Systemic Arterial Pressure Signals Research Articles

Investigation of Cerebral Autoregulation Using Time-Frequency Transformations.

The authors carried out the study of the state of systemic and cerebral hemodynamics in normal conditions and in various neurosurgical pathologies using modern signal processing methods. The results characterize the condition for the mechanisms of cerebral circulation Institute of Computer Science and Control, Higher School of Cyber-Physical Systems and Control regulation, which allows for finding a solution to fundamental and specific clinical problems for the effective treatment of patients with various pathologies. The proposed method is based on the continuous wavelet transform of systemic arterial pressure and blood flow velocity signals in the middle cerebral artery recorded by non-invasive methods of photoplethysmography and transcranial doppler ultrasonography. The study of these signals in real-time in the frequency range of Mayer waves makes it possible to determine the cerebral autoregulation state in certain diseases before and after surgical interventions. The proposed method uses a cross-wavelet spectrum, which helps obtain wavelet coherence and a phase shift between the wavelet coefficients of systemic arterial pressure signals and blood flow velocity in the Mayer wave range. The obtained results enable comparing the proposed method with that based on the short-time Fourier transform. The comparison showed that the proposed method has higher sensitivity to changes in cerebral autoregulation and better localization of changes in time and frequency.

Implementation and Calibration of a Deep Neural Network to Predict Parameters of Left Ventricular Systolic Function Based on Pulmonary and Systemic Arterial Pressure Signals.

The evaluation of cardiac contractility by the assessment of the ventricular systolic elastance function is clinically challenging and cannot be easily obtained at the bedside. In this work, we present a framework characterizing left ventricular systolic function from clinically readily available data, including systemic and pulmonary arterial pressure signals. We implemented and calibrated a deep neural network (DNN) consisting of a multi-layer perceptron with 4 fully connected hidden layers and with 16 neurons per layer, which was trained with data obtained from a lumped model of the cardiovascular system modeling different levels of cardiac function. The lumped model included a function of circulatory autoregulation from carotid baroreceptors in pulsatile conditions. Inputs for the DNN were systemic and pulmonary arterial pressure curves. Outputs from the DNN were parameters of the lumped model characterizing left ventricular systolic function, especially end-systolic elastance. The DNN adequately performed and accurately recovered the relevant hemodynamic parameters with a mean relative error of less than 2%. Therefore, our framework can easily provide complex physiological parameters of cardiac contractility, which could lead to the development of invaluable tools for the clinical evaluation of patients with severe cardiac dysfunction.

Influence of Propofol on Blood Pressure Spectrum in Sepsis and the Role of Inducible Nitric Oxide Synthase

Sepsis is characterized by an increase in nitric oxide (NO) production, hemodynamic dysfunction and multiple organ failure. Propofol, a commonly used anesthetic in the intensive care unit for sedation and hypnosis, is thought to exert a protective effect on NO overproduction by inhibiting the expression of inducible NO synthase (iNOS) in sepsis. The aim of this study was to examine the influence of propofol on the temporal changes in the power density of frequency components of systemic arterial pressure (SAP) variability in rats subject to Escherichia coli lipopolysaccharide (LPS)-induced endotoxemia and to delineate the role of iNOS. Twenty-four Sprague-Dawley rats were used in this study. Arterial catheters were inserted for direct SAP monitoring, and SAP signals were subjected to online real-time power spectral analysis via fast Fourier transformation. Animals were divided into four groups to receive different dosages of propofol infusion (15 or 30 mg/kg/hr) with or without the iNOS synthase inhibitor, S-methylisothiourea (SMT, 2 mg/kg). Changes in the power density of high-frequency (BHF), low-frequency (BLF) or very-low-frequency (BVLF) components of the SAP spectrum in each group were analyzed. Systemic injection of LPS resulted in a transient decrease, followed by a rebound increase and a second-phase decrease in the power density of BHF, BLF and BVLF of the SAP spectrum. Compared with low dose (15 mg/kg/hr), high-dose (30 mg/kg/hr) propofol anesthesia profoundly suppressed the power density of BHF, BLF and BVLF of SAP signals during LPS-induced endotoxemia. Such suppression was not affected by SMT pretreatment. SMT treatment, on the other hand, augmented the rebound increase in the power density of BHF and BLF, and ameliorated the second phase decrease in the power density of BHF in the endotoxemic rats that were maintained under low dose propofol anesthesia. We concluded that iNOS-induced NO might be involved in the manifestation of the BHF and BLF components of the SAP spectrum during endotoxemia when low-dose propofol is used, and this effect of NO is blunted when high-dose propofol is administered.

Activation of estrogen receptor β-dependent nitric oxide signaling mediates the hypotensive effects of estrogen in the rostral ventrolateral medulla of anesthetized rats

BackgroundApart from their well-known peripheral cardiovascular effects, emerging evidence indicates that estrogen acts as a modulator in the brain to regulate cardiovascular functions. The underlying mechanisms of estrogen in central cardiovascular regulation, however, are poorly understood. The present study investigated the cardiovascular effects of 17β-estradiol (E2β) in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons are located, and delineated the engagement of nitric oxide (NO) in E2β-induced cardiovascular responses.MethodsIn male Sprague-Dawley rats maintained under propofol anesthesia, the changes of blood pressure, heart rate and sympathetic vasomotor tone after microinjection bilaterally into the RVLM of a synthetic estrogen, E2β were examined for at least 120 min. The involvement of ERα and/or ERβ subtypes was determined by microinjection of selective ERα or ERβ agonist into bilateral RVLM. Different NO synthase (NOS) inhibitors were used to evaluate the involvement of differential of NOS isoforms in the cardiovascular effects of E2β.ResultsBilateral microinjection of E2β (0.5, 1, or 5 pmol) into the RVLM dose-dependently decreased systemic arterial pressure (SAP) and the power density of the vasomotor components of SAP signals, our experimental index for sympathetic neurogenic vasomotor tone. These cardiovascular depressive effects of E2β (1 pmol) were abolished by co-injection of ER antagonist ICI 182780 (0.25 or 0.5 pmol), but not a transcription inhibitor actinomycin D (10 nmol). Like E2β, microinjection bilaterally into the RVLM of a selective ERβ agonist 2,3-bis(4-hydroxyphenyl) propionitrile (DPN, 1, 2, or 5 pmol) induced significant decreases in these hemodynamic parameters in a dose-dependent manner. In contrast, the selective ERα agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (5 pmol) did not influence the same cardiovascular parameters. Co-administration bilaterally into the RVLM of NOS inhibitor NG-nitro-L-arginine methyl ester (5 nmol) or selective inducible NOS (iNOS) inhibitor S-methylisothiourea (25 pmol), but not selective neuronal NOS inhibitor 7-nitroindazole (0.5 pmol) or endothelial NOS inhibitor N5-(1-Iminoethyl)-L-ornithine (2.5 pmol), significantly attenuated the cardiovascular depressive effects elicited by DPN (2 pmol).ConclusionOur results indicate that E2β in the RVLM elicited short-term cardiovascular depressive effects via an ERβ-dependent nontranscriptional mechanism. These vasodepressor effects of E2β are likely to be mediated by the iNOS-derived NO in the RVLM.

Nitric oxide and GABA mediate bi-directional cardiovascular effects of orexin in the nucleus tractus solitarii of rats

The present study investigated the cardiovascular effects of orexin (OX)-A and OX-B in the nucleus tractus solitarii (NTS) and delineated the engagement of nitric oxide (NO) and GABA in OX-induced cardiovascular responses. In adult male Sprague–Dawley rats maintained under propofol anesthesia, microinjection bilaterally into the NTS of OX-A or OX-B evoked bi-directional cardiovascular effects in a dose-dependent manner. At a lower dose (5 pmol), OX-A or OX-B decreased systemic arterial pressure (SAP), heart rate (HR), and power density of the vasomotor components of SAP signals, our experimental index for sympathetic neurogenic vasomotor tone. At higher doses (>20 pmol), these two compounds elicited cardiovascular excitatory responses. These bi-directional cardiovascular effects of OX were abolished by co-injection of an OX 1 receptor antagonist, 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl-urea hydrochloride (SB-334867, 0.75 nmol) or the OX 2 receptor antiserum (1:20). In addition, the vasodepressor effects of low dose (5 pmol) OX-A or OX-B in the NTS were attenuated by a nitric oxide synthase (NOS) inhibitor, N G-nitro- l-arginine methyl ester ( l-NAME, 5 nmol), a neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (2.5 pmol) or the soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazole[4,3-α]quinoxalin-1-one (250 pmol). The vasopressor effects of high dose (200 pmol) OX were reversed by co-administration with GABA A or GABA B receptor antagonist, bicuculline methiodine (10 pmol) or 2-hydroxy saclofen (100 pmol), or l-NAME (5 nmol). Our results indicate that OX-A or OX-B elicited bi-directional cardiovascular effects via OX receptor-dependent mechanisms. The vasodepressor effects of OX were induced by the nNOS-derived NO and activation of sGC-associated signaling pathway, whereas the vasopressor effects were mediated by interaction with GABAergic or nitrergic neurotransmission in the NTS.

Neuroprotective effects of coenzyme Q10 at rostral ventrolateral medulla against fatality during experimental endotoxemia in the rat.

Coenzyme Q10 (CoQ10, ubiquinone) is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an antioxidant. We evaluated the neuroprotective efficacy of CoQ10 against fatality in an experimental model of endotoxemia that mimics systemic inflammatory response syndrome using a novel water-soluble formulation of this quinone derivative. Experiments were conducted in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Intravenous administration of Escherichia coli lipopolysaccharide (LPS; 30 mg/kg) induced progressive hypotension, with death ensuing within 4 h. The sequence of cardiovascular events during this LPS-induced endotoxemia can be divided into a reduction (Phase I), followed by an augmentation (Phase II; "pro-life" phase) and a secondary decrease (Phase III; "pro-death" phase) in the power density of the vasomotor components (0-0.8 Hz) of systemic arterial pressure signals. Pretreatment by microinjection bilaterally of CoQ10 (1 or 2 microg) into the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, significantly diminished mortality, prolonged survival time, and reduced the slope or magnitude of the LPS-induced hypotension. CoQ10 pretreatment also significantly prolonged the duration of and augmented the total power density of the vasomotor components of systemic arterial pressure signals in Phase II endotoxemia. The increase in superoxide anion production induced by LPS at the RVLM during Phases II and III endotoxemia was also significantly blunted. We conclude that CoQ10 provides neuroprotection against fatality during experimental endotoxemia by reducing superoxide anion production at the RVLM, whose neuronal activity is intimately related to the "life-and-death" process.

Dysfunction of the Mitochondrial Respiratory Chain in the Rostral Ventrolateral Medulla during Experimental Endotoxemia in the Rat

We investigated the functional changes in the mitochondrial respiratory chain at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, in an experimental model of endotoxemia that mimics systemic inflammatory response syndrome. In Sprague-Dawley rats maintained under propofol anesthesia, intravenous administration of Escherichia coli lipopolysaccharide (LPS; 30 mg/kg) induced a reduction (Phase I), followed by an augmentation (Phase II) and a secondary decrease (Phase III) in the power density of vasomotor components (0–0.8 Hz) in systemic arterial pressure signals. LPS also elicited progressive hypotension, and death ensued within 4 h. Enzyme assay revealed significant depression of the activity of nicotinamide adenine dinucleotide cytochrome c reductase (Complexes I + III) and cytochrome c oxidase (Complex IV) in the RVLM during all three phases of endotoxemia. On the other hand, the activity of succinate cytochrome c reductase (Complexes II + III) remained unaltered. We conclude that selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain at the RVLM, whose neuronal activity is intimately related to the death process, is closely associated with fatal endotoxemia in the rat.

Dysfunction of the mitochondrial respiratory chain in the rostral ventrolateral medulla during experimental endotoxemia in the rat

We investigated the functional changes in the mitochondrial respiratory chain at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, in an experimental model of endotoxemia that mimics systemic inflammatory response syndrome. In Sprague-Dawley rats maintained under propofol anesthesia, intravenous administration ofEscherichia coli lipopolysaccharide (LPS; 30 mg/kg) induced a reduction (Phase I), followed by an augmentation (Phase II) and a secondary decrease (Phase III) in the power density of vasomotor components (0–0.8 Hz) in systemic arterial pressure signals. LPS also elicited progressive hypotension, and death ensued within 4 h. Enzyme assay revealed significant depression of the activity of nicotinamide adenine dinucleotide cytochromec reductase (Complexes I + III) and cytochromec oxidase (Complex IV) in the RVLM during all three phases of endotoxemia. On the other hand, the activity of succinate cytochromec reductase (Complexes II + III) remained unaltered. We conclude that selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain at the RVLM, whose neuronal activity is intimately related to the death process, is closely associated with fatal endotoxemia in the rat.

ARTERIAL PRESSURE VARIABILITY FOR EVALUATION OF THE STRESS ON AUTONOMIC NERVOUS SYSTEM OF PATIENTS WITH CARDIAC PACING

Background: The power density values of high frequency (0.15 to 0.4 Hz) and low frequency (0.04 to 0.15 Hz) components of systemic arterial pressure signals (APV arterial pressure variability) have been regarded as the function of autonomic nervous system(ANS). In this study, APV was adopted for evaluation of the sties on ANS of patients with cardiac pacing. Methods: Arterial pressure signals were acquired every 2 hours at 100 Hz for 6 minutes. Power spectral analysis was carried out, and trends of changes in the spectral components of arterial pressure variability-(APV) were observed in patients with cardiac pacing (n = 5) and in patients without pacing (n = 22). including patients with mechanical circulatory support (MCS n = 12). Results: The normalized power spectral component in low frequency (LFAnorm) was depressed initially in MCS patients. Sustained low values in LFAnorm in 4 patients were related to prolonged MCS and poor outcome. On the contrary, LFAnorm of 5 patients with cardiac pacing showed no LFAnorm depression. There was no statistically significant difference in LFAnorm values and the duration of ICU stay between patients with cardiac pacing and those with neither pacing nor MCS. Conclusions: Depressed LFAnorm of APV represented marked stress on ANS and prolongation of the depression was related to poor outcome of patients. The analysis of APV offers a reasonable tool for evaluation of the stress on ANS of patients with cardiac pacing.

Engagement of inducible nitric oxide synthase at the rostral ventrolateral medulla during mevinphos intoxication in the rat.

We evaluated the relationship between the toxicity induced by the organophosphate mevinphos (Mev) and inducible nitric oxide synthase (iNOS) in the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic neurogenic vasomotor tone. Adult Sprague-Dawley rats that were anesthetized and maintained with propofol were used. Laser scanning confocal microscopic analysis revealed colocalization of the M2 subtype of muscarinic receptors (M(2)R) and iNOS immunoreactivity in RVLM neurons. Comicroinjection bilaterally of Mev (10 nmol) and artificial cerebrospinal fluid (aCSF) into the RVLM elicited a progressive decline in systemic arterial pressure (SAP) and heart rate. This was accompanied during phase 1 Mev intoxication by an increase in the power density of the very high-frequency (VHF; 5-9 Hz), high-frequency (HF; 0.8-2.4 Hz), low-frequency (LF; 0.25- 0.8 Hz) and very low-frequency (VLF; 0-0.25 Hz) components of SAP signals. Phase 2 exhibited a reversal of the VHF and VLF power to control levels and a further reduction in the power density of both HF and LF components to below baseline. Hypotension and bradycardia promoted by Mev were significantly blunted on coadministration into the RVLM of the selective iNOS inhibitors S-methylisothiourea (250 pmol) or aminoguanidine (250 pmol). Not only was the augmented power density of HF and LF components during phase 1 Mev intoxication further enhanced, the reduced power of these two spectral components during phase 2 was appreciably antagonized. On the other hand, the temporal changes in VHF and VLF power were essentially the same as with coadministration of Mev and aCSF. We conclude that, as a cholinesterase inhibitor, Mev may induce toxicity via nitric oxide produced by iNOS on activation of the M(2)R by the accumulated acetylcholine in the RVLM.

EVALUATION OF THE STRESS ON AUTONOMIC NERVOUS SYSTEM OF PATIENTS DURING MECHANICAL CIRCULATORY SUPPORT

Background: The power density values of high frequency (0.15 to 0.4 Hz) and low frequency (0.04 to 0.15 Hz) components of systemic arterial pressure (SAP) signals have been regarded as the function of autonomic nervous system(ANS). In this study, the power spectral analysis (PSA) of SAP was adopted for evaluation of the stress on ANS of patients during mechanical circulatory support. Methods: SAP signals were acquired every 2 hours at 100 Hz for 6 minitutes in patients during mechanical circulatory support (MCS). PSA was carried out, and trends of changes in the spectral components of SAP were observed in patients with MCS (IABP and/or PCPS; n=13) and without the support (n=10). Results: The normalized power spectral component in low frequency (LFAnorm) was depressed initially in all patients. The value increased gradually in all patients except 4 with MCS. Sustained low values in LFAnorm in the 4 patients were related to prolonged MCS, and 3 patients among them were expired consequently. On the contrary, the duration of MCS in 3 patients showing no LFAnorm depression in weaning from MCS was significantly shorter than that of patients weaned from MCS with LFAnorm depression. Conclusions: Depressed LFAnorm ofSAP signals represented marked stress on ANS and prolongation of the depression was related to poor outcome of patients. The depression in weaning from MCS also indicated the stress on ANS during the process. PSA of SAP offers a reasonable tool for evaluation of the stress on ANS and prediction of the prognosis of patients with circulatory assist devices.

SPECTRAL CHANGES IN SYSTEMIC ARTERIAL PRESSURE SIGNALS DURING ACUTE MEVINPHOS INTOXICATION IN THE RAT

We investigated the cardiovascular consequences of acute intoxication by the organophosphate poison, mevinphos (Mev), and delineated the underlying mechanism. Based on on-line power spectral analysis of systemic arterial pressure (SAP) signals in rats anesthetized and maintained by propofol, we identified two distinct phases after intravenous administration of Mev (160 or 320 microg/kg). Phase I was characterized by transient hypertension and mild tachycardia, concurrent with an increase in the very high-frequency (BVHF; 5-9 Hz), high-frequency (BHF; 0.8-2.4 Hz), low-frequency (BLF; 0.25-0.8 Hz),and very low-frequency (BVLF; 0-0.25 Hz) components of SAP signals. Phase II exhibited significant hypotension, a reversal of the BVHF and BVLF power to control levels, and further reduction in the power density of both BHF and BLF components to below baseline. Microinjection of Mev (2 microg) into the bilateral nucleus reticularis ventrolateralis (NRVL), the medullary origin of sympathetic neurogenic vasomotor tone, essentially duplicated those phasic cardiovascular changes. Similarly, sympathoexcitatory NRVL neurons exhibited respectively an elevation and a decline in their spontaneous activities during Phase I and Phase II Mev intoxication. We conclude that the progressive accumulation of acetylcholine over time induced by a direct inhibition of Mev on cholinesterase in the NRVL may be responsible for the phasic changes in cardiovascular events over the course of acute Mev intoxication. Whereas the initial amount of acetylcholine is excitatory to NRVL neurons, overstimulation by the amassed acetylcholine results instead of an inhibitory action.

Engagement of Inducible Nitric Oxide Synthase at the Rostral Ventrolateral Medulla during Mevinphos Intoxication in the Rat

We evaluated the relationship between the toxicity induced by the organophosphate mevinphos (Mev) and inducible nitric oxide synthase (iNOS) in the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic neurogenic vasomotor tone. Adult Sprague-Dawley rats that were anesthetized and maintained with propofol were used. Laser scanning confocal microscopic analysis revealed colocalization of the M2 subtype of muscarinic receptors (M₂R) and iNOS immunoreactivity in RVLM neurons. Comicroinjection bilaterally of Mev (10 nmol) and artificial cerebrospinal fluid (aCSF) into the RVLM elicited a progressive decline in systemic arterial pressure (SAP) and heart rate. This was accompanied during phase 1 Mev intoxication by an increase in the power density of the very high-frequency (VHF; 5–9 Hz), high-frequency (HF; 0.8–2.4 Hz), low-frequency (LF; 0.25– 0.8 Hz) and very low-frequency (VLF; 0–0.25 Hz) components of SAP signals. Phase 2 exhibited a reversal of the VHF and VLF power to control levels and a further reduction in the power density of both HF and LF components to below baseline. Hypotension and bradycardia promoted by Mev were significantly blunted on coadministration into the RVLM of the selective iNOS inhibitors S-methylisothiourea (250 pmol) or aminoguanidine (250 pmol). Not only was the augmented power density of HF and LF components during phase 1 Mev intoxication further enhanced, the reduced power of these two spectral components during phase 2 was appreciably antagonized. On the other hand, the temporal changes in VHF and VLF power were essentially the same as with coadministration of Mev and aCSF. We conclude that, as a cholinesterase inhibitor, Mev may induce toxicity via nitric oxide produced by iNOS on activation of the M₂R by the accumulated acetylcholine in the RVLM.

SYMPATHOINHIBITION IN CRITICAL ILLNESS DURING MECHANICAL CIRCULATORY SUPPORT

In variability of systemic blood pressure, the power spectral component with high frequency (0.15 to 0.4 Hz) is usually regarded as a marker of the para-sympathetic activity, and the component with low frequency (0.04 to 0.15 Hz) has been related to the sympathetic activity. Purpose: To evaluate the applicability of power spectral analysis of systemic blood pressure in estimating the state of patients after cardiac surgery. Methods: Hemodynamic data were sampled every 2 hours at 100 Hz for 6 minitutes in patients undergone cardiac surgery. Power spectral analysis of systemic arterial pressure signals was carried out. A trend of changes in the spectral components of systemic arterial pressure were obsereved in the patients with mechanical circulatory support (group M; n=9) for low cardiac output syndrome (LOS) and in control patients without mechanical circulatory support (group N; n=9). Results: The power spectral component with low frequency have the tendency to increase in both groups except 3 patients in group M, and the increment of group M is behind that of group N. Sustained low values in the low frequency component of systemic arterial pressure signals in the 3 patients were related to prolonged mechanical circulatory support, and 2 patients among them were expired consequently. Conclusion: Recovery from the postoperative sympathoinhibitory state in patients with mechanical circulatory support significantly delayed comparing with that in patients without the support. Power spectral analysis of systemic arterial pressure provides a reasonable tool to evaluate the severity of patients' condition regarding the activity of autonomic nervous system which regulates the heart and blood vessels.

Power spectral analysis of arterial and central venous pressure signals during graded hemorrhage in anesthetized rats.

Based on simultaneous power spectral analysis of systemic arterial pressure (SAP) and central venous pressure (CVP) signals in rats anesthetized with pentobarbital sodium, we assessed the hypotheses that subtle changes in the SAP spectrum exist during hemorrhagic shock, and that the CVP spectrum is a feasible index for central blood volume during acute graded blood loss. During Stage I hemorrhagic shock seen after reduction in 10% of total blood volume (TBV), there was a significant increase in the power of both the very low frequency (VLF, 0-.25 Hz) and low frequency (LF, .25-.8 Hz) components, along with a moderate decrease in the very high frequency (VHF, 5-9 Hz) component, of SAP signals. Substantial reduction in VLF, LF, and VHF components in the SAP spectrum occurred after a blood loss of 25% of TBV (Stage II), which persisted during Stage III hemorrhagic shock when the withdrawn blood reached 50% of TBV and the mean SAP maintained at 40 mm Hg. The depressed SAP-VLF and SAP-LF components sustained the period of spontaneous recovery and subsequent retransfusion of shed blood, although the power of SAP-VHF component gradually elevated during these two periods. The power of the high-frequency (HF, .8-2.4 Hz) component of SAP signals increased discernibly only during Stage III, became significant on spontaneous recovery, and declined during retransfusion. Although CVP and CVP-VHF component progressively declined, the power of the CVP-HF component manifested a gradual increase that was significantly and reversely correlated with the reduction in TBV. We conclude that differential changes in individual components of the SAP spectrum occur during hemorrhagic shock, and that the CVP-HF component may be a reliable indicator for central blood volume during acute graded blood loss.

Enhancement of spontaneous baroreflex by antisense c-fos oligonucleotide treatment in the NTS of the rat.

We evaluated the hypothesis that basal Fos protein at the nucleus tractus solitarii (NTS), the primary terminal site for baroreceptor afferents, exerts a tonic inhibitory modulation on the spontaneous baroreceptor reflex (BRR) control machinery, which is responsible for beat-to-beat regulation of resting systemic arterial pressure (SAP). In adult male Sprague-Dawley rats anesthetized and maintained with pentobarbital sodium, microinjection bilaterally into the caudal NTS of a 15-mer antisense oligonucleotide that targets against the initiation codon of c-fos mRNA (5'-129 to 143-3') significantly enhanced the spontaneous BRR response, as determined by transfer function analysis of SAP and heart rate signals. The same treatment also diminished baseline Fos-like immunoreactivity in the absence of acute cardiovascular perturbation. Control treatments with artificial cerebrospinal fluid, sense cDNA, or antisense oligonucleotides that either target against a different site of the c-fos mRNA (5'-135 to 149-3') or with three mismatched nucleotides in the antisense sequence, were ineffective. These observations support the notion that, under minimal cardiovascular perturbation, basal expression of Fos protein in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of beat-to-beat baroreflex control of blood pressure.

Diminished vasomotor component of systemic arterial pressure signals and baroreflex in brain death.

We compared the cardiovascular autonomic regulatory mechanisms between patients with brain death or under a persistent vegetative state and healthy volunteers, based on auto- and cross-spectral analysis of systolic blood pressure (SBP) and interpulse interval (PPI) signals. Brain-dead patients exhibited a significant reduction in the absolute and relative power of the low-frequency (LF; 0.04-0.15 Hz) component in both SBP and PPI spectra, along with appreciable decrease in the very low frequency (VLF; 0.004-0.04 Hz), LF, and high-frequency (HF; 0.15-0.4 Hz) power of the PPI signals. Patients in a persistent vegetative state exhibited a power of the VLF and LF component in the SBP spectrum that was comparable to that in healthy subjects, although a discernible reduction in the VLF, LF, and HF power of the PPI spectrum was manifested by the former group. Assessments with the magnitude of SBP-PPI transfer function and linear regression analysis of beat-to-beat fluctuations in SBP and PPI revealed a progressive decline in spontaneous baroreflex sensitivity from healthy subjects to patients in a persistent vegetative state or with brain death. We conclude that the vasomotor component of systemic arterial pressure signals and spontaneous baroreflex are highly correlated with the functional integrity of the brain stem.

Selective activation of vasomotor component of SAP spectrum by nucleus reticularis ventrolateralis in rats.

We evaluated the contribution of the rostral nucleus reticularis ventrolateralis (NRVL) to the vasomotor component in the spectrum of systemic arterial pressure (SAP) signals by quantifying the transfer function between electrical stimulation of this medullary nucleus and the SAP response. Sprague-Dawley rats anesthetized with pentobarbital sodium, paralyzed with pancuronium, and mechanically ventilated were used. Broad-band stimulation of the NRVL with computer-generated rectangular current pulses (10-50 microA, 1 ms), at a mean spike rate of 50 pulses/s and randomized modulation frequency of 0-3 Hz, elicited a site-specific and intensity-related pressor response. Intriguingly, the corresponding autospectrum of SAP signals exhibited prevailing power density only in the lower frequency range (0-0.8 Hz). This low-pass response characteristic was confirmed by the observation that 90% of the total magnitude of transfer function between NRVL stimulation and SAP response concentrated between 0 and 0.6 Hz. The magnitude of NRVL-SAP transfer function was significantly reduced by phentolamine or prazosin but appreciably enhanced by yohimbine. We conclude that the NRVL may contribute to the very-low (0-0.25 Hz)- and low (0.25-0.8 Hz)-frequency components of the SAP spectrum, which are belived to reflect sympathetic modulation on vasomotor activity via alpha-adrenergic neurotransmission.

Transfer function analysis of ventilatory influence on systemic arterial pressure in the rat.

We evaluated the hypothesis that fluctuations in systemic arterial pressure (SAP) are under the influence of the respiratory pumping mechanism subjected to a modulatory action by the autonomic nervous system that is exerted primarily on the heart. Computer-generated broad-band mechanical ventilation (0-3 Hz) was applied to Sprague-Dawley rats that were anesthetized with ketamine and paralyzed with pancuronium. We observed excellent coherence between lung volume and SAP signals at ventilatory rates between 0.5 and 2.5 Hz; this coherence was unaffected by phentolamine, propranolol, atropine, bilateral vagotomy, or ventilatory stroke volume at 2-4 ml. Whereas bilateral vagotomy exerted no discernible effect, propranolol elicited a significant frequency-dependent (0.5-1.5 Hz) reduction in the magnitude of lung volume-SAP and lung volume-pulse pressure transfer functions. There was also a shift toward 0 degree for the phase of the lung volume-SAP transfer function over the same frequency range. We conclude that the high-frequency component (0.8-2.4 Hz) of the SAP spectrum may be generated by the respiratory pumping mechanism. However, the lower-frequency end of this mechanical influence is subjected to additional amplification by the autonomic nervous system, in which the beta-adrenergic system played a major role via its influence on the heart.

Auto- and cross-spectral analysis of cardiovascular fluctuations during pentobarbital anesthesia in the rat.

We applied auto- and cross-spectral analysis of systemic arterial pressure (SAP) and heart rate (HR) signals to quantify the effects of pentobarbital sodium on short-term cardiovascular fluctuations in adult, male Sprague-Dawley rats. Intravenous administration of pentobarbital, delivered as a bolus injection (5, 10, or 20 mg/kg) or continuous infusion (10, 20, or 40 mg.kg-1.h-1), elicited only mild hypotension and tachycardia. This was accompanied by a dose-related depression of the very low (0-0.25 Hz) and low (0.25-0.8 Hz)-frequency components of both SAP and HR signals and high (0.8-2.4 Hz)-frequency component of HR signals. Cross-spectral analysis of SAP and HR signals during intravenous infusion of pentobarbital revealed a maintained coherence in the high-frequency range, together with a gradual and dose-related decrease in magnitude of transfer function and baro-receptor reflex sensitivity. Stable plasma concentration and all hemodynamic parameters were observed during 120 min of infusion at 20 mg.kg-1.h-1. Under this dosing condition, autonomic blockade by phentolamine, propranolol, or atropine still evoked discernible but differential reductions in the SAP and HR spectral components. Our data suggest that continuous intravenous administration of pentobarbital at 20 mg.kg-1.h-1 offers maintained anesthesia while preserving the capacity of cardiovascular regulation.