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Biomedical subjects

John M Karemaker

Publications and source records attributed to John M Karemaker.

At least 19 recordsLinked to original sources
PubMed2006

Quantification of wave reflection in the human aorta from pressure alone: a proof of principle.

Wave reflections affect the proximal aortic pressure and flow waves and play a role in systolic hypertension. A measure of wave reflection, receiving much attention, is the augmentation index (AI), the ratio of the secondary rise in pressure and pulse pressure. AI can be limiting, because it depends not only on the magnitude of wave reflection but also on wave shapes and timing of incident and reflected waves. More accurate measures are obtainable after separation of pressure in its forward (P(f)) and reflected (P(b)) components. However, this calculation requires measurement of aortic flow. We explore the possibility of replacing the unknown flow by a triangular wave, with duration equal to ejection time, and peak flow at the inflection point of pressure (F(tIP)) and, for a second analysis, at 30% of ejection time (F(t30)). Wave form analysis gave forward and backward pressure waves. Reflection magnitude (RM) and reflection index (RI) were defined as RM=P(b)/P(f) and RI=P(b)/(P(f)+P(b)), respectively. Healthy subjects, including interventions such as exercise and Valsalva maneuvers, and patients with ischemic heart disease and failure were analyzed. RMs and RIs using F(tIP) and F(t30) were compared with those using measured flow (F(m)). Pressure and flow were recorded with high fidelity pressure and velocity sensors. Relations are: RM(tIP)=0.82RM(mf)+0.06 (R(2)=0.79; n=24), RM(t30)=0.79RM(mf)+0.08 (R(2)=0.85; n=29) and RI(tIP)=0.89RI(mf)+0.02 (R(2)=0.81; n=24), RI(t30)=0.83RI(mf)+0.05 (R(2)=0.88; n=29). We suggest that wave reflection can be derived from uncalibrated aortic pressure alone, even when no clear inflection point is distinguishable and AI cannot be obtained. Epidemiological studies should establish its clinical value.

Adult↗
PubMed2006

Time course analysis of baroreflex sensitivity during postural stress.

Postural stress requires immediate autonomic nervous action to maintain blood pressure. We determined time-domain cardiac baroreflex sensitivity (BRS) and time delay (tau) between systolic blood pressure and interbeat interval variations during stepwise changes in the angle of vertical body axis (alpha). The assumption was that with increasing postural stress, BRS becomes attenuated, accompanied by a shift in tau toward higher values. In 10 healthy young volunteers, alpha included 20 degrees head-down tilt (-20 degrees), supine (0 degree), 30 and 70 degrees head-up tilt (30 degrees, 70 degrees), and free standing (90 degrees). Noninvasive blood pressures were analyzed over 6-min periods before and after each change in alpha. The BRS was determined by frequency-domain analysis and with xBRS, a cross-correlation time-domain method. On average, between 28 (-20 degrees) to 45 (90 degrees) xBRS estimates per minute became available. Following a change in alpha, xBRS reached a different mean level in the first minute in 78% of the cases and in 93% after 6 min. With increasing alpha, BRS decreased: BRS = -10.1.sin(alpha) + 18.7 (r(2) = 0.99) with tight correlation between xBRS and cross-spectral gain (r(2) approximately 0.97). Delay tau shifted toward higher values. In conclusion, in healthy subjects the sensitivity of the cardiac baroreflex obtained from time domain decreases linearly with sin(alpha), and the start of baroreflex adaptation to a physiological perturbation like postural stress occurs rapidly. The decreases of BRS and reduction of short tau may be the result of reduced vagal activity with increasing alpha.

Adaptation, Physiological↗
PubMed2006

Changes in finger-aorta pressure transfer function during and after exercise.

Noninvasive finger blood pressure has become a surrogate for central blood pressure under widely varying circumstances. We tested the validity of finger-aorta transfer functions (TF) to reconstruct aortic pressure in seven cardiac patients before, during, and after incremental bicycle exercise. The autoregressive exogenous model method was used for calculating finger-aorta TFs. Finger pressure was measured noninvasively using Finapres and aortic pressure using a catheter-tip manometer. When applying the individual TFs found during rest for reconstruction of aortic pressure during all workloads, systolic pressure was increasingly underestimated, with large variation between subjects: +4.0 to -18.1 mmHg. In most subjects, diastolic pressure was overestimated: -3.9 to +5.5 mmHg. Pulse pressure estimation varied between +4.5 and -21.9 mmHg. In all cases, wave distortion was present. Postexercise, error in reconstructed aortic systolic pressure slowly declined, and diastolic pressure was overestimated. During rest, the TF gain had a minimum between 3.65 and 4.85 Hz (Fmin). During exercise, Fmin shifted to frequencies between 4.95 and 7.15 Hz at the maximum workload, with no change in gain. Postexercise, gain in most subjects shifted to values closer to unity, whereas Fmin did not return to resting values. Within each subject, aorta-Finapres travel time was linearly related to mean pressure. During exercise, Fmin was linearly related to both delay and heart rate. We conclude that, during increasing exercise, rest TFs give an increasingly unreliable reconstruction of aortic pressure, especially at higher heart rates.

Adult↗
PubMed2006

Increased sympathetic activity present in early hypertensive pregnancy is not lowered by plasma volume expansion.

OBJECTIVE: To evaluate whether sympathetic activity is increased in early-onset hypertensive pregnancy and whether this can be influenced by management with plasma volume expansion. METHODS: The study group consisted of 74 subjects, of which 37 had early-onset hypertensive disorders of pregnancy (preeclampsia or gestational hypertension with fetal growth restriction), who were included at 24 to 34 weeks in a randomized controlled trial of management with (n = 18) or without (n = 19) plasma volume expansion. Heart rate and blood pressure variabilities, LF/HF ratio for heart rate, baroreflex sensitivity, and phase difference at low frequency (LF approximately 0.1 Hz) were calculated by spectral analysis from continuous heart rate and blood pressure recordings of the finger pulse wave (Portaprestrade mark, TNO). Measurements were performed at inclusion, after 20 to 40 hours and after 65 to 100 hours. The control group consisted of 29 women with a normal pregnancy and 8 women who had late-onset preeclampsia after 34 weeks. Controls were measured at 32 weeks. All controls had a normal blood pressures at that time. RESULTS: LF variability of heart rate and blood pressure were significantly higher and baroreflex sensitivity was significantly lower in early-onset patients compared with normal controls. A significant trend towards higher LF variability of blood pressure and lower baroreflex sensitivity was found from normal controls to late-onset controls to early-onset patients. Parameters of sympathetic activity were not influenced by plasma volume expansion. CONCLUSION: Sympathetic activity was increased in early-onset hypertensive pregnancy. However, this was not affected by management with plasma volume expansion, suggesting that hypovolaemia in preeclampsia is a secondary phenomenon.

Adult↗
PubMed2005

Dynamic cerebral autoregulation in acute lacunar and middle cerebral artery territory ischemic stroke.

BACKGROUND AND PURPOSE: We addressed whether dynamic cerebral autoregulation (dCA) is affected in middle cerebral artery (MCA) territory (MCAS) and lacunar ischemic stroke (LS). METHODS: Blood pressure (MAP) and MCA velocity (V) were measured in 10 patients with large MCAS (National Institutes of Health Stroke score, 17+/-2; mean+/-SEM), in 10 with LS (score, 9+/-1), and in 10 reference subjects. dCA was evaluated in time (delay of the MCA Vmean counter-regulation during changes in MAP) and frequency domains (cross-spectral MCA Vmean-to-MAP phase lead). RESULTS: In reference subjects, latencies for MAP increments (5.3+/-0.5 seconds) and decrements (5.6+/-0.5 seconds) were comparable, and low frequency MCA Vmean-to-MAP phase lead was 56+/-5 and 59+/-5 degrees (left and right hemisphere). In MCAS, these latencies were 4.6+/-0.7 and 5.6+/-0.5 seconds in the nonischemic hemisphere and not detectable in the ischemic hemisphere. In the unaffected hemisphere, phase lead was 61+/-6 degrees versus 26+/-6 degrees on the ischemic side (P<0.05). In LS, no latency and smaller phase lead bilaterally (32+/-6 and 33+/-5 degrees) conformed to globally impaired dCA. CONCLUSIONS: In large MCAS infarcts, dynamic cerebral autoregulation was impaired in the affected hemisphere. In LS, dynamic cerebral autoregulation was impaired bilaterally, a finding consistent with the hypothesis of bilateral small vessel disease in patients with lacunar infarcts.

Blood Flow Velocity↗
PubMed2004

Impaired cerebral autoregulation in patients with malignant hypertension.

BACKGROUND: In patients with a malignant hypertension, immediate parenteral treatment with blood pressure-lowering agents such as intravenous sodium nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic cerebral autoregulation (CA) during acute blood pressure lowering with SNP in these patients. METHODS AND RESULTS: In 8 patients with mean arterial pressure (MAP) >140 mm Hg and grade III or IV hypertensive retinopathy at hospital admission, middle cerebral artery blood velocity (MCA V) and blood pressure were monitored. Dynamic CA was expressed as the 0.1-Hz MCA V(mean) to MAP phase lead and static CA as the MCA V(mean) to MAP relationship during SNP treatment. Eight normotensive subjects served as a reference group. In the patients, the MCA V(mean) to MAP phase lead was lower (30+/-8 degrees versus 58+/-5 degrees , mean+/-SEM; P<0.05), whereas the transfer gain tended to be higher. During SNP treatment, target MAP was reached within 90 minutes in all patients. The MCA V(mean) decrease was 22+/-4%, along with a 27+/-3% reduction in MAP (from 166+/-4 to 121+/-6 mm Hg; P<0.05) in a linear fashion (averaged slope, 0.82+/-0.15% cm x s(-1) . % mm Hg(-1); r=0.70+/-0.07). CONCLUSIONS: In patients with malignant hypertension, dynamic CA is impaired. An MCA V(mean) plateau was not detected during the whole SNP treatment, indicating loss of static CA as well. This study showed that during the whole rapid reduction in blood pressure with SNP, MCA V(mean) decreases almost one on one with MAP.

Adrenal Cortex Hormones↗
PubMed2004

Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated vasovagal response.

OBJECTIVES: We set out to determine the effect of sublingual nitroglycerin (NTG), as used during routine tilt testing in patients with unexplained syncope, on hemodynamic characteristics and baroreflex control of heart rate (HR) and systemic vascular resistance (SVR). BACKGROUND: Nitroglycerin is used in tilt testing to elicit a vasovagal response. It is known to induce venous dilation and enhance pooling. Also, NTG is lipophilic and readily passes cell membranes, and animal studies suggest a sympatho-inhibitory effect of NTG on circulatory control. METHODS: Routine tilt testing was conducted in 39 patients with suspected vasovagal syncope (age 36 +/- 16 years, 18 females). Patients were otherwise healthy and free of medication. Before a loss of consciousness set in, oncoming syncope was cut short by tilt-back or counter-maneuvers. Finger arterial pressure was monitored continuously (Finapres). Left ventricular stroke volume (SV) was computed from the pressure pulsations (Modelflow). Spontaneous baroreflex control of HR was estimated in the time and frequency domains. RESULTS: During tilt testing, 22 patients developed presyncope. After NTG administration but before presyncope, SV and cardiac output (CO) decreased (p < 0.001), whereas SVR and HR increased (p < 0.001) in all patients. Arterial pressure was initially maintained. Baroreflex sensitivity decreased after NTG. On Cox regression analysis, the occurrence of a vasovagal response was related to a drop in SV after NTG (hazard ratio 0.86, p = 0.005). CONCLUSIONS: The cardiovascular response to NTG is similar in vasovagal and non-vasovagal patients, but more pronounced in those with tilt-positive results. The NTG-facilitated presyncope appears to be CO-mediated, and there is no evidence of NTG-induced sympathetic inhibition.

Administration, Sublingual↗
PubMed2004

Long-term effects of unilateral carotid endarterectomy on arterial baroreflex function.

BACKGROUND AND PURPOSE: Carotid endarterectomy (CE) may be complicated by the clinical syndrome of baroreflex failure. Alterations of baroreflex function may also account for the frequently observed blood pressure lability in the first hours following surgery. We investigated the long-term effects of unilateral CE on baroreflex control of function and blood pressure. METHODS: We investigated 14 patients after unilateral CE (13 m:1 f, 64.8 +/- 6.5 years), 9 patients with a surgically untreated uni-/bilateral carotid stenosis (CS, 7 m:2 f, 57.6 +/- 10.7 years) and 12 healthy controls (HC, 11 m:1 f, 60.9 +/- 7.9 years) by means of Valsalva maneuver, active standing, forced breathing, cold face test, cold pressor test and mental arithmetic. Ambulatory blood pressure level and variability were determined from 24-hour Spacelabs and 5-hour beat-to-beat Portapres recordings. RESULTS: Baroreflex sensitivity (derived from phase IV Valsalva maneuver) was significantly lower in CE (1.53 +/- 0.83 ms/mmHg) than in CS (4.39 +/- 2.27, p = 0.002) and HC (5.34 +/- 3.78, p = 0.003). CE patients exhibited a decreased reflex control of heart rate in response to Valsalva's maneuver and active standing without orthostatic hypotension. Office blood pressure levels before and after endarterectomy were similar, as were ambulatory blood pressure levels in the three groups. Ambulatory blood pressure variability was higher in CE and CS than in HC, but not different between CE and CS. CONCLUSIONS: Unilateral CE causes a long-term impairment of baroreflex function, resulting in an attenuated reflex control of heart rate, but no hypertension or blood pressure lability.

Adult↗
PubMed2004

Use of lower abdominal compression to combat orthostatic hypotension in patients with autonomic dysfunction.

The aim of this study was to investigate in patients with neurogenic orthostatic hypotension the mechanism and usefulness of abdominal compression to increase standing blood pressure. In three protocols, 23 patients underwent abdominal compression. Protocol 1 evaluated in a 40-60 degrees head-up-tilt position, the effect of abdominal compression on caval vein and femoral diameter, arterial blood pressure and hemodynamics. Protocol 2 documented the relationship between the level of compression and the arterial pressure response. Protocol 3 investigated the ability to maintain standing blood pressure by an elastic binder. During head-up-tilt, compression (40 mm Hg) resulted in a reduction in diameter of the caval vein (mean -2.6mm, range -1.4 to 0.6), without a change in femoral vein diameter. Stroke volume increased by 14 % (range -1 to 23) and blood pressure (systolic/diastolic) by 30/14 mmHg (range 7/2 to 69/36), both p < 0.05; 40 mmHg compression was associated with a higher pressure response than 20 mmHg (mean 18/8 mmHg, range 6/2 to 43/20 vs. mean 9/4 mmHg, range -1/0 to 18/8, p < 0.05). Elastic abdominal binding increased standing blood pressure with 15/6 mmHg (range -3/3 to 36/14, p < 0.05). We conclude that in patients with neurogenic orthostatic hypotension, abdominal compression increases standing blood pressure to a varying degree by increasing stroke volume.

Abdomen↗
PubMed2004

The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans.

The direct vasodilatory and negative chronotropic effects of adenosine in humans are counterbalanced by a reflex increase in sympathetic nerve traffic. A suggested mechanism for this reflex includes peripheral chemoreceptor activation. We, therefore, assessed the contribution of carotid chemoreceptors to sympatho-excitation by adenosine. Muscle sympathetic nerve activity was recorded during adenosine infusion (140 microg.kg(-1).min(-1) for 5 min) in five patients lacking carotid chemoreceptors after bilateral carotid body tumour resection (one male and four female, mean age 51 +/- 11 years) and in six healthy controls (two male and four female, mean age 50 +/- 7 years). Sympathetic responses to sodium nitroprusside injections were assessed to measure baroreceptor-mediated sympathetic activation. In response to adenosine, controls showed no change in blood pressure, an increase in heart rate (+48.2 +/- 13.2%; P<0.003) and an increase in sympathetic nerve activity (+195 +/- 103%; P<0.022). In contrast, patients showed a decrease in blood pressure (-14.6 +/- 4.9/-17.6 +/- 6.0%; P<0.05), an increase in heart rate (+25.3 +/- 8.4%; P<0.032) and no significant change in sympathetic activity. Adenosine-induced hypotension in individual patients elicited less sympathetic activation than equihypotensive sodium nitroprusside injections. In humans lacking carotid chemoreceptors, adenosine infusion elicits hypotension due to the absence of significant sympatho-excitation. Chemoreceptor activation is essential for counterbalancing the direct vasodilation by adenosine. In addition, blunting of the baroreflex sympathetic response to adenosine-induced hypotension may indicate a direct sympatho-inhibitory effect of adenosine.

Adenosine↗
PubMed2004

Time-domain cross-correlation baroreflex sensitivity: performance on the EUROBAVAR data set.

OBJECTIVE: To test a new method (cross-correlation baroreflex sensitivity, xBRS) for the computation of time-domain baroreflex sensitivity on spontaneous blood pressure and heart interval variability using the EUROBAVAR data set. METHODS: We applied xBRS to the 42 records in the EUROBAVAR data set, obtained from 21 patients in the lying and standing positions. One patient had a recent heart transplant and one was diabetic with evident cardiac autonomic neuropathy. xBRS computes the correlation between beat-to-beat systolic blood pressure and R-R interval, resampled at 1 Hz, in a sliding 10 s window, with delays of 0-5 s for interval. The delay with the greatest positive correlation is selected and, when significant at P = 0.01, slope and delay are recorded as one xBRS value. Each 1 s of the recording is the start of a new computation. Non-parametric tests are used. RESULTS: With patients in the lying position, xBRS yielded a value of 12.4 ms/mmHg compared with the EUROBAVAR sequential 16.2 ms/mmHg, and for the standing positions the respective values were 6.2 and 6.7 ms/mmHg, giving lying to standing ratios of 1.96 and 2.10, respectively. xBRS yielded results for all files, with 20 values per minute on average at a lower within-patient variance. Best delays were 0, 1 and 2 s, and the delay increased by 102 ms when the patient was in the standing position. The xBRS method was successful in the patients with diabetes and the heart transplant. CONCLUSION: The xBRS method should be considered for experimental and clinical use, because it yielded values that correlated strongly with and were close to the EUROBAVAR averages, yielded more values per minute, had lower within-patient variance and measured baroreflex delay.

Adult↗
PubMed2004

Cardiovascular responses to stress after carotid baroreceptor denervation in humans.

Iatrogenic bilateral denervation of carotid sinus baroreceptors may occur as a complication of carotid body tumor resection and radiation therapy of the neck. The acute phase of the resulting syndrome of baroreflex failure is characterized by a limited blood pressure buffering capacity against excessive rise or fall in response to emotional and physical stimuli like sexual arousal and cold. Paroxysms of severe hypertension and tachycardia, accompanied by excessive increments in sympathetic tone and catecholamine plasma levels, were ascribed to loss of tonic inhibitory influence of baroreceptors on sympathetic tone. Bilateral anesthetic blockade of baroreceptor afferent nerves was shown to result in a strong increase in muscle sympathetic nerve activity and disruption of its normal patterning. This chapter reviews our findings on the long-term effects of iatrogenic baroreflex trauma on the hemodynamic responses to pharmacological, physical, and emotional stress in the autonomic function laboratory as well as under daily life conditions. Chronic attenuation of baroreflex sensitivity after carotid body tumor resection and neck irradiation results in an increased blood pressure variability. However, unopposed sympathetic activation in response to physical and emotional stress appears to be limited to the acute phase of baroreflex failure.

Carotid Arteries↗
PubMed2004

Tilt table design for rapid and sinusoidal posture change with minimal vestibular stimulation.

INTRODUCTION: Cardiovascular response to fast posture change can be used to model individual orthostatic response under normal circumstances and after spaceflight. We set out to construct a computer-controlled tilt table suitable for repeated sinusoidal tilt motion as well as fast, single head-up tilt (HUT). The movement profile of the table was designed to prevent muscle tensing and limit vestibular stimulation. METHODS: On the new table, 20 healthy subjects underwent a protocol of fast HUT and sinusoidal tilt motion at 2.5 tilts per minute. BP was measured non-invasively (Finapres). Time domain dynamic response to HUT and frequency domain response to sinusoidal tilts were derived from the beat-to-beat BP and from interbeat-interval (IBI) series. RESULTS: Tilt motion did not induce dizziness and was experienced by all subjects as smooth. The systolic BP response to fast HUT correlated mildly with the systolic BP spectral power at the sinusoidal tilt frequency (R = 0.47). The IBI response to fast HUT correlated well with the IBI power at the sinusoidal tilt frequency (R = 0.74). DISCUSSION: In this study we presented a computer controlled tilt table capable of fast posture change and sinusoidal tilts. An exploratory protocol demonstrated that the table is suitable for obtaining cardiovascular response to posture change for modeling purposes.

Adult↗
PubMed2003

Tidal volume, cardiac output and functional residual capacity determine end-tidal CO2 transient during standing up in humans.

In man assuming the upright position, end-tidal P(CO(2)) (P(ETCO(2))) decreases. With the rising interest in cerebral autoregulation during posture change, which is known to be affected by P(ETCO(2)), we sought to determine the factors leading to hypocapnia during standing up from the supine position. To study the contribution of an increase in tidal volume (V(T)) and breathing frequency, a decrease in stroke volume (SV), a ventilation-perfusion (V/Q) gradient and an increase in functional residual capacity (FRC) to hypocapnia in the standing position, we developed a mathematical model of the lung to follow breath-to-breath variations in P(ETCO(2)). A gravity-induced apical-to-basal V/Q gradient in the lung was modelled using nine lung segments. We tested the model using an eight-subject data set with measurements of V(T), pulmonary O(2) uptake and breath-to-breath lumped SV. On average, the P(ETCO(2)) decreased from 40 mmHg to 36 mmHg after 150 s standing. Results show that the model is able to track breath-to-breath P(ETCO(2)) variations (r(2)= 0.74, P P 0.05). Model parameter sensitivity analysis demonstrates that the decrease in P(ETCO(2)) during standing is due primarily to increased V(T), and transiently to decreased SV and increased FRC; a slight gravity-induced V/Q mismatch also contributes to the hypocapnia. The influence of cardiac output on hypocapnia in the standing position was verified in experiments on human subjects, where first breathing alone, and then breathing, FRC and V/Q were controlled.

Adult↗
PubMed2003

Denervation of carotid baro- and chemoreceptors in humans.

Experimental denervation in animals has shown that carotid baro- and chemoreceptors play an eminent role in maintaining blood pressure and blood gas homeostasis. Denervation of carotid sinus baro- and chemoreceptors in humans may occur as a complication of invasive interventions on the neck or after experimental surgical treatment in asthma. In this topical review, the short- and long-term effects of carotid baro- and chemoreceptor denervation on the control of circulation and ventilation in humans are discussed. Carotid baroreceptor denervation in humans causes a persistent decrease in vagal and sympathetic baroreflex sensitivity and an increase in blood pressure variability; however, carotid denervation does not lead to chronic hypertension. Therefore, although carotid baroreceptors contribute to short-term blood pressure control, other receptors are able to maintain normal chronic blood pressure levels in the absence of carotid baroreceptors. Conversely, carotid chemoreceptor denervation leads to permanent abolition of normocapnic ventilatory responses to hypoxia and reduced ventilatory responses to hypercapnia.

Animals↗
PubMed2003

Comparison of various techniques used to estimate spontaneous baroreflex sensitivity (the EuroBaVar study).

This study compared spontaneous baroreflex sensitivity (BRS) estimates obtained from an identical set of data by 11 European centers using different methods and procedures. Noninvasive blood pressure (BP) and ECG recordings were obtained in 21 subjects, including 2 subjects with established baroreflex failure. Twenty-one estimates of BRS were obtained by methods including the two main techniques of BRS estimates, i.e., the spectral analysis (11 procedures) and the sequence method (7 procedures) but also one trigonometric regressive spectral analysis method (TRS), one exogenous model with autoregressive input method (X-AR), and one Z method. With subjects in a supine position, BRS estimates obtained with calculations of alpha-coefficient or gain of the transfer function in both the low-frequency band or high-frequency band, TRS, and sequence methods gave strongly related results. Conversely, weighted gain, X-AR, and Z exhibited lower agreement with all the other techniques. In addition, the use of mean BP instead of systolic BP in the sequence method decreased the relationships with the other estimates. Some procedures were unable to provide results when BRS estimates were expected to be very low in data sets (in patients with established baroreflex failure). The failure to provide BRS values was due to setting of algorithmic parameters too strictly. The discrepancies between procedures show that the choice of parameters and data handling should be considered before BRS estimation. These data are available on the web site (http://www.cbi.polimi.it/glossary/eurobavar.html) to allow the comparison of new techniques with this set of results.

Adult↗