Small Vein Pressure Research Articles

Effects of ANP on venous pressures and microvascular protein permeability in dog forelimb

Intravenous administration of alpha-atrial natriuretic peptide (ANP) produces a decrease in arterial blood pressure due to a decrease in cardiac output. The mechanism of the decrease in cardiac output is unknown but has been suggested to result from transcapillary fluid efflux caused by venoconstriction and/or increased permeability of the microvascular membrane to plasma proteins. We investigated these possibilities in the dog forelimb perfused at constant flow and prepared to measure 1) large and small vessel pressures in the two parallel skin and skeletal muscle vascular beds, and limb weight; or 2) skin lymph flow and skin lymph protein concentration. In both preparations, human ANP was injected and infused into the brachial artery. Bolus injections of ANP (0.1-0.4 micrograms) depressed perfusion pressure much less than acetylcholine or an isotonic solution of potassium chloride and did not raise small vein pressures. ANP infused at nine different rates ranging from 0.1 ng to 38.8 micrograms/min failed to influence skin and muscle small and large vein pressures, limb weight, skin lymph flow, and skin lymph protein concentration. It also failed to affect perfusion pressure and skin and muscle small artery pressures until the infusion was shut off, at which time they increased above control levels. These studies suggest that human alpha-ANP is neither a direct venous constrictor nor a potent arteriolar dilator and does not directly influence the permeability of the microvascular membrane to plasma proteins in the skin and skeletal muscle of the dog forelimb.

Analysis of responses to leukotriene D4 in the pulmonary vascular bed.

Pulmonary vascular responses to leukotriene D4 were investigated in the intact-chest animal under conditions of controlled pulmonary blood flow. Intralobar injections of leukotriene D4 in the sheep caused dose-dependent increases in lobar arterial and small vein pressures without influencing left atrial or systemic arterial pressure. Leukotriene D4 was very potent in increasing pulmonary vascular resistance in the sheep, with activity similar to that of U-46619, a thromboxane A2 mimic. Pulmonary vascular responses to leukotriene D4 in the sheep were similar when the lung was ventilated and when lobar ventilation was arrested. Responses to leukotriene D4 were similar when the lung was perfused with blood or with dextran. Pulmonary vascular responses to leukotriene D4 but not U-46619 in the sheep were reduced by inhibitors of cyclooxygenase and thromboxane synthesis. In contrast, leukotriene D4 had modest pressor activity in the pulmonary vascular bed of the cat whereas U-46619 had marked activity in this species. Responses to leukotriene D4 in the cat were not altered by cyclooxygenase inhibitors. It is concluded that leukotriene D4 has marked pulmonary vasoconstrictor activity in the sheep, increasing pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In this species, responses to leukotriene D4 were independent of changes in ventilation or interaction with formed elements but were dependent on the formation of cyclooxygenase products including thromboxane A2. However, in the cat, leukotriene D4 had very modest pressor activity, and this activity was not dependent on the integrity of the cyclooxygenase pathway. These data suggest considerable species difference in responses to leukotriene D4, a major component of the slow-reacting substance of anaphylaxis, in the pulmonary vascular bed.

Potential use of computer simulation in treatment of burns with special regard to oedema formation.

The potential usefulness of computer-based 'patient-simulators' in burn care is discussed and illustrated in the special case of oedema formation in three patients with severe thermal injuries. The present model was derived from a model by Wiederhielm (1978), and modified to be applicable to thermal injuries. The model seems to describe accurately the oedema formation as well as the distribution and composition of local and general oedema. Following thermal injuries the general oedema is characterized by typical disturbances in the circulatory state variables such as capillary pressure and plasma colloid osmotic pressure. The net water flow is increased because of an increase in filtration rate and a decrease in reabsorption rate. The resulting interstitial oedema leads to dilution of the free water proteins and a decrease in interstitial colloid osmotic pressure. The elevation of interstitial pressure leads to an increase in lymph flow. The local oedema is caused by changes in both the circulatory system and the interstitial space. There is an increase in both water and protein net flows. The latter is due to increased protein leakage to the interstitium. This results in an interstitial oedema with a higher protein concentration in free water than in general oedema. Because of the higher protein concentration in free water, the interstitial colloid osmotic pressure is at all times larger than the corresponding pressure in general oedema. In all three patients the general shape of the simulated and measured oedema curve were the same, but with minor differences in numerical values. It is interesting to note that the general oedema was larger than the local oedema in all three extensively burned patients. The results from the present investigation indicate the importance of monitoring either the total plasma protein concentration or the plasma colloid osmotic pressure and small vein pressure for guidance of a proper fluid resuscitation. The steady state 'oedema vs. venous pressure'-diagram obtained may also be used for evaluating the dynamic effects on general oedema formation due to changes in venous pressure and plasma protein concentration. It thus turned out that for a typical thermal injury with a decreased small vein pressure a continuous colloid infusion is to be preferred instead of an intermittent model of administration.

Lung injury edema in dogs. Influence of sympathetic ablation.

Increased vascular permeability characterizes lung injury pulmonary edema and renders fluid balance in the injured lung especially sensitive to changes in hydrostatic pressure. Pulmonary edema is often associated with increased sympathetic nervous system activity which can lead to pulmonary venoconstriction. This postcapillary venoconstriction could raise microvascular pressure and might therefore increase edema in the injured lung. We produced lung injury edema in dogs with oleic acid and directly measured small (less than 2 mm) pulmonary vein pressure. We found that the small pulmonary vein pressure was increased from 9.8 +/- 0.5 mmHg to 12.6 +/- 0.5 mmHg (n = 10) by oleic acid injury edema. The increase was not due to a rise in left atrial pressure since the small pulmonary vein-left atrial pressure gradient also increased. To test if this increase in the postcapillary pressure gradient was sympathetically mediated, we either unilaterally ablated the stellate ganglion or produced unilateral alpha adrenergic blockade with phenoxybenzamine before giving oleic acid. Both of these "antisympathetic" interventions prevented the increase in pulmonary vein pressure caused by oleic acid edema in the protected lung but not in the intact contralateral lung. These interventions produced a 30 +/- 6.8% reduction in the amount of edema caused by oleic acid. Restoring the increase in small vein pressure by inflating a balloon in the left atrium of dogs with bilateral stellate ganglion ablations abolished the reduction in edema produced by antisympathetic treatment. However, the decrease in edema was not significantly correlated with the reduction in pulmonary vein pressure. Thus, the mechanism of the effects of these antisympathetic interventions remains unclear. We conclude that lung injury edema causes sympathetically mediated pulmonary venoconstriction and that antisympathetic interventions significantly reduce lung injury edema and microvascular pressure.

Effect of norepinephrine on lymph flow and edema formation in the canine forelimb.

In the present study we sought evidence for the hypothesis that norepinephrine (NE) can cause constriction of lymph vessels in the canine forelimb perfused at constant flow. Mechanical venous compression (small-vein pressure approximately equal to 45 mmHg), intra-arterial infusion of histamine (16 micrograms base/min), and intra-arterial infusion of NE (16 micrograms base/min) caused the limbs to gain weight at similar rates due to edema formation; the first two maneuvers caused a sustained increase in skin lymph flow, but the increase in lymph flow with NE was only transient. Similar changes were seen during infusion of NE at 1 and 2 micrograms/min, and studies with radioactive microspheres indicated that NE increased capillary blood flow. When venous pressure was elevated and held constant at 45 mmHg. NE (4 micrograms base/min ia) antagonized and phentolamine (400 micrograms/min ia) potentiated the increase in skin lymph flow. Finally, NE (16 micrograms base/min ia) caused a reduction in histamine (16 micrograms base/min)-elevated skin lymph flow, despite the fact that capillary pressure was greatly increased due to active venous constriction. We conclude that intra-arterial infusion of norepinephrine in the dog forelimb perfused at constant flow causes constriction of lymphatic trunk vessels in skin, resulting in increased resistance to the flow of lymph.

Blockade of histamine-mediated increases in microvascular permeability by H 1- and H 2-receptor antagonists

The receptor mechanisms by which histamine increases microvascular fluid and protein efflux were studied in the canine forelimb perfused at constant flow. Skin lymph flow, protein concentration, and protein transport (flow × concentration) were examined during the intraarterial infusion of histamine alone and during the simultaneous infusion of histamine and the histamine antagonists tripelennamine or cimetidine. The infusion of histamine alone at 1.4 μg base/min resulted in a significant decrease in forelimb perfusion pressure and skin small-artery pressure and a small but significant increase in skin small-vein pressure. Histamine produced a 2 1 2 - fold increase in lymph flow, a 2-fold increase in lymph protein concentration, and a 5-fold increase in lymph protein transport. Infusion of this same dose of histamine during the simultaneous infusion of the H 1-receptor antagonist tripelennamine (10 μg/min) produced essentially the same changes in forelimb vascular pressures but failed to produce significant changes in lymph flow, lymph protein concentration, or lymph protein transport. Similarly, the infusion of cimetidine (250 μg/min), an H 2-receptor antagonist, concurrent with the infusion of histamine elicited no significant changes in lymph parameters but the fall in arterial pressures was attenuated. Since either an H 1- or an H 2-receptor antagonist is capable of blocking histamine-mediated increases in lymph flow and protein concentration, these data indicate a role for both H 1 and H 2 receptors in histamine-mediated increases in microvascular permeability.

Pulmonary vasodilator responses to nitroprusside and nitroglycerin in the dog.

The objective of this study was to determine the direct actions of nitroprusside and nitroglycerin on the pulmonary vascular bed in the intactchest dog. These widely used nitrogen oxide-containing vasodilator agents decreased pulmonary arterial pressure and increased cardiac output without altering left atrial pressure. Reductions in pulmonary arterial pressure and pulmonary vascular resistance were small under resting conditions, but were enhanced when pulmonary vascular tone was elevated by infusion of a stable prostaglandin analog that increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In studies in which pulmonary blood flow to the left lower lobe was maintained constant, nitroprusside and nitroglycerin caused small but significant reductions in lobar arterial and small-vein pressures without significantly affecting left atrial pressure. With constant blood flow, lobar vascular pressures that were reduced in response to the vasodilators were more greatly reduced when lobar vascular resistance was increased by infusion of the prostaglandin analog or serotonin. However, when lobar vascular pressures were elevated by passive obstruction of lobar venous outflow, vasodilator responses to nitroprusside and nitroglycerin were not enhanced. These data suggest that nitroprusside and nitroglycerin decrease pulmonary vascular resistance by dilating intrapulmonary veins and upstream segments. These responses were minimal under control conditions but were enhanced when vascular tone was increased. This vasodilator action is independent of passive factors such as changes in pulmonary blood flow or left atrial pressure and is not secondary to an effect of these agents on the systemic circulation. Pulmonary vasodilator responses to nitroprusside and nitroglycerin were, however, found to be dependent on the existing level of vasomotor tone in the pulmonary vascular bed.

Effects of intravenously infused histamine on canine forelimb transvascular protein efflux following adrenergic receptor blockade.

The intravenous infusion of high doses of histamine (400 micrograms base/min) produced only small increases in weight (approximately equal to +30 g) and lymph total protein concentration (+ 0.9 g/100 ml) in canine forelimbs perfused at constant inflow. The weight gain was associated with profound decreases in aortic pressure (112 to 30 mm Hg) and in forelimb perfusion pressure (105 to 75 mm Hg) and marked increases in forelimb skin small-vein pressure (from 12 to 25 mm Hg). After treatment with phentolamine, the intravenous infusion of these doses of histamine under the same conditions produced marked decreases in forelimb perfusion pressure (120 to 60 mm Hg) and failed to increase forelimb skin small-vein pressure, yet still produced only minimal increases in weight (+ 12 g) and lymph total protein concentration (+ 0.8 g/100 ml). Following treatment with both phentolamine and propranolol, the intravenous infusion of histamine caused very marked increases in forelimb weight (approximately equal to +75 g) and lymph total protein concentration (+ 2.9 g/100 ml). These marked increases in forelimb weight and lymph formation were associated with profound decreases in perfusion pressure (112 to 60 mm Hg) but no change in skin small-vein pressure relative to control. These same increases in weight and lymph total protein concentration were observed after treatment with propranolol alone. Thus, treatment with propranolol markedly increased net fluid filtration and protein efflux during intravenous infusions of massive doses of histamine, idicating that this edemogenic agent causes an endogenous release of catecholamines which tend to antagonize the direct actions of histamine on the microvascular membrane via stimulation of beta-adrenergic receptors.

Pulmonary and systemic hemodynamics during hemorrhagic shock in baboons.

The pulmonary and systemic hemodynamic response to four hours of hemorrhagic shock and resuscitation has been studied in 17 baboons using both open and closed chest models. No pulmonary artery (PA) hypertension occurred during shock or resuscitation except for an increase in lft ventricular end diastolic pressure (LVEDP) secondary to intravascular volumee overload with Dextran. Pulmonary vascular resistance (PVR) increased during shock but returned to control levels with reinfusion of shed blood and correction of acidosis. PVR was moderately elevated following reinfusion of shed blood if acidosis was not corrected or if volum resuscitation was inadequate. No increase in gradients occurred between PA pressure and left atrial (LA) pressure or LVEDP and there was no gradients between small pulmonary vein and LA pressure. Arterial PO2 uniformly increased during shock and remained at or above control levels of reinfusion. Gross or histologic evidence of "congestive atelectasis" or "shock lung" was not observed. These observations suggest that in the subhuman primate, hemorrhage alone does not produce significant injury to the lung during shock or the immediate postresuscitation interval. Hemorrhage alone did not produce changes in the lung which would result in increased pulmonary microvascular hydrostatic pressure following appropriate resuscitation.

Determinants of small coronary vein pressure

Determinants of small coronary vein pressure

Anatomic response of canine hindlimb vasculature to chronic venous occlusion.

Total limb (iliac) flow, small-vein pressure, and total small-vessel and venous resistances were measured in the fully dilated bed 2 h, 2 wk, and 8 wk after extensive ligation of veins. Values were compared to similar measurements in the contralateral unoccluded extremity. Wall thickness, lumen size and distensibility of noncollateral veins, and enlargement of collateral veins were evaluated 8 wk after venous ligation. Two hours after ligation, anatomic vascular resistance was twice normal, and venous resistance was increased sevenfold. Eight weeks later, total limb anatomic resistance had decreased to a value slightly less than normal, suggesting an "overcompensation" in anatomic resistance. Wall thickness of noncollateral veins was greater than normal at 8 wk postligation, and lumen size and distensibility were less than normal in spite of a return of supine venous pressure to normal levels.

Influence of a prostaglandin endoperoxide analogue on the canine pulmonary vascular bed.

We evaluated the effects of an analogue of the prostaglandin endoperoxide, PGH2, in the canine pulmonary vascular bed. The analogue increased pulmonary arterial pressure whereas cardiac output and left atrial pressure were unchanged. Although pulmonary vascular resistance was increased markedly, only small increases in systemic vascular resistance were observed. In experiments in which blood flow to a lobe was maintained constant, the analogue produced dose-related increases in lobar arterial and small vein pressure but little change in left atrial pressure. These data suggest that the analogue increased resistance to flow by constricting intrapulmonary veins and upstream vessels presumed to be small arteries. The increase in resistance was similar when the lung was perfused with dextran or with blood. In addition, the analogue increased inflation pressure; however, similar increments in vascular resistance were obtained in ventilated and nonventilated lung lobes. Indomethacin, in doses which abolished responses to arachidonic acid, did not attenuate the response to the analogue. These results suggest that interaction with formed elements, increases in airway tone, or stimulation of prostaglandin synthesis contribute little if anything to the pressor response to the analogue. These data show that the analogue is far more potent than the bisenoic prostaglandins in the pulmonary vascular bed and suggest that endoperoxides may represent an active form of the prostaglandins in the lung.

Acute response to venous distention in the extremity of the dog.

Aortic and vena caval pressures, right and left iliac flows. and pedal small artery and small vein pressures were recorded in mongrel dogs prior to and for 90 min following ligation of the right iliac, femoral, medical saphenous, and lateral saphenous veins. Total, arterial, small vessel and venous resistances were calculated. Measurements were repeated following alpha-receptor blockade (phenoxybenzamine) and perfusion of the extremities with a calcium chelator (EGTA). Results indicated that venous ligation resulted in constriction of small vessels in both the occluded and contralateral extremities and constriction of veins in the occluded extremity only. Relative responses of right and left vascular bed to alpha-blockade and EGTA perfusion suggested that small vessels were constricted bilaterally by enhanced sympathetic stimulation and that veins and small vessels were constricted on the occluded side in response to a local myogenic stimulus.

Effects of histamine and acetylcholine on equine digital lymph flow and composition.

We measured the flow rate and protein concentration of lymph collected from a digital lymphatic in eight anesthetized ponies. Additionally, we recorded systemic arterial pressure (Part), and small vein pressure (Psv). Control lymph flow averaged 0.068 ml/min, and contained 3.11 g/100 ml of protein with albumin/globulin ratio of 0.75. Twenty-minute local intra-arterial infusion of acetylcholine (10 mug/min.) elevated Psv but did not increase lymph flow rate or protein concentration. A 60-min local intra-arterial infusion of histamine (10 mug/min) produced a marked sustained increase in Psv and both lymph flow and protein concentration. Edema developed in the digit receiving histamine. These data support the conclusion that in the horse, as in other species, histamine edema is due primarily to a decreased transcapillary colloid osmotic pressure gradient rather than an increased transcapillary hydrostatic pressure gradient.

The effect of bretylium tosylate on the pulmonary arterial and venous circulations of the intact anesthetized dog.

SummaryThe effects of intravenous bretylium tosylate on the pulmonary circulation, including the small pulmonary veins, were studied in 9 intact dogs anesthetized with urethane. Bretylium produced a transient rise in femoral and pulmonary arterial pressures and in cardiac output and heart rate. The small pulmonary vein pressure did not change; and, since pulmonary blood volume did not change, there was no significant change in pulmonary venous tone. It is concluded that the initial pulmonary hypertensive effects of intravenous bretylium are primarily due to constriction of small arterial vessels.

Reflex vascular responses to stimulation of chemoreceptors with nicotine and cyanide. Activation of adrenergic constriction in muscle and noncholinergic dilatation in dog's paw.

Experiments were done to characterize the vascular responses to stimulation of aortic and carotid chemoreceptors and to identify the efferent components of the sympathetic system which are activated in different vascular beds. The chemoreceptors were stimulated with nicotine and cyanide in anesthetized and artificially ventilated dogs. The gracilis muscle and hindpaw were isolated and perfused with blood at constant flow. Changes in perfusion pressure reflected changes in total vascular resistance, and changes in small vein pressure reflected changes in venous resistance. The results indicate that stimulation of carotid and aortic chemoreceptors activates selectively efferent adrenergic constrictor fibers supplying prevenous resistance vessels in the gracilis muscle and venous resistance vessels in the paw. In contrast, there was a dilatation of prevenous resistance vessels in the paw caused by activation of efferent sympathetic dilator fibers and not by withdrawal of sympathetic constrictor tone. The dilatation was not mediated through the release of acetylcholine, histamine, or bradykinin nor through beta receptors. Bilateral denervation of the carotid sinus and body and bilateral vagotomy abolished the reflex responses caused by injections of the chemicals. These responses were not the result of activation of baroreceptors since they were not reproduced during electrical stimulation of the carotid sinus nerve.

Vascular responses after alpha adrenergic receptor blockade

The effects of nerve stimulation and of intraarterial injections of norepinephrine on arterial and venous resistances were studied in the perfused forelimb of dog before and after administration of the alpha adrenergic receptor blocker phenoxybenzamine.Pressures were recorded from the perfused brachial artery and a small metacarpal vein in the forepaw. Blood flow to the whole forelimb was maintained constant. Changes in perfusion pressure in the brachial artery reflected primarily changes in arterial resistance and changes in small vein pressure reflected changes in resistance of venous segments downstream from the point of pressure measurement.Alpha receptor blockade reduced vasoconstrictor responses to both nerve stimulation and norepinephrine. Responses to angiotensin, used in these experiments as an internal control, were not blocked consistently in a dose-related manner indicating that the effects of phenoxybenzamine were specific to adrenergic stimuli.Increases in venous pressure in response to norepinephrine and to nerve stimulation were blocked almost completely whereas increases in arterial pressure were reduced only in part by the blocker. The more effective reduction of pressor responses in the small vein was not caused by a passive reduction in blood flow through the paw nor was it caused by a reduction in the concentration of norepinephrine in the venous effluent reaching the venous segments.This differential effect of alpha receptor blockade on increases in venous and arterial resistances may account for the beneficial effect of phenoxybenzamine in shock.

VASCULAR EFFECTS OF ANGIOTENSIN AND NOREPINEPHRINE IN THE DOG, CAT, AND MONKEY.

The direct effects of angiotensin and norepinephrine on forelimb vessels were compared in the dog, cat, and monkey in constant-flow forelimb preparations. Equiweight and equimolar injections and in some instances equiweight infusions were carried out. Brachial artery pressure (BAP), small vein pressure (SVP), and limb weight changes were continuously recorded. In some instances, intact, natural-flow preparations were employed. With equimolar injections in constant-flow limbs, angiotensin increased limb BAP and SVP more than norepinephrine in the dog and cat, and caused a significantly greater loss of limb weight in the dog. With equiweight doses, angiotensin caused a greater increase of cat forelimb BAP and SVP and monkey SVP; norepinephrine injection resulted in a greater increase of dog limb BAP and SVP and approximately the same increase of monkey BAP as angiotensin. Limb weight loss was not significantly different in any species. The initial SVP elevations produced by angiotensin and norepinephrine infusion were about equal, but the small veins became unresponsive to angiotensin after several minutes of infusion.

Small artery and vein pressures in the subarachnoid space of the dog

Summary The mean arterial pressure in vessels of 0.5 mm. diameter in the subarachnoid space is in the range of 63 mm. Hg, which is less than 50 per cent of mean systemic blood pressure. In the small veins of this space, the pressure is in the range of 255 mm. H 2 O (19 mm. Hg) with a gradient of pressure between subarachnoid vein and membranous sagittal sinus of approximately 150 mm H 2 O. A major determinant of SAVP is CSFP, and elevations of the latter increase subarachnoid venous pressure without elevating sagittal sinus venous pressure.

ANALYSIS OF VASCULAR RESPONSES IN THE SPLEEN.

Canine spleens were isolated and perfused at constant flow with blood from a femoral artery. Perfusion pressure, small vein pressure, tissue cannula pressure, organ weight, and capsular tension were monitored continuously. Splenic nerve stimulation and epinephrine elevated total resistance and increased small vein pressure more than tissue cannula pressure Evidence was provided which demonstrated that the venous pressure increment resulted primarily from active contraction of the splenic veins. Norepinephrine produced equivalent changes in total resistance but was significantly less effective than nerve stimulation and epinephrine, both in raising venous pressure and contracting the splenic capsule. Acetylcholine decreased total resistance, whereas venous pressure was increased by a passive mechanism. The effect of synthetic angiotensin was restricted to contraction of the splenic arterial segments. The highly distensible nature of the spleen was illustrated in experiments where total occlusion of venous flow had only minor effects upon the resistance to arterial inflow. Retrograde perfusion through the splenic vein failed to result in flow out of the splenic artery, indicating that valves or a valvelike mechanism are located at some presinusoidal site along the vascular tree.