Vascular Flows Research Articles

Vasodilator tone in the llama fetus: the role of nitric oxide during normoxemia and hypoxemia

The fetal llama responds to hypoxemia, with a marked peripheral vasoconstriction but, unlike the sheep, with little or no increase in cerebral blood flow. We tested the hypothesis that the role of nitric oxide (NO) may be increased during hypoxemia in this species, to counterbalance a strong vasoconstrictor effect. Ten fetal llamas were operated under general anesthesia. Mean arterial pressure (MAP), heart rate, cardiac output, total vascular resistance, blood flows, and vascular resistances in cerebral, carotid and femoral vascular beds were determined. Two groups were studied, one with nitric oxide synthase (NOS) blocker N(G)-nitro-L-arginine methyl ester (L-NAME), and the other with 0.9% NaCl (control group), during normoxemia, hypoxemia, and recovery. During normoxemia, L-NAME produced an increase in fetal MAP and a rapid bradycardia. Cerebral, carotid, and femoral vascular resistance increased and blood flow decreased to carotid and femoral beds, while cerebral blood flow did not change significantly. However, during hypoxemia cerebral and carotid vascular resistance fell by 44% from its value in normoxemia after L-NAME, although femoral vascular resistance progressively increased and remained high during recovery. We conclude that in the llama fetus: 1) NO has an important role in maintaining a vasodilator tone during both normoxemia and hypoxemia in cerebral and femoral vascular beds and 2) during hypoxemia, NOS blockade unmasked the action of other vasodilator agents that contribute, with nitric oxide, to preserving blood flow and oxygen delivery to the tissues.

Bifurcation asymmetry of the porcine coronary vasculature and its implications on coronary flow heterogeneity

The branching pattern of the coronary arteries and veins is asymmetric, i.e., many small vessels branch off of a large trunk such that the two daughter vessels at a bifurcation are of unequal diameters and lengths. One important implication of the geometric vascular asymmetry is the dispersion of blood flow at a bifurcation, which leads to large spatial heterogeneity of myocardial blood flow. To document the asymmetric branching pattern of the coronary vessels, we computed an asymmetry ratio for the diameters and lengths of all vessels, defined as the ratio of the daughter diameters and lengths, respectively. Previous data from silicone elastomer cast of the entire coronary vasculature including arteries, arterioles, venules, and veins were analyzed. Data on smaller vessels were obtained from histological specimens by optical sectioning, whereas data on larger vessels were obtained from vascular casts. Asymmetry ratios for vascular areas, volumes, resistances, and flows of the various daughter vessels were computed from the asymmetry ratios of diameters and lengths for every order of mother vessel. The results show that the largest orders of arterial and venous vessels are most asymmetric and the degree of asymmetry decreases toward the smaller vessels. Furthermore, the diameter asymmetry at a bifurcation is significantly larger for the coronary veins (1.7-6.8 for sinus veins) than the corresponding arteries (1.5-5.8 for left anterior descending coronary artery) for orders 2-10, respectively. The reported diameter asymmetry at a bifurcation leads to significant heterogeneity of blood flow at a bifurcation. Hence, the present data quantify the dispersion of blood flow at a bifurcation and are essential for understanding flow heterogeneity in the coronary circulation.

Color Doppler sonography with contrast in the differentiation of ovarian tumors.

The objective of this study was to differentiate benign ovarian tumors from malignant ones before surgery using color and pulsed Doppler sonography, and to compare results obtained before and after use of contrast medium, thereby verifying whether contrast results in an improvement in the diagnostic sensitivity. Sixty two women (mean age 49.9 years) with ovarian tumors were studied, 45 with benign and 17 with malignant tumors. All women underwent a transvaginal color Doppler ultrasonographic exam. A study of the arterial vascular flow was made in all tumor areas, as well as an impedance evaluation of arterial vascular flow using the resistance index. Localization of the vessels in the tumor revealed a greater proportion of malignant tumors with detectable internal vascular flows (64%) than benign tumors with such flows (22%). There was a considerable overlap of these findings. The use of contrast identified a greater number of vessels with confirmation in the totality of tumors, but did not improve the Doppler capacity in tumoral differentiation. Malignant tumors presented lower values of resistance index than the benign ones, whether or not contrast was used. The cutoff value for resistance index that better maximized the Doppler sensitivity and specificity was 0.55. Through this value, an increase of the sensitivity after contrast use was obtained, varying from 47% to 82%, while specificity remained statistically unchanged. Although the injection of a microbubble agent improved the sensitivity of the method detecting vascularization of tumors, a positive finding for vascularization by this method was not clinically useful in the differentiation of benign and malignant ovarian tumors.

High‐order algorithms for vascular flow modelling

AbstractThis paper presents the development of spectral/hp high‐order elements for vascular flows with particular attention to surface reconstruction and high‐order mesh generation. Using ideas from computer visualization we apply a technique of constructing smooth implicit functions to reconstruct incomplete sectional imaging data from magnetic resonance imaging. Using this as a starting point we outline techniques to discretize and computationally solve the Newtonian flow within these geometries using high‐order spectral/hp element methods. Finally we demonstrate the application of these ideas to anatomically correct and model distal bypass grafts. Copyright © 2002 John Wiley & Sons, Ltd.

The insulin-mediated vascular and blood pressure responses are suppressed in CGRP-deficient normal and diabetic rats.

Calcitonin gene-related peptide (CGRP) is extensively localized in the perivascular or periadventitia nerves throughout the body. CGRP is a potent vasodilator and its release is associated with dilation of these blood vessels. The present study investigated the contribution of the CGRP-mediated vasodilation to the insulin-induced vasodilatory response. Male Wistar rats were treated with capsaicin (50 mg/kg) at 1-3 days of age to ablate the CGRP-containing neurons. After 8 weeks some animals were made diabetic using streptozotocin. Vehicle-treated animals were used as controls. At 12-13 weeks the animals were fasted, anesthetized with chloralose/urethane and instrumented for recording of cardiovascular dynamics. Body weights and basal, insulin, glucose, mean arterial pressure (MAP), heart rate (HR), and vascular flows were not different in CGRP-deficient rats versus controls. Insulin infusion significantly decreased the MAP in vehicle-treated controls but this response was completely attenuated in CGRP-deficient rats. The decreased response to insulin was associated with a diminished vascular dilatory response in the iliac, renal, and superior mesenteric vessel beds. When insulin was infused in CGRP-deficient diabetic animals there was also a diminished response. Diabetes resulted in an increased renal vascular flow in response to insulin. From the present studies we conclude that the insulin-mediated vasodilation was due, in part, to the stimulation of perivascular nerves to release CGRP, and the action of CGRP on vascular smooth muscle enhanced directly or indirectly the vasodilatory response to insulin.

Vascular renal flows during pregnancy in normotensive, preeclamptic and hypertensive women

Vascular renal flows during pregnancy in normotensive, preeclamptic and hypertensive women

Theoretical Analysis of Systematic Errors Introduced by a Pedicel-Girdling Technique used to Estimate Separately the Xylem and Phloem Flows

The water budget of fruits was analysed by means of a biophysical model of fruit growth, built and calibrated recently for peaches [Prunus persica (L.) Batsch]. This analysis was applied to the evaluation of systematic errors introduced by a pedicel-girdling method (with the observations being treated by means of a subtractive technique) used to separate the contributions of xylem and phloem flow to the total water inflow to the fruit. The flows were considered as solution transport through composite membranes and were calculated by means of equations drawn from non-equilibrium thermodynamics. The total inflow of water was simulated as dependent on the water status in the tree. The hourly time step was used for the simulation. The flows obtained by simulation of the pedicel-girdled fruit were compared with those found by simulation of the intact-pedicel fruit. The error introduced by the pedicel-girdling technique was evaluated theoretically and was shown to vary during the day, ranging from very small (relative error of 3–7%) at the period when the rate of fruit growth is maximal to 100% when the fruit volume does not change. The vascular flows obtained from the “girdling experiments” are discussed in relation to the possible theoretically estimated errors.

The effect of diabetes and sex on nitric oxide-mediated cardiovascular dynamics.

Diabetes is associated with impaired cardiovascular responses that are especially prominent in females. Since nitric oxide (NO)-mediated effects on cardiovascular dynamics are altered in diabetes, we evaluated the effect of L-NAME, a nitric oxide synthase (NOS) antagonist, on mean arterial pressure (MAP), heart rate (HR), and selective vascular flows in both male and female normal and diabetic rats as an index of NO activity. Rats were made diabetic using streptozotocin and maintained for 5-6 weeks. Following anesthesia with urethane/alpha-chloralose, the femoral artery and vein were cannulated for recording and sampling, and flow probes were placed on the iliac, renal, and superior mesenteric arteries. A bolus infusion of L-NAME (10mg/ kg) resulted in a rapid +52% and +68% increase in MAP in normal female and male rats, respectively. However, diabetic females' and males' responses were significantly lower (44% and 45%, respectively) when compared with their normal counterparts. The decreased HR in response to the peak pressor effect of L-NAME was more prominent in normal females compared with normal males (-14% vs 2%). The results in diabetic females and males were equivalent (-6% vs -9%, respectively). L-NAME decreased the conductance (flow/MAP) an average of 65% in all three vascular beds in normal female rats. In diabetic females, the iliac and superior mesenteric responses to L-NAME were less, and the renal conductance was contrastingly increased 23%. The response to L-NAME was comparable (-62%) in the renal and superior mesenteric and less (-40%) in the iliacs of normal versus diabetic males. We concluded that diabetes is associated with a decreased pressor response to NOS inhibition. And the impaired constriction response of the renal vessels noted in female diabetic rats may provide a basis for the increased renal pathology observed in diabetic humans.

Alterations in endogenous nitric oxide production after cardiopulmonary bypass in lambs with normal and increased pulmonary blood flow.

After cardiopulmonary bypass (CPB), altered vascular reactivity is a major source of complications, particularly for children with increased pulmonary blood flow. Although changes in agonist-induced NO activity are well described after CPB, potential changes in basal NO production and their role in post-CPB pulmonary hypertension remain unclear. By using aortopulmonary vascular graft placement in the fetal lamb (shunt lambs), we established a unique model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. The objective of the present study was to investigate potential alterations in endogenous NO production after CPB in lambs with normal and increased pulmonary blood flow. Vascular pressures and blood flows were monitored in 1-month-old lambs (n=7) with increased pulmonary blood flow and 6 age-matched control lambs. After shunt closure, hypothermic CPB (25 degrees C) was performed for 2 hours. The hemodynamic variables were monitored for 4 hours after CPB. Before, during, and after CPB, peripheral lung biopsies were performed to determine tissue NO, nitrite, nitrate, and cGMP concentrations; total NO synthase (NOS) activity; and endothelial NOS protein levels. Hypothermic CPB increased both mean pulmonary arterial pressure and left pulmonary vascular resistance (P:<0.05). The increase in pulmonary arterial pressure induced in shunt lambs was greater than that induced in control lambs (P:<0.05). Four hours after CPB, tissue concentrations of NO, nitrite, nitrate, and cGMP were decreased to approximately 70% of pre-CPB levels in both control and shunt lambs (P:<0.05). Total NOS activity and endothelial NOS protein levels were unchanged. Modest decreases in basal NO production, the inability to increase NO production, or both may play a role in the altered pulmonary vascular reactivity after CPB. The decrease in NO is independent of gene expression. However, other mechanisms for this decrease, such as substrate or cofactor availability, warrant further study.

Alterations in Endogenous Nitric Oxide Production After Cardiopulmonary Bypass in Lambs With Normal and Increased Pulmonary Blood Flow

Background —After cardiopulmonary bypass (CPB), altered vascular reactivity is a major source of complications, particularly for children with increased pulmonary blood flow. Although changes in agonist-induced NO activity are well described after CPB, potential changes in basal NO production and their role in post-CPB pulmonary hypertension remain unclear. By using aortopulmonary vascular graft placement in the fetal lamb (shunt lambs), we established a unique model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. The objective of the present study was to investigate potential alterations in endogenous NO production after CPB in lambs with normal and increased pulmonary blood flow. Methods and Results —Vascular pressures and blood flows were monitored in 1-month-old lambs (n=7) with increased pulmonary blood flow and 6 age-matched control lambs. After shunt closure, hypothermic CPB (25°C) was performed for 2 hours. The hemodynamic variables were monitored for 4 hours after CPB. Before, during, and after CPB, peripheral lung biopsies were performed to determine tissue NO, nitrite, nitrate, and cGMP concentrations; total NO synthase (NOS) activity; and endothelial NOS protein levels. Hypothermic CPB increased both mean pulmonary arterial pressure and left pulmonary vascular resistance ( P &lt;0.05). The increase in pulmonary arterial pressure induced in shunt lambs was greater than that induced in control lambs ( P &lt;0.05). Four hours after CPB, tissue concentrations of NO, nitrite, nitrate, and cGMP were decreased to ≈70% of pre-CPB levels in both control and shunt lambs ( P &lt;0.05). Total NOS activity and endothelial NOS protein levels were unchanged. Conclusions —Modest decreases in basal NO production, the inability to increase NO production, or both may play a role in the altered pulmonary vascular reactivity after CPB. The decrease in NO is independent of gene expression. However, other mechanisms for this decrease, such as substrate or cofactor availability, warrant further study.

Cardiorespiratory responses of the toad (Bufo marinus) to hypoxia at two different temperatures.

Central vascular blood flows and ventilation were measured in conscious toads (Bufo marinus) at 15 and 25 degrees C. The animals were exposed to hypoxia (Fi(O)(sum)=0.10 and 0.05, where Fi(O)(sum) is the fractional oxygen concentration of inspired air) at both temperatures. In addition, the cardiorespiratory responses to hypercapnia (Fi(CO)(sum)=0.05) and atropine injection (5 mg kg(-)(1); 7.4 micromol kg(-)(1)) were studied at 25 degrees C. At 25 degrees C, systemic blood flow ( q_dot (sys)) exceeded pulmocutaneous blood flow ( q_dot (pc)), indicating a large net right-to-left shunt ( q_dot (pc)/ q_dot (sys) was 0.39). q_dot (pc)/ q_dot (sys) was reduced significantly to 0.22 at 15 degrees C. At both temperatures, q_dot (pc) increased significantly during hypoxia (from 26.2 to 50.8 ml min(-)(1 )kg(-)(1) at 25 degrees C and from 11. 2 to 18.9 ml min(-)(1 )kg(-)(1) at 15 degrees C), whereas q_dot (sys) changed little (from 77.2 to 66.2 ml min(-)(1 )kg(-)(1) at 25 degrees C and from 54.3 to 50.1 ml min(-)(1 )kg(-)(1) at 15 degrees C). As a result, the net right-to-left shunt was greatly reduced, while total cardiac output remained almost unaffected. The ventilatory response was more pronounced during hypercapnia but, since q_dot (pc) and q_dot (sys) were affected similarly, there was no change in the shunt pattern. In undisturbed toads at 25 degrees C, atropine injection increased q_dot (pc) and eliminated the net right-to-left shunt. This is consistent with the known vagal innervation of the pulmonary artery. The present study shows that the cardiac right-to-left shunt that prevails in undisturbed and resting toads is reduced with increased temperature and during hypoxia. These findings are consistent with the general view that the cardiac right-to-left shunt is regulated and reduced whenever oxygen delivery is compromised or metabolic rate is increased.

Vascular Dilatatory Responses to Sodium Nitroprusside (SNP) and α‐Adrenergic Antagonism in Female and Male Normal and Diabetic Rats

Abstract.Diabetes is associated with impaired vascular dilatatory responses that appear to be influenced by sex as well as diabetic state. Therefore, we hypothesized that vascular and sympathetic control function exhibit a greater deterioration following the induction of diabetes in female than in male rats. We conducted a comparative determination of the effect of sodium nitroprusside (SNP, a nitrous oxide donor) and that of an α1‐adrenergic antagonist, prazosin, on selective vascular flows, mean arterial pressure (MAP), and heart rate (HR), in female and male normal and diabetic rats. Rats were made diabetic using streptozotocin (50 mg/kg, iv) and maintained for 5–6 weeks. Following anesthesia with urethane/α‐chloralose, the femoral artery and vein were cannulated for recording and sampling. Flow probes were placed on the iliac, renal, and superior mesenteric arteries. SNP (1, 5, 10, and 20 μg/kg) infusions resulted in a dose‐dependent decrease in MAP in normal and diabetic rats. The decrease in MAP in normal males was 37% less at the 20 μg/kg concentration of SNP when compared to normal females. The HR was not significantly changed in response to the hypotensive effect of SNP; however, reflex tachycardia was more prominent in diabetic males. The vascular conductance (flow/MAP) was increased by SNP in normal and diabetic rats in a dose‐dependent fashion; however, the responsiveness was decreased in the iliac and superior mesenteric and increased in the renal arteries in diabetics when compared to normals. Diabetic males were 42% and 28% less responsive to SNP in the iliac and superior mesenteric arteries, respectively. On the other hand, diabetic females were 1.5‐fold more responsive in the renal artery when compared to normals. Prazosin (4 mg/kg) decreased the MAP in normal and diabetic rats to a comparable degree. Prazosin increased the vascular conductance in all three vascular beds in normal and diabetic rats with the greater increase occurring in the iliac (118%) and superior mesenteric (110%) arteries. We concluded that diabetes is associated with an increased response to NO in the renal vessels and a decreased response in the iliac and superior mesenteric vessels in both females and males. α‐Adrenergic tone was greatest in diabetic female and male rats. This study suggests that decreased vascular flow in diabetes is a result of a combination of decreased sensitivity to NO and increased adrenergic tone.

Vascular dilatatory responses to sodium nitroprusside (SNP) and alpha-adrenergic antagonism in female and male normal and diabetic rats.

Diabetes is associated with impaired vascular dilatatory responses that appear to be influenced by sex as well as diabetic state. Therefore, we hypothesized that vascular and sympathetic control function exhibit a greater deterioration following the induction of diabetes in female than in male rats. We conducted a comparative determination of the effect of sodium nitroprusside (SNP, a nitrous oxide donor) and that of an alpha1-adrenergic antagonist, prazosin, on selective vascular flows, mean arterial pressure (MAP), and heart rate (HR), in female and male normal and diabetic rats. Rats were made diabetic using streptozotocin (50 mg/kg, iv) and maintained for 5-6 weeks. Following anesthesia with urethane/alpha-chloralose, the femoral artery and vein were cannulated for recording and sampling. Flow probes were placed on the iliac, renal, and superior mesenteric arteries. SNP (1, 5, 10, and 20 microg/kg) infusions resulted in a dose-dependent decrease in MAP in normal and diabetic rats. The decrease in MAP in normal males was 37% less at the 20 microg/kg concentration of SNP when compared to normal females. The HR was not significantly changed in response to the hypotensive effect of SNP; however, reflex tachycardia was more prominent in diabetic males. The vascular conductance (flow/MAP) was increased by SNP in normal and diabetic rats in a dose-dependent fashion; however, the responsiveness was decreased in the iliac and superior mesenteric and increased in the renal arteries in diabetics when compared to normals. Diabetic males were 42% and 28% less responsive to SNP in the iliac and superior mesenteric arteries, respectively. On the other hand, diabetic females were 1.5-fold more responsive in the renal artery when compared to normals. Prazosin (4 mg/kg) decreased the MAP in normal and diabetic rats to a comparable degree. Prazosin increased the vascular conductance in all three vascular beds in normal and diabetic rats with the greater increase occurring in the iliac (118%) and superior mesenteric (110%) arteries. We concluded that diabetes is associated with an increased response to NO in the renal vessels and a decreased response in the iliac and superior mesenteric vessels in both females and males. alpha-Adrenergic tone was greatest in diabetic female and male rats. This study suggests that decreased vascular flow in diabetes is a result of a combination of decreased sensitivity to NO and increased adrenergic tone.

Effects of Hyperinsulinemia on vascular blood flows in experimental obesity

Human obesity, which is very common in Polycystic Ovaries Syndrome and in “ X Syndrome”, constitutes an insulin-resistance state in which multiple clinical, biochemical and hemodynamic alterations coexist. Insulin resistance in the obese has been recently associated with an endothelial dysfunction. To investigate the possibility that clinical and metabolic derangements related to insulin resistance could induce changes in vascular blood flows, we have studied the levels of mesenteric (MBF), renal (RBF) and femoral (FBF) blood flows in Beagle dogs kept for 2 years on a normal (control group) or high fat diet (obese group). This experimental model exhibits many of the abnormalities with the human syndrome. In addition, we have tested the effects of chronic treatment with captopril (capto group) in monotherapy or in association with pravastatin (prava+capto group) on the hemodynamic changes associated with this diet. After the two year follow-up, Transonic flow probes were placed around the three arteries to measure basal blood flows and their response to a hyperinsulinemic-normoglycemic test in anesthetized animals. During this test the degree of insulin sensitivity was estimated. In association with higher body weight, blood pressure, insulin resistance, and fasting levels of insulin and total cholesterol, the obese group exhibited decreased basal levels of FBF and a greater femoral vasoconstriction during hyperinsulinism ( P<0.05 vs control). Combined therapy with captopril and pravastatin ameliorated the reduction in basal FBF and hyperinsulinism-induced vasoconstriction ( P<0.05), in addition to the beneficial effects on insulin sensitivity, and clinical and metabolic parameters. Synergistic beneficial effects of both drugs on lipid and carbohydrate profiles may account for this positive outcome, by attenuating the atherogenic process associated with this model.

Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow

Background: Children with increased pulmonary blood flow may experience morbidity as the result of increased pulmonary vascular resistance after operations in which cardiopulmonary bypass is used. Plasma levels of endothelin-1, a potent vasoactive substance implicated in pulmonary hypertension, are increased after cardiopulmonary bypass. Objectives: In a lamb model of increased pulmonary blood flow after in utero placement of an aortopulmonary shunt, we characterized the changes in pulmonary vascular resistance induced by hypothermic cardiopulmonary bypass and investigated the role of endothelin-1 and endothelin-A receptor activation in postbypass pulmonary hypertension. Methods: In eleven 1-month-old lambs, the shunt was closed, and vascular pressures and blood flows were monitored. An infusion of a selective endothelin-A receptor blocker (PD 156707; 1.0 mg/kg/h) or drug vehicle (saline solution) was then begun 30 minutes before cardiopulmonary bypass and continued for 4 hours after bypass. The hemodynamic variables were monitored, and plasma endothelin-1 concentrations were determined before, during, and for 6 hours after cardiopulmonary bypass. Results: After 90 minutes of hypothermic cardiopulmonary bypass, both pulmonary arterial pressure and pulmonary vascular resistance increased significantly in saline-treated lambs during the 6-hour study period ( P < .05). In lambs pretreated with PD 156707, pulmonary arterial pressure and pulmonary vascular resistance decreased ( P < .05). After bypass, plasma endothelin-1 concentrations increased in all lambs; there was a positive correlation between postbypass pulmonary vascular resistance and plasma endothelin-1 concentrations ( P < .05). Conclusions: This study suggests that endothelin-A receptor–induced pulmonary vasoconstriction mediates, in part, the rise in pulmonary vascular resistance after cardiopulmonary bypass. Endothelin-A receptor antagonists may decrease morbidity in children at risk for postbypass pulmonary hypertension. This potential therapy warrants further investigation. (J Thorac Cardiovasc Surg 1999;117: 314-23)

Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats.

Obesity and hyperinsulinism are known to be major stimuli of leptin production by adipose tissue, leading to increased leptin levels in the circulation. It has also been demonstrated that increased leptin production leads to satiety, possibly by decreasing the levels of neuropeptide Y (NPY) in the central nervous system (CNS). Because obesity and hyperinsulinism are also frequently associated with hypertension, we studied the effect of the intracerebroventricular (ICV) administration of leptin on mean arterial pressure (MAP), heart rate, vascular flows, and lumbar and renal sympathetic nerve activity (SNA). Normal Wistar rats were implanted with an ICV cannula and allowed to recover. On the day of the study, the animals were fasted and anesthetized with chloralose/urethane. Catheters were placed in a femoral artery and vein, and Doppler flow probes were placed around the iliac, renal, and superior mesenteric arteries for measurement of MAP, heart rate, and blood flows. In other experiments, lumbar SNA and renal SNA were recorded. ICV leptin administration resulted in an MAP that was slowly but progressively increasing. Blood flows decreased in the iliac and superior mesenteric arteries, but not in the renal artery. Leptin injection increased the lumbar SNA and renal SNA. The plasma glucose and insulin levels were not changed. We concluded that ICV leptin increases MAP by decreasing arterial blood flow to the skeletal muscle and the splanchnic vascular bed. This increased peripheral resistance is the result of an increased activity of the sympathetic nerves. We suggest that increased leptin may serve as a link in the triad of obesity and hyperinsulinism and hypertension.

The Effects of Artificial Lung Inflation on Pulmonary Blood Flow And Heart Rate In The Turtle Trachemys Scripta

As for most ectothermic vertebrates, the breathing pattern of turtles is episodic, and pulmonary blood flow (Qpul) and heart rate (fH) normally increase several-fold during spontaneous ventilation. While some previous studies suggest that these cardiovascular changes are caused by stimulation of pulmonary stretch receptors (PSRs) during ventilation, it has been noted in other studies that blood flows often change prior to the initiation of breathing. Given the uncertainty regarding the role of PSRs in the regulation of central vascular blood flows, we examined the effect of manipulating lung volume (and therefore PSR stimulation) on blood flows and heart rate in the freshwater turtle Trachemys scripta. Turtles were instrumented with blood flow probes on the left aortic arch and the left pulmonary artery for measurements of blood flow, and catheters were inserted into both lungs for manipulation of lung volume. In both anaesthetized and fully recovered animals, reductions or increases in lung volume by withdrawal of lung gas or injection of air, N2, O2 or 10% CO2 (in room air) had no effect on blood flows. Furthermore, simulations of normal breathing bouts by withdrawal and injection of lung gas did not alter Qpul or fH. We conclude that stimulation of PSRs is not sufficient to elicit cardiovascular changes and that the large increase in Qpul and fH normally observed during spontaneous ventilation are probably caused by a simultaneous feedforward control of central origin.

Cerebrospinal fluid pulsation amplitude and its quantitative relationship to cerebral blood flow pulsations: a phase-contrast MR flow imaging study.

Our purpose in this investigation was to explain the heterogeneity in the cerebrospinal fluid (CSF) flow pulsation amplitudes. To this end, we determined the contributions of the cerebral arterial and jugular venous flow pulsations to the amplitude of the CSF pulsation. We examined 21 healthy subjects by cine phase-contrast MRI at the C2-3 disc level to demonstrate the CSF and vascular flows as waveforms. Multiple regression analysis was performed to calculate the contributions of (a) the arterial and venous waveform amplitudes and (b) the delay between the maximum systolic slopes of the arterial and venous waveforms (AV delay), in order to predict the amplitude of the CSF waveform. The contribution of the arterial waveform amplitude was positive (r = 0.61; p = 0.003) to the CSF waveform amplitude and that of the venous waveform amplitude was negative (r = -0.50; p = 0.006). Both in combination accounted for 56% of the variance in predicting the CSF waveform amplitude (p < 0.0006). The contribution of AV delay was not significant. The results show that the variance in the CSF flow pulsation amplitudes can be explained by concurrent evaluation of the CSF and vascular flows. Improvement in the techniques, and controlled experiments, may allow use of CSF flow pulsation amplitudes for clinical applications in the non-invasive assessment of intracranial dynamics by MRI.

Post-cardiopulmonary bypass pulmonary hypertension in lambs with increased pulmonary blood flow. A role for endothelin 1.

After cardiopulmonary bypass (CPB), pulmonary hypertension and its associated increased vascular reactivity are a major source of morbidity, particularly for children with increased pulmonary blood flow. Although post-CPB pulmonary hypertension is well described, its mechanisms remain incompletely understood. Plasma levels of endothelin 1. a potent vasoactive substance implicated in pulmonary hypertension, are increased after CPB. The purpose of the present study was threefold: to characterize the changes in pulmonary vascular resistance and vascular reactivity induced by hypothermic CPB; to investigate the effects of preexisting increased pulmonary blood flow on these changes; and to better define the role of endothelin 1 in the pathogenesis of post-CPB pulmonary hypertension. Vascular pressures and blood flows were monitored in 14 1-month-old lambs with increased pulmonary blood flow (after in utero placement of an aortopulmonary shunt) and 6 age-matched control lambs. During the 2-hour study period after 105.3 +/- 20.6 minutes of hypothermic CPB the increase in pulmonary vascular resistance was significantly augmented in lambs with increased pulmonary blood flow compared with control lambs (P < .05). Pretreatment with PD 145065 (a nonselective endothelin receptor blocker; 50 micrograms.kg-1.min-1) completely blocked this increase in pulmonary vascular resistance and blocked the increase in pulmonary vascular resistance in response to acute alveolar hypoxia after CPB (96.3 +/- 88.5% versus -9.7 +/- 16.4%; P < .05). Plasma endothelin 1 levels increased after CPB in all lambs. Preexisting increased pulmonary blood flow alters the response of the pulmonary circulation to hypothermic CPB; the increase in pulmonary vascular resistance induced by CPB is augmented in lambs with increased pulmonary blood flow. Pretreatment with endothelin 1 receptor blockers eliminated the increase in pulmonary vascular resistance and the pulmonary vasoconstricting response to alveolar hypoxia, suggesting a role for endothelin 1 in post-CPB pulmonary hypertension. Endothelin 1 receptor blockers may decrease morbidity in children at risk for pulmonary hypertension after surgical repair with CPB and warrants further study.

Altered endothelium-dependent responses in lambs with pulmonary hypertension and increased pulmonary blood flow.

To investigate early endothelial function associated with increased pulmonary blood flow, vascular shunts were placed between the ascending aorta and main pulmonary artery in 18 late-gestation fetal sheep. Four weeks after delivery, the lambs were instrumented to measure vascular pressures and blood flows, and blood was collected to measure plasma concentrations of guanosine 3',5'-cyclic monophosphate [cGMP, the second messenger to nitric oxide (NO)-mediated vasodilation] and L-arginine (the precursor for NO synthesis). The responses to the endothelium-dependent vasodilators acetylcholine (ACh, 1.0 microgram/kg) and ATP (0.1 mg.kg-1.min-1), the endothelium-independent vasodilators M & B-22948 (a cGMP-specific phosphodiesterase inhibitor, 2.5 mg/kg) and inhaled NO (40 ppm), and N omega-nitro-L-arginine (an inhibitor of NO synthase, 5 mg/kg) were then compared with responses in 12 age-matched controls. Vasodilator responses in control lambs were determined during pulmonary hypertension induced by U-46619 (a thromboxane A2 mimic). Shunted lambs displayed a selective impairment of endothelium-dependent pulmonary vasodilation, an augmented pulmonary vasoconstricting response to NO synthase inhibition, increased plasma cGMP concentrations, and decreased L-arginine concentrations. Taken together, these data suggest that lambs with pulmonary hypertension and increased pulmonary blood flow have early aberrations in endothelial function, as manifested by increased basal NO activity, that cannot be further increased by agonist-induced endothelium-dependent vasodilators.