Radial Artery Pulse Pressure Research Articles

Changes in arterial blood pressure induced by passive leg raising predict hypotension during the induction of sedation in critically ill patients without severe cardiac dysfunction

Background Hypotension due to the induction of sedation with dexmedetomidine infusion may be harmful in critically ill patients. Changes in pulse pressure induced by the passive leg raising test (PLR-ΔPP) as marker of fluid responsiveness, assessed prior to sedation, may predict hemodynamic changes. The present study was to investigate the power of the PLR test in critically ill patients in predicting hypotension induced by the induction of dexmedetomidine sedation. Methods Fluid responsiveness was estimated by a passive leg raising (PLR) test before dexmedetomidine sedation. Patients were assigned to either the “Nonresponders” or “Responders” group according to their hemodynamic responses to the PLR test (“Nonresponders”, PLR-ΔPP <10.3%; “Responders”, PLR-ΔPP ≥10.3%). Sedation was performed with a dexmedetomidine infusion (0.5 μg/kg over a 10-minute loading period, then 0.2-0.7 μg·kg-1·h-1) and titrated to maintain the target Richmond agitation sedation scale (RASS) score in the range of −2 to −1 and the bispectral index value in the range of 60 to 75. Radial artery pulse pressure, heart rate (HR), and central venous pressure (CVP) were measured at each phase of the study procedure. Hemodynamic fluctuations during the use of dexmedetomidine sedation were recorded and compared between the two groups. Results Fifty patients had a median (25%-75% interquartile range) of 71 (61-78) years old were studied. At baseline, 39 of the 50 patients were “Nonresponders” and 11 were “Responders”. Following dexmedetomidine sedation, patients classified as “Responders” had a significantly greater systolic blood pressure decrease during the induction of dexmedetomidine sedation than the “Nonresponders” ((−26.3 ± 6.8)% vs. (−11.8 ± 8.5)%, P <0.001). In addition, the “Responders” group required significantly more fluid boluses (8 vs. 3; P <0.001) and vasopressors (2 vs. 0; P <0.05) than the “Nonresponders” group to restore blood pressure. Finally, PLR-ΔPP was positively correlated with changes in systolic blood pressure (PLR-ΔSBP) (r 2 = 0.576; P <0.001) and significantly correlated with dexmedetomidine infusion-induced changes in SBP (r 2=0.202; P <0.05). AUC for PLR-ΔPP was 0.84 (95%CI 0.71-0.93). PLR-ΔPP predicted hypotension with a sensitivity of 73% and a specificity of 92%. Conclusions The fluid responsiveness assessment pre-sedation was found to predict blood pressure fluctuation during the induction of dexmedetomidine sedation. The PLR test conducted prior to sedation may be a useful tool to identify patients with a high risk of hemodynamic events and may be used to indicate the need for prophylactic treatment.

Effect of systemic α1-adrenergic receptor blockade on central blood pressure response during exercise

The aortic pulse pressure (PP), which consists mainly of the incident wave and the reflected wave, has emerged as an important property of systemic blood vessels underlying the pathophysiology of cardiovascular disease. To determine the role of sympathetic nerve activity on the aortic PP response during dynamic exercise, we evaluated aortic hemodynamics during the right-leg knee-extension (40 and 60% of maximal voluntary contraction) in six young adults with and without the systemic α1-adrenergic receptor blockade using prazosin (1mg/20kg body weight). The use of prazosin attenuated the exercise-induced increase in aortic PP (P<0.05) but not in radial arterial PP. The amplitude of the reflected waves (via augmentation index) significantly decreased with the exercise and decreased more with the use of prazosin. These results suggest that during dynamic exercise the α1-adrenergic-mediated vasoconstrictor tone of the peripheral resistance vessels is manifestly involved in the magnitude of the reflected wave and the modulation of the aortic PP responses.

Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery. A multi-center, prospective, randomized study [NCT014001283

Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery. A multi-center, prospective, randomized study [NCT014001283

Modeling carotid and radial artery pulse pressure waveforms by curve fitting with Gaussian functions

Modeling arterial pressure waveforms holds the potential for identifying physiological changes. There is a clinical need for a simple waveform analysis method with a high accuracy in reproducing the original waveforms. The aim of this study was to determine the accuracy of modeling carotid and radial pulses using Gaussian functions, making no physiological assumptions. Carotid and radial pulses were recorded from 20 normal volunteers. Ten consecutive beats from each volunteer were analyzed to determine beat-to-beat variability. Each pulse was decomposed using seven combinations of up to three Gaussian functions. The first function was always positive, but the second or third could be either positive or negative. Three positive Gaussian functions reproduced the original waveforms best with a mean absolute error (MAE) of 1.2% and 1.3% for the carotid and radial pulses respectively, and a maximum residual error of only 4.1% for both. This model had significantly smaller errors than any of the other six (all P<0.001). Four positive Gaussian functions were then used to test the stability of this model. An insignificant change of the mean MAE (1.2% for both carotid and radial pulses) was obtained, showing that the stability has been reached with three positive Gaussian functions. The variability of MAE calculated as the standard deviation (SD) over the 10 beats was small at 0.2% for both pulses confirming the repeatability of using three positive Gaussian functions.

Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery: a multi-center, prospective, randomized study

IntroductionSeveral single-center studies and meta-analyses have shown that perioperative goal-directed therapy may significantly improve outcomes in general surgical patients. We hypothesized that using a treatment algorithm based on pulse pressure variation, cardiac index trending by radial artery pulse contour analysis, and mean arterial pressure in a study group (SG), would result in reduced complications, reduced length of hospital stay and quicker return of bowel movement postoperatively in abdominal surgical patients, when compared to a control group (CG).Methods160 patients undergoing elective major abdominal surgery were randomized to the SG (79 patients) or to the CG (81 patients). In the SG hemodynamic therapy was guided by pulse pressure variation, cardiac index trending and mean arterial pressure. In the CG hemodynamic therapy was performed at the discretion of the treating anesthesiologist. Outcome data were recorded up to 28 days postoperatively.ResultsThe total number of complications was significantly lower in the SG (72 vs. 52 complications, p = 0.038). In particular, infection complications were significantly reduced (SG: 13 vs. CG: 26 complications, p = 0.023). There were no significant differences between the two groups for return of bowel movement (SG: 3 vs. CG: 2 days postoperatively, p = 0.316), duration of post anesthesia care unit stay (SG: 180 vs. CG: 180 minutes, p = 0.516) or length of hospital stay (SG: 11 vs. CG: 10 days, p = 0.929).ConclusionsThis multi-center study demonstrates that hemodynamic goal-directed therapy using pulse pressure variation, cardiac index trending and mean arterial pressure as the key parameters leads to a decrease in postoperative complications in patients undergoing major abdominal surgery.Trial registrationClinicalTrial.gov, NCT01401283.

Peripheral vascular decoupling in porcine endotoxic shock

Cardiac output measurement from arterial pressure waveforms presumes a defined relationship between the arterial pulse pressure (PP), vascular compliance (C), and resistance (R). Cardiac output estimates degrade if these assumptions are incorrect. We hypothesized that sepsis would differentially alter central and peripheral vasomotor tone, decoupling the usual pressure wave propagation from central to peripheral sites. We assessed arterial input impedance (Z), C, and R from central and peripheral arterial pressures, and aortic blood flow in an anesthetized porcine model (n = 19) of fluid resuscitated endotoxic shock induced by endotoxin infusion (7 μg·kg⁻¹·h⁻¹ increased to 14 and 20 μg·kg⁻¹·h⁻¹ every 10 min and stopped when mean arterial pressure <40 mmHg or Sv(O₂) < 45%). Aortic, femoral, and radial artery pressures and aortic and radial artery flows were measured. Z was calculated by FFT of flow and pressure data. R and C were derived using a two-element Windkessel model. Arterial PP increased from aortic to femoral and radial sites. During stable endotoxemia with fluid resuscitation, aortic and radial blood flows returned to or exceeded baseline while mean arterial pressure remained similarly decreased at all three sites. However, aortic PP exceeded both femoral and radial arterial PP. Although Z, R, and C derived from aortic and radial pressure and aortic flow were similar during baseline, Z increases and C decreases when derived from aortic pressure whereas Z decreases and C increases when derived from radial pressure, while R decreased similarly with both pressure signals. This central-to-peripheral vascular tone decoupling, as quantified by the difference in calculated Z and C from aortic and radial artery pressure, may explain the decreasing precision of peripheral arterial pressure profile algorithms in assessing cardiac output in septic shock patients and suggests that different algorithms taking this vascular decoupling into account may be necessary to improve their precision in this patient population.

Maternal small arterial elasticity decreases with gestation in normal pregnancy

Changes in maternal blood pressure are seen in normal pregnancy. Mean arterial pressure falls until the end of the second trimester and then rises again to prepregnancy levels in the...

Impaired endothelium-dependent vasodilatation is a novel predictor of mortality in intensive care*

Endothelial function may be impaired in critical illness. We hypothesized that impaired endothelium-dependent vasodilatation is a predictor of mortality in critically ill patients. Prospective observational cohort study. Seventeen-bed adult intensive care unit in a tertiary referral university teaching hospital. Patients were recruited within 24 hrs of admission to the intensive care unit. The SphygmoCor Mx system was used to derive the aortic augmentation index from radial artery pulse pressure waveforms. Endothelium-dependent vasodilatation was calculated as the change in augmentation index in response to an endothelium-dependent vasodilator (salbutamol). Demographics, severity of illness scores, and physiological parameters were collected. Statistically significant predictors of mortality identified using single regressor analysis were entered into a multiple logistic regression model. Receiver operator characteristic curves were generated. Ninety-four patients completed the study. There were 80 survivors and 14 nonsurvivors. The Simplified Acute Physiology Score II, the Sequential Organ Failure Assessment score, leukocyte count, and endothelium-dependent vasodilatation conferred an increased risk of mortality. In logistic regression analysis, endothelium-dependent vasodilatation was the only predictor of mortality with an adjusted odds ratio of 26.1 (95% confidence interval [CI], 4.3-159.5). An endothelium-dependent vasodilatation value of 0.5% or less predicted intensive care unit mortality with a sensitivity of 79% (CI, 59-88%) and specificity of 98% (CI, 94-99%). In vivo bedside assessment of endothelium-dependent vasodilatation is an independent predictor of mortality in the critically ill. We have shown it to be superior to other validated severity of illness scores with high sensitivity and specificity.

Hybrid Cardiopulmonary Model for Analysis of Valsalva Maneuver with Radial Artery Pulse

A comprehensive model, which has the advantages of both lumped parameter and distributed parameter, has been developed with the objective of investigating the respiratory influences in radial artery pressure pulse as in photoplethysmography (PPG). It integrates lumped parameter cardiopulmonary (CP) model and transmission line arterial tree model from aorta to radial artery. The cardio-pulmonary interaction is realized by incorporating respiratory-induced variations in intrapleural pressure (Ppl) in circulatory system. The PPG signal of the model is considered as the radial artery pulse. To investigate the interaction Valsalva Maneuver (VM) condition has been simulated for different Ppl magnitude (10, 20, 30, and 40mmHg) and for different time duration (5, 10, 15, and 20s), and validated with PPG signal recorded in 10 normal subjects performing VM. The effects of test duration and VM pressure are studied in both the simulation and the experiments with specific focus on the maximal (%∆) changes in Heart Rate (HR), and Mean Arterial Pressure (MAP) during phases II and IV of VM. The correlation coefficients derived from model result have good agreement with experimental results. As radial artery pulse plays important role in both allopathy and alternate medicine systems, this model can serve to study its clinical importance in detecting cardiac and respiratory pathologies.

Relationship of low birth weight to pulsatile arterial function in asymptomatic younger adults: the Bogalusa Heart Study.

Low birth weight, an indicator of intrauterine growth restriction, is associated with adult cardiovascular (CV) disease, type 2 diabetes, and adverse levels of CV risk factors. Impaired pulsatile arterial function is also an independent predictor of early vascular damage and related CV outcome. However, information is scant regarding the influence of low birth weight on pulsatile arterial function. The study cohort consisted of 538 black and white subjects (29% black, 42% male) aged 18-44 years (mean 36.7 years) enrolled in the Bogalusa Heart Study. Subjects were categorized into low birth weight and normal birth weight. Pulsatile arterial function was assessed in terms of large artery compliance, small artery compliance, and systemic vascular resistance by noninvasive radial artery pressure pulse contour analysis. Blacks and females had significantly lower birth weight compared to their counterparts. Low vs. normal birth weight group had lower large artery compliance (13.3 ml/mm Hg x 10 vs. 15.5 ml/mm Hg x 10, P = 0.0002). Further, after adjusting for age, race, and sex, the large artery compliance increased across quartiles of increasing birth weight specific for race, sex, and gestational age (P for trend = 0.03). In multivariate regression model, adding race, sex, age, body surface area, systolic blood pressure, diastolic blood pressure, triglycerides/high-density lipoprotein cholesterol ratio one by one, the effect was attenuated but significant (beta = -0.067, P = 0.033). The observed deleterious association of low birth weight on arterial wall dynamics in asymptomatic younger adults may account in part for the adverse CV risk in the Bogalusa sample.

Association of serum bilirubin with pulsatile arterial function in asymptomatic young adults: the Bogalusa Heart Study

The inverse association between serum bilirubin, a potent antioxidant, and oxidative stress–mediated diseases like cardiovascular disease is known. However, information is scant regarding the influence of bilirubin in relation to traditional cardiovascular risk factors on pulsatile arterial function in asymptomatic younger adults. The present study examines this aspect in 777 black and white subjects (71% white, 42% male) aged 18 to 44 years. Pulsatile arterial function was assessed in terms of large-artery (capacitive) and small-artery (oscillatory) compliances by radial artery pressure pulse contour analysis. In bivariate analysis adjusted for race and sex, bilirubin related significantly and positively to large- and small-artery compliances and high-density lipoprotein cholesterol, and inversely to age, body mass index, blood pressure variables, non–high-density lipoprotein cholesterol, triglycerides, and insulin resistance index. In multivariable analysis including race, sex, body surface area, and risk factor variables mentioned above, bilirubin did not relate to large-artery compliance, without or with smoking status in the model, whereas bilirubin associated beneficially with small-artery compliance ( P = .01) in a model that excluded smoking status. When smoking status was included in the model, this association became less strong ( P = .04); and smoking entered the model as an adverse predictor ( P = .003). The observed beneficial association of serum bilirubin on pulsatile arterial function, albeit the attenuating effect of smoking on this relationship, in asymptomatic younger adults supports the antioxidant function of bilirubin in providing protection against oxidative stress–mediated vascular dysfunction.

Central Aortic Blood Pressure and Cardiovascular Risk

The provocative proposition of “hypertension is a myth” has generated many a debate and editorial commentary.1,2 In contrast, the realities of high blood pressure and the associated cardiovascular risks have been ascertained from data obtained by the conventional brachial cuff sphygmomanometer. Notwithstanding the inherent limitations of the technique, there is yet no equivalent and suitable device that can be universally accepted to replace the cuff sphygmomanometer for practical and noninvasive measurement of arterial blood pressure in large population groups and with wide clinical applications. Attempts at complementing information obtained from cuff measurements have resorted to basic physiological studies in humans and experimental animals, which have shown that pulsatile blood flow in arteries can be described in terms of characteristics common to systems of wave propagation.3 These concepts explain the complex relationship between oscillatory blood pressure and flow, the difference in pressure wave shape, and the increase in pulse pressure between the aorta and peripheral arteries. Such wave propagation characteristics can be described in terms of mathematical entities known as transfer functions, with associated assumptions of stability and linearity.3,4 The study by McEniery et al in this issue of Hypertension 5 uses methodologies for both the cuff sphygmomanometer and transfer functions4 to determine central aortic pressure from the brachial cuff pressure measurement and the tonometric radial artery pressure pulse in >10 000 adults of age range 18 to 101 years. This is the largest study of its kind with conventional pressure measurements and pulse waveform data. The study allows analysis that can produce potentially groundbreaking results and poses important and possibly perplexing and challenging questions related not only to the role of central aortic pressure as an improved measure of the hemodynamic burden on the ejecting ventricle but also on the interpretation of guidelines for the management …

Radial Artery Pulse Pressure Variation Correlates With Brachial Artery Peak Velocity Variation in Ventilated Subjects When Measured by Internal Medicine Residents Using Hand-Carried Ultrasound Devices

Rapid prediction of the effect of volume expansion is crucial in unstable patients receiving mechanical ventilation. Both radial artery pulse pressure variation (DeltaPP) and change of aortic blood flow peak velocity are accurate predictors but may be impractical point-of-care tools. We sought to determine whether respiratory changes in the brachial artery blood flow velocity (DeltaVpeak-BA) as measured by internal medicine residents using a hand-carried ultrasound (HCU) device could provide an accurate corollary to DeltaPP in patients receiving mechanical ventilation. Thirty patients passively receiving volume-control ventilation with preexisting radial artery catheters were enrolled. The brachial artery Doppler signal was recorded and analyzed by blinded internal medicine residents using a HCU device. Simultaneous radial artery pulse wave and central venous pressure recordings (when available) were analyzed by a blinded critical care physician. A Doppler signal was obtained in all 30 subjects. The DeltaVpeak-BA correlated well with DeltaPP (r = 0.84) with excellent agreement (weighted kappa, 0.82) and limited intraobserver variability (2.8 +/- 2.8%) [mean +/- SD]. A DeltaVpeak-BA cutoff of 16% was highly predictive of DeltaPP > or = 13% (sensitivity, 91%; specificity, 95%). A poor correlation existed between the CVP and both DeltaVpeak-BA (r = - 0.21) and DeltaPP (r = - 0.16). The HCU Doppler assessment of the DeltaVpeak-BA as performed by internal medicine residents is a rapid, noninvasive bedside correlate to DeltaPP, and a DeltaVpeak-BA cutoff of 16% may prove useful as a point-of-care tool for the prediction of volume responsiveness in patients receiving mechanical ventilation.

RESPIRATORY CHANGE IN BRACHIAL BLOOD VELOCITY AS A NONINVASIVE, BEDSIDE CORRELATE TO PULSE PRESSURE VARIATION IN THE VENTILATED PATIENT

PURPOSE: Rapid prediction of the effect of volume expansion (VE) is crucial in hemodynamically unstable patients on mechanical ventilation. While accurate, both radial artery pulse pressure variation (ΔPP) and changes of aortic blood flow peak velocity (ΔVPeakAo) have limitations that make them impractical as point-of-care tools. In this study, we sought to determine whether respiratory changes in the brachial artery blood flow velocity (VPeakBA) as measured by Internal Medicine residents using a hand-carried ultrasound (HCU) could provide an accurate corollary to ΔPP in mechanically ventilated patients.

Comparison of the Measures of Pulsatile Arterial Function Between Asymptomatic Younger Adult Smokers and Former Smokers: The Bogalusa Heart Study

Cigarette smoking, an established cardiovascular (CV) disease risk factor, is known to impair pulsatile arterial function. However, information is scant in this regard on asymptomatic younger adult former smokers. As part of the Bogalusa Heart Study, the pulsatile arterial function was examined noninvasively in 278 nonsmokers, 277 current smokers, and 104 former smokers, aged 18 to 44 years, mean 36.4 years by radial artery pressure pulse contour analysis. Compared to current smokers, former smokers had higher body mass index (BMI, 29.6 v 27.7 kg/m2, P=.02), after adjusting for age, ethnicity, and sex, and higher levels of glucose (94.8 v 85.3 mg/dL, P=.008) and insulin (15.0 v 10.9 microU/mL, P=.01), after adjusting for age, ethnicity, sex, and BMI. Compared to nonsmokers, former smokers had similar BMI, but marginally high glucose (P=.08) and insulin (P=.11). With respect to measures of pulsatile arterial function, nonsmokers versus current smokers versus former smokers had similar large artery compliance (15.2 v 15.1 v 15.1 mL/mmHgx10) but increased (P=.01) small artery compliance after smoking cessation (6.6 v 5.8 v 6.5 mL/mmHgx100), and decreased (P=.03) systemic vascular resistance after smoking cessation (1300.5 v 1376.9 v 1292.2 dynes.sec.cm-5), and increases in small artery compliance (P=.0003) and decreases in systemic vascular resistance (P=.01) were found among those who quit smoking 10 years or more, after adjusting for ethnicity, sex, age, glucose, insulin, and alcohol use. These findings, although cross-sectional in nature, indicate the potential for improving arterial wall dynamics after smoking cessation in younger adults.

Distribution and Correlates of Arterial Compliance Measures in Asymptomatic Young Adults: The Bogalusa Heart Study

Impaired arterial compliance is an independent predictor of early vascular damage and related adverse cardiovascular (CV) outcome. Information is scant on the distributions and correlates of measures of arterial pulsatile function in a community-based, biracial cohort of young adults. In 800 African American and white subjects aged 18 to 44 years, pulsatile arterial function was assessed in terms of large artery (capacitive) compliance, small artery (oscillatory) compliance, systemic vascular resistance, and vascular impedance by noninvasive radial artery pressure pulse contour analysis. African Americans versus whites and women versus men had lower large and small artery compliances and higher systemic vascular resistance and vascular impedance (P < .001). In multiple regression analysis, mean arterial pressure, body mass index (BMI), insulin levels, and age were correlated inversely and body surface area positively with large artery compliance and accounted for 39.2% of the variance; mean arterial pressure, female gender, age, and triglyceride levels inversely and cardiac output positively with small artery compliance and explained 56.4% of the variance; mean arterial pressure and age positively and cardiac output inversely with systemic vascular resistance and accounted for 91.4% of variance; and mean arterial pressure and BMI positively and cardiac output and body surface area inversely with vascular impedance and contributed to 37.6% of the variance. The observed deleterious impact of traditional CV risk factors on the arterial wall dynamics in asymptomatic young adults has important implications for preventive cardiology. Noninvasive pulsatile arterial function assessment may be helpful for evaluation of early vascular damage in a high-risk young population group.

Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia

Mortality increases when acute coronary syndromes are complicated by stress-induced hyperglycemia. Early pulse wave reflection can augment central aortic systolic blood pressure and increase left ventricular strain. Altered pulse wave reflection may contribute to the increase in cardiac risk during acute hyperglycemia. Chronic ascorbic acid (AA) supplementation has recently been shown to reduce pulse wave reflection in diabetes. We investigated the in vivo effects of acute hyperglycemia, with and without AA pretreatment, on pulse wave reflection and arterial hemodynamics. Healthy male volunteers were studied. Peripheral blood pressure (BP) was measured at the brachial artery, and the SphygmoCor pulse wave analysis system was used to derive central BP, the aortic augmentation index (AIx; measure of systemic arterial stiffness), and the time to pulse wave refection (Tr; measure of aortic distensibility) from noninvasively obtained radial artery pulse pressure (PP) waveforms. Hemodynamics were recorded at baseline and then every 30 min during a 120-min systemic hyperglycemic clamp (14 mmol/l). The subjects, studied on two separate occasions, were randomized in a double-blind, crossover manner to placebo or 2 g intravenous AA before the initiation of hyperglycemia. During hyperglycemia, AIx increased and Tr decreased. Hyperglycemia did not change peripheral PP but did magnify central aortic PP and diminished the normal physiological amplification of PP from the aorta to the periphery. Pulse wave reflection, as assessed from peripheral pulse wave analysis, is enhanced during acute hyperglycemia. Pretreatment with AA prevented the hyperglycemia-induced hemodynamic changes. By protecting hemodynamics during acute hyperglycemia, AA may have therapeutic use.

Respiratory effect on the pulse spectrum

During the last decade, progressive achievements in haemodynamics have shown that radial artery pulse pressure can be used to estimate the vascular properties of the internal organs. Clinical experiments have shown that slow and regular respiration has a large effect on the heart rate variability (HRV). This phenomenon is called respiratory sinus arrhythmia (RSA). It is known that respiration-related oscillations in venous return cause oscillations in stroke volume and blood pressure. It also can be inferred from cardiac output that systemic blood pressure has a similar respiration-related cycle. Moreover we found that the fluctuations of harmonics of arterial pulse are consistent with the fluctuation of HRV. This means that the whole cardiovascular system (CVS) makes rapid adaptation during respiration, and the harmonic proportions of arterial pulse were modified during different breath rates. This result shows that the regular respiration also has a large effect upon Windkessel properties of CVS.

Platelet Nitric Oxide and Superoxide Release During the Development of Nitrate Tolerance

The therapeutic benefits that accompany the continuous administration of organic nitrates are attenuated by the development of tolerance to the compounds. Altered superoxide production and NO bioavailability have been implicated in contributing to the development of tolerance, an effect that may be ameliorated by the administration of antioxidants. We studied the effect of 3 days of continuous transdermal administration of nitroglycerin (NTG) (10 mg/24 hours) on platelet free radical (NO and superoxide anion [O2*-] activity) with and without coadministration of supplemental ascorbate (2.4 g/24 hours). NAD(P)H oxidase activity, nitric oxide synthase (NOS) activity, and cyclic guanosine monophosphate (cGMP) content were also assessed. Radial artery pressure pulse waveforms were used to track the hemodynamic actions of NTG. Three days of NTG/placebo was associated with a significant increase in platelet NO and O2*- production from 1.0+/-1.17 to 2.52+/-0.88 pmol/10(8) platelets and 13.2+/-4.8 to 72.5+/-34.4 pmol/10(8) platelets, respectively (P<0.01 for both). These changes were accompanied by increased platelet NADH oxidase activity from 47.9+/-11.0 to 65.3+/-13.6 pmol O2*- min/mg protein and cGMP content from 0.60+/-0.10 to 0.89+/-0.16 pmol/10(9) platelets (P<0.05 for both). Administration of NTG/ascorbate attenuated both NO and O2*- release in platelets. Three days of continuous transdermal administration of NTG was accompanied by increased platelet NO and O2*- production and NADH oxidase activity that was suppressed by coadministration of oral ascorbate. Although a significant degree of tolerance would be expected during continuous nitrate administration, a residual hemodynamic action could be identified by arterial pulse contour analysis.

Changes in BP Induced by Passive Leg Raising Predict Response to Fluid Loading in Critically Ill Patients

To test the hypothesis that passive leg raising (PLR) induces changes in arterial pulse pressure that can help to predict the response to rapid fluid loading (RFL) in patients with acute circulatory failure who are receiving mechanical ventilation. Prospective clinical study. Two medical ICUs in university hospitals. Thirty-nine patients with acute circulatory failure who were receiving mechanical ventilation and had a pulmonary artery catheter in place. PLR for > 4 min and a subsequent 300-mL RFL for > 20 min. Radial artery pulse pressure (PPrad), heart rate, right atrial pressure, pulmonary artery occlusion pressure (PAOP), and cardiac output were measured invasively in a population of 15 patients at each phase of the study procedure (i.e., before and during PLR, and then before and after RFL). PPrad, PAOP, and stroke volume (SV) significantly increased in patients performing PLR. These changes were rapidly reversible when the patients' legs were lowered. Changes in PPrad during PLR were significantly correlated with changes in SV during PLR (r = 0.77; p < 0.001). Changes in SV induced by PLR and by RFL were significantly correlated (r = 0.89; p < 0.001). Finally, PLR-induced changes in PPrad were significantly correlated to RFL-induced changes in SV (r = 0.84; p < 0.001). In a second population of 24 patients, we found the same relationship between PLR-induced changes in PPrad and RFL-induced changes in SV (r = 0.73; p < 0.001). The response to RFL could be predicted noninvasively by a simple observation of changes in pulse pressure during PLR in patients with acute circulatory failure who were receiving mechanical ventilation.