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Biomedical subjects

V Novak

Publications and source records attributed to V Novak.

At least 19 recordsLinked to original sources
PubMed2000

Mechanisms of blood pressure alterations in response to the Valsalva maneuver in postural tachycardia syndrome.

The postural tachycardia syndrome (POTS) is characterized clinically by orthostatic lightheadedness and tachycardia. When these patients perform a Valsalva maneuver, there is an excessive blood pressure increment after cessation of the maneuver (phase IV) that is sometimes associated with headaches. It is not known whether excessive phase IV is due to excessive peripheral vascular tone (an alpha-adrenergic mechanism) or is a manifestation of increased beta-adrenergic tone (hyperadrenergic state). The authors undertook a pharmacologic study evaluating the effect of intravenous phentolamine (alpha-adrenergic antagonist) and propranolol (beta-adrenergic antagonist) on the different phases of the Valsalva maneuver in a group of patients with POTS and age-matched normal control subjects. Patients with POTS had mean phases, when compared with controls, that were characterized by more negative II_E (p = 0.07), smaller II_L (p = 0.04), and significantly larger phase IV (p = 0.001). The effect of phentolamine was qualitatively and quantitatively different in POTS when compared with controls. Ten mg phentolamine in controls resulted in a significant accentuation of phase II_E (p = 0.001), attenuation of phase II_L (p = 0.002), and increase of phase IV (57.6 vs 30.7 mm Hg; p = 0.025). These changes resembled those of patients with POTS at baseline. In patients with POTS, the phase II abnormalities, already present, were further accentuated (p <0.001), and phase IV became smaller (50.6 vs 73.8 mm Hg; p = 0.09). Propranolol had no significant effect on phases II_E and II_L, but significantly reduced phase IV in both controls (p <0.05) and in patients with POTS (p <0.001) and improved the headache symptoms, when present, during and after phase IV. The authors conclude that phase IV is mainly under beta-adrenergic regulation and that the exaggerated phase IV in POTS is a result of a hyperadrenergic state.

Adrenergic alpha-Antagonists↗
PubMed2000

Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome.

A variety of approaches have been used to alleviate symptoms in postural tachycardia syndrome (POTS). Drugs reported to be of benefit include midodrine, propranolol, clonidine, and phenobarbital. Other measures used include volume expansion and physical countermaneuvers. These treatments may influence pathophysiologic mechanisms of POTS such as alpha-receptor dysfunction, beta-receptor supersensitivity, venous pooling, and brainstem center dysfunction. The authors prospectively studied hemodynamic indices and symptom scores in patients with POTS who were acutely treated with a variety of interventions. Twenty-one subjects who met the criteria for POTS were studied (20 women, 1 man; mean age, 28.7 +/- 6.8 y; age range, 14-39 y). Patients were studied with a 5-minute head-up tilt protocol, ECG monitoring, and noninvasive beat-to-beat blood pressure monitoring, all before and after the administration of an intervention (intravenous saline, midodrine, propranolol, clonidine, or phenobarbital). The hemodynamic indices studied were heart rate (ECG) and systolic, mean, and diastolic blood pressure. Patients used a balanced verbal scale to record any change in their symptoms between the tilts. Symptom scores improved significantly after the patients received midodrine and saline. Midodrine and propranolol reduced the resting heart rate response to tilt (p <0.005) and the immediate and 5-minute heart rate responses to tilt (p <0.002). Clonidine accentuated the immediate decrease in blood pressure on tilt up (p <0.05). It was concluded that midodrine and intravenous saline are effective in decreasing symptoms on tilt in patients with POTS when given acutely. Effects of treatments on heart rate and blood pressure responses generally reflected the known pharmacologic mechanisms of the agents.

Adolescent↗
PubMed1999

Painful sensory neuropathy: prospective evaluation using skin biopsy.

OBJECTIVE: In patients presenting with painful, burning feet with minimal signs of neuropathy, the following questions were addressed: 1) How many of these patients have a peripheral neuropathy? 2) What is the role of skin biopsy in establishing a diagnosis of neuropathy? 3) What conditions are associated with the neuropathy? and 4) What laboratory studies are useful in this patient population? METHODS: A total of 117 consecutive patients referred for evaluation were prospectively studied. All underwent nerve conduction studies (NCS) and a battery of blood tests, including antinerve antibodies. If NCS were normal, a punch biopsy of the skin of the distal leg was performed to ascertain the intraepidermal nerve fiber (IENF) density. In a subset of 32 patients, the sensitivity of skin biopsy was compared to quantitative sudomotor axon test (QSART) and quantitative sensory tests (QST). RESULTS: Three groups emerged. Group 1, with abnormal NCS (n = 60, 34 F/26 M, mean age 60 +/- 14 years), represented 51% of the cohort. The majority had neuropathies of undetermined cause, but 18 (30%) had associated conditions. Group 2, with normal NCS and reduced IENF density (n = 44, 29 F/15 M, mean age 57 +/- 14 years), represented 38% of the cohort. Three in this group had associated conditions. Group 3, with normal NCS and IENF density (n = 13, 6 F/7 M, mean age 53 +/- 13 years), represented 11% of the cohort; most had no diagnoses but two had MS. In a comparative subset analysis, skin biopsy was more sensitive than QSART or QST in diagnosing a neuropathy. CONCLUSIONS: Patients presenting with painful feet are heterogeneous, consisting of both large and small fiber sensory neuropathies. In rare cases, a central cause for pain can be found. Over one-third of patients required a skin biopsy to diagnose a small fiber sensory neuropathy. A limited battery of blood tests facilitated diagnosis, but serum antinerve antibodies were not helpful.

Aged↗
PubMed1999

Time-frequency mapping of R-R interval during complex partial seizures of temporal lobe origin.

BACKGROUND: Activation of autonomic nervous system is common with seizures. No reliable biological markers of impending seizures have been found. Evaluation of autonomic changes might help elucidate the transition from interictal to ictal states. METHODS: We studied twelve patients (eight females, four males), from 19 to 62 years old with temporal lobe complex partial seizures (CPS). Dynamics of autonomic functions from oscillations in R-R interval (RRI) using time-frequency mapping based upon a Wigner distribution during pre-ictal, ictal and post-ictal periods. Oscillations in RRI at respiratory frequencies (RF) (> 0.1 Hz) are parasympathetically mediated and at nonrespiratory frequencies (NONRF) (0.01-0.09 Hz) are under combined sympathetic and parasympathetic influence. RESULTS: CPS evoked marked autonomic imbalance and tachycardia. Spectral powers at both RF_RRI and NONRF_RRI increased over the pre-ictal period. RF_RRI power then fell rapidly over the 30 s before seizure onset and remained markedly reduced during seizure (P < 0.004). NONRF_RRI power reached a maximum at seizure onset and declined to a minimum before the seizure cessation (P < 0.05). CONCLUSION: Time-frequency analysis revealed that autonomic activation hallmarks clinical seizure onset for several minutes. After combined parasympathetic and sympathetic activation, rapid parasympathetic withdrawal occurred approximately 30 s before the seizure, and sympathetic activation peaks at seizure onset. Therefore, the transition from interictal to ictal states is relatively long and associated with subclinical autonomic changes.

Adult↗
PubMed1999

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS).

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Blood Flow Velocity↗
PubMed1998

Autoregulation of cerebral blood flow in orthostatic hypotension.

BACKGROUND AND PURPOSE: We sought to evaluate cerebral autoregulation in patients with orthostatic hypotension (OH). METHODS: We studied 21 patients (aged 52 to 78 years) with neurogenic OH during 80 degrees head-up tilt. Blood flow velocities (BFV) from the middle cerebral artery were continuously monitored with transcranial Doppler sonography, as were heart rate, blood pressure (BP), cardiac output, stroke volume, CO2, total peripheral resistance, and cerebrovascular resistance. RESULTS: All OH patients had lower BP (P<.0001), BFV_diastolic (P<.05), CVR (P<.007), and TPR (P<.02) during head-up tilt than control subjects. In control subjects, no correlations between BFV and BP were found during head-up tilt, suggesting normal autoregulation. OH patients could be separated into those with normal or expanded autoregulation (OH_NA; n=16) and those with autoregulatory failure (OH_AF; n=5). The OH_NA group showed either no correlation between BFV and BP (n=8) or had a positive BFV/BP correlation (R2>.75) but with a flat slope. An expansion of the "autoregulated" range was seen in some patients. The OH_AF group was characterized by a profound fall in BFV in response to a small reduction in BP (mean deltaBP <40 mm Hg; R2>.75). CONCLUSIONS: The most common patterns of cerebral response to OH are autoregulatory failure with a flat flow-pressure relationship or intact autoregulation with an expanded autoregulated range. The least common pattern is autoregulatory failure with a steep flow-pressure relationship. Patients with patterns 1 and 2 have an enhanced capacity to cope with OH, while those with pattern 3 have reduced capacity.

Aged↗
PubMed1998

Hypocapnia and cerebral hypoperfusion in orthostatic intolerance.

BACKGROUND AND PURPOSE: Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS: Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS: The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by linear regressions, and the slope was not different between control subjects and patients with OI. CONCLUSIONS: Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO2 rebreathing.

Adult↗
PubMed1998

Clinical and laboratory indices that enhance the diagnosis of postural tachycardia syndrome.

OBJECTIVE: To identify clinical and laboratory indices that improve the diagnosis of the postural tachycardia syndrome (POTS). DESIGN: We assessed associations of orthostatic intolerance by using multivariate regression analysis. MATERIAL AND METHODS: We evaluated autonomic symptoms and autonomic function in 30 patients with POTS, 30 patients with mild orthostatic intolerance, and 19 age- and gender-matched control subjects. Indices of parasympathetic and sympathetic functions were analyzed on the basis of (1) autonomic function tests (head-up tilt), (2) oscillations at respiratory and nonrespiratory frequencies (0.01 to 0.09 Hz) in R-R interval and blood pressure (Wigner distribution), and (3) deterministic component (rescaled range analysis). RESULTS: The four clinical and laboratory indices that independently supported the diagnosis of POTS are as follows: (1) orthostatic heart rate during the first minute of head-up tilt, (2) autonomic deficit (adrenergic autonomic score), (3) loss of spectral powers in R-R interval during head-up tilt at the fifth minute, and (4) severity of orthostatic dizziness, fatigue, palpitations, and shortness of breath. CONCLUSION: Enhancing the sensitivity and specificity of the diagnosis of POTS should be possible by using these four indices. A hyperadrenergic state and distal neuropathy, affecting adrenergic sympathetic cardiovagal fibers, seem to be involved in the pathophysiology of POTS. Certain features suggest brain-stem dysregulation.

Adult↗
PubMed1997

Effect of perturbations and a meal on superior mesenteric artery flow in patients with orthostatic hypotension.

UNLABELLED: Our aims were to evaluate to role of superior mesenteric blood flow in the pathophysiology of orthostatic hypotension in patients with generalized autonomic failure. METHODS: Twelve patients with symptomatic neurogenic orthostatic hypotension and 12 healthy controls underwent superior mesenteric artery flow measurements using Doppler ultrasonography during head-up tilt and tilt plus meal ingestion. Autonomic failure was assessed using standard tests of the function of the sympathetic adrenergic, cardiovagal and postganglionic sympathetic sudomotor function. RESULTS: Superior mesenteric flow volume and time-averaged velocity were similar in patients and controls at supine rest; however, responses to cold pressor test and upright tilt were attenuated (p < 0.05) in patients compared to controls. Head-up tilt after the meal evoked a profound fall of blood pressure and mesenteric blood flow in the patients; the reduction of mesenteric blood flow correlated (r = 0.89) with the fall of blood pressure in these patients, providing another manifestation of failed baroreflexes. We make the novel finding that the severity of postprandial orthostatic hypotension regressed negatively with the postprandial increase in mesenteric flow in patients with orthostatic hypotension. CONCLUSION: Mesenteric flow is under baroreflex control, which when defective, results in, or worsens orthostatic hypotension. Its large size and baroreflexivity renders it quantitatively important in the maintenance of postural normotension. The effects of orthostatic stress can be significantly attenuated by reducing the splanchnic-mesenteric volume increase in response to food. Evaluation of mesenteric flow in response to eating and head-up tilt provide important information on intra-abdominal sympathetic adrenergic function, and the ability of the patient to cope with orthostatic stress.

Adult↗
PubMed1997

Alpha 2-adrenergic modulation of colonic tone during hyperventilation.

Our aims were to assess the role of adrenergic modulation in the hyperventilation-induced increase in colonic tone. Of 40 healthy volunteers, 12 received placebo (saline) and the remaining 28 received either clonidine, yohimbine, phenylephrine, or ritodrine. Time-frequency mapping of heart rate based on Wigner distribution assessed variations in parasympathetic and sympathetic activity during hyperventilation. Tone in the descending colon was recorded by a barostat balloon before, during, and after 5 min of hyperventilation. Heart rate spectral analysis suggested diminished sympathetic and vagal activity during hyperventilation and increased sympathetic and vagal activity after hyperventilation. Adrenergic agents influenced (P = 0.01) the tonic response after, but not during, hyperventilation. Yohimbine reduced the increment in colonic tone after hyperventilation compared with saline (P < 0.05) and clonidine (P = 0.002); phenylephrine and ritodrine had no effects. Different mechanisms modulate the increase in colonic tone during and after hyperventilation. Yohimbine attenuates the increase in colonic tone after hyperventilation probably by enhancing inhibitory sympathetic input to the colon.

Adrenergic alpha-Agonists↗
PubMed1996

Postural tachycardia syndrome: time frequency mapping.

Orthostatic tachycardia is common but its specificity remains uncertain. Our preliminary work suggested that using autonomic function testing in conjunction with time-frequency mapping (TFM), it might be possible to characterize a subset of the postural tachycardia syndrome (POTS), that is due to a restricted autonomic neuropathy. We describe 20 patients (17 women and 3 men, aged 14-43 years) with florid POTS and 20 controls (14 women and 6 men, aged 20-41 years). Autonomic failure was quantified by its distribution (cardiovagal, adrenergic and sudomotor) and severity, a symptom profile was generated, and spectral indices, based on modified Wigner distribution during rest and head-up tilt (80 degrees) were evaluated. During tilt-up POTS patients differed from controls by an excessive heart rate (> 130 bpm) (P < 0.001), and higher diastolic pressure (P < 0.01). During rest, cardiovagal oscillations (at respiratory frequencies [RF]) and slow rhythms at nonrespiratory frequencies (NONRF) (from 0.01 to 0.07 Hz) in R-R intervals (RRI) (P < 0.01) were reduced. Both RF and NONRF rhythms in RRI were further blunted with tilt-up (P < 0.001). Slow adrenergic vasomotor rhythms in blood pressure (BP) (approximately 0.07 Hz) surged with tilt-up and returned to normal levels afterwards. The index of sympatho-vagal balance (NONRF-Systolic BP (SBP)/RF-RRI) was dramatically increased in POTS (P < 0.001). Distal postganglionic sudomotor failure was observed, and impairment of the BP responses to the Valsalva maneuver (phase II) suggested peripheral adrenergic dysfunction. Persistent orthostatic dizziness, tiredness, gastrointestinal symptoms and palpitations were common in POTS patients. It is possible to identify a subset of POTS patients who have a length-dependent autonomic neuropathy, affecting the peripheral adrenergic and cardiovagal fibers, with relative preservation of cardiac adrenergic fibers.

Adolescent↗
PubMed1996

Is the heart "empty' at syncope?

Neurally-mediated syncope (NMS) is thought to be reflexly triggered by vagal cardiac ventricular afferents that are activated by impaired cardiac filling. If this hypothesis is true then maneuvers that increase venous pooling should progressively diminish cardiac volume triggering syncope once a threshold decrease in cardiac filling is reached. Beat-to-beat recordings of heart rate, blood pressure (Finapres) and stroke volume (impedance cardiograph) were made at rest and during head-up tilt (80 degrees) in twenty controls and in fourteen patients with recurrent NMS (group 1). Hemodynamic profiles of controls and group 1 were compared. In eleven additional patients with NMS (group 2) we measured cardiac chamber volume from apical two or four-chamber views or stroke volume from Doppler measurements of the left ventricular outflow tract at rest and during tilt. Baseline values and initial response to head-up tilt of controls and group 1 patients were similar. A small negative trend in blood pressure and total peripheral resistance was present for at least 250 s before the onset of syncope. Stroke volume remained stable during this presyncopal period and increased at syncope. The profile of stroke volume changes using impedance cardiography mirrored those obtained using Doppler (5 subjects). Reliable echocardiographic measurements of cardiac chamber size were obtained in five subjects and did not change during tilt, presyncope or syncope. These data show that there is no significant decrease in cardiac volume before syncope that could serve as a trigger of syncope.

Adult↗
PubMed1996

Spontaneous blood pressure fluctuations and renal blood flow dynamics.

Two mechanisms operating at 0.03-0.05 and 0.1-0.2 Hz are involved in autoregulation of renal blood flow (RBF). To examine the behavior of the faster system, the response of RBF to spontaneous fluctuations of arterial pressure was assessed in Sprague-Dawley rats anesthetized by isoflurane or halothane. During halothane anesthesia, autonomous oscillation of total RBF was observed at 0.10-0.15 Hz, and normalized admittance gain became negative at 0.11 +/- 0.01 Hz. During isoflurane anesthesia, there was autonomous power in blood flow in a broad peak between 0.15 and 0.25 Hz, and gain became negative at 0.15 +/- 0.01 Hz. Increasing inspired isoflurane concentration from 1.4 +/- 0.1% to 2.2 +/- 0.1% reduced pressure by 22 +/- 2 mmHg but did not alter blood flow or the transfer function, indicating that the operating frequency was not changed. In another experiment, changing from isoflurane to halothane increased peak power in the autonomous blood flow oscillation fivefold and reduced its frequency from 0.18 +/- 0.01 to 0.14 +/- 0.01 Hz. Gain became negative at a higher frequency (0.16 +/- 0.01 Hz) during isoflurane than halothane anesthesia (0.12 +/- 0.01 Hz). The results show that the 0.1-0.2 Hz system is reliably detected under unforced conditions and provides modest attenuation of pressure fluctuations at < or = 0.1 Hz. Its operating frequency under isoflurane anesthesia is consistent with previous estimates from barbiturate-anesthetized rats, whereas it operates significantly slower under halothane anesthesia.

Administration, Inhalation↗
PubMed1995

The effect of severe brainstem injury on heart rate and blood pressure oscillations.

To determine whether an intact brainstem is essential for the generation of neurogenically mediated fluctuations of R-R intervals and blood pressure, three patients with cerebellar lesions causing severe brainstem compression or death, one patient with a large pontine infarct and one patient with a pontine haemorrhage, were studied. Time-frequency maps (based on a modified Wigner distribution) were constructed from blood pressure and R-R interval signals in these patients with brainstem injury and were compared with maps of normal control subjects. Low frequency sympathetically mediated rhythms (0.01-0.12 Hz) in systolic and diastolic pressure remained detectable but attenuated in patients with brainstem injury whereas there was an almost complete loss of normal R-R intervals rhythmicity over 0.01 to 0.5 Hz range. These data suggest that fluctuations in R-R intervals require an intact brainstem, whereas low frequency approximately 0.06 +/- 0.02 Hz blood pressure rhythms may be preserved by spinal sympathetic circuitry.

Aged↗
PubMed1995

Slow cardiovascular rhythms in tilt and syncope.

The cardiovascular oscillations during orthostasis were analyzed by time-frequency mapping in 23 patients with history of vasodepressor (VD) syncope and in 10 control subjects. Syncope was induced by head-up tilt (80 degrees, 25 min) alone in 11 patients (VD-1). Twelve patients remained asymptomatic (VD-2) during this tilt, but presented VD syncope or presyncope during tilt with an isoproterenol infusion. Data from the first tilt without isoproterenol infusion are presented here. Amplitude of sympathetically-mediated nonrespiratory fluctuations [0.01 Hz-respiratory frequency (Rf)] in blood pressure was greater at the beginning of the tilt in both (VD-1 and VD-2) groups compared to controls. Nonrespiratory oscillations were present throughout the tilt and their amplitude increased toward its end (p < 0.001) in VD-2 and control groups. In contrast, in the VD-1 group, the amplitude of 0.01-0.05 Hz rhythm in blood pressure diminished shortly after the beginning of tilt and continued to decline toward the syncope. Nonrespiratory fluctuations in R-R intervals were greatest in VD-1 group. The slow blood pressure rhythms reflect an integrity of feedback loops, and their disappearance is an early sign of an impending syncope.

Adult↗
PubMed1994

Time-frequency analysis of slow cortical activity and cardiovascular fluctuations in a case of Alzheimer's disease.

The dynamics and relationship of slow cortical activity (amplitude modulation of electroencephalograph at 0.02-0.05 Hz) and cardiovascular fluctuations (0.01-0.05 Hz range) was studied by time-frequency mapping (modified Wigner distribution) in a patient with Alzheimer's disease. The amplitude modulating at rest basal alpha and theta activity (lead Oz) was exaggerated compared with control subjects. Fluctuations at respiratory and nonrespiratory (0.01-0.05 Hz) frequencies in R-R intervals and blood pressure were present and within normal range. Spontaneous hypotension (by 20 to 80 mmHg lasting 15-20 s) accompanied by cardioacceleration occurred repeatedly in the supine position and during hyperventilation. Slow cortical activity and nonrespiratory fluctuations (0.01-0.05 Hz) in blood pressure increased concurrently with hypotensions. No signs of peripheral autonomic dysfunction or malfunction of baroreceptors were observed and the vasomotor instability appeared to be of central origin. The results suggested that slow cortical activity was functionally related to the central autonomic nervous system and reflected cortico-thalamo-brainstem interaction.

Alpha Rhythm↗