Increase In Venous Resistance Research Articles

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.

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.

Effects of venous pressure and posture on skin capillary perfusion.

Various vasoconstriction mechanisms after a change in posture are involved in controlling skin blood flow and capillary transmural pressure to maintain adequate transcapillary exchange. The role of venous orthostatic pressure in the regulation of capillary nutritive perfusion, however, is less clear. We investigated capillary perfusion in 30 healthy subjects using intravital capillary microscopy of the big toenail-fold. Measurements were made in the supine and the sitting positions before and after incremental elevation of venous resistance, and thus the pre- to post-capillary pressure difference, by inflating a cuff around the ankle. On dependency, median capillary density rose (P < 0.0001), whereas red blood cell perfusion decreased (P < 0.0001). Cuff inflation of 30-60 mmHg in the supine position induced similar phenomena. Repeatedly, the same capillaries were found to be recruited after an increase in transmural pressure. We conclude that post-capillary pressure appears to be an important factor in the regulation of capillary perfusion, because an increase in venous resistance mimics the effects of dependency. The findings in this study support the theory of 'minimum perfusion pressure' for each capillary to be perfused with erythrocytes.

Effects of PEEP on liver arterial and venous blood flows.

Total venous return decreases with positive end-expiratory pressure (PEEP). It is likely that the liver plays an important role in this response, either through the development of an increase in venous resistance or through an increase in the venous backpressure at the outflow end of the liver. In addition, hepatic arterial flow is reported to be selectively decreased by the application of PEEP. Therefore, to clarify the effects of PEEP on liver hemodynamics, we generated pressure-flow (P-Q) relationships in both liver vascular beds of anesthetized, mechanically ventilated pigs at PEEP of 0, 5, 10, and 15 cm H2O to obtain values of backpressure (Pback, mm Hg) from linear extrapolation of the P-Q relationships and resistance (mm Hg/ml/min/kg) from its slope. PEEP decreased portal vein flow (Qpv) and caused an increase in the liver venous resistance (from 0.08 +/- 0.01 to 0.16 +/- 0.02 mm Hg/ml/min/kg; p < 0.05). Ppvback and right atrial pressure (Pra) increased equally (from 5.1 +/- 0.3 to 9.9 +/- 0.4 mm Hg, p < 0.05, and from 4.0 +/- 0.2 to 8.6 +/- 0.5 mm Hg, p < 0.05, respectively, at PEEP 15). The reduction in portal venous flow was related to an increase in the backpressure to flow (as a result of an increase in Pra) and to an increase in liver venous resistances that may cause blood pooling in the splanchnic compartment and decrease venous return through the liver. PEEP increased Phaback (from 11.2 +/- 0.9 to 14.5 +/- 0.7 mm Hg at PEEP 15, p < 0.05) but did not change hepatic arterial resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Protamine-Induced Pulmonary Venoconstriction in Heparinized Pigs

Reversal of heparin anticoagulation with protamine may be associated with acute pulmonary vasoconstriction. The specific site of pulmonary vasoconstriction has not been determined. This study was designed to determine the site of protamine-induced pulmonary vasoconstriction and the role of nitric oxide (NO) after protamine injection. Pigs were anesthetized and instrumented with catheters for monitoring pulmonary arterial, systemic arterial, and central venous pressures. Pulmonary capillary pressure was estimated using the arterial occlusion concept, while left atrial pressure was estimated from the equilibrium wedge pressure. Hemodynamic measurements were made during baseline, before and after heparin (200 U/kg), at peak pressure response after protamine injection (2 mg/kg), and 10 and 30 min thereafter. In the control group, pulmonary vascular resistance (PVR) values during baseline and after heparin were identical (2.7 +/- 0.4 mm Hg.L-1.min-1). At peak protamine response (1-2 min) PVR increased to 8.0 +/- 1.6, but returned to baseline value after 10 min (2.8 +/- 0.3) and remained stable for 30 min (2.2 +/- 0.3). The increase in PVR after protamine was primarily due to an increase in venous resistance from 1.0 +/- 0.2 to 4.9 +/- 1.4 mm Hg.L-1.min-1, and a much smaller increase in arterial resistance from 1.7 +/- 0.3 to 3.4 +/- 0.6 mm Hg.L-1.min-1. A second group was treated with nitrow-L-arginine (LNA, 20 mg/kg) to inhibit NO release, and then heparin and protamine were administered as in the first group. Heparin had no effect on pressures, but protamine increased PVR by the same magnitude as in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

In-vivo effects of endothelin-1 and ETA receptor blockade on arterial, venous and capillary functions in skeletal muscle.

Results from in vitro studies have indicated that endothelin-1 is a main candidate for endothelium-derived contracting factors. The aim of this in vivo study was to describe in quantitative terms the effects of endothelin-1 (ET-1), and of ETA receptor blockade, on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 microns), small arterioles (< 25 microns) and the veins, as well as on capillary pressure and fluid exchange in cat gastrocnemius muscle. Endothelin-1 (100-1600 ng kg-1 min-1, i.a.) elicited, after an initial transient dilation, a strong dose-dependent constrictor response in all three consecutive vascular sections, yet with a preferential action on the small arterioles and the veins. The vasoconstriction developed very slowly over about 1 h and was also long-lasting after cessation of the infusion. Our main quantitative analysis refers to effects elicited by 20 min long i.a. infusions of ET-1 at a dose of 400 ng kg-1 min-1. At the end of this period, the peptide caused, on average, a three-fold increase in total regional vascular resistance, in turn explained by a 70% increase in large-bore arterial resistance, a 280% increase in arteriolar resistance and a 220% increase in venous resistance. The latter effect was also manifested as a pronounced capacitance response, and as a decrease in the pre- to post-capillary resistance ratio leading regularly to a rise in capillary pressure, net transcapillary fluid filtration and oedema formation which is unusual for a vasoconstrictor. The new specific competitive ETA receptor antagonist FR 139317 was found to be fully effective in vivo, insofar as it abolished the constrictor response to endothelin-1. ETA receptor blockade, or administration of phosphoramidon, an inhibitor of ET-1 production, did not influence the level of basal vascular tone, indicating no significant endogenous release of ET-1 under resting conditions. This contrasts to the established pronounced endogenous release of endothelium-derived nitric oxide. Finally, vascular myogenic regulation was found not to be mediated by ET-1. The results, taken together, suggest a possible role of ET-1 in long-term, rather than short-term, regulation of vascular tone in vivo, perhaps especially during pathophysiological conditions.

Effect of edema on segmental vascular resistance in isolated perfused rat lungs

We have determined the effect of hydrostatic edema on total and segmental vascular resistances in the rat lung. Lungs of 12 adult rats, body weight 515 +/- 42 g, were isolated and perfused with blood. To investigate the role of vasoactivity on edema effects, we studied two groups of lungs; group I (n = 6) were untreated and group II (n = 6) were treated with papaverine hydrochloride to paralyze the vasculature. Initially blood flow was adjusted to keep pulmonary artery pressure approximately 15 cmH2O, left atrial and airway pressures being 8 and 7 cmH2O, respectively, and then kept unchanged thereafter (18 +/- 3 ml/kg/min). Hydrostatic edema was induced by raising venous pressure and pulmonary artery pressure measured continuously. In 4 lungs from each group, during baseline and after the development of severe edema, we partitioned the pulmonary circulation into arteries, microvessels, and veins by measuring pressures in 20-50 microns diameter subpleural arterioles and venules with the micropipette-Servonull method. Baseline total vascular resistance was similar in the two groups. Interstitial and early alveolar edema did not affect pulmonary vascular pressures. With severe edema (W/D ratio: 17 +/- 2), pressures in pulmonary artery and arterioles increased significantly in both groups; venular pressures did not change. Total resistance increased by 250% in group I and by 224% in group II lungs. Arterial resistance increased 3-5-fold in both groups, as did microvascular resistance. Venous resistances also increased in both groups, although to a lesser extent. The increase in total and segmental vascular resistances was not significantly different in the two groups of lungs. We conclude that in isolated rat lungs only severe edema results in an increase in total vascular resistance, mainly due to an increase in arterial and microvascular resistances, with a smaller increase in venous resistance. This appears to be a mechanical effect of edema on the vasculature and not a result of active vasomotion.

Developmental changes in effects of histamine on segmental pulmonary vascular resistances

In mature animals histamine infusion typically causes an H1-mediated increase and H2-mediated decrease in pulmonary vascular resistance (PVR). Moreover, low histamine concentrations can cause H1-mediated relaxation of vascular strips in mature animals, and in newborn animals histamine infusion causes only H1-mediated decreases in PVR. The mechanisms responsible for the different H1-mediated responses are unknown. We used an inflow-outflow occlusion technique to identify the sites of H1- and H2-mediated responses in lungs of developing lambs. Histamine was infused at 1.0 and 10.0 micrograms.kg-1.min-1 in control and H1- and H2-blocked lungs of newborn and juvenile lambs under "normoxic" and hypoxic conditions and in hypoxic H2-blocked lungs of mature sheep. In newborns histamine caused significant H1-mediated decreases in resistance across the arterial (delta Pa) and middle (delta Pm) segments of the circuit during both normoxia and hypoxia. In normoxic juveniles low-dose histamine caused H1-mediated decreases in the resistance across delta Pa and delta Pm, but the resistances across delta Pm rose above baseline at the higher dose. The venous segment exhibited only a high-dose increase in resistance. During hypoxia, the high-dose H1-mediated pressor response of delta Pm was attenuated compared with that during normoxia; however, the increase in venous resistance was unaffected. In hypoxic mature sheep, no low dose H1-mediated decrease in segmental resistances was seen, but at the higher dose an increase in all resistances occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of the sites of pulmonary vasomotion by use of arterial and venous occlusion

In this study, we present a new approach for using the pressure vs. time data obtained after various vascular occlusion maneuvers in pump-perfused lungs to gain insight into the longitudinal distribution of vascular resistance with respect to vascular compliance. Occlusion data were obtained from isolated dog lung lobes under normal control conditions, during hypoxia, and during histamine or serotonin infusion. The data used in the analysis include the slope of the arterial pressure curve and the zero time intercept of the extrapolated venous pressure curve after venous occlusion, the equilibrium pressure after simultaneous occlusion of both the arterial inflow and venous outflow, and the area bounded by equilibrium pressure and the arterial pressure curve after arterial occlusion. We analyzed these data by use of a compartmental model in which the vascular bed is represented by three parallel compliances separated by two series resistances, and each of the three compliances and the two resistances can be identified. To interpret the model parameters, we view the large arteries and veins as mainly compliance vessels and the small arteries and veins as mainly resistance vessels. The capillary bed is viewed as having a high compliance, and any capillary resistance is included in the two series resistances. With this view in mind, the results are consistent with the major response to serotonin infusion being constriction of large and small arteries (a decrease in arterial compliance and an increase in arterial resistance), the major response to histamine infusion being constriction of small and large veins (an increase in venous resistance and a decrease in venous compliance), and the major response to hypoxia being constriction of the small arteries (an increase in arterial resistance). The results suggest that this approach may have utility for evaluation of the sites of action of pulmonary vasomotor stimuli.

Compartmental vascular changes in dogs after nephrectomy, DOCA, and saline: effect of nifedipine

Hypertension (mean arterial pressure, (MAP) 131 +/- 3 mmHg) developed in 18 dogs 4 weeks after left nephrectomy, deoxycorticosterone acetate (DOCA), 5 mg/kg sc twice weekly), and 0.5% NaCl drinking solution. This can be compared with MAP (95 +/- 7 mmHg) of 13 dogs with nephrectomy alone and MAP (86 +/- 4 mmHg) of dogs without nephrectomy. The two-compartment model of the circulation revealed no differences in systemic vascular compliance, compartmental compliance, or flow distribution to the compartments. However, the time constant for venous return for the compartment with the rapid time constant was increased from 0.05 +/- 0.004 min in control animals to 0.07 +/- 0.006 min in the nephrectomy alone group and 0.09 +/- 0.008 min in the hypertensive group (p less than 0.001), as a result of an increase in venous resistance. Arteriolar resistance in this compartment was also increased in the hypertensive animals, as was the mean circulatory filling pressure and overall resistance to venous return. Nifedipine (0.025-0.05 mg/kg) reduced MAP by 15% in the nephrectomy alone group and by 22% in the hypertensive group, with reduction in arteriolar resistance only in the fast time constant compartment. In the slow time constant compartment, arteriolar resistance was increased by more than 100% and flow decreased by more than 50% after nifedipine. Unilateral nephrectomy, DOCA, plus NaCl resulted in hypertension by increasing arteriolar resistance in a vascular compartment with a fast time constant for venous return. Nifedipine countered this effect by inducing arteriolar vasodilation in this compartment. In addition, nifedipine reduced the mean circulatory filling pressure and overall resistance to venous return.

Effects of Escherichia coli endotoxin on pulmonary vascular resistance in intact dogs.

The effects of endotoxin on pulmonary hemodynamics were studied in seven intact dogs. The distribution of pulmonary vascular resistance was estimated by the effective pulmonary capillary pressure, which was derived from the pressure transient recorded while the pulmonary artery catheter was rapidly wedged. After the injection of endotoxin, cardiac output and aortic pressure consistently fell. Pulmonary artery occlusion (wedge) pressure also decreased, but not significantly. Although pulmonary artery pressure did not necessarily rise, total pulmonary vascular resistance increased in every dog. The absolute increase in pulmonary artery resistance was greater (142 mm Hg/L X min/kg); than in venous resistance (111 mm Hg/L X min/kg); however, the relative increase in venous resistance was higher (410% for venous resistance vs. 220% for pulmonary artery resistance). As a result of venoconstriction, there was a consistent increase in effective pulmonary capillary pressure (from 2.5 to 6.3 mm Hg). Our data indicate that the pulmonary vascular response to endotoxin injection is characterized by constriction of both pulmonary arteries and pulmonary veins. The capillary wedge pressure did not reflect the pulmonary microvascular pressure, since it varied in the opposite direction to the effective capillary pressure.

Response of the soft tissue microcirculation to prostacyclin infusion

We studied the effect of prostacyclin infusion on the soft tissue microcirculation. We used lymph flow Q L and the lymph/plasma L/P protein ratio to reflect transvascular fluid flux and changes in microvescular hydrostatic pressure, Pmv. Unanesthetized sheep with prefemoral lymph fistulae were infused with PGI 2 (0.2 ug/kg/min) for two hours. Changes in Q L and L/P were compared to animals in which P mv was increased by volume loading. During PGI 2, Q L was significantly increased, as was cardiac output while mean aortic pressure decreased. The UP ratio did not decrease to the degree seen with a comparable increase in Q L, due to an increase in P mv. The increase in Q L was most likely due to an increase in microvescular surface area. Q L remained significantly increased for several hours after infusion and L/P decreased to the same degree as seen with an increase in P mv. This indicates that Pmv is increased for several hours in soft tissue after PGI 2 infusion, due to a relative increase in venous resistance probably secondary to activation of the renin-angiotensin system.

Role of the peripheral vasculature in changes in venous return caused by isoproterenol, norepinephrine, and methoxamine in anesthetized dogs.

We studied effects on venous return of alpha- and beta-adrenergic agonists in anesthetized dogs. Blood from the superior and inferior venae cavae (venous return) was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant rate. Isoproterenol infused into the ascending aorta or the right atrium increased the venous return and heart rate and decreased systemic blood pressure. The increase in venous return produced by isoproterenol given into the right atrium was not significantly different from that produced by isoproterenol administered into the ascending aorta, although the increase in heart rate was more marked with the latter route of administration. Norepinephrine infused into the ascending aorta increased the systemic blood pressure, venous return, and heart rate. Methoxamine infused into the ascending aorta increased the systemic blood pressure and decreased the venous return but produced no change in heart rate. Isoproterenol increased the venous return even when the sinoaortic baroreceptor reflex was eliminated. Propranolol abolished the increase in venous return caused by isoproterenol and reversed the increase in venous return caused by norepinephrine. The results suggest that a decrease in venous resistance mediated through a beta-adrenergic mechanism is important in increasing venous return, whereas an increase in venous resistance mediated through an alpha-adrenergic mechanism is responsible for a decrease in venous return.

COMPARISON OF THE EFFECTS OF SYMPATHOMIMETIC AMINES UPON VENOUS AND TOTAL VASCULAR RESISTANCE IN THE FORELEG OF THE DOG

The effects of seven sympathomimetic amines upon total vascular and venous resistance were compared in the perfused foreleg of the dog. All the agents tested were less potent than norepinephrine with respect to total vasoconstrictor activity. The order of potency was: norepinephrine > metaraminol = phenylephrine > methoxamine > tyramine > ephedrine = mephentermine. The pressor amines had a differential ability to constrict the veins in the foreleg. Different degrees of venoconstriction were produced for similar changes in total resistance. Norepinephrine was by far the strongest venoconstrictor agent of the seven drugs. Metaraminol had a significantly greater venoconstrictor effect than methoxamine. Methoxamine, phenylephrine, and mephentermine all produced very small venoconstrictor responses, and ephedrine appeared to be intermediate among the seven agents in its action upon veins. The percentage contribution of the increase in venous resistance to the increase in total resistance was greater as dosage was increased. These results suggest that the sympathomimetic amines constrict the venous segment proportionately more at higher doses than at lower doses, whereas the resistance vessels are relatively more sensitive to lower doses.

Evidence for local arteriovenous reflex in intestine.

Studies were made on the hemodynamics of the isolated autoperfused dog intestine preparation. An attempt was made to explain the mechanism involved in the observed increase in venous resistance seen as the arterial pressure in the segment was reduced. This rise in venous resistance was reduced or abolished by sympatholytic agents (phentolamine and Dibenzyline) and by local anesthetics (tetracaine). When areas of intestine were surgically denervated and then subjected to hemodynamic studies 10–19 days later the venous resistance response was nearly or completely absent in all cases. The response was not significantly affected by the infusion of hexamethonium or dichloroisoproterenol or by changes in hematocrit ratio. It was concluded that the rise in venous resistance seen as arterial pressure is reduced is mediated by a local sympathetic axon reflex with the receptor on the arterial side of the circulation and the effector located on the venous side. The decrease in arterial resistance seen as arterial pressure is reduced (autoregulation) is also discussed. None of the drugs mentioned above or chronic denervation had any effect upon this phenomenon, strengthening the concept that it is the result of a myogenic response of the arterial vessels. Submitted on November 6, 1961

Effect of arterial pressure on arterial and venous resistance of intestine.

The effect of local alteration of arterial pressure on arterial and venous resistance of the intestine was investigated by means of the Pappenheimer isogravimetric technique. Reduction of arterial pressure caused a decrease in total vascular resistance in 70% of the experiments (autoregulation). This response was localized to the arterial portion of the circuit, specifically to vessels less than 0.5 mm o.d. Also associated with the reduction in arterial pressure was an increase in venous resistance. Venous resistance increased threefold as arterial pressure was reduced from 100 to 30 mm Hg. This venous response was seen in all preparations tested. It is suggested that both the venous response and autoregulation of arterial vessels aid in maintenance of a normal capillary pressure. Submitted on November 6, 1961

Relative importance of venous and arterial resistances in controlling venous return and cardiac output.

In dogs with cardiovascular reflexes completely blocked by total spinal anesthesia, the total peripheral resistance was increased five- or more fold in two ways: first, by injecting small plastic microspheres into the arteries, thereby increasing the arterial resistance, and, second, by inflating pneumatic cuffs around the major veins, thereby increasing venous resistance. A small increase in venous resistance decreased cardiac output eight times as much as an increase in arterial resistance of similar magnitude. This difference was caused principally by a) a marked rise in systemic arterial pressure when arterial resistance was increased; this maintained the cardiac output at almost normal levels and b) a fall in systemic arterial pressure when venous resistance was increased; this promoted even more fall in cardiac output than increased total peripheral resistance alone would have caused.