heart period relationship and an augmentation in the depressor response to ganglionic blockade with hexamethonium. These data indicate that removal of the aortic baroreceptors causes a reduction in the sensitivity of the heart rate baroreflex and subsequent increase in arterial pressure that is a result of an increased sympathetic nervous system function.     

Warm-up phenomenon and cardiac autonomic control in patients with coronary artery disease

Decreased heart rate variability (HRV) and heart rate turbulence (HRT) are independent predictors of mortality after acute myocardial infarction (AMI). There are no previous studies on the relationship between warm-up phenomenon and cardiac autonomic control in stable coronary artery disease (CAD). We investigated the responses in HRV to repeated exercise induced ischemia and differences in global HRV and HRT in patients with and without adaptation to ischemia (warm-up phenomenon). Fifty male patients with CAD underwent two successive exercise tests with ambulatory electrocardiogram (ECG) recordings. HRV was evaluated using time and frequency domain measures and HRT was determined among patients with ventricular premature complexes (VPCs). The patients were divided in two groups on the basis of either positive (warm-up+) or negative (warm-up-) ischemia adaptation. Total power, ULF and VLF power and pNN50 calculated from the entire ECG recording were higher in the group demonstrating warm-up phenomenon (P<0.05 for all). In the assessment of the four short-term stationary phases (pre-and post-test 1 and 2) total power, VLF power and pNN50 were significantly higher in the warm-up positive group already at the baseline (P<0.05 for all). Furthermore, in the entire recordings total power, ULF and VLF power and SDNN correlated positively with the decrease in ischemic burden in the recovery phase (P相似文献   

Abolition of clonidine's effects on ventricular refractoriness by naloxone in the conscious dog

The interaction between opiate and adrenergic receptors on cardiac electrophysiologic function in the conscious dog was addressed in our study. We examined the effects of opiate receptor blockade with naloxone on clonidine-induced changes in refractoriness of the cardiac ventricle. Nine dogs were chronically instrumented for recording mean arterial blood pressure, administration of drugs and for measurement of effective refractory period of the ventricle. Clonidine (10 micrograms/kg, i.v.) significantly (p less than 0.05) decreased heart rate to 72 +/- 5 beats/minute from 108 +/- 8 beats/minute; mean arterial pressure decreased significantly (p less than 0.05) to 83 +/- 3 mmHg from 91 +/- 4 mmHg. Ventricular refractoriness was increased significantly (p less than 0.05) at current levels of 7 and 10 mA and pacing rates 180 and 200 beats/minute. Naloxone (3-10 mg/kg, i.v.) abolished clonidine's effects on heart rate, mean arterial pressure and ventricular refractoriness. We conclude that ventricular refractoriness may be regulated in part by interactions between central adrenergic and opioidergic systems.     

Circadian Variations of Heart Rate and Premature Beats in Healthy Subjects and in Patients with Previous Myocardial Infarction

Chronobiological analysis of the circadian variations of heart rate, ventricular and atrial ectopies, was carried out on 11 patients with previous myocardial infarction matched with 11 controls. Individual circadian rhythms in heart rate were seen in all the control subjects but only in 6 patients with previous myocardial infarction. The behaviour of the individual circadian rhythms of premature beats was not significantly different between the two groups. A significant group rhythm in ectopies was not demonstrated, nevertheless a trend to higher frequency of arrhythmias during the activity span was detected. These results do not allow to postulate a circadian pattern of arrhythmias common to all the subjects examined. Therefore, the individual circadian behaviour of premature atrial and ventricular beats should be recognized for monitoring antiarrhythmic therapy. A significant group rhythm in heart rate was demonstrated for the two populations studied and linear discriminant analysis showed that the amplitude of this rhythm was significantly lower in patients than in controls. Possibly, myocardial infarction may affect the sinus node function producing a “flattened” range of heart rates during the 24 hours.     

The effect of alcohol and barbiturate on the frequency of atrial and ventricular premature beats during sleep.

Repeated EEG and ECG monitoring during sleep was carried out in two subjects with ischemic heart disease and one presumably healthy control. All three displayed frequent ectopic heart beats. Two had ventricular and the third atrial premature beats. The study had two objectives: (1) to ascertain the distribution of ectopic beats among the stages of sleep; and (2) to ascertain the effect of alcohol and barbiturates on the frequency of premature beats. Both drugs are known to alter the pattern of sleep stages. It was found that neither atrial nor ventricular premature beats favored a particular sleep stage. Neither drug had a consistent effect on their frequency and there was no correlation with heart rate. For the most part premature beats were fewer on the second night of a procedure although a day filled with anxiety appeared to greatly increase the frequency of premature contractions.     

Reduced oxygen supply explains the negative force-frequency relation and the positive inotropic effect of adenosine in buffer-perfused hearts

In isolated rat hearts perfused with HEPES and red blood cell-enriched buffers, we examined changes in left ventricular pressure induced by increases in heart rate or infusion of adenosine to investigate whether the negative force-frequency relation and the positive inotropic effect of adenosine are related to an inadequate oxygen supply provided by crystalloid perfusates. Hearts perfused with HEPES buffer at a constant flow demonstrated a negative force-frequency relation, whereas hearts perfused with red blood cell-enriched buffer exhibited a positive force-frequency relation. In contrast, HEPES buffer-perfused hearts showed a concentration-dependent increase in left ventricular systolic pressure [EC50 = 7.0 +/- 1.2 nM, maximal effect (Emax) = 104 +/- 2 and 84 +/- 2 mmHg at 0.1 microM and baseline, respectively] in response to adenosine, whereas hearts perfused with red blood cell-enriched buffer showed no change in left ventricular pressure. The positive inotropic effect of adenosine correlated with the simultaneous reduction in heart rate (r = 0.67, P < 0.01; EC50 = 3.8 +/- 1.4 nM, baseline 228 +/- 21 beats/min to a minimum of 183 +/- 22 beats/min at 0.1 microM) and was abolished in isolated hearts paced to suppress the adenosine-induced bradycardia. In conclusion, these results indicate that the negative force-frequency relation and the positive inotropic effect of adenosine in the isolated rat heart are related to myocardial hypoxia, rather than functional peculiarities of the rat heart.     

Reduced central blood volume and cardiac output and increased vascular resistance during static handgrip exercise in postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is characterized by exercise intolerance and sympathoactivation. To examine whether abnormal cardiac output and central blood volume changes occur during exercise in POTS, we studied 29 patients with POTS (17-29 yr) and 12 healthy subjects (18-27 yr) using impedance and venous occlusion plethysmography to assess regional blood volumes and flows during supine static handgrip to evoke the exercise pressor reflex. POTS was subgrouped into normal and low-flow groups based on calf blood flow. We examined autonomic effects with variability techniques. During handgrip, systolic blood pressure increased from 112 +/- 4 to 139 +/- 9 mmHg in control, from 119 +/- 6 to 143 +/- 9 in normal-flow POTS, but only from 117 +/- 4 to 128 +/- 6 in low-flow POTS. Heart rate increased from 63 +/- 6 to 82 +/- 4 beats/min in control, 76 +/- 3 to 92 +/- 6 beats/min in normal-flow POTS, and 88 +/- 4 to 100 +/- 6 beats/min in low-flow POTS. Heart rate variability and coherence markedly decreased in low-flow POTS, indicating uncoupling of baroreflex heart rate regulation. The increase in central blood volume with handgrip was absent in low-flow POTS and blunted in normal-flow POTS associated with abnormal splanchnic emptying. Cardiac output increased in control, was unchanged in low-flow POTS, and was attenuated in normal-flow POTS. Total peripheral resistance was increased compared with control in all POTS. The exercise pressor reflex was attenuated in low-flow POTS. While increased cardiac output and central blood volume characterizes controls, increased peripheral resistance with blunted or eliminated in central blood volume increments characterizes POTS and may contribute to exercise intolerance.     

Heart rate modulates the slow enhancement of contraction due to sudden left ventricular dilation

In isovolumic blood-perfused dog hearts, left ventricular developed pressure (DP) was recorded while a sudden ventricular dilation was promoted at three heart rate (HR) levels: low (L: 52 +/- 1.7 beats/min), intermediate (M: 82 +/- 2.2 beats/min), and high (H: 117 +/- 3.5 beats/min). DP increased instantaneously with chamber expansion (Delta(1)DP), and another continuous increase occurred for several minutes (Delta(2)DP). HR elevation did not alter Delta(1)DP (32.8 +/- 1.6, 33.6 +/- 1.5, and 34.3 +/- 1.2 mmHg for L, M, and H, respectively), even though it intensified Delta(2)DP (17.3 +/- 0.9, 20.7 +/- 1.0, and 26.8 +/- 1.2 mmHg for L, M, and H, respectively), meaning that the treppe phenomenon enhances the length dependence of the contraction component related to changes in intracellular Ca(2+) concentration. Frequency increments reduced the half time of the slow response (82 +/- 3.6, 67 +/- 2.6, and 53 +/- 2.0 s for L, M, and H, respectively), while the number of beats included in half time increased (72 +/- 2.9, 95 +/- 2.9, and 111 +/- 3.2 beats for L, M, and H, respectively). HR modulation of the slow response suggests that L-type Ca(2+) channel currents and/or the Na(+)/Ca(2+) exchanger plays a relevant role in the stretch-triggered Ca(2+) gain when HR increases in the canine heart.     

Arterial baroreflex control of heart rate during exercise in postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) have excessive tachycardia without hypotension during orthostasis as well as exercise. We tested the hypothesis that excessive tachycardia during exercise in POTS is not related to abnormal baroreflex control of heart rate (HR). Patients (n = 13) and healthy controls (n = 10) performed graded cycle exercise at 25, 50, and 75 W in both supine and upright positions while arterial pressure (arterial catheter) and HR (ECG) were measured. Baroreflex sensitivity of HR was assessed by bolus intravenous infusion of phenylephrine at each workload. In both positions, HR was higher in the patients than the controls during exercise. Supine baroreflex sensitivity (HR/systolic pressure) in POTS patients was -1.3 +/- 0.1 beats.min(-1).mmHg(-1) at rest and decreased to -0.6 +/- 0.1 beats.min(-1).mmHg(-1) during 75-W exercise, neither significantly different from the controls (P > 0.6). In the upright position, baroreflex sensitivity in POTS patients at rest (-1.4 +/- 0.1 beats.min(-1).mmHg(-1)) was higher than the controls (-1.0 +/- 0.1 beats.min(-1).mmHg(-1)) (P < 0.05), and it decreased to -0.1 +/- 0.04 beats.min(-1).mmHg(-1) during 75-W exercise, lower than the controls (-0.3 +/- 0.09 beats.min(-1).mmHg(-1)) (P < 0.05). The reduced arterial baroreflex sensitivity of HR during upright exercise was accompanied by greater fluctuations in systolic and pulse pressure in the patients than in the controls with 56 and 90% higher coefficient of variations, respectively (P < 0.01). However, when baroreflex control of HR was corrected for differences in HR, it was similar between the patients and controls during upright exercise. These results suggest that the tachycardia during exercise in POTS was not due to abnormal baroreflex control of HR.