Systemic Circulatory Changes Research Articles

Lateral position does not cause an interhemicerebral difference of cerebral hemodynamic in healthy adult volunteers

Cerebral perfusion is maintained at a consistent value irrespective of changes in systemic blood pressure or disease-induced changes in general physical condition. This regulatory mechanism is effective despite postural changes, working even during changes in posture, such as those from sitting to standing or from the head-down to the head-up position. However, no study has addressed changes in perfusion separately in the left and right cerebral hemispheres, and there has been no specific investigation of the effect of the lateral decubitus position on perfusion in each hemisphere. Surgery, particularly respiratory surgery, is often performed with the patient in the lateral decubitus position, and since intraoperative anesthesia may also have an effect, it is important to ascertain the effect of the lateral decubitus position on perfusion in the left and right cerebral hemispheres in the absence of anesthesia. The effects of the lateral decubitus position on heart rate, blood pressure, and hemodynamic in the left and right cerebral hemispheres assessed by regional saturation of oxygen measured by near-infrared spectroscopy were investigated in healthy adult volunteers. Although the lateral decubitus position causes systemic circulatory changes, it may not cause any difference in hemodynamic between the left and right cerebral hemispheres.

Chapter 28 - Hemodynamics in acute stroke: Cerebral and cardiac complications

Hemodynamics is the study of blood flow, where parameters have been defined to quantify blood flow and the relationship with systemic circulatory changes. Understanding these perfusion parameters, the relationship between different blood flow variables and the implications for ischemic injury are outlined in the ensuing discussion. This chapter focuses on the hemodynamic changes that occur in ischemic stroke, and their contribution to ischemic stroke pathophysiology. We discuss the interaction between cardiovascular response and hemodynamic changes in stroke. Studying hemodynamic changes has a key role in stroke prevention, therapeutic implications and prognostic importance in acute ischemic stroke: preexisting hemodynamic and autoregulatory impairments predict the occurrence of stroke. Hemodynamic failure predisposes to the formation of thromboemboli and accelerates infarction due to impairing compensatory mechanisms. In ischemic stroke involving occlusion of a large vessel, persistent collateral circulation leads to preservation of ischemic penumbra and therefore justifying endovascular thrombectomy. Following thrombectomy, impaired autoregulation may lead to reperfusion injury and hemorrhage.

Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia

Preeclampsia is the most severe type of hypertensive disorder of pregnancy, affecting one in 10 pregnancies worldwide and increasing significantly maternal and neonatal morbidity and mortality. Women developing preeclampsia display an array of symptoms encompassing uncontrolled hypertension and proteinuria, with neurological symptoms including seizures at the end of pregnancy. The main causes of preeclampsia are still unknown. However, abnormal placentation and placenta vascularization seem to be common features in preeclampsia, also leading to fetal growth restriction mainly due to reduced placental blood flow and chronic hypoxia. An over activation of maternal immunity cells against the trophoblasts, the main cells forming the placenta, has been recently shown as an important mechanism triggering trophoblast apoptosis and death. This response will further disrupt the remodeling of maternal uterine arteries, in a first stage, and the formation of new placental vessels in a later stage. A consequent chronic hypoxia stress will further contribute to increase placental stress and exacerbate systemic circulatory changes in the mother. The molecular mechanisms driving these processes of apoptosis and anti-angiogenesis are also not well-understood. In this review, we group main evidences suggesting potential targets and molecules that should be better investigated in preeclampsia. This knowledge will contribute to improve therapies targeting a better placenta formation, having a positive impact on maternal disease prevention and on fetal development.

Abstract A121: Transient increase of tumor perfusion using hypertonic saline

Abstract Intravenous administration of hypertonic saline solution (HSS) induces systemic circulatory changes including increases in systemic blood pressure and effective circulating volume, as well as local effects on microvasculature. We analyzed the effects produced by 7.5% HSS administration on tumor hemodynamics through functional imaging studies. Blood velocity assessed by color Doppler ultrasound was increased after HSS injection compared to PBS in B16F10 (p=0.019), SK-MEL-147 (p=0.028), and 4T1 (p=0.015). No statistical differences were observed on the segmental kidney arteries (p=0.476). Dynamic contrast-enhanced ultrasound (CEUS) was used to assess functional blood volume in B16F10, HCT-116, and MDA-MB-231 tumor xenografts, kidney and muscle tissues (n=3 per group). After HSS injection, relative blood volume was increased in B16F10 (p=0.022) and HCT-116 (p=0.039) but not on MDA-MB-231 (p=0.186). There was a mild change that was not statistically significant on the normal tissues (kidney p=0.957; muscle p=0.104). Finally, dynamic contrast-enhanced MRI (DCE-MRI) was performed in B16F10 tumors (n=4) and showed that contrast distribution increases in the HSS group (p=0.002). All statistical tests were two sided. HSS 7.5% is a potential vehicle to transiently increase blood supply in specific tumors, and therefore could be used to enhance intratumoral delivery of different molecules for either tumor diagnosis or treatment. Supported by an UICC Yamagiwa-Yoshida grant and FAPESP (2013/06120-8 and 2015/22814-5). Citation Format: Angelica M. Patiño, Mara S. Junqueira, Xiaomeng Zhang, Kate Bailey, Arig Ibrahim-Hashim, Robert J. Gillies, Roger Chammas. Transient increase of tumor perfusion using hypertonic saline [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A121.

Acute Kidney Injury after ALPPS Procedure (Case Report)

Acute kidney injury (AKI) is a serious complication after major liver resection. It may be caused by post-hepatectomy liver failure (PLF). ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy) procedure is an effective way for PLF prevention in cases of small future remnant volume or bilobar liver lesions, but the risk of AKI following this procedure is unknown. Herein we present and discuss the case of a 23-year-old man with hepatic alveococcosis who underwent ALPPS procedure. Despite absence of any risk factors AKI (RIFLE-F) followed by renal replacement therapy (RRT) has occurred within few hours after the first surgical stage. Only the combination of albumin and terlipressin resulted function improvement and RRT with drawal after three weeks of AKI onset. Renal dysfunction didn’t affect the liver regeneration and the second stage of ALPPS has been performed in six days after the first one. There were no signs of serious liver synthetic function deterioration, coagulopathy, jaundice or encephalo pathy. The mechanisms of AKI progression as well as the portal and systemic circulatorychanges after the first stage of ALPPS seem to be similar with hepatorenal syndrome type I. Intra- and postoperative maintenance of physiologic hemodynamics may be the key point for AKI prevention. Norepinephrine and/or terlipressin could be considered as the drugs of choice.

NONINVASIVE METHODS ASSESSMENT BLOOD FLOW IN ANTERIOR SEGMENT AND CLINICAL APPLICATION PERSPECTIVE

The literature review contains information on the anatomical and physiological features of the vessels of the conjunctiva, iris, ciliary body. There are data on the development and application of new non-invasive methods for the study of hemodynamics in the microvessels of anterior eye segment. To study the blood flow of the anterior segment of the eye, biomycroscopy, photography and videobiomicroscopy, television biomicroscopy of vessels, darkfield visualization, application fluorescence angiography, photoacoustic angiography, orthogonal polarization spectroscopy, laser Doppler flowmetry and OCT-angiography were used in recent years. These methods allow to determine the qualitative and quantitative characteristics of conjunctiva, iris, ciliary body microcirculation. They are highly informative for assess of various drugs effect on the vascular eye system. Investigation of hemodynamics in the eye microvessels is necessary for a fundamental approach to the study of the pathophysiology of systemic circulatory pathologies (with arterial hypertension, diabetes, etc.) and changes in regional blood flow in organ of vision disease. Monitoring of anterior segment microcirculation in clinical practice makes possible to monitor the effectiveness of drug and surgical treatment.

The Imbalance of Vascular Molecules in Alzheimer's Disease

The vascular system plays an integral role during Alzheimer's disease (AD). Both systemic circulatory changes and alterations directly within the brain vasculature have been suggested to contribute to both the onset and progression of neurological conditions such as AD. It is now well established that vascular risk factors including hypertension, diabetes, obesity, atherosclerosis, metabolic syndrome, and stroke significantly increase one's risk of later developing AD. Research within the last decade has begun to identify specific vascular molecules associated with such risk factors as well as elucidate the biological role they may play in the pathological processes linked to AD. This review aims to provide an overview of some of the key molecules within vascular cells and circulating in blood that have been identified to be altered in AD pathogenesis. In particular, the vascular-specific transcription factors MEOX2, MYOCD, and SRF, genetic risk factor APOE4, transport proteins LRP1 and RAGE, and circulating molecules such as sLRP1, homocysteine, and albumin are discussed. I aim to clarify how these identified vascular molecules may help to predict, explain, and influence the incidence AD. A strong emphasis is placed on the concept that these molecules play overlapping roles in cardiovascular disease progression, neurovascular dysfunction, and amyloid-β pathology. The studies reviewed here have identified vascular-based molecular targets in AD and thus provide new therapeutic avenues for the treatment of this devastating disease.

Regional differences in facial skin blood flow responses to the cold pressor and static handgrip tests

We have previously reported the unique regional responses of facial skin blood flow (SkBF) to oral application of the basic tastes without simultaneous systemic circulatory changes. In the present study, we determined whether a systemic circulatory challenge due to sympathetic activation induces regional differences in facial SkBF by observing the responses in facial SkBF and blood pressure to a 2-min cold pressor test (CPT) and static handgrip exercise (HG) by right hand in 20 healthy subjects. The CPT significantly increased SkBF in the forehead, eyelid, cheek, upper lip and lower lip by 6 ± 2 to 8 ± 2 % (mean ± SEM) as compared to resting baseline, with a significant simultaneous increase (13 ± 2 %) in mean arterial pressure (MAP), whereas it significantly decreased the SkBF in the nose by 5 ± 2 %. The HG significantly increased SkBF in the forehead, cheek and lower lip by 6 ± 3 to 10 ± 3 %, with a significant simultaneous increase in MAP (13 ± 2 %), while it induced no significant change in the other regions. Increases in SkBF were greater in the right than left cheek during CPT. These results demonstrate that a systemic circulatory challenge via sympathetic activation elicits regional differences in the facial SkBF response.

Hepatorenal syndrome

Hepatorenal syndrome (HRS) is defined as a functional renal failure in patients with liver disease with portal hypertension and it constitutes the climax of systemic circulatory changes associated with portal hypertension. This term refers to a precisely specified syndrome featuring in particular morphologically intact kidneys, where regulatory mechanisms have minimised glomerular filtration and maximised tubular resorption and urine concentration, which ultimately results in uraemia. The syndrome occurs almost exclusively in patients with ascites. Type 1 HRS develops as a consequence of a severe reduction of effective circulating volume due to both an extreme splanchnic arterial vasodilatation and a reduction of cardiac output. Type 2 HRS is characterised by a stable or slowly progressive renal failure so that its main clinical consequence is not acute renal failure, but refractory ascites, and its impact on prognosis is less negative. Liver transplantation is the most appropriate therapeutic method, nevertheless, only a few patients can receive it. The most suitable "bridge treatments" or treatment for patients ineligible for a liver transplant include terlipressin plus albumin. Terlipressin is at an initial dose of 0.5-1 mg every 4 h by intravenous bolus to 3 mg every 4 h in cases when there is no response. Renal function recovery can be achieved in less than 50% of patients and a considerable decrease in renal function may reoccur even in patients who have been responding to therapy over the short term. Transjugular intrahepatic portosystemic shunt plays only a marginal role in the treatment of HRS.

Sodium tanshinone IIA sulfonate increased intestinal hemodynamics without systemic circulatory changes in healthy newborn piglets

In traditional Chinese medicine, tanshinone IIA is a lipid-soluble component of Danshen that has been widely used for various cardiovascular and cerebrovascular disorders, including neonatal asphyxia. Despite promising effects, little is known regarding the hemodynamic effects of tanshinone IIA in newborn subjects. To examine the dose-response effects of sodium tanshinone IIA sulfonate (STS) on systemic and regional hemodynamics and oxygen transport, 12 newborn piglets were anesthetized and acutely instrumented for the placement of femoral arterial and venous, pulmonary arterial catheters to measure mean arterial, central venous, and pulmonary arterial pressures, respectively. The blood flow at the common carotid, renal, pulmonary, and superior mesenteric (SMA) arteries were continuously monitored after treating the piglets with either STS (0.1-30 mg/kg iv) or saline treatment (n = 6/group). To further delineate the underlying mechanisms for vasorelaxant effects of STS, in vitro vascular myography was carried out to compare its effect on rat mesenteric and carotid arteries (n = 4-5/group). STS dose-dependently increased the SMA blood flow and the corresponding oxygen delivery with no significant effect on systemic and pulmonary, carotid and renal hemodynamic parameters. In vitro studies also demonstrated that STS selectively dilated rat mesenteric but not carotid arteries. Vasodilation in mesenteric arteries was inhibited by apamin and TRAM-34 (calcium-activated potassium channel inhibitors) but not by meclofenamate (cyclooxygenase inhibitor) or N-nitro-l-arginine methyl ester hydrochloride (nitric oxide synthase inhibitor). In summary, without significant hemodynamic effects on newborn piglets, intravenous infusion of STS selectively increased mesenteric perfusion in a dose-dependent manner, possibly via an endothelium-derived hyperpolarizing factor vasodilating pathway.

Scale-space analysis of time series in circulatory research

Statistical analysis of time series is still inadequate within circulation research. With the advent of increasing computational power and real-time recordings from hemodynamic studies, one is increasingly dealing with vast amounts of data in time series. This paper aims to illustrate how statistical analysis using the significant nonstationarities (SiNoS) method may complement traditional repeated-measures ANOVA and linear mixed models. We applied these methods on a dataset of local hepatic and systemic circulatory changes induced by aortoportal shunting and graded liver resection. We found SiNoS analysis more comprehensive when compared with traditional statistical analysis in the following four ways: 1) the method allows better signal-to-noise detection; 2) including all data points from real time recordings in a statistical analysis permits better detection of significant features in the data; 3) analysis with multiple scales of resolution facilitates a more differentiated observation of the material; and 4) the method affords excellent visual presentation by combining group differences, time trends, and multiscale statistical analysis allowing the observer to quickly view and evaluate the material. It is our opinion that SiNoS analysis of time series is a very powerful statistical tool that may be used to complement conventional statistical methods.

General Trends in Hemodynamic Disorders in Acute Vertebrocerebrospinal Injury at the Cervical Level

The present study was undertaken to define the general trends in hemodynamic changes in acute vertebrocerebrospinal injury at the cervical level in relation to the severity of cerebrospinal conduction disorders. An invasive central hemodynam-ic study was conducted in 8 and 7 patients with complete and partial spinal cord conduction disturbance, respectively. Magnetic resonance imaging and neurophysiological studies (electromyography and somatosensory evoked potentials) verified the degree of an impairment of the spinal cord and its function. The performed study has demonstrated that in complete spinal cord conduction disturbance, mainly hypokinetic circulation develops in acute vertebrocerebrospinal injury at the cervical level, normokinetic circulation occurred in 15.4% of cases. In partial conduction disturbance, hypokinetic circulation also predominates, but with a 2.8-fold increase in the proportion of normokinetic circulation. In complete and partial spinal cord conduction disturbance, hemodynamic parameters other than stroke volume are statistically significantly decreased to a greater extent. The pulmonary hemodynamic response is unidirectional, by showing systemic circulatory changes.

Norfloxacin Reduces Aortic NO Synthases and Proinflammatory Cytokine Up-Regulation in Cirrhotic Rats: Role of Akt Signaling

Arterial vasodilation plays a role in the pathogenesis of the complications of cirrhosis. This vasodilation is caused by the overproduction of arterial nitric oxide (NO). Bacterial translocation may be involved in NO synthase (NOS) up-regulation by activating both endothelial NOS (eNOS) and inducible NOS (iNOS). The prevention of intestinal gram-negative translocation by norfloxacin administration corrects systemic circulatory changes by decreasing NO production in cirrhosis. However, the signaling mechanisms for NO overproduction from bacterial translocation are unknown. In this study, we investigated the signal transduction pathway of bacterial translocation-induced aortic NOS up-regulation in cirrhotic rats. Proinflammatory cytokine levels, Akt and NOS activities, eNOS phosphorylation, and NOS expressions were assessed in aorta from norfloxacin-treated and untreated cirrhotic rats. Norfloxacin was administered to reduce intestinal bacterial translocation. Aortic eNOS and iNOS protein expressions, Akt activity, and eNOS phosphorylation by Akt at serine 1177 were up-regulated in cirrhotic rats. Norfloxacin administration significantly decreased the incidence of gram-negative translocation and proinflammatory cytokine (tumor necrosis factor-alpha, interferon-gamma, and interleukin-6) levels; norfloxacin also decreased aortic Akt activity, eNOS phosphorylation, and NOS expressions and activities. The decrease in aortic Akt activity and NOS expressions also was obtained after colistin or anti-tumor necrosis factor-alpha antibody administration to cirrhotic rats. This study identifies a signaling pathway in which bacterial translocation induces aortic NOS up-regulation and thus NO overproduction in cirrhotic rats. These results strongly suggest that bacterial translocation and proinflammatory cytokines play a role in systemic NO overproduction in cirrhosis by the Akt pathway.

Fluid resuscitation improves intestinal blood flow and reduces the mucosal damage associated with strangulation obstruction in pigs

Background Strangulation obstruction of the small bowel is associated with local and systemic circulatory changes, local loss of fluid, and damage of the strangulated bowel segment. We wanted to examine to which extent these changes can be prevented by intravenous fluid administration. Materials and methods In anesthetized pigs, strangulation obstruction was induced by increasing the pressure in a baby pressure gasket placed around a loop of ileum until venous pressure in the loop reached 50 mm Hg. During the strangulation period (180 min), a group of eight animals (Fluid min group) received 10 ml · kg -1 · hour -1 Ringer acetate solution intravenously, whereas another eight animals (Fluid max group) received 55 ml · kg -1 · hour -1 Ringer acetate solution intravenously. Blood flow to the strangulated bowel was measured by transit time flowmetry and colored microspheres. After completed experiments, whole wall samples of the strangulated loop were selected for microscopy. Results In the Fluid min group, the heart rate increased, the arterial pressure decreased markedly, and the urine output decreased toward zero. In the Fluid max group, the heart rate and arterial pressure remained fairly constant and the urine output increased. Blood flow to the strangulated bowel decreased in both groups, but significantly more in the Fluid min group. The intestinal blood flow was highly dependent on the arterial blood pressure. The strangulated mucosa showed markedly more damage in the Fluid min group than the Fluid max group. The degree of mucosal damage correlated linearly with the mucosal blood flow. Conclusion The administration of large amounts of fluid to animals with strangulation obstruction normalized the arterial pressure and improved the intestinal blood flow thus minimizing damage to the intestinal mucosa.

Effect of electro-acupuncture stimulation of different frequencies and intensities on ovarian blood flow in anaesthetized rats with steroid-induced polycystic ovaries

BackgroundMaintenance of ovarian blood flow (OBF) is suggested to be important for regular ovulation in women with polycystic ovaries (PCO). The purpose of the present study was to investigate whether electro-acupuncture (EA) of different frequencies and intensities can improve the OBF of anaesthetized rat in the animal model of PCO.MethodsPCO was experimentally induced by a single intramuscular (i.m.) injection of estradiol valerate (EV) in rats. Control rats were given i.m. injection of oil. The involvement of the two ovarian sympathetic nerves; superior ovarian nerve (SON) and plexus ovarian nerve (OPN), in OBF responses was elucidated by severance of SON and OPN in both control and PCO rats. How systemic circulatory changes affect OBF was evaluated by continuous recording of the blood pressure. OBF was measured on the surface of the ovary-using laser Doppler flowmetry. Acupuncture needles were inserted bilaterally into the abdominal and hind limb muscles and connected to an electrical stimulator. Two frequencies – 2 Hz (low) and 80 Hz (high) – with three different intensities – 1.5, 3, and 6 mA – were applied for 35 s.ResultsLow-frequency EA at intensities of 3 and 6 mA elicited significant increases in OBF in the Control group compared to baseline. In the PCO group the increases in OBF were significant only when stimulating with low-frequency EA at 6 mA. After severance of the ovarian sympathetic nerves, the increased response of OBF that had been induced by low-frequency EA in both the Control and PCO group was abolished, indicating that the OBF response is mediated via the ovarian sympathetic nerves. High-frequency EA at 6 mA significantly decreased OBF and mean arterial blood pressure (MAP) in the Control group compared to baseline. In the PCO group, the same stimulation produced similar decreases in MAP, but not in OBF.ConclusionLow-frequency EA stimulation with a strong intensity (6 mA) increases OBF in rats with steroid-induced PCO whereas less strong intensity (3 mA) induces similar changes in control rats. Severance of the ovarian sympathetic nerves, abolish this OBF increase in both study groups, which suggests that the responses of OBF to EA are mediated via the ovarian sympathetic nerves.

Ovarian blood flow responses to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats

The purpose of the present study was to investigate changes in ovarian blood flow (OBF) in response to electro-acupuncture (EA) stimulation at different frequencies and intensities in anaesthetized rats. Whether the ovarian sympathetic nerves were involved in OBF responses was elucidated by severance of the ovarian sympathetic nerves. In addition, how changes in the systemic circulation affected OBF was evaluated by continuously recording blood pressure. OBF was measured on the surface of the left ovary using laser Doppler flowmeter. Acupuncture needles with a diameter of 0.3 mm were inserted bilaterally into the abdominal and the hindlimb muscles and connected to an electrical stimulator. Two frequencies—2 Hz (low) and 80 Hz (high)—with three different intensities—1.5, 3, and 6 mA—were applied for 35 s. Both low- and high-frequency EA at 1.5 mA and high-frequency EA at 3 mA had no effect on OBF or mean arterial blood pressure (MAP). Low-frequency EA at 3 and 6 mA elicited significant increases in OBF. In contrast, high-frequency EA with an intensity of 6 mA evoked significant decreases in OBF, followed by decreases in MAP. After severance of the ovarian sympathetic nerves, the increases in the OBF responses to low-frequency EA at 3 and 6 mA were totally abolished, and the responses at 6 mA showed a tendency to decrease, probably because of concomitant decreases in MAP. The decreased OBF and MAP responses to high-frequency EA at 6 mA remained after the ovarian sympathectomy, and the difference in the responses before and after ovarian sympathectomy was nonsignificant. In conclusion, the present study showed that low-frequency EA stimulation increases OBF as a reflex response via the ovarian sympathetic nerves, whereas high-frequency EA stimulation decreases OBF as a passive response following systemic circulatory changes.

Asphyxia aggravates systemic hypotension but not pulmonary hypertension in piglets with meconium aspiration.

Meconium aspiration and birth asphyxia are both separately connected to significant pulmonary and systemic hemodynamic changes in newborns, but, although these insults frequently coexist, their combined effects on the neonatal circulation are still controversial. To determine the pulmonary and systemic circulatory changes induced by pulmonary meconium contamination with concurrent asphyxia, 41 anesthetized and ventilated newborn piglets (10-12 d) were studied for 6 h. Eleven piglets were instilled with a bolus of human meconium intratracheally, and 10 piglets had meconium instillation with immediate induction of an asphyxic insult. Eight piglets had only asphyxia and 12 ventilated piglets served as controls. Meconium instillation (with and without asphyxia) resulted in a sustained decrease in the oxygenation, which remained, however, on the control level in the asphyxic group. Although meconium insufflation (with and without asphyxia) increased pulmonary artery pressure and vascular resistance progressively during the study period, the meconium-induced hypertensive effect was actually diminished by additional asphyxia. Asphyxia alone did not have any effect on these pulmonary hemodynamic parameters. On the other hand, whereas systemic arterial pressure and vascular resistance remained on the control level after meconium instillation alone, asphyxia (with and without pulmonary meconium insult) resulted in a sustained fall in systemic pressure already by 4 h. Our data thus indicate that although the coexisting asphyxia seems to moderate the meconium aspiration-induced pulmonary hypertensive response, this additional asphyxic insult does not affect the associated hypoxemia, but rather significantly exacerbates systemic hypotension.

Hepatic blood flow responses to mechanical stimulation of the skin in anaesthetised rats

The aim of the present study was to investigate how hepatic blood flow (HBF) changes in response to mechanical stimulation of different areas of the skin in anaesthetised rats, by focusing on involvement of the hepatic sympathetic nerves in and contribution of systemic circulatory changes to the HBF responses. HBF was measured at the surface of the left lateral lobe using the laser Doppler flowmetry. Both innocuous and noxious mechanical stimuli were applied to skin areas of the abdomen and hindlimb. Innocuous mechanical stimulation (brushing) of the abdomen and hindlimb did not significantly change HBF, while noxious mechanical stimulation (pinching) of the abdomen and hindlimb did. The responses to pinching were dependent on the sites stimulated. Pinching of the abdomen decreased, while pinching of the hindlimb increased the HBF. The decrease of HBF in response to abdominal pinching remained after the spinal cord was transected at T1–2 level, but the response was diminished after hepatic sympathetic nerves were severed. On the other hand, the increase of HBF in response to hindlimb pinching was dependent on the increase in blood pressure, and was not influenced by the severance of hepatic sympathetic nerves, and the responses to hindlimb pinching were almost absent after the spinal cord was transected. Based on these results, we suggest that noxious mechanical stimulation of the skin produces changes of HBF, either as a reflex response via activation of the hepatic sympathetic nerves or as a passive response to systemic circulatory changes, depending on the sites stimulated.

Role of sympathetic nervous system in cardiovascular effects of centrally administered endothelin-1 in rats.

Centrally administered endothelin-1 (ET-1) produces a biphasic response, an initial increase followed by a decrease in blood pressure (BP). The pressor effect is due to stimulation of the sympathetic nervous system and/or release of vasopressin. The mechanism responsible for the depressor effect after central administration of ET-1 is still not known. Systemic and regional circulatory effects of intracerebroventricular (i.c.v.) administration of ET-1 (100 ng) were determined in anesthetized rats, using a radioactive microsphere technique. BP, cardiac output, and stroke volume were significantly decreased 30, 60, and 120 min after central administration of ET-1. Heart rate and total peripheral resistance were not altered. ET-1 produced a reduction in blood flow to the brain (83%), heart (62%), kidneys (53%), gastrointestinal tract (43%), portal system (46%), and musculoskeletal system (55%). To determine the role of the central nervous system in cardiovascular effects of centrally administered ET-1, experiments were performed in cervical-sectioned rats. The changes in systemic and regional blood circulation induced by centrally administered ET-1 in normal rats were not observed in cervical-sectioned rats. Pretreatment with a specific antagonist of ETA receptors, BQ-123 (10 micrograms i.c.v.), antagonized systemic and regional circulatory effects of ET-1. Centrally administered clonidine (1 microgram i.c.v.) produced hypotension and bradycardia, known to be mediated through the sympathetic nervous system. Pretreatment with an ETA receptor antagonist, BMS-182874 (50 micrograms/kg iv), blocked clonidine-induced hypotension and bradycardia. We conclude that centrally administered ET-1 stimulates ETA receptors to produce systemic and regional circulatory changes mediated by the sympathetic nervous system.

Volume loading with hypertonic saline solution: Endocrinologic and circulatory responses

Hypertonic saline solution appears to be an attractive method of volume expansion. In 45 patients undergoing elective aorto-coronary bypass grafting, endocrinologic and circulatory responses to volume loading with hypertonic saline solution prepared in low molecular weight (MW) hydroxyethyl starch (HES) solution (72 g/L NaCl, HES concentration: 6%; MW: 200,000 D; degree of substitution [DS]: 0.5) (HS-HES) was compared randomly to patients who had received low molecular weight HES solution (LMW-HES). A group of patients without volume loading served as a control. Volume was infused to double the low pulmonary capillary wedge pressure (PCWP < 5 mmHg) after induction of anesthesia. Plasma levels of atrial natriuretic peptide (ANP), endothelin, vasopressin, and catecholamines were measured before, during, and after cardiopulmonary bypass (CPS) until the first postoperative day. In addition to systemic circulatory changes, capillary skin blood flow was measured by laser Doppler flowmetry. ANP plasma concentration increased in both volume groups (HS-HES: +79%; HES: +32%), whereas it decreased in the control (−20%). Infusion of HS-HES resulted in an increase in plasma endothelin concentration before and after CPS (from 3 to 6 pg/mL). Five hours after CPB, both treatment groups had higher endothelin plasma concentrations than the control patients ( P < 0.05). Epinephrine and norepinephrins plasma levels increased most markedly in the control patients and were highest in the postbypass period in these patients. Cl increased most after infusion of HS-HES (+65%) ( P < 0.05). In the postbypass period, Cl remained significantly higher in both volume groups than in the controls. SVR decreased most in the HS-HES patients (−44%) and was lowest after CPS in these patients. Laser Doppler flow was most increased in the HS-HES patients before as well as after CPS. It is concluded that both kinds of volume given before CPS resulted in an improvement in hemodynamics into the postbypass period. Infusion of HSHES led to the most improved systemic and microcirculatory perfusion, which cannot be explained by the endocrinologic response alone.