General anesthesia with sevoflurane decreases myocardial blood volume and hyperemic blood flow in healthy humans

BACKGROUND Preservation of myocardial perfusion during general anesthesia is likely important in patients at risk for perioperative cardiac complications. Data related to the influence of general anesthesia on the normal myocardial circulation are limited. In this study, we investigated myocardial microcirculatory responses to pharmacological vasodilation and sympathetic stimulation during general anesthesia with sevoflurane in healthy humans immediately before surgical stimulation. METHODS Six female and 7 male subjects (mean age 43 years, range 28-61) were studied at baseline while awake and during the administration of 1 minimum alveolar concentration sevoflurane. Using myocardial contrast echocardiography, myocardial blood flow (MBF) and microcirculatory variables were assessed at rest, during adenosine-induced hyperemia, and after cold pressor test-induced sympathetic stimulation. MBF was calculated from the relative myocardial blood volume multiplied by its exchange frequency (β) divided by myocardial tissue density (ρT), which was set at 1.05 g·mL(-1). RESULTS During sevoflurane anesthesia, MBF at rest was similar to baseline values (1.05 ± 0.28 vs 1.05 ± 0.32 mL·min(-1)·g(-1); P = 0.98; 95% confidence interval [CI], -0.18 to 0.18). Myocardial blood volume decreased (P = 0.0044; 95% CI, 0.01-0.04) while its exchange frequency (β) increased under sevoflurane anesthesia when compared with baseline. In contrast, hyperemic MBF was reduced during anesthesia compared with baseline (2.25 ± 0.5 vs 3.53 ± 0.7 mL·min(-1)·g(-1); P = 0.0003; 95% CI, 0.72-1.84). Sympathetic stimulation during sevoflurane anesthesia resulted in a similar MBF compared to baseline (1.53 ± 0.53 and 1.55 ± 0.49 mL·min(-1)·g(-1); P = 0.74; 95% CI, -0.47 to 0.35). CONCLUSIONS In otherwise healthy subjects who are not subjected to surgical stimulation, MBF at rest and after sympathetic stimulation is preserved during sevoflurane anesthesia despite a decrease in myocardial blood volume. However, sevoflurane anesthesia reduces hyperemic MBF, and thus MBF reserve, in these subjects.

Red Cell Volume Expansion at Altitude: A Meta-analysis and Monte Carlo Simulation

Meta-análisis del volumen de eritrocitos en altitud

Myocardial blood volume and perfusion reserve responses to combined dipyridamole and exercise stress: A quantitative approach to contrast stress echocardiography

Background: Qualitative interpretation of myocardial contrast echocardiography (MCE) improves the accuracy of wall-motion analysis for assessment of coronary artery disease (CAD). We examined the feasibility and accuracy of quantitative MCE for diagnosis of CAD. Methods: Dipyridamole/exercise stress MCE (destruction-replenishment protocol with real-time imaging) was performed in 90 patients undergoing quantitative coronary angiography, 48 of whom had significant (> 50%) stenoses. MCE was repeated with exercise alone in 18 patients. Myocardial blood flow (A*beta) was obtained from blood volume (A) and time to refill (beta). Results: Quantification of flow reserve was feasible in 88%. The mean A*beta reserve in the anterior wall was significantly impaired for patients with left anterior descending coronary artery disease (n = 28) compared with those with no disease (1.6 +/- 1.2 vs; 4.0 +/- 2.5, P <=.001). This reflected impaired beta reserve, with no difference in the A reserve. Applying a receiver operating characteristic curve derived cutoff of 2.0 for A*beta reserve, quantitative MCE was 76% sensitive and 71% specific for the diagnosis of significant left anterior descending coronary artery stenosis. Posterior circulation results were similar, with 78% sensitivity and 59% specificity for detection of posterior CAD. Overall, quantitative MCE was similarly sensitive to qualitative approach for diagnosis of CAD (88% vs 93%), but with lower specificity (52% vs 65%, P =.07). In 18 patients restudied with pure exercise stress, the mean myocardial blood flow reserve was less than after combined stress (2.1 +/- 1.6 vs 3.7 +/- 1.9, P =.01). Conclusion: Quantitative MCE is feasible for the diagnosis of CAD with dipyridamole/exercise stress. Dipyridamole prolongs postexercise hyperemia, augmenting the degree of hyperemia at the time of imaging.

Atrial stretch increases the gastric tonus of anesthetized rats

Aims: We assessed the effects of right atrial stretch on gastric tone and neuro-humoral pathways involved in this phenomenon. Main methods: Anesthetized male rats were submitted for monitoring of the mean arterial pressure (MAP) and central venous pressure (CVP). A balloon catheter positioned into the stomach monitored by plethysmography the gastric volume (GV). All rats were monitored for 55-min. After the first 20-min of monitoring (basal period), rats were either submitted to a 5-min interval of atrial stretch (AS) or maintained as controls. An intra-atrial balloon catheter was distended with 30,50, or 70 mu L of saline. GV and hemodynamic data were also monitored for a further 30-min. Another set of rats, either previously submitted to subdiaphragmaic vagotomy or splanchnicectomy plus celiac ganglionectomy or maintained as controls (sham), were also submitted to AS. Each subset consisted of six rats. The plasma level of the atrial natriuretic peptide (ANP) was measured in another group of rats. Data were compared by ANOVA followed by Bonferroni`s test. Key findings: In control rats, the GV, MAP, and CVP remained at stable levels throughout the studies. In addition to increase the CVP, AS also decreased (P<0.05) the GV by 14%, 11.5%, and 16.5% in the 30, 50, and 70 mu L groups, respectively. Vagotomy prevented the GV decrease. In contrast, the AS decreased (P<0.05) the GV by 21.3% in splanchnicectomized rats. Significance: AS decreased the GV of rats in a volume-dependent manner, a phenomenon prevented by vagotomy but enhanced by celiac ganglionectomy. (C) 2010 Elsevier Inc. All rights reserved.

Neuroendocrine regulation of salt and water metabolism

Neurons which release atrial natriuretic peptide (ANPergic neurons) have their cell bodies in the paraventricular nucleus and in a region extending rostrally and ventrally to the anteroventral third ventricular (AV3V) region with axons which project to the median eminence and neural lobe of the pituitary gland. These neurons act to inhibit water and salt intake by blocking the action of angiotensin II. They also act, after their release into hypophyseal portal vessels, to inhibit stress-induced ACTH release, to augment prolactin release, and to inhibit the release of LHRH and growth hormone-releasing hormone. Stimulation of neurons in the AV3V region causes natriuresis and an increase in circulating ANP, whereas lesions in the AV3V region and caudally in the median eminence or neural lobe decrease resting ANP release and the response to blood volume expansion. The ANP neurons play a crucial role in blood volume expansion-induced release of ANP and natriuresis since this response can be blocked by intraventricular (3V) injection of antisera directed against the peptide. Blood volume expansion activates baroreceptor input via the carotid, aortic and renal baroreceptors, which provides stimulation of noradrenergic neurons in the locus coeruleus and possibly also serotonergic neurons in the raphe nuclei. These project to the hypothalamus to activate cholinergic neurons which then stimulate the ANPergic neurons. The ANP neurons stimulate the oxytocinergic neurons in the paraventricular and supraoptic nuclei to release oxytocin from the neural lobe which circulates to the atria to stimulate the release of ANP. ANP causes a rapid reduction in effective circulating blood volume by releasing cyclic GMP which dilates peripheral vessels and also acts within the heart to slow its rate and atrial force of contraction. The released ANP circulates to the kidney where it acts through cyclic GMP to produce natriuresis and a return to normal blood volume

Oxytocin is a cardiovascular hormone

Oxytocin (OT), a nonapeptide, was the first hormone to have its biological activities established and chemical structure determined. It was believed that OT is released from hypothalamic nerve terminals of the posterior hypophysis into the circulation where it stimulates uterine contractions during parturition, and milk ejection during lactation. However, equivalent concentrations of OT were found in the male hypophysis, and similar stimuli of OT release were determined for both sexes, suggesting other physiological functions. Indeed, recent studies indicate that OT is involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of cardiovascular functions. It has long been known that OT induces natriuresis and causes a fall in mean arterial pressure, both after acute and chronic treatment, but the mechanism was not clear. The discovery of the natriuretic family shed new light on this matter. Atrial natriuretic peptide (ANP), a potent natriuretic and vasorelaxant hormone, originally isolated from rat atria, has been found at other sites, including the brain. Blood volume expansion causes ANP release that is believed to be important in the induction of natriuresis and diuresis, which in turn act to reduce the increase in blood volume. Neurohypophysectomy totally abolishes the ANP response to volume expansion. This indicates that one of the major hypophyseal peptides is responsible for ANP release. The role of ANP in OT-induced natriuresis was evaluated, and we hypothesized that the cardio-renal effects of OT are mediated by the release of ANP from the heart. To support this hypothesis, we have demonstrated the presence and synthesis of OT receptors in all heart compartments and the vasculature. The functionality of these receptors has been established by the ability of OT to induce ANP release from perfused heart or atrial slices. Furthermore, we have shown that the heart and large vessels like the aorta and vena cava are sites of OT synthesis. Therefore, locally produced OT may have important regulatory functions within the heart and vascular beds. Such functions may include slowing down of the heart or the regulation of local vascular tone.

Neuroendocrine control of body fluid homeostasis

Angiotensin II and atrial natriuretic peptide (ANP) play important and opposite roles in the control of water and salt intake, with angiotensin II promoting the intake of both and ANP inhibiting the intake of both. Following blood volume expansion, baroreceptor input to the brainstem induces the release of ANP within the hypothalamus that releases oxytocin (OT) that acts on its receptors in the heart to cause the release of ANP. ANP activates guanylyl cyclase that converts guanosine triphosphate into cyclic guanosine monophosphate (cGMP). cGMP activates protein kinase G that reduces heart rate and force of contraction, decreasing cardiac output. ANP acts similarly to induce vasodilation. The intrinsic OT system in the heart and vascular system augments the effects of circulating OT to cause a rapid reduction in effective circulating blood volume. Furthermore, natriuresis is rapidly induced by the action of ANP on its tubular guanylyl cyclase receptors, resulting in the production of cGMP that closes Na+ channels. The OT released by volume expansion also acts on its tubular receptors to activate nitric oxide synthase. The nitric oxide released activates guanylyl cyclase leading to the production of cGMP that also closes Na+ channels, thereby augmenting the natriuretic effect of ANP. The natriuresis induced by cGMP finally causes blood volume to return to normal. At the same time, the ANP released acts centrally to decrease water and salt intake.

A Comparison Between Pulse Pressure Variation and Right End Diastolic Volume Index as Guides to Resuscitation in a Model of Hemorrhagic Shock in Pigs

Background: Different hemodynamic parameters including static indicators of cardiac preload as right ventricular end-diastolic volume index (RVEDVI) and dynamic parameters as pulse pressure variation (PPV) have been used in the decision-making process regarding volume expansion in critically ill patients. The objective of this study was to compare fluid resuscitation guided by either PPV or RVEDVI after experimentally induced hemorrhagic shock. Methods: Twenty-six anesthetized and mechanically ventilated pigs were allocated into control (group I), PPV (group II), or RVEDVI (group III) group. Hemorrhagic shock was induced by blood withdrawal to target mean arterial pressure of 40 mm Hg, maintained for 60 minutes. Parameters were measured at baseline, time of shock, 60 minutes after shock, immediately after resuscitation with hydroxyethyl starch 6% (130/0.4), 1 hour and 2 hours thereafter. The endpoint of fluid resuscitation was determined as the baseline values of PPV and RVEDVI. Statistical analysis of data was based on analysis of variance for repeated measures followed by the Bonferroni test (p < 0.05). Results: Volume and time to resuscitation were higher in group III than in group II (group III = 1,305 +/- 331 mL and group II = 965 +/- 245 mL, p < 0.05; and group III = 24.8 +/- 4.7 minutes and group II = 8.8 +/- 1.3 minutes, p < 0.05, respectively). All static and dynamic parameters and biomarkers of tissue oxygenation were affected by hemorrhagic shock and nearly all parameters were restored after resuscitation in both groups. Conclusion: In the proposed model of hemorrhagic shock, resuscitation to the established endpoints was achieved within a smaller amount of time and with less volume when guided by PPV than when guided by pulmonary artery catheter-derived RVEDVI.

Dynamic arterial elastance to predict arterial pressure response to volume loading in preload-dependent patients

INTRODUCTION Hemodynamic resuscitation should be aimed at achieving not only adequate cardiac output but also sufficient mean arterial pressure (MAP) to guarantee adequate tissue perfusion pressure. Since the arterial pressure response to volume expansion (VE) depends on arterial tone, knowing whether a patient is preload-dependent provides only a partial solution to the problem. The objective of this study was to assess the ability of a functional evaluation of arterial tone by dynamic arterial elastance (Ea(dyn)), defined as the pulse pressure variation (PPV) to stroke volume variation (SVV) ratio, to predict the hemodynamic response in MAP to fluid administration in hypotensive, preload-dependent patients with acute circulatory failure. METHODS We performed a prospective clinical study in an adult medical/surgical intensive care unit in a tertiary care teaching hospital, including 25 patients with controlled mechanical ventilation who were monitored with the Vigileo(®) monitor, for whom the decision to give fluids was made because of the presence of acute circulatory failure, including arterial hypotension (MAP ≤65 mmHg or systolic arterial pressure <90 mmHg) and preserved preload responsiveness condition, defined as a SVV value ≥10%. RESULTS Before fluid infusion, Ea(dyn) was significantly different between MAP responders (MAP increase ≥15% after VE) and MAP nonresponders. VE-induced increases in MAP were strongly correlated with baseline Ea(dyn) (r(2) = 0.83; P < 0.0001). The only predictor of MAP increase was Ea(dyn) (area under the curve, 0.986 ± 0.02; 95% confidence interval (CI), 0.84-1). A baseline Ea(dyn) value >0.89 predicted a MAP increase after fluid administration with a sensitivity of 93.75% (95% CI, 69.8%-99.8%) and a specificity of 100% (95% CI, 66.4%-100%). CONCLUSIONS Functional assessment of arterial tone by Ea(dyn), measured as the PVV to SVV ratio, predicted arterial pressure response after volume loading in hypotensive, preload-dependent patients under controlled mechanical ventilation.

Réduction d'expansion volumique au cours de la gestation : conséquence sur la circulation utéro-placentaire.

La grossesse est caractérisée par une augmentation du volume circulant maternel et du débit sanguin afin de subvenir aux besoins croissants du foetus. En diminuant l'expansion volumique maternelle, nous avons développé un modèle de restriction de croissance intra-utérine (RCIU) chez la rate dans lequel on observe une diminution du diamètre des artères utérines arquées ainsi qu'une diminution de la réponse à l'angiotensine II. Nous avons émis l'hypothèse que comparativement aux rates normales, les vaisseaux utérins des rates RCIU présentent une dysfonction des mécanismes de relaxation dépendant de l'endothélium lors de la réponse à des agents vasoactifs. Notre objectif était de caractériser l'influence de l'endothélium sur la régulation de la réactivité des artères utérines radiales dans notre modèle RCIU. À l'aide d'un myographe pressurisé, des courbes de concentration-réponse à des agents vasoactifs (Phényléphrine (Pe), Carbachol (Cbc) et Nitroprussiate de sodium (SNP)) ont été effectuées, en présence ou en absence d'inhibiteurs des voies principales de la relaxation dépendante de l'endothélium (monoxyde d'azote (NO), prostacycline (PGI2) et facteurs hyperpolarisants dépendant de l'endothélium (EDHF)). Nous avons ainsi démontré que les artères utérines radiales des rates RCIU ont un diamètre plus petit que celles des rates contrôles. Une utilisation plus grande du NO dans la réponse dilatatrice au Cbc a été observée chez les rates RCIU. De plus, l'inhibition de la voie de l'EDHF par l'ajout de KCl aux inhibiteurs de la voie du NO (L-NAME) et des PGI2 (Ibuprofène) bloque presque complètement la relaxation au Cbc chez les deux groupes. En conclusion, dans les artères utérines radiales des deux groupes, il y a une participation importante de l'EDHF lors de la dilatation au Cbc. De plus, dans notre modèle RCIU, la voie du NO est activée, probablement afin de compenser la diminution du diamètre des artères et la réduction de la perfusion utérine.

Model estimation of cerebral hemodynamics between blood flow and volume changes: A data-based modeling approach

It is well known that there is a dynamic relationship between cerebral blood flow (CBF) and cerebral blood volume (CBV). With increasing applications of functional MRI, where the blood oxygen-level-dependent signals are recorded, the understanding and accurate modeling of the hemodynamic relationship between CBF and CBV becomes increasingly important. This study presents an empirical and data-based modeling framework for model identification from CBF and CBV experimental data. It is shown that the relationship between the changes in CBF and CBV can be described using a parsimonious autoregressive with exogenous input model structure. It is observed that neither the ordinary least-squares (LS) method nor the classical total least-squares (TLS) method can produce accurate estimates from the original noisy CBF and CBV data. A regularized total least-squares (RTLS) method is thus introduced and extended to solve such an error-in-the-variables problem. Quantitative results show that the RTLS method works very well on the noisy CBF and CBV data. Finally, a combination of RTLS with a filtering method can lead to a parsimonious but very effective model that can characterize the relationship between the changes in CBF and CBV.