Venous Segment Resistances Research Articles

Effects of systemic hemodynamics on flow within vascular accesses used for hemodialysis.

Absolute value of access flow (QA) and change in flow (deltaQA) over time are major determinants of access patency. However, QA may change in response to variation in systemic hemodynamics among dialysis sessions. We examined the effect of mean arterial pressure (MAP), cardiac output (CO), and segmental resistances (R) on QA. Access flow and CO (L/min) were determined by Transonic ultrasound dilution. Static intra-access pressures (mm Hg) at the arterial segment (AS) and venous segment (VS) were determined with the access unoccluded. During access occlusion (O), the AS pressure was equated to arterial pressure (MAPo), whereas the VS pressure reflected venous pressure (VP). Total and segmental vascular resistances (mm Hg-min/L) were calculated as deltaP/Q. We studied 58 arteriovenous (AV) grafts and 35 autologous AV fistulae (AVF) with measurements on two or more occasions in 43 grafts and 25 AVF. MAPC differed from MAPo by >20 mm Hg in 22% of patients. AS (58 +/- 2 vs. 31 +/- 2) and VS (40 +/- 1 vs. 25 +/- 2) were greater in grafts than in AVF, whereas VP was equal. Access flow (0.91 +/- 0.03 vs. 0.91 +/- 0.05 L/min), cardiac output (5.1 +/- 0.1 vs. 5.5 +/- 0.2 L/min), and total access resistance (115 +/- 5 vs. 11 +/- 6) were equal in grafts and AVF, but non-access systemic R was lower in patients with AVF that those with grafts (26 +/- 1 vs. 30 +/- 1). AS and VS resistances were greater in AVF than grafts (87 +/- 6 vs. 54 +/- 3 and 37 +/- 3 vs. 16 +/- 3). Multivariate analysis indicated that CO and ipsilateral MAPo affected flow in both access types. In grafts, all three access resistance elements, AS, VS, and total independently influenced flow, whereas in AVF, the VS did not. Unexpectedly, the ratio of systemic to access resistance also influenced access flow. The pressure in the venous system draining the access affected access flow in AVF but not grafts. We conclude that the hemodynamics of grafts and AVF differ. Cardiac output, MAP, and the arterial segment resistance influence QA in both access types and need to be considered when evaluating QA as part of the trend analysis for detecting access dysfunction.

Doxapram preserves the pulmonary vascular response to hypoxia in endotoxin-treated canine lung lobes

We studied the direct effects of doxapram on pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in normal canine lung lobes (N = 6) before and after endotoxin administration. We used the technique of arterial and venous occlusions to subdivide pulmonary vascular resistance into total (Rtot), arterial, venous, and middle (Rm) segment resistances. We sequentially ventilated the lobes with control (35% O 2) and hypoxic (3% 0 2) gas mixtures prior to and following both low-dose (20 μg/kg/min) and high-dose (200 μg/kg/min) infusions of doxapram. We then administered endotoxin (1 mg/kg) and repeated control and hypoxic ventilatory periods during low-dose doxapram infusion. An additional six lobes were identically treated except that saline was infused instead of doxapram, and all measurements were repeated. Rtot and Rm increased ( P < .05) during hypoxic ventilation compared with control gas ventilation before endotoxin administration. We found that during hypoxic ventilation, Rm was significantly higher ( P < .01) during low-dose doxapram infusion compared with the equivalent period during saline infusion. Following endotoxin administration, values of Rm increased significantly ( P < .05) from control to hypoxic ventilation periods during doxapram infusion (0.006 ± 0.003 cm H 2O/mL/min and 0.027 ± 0.015 cm H 2O/mL/min, respectively) but not during saline infusion (0.007 ± 0.004 cm H 2O/mL/min and 0.006 ± 0.003 cm H 2O/mL/min, respectively). We conclude that doxapram can directly augment hypoxic pulmonary vasoconstriction even in the absence of systemic neuronal or humeral input. Of more clinical importance, doxapram infusion may allow expression of hypoxic pulmonary vasoconstriction following endotoxin. This in turn could act to improve ventilation/ perfusion matching and also to decrease pulmonary edema.

Vasodilators or vasoconstrictors prevent hypoxic pulmonary vasoconstriction

Prostaglandins modulate pulmonary vascular resistance (PVR) and hypoxic pulmonary vasoconstriction (HPV). We studied the effects of a prostaglandin vasodilator (PGI 2) and vasoconstrictor (PGE 2) in the pulmonary circulation and compared these effects to the nonprostaglandin vasodilator sodium nitroprusside (SNP) and vasoconstrictor norepinephrine (NE) during 35% and 3% O 2 ventilation. Pulmonary vascular resistance was divided into arterial, middle (Rm), and venous segmental resistances in 20 isolated left lower canine lobes using a stop-flow technique. Pulmonary vascular resistance was also analyzed as the slope and intercept (P CRIT) of the pressure-flow relationship. We found that only PGI 2 specifically prevented the increase in Rm and P CRIT due to hypoxia. Sodium nitro prusside predominantly decreased venous segment resistance and, even in the presence of SNP, hypoxia significantly ( P < .05) increased Rm (0.0179 ± 0.0075 cm H 2O/mL/min) compared with control ventilation (0.0078 ± 0.0043 cm H 2O/mL/min). Both PGE 2 and NE increased PVR primarily by increasing the venous segmental resistance. After the addition of PGE 2 or NE, hypoxic ventilation did not result in further increases of Rm or P CRIT. We conclude that PGI 2 but not SNP selectively inhibits HPV and that neither PGE 2 nor NE further augment HPV. The direct effect of these drugs on the pulmonary circulation and their resultant changes in systemic oxygen delivery must be considered prior to their use in the clinical setting.

Effects of Halothane on Hypoxic Pulmonary Vasoconstriction in Canine Atelectasis

We studied the interactions of atelectasis and halothane on hypoxic pulmonary vasoconstriction using an isolated canine lobe. We divided pulmonary vascular resistance into arterial, venous, and middle segmental resistances by a vascular occlusion technique. We found that middle segmental resistance significantly increased (P less than 0.05) from 0.016 +/- 0.007 cm H2O.mL-1.min-1 during normoxic ventilation to 0.06 +/- 0.007 cm H2O.mL-1.min-1 during hypoxic ventilation. We then produced sublobar atelectasis by introducing 4.5-mm steel ball bearings into the lobar bronchus, which resulted in a significant increase (P less than 0.05) of middle segmental resistance to 0.046 +/- 0.014 cm H2O.mL-1.min-1 during normoxic ventilation and a further significant increase (P less than 0.05) to 0.084 +/- 0.02 cm H2O.mL-1.min-1 during hypoxic ventilation. Ventilation with 2.0% halothane but not 0.5% halothane prevented the increases in middle segmental resistance observed with either atelectasis or hypoxic ventilation. Values of arterial and venous segmental resistances were not similarly affected. We conclude that sublobar atelectasis increases pulmonary vascular resistance by stimulating hypoxic pulmonary vasoconstriction. Both halothane and hypoxia primarily act upon the middle vascular segment, but their effects are in opposite directions and, in the former instance, are concentration-dependent.

Segmental vascular resistance in postobstructive pulmonary vasculopathy

Chronic unilateral pulmonary arterial ligation has been touted as a model of arteriopathy resulting in a tremendous increase in anastomotic bronchial flow (Qbr) via collaterals. To investigate its effects on the pulmonary vasculature, we ligated the left main pulmonary artery of seven dogs and 120 days later pump perfused their left lower lobes (LLL) via a cannula in the pulmonary artery at pulmonary arterial flow (Qpa) of 250 ml/min. We measured Qbr (330 ml/min) and compared LLL with control contralateral right lower lobes (RLL) and three LLL from normal dogs. Pressure-flow (P-Q) curves were obtained by varying Qpa. With arterial and venous occlusion we measured total, arterial, venous, and middle segment resistances under baseline conditions, after serotonin and histamine, either with or without Qpa and with antegrade and retrograde Qbr. Light microscopy was done postmortem. The slope of the P-Q curve was 33.4 mmHg.l-1.min in the ligated lobes compared with 15.9 in the controls, attributable by the occlusion technique mainly to a rise in arterial resistance (22.4 mmHg.l-1.min compared with 7.4 in the controls) with a small rise in venous resistance. This was explained by significant arterial medial muscle thickening and some loss of LLL volume. The arterial segment was markedly hypersensitive to serotonin, and the venous segment was mildly hypersensitive to histamine compared with controls. The occlusion data also enabled us to model the point of entry of the bronchial circulation into the pulmonary circuit at the precapillary level and to calculate bronchial vascular resistance. We conclude that postobstructive vasculopathy substantially raises pulmonary vascular resistance, mainly upstream from the site of entry of the bronchial circulation. The role of the latter may be to keep it from rising excessively in the segments it perfuses, i.e., the middle and venous ones.

Vasodilators do not abolish pulmonary vascular critical closing pressure

To examine whether the critical closing pressure (Pcrit) of the pulmonary vasculature is dependent upon vasomotor tone, we measured Pcrit in six dog lobes before and after the administration of vasodilators. We evaluated the pressure-flow (P-Q̇) relationship in zone 2 flow conditions in situ perfused dog lobe (control period). We calculated Pcrit as the mean extrapolated zero-flow pressure intercepts for the P-Q̇ relationship. We also used arterial and venous occlusions under zone 3 conditions to partition pulmonary vascular resistance into arterial, middle and venous segment resistances. We then repeated all measurements following administration of papaverine (150 μg/ml) and sodium nitroprusside (200 μg/min) into the venous reservoir (vasodilator period). Resistance in all three vascular segments was significantly reduced during vasodilator conditions. Pcrit decreased from 3.68 ± 0.76 cm H 2O to 2.53 ± 0.92 cm H 2O during control and vasodilator periods respectively ( P<0.05). The slopes of the P-Q̇ relationships were similar during both conditions. Our data support a model in which vasomotor tone normally sets Pcrit but in which the pulmonary vasculature can exhibit the phenomenon of critical closure even with vasomotor tone pharmacologically ablated.

Halothane inhibits hypoxic pulmonary vasoconstriction in the presence of cyclooxygenase blockade

Using an isolated lung the effects of halothane on hypoxic pulmonary vasoconstriction (HPV) were studied in the presence of cyclooxygenase blockade. The pulmonary vasculature can be divided into arterial, middle and venous segment resistances. Analysis of the vascular pressure-flow relationship further separates resistance into a flow dependent resistance (1/slope) and a zero-flow pressure intercept (PCRIT). We ventilated six lobes with control (35 per cent O2) and hypoxic (three per cent O2) gas mixtures with the addition of either 0, 0.5, 1.0, or 2.0 per cent halothane. We found that after addition of indomethacin (5 mg.kg-1), ventilation with three per cent O2 increased total resistance by 87 per cent over baseline with the increase primarily in the middle vascular segment. During normoxic ventilation PCRIT was 7.9 cm H2O and this increased significantly with hypoxia to 11.5 cm H2O). Only 2.0 per cent halothane blocked the increases in middle segment resistance and in PCRIT. We conclude that following cyclooxygenase blockade, halothane inhibits HPV by acting on middle segment vessels.

Separation of responses of arteries and veins to sympathetic stimulation.

Lumbar sympathetic nerve stimulation produced an increase in arterial, small vessel and venous segmental resistances in the perfused hind paw of the dog. Repeating the stimulation, after having sectioned the somatic nerve bundles accompanying the main arterial supply of the paw, brought about an increase only in venous resistance which was equal to or greater than that obtained in the control period. This venous constrictor response was reduced greatly by the intravenous administration of adrenergic neuronal blocking drugs, by local infiltration of procaine around the paw, or by transection of the subcutaneous tissue around the paw and the nerves accompanying the veins. These results indicated that sympathetic postganglionic fibers supplying the arteries and small vessels were derived from nerve bundles accompanying the arteries (tibial and deep fibular nerves). The fibers supplying the veins are distributed more diffusely in that they are found in somatic nerve bundles accompanying the veins themselves, in the tibial nerve, and in the subcutaneous tissue of the paw.

PERIPHERAL VASCULAR EFFECTS OF THE INSECTICIDE ENDRIN.

The peripheral vascular actions of insecticides are relatively unexplored. The effects of the chlorinated hydrocarbon insecticide endrin on vascular resistances were investigated in forelimbs of anesthetized dogs. Total arterial, small-vessel, and venous segmental resistances were determined in innervated and denervated limbs following lethal infusions of endrin. Limb weight was recorded continuously in some experiments. Endrin administration resulted in large increases in total limb vascular resistance, most of which were due to an increase in small-vessel (small artery to small vein) resistance. Arterial and venous segmental resistances also increased. Early responses of innervated and denervated limbs were similar. Limb blood flow decreased markedly, and when measured, limb weight fell progressively. These effects appear to result primarily from an increased level of circulating catecholamines. Hyperexcitability to noise, bradycardia, and hypertension preceded the development of systemic hypotension.

VASCULAR EFFECTS OF THE KREBS INTERMEDIATE METABOLITES.

The vascular effects of seven intermediary products of oxidative metabolism (acetate, citrate, fumarate, malate, α-ketoglutarate, oxalacetate, and succinate) were studied on the constantly perfused kidney or forelimb in 32 dogs. Significant vasodilation was obtained at submaximal dosages, usually 2.47 µmole/min, in both vascular beds for all agents without changing systemic pressure. At maximal infusion rates renal resistance decreased approximately 20%. Saline had no effect. When segmental resistances were calculated for the forelimb by measuring pressures in large and small arteries and veins, active dilation was localized to small vessel segment (25% fall). Arterial and venous segment resistances were unchanged. It is concluded that the Krebs intermediates should be included among those agents termed "vasodilating metabolites," and that these compounds could be exceedingly important in the local regulation of blood flow.

EFFECT OF CAROTID BAROCEPTOR STIMULATION UPON THE FORELIMB VASCULAR BED OF THE DOG.

The response of the musculocutaneous vascular bed of the dog's forelimb to carotid baroceptor stimulation was determined by measuring pressures at the level of the large artery, small artery, small vein, and large vein along with limb blood flow. In one series, limb blood flow was uncontrolled. In two other series, the limb was perfused at a constant flow rate and was also isolated from collateral flow in one of these. Elevation of carotid sinus pressure in the constant flow isolated (CFI) series produced an average fall in total limb, small vessel, and venous segment resistance of 27%, 36%, and 22% respectively but no significant change in arterial segment resistance. Since transmural pressure fell significantly in all three segments, active vasodilatation must also have occurred in all, including the arterial. This is reflected in the significant increase in compliance calculated for both the lumped arterial and lumped venous segments. In any given animal, there was a positive correlation between the percentage reduction in systemic pressure and total limb resistance, but this correlation was not evident between animals. In the series in which limb blood flow was uncontrolled, flow decreased consistently and significantly when carotid sinus pressure was elevated, the average decrease being 30%. Despite possible confusion introduced by the presence of an added fixed resistance in the limb circuit (rotameter), it is probable that this finding faithfully reflects the behavior of the intact limb.

Mechanisms of intrarenal hemodynamic changes following acute arterial occlusion.

The hemodynamic response of the kidney to acute arterial occlusion is poorly understood. The purpose of the present study was to determine intrarenal hemodynamic changes in intact and isolated kidneys following arterial occlusion. The relative roles of metabolic, myogenic, and tissue pressure influences on the postocclusion response were evaluated. The response of the kidney to occlusion was found to be complex, depending on the interaction of a variety of physical and humoral forces. Increases in renal resistance appeared to be due, in part, to adrenergic agents and were enhanced by extending time of occlusion and lowering the arterial pressure. The combined effects of prevenous dilatation and diminished tissue pressure resulted in a decreased resistance following shorter periods of occlusion. Prevenous dilatation was accounted for by depressed vascular sensitivity to pressor agents and the presence of vasodilator substances. Changes in venous segment resistance were found to be of primary importance in both the autoregulatory phenomenon and the postocclusion hyperemic response to short (15-sec) occlusion periods.

Effect of increased venous pressure on renal hemodynamics

Evidence is conflicting regarding the effects of increased venous pressure on renal hemodynamics. Experiments to clarify its role were carried out on 28 intact, innervated or isolated, perfused dog kidneys. Findings indicate the absence of a "venous-arteriolar" reflex. Decreases in total resistance occur as venous pressure is increased through a wide range in both innervated and isolated perfused kidneys. Intrarenal venous and tissue pressures and blood flow are unaffected by large increases in venous pressure (21–75 mm Hg) although venous segment resistance declines markedly. Decreases in blood flow are seen when renal vein pressure approaches or exceeds intrarenal venous and tissue pressures. Results confirm previous investigations regarding the importance of tissue pressure and intrarenal venous pressure in renal hemodynamics, which appear to "buffer" the kidney against effects of elevated venous pressure through a variable but unusually large venous pressure range. The phenomenon of autoregulation may be extended to include a tendency for renal blood flow constancy in the face of wide swings in both renal artery and venous pressures.

Venous response of intestine to endotoxin.

Extensive congestion of the splanchnic bed has been observed in the dog after lethal injections of endotoxin. The purpose of this investigation was to determine the role of small mesenteric veins in the development of visceral pooling; isolated sections of small intestines were removed from dogs and continuously perfused with blood obtained from intact dogs administered lethal injections of E. coli endotoxin. Results show significant mesenteric venous responses to blood-borne agents. Increases in venous segment resistance and intestine weight were found during the postendotoxin period. Evidence indicates that the progressive development of splanchnic pooling is primarily due to active constriction of small veins in which responsiveness to epinephrine is enhanced by endotoxin.

Effects of histamine, 5 hydroxytryptamine and epinephrine on pulmonary hemodynamics with particular reference to arterial and venous segment resistances.

Studies were made of the effects of histamine and 5 hydroxytryptamine (5HT) on arterial and venous segmental resistances in the isolated perfused dog lung. The lung was perfused at constant flow while pressures were measured in the pulmonary artery (PA), left atrium (PV) and in either the pulmonary artery wedge position (PAw) or a small pulmonary vein (PVs). Arterial resistance changes were inferred from changes in the PA-PAw pressure drop, and venous resistance from the PAw-PV pressure gradient. Changes in lung weight were recorded continuously. It was found that histamine usually caused a greater increase of the venous resistance than of the arterial resistance, while 5HT usually increased the arterial resistance more than the venous resistance. When the predominant resistance increase was arterial the lung weight fell, but when there was a sizeable increase of the venous resistance the lung weight rose, presumably as a result of increased capillary blood content. The correlation coefficient between the change in lung weight and the change in venous resistance was + .791. Small pulmonary vein pressures rose after administration of epinephrine, norepinephrine, histamine and 5HT. This result gives further proof of constriction of pulmonary veins by these agents.