Isoprostane 8-epi-prostaglandin F2 alpha decreases lymph capillary pressure in patients with primary lymphedema

In patients with lymphedema, reduced lymph drainage capacity results in an overloaded superficial microlymphatic network and microlymphatic hypertension. In in vitro experiments, it has been shown that 8-epi-prostaglandin F2 alpha (PGF) induced contractions in human lymphatics. Since lymphatic contractility plays a crucial role in the regulation and generation of lymph transport, we studied the effect of PGF on microlymphatic dynamics by measuring lymph capillary pressure (LCP). Twenty healthy volunteers and 13 patients with primary lymphedema were studied after either PGF or placebo was applied to the skin and occlusively covered for 30 min. Glass micropipettes (7-9 microm) were inserted under microscopic control into initial lymphatics visualized by fluorescence microlymphography and pressure measurements were performed using the servo-nulling technique. The mean LCP in patients with lymphedema was significantly higher (19.8 +/- 12.1 mm Hg) than that in healthy controls (8.4 +/- 4.1 mm Hg) at the placebo-treated site and decreased to normal values after PGF (10.0 +/- 7.7 mm Hg). In healthy volunteers, there was no significant decrease of LCP with PGF compared to placebo. PGF normalizes microlymphatic hypertension in patients with lymphedema by improving lymph transport into deeper channels.     

The effect of walking with high-heeled shoes on the leg venous pressure

It is common belief that the use of high-heeled shoes is deleterious to venous return, by impairing the efficiency of the muscular calf pump. Ambulatory venous pressure obtained with dorsal foot venipuncture is the gold standard in the evaluation of venous pressure during walking, but it is not routinely used in clinical practice. The objective of the present study was to determine the variations in leg venous pressure obtained with a new noninvasive method, in individuals without venous disease, walking without shoes and wearing high-heeled shoes. A new method of evaluation of the venous pressure by means of air plethysmography was applied to 10 volunteers (20 limbs). The patients were evaluated while standing, with orthostatic flexion and extension foot movements, and while walking on a treadmill barefooted and wearing high-heeled shoes. It was found that the variation on the cuff pressure during walking with high-heeled shoes was higher than the variation on the cuff pressure walking barefooted (52.2 +/- 8.89 X 26.65 +/- 6.7 mm Hg, p < 0.0001), and the final hydrostatic venous pressure was lower (51.5 +/- 12.78 X 61.5 +/- 8.44 mm Hg). The use of high-heeled shoes increases muscular effort during walking and diminishes the leg venous pressure compared with barefooted.     

Microlymphatic aneurysms in patients with lipedema.

"Lipedema," a special form of obesity syndrome, represents swelling of the legs due to an increase of subcutaneous adipose tissue. In 12 patients with lipedema of the legs and in 12 healthy subjects (controls), fluorescence microlymphography was performed to visualize the lymphatic capillary network at the dorsum of the foot, at the medial ankle, and at the thigh. Microaneurysm of a lymphatic capillary was defined as a segment exceeding at least twice the minimal individual diameter of the lymphatic vessel. In patients with lipedema, the propagation of the fluorescent dye into the superficial lymphatic network of the skin was not different from the control group (p > 0.05). In all 8 patients with lipedema of the thigh, microaneurysms were found at this site (7.9 +/- 4.7 aneurysms per depicted network) and in 10 of the 11 patients with excessive fat involvement of the lower leg, multiple microlymphatic aneurysms were found at the ankle region. Two obese patients showed lymphatic microaneurysms in the unaffected thigh and in only 4 patients were microaneurysms found at the foot. None of the healthy controls exhibited microlymphatic aneurysms at the foot and ankle, but in one control subject a single microaneurysm was detected in the thigh. Multiple microlymphatic aneurysms of lymphatic capillaries are a consistent finding in the affected skin regions of patients with lipedema. Its significance remains to be elucidated although its occurrence appears to be unique to these patients.     

Assessment of the peripheral microcirculation using computer-assisted venous congestion plethysmography in post-traumatic complex regional pain syndrome type I

In complex regional pain syndrome type I (CRPS-I), edema of the affected limb is a common finding. Therefore, the changes in macro- and microcirculatory parameters were investigated to elucidate the underlying pathophysiology. Twenty-four patients with post-traumatic CRPS-I and 25 gender- and age-matched healthy subjects were examined by means of an advanced computer-assisted venous congestion strain-gauge plethysmograph. The recording of the volume response of the forearm to a stepwise inflation of an occlusion cuff placed at the upper arm enabled the calculation of the arterial blood flow into the arm (Q(a)), the vascular compliance (C), the peripheral venous pressure (P(v)), the isovolumetric venous pressure (P(vi); = hydrostatic pressure needed to achieve net fluid filtration) and the capillary filtration capacity (CFC)--an index of microvascular permeability. The study revealed no difference in any of the parameters between the right and left hand of healthy subjects. In CRPS-I patients, however Q(a), P(v), P(vi) and CFC were significantly (p < 0.01/0.001) elevated in the affected arm (Q(a) 11.2 +/- 7.0 ml x min(-1) x 100 ml(-1), P(v) 20.2 +/- 8.1 mm Hg, P(vi) 24.7 +/- 4.2 mm Hg, CFC 0.0058 +/- 0.0015 ml x min(-1) x 100 ml(-1) x mm Hg(-1)) compared to the unaffected arm (Q(a) 4.2 +/- 2.4 ml x min(-1) x 100 ml(-1), P(v) 10.0 +/- 5.1 mm Hg, P(vi) 13.2 +/- 3.7 mm Hg, CFC 0.0038 +/- 0.0005 ml x min(-1) x 100 ml(-1) x mm Hg(-1)) and the values obtained in healthy controls (Q(a) 5.1 +/- 1.3 ml x min(-1) x 100 ml(-1), P(v) 10.4 +/- 4.3 mm Hg, P(vi) 15.7 +/- 3.3 mm Hg, CFC 0.0048 +/- 0.0012 ml x min(-1) x 100 ml(-1) x mm Hg(-1)). Whereas the values in the unaffected arm of CRPS-I patients revealed no difference in Q(a), P(v) and P(vi) but a lower CFC (p < 0.01) compared to those from healthy controls. These results suggest profound changes in both macro- and microvascular perfusion in the affected arm of CRPS-I patients. The high CFC contributes to the edema formation, and combined with the elevated P(vi), they are in agreement with the hypothesis of an inflammatory origin of CRPS.     

Increased skin capillary density in treated essential hypertensive patients

BACKGROUND: Microvascular rarefaction is a hallmark of essential hypertension. We measured the skin capillary density in nondiabetic hypertensive subjects with effective antihypertensive treatment and evaluated possible correlations with arterial blood pressure (BP). METHODS: This cross-sectional observational study included 76 (55 +/- 1 years) consecutive outpatients with essential hypertension under chronic antihypertensive drug treatment (BP < 140/90 mm Hg), 24 age- and sex-matched patients with recently discovered and never-treated hypertension and 70 normotensive (BP < 140/90 mm Hg) age- and sex-matched healthy controls. We used intravital video-microscopy to measure basal and maximal (during venous congestion) skin capillary densities in the dorsum of the fingers. Aortic stiffness was evaluated using pulse wave velocity and central aortic pressure calculated from radial artery applanation tonometry. RESULTS: Baseline and maximal capillary densities (number/mm2) were significantly lower (59.6 +/- 2.0 and 62.0 +/- 1.9) in untreated than in treated hypertensive patients (74.0 +/- 1.4 and 79.4 +/- 1.5; P < .001) and than in normotensives (68.2 +/- 1.5 and 72.4 +/- 1.5; P < .001). Based on multiple regression analysis, after adjustment to tobacco consumption, aortic (and not brachial) systolic BP was inversely correlated with basal and postocclusive capillary densities in normotensive subjects. In hypertensives, this correlation disappears and capillary density was influenced by two independent variables, antihypertensive drug treatment and overweight. CONCLUSIONS: In nondiabetic hypertensive patients, capillary density is reduced in association with a cluster of cardiovascular risk factors involving tobacco consumption and obesity. The finding of an increased capillary density in effectively treated antihypertensives suggests that a cause-to-effect relationship between BP and capillary density should be evaluated in a long-term prospective follow-up.     

Evaluation of the time course of vascular responses to venous congestion in the human lower limb

This study examined the time course of changes in blood flow to the lower leg in response to venous distension--the veni-arteriolar vasoconstrictor response--in 31 healthy males. During a 5-min period of venous distension (thigh cuff pressure 50 mm Hg), calf blood flow (venous occlusion plethysmography) decreased more rapidly (within 30 s) compared to skin perfusion (after 2 min, Laser Doppler flowmetry), consistent with disparate filling times of superficial and deeper veins and a greater increase in deep vein volume. On completion of venous filling, vascular resistance in the skin was unchanged from baseline, implying that the reduction in perfusion was solely the result of reduced perfusion pressure. For the whole calf, vascular resistance was unchanged after 1 min but decreased thereafter by 35-45% from baseline, indicating adjustment of pre- or post-capillary resistances to maintain flow. Repeated plethysmographic flow measurements assisted the decrease in resistance, most likely by intermittent compression of the thigh cuff acting to displace blood volume centrally and alleviate congestion. These findings do not support an active veni-arteriolar vasoconstrictor mechanism in response to venous distension alone in the lower leg, and provide evidence of dynamic flow adjustments that should be acknowledged during procedures that involve prolonged periods of venous congestion.     

Structural skin capillary rarefaction in essential hypertension

A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension. This rarefaction may play a role in increasing peripheral resistance. However, the mechanism underlying this capillary rarefaction is not understood. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of dorsum of fingers in essential hypertension. The capillary microcirculation was examined with video microscopy before and after maximizing the number of perfused capillaries by venous congestion. The study group comprised 17 patients with essential hypertension (mean supine blood pressure, 155/96 mm Hg) and 17 closely matched normotensive controls (mean blood pressure, 127/77 mm Hg). We used intravital video microscopy with an epi-illuminated microscope to examine the skin of the dorsum of left middle phalanx before and after venous congestion at 60 mm Hg for 2 minutes. A significantly lower mean capillary density occurred at baseline in hypertensive subjects versus normotensive subjects. With venous occlusion, capillary density increased significantly in both groups; however, maximal capillary density remained significantly lower in the hypertensive subjects than in the normotensive subjects. The study strongly suggests that much of the reduction in capillary density in the hypertensive subjects is caused by structural (anatomic) absence of capillaries rather than functional nonperfusion.     

Lymph and pulmonary response to isobaric reduction in plasma oncotic pressure in baboons.

Plasma colloid osmotic pressure was reduced by 76% (from 19.6 +/- 0.6 to 4.7 +/- 1.5 mm Hg) in five baboons while pulmonary capillary hydrostatic pressure was maintained at a normal level. This resulted in fluid retention, weight gain, peripheral edema and ascites, but no pulmonary edema. Thoracic duct lymph flow increased 6-fold and pulmonary lymph flow 7-fold. Thoracic duct lymph had a lower colloid osmotic pressure (2.0 +/- 0.7 mm Hg) than plasma (4.7 +/- 1.5 mm Hg), whereas the colloid osmotic pressure of pulmonary lymph (4.7 +/- 0.7 mm Hg) was the same as that of plasma. The lymph-plasma ratio for albumin fell in thoracic duct lymph but remained unchanged in pulmonary lymph. The difference between plasma colloid osmotic pressure and pulmonary artery wedge pressure decreased from 15.3 +/- 1.9 to -0.7 +/- 2.9 mm Hg. Despite this increase in filtration force, the lungs were protected from edema formation by a decrease of 11 mm Hg in pulmonary interstitial colloid osmotic pressure and a 7-fold increase in lymph flow.     

Effects of passive tilting on capillary filtration in the lower leg in idiopathic dilated cardiomyopathy and after heart transplantation for the same condition

Abnormal reflex control of the peripheral microvasculature during orthostasis in congestive heart failure (CHF) and after heart transplantation (HT) may cause failure of microvascular homeostasis and peripheral edema. We explored the effect of passive head-up tilt on lower leg capillary filtration measured by strain-gauge plethysmography in 24 patients with CHF, in 20 patients after HT (12 patients with preserved native right atrium, 8 patients without native right atrium), and in 18 controls. We hypothesized that an impaired peripheral microvascular reflex during orthostasis in CHF and HT might allow increased arterial hydrostatic pressure to increase pressure at the capillary level. To identify an impact of changes in arterial hydrostatic pressure, capillary fluid filtration was expressed per mm Hg arterial hydrostatic pressure (capillary filtration coefficient(arterial pressure) [CFC(AP)]) and was measured (1) during elevated venous pressure alone (50 mm Hg venous stasis in supine position), and (2) during elevated hydrostatic pressure at both the venous and arterial side of the vascular tree (head-up tilt with a vertical distance from the right atrium to the strain-gauge of 68 cm of water [50 mmHg]). Elevated venous pressure alone resulted in the highest CFC(AP) in controls (0.79+/-0.28 ml/min x 100 ml mm Hg x 10(-3)+/-SD) versus those with CHF (0.44+/-0.23, p <0.0001) and those after HT (0.54+/-0.22, p <0.01). However, during head-up tilt, CFC(AP) was similar in all 3 groups, because CFC(AP) decreased in controls (to 0.49+/-0.22, p <0.0001), in contrast to unchanged CFC(AP) in those with CHF (0.43+/-0.24) and in those with HT (0.50+/-0.21). HT patients with complete removal of the native right atrium had higher CFC(AP) (0.62+/-0.17) during head-up tilt than patients with preserved native right atrium (0.36+/-0.16, p <0.005). In conclusion, patients with CHF and those after HT have increased capillary filtration to a lesser degree than controls during elevated venous pressure alone. However, during orthostasis this apparent edema-protective mechanism vanishes, probably because of compromised microvascular reflex control. During daily upright activities, this may be one important factor in the edema pathogenesis. The phenomenon is particularly distinct in HT patients without preserved native right atrium.     

Relation between hemodynamic and ventilatory responses in determining exercise capacity in severe congestive heart failure

The cause of exercise intolerance in congestive heart failure is unclear. Hemodynamic and ventilatory responses were measured during symptomatic maximal upright bicycle exercise in 28 patients with chronic severe left ventricular failure who achieved a maximal oxygen uptake of only 12 +/- 4 ml/min/kg (+/- standard deviation). All patients reached anaerobic metabolism as the respiratory exchange ratio rose and arterial pH fell significantly. Pulmonary capillary wedge pressure increased from 20 +/- 10 mm Hg at rest to 38 +/- 9 mm Hg at peak exercise and cardiac index increased from 2.51 +/- 0.73 to 4.54 +/- 1.65 liters/min/m2 (both p less than 0.001). Systemic vascular resistance decreased, but pulmonary vascular resistance did not change during exercise. Despite the marked pulmonary venous hypertension at peak exercise, blood gases were unchanged (PaO2, 96 +/- 15 mm Hg; PaCO2, 35 +/- 7 mm Hg). Systemic arterial oxygen content increased from 16 +/- 2 to 17 +/- 2 vol% (p less than 0.01). Changes in pulmonary capillary wedge pressure did not correlate with changes in arterial oxygen content. Results were similar whether patients were limited by dyspnea or fatigue. Thus, exercise intolerance in patients with severe left ventricular failure is associated with marked elevation of pulmonary capillary wedge pressure and anaerobic metabolism without hypoxemia or altered carbon dioxide tension. These findings suggest that exercise ability in congestive heart failure is more dependent on cardiac output than on ventilatory consequences of pulmonary congestion.     

Changes in Subcutaneous Interstitial Fluid Pressure,Tissue Oxygenation,and Skin Red Cell Flux during Venous Congestion Plethysmography in Men

Objective : Venous congestion plethysmography enables noninvasive assessment of microvascular filtration capacity (K_f) in limbs. However, increases in fluid filtration might alter the balance of Starling forces; for example, progressive increases in interstitial fluid pressure (P_i) would reduce net fluid flux, thus underestimating K_f. Furthermore, elevation of cuff pressure to values close to diastolic blood pressure, as used in the protocol, may by itself impair tissue perfusion with unknown effects on the microvascular parameters investigated. Methods : P_i was measured in healthy volunteers (n = 14) with a modified “Wick in needle” technique during small (8 mm Hg) cumulative increases in venous pressure (0–95 mm Hg). Changes in the hemoglobin (Hb) concentration, oxygenated hemoglobin (HbO₂) concentration, and oxidized cytochrome aa3 concentration were assessed in the calf using noninvasive near-infrared spectroscopy. Skin red blood cell flux close to the strain gauge was evaluated by laser Doppler fluxmetry. Results : P_i at control was ?0.89 ± 0.8 mm Hg and during elevation of venous pressure remained constant until a cuff pressure of 30 mm Hg was reached. It rose thereafter to 1.57 ± 1.3 mm Hg (mean SD). Skin red cell flux was significantly reduced when cuff pressure exceeded 30 mm Hg and, following cuff deflation, evidence of reactive hyperemia was obtained. Hb concentration increased significandy as a result of venous pressure elevation. No change in either HbO₂ or cytochrome aa3 concentration was observed as long as cuff pressure remained under diastolic blood pressure. Conclusions : The small increase in P_i together with an absence of impaired tissue oxygenation during the venous congestion plethysmography protocol described by Gamble et al. supports the contention mat this protocol enables accurate assessment of filtration capacity.     

Fluorescence microlymphography of the upper extremities. Evaluation with a new computer programme.

BACKGROUND: To evaluate the initial lymphatics of the superficial skin in healthy volunteers using fluorescence microlymphography and to establish controls values for comparison with lymphedema patients. METHODS: Fluorescence microlymphography was performed on the hand dorsum, on the lower and the upper arm in 12 healthy subjects (58.7+/-8.0 years). At each of these sites 10 microl FITC-dextran was injected subepidermally using a steel cannula. The studies were recorded on video tape using a fluorescence microscope and a CCD video camera. Final magnification was 24 and 62. The maximum spread of the fluorescent contrast medium was measured 10 minutes after injection. The area of the visualized lymph capillaries was determined using a computer programme. SETTING: University Hospital, Department of Medicine, Division of Vascular Medicine (Angiology). RESULTS: The mean area of the visualised lymph capillary network 95.3+/-41.3 mm2 (42-174 mm) at the upper and 89.4+/-45.5 mm2 (44-171 mm). The maximum spread was 4.8+/-3.5 mm (1.9-13.6 mm) and 4.4+/-3.7 mm, respectively. The mean diameter of the lymph capillaries was 84.1+/-19.9 microm and 75.5+/-14.8 microm, respectively. CONCLUSIONS: The extension of the lymph capillary network at the upper and lower arm are comparable to those at the lower extremities. Considering the two-dimensional nature and the irregular shape of the network the area measurement seems to be more appropriate than the maximum spread in one direction.     

Postural effects on interstitial fluid pressure in humans

BACKGROUND: Direct assessment of the effect of postural changes on interstitial fluid pressure (IFP) in the human skin under physiological conditions is important for the understanding of mechanisms involved in diseases resulting in lower limb edema. Previous techniques to measure IFP had limitations of being invasive, and acute measurements were not possible. Here we describe the effect of postural changes on IFP in the skin of the foot using the minimally invasive servonulling technique. RESULTS: Measurements were performed in 12 healthy subjects. IFP (means +/- SD) was significantly higher in the sitting (5.1 +/- 2.9 mm Hg) than in the supine position (-0.3 +/- 3.6 mm Hg, p = 0.04) when measured in the sitting position first. The difference between the sitting and the supine position was not significant when measurements were taken in the supine position first [from 1.0 +/- 4.3 (supine) to 3.6 +/- 6.7 mm Hg (sitting), p = 0.46]. Spontaneous low-frequency pressure fluctuations occurred in 58% of the recordings during sitting, which was almost twice as frequent as in the supine position (33%; p = 0.001), while no effects on lymphatic capillary network extension were observed (p = 0.12). CONCLUSION: Using the servonulling micropressure system, postural effects on IFP can be directly assessed. IFP is higher in the sitting position, but differences are influenced by the time in the upright position.     

Endothelial function in patients with type 1 diabetes evaluated by skin capillary recruitment

The aim of the present study was to evaluate skin capillary density and recruitment of the upper and lower extremities of patients with type 1 diabetes under chronic treatment without clinical manifestations of diabetes-related complications. This cross-sectional observational study included 59 (27.1+/-10.6 years) consecutive outpatients with type 1 diabetes [duration 10 (1; 45) years] and 41 age- and sex-matched healthy controls. We used intravital video-microscopy to measure basal and maximal (during venous congestion) skin capillary densities as well as capillary recruitment using post-occlusive reactive hyperemia (PORH) in the dorsum of the fingers and toes. Mean capillary density (MCD) of the fingers at baseline was not different between controls and patients (123.02+/-22.6 and 132.3+/-28.9 capillaries/mm(2), respectively; P=0.08). In contrast, baseline MCD of the toes was lower in controls, when compared to patients (84.6+/-19.8 and 96.2+/-23.4 capillaries/mm(2), respectively; P=0.01). Capillary recruitment during PORH (% increase of the number of capillaries/mm(2)) was significantly higher in controls compared to patients both in fingers [7 (-8; 33) and -1.0 (-35, 13), respectively; P=0.000] and toes [6 (-20; 46) and 0 (-24; 20), respectively; P=0.000]. During venous occlusion, capillary density increase (% increase of the number of capillaries/mm(2)) was also higher in controls compared to patients both in fingers [3 (-14; 23) and 0.0 (-30; 29.2), respectively; P=0.02] and toes [9.3 (-18; 51) and -7 (-34; 22), respectively; P=0.000]. Our results showed that patients with type 1 diabetes, although not presenting skin capillary rarefaction, display skin microvascular functional alterations in both extremities characterized by an absence of capillary reserve.     

Flow in lymphatic networks: interaction between hepatic and intestinal lymph vessels

OBJECTIVE: Lymph from both the liver and intestine flows into the cisterna chyli. We hypothesized that increasing liver lymph flow would increase cisterna chyli pressure and, thereby, decrease intestinal lymph flow, potentiating intestinal edema formation. METHODS: Anesthetized dogs were instrumented to measure and manipulate portal vein pressure and cisterna chyli pressure. The effects of directly increasing portal pressure with and without directly increasing cisterna chyli pressure on intestinal wet-to-dry ratio and intestinal ascites formation rate were determined. Target values for portal and cisterna chyli pressures were determined following elevation of inferior vena caval pressure to levels seen in patients with obstructive caval disease. RESULTS: Direct elevation of portal pressure (P(port)) alone to 17.5 mm Hg caused a significant increase in intestinal wet-to-dry ratio (3.98 +/- 0.24 vs. 3.40 +/- 0.43) and the rate of ascites formation (0.36 +/- 0.12 vs. 0.05 +/- 0.03 mL/g dry wt/h). Simultaneous direct elevation of cisterna chyli pressure to 6.0 mm Hg and P(port) to 17.5 mm Hg caused further increases in intestinal wet-to-dry ratio (5.52 +/- 1.20) and ascites formation (0.57 +/- 0.11 mL/g dry wt./h). CONCLUSIONS: Inferior vena caval hypertension increases liver lymph flow that elevates cisterna chyli pressure, which inhibits intestinal lymph flow and augments intestinal edema formation.     

Clinical, radiographic, and hemodynamic correlations in chronic congestive heart failure: conflicting results may lead to inappropriate care.

PURPOSE: Clinical and radiographic examinations are commonly used for estimating severity and titrating therapy of chronic congestive heart failure. The purpose of this study was to establish the relationship between findings on history, physical examination, chest roentgenogram, and pulmonary capillary wedge pressure (PCWP). PATIENTS AND METHODS: Fifty-two consecutive patients with chronic congestive heart failure, referred for evaluation for heart transplantation, were studied; all patients underwent history, physical examination, upright chest roentgenogram, and cardiac catheterization. The mean left ventricular ejection fraction was 0.19 +/- 0.06. Patients were divided into three groups according to their PCWP: Group 1, normal PCWP (less than or equal to 15 mm Hg, n = 19); Group 2, mild to moderately elevated PCWP (16 to 29 mm Hg, n = 15); Group 3, markedly elevated PCWP (greater than or equal to 30 mm Hg, n = 18). RESULTS: Physical and radiographic signs of congestion were more common in the groups with higher PCWP, but they could not be used to reliably separate patients with different filling pressures. Physical findings (orthopnea, edema, rales, third heart sound, elevated jugular venous pressure) or radiographic signs (cardiomegaly, vascular redistribution, and interstitial and alveolar edema) had poor predictive value for identifying patients with PCWP values greater than or equal to 30 mm Hg. These findings had poor negative predictive value to exclude significantly elevated PCWP (greater than 20 mm Hg). Radiographic pulmonary congestion was absent in eight (53%) patients in Group 2 and seven (39%) in Group 3. In patients in Group 2 and 3, those without radiographic congestion were in a better New York Heart Association functional class (3.5 +/- 0.5 versus 2.8 +/- 0.6, p less than 0.01). There was good correlation between right atrial pressure and PCWP (r = 0.64, p less than 0.001). A normal right atrial pressure had no predictive value, but a pressure greater than 10 mm Hg was seen in all but one patient with a PCWP value greater than 20 mm Hg. CONCLUSION: Clinical, radiographic, and hemodynamic evaluations of chronic congestive heart failure yield conflicting results. Absence of radiographic or physical signs of congestion does not ensure normal PCWP values and may lead to inaccurate diagnosis and inadequate therapy. It is not known whether therapy aimed at normalizing PCWP is superior to relieving clinical and radiographic signs of congestion.     

Transcutaneous oxygen tension (TcPO2) measurement as a diagnostic tool in patients with peripheral vascular disease

Transcutaneous oxygen tension (TcPO2) was measured through Clark's electrode at the dorsum of the foot in 52 healthy controls whose ages ranged from twenty to sixty-five years (mean 45.05 +/- 14.09) and 36 nondiabetic patients with peripheral vascular disease (PVD) (5 stage I, 16 stage II, 4 stage III, 11 stage IV), under standardized conditions at rest and during recovery from limb ischemia obtained with pneumatic cuff compression for 3 minutes. At rest the TcPO2 averaged 71.20 +/- 14.26 mm Hg (range 46-92) in the controls and 51.56 +/- 26.38 in the PVD patients (p less than .01). A wide overlap was observed between the two groups and among the different stages of the disease, and consequently, the diagnostic value of TcPO2 at rest was limited (sensitivity equal to 32%). During the recovery from ischemia the time constant (recovery half-time, T1/2) averaged 38.01 +/- 7.23 sec in the controls and 55.84 +/- 19.82 in the PVD patients (p less than .01). The T1/2 added to the diagnostic value of the method, making it more sensitive (55%), especially for stage II patients. The TcPO2 at rest was lower with increasing severity of the disease; both the TcPO2 at rest and the T1/2 correlated with the ankle-arm pressure index in the diseased limbs (r = .48 and -.41 respectively, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

The production of acute pericardial effusion: the effects of various degrees of interference with venous blood and lymph drainage from the heart muscle in the dog

Obstruction to the venous blood and lymph outflow from the heart muscle leads to the formation of a pericardial effusion originating primarily from the epicardial surface of the heart (the visceral pericardium). The degree of effusion is proportionate to the extent of interference with the venous blood and lymph flow. Pathologic changes found in the myocardium include venous and lymphatic congestion, perivascular and interstitial edema, and early myocardial necrosis.     

Effects of vacuum compression therapy on skin microcirculation in patients suffering from lower limb ischaemia

BACKGROUND: We investigated the short-term effect of vacuum compression (VC) treatment on skin microcirculatory perfusion in the foot of patients with lower limb ischaemia and healthy controls. PATIENTS AND METHODS: Ten patients with intermittent claudication or rest pain and 5 healthy controls underwent vacuum-compression treatment for half an hour. The leg was positioned in an air-tight plexiglass cylinder in which hypobaric (-115 mm Hg) and hyperbaric (75 mm Hg) pressure could be generated alternately, in order to improve peripheral circulation. The effect on skin microcirculation was investigated using nailfold capillary microscopy (measuring nutritive perfusion), laser Doppler fluxmetry (LDF) (total skin perfusion) and transcutaneous oxygen tension measurements (TcpO2). RESULTS: A few patients experienced ischaemic symptoms during VC, probably because the leg was pinched off through inflation of the cuff. In both patients and controls capillary microscopic parameters did not change significantly. In some cases, microcirculatory perfusion decreased because the leg had cooled during the treatment. Application of a heating matrass annihilated this effect. Only in the patient group a few LDF- and TcpO2 parameters improved slightly, but significantly. CONCLUSION: Vacuum-compression therapy only slightly improves total skin perfusion and oxygenation, but not the nutritive microcirculation, being an essential factor in the occurrence of ischaemic symptoms. We therefore conclude that this instrument in its present form is not an aid in the treatment of lower limb ischaemia.     

Rarefaction of skin capillaries in patients with anginal chest pain and normal coronary arteriograms.

AIMS: Patients with arterial hypertension often have a reduction in capillary density (rarefaction) and a reduction in coronary flow reserve because of functional and structural alterations of the coronary microcirculation. Patients with chest pain and normal coronary arteriograms may have coronary microvascular dysfunction, but it is not known whether capillary rarefaction plays a role in the pathogenesis of this syndrome. The aim of this study was to compare capillary density in hypertensive and normotensive subjects with anginal chest pain and normal coronary arteriograms vs asymptomatic hypertensives and healthy controls. METHODS AND RESULTS: We studied 49 patients with typical anginal chest pain, positive exercise testing and normal coronary arteriograms; 22 were hypertensive and 27 were normotensive. We used intra-vital video-microscopy to examine the skin of the dorsum of the middle finger of the non-dominant hand before and after maximization of perfused capillaries with venous congestion. Mean capillary density was significantly lower in patients with chest pain and normal coronary arteriograms independent of their blood pressure level, compared to normotensive healthy controls. Differences were found both at baseline [51+/-2 (hypertensive) and 52+/-2 (normotensive) vs 65+/-2 (controls) per 0.56 mm(2) respectively], (P<0.0001) and after maximization [57+/-3 (hypertensive) and 59+/-2 (normotensive) versus 75+/-3 (controls) respectively] (P<0.0001). CONCLUSIONS: Skin capillary density is significantly lower in patients with chest pain and normal coronary arteriograms compared to normotensive controls. The pathophysiological importance of capillary rarefaction in patients with chest pain and normal coronary arteriograms remains unknown. Further studies are needed to determine whether the abnormality is associated with myocardial flow disturbances such that the findings can be extended to the heart.