Venous Resistance Research Articles

Cardiovascular hemodynamics and exercise tolerance in thyroid disease.

The heart is an organ sensitive to the action of thyroid hormone, and measurable changes in cardiovascular performance are detected with small variations in thyroid hormone serum concentrations. Most patients with thyroid disease experience cardiovascular manifestations, and the most serious complications of thyroid dysfunction occur as a result of cardiac involvement. The increased metabolic state and oxygen consumption that occur in hyperthyroid patients require an increased supply of oxygen and removal of metabolic products from the periphery. This is accomplished by increasing the cardiac output to meet the needs of the periphery. Circulation time is decreased in hyperthyroid patients, and a lowered arterial resistance and increased venous resistance promote the return of blood to the heart. Thyroid hormones may significantly decrease the strength of respiratory and skeletal muscles and affect regulatory mechanisms of adaptation to incremental effort. In hyperthyroidism, cardiovascular exercise testing and analysis of respiratory gas exchange demonstrate low efficiency of cardiopulmonary function as well as impaired chronotropic, contractile, and vasodilatatory reserves, which are reversible when euthyroidism is restored. During exercise, the increment (delta) of minute ventilation (respiratory rate x tidal volume), and oxygen pulse (oxygen uptake per heart beat) are significantly lower in dysthyroidism versus euthyroidism. Especially in older patients with thyroid dysfunction, markedly reduced workload, delta ejection fraction, and delta heart rate, both at the anaerobic threshold as well as at maximal exercise, are observed. In thyrotoxicosis, mitochondria oxidative dysfunction during exercise mostly causes intracellular acidosis, whereas in hypothyroidism, inadequate cardiovascular support appears to be one of the principal factors involved. These abnormalities partly explain why subjects with dysthyroidism are intolerant to exertion. Thus, in thyroid disease, both cardiac structures and function may remain normal at rest, however impaired cardiovascular and respiratory adaptation to effort becomes unmasked during exercise.

Importance of hypoxic vasoconstriction in maintaining oxygenation during acute lung injury.

To investigate the role of hypoxic pulmonary vasoconstriction in the intrapulmonary blood flow redistribution and gas exchange protection during oleic acid acute lung injury. Prospective, controlled animal study. Research laboratory of an academic institution. Three groups of five mongrel dogs. Induction of acute lung injury by 0.08 mL/kg oleic acid intravenously. Hypoxic pulmonary vasoconstriction inhibition by Escherichia coli endotoxin microdose (15 microg/kg) pretreatment or by metabolic alkalosis (pH 7.60). Pulmonary arterial and venous resistances were determined by flow-pressure curves and by capillary pressure estimation. Regional lung water and pulmonary blood flow were assessed by positron emission tomography. Oleic acid alone increased the arterial and venous resistances, redistributed blood flow away from edematous areas, and decreased the Pao2 from 507 +/- 16 to 373 +/- 60 torr. on Fio2 1.0 and positive end-expiratory pressure 5 cm H2O. Endotoxin pretreatment inhibited the increase in arterial resistance, suppressed the redistribution, and decreased the Pao2 to 105 +/- 22 torr. Alkalosis inhibited the increase in arterial and venous resistances, suppressed the redistribution, and decreased the Pao2 to 63 +/- 12 torr. Reversal of the alkalosis increased the arterial and venous resistances, restored the perfusion redistribution, and improved the Pao2 to 372 +/- 63 torr. Changes in blood gases conformed to predictions of a computer lung model in which hypoxic pulmonary vasoconstriction was suppressed by endotoxin and alkalosis. We conclude that in oleic acid-induced lung injury, a) pulmonary hypertension results from increases in both arterial and venous resistances; b) the increase in arterial resistance is the primary mechanism responsible for the perfusion redistribution and the gas exchange protection; and c) the increase in arterial resistance is most consistent with hypoxic pulmonary vasoconstriction.

Ex vivo exposure to carbon monoxide prevents hepatic ischemia/reperfusion injury through p38 MAP kinase pathway

A direct role of carbon monoxide (CO), an effector-signaling molecule during heme oxygenase-1 (HO-1) catalysis of heme, in the protection against hepatic ischemia/reperfusion (I/R) injury needs to be established. This study was designed to determine the effects and downstream mechanisms of CO on cold I/R injury in a clinically relevant isolated perfusion rat liver model. After 24 hours of cold storage, rat livers perfused ex vivo for 2 hours with blood supplemented with CO (300 parts per million) showed significantly decreased portal venous resistance and increased bile production, as compared with control livers perfused with blood devoid of CO. These beneficial effects correlated with improved liver function (serum glutamic oxaloacetic transaminase levels) and diminished histological features of hepatocyte injury (Banff's scores). The CO-mediated cytoprotective effects were nitric oxide synthase- and cyclic guanine monophosphate-independent, but p38 mitogen-activated protein kinase (MAPK)-dependent. Moreover, adjunctive use of zinc protoporphyrin, a competitive HO-1 inhibitor, has shown that exogenous CO could fully substitute for endogenous HO-1 in preventing hepatic I/R insult. This study performed in a clinically relevant ex vivo cold ischemia model is the first to provide the evidence that HO-1-mediated cytoprotection against hepatic I/R injury depends on the generation of, and can be substituted by, exogenous CO. The p38 MAPK signaling pathway represents the key downstream mechanism by which CO prevents the I/R insult. In conclusion, regimens that employ exogenous CO should be revisited, as they may have potential applications in preventing/mitigating I/R injury, and thus expanding the liver donor pool for clinical transplantation. (HEPATOLOGY 2002;35:815-823.)

Role of endothelin ET(A)- and ET(B)-receptors in haemodynamic compensation following haemorrhage in anaesthetized rats.

1. This study examined the role of endothelin ET(A) and ET(B) receptors on haemodynamic compensation following haemorrhage (-17.5 ml kg(-1)) in thiobutabarbitone-anaesthetized rats. Rats were divided into four groups (n=6 each): time-control, haemorrhage-control, haemorrhage after treatment with FR 139317 (ET(A)-receptor antagonist), and haemorrhage after treatment with BQ-788 (ET(B)-receptor antagonist). 2. In the time-control rats, there were no significant changes in any haemodynamics for the duration of the experiments. Relative to the time-control rats, rats given haemorrhage had reduced mean arterial pressure (MAP), cardiac output (CO) and mean circulatory filling pressure (MCFP), but increased systemic vascular resistance (R(SV)). Venous resistance (R(V)) was slightly (but insignificantly) reduced by haemorrhage. MAP, however, gradually returned towards baseline (-17+/-4 and -3+/-2 mmHg at 10 and 60 min after haemorrhage, respectively) as a result of a further increase in R(SV). 3. Pre-treatment with FR 139317 (i.v. 1 mg kg(-1), followed by 1 mg kg(-1) h(-1)) accentuated haemorrhage-induced hypotension through abolition of the increase in R(SV). FR 139317 did not modify haemorrhage-induced changes in CO, MCFP and R(V). 4. Pre-treatment of BQ-788 (3 mg kg(-1)) did not affect MAP or MCFP following haemorrhage; however, CO was lower, and R(SV) as well as R(V) were higher relative to the readings in the haemorrhaged-control rats. 5. These results show that following compensated haemorrhage, ET maintains arterial resistance and blood pressure via the activation of ET(A) but not ET(B) receptors.

Endothelin Receptor A Blockade Ameliorates Hypothermic Ischemia–Reperfusion-Related Microhemodynamic Disturbances during Liver Transplantation in the Rat

Background. The objective of this study was to investigate the effect of graft treatment with specific endothelin receptor antagonists (ETA and ETB) on the microhemodynamic disturbances which occur following ischemia/reperfusion injury during orthotopic liver transplantation (OLT) in the rat.Materials and methods. OLT was performed in male Sprague–Dawley rats. An ETA receptor antagonist (BQ-610; 0.3 mg/kg) or ETB receptor antagonist IRL-1038 (20 nmol/kg) was administered intraportally into liver grafts in vitro at the beginning of 2- and 6-h cold storage (4°C) using physiological saline. Sham-operated animals served as controls (Cont). Seven groups were studied: Cont; vehicle—2 h (saline treated); ETB antagonist—2 h; ETA antagonist—2 h; vehicle—6 h; ETA antagonist—6 h; and ETB antagonist—6 h. At 1 h after graft implantation, the liver microcirculation was investigated by intravital fluorescence microscopy.Results. In vehicle-treated livers, the hepatic microcirculation was markedly impaired compared with the Cont as manifested by a reduced lobular perfusion index, increased incidence of sinusoidal nonperfusion, elevated leukocyte adhesion in sinusoids and terminal hepatic venules, and increased hepatic venous resistance (23-fold; 6-h group). In addition, plasma liver enzymes were significantly elevated in the vehicle treated groups. Alterations to all these parameters were markedly reduced in the ETA receptor antagonist-treated liver grafts although there was still evidence of hepatic injury. The ETB receptor antagonist had little effect on the I/R-induced changes to the hepatic microcirculation.Conclusions. Our results indicate that the ETA antagonism ameliorates hypothermic I/R-related microhemodynamic disturbances during OLT in the rat, suggesting that application of an ETA antagonist to liver grafts may have therapeutic potential in human liver transplantation.

Hemodynamic Effects of a Combination of Octreotide and Terlipressin Patients with Viral Hepatitis Related Cirrhosis

Background: Terlipressin or octreotide given alone has been used as the first-line pharmacological treatment for acute variceal bleeding. In portal hypertensive animals, pre-infusion of octreotide followed by the addition of terlipressin has an additive or complementary effect on splanchnic hemodynamics. The current study was aimed at evaluating such a combination treatment in patients with cirrhosis and portal hypertension. Methods: Patients were randomly assigned to receive either a placebo ( n = 11) or an intravenous infusion of octreotide 100 μg/h after an initial bolus of 100 μg ( n = 13). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after octreotide or placebo, and 60 min after terlipressin. Results: Placebo administration did not affect any of the hemodynamic values. Terlipressin administration resulted in expected changes in hepatic venous pressure gradient, hepatic blood flow and systemic hemodynamics. In contrast, octreotide administration significantly decreased hepatic blood flow but did not affect other hemodynamic values. After terlipressin administration, significant hemodynamic changes were observed that were similar to the hemodynamic changes with terlipressin alone. The magnitude of changes in hepatic venous pressure gradient, cardiac index and systemic vascular resistance were no different between the two groups of patients. The heart rate was significantly lower in patients receiving octreotide plus terlipressin than those receiving terlipressin alone. Conclusion: The current study showed that a combination of octreotide and terlipressin did not exert an additive effect in reducing hepatic venous pressure gradient in patients with cirrhosis. In addition, the systemic hemodynamic changes were comparable between the two groups.

Anionic polysaccharides. A class of substances with hepatoprotective and antiadhesive properties in rat liver preservation

Abstract In liver preservation, the substitution of the anion Cl by lactobionic acid (LB) prevents reperfusion edema and extends the preservation time for human livers. We studied the effect of compounds that are structurally related to lactobionic acid: anionic polycarbohydrates (sulfated anionic polysaccharide, SAP, and pentosan polysulfate, PPS) on liver function and leukocyte-endothelial cell interaction in isolated perfusion and liver transplant models. Rat livers, coldstored (24 h) in a Cl -containing control solution, became edematous during 1 h of reperfusion. Substitution of Cl- by either LB, SAP, or PPS decreased reperfusion edema in a Cl- concentration-dependent fashion. Reperfusion edema was abolished completely after preservation in 100 mM SAP solution or PPS solution. Also hepatic lactic dehydrogenase (LDH) and aspartate aminotransferase (ASAT) release was lowest after preservation in those solutions. After preservation in LB or anionic polycarbohydrate solutions, portal venous resistance was significantly higher than after preservation in Cl--containing control solution. Capillary blood flow was 391 ± 83 pl/s and 398 ± 174 pl/s after preservation in SAP solution (SAPs) and PPSs, and 803 ± 117 pl/s and 641 ± 219 pl/s after preservation in LB or Cl -containing control solution. The number of leukocytes sticking to the vascular wall was lower (P<0.05) after preservation in SAPs or PPSs (109 ± 31 cells/mm2 and 108 ± 60 cells/mm2, respectively), when compared with preservation in Cl -containing control or LB solutions (429 ± 63 cells/mm2 and 277 ± 59 cells/mm2). In rat liver preservation, anionic polysaccharides are antiedematous compounds, with a higher potency than LB and additional antiadhesive properties.

Evolution of deep venous thrombosis: A 2-year follow-up using duplex ultrasound scan and strain-gauge plethysmography

Objective: The development of the post-thrombotic syndrome (PTS) and recurrence of deep venous thrombosis (DVT) are not yet fully understood. The aim of the study was to identify factors that lead to the long-term complications of DVT. Methods: In a 2-year prospective follow-up study, duplex scanning and strain-gauge plethysmography were used to evaluate DVT in relation to the development of long-term complications. Each of the 12 segments examined was assigned as a thrombosis score (TS). A total TS was calculated for each leg. Patent segments were assigned a TS = 0, noncompressible vein segments with flow TS = 1 and noncompressible vein segments without flow TS = 2. The degree of resolution of DVT and the incidence, timing, and outcome of further thrombotic events were measured during 24 months of follow-up. Results: The study involved 86 legs with DVT. The 2-year follow-up was completed for 70 legs. Within 3 months, only 1% of the originally occluded proximal deep vein segments were still occluded. Between all time intervals, from month 12 to month 24, for example, thrombus regression continued in 36% of the legs and thrombus propagation continued in 27%. Multiple regression analysis revealed that an increase in age (P =.008) and proximal location of the original DVT (P =.05) was significantly related to thrombus propagation. Multiple regression analysis showed that the risk factors for clinical signs of PTS were a high venous outflow resistance after 1-month and 12-month follow-ups (P ≤.002) and a high thrombosis score in the proximal veins after 3 months (P =.008). Conclusions: In the follow-up of older patients and patients with proximal DVT, evolution was shown to be an unstable process with continuing propagation for 2 years. The risk factors for the development of PTS were a slow decrease in venous outflow resistance or a high thrombosis score of the proximal veins after 3 months. (J Vasc Surg 2001;34:649-55.)

The effects of hemoglobin glutamer-200 (bovine) on the microcirculation in a canine hypovolemia model: a noninvasive computer-assisted intravital microscopy study.

We sought to correlate in vivo microvascular, systemic function, hemodynamic, and oxygenation changes in autologous shed blood (n = 4) and hemoglobin glutamer-200 (Hb-200) (n = 4) resuscitations in hypovolemic dogs. Hemorrhage (approximately 40% blood loss) reduced mean arterial pressure to approximately 50 mm Hg and caused significant (P < 0.01) decreases in hematocrit, total hemoglobin, mean pulmonary arterial pressure, cardiac output, and oxygen delivery and significant (P < 0.01) increases in heart rate, systemic vascular resistance, and lactic acidosis. Significant (P < 0.01) changes in conjunctival microvascular variables also occurred, including a 19% decrease in venular diameter and 79% increase in average blood flow velocity. Shed blood resuscitation returned microvascular, systemic function, hemodynamic, and oxygenation variables to prehemorrhagic baseline values. In contrast, Hb-200 failed to restore hematocrit, total hemoglobin, cardiac output, oxygen delivery index, and systemic venous resistance to baseline, but it restored other systemic functions and all hemodynamic and microvascular changes. In addition, Hb-200 resuscitation in hypovolemic dogs (approximately 40% blood loss) did not cause extreme hemodilution or fatal outcome. This study confirms that real-time (in vivo) microvascular studies, which were conducted only in small rodent models in the past, can be performed simultaneously with systemic function, hemodynamic, and oxygenation studies in a large animal model for relevant data correlation. This is the first time that changes in the blood circulation have been studied, quantified, and correlated with systemic function, hemodynamic, and oxygenation changes in shock and during shock treatment in a large animal model. This study was performed by a new technology developed in-house to noninvasively and quantitatively study blood vessels in real time.

Hepatic arterial perfusion regulates portal venous flow between hepatic sinusoids and intrahepatic shunts in the normal rat liver in vitro.

Intrahepatic shunts regulate portal venous pressure during periods of acute portal hypertension when the transhepatic portal resistance is momentarily increased in the normal rat liver in vivo. Hepatic arterial inflow may also increase the transhepatic portal resistance and activate intrahepatic shunts. In the present study, the transhepatic portal resistance and the activity of intra-hepatic shunts were measured in vitro and the point of confluence between the hepatic artery and portal vein in the rat determined. Livers of male Sprague-Dawley rats were single-pass, dual-perfused in vitro. Total cessation or diversion of the hepatic arterial inflow to the portal venous vasculature, whilst maintaining total hepatic perfusate flow, decreased intrasinusoidal pressure, increased transhepatic portal venous resistance and opened the portal venous intrahepatic shunts in a manner similar to intraportal injection of 15-microm diameter microspheres. Injections of the microspheres into the hepatic arterial circulation increased hepatic arterial pressure dramatically, consistent with complete occlusion of the arterial vasculature. The intrahepatic shunts are located at a pre-sinusoidal level because no increases were detected in hepatic arterial pressure following intraportal injection of microspheres. The hepatic arterial vasculature, unlike the portal supply, does not possess a collateral shunt circulation and coalesces with the portal vein at an intrasinusoidal location

Erythrocyte margination and sedimentation in skeletal muscle venules.

Previous studies in skeletal muscle of the dog and cat have shown that venous vascular resistance changes inversely with blood flow and may be due mainly to red blood cell aggregation, a phenomenon present in these species. To determine whether red blood cell axial migration and sedimentation contribute to this effect, we viewed either vertically or horizontally oriented venules of the rat spinotrapezius muscle with a horizontally oriented microscope during acute arterial pressure reduction. With normal (nonaggregating) rat blood, reduction of arterial pressure did not significantly change the relative diameter of the red blood cell column with respect to the venular wall. After induction of red blood cell aggregation in the rat by infusion of Dextran 500, red blood cell column diameter decreased up to 35% at low pseudoshear rates (below approximately 5 s(-1)); the magnitude was independent of venular orientation. In vertically oriented venules, the plasma layer was symmetrical, whereas in horizontally oriented venules, the plasma layer formed near the upper wall. We conclude that, although red blood cell axial migration and sedimentation develop in vivo, they occur only for larger flow reductions than are needed to elicit changes in venous resistance.

Hypoxia and cold stress on pulmonary venous obstruction.

Hemodynamic changes induced by hypoxia and cold stress were examined on the model of pulmonary venous obstruction (PVO) to investigate the mechanism of pulmonary hypertensive crisis. Bilateral pulmonary venous stenosis was surgically created in 7 newborn piglets of the PVO group. Sham operations were performed on 6 piglets of the control group. Following the baseline hemodynamic measurement (FiO2 = 0.3) at 8 weeks after the operation, the piglets were exposed to hypoxia (FiO2 = 0.14) for 10 minutes, and were also exposed to cold stress for 20 minutes. Hypoxia significantly increased mean pulmonary arterial pressure in the PVO group. Hypoxia increased not only pulmonary arterial resistance, but also pulmonary venous resistance in the PVO group. Cold stress did not change pulmonary arterial resistance or pulmonary venous resistance in each group. In the lungs of the PVO group, the medial muscular layer of the pulmonary arteries and pulmonary veins were thickened. This probably accelerates hypoxia-induced vasoconstriction, which in turn increases pulmonary arterial and venous resistances.

Endothelin receptor blockade improves oxygenation in contralateral TRAM flap tissue in pigs

Partial skin and fat necrosis is the most common complication occurring in TRAM flaps. It is related to disturbances of the microcirculation and oxygenation in the contralateral part of the flap. It may be hypothesised that the development of necrosis is promoted by the vasoconstrictor endothelin, the production of which is enhanced in ischaemic flap tissues. The purpose of this study was to evaluate the effect of tezosentan, a new endothelin receptor blocker, on microcirculation and oxygenation in experimental TRAM flaps. The administration of tezosentan began preoperatively (3 mg/kg body weight) and then continued at a rate of 1.5 mg/kg/h. A TRAM flap with a skin island measuring 16 x 8 cm was raised in the middle of the epigastrium in minipigs. The flap was pedicled on the right superior epigastric vessels. Microcirculatory blood flow was measured with laser Doppler flowmetry and tissue oxygen tension was measured with a Clark-type microprobe. Dominant subcutaneous veins were cannulated in both the ipsilateral and the contralateral parts of the flap. Subdermal tissue oxygen tension in the contralateral part of the flap was significantly reduced 4h after surgery to 5 mmHg (ca. 48 mmHg in normal tissue) in the control group, but to only 12 mmHg in the group that had been administered tezosentan (P< 0.05). Furthermore, tezosentan significantly attenuated venous hypertension (14 mmHg versus 24 mmHg), as well as lactate (4.0 mmol/l versus 5.6 mmol/l) and haemoglobin (10.2 g/dl versus 11.4 g/dl) concentrations in the venous effluent of the contralateral part of the flap, although microcirculatory blood flow remained virtually unchanged. Our findings suggest that tezosentan improves oxygenation and metabolism in the jeopardised contralateral flap tissue, probably as a result of a decrease in venous vascular resistance and fluid extravasation.

Effect of protein kinase C inhibition on hypoxic pulmonary vasoconstriction.

The current study was done to test the hypothesis that protein kinase C (PKC) inhibitors prevent the increase in pulmonary vascular resistance and compliance that occurs in isolated, blood-perfused dog lungs during hypoxia. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. Hypoxia significantly increased pulmonary arterial resistance, pulmonary venous resistance, and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The nonspecific PKC inhibitor staurosporine (10(-7) M), the specific PKC blocker calphostin C (10(-7) M), and the specific PKC isozyme blocker Gö-6976 (10(-7) M) inhibited the effect of hypoxia on pulmonary vascular resistance and compliance. In addition, the PKC activator thymeleatoxin (THX; 10(-7) M) increased pulmonary vascular resistance and compliance in a manner similar to that in hypoxia, and the L-type voltage-dependent Ca(2+) channel blocker nifedipine (10(-6) M) inhibited the response to both THX and hypoxia. These results suggest that PKC inhibition blocks the hypoxic pressor response and that the pharmacological activation of PKC by THX mimics the hypoxic pulmonary vasoconstrictor response. In addition, L-type voltage-dependent Ca(2+) channel blockade may prevent the onset of the hypoxia- and PKC-induced vasoconstrictor response in the canine pulmonary vasculature.

Arterial and venous cathecolamines, leptin and insulin resistance in obese hypertensive patients

Arterial and venous cathecolamines, leptin and insulin resistance in obese hypertensive patients

Spatial interaction between tissue pressure and skeletal muscle perfusion during contraction

The vascular waterfall theory attributes decreased muscle perfusion during contraction to increased intramuscular pressure ( P IM) and concomitant increase in venous resistance. Although P IM is distributed during contractions, this theory does not account for heterogeneity. This study hypothesises that pressure heterogeneity could affect the interaction between P IM rise and perfusion. Regional tissue perfusion during submaximum (100 kPa) tetanic contraction is studied, using a finite element model of perfused contracting skeletal muscle. Capillary flow in muscles with one proximal artery and vein (SIM 1) and with an additional distal artery and vein (SIM 2) is compared. Blood flow and pressures at rest and P IM during contraction (∼25 kPa maximally) are similar between simulations, but capillary flow and venous pressure differ. In SIM 2, venous pressure and capillary flow correspond to P IM distribution, whereas capillary flow in SIM 1 is less than 10% of flow in SIM 2, in the muscle half without draining vein. This difference is caused by a high central P IM, followed by central venous pressure rise, in agreement with the waterfall theory. The high central pressure (SIM 1), obstructs outflow from the distal veins. Distal venous pressure rises until central blood pressure is reached, although local P IM is low. Adding a distal vein (SIM 2) restores the perfusion. It is concluded that regional effects contribute to the interaction between P IM and perfusion during contraction. Unlike stated by the vascular waterfall theory, venous pressure may locally exceed P IM. Although this can be explained by the principles of this theory, the theory does not include this phenomenon as such.

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration.

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.

In-Vitro Evaluation of the Hemolytic Effects of Augmented Venous Drainage

Augmentation of venous drainage with either kineticassisted drainage (KAVD) or vacuum-assisted (VAVD) has been used clinically in order to overcome added venous resistance due to smaller venous cannulae or tubing. This in-vitro study evaluates the extent of hemolysis and sub-lethal red blood cell membrane damage than occurs with augmented (kinetic or vacuum) when compared to conventional gravity drainage. Four trials were conducted using each test circuit. The circuits were primed with 6 liters of fresh heparinized bovine blood, which was diluted to a hematocrit of 32% and was recirculated at 5 L/min for 8 hours. Hemolysis was determined by the change in plasma free-hemoglobin (Hb), hematocrit, and potassium at two hour intervals. The red cell osmotic fragility index was used to quantify the sub-lethal red blood cell membrane damage and was also measured every two hours. After 8 hours, the mean +/− SD of the plasma free-Hb were: 96.27 +/− 69.45 mg/dl for gravity, 83.87 +/− 48.14 mg/dl for vacuum-assist, and 134.45 +/−83.78 mg/dl for kinetic-assist. Two-hour increases in the plasma free-Hb revealed the following median values (mg/dL/2h): 16.90 for gravity, 13.75 for vacuum–assist, and 19.40 for kinetic-assist. Analysis of the two-hour increases in plasma free-Hb with Kruskal-Wallis One-Way ANOVA did not reveal a significant difference among the groups. After 8 hours, the red cell osmotic fragility test results at the 0.55% sodium chloride concentration were compared. The medians of the percent hemolysis were 52.67% for gravity, 49.8% for vacuum-assist, and 57.2% for kinetic- assist. Analysis with the Kruskal-Wallis Wallis One-Way ANOVA did not reveal a significant difference among the groups. Therefore, there is no significant increase in hemolysis or sub-lethal red blood cell membrane damage associated with the use of augmented venous drainage.

Effect of erythrocyte aggregation on velocity profiles in venules.

A recent whole organ study in cat skeletal muscle showed that the increase in venous resistance seen at reduced arterial pressures is nearly abolished when the muscle is perfused with a nonaggregating red blood cell suspension. To explore a possible underlying mechanism, we tested the hypothesis that red blood cell aggregation alters flow patterns in vivo and leads to blunted red blood cell velocity profiles at reduced shear rates. With the use of fluorescently labeled red blood cells in tracer quantities and a video system equipped with a gated image intensifier, we obtained velocity profiles in venous microvessels (45-75 microm) of rat spinotrapezius muscle at centerline velocities between 0.3 and 14 mm/s (pseudoshear rates 3-120 s(-1)) under normal (nonaggregating) conditions and after induction of red blood cell aggregation with Dextran 500. Profiles are nearly parabolic (Poiseuille flow) over this flow rate range in the absence of aggregation. When aggregation is present, profiles are parabolic at high shear rates and become significantly blunted at pseudoshear rates of 40 s(-1) and below. These results indicate a possible mechanism for increased venous resistance at reduced flows.

Capillary filtration is reduced in lungs adapted to chronic heart failure: morphological and haemodynamic correlates.

To determine pulmonary capillary filtration in experimental chronic heart failure and to investigate some morphological and haemodynamic mechanisms that could account for reduced filtration in lungs adapted to chronic heart failure. We studied pulmonary capillary filtration, vascular resistances and morphology in lungs from guinea-pigs adapted to chronic heart failure. Heart failure was induced by banding of the ascending aorta (n=66) or sham control operation (n=78) in guinea-pigs which were studied at 150+/-8 days post-operation. Reduced cardiac output, increased systemic vascular resistance and LV end diastolic pressure and increased LV and RV weight:body weight ratio (all P<0.05) indicated chronic heart failure at 5 months following aortic banding in guinea-pigs. Lung weight was increased (61%, P<0.05) in heart failure compared with controls, but lung water content was reduced (5.5%, P<0.05), a reversal of the pattern seen acutely. Studies in isolated perfused lungs demonstrated a reduced capillary filtration coefficient (0. 018+/-0.003 vs. 0.003+/-0.002 ml min(-1)mmHg(-1)g(-1), P<0.001), increased arterial (61%) and venous resistance (50%) in heart failure lungs, P<0.05. Wall thickness:lumen ratio was increased in small (<250 microm) pulmonary arterioles (0.15+/-0.02 vs. 0.08+/-0. 01) and venules (0.06+/-0.005 vs. 0.04+/-0.002) in heart failure, P<0.01. Alveolar septal volume fractions (35.2+/-5.1 vs. 23.1+/-2.7) and septal:air-space volume ratios (60.5+/-13.6 vs. 31.9+/-5.3) were also increased in heart failure, P<0.05. Pulmonary adaptation to chronic heart failure is associated with vascular and alveolar remodelling that contributes to increased vascular resistance and reduced capillary filtration. These changes are likely to be important in mediating resistance to pulmonary oedema in chronic heart failure.