Myocardial Fluid Balance in Acute Hypertension

Objectives: We hypothesized that (1) acute arterial hypertension increases myocardial microvascular fluid filtration and (2) the combination of acute arterial hypertension and coronary sinus pressure elevation may increase myocardial microvascular filtration sufficiently to estimate the osmotic reflection coefficient of the myocardial exchange vessels. Methods: In nine mechanically ventilated dogs we cannulated the prenodal major cardiac lymph trunk. With the use of central venous phenylephrine infusion, mean arterial pressure (MAP) was raised progressively to 120, 160, and 180 mm Hg. In five dogs we additionally raised coronary sinus pressure (CSP) to 20 and 40 mm Hg. At each manipulation of MAP and/or CSP, we measured indexes of myocardial lymphatic function and lymph-to-plasma concentration ratios for total protein (C_L(TP)/C_P(TP)) and albumin (C_L(alb)/C_P(alb)). Results: Myocardial lymph flow rate (Q_L; μL/min) increased exponentially (Q_L= 10.9 e^0.014-(MAP)) and myocardial lymph driving pressure (P_L; mm Hg) increased linearly (P_L= 2.30 + 0.20 MAP) following MAP increases, whereas C_L(TP)/C_P(TP) and C_L(alb)/C_P(alb) decreased from 0.67 ± 0.07 (SD) to 0.56 ± 0.10 and from 0.91 ± 0.05 to 0.75 ± 0.11, respectively. Adding CSP elevation increased Q_L up to 12 times control associated with further C_L(TP)/C_P(TP) and C_L(alb)/C_P(alb) decreases to 0.49 ± 0.05 and 0.59 ± 0.02, respectively. Conclusions: We conclude that hypertensive arterial pressures are, at least in part, transmitted to the myocardial microvascular exchange vessels in the intact animal leading to increased microvascular fluid filtration. However, the combination of acute arterial hypertension and coronary sinus pressure elevation is not sufficient to produce filtration independence required for myocardial osmotic reflection coefficient determination.     

Interstitial fluid pressure in rats measured with a modified wick technique

Subcutaneous interstitial fluid pressure (P_i) was measured in anesthetized rats with the “wick-in-needle” technique: A thin hypodermic needle was provided with a 2- to 4-mm-long sidehole and filled with multifilamentous nylon thread. A polyethylene tube, connecting the needle to a pressure transducer, could be compressed by a screw clamp, displacing a volume of about 0.2 μl. Compression caused a marked rise in pressure, but return to control level was obtained within 1 to 5 min. Decompression caused opposite pressure changes, confirming satisfactory fluid communication between needle and tissue fluid. Control P_i (measured with saline-filled needle) ranged from ?2.5 to +1.0 mm Hg, with mean values of ?0.65 mm Hg (SD 0.82, n = 44) on the back and ?1.2 mm Hg (SD 0.8, n = 11) on the hindlimb. Similar values were obtained with the needle filled with serum or 1% hyaluronic acid. Severe reduction of femoral arterial pressure reduced hindlimb P_i gradually to ?3 to ?4 mm Hg in the course of 1 to 2 hr. P_i was also reduced after 3–7 days of dehydration (?2 to ?6 mm Hg) and rose rapidly with rehydration. Edema and a rise of hindlimb P_i to positive values were observed when femoral venous pressure was increased from the control level of 3 to 12 mm Hg or more for a period of 24 hr.     

Automatic recording of venous hysteresis. Results in the normal subject and in varicose patients

The measurement of the venous distensibility by straingauge plethysmography during a semi-continuous variation (3 mm Hg every 20 seconds) of the cuff pressure during its inflation from 0 to 100 mm Hg and its deflation allow to record the venous hysteresis and to determine accurately the venous pressure. The standardized and automatic (Periflow J.S.I.) new method is highly discriminative between controls and varicose patients.     

Effects of altered carbon dioxide tension on hemoglobin oxygenation in hamster cheek pouch microvessels

Simultaneous determinations of percentage HbO₂ and PO₂ were made at various sites moving progressively downstream from large to small arterioles in the suffused hamster cheek pouch microcirculation. A new video densitometric technique was employed to measure intravascular percentage oxyhemoglobin (% HbO₂), and oxygen tension (PO₂) was determined polarographically with oxygen microcathodes. Microvascular diameter and red cell velocity were also measured. The above measurements were made under conditions of sustained maximal vasodilation with with 10^?4M adenosine in the suffusion solution. The pairs of values for % HbO₂ and PO₂ at each of the measurement sites were used to construct apparent in vivo HbO₂ saturation curves. Lateral shifts of the saturation curve were produced by altering the carbon dioxide tension (PCO₂) of the suffusion solution from 32 to 10 mm Hg, and from 32 to 75 mm Hg. Hill's equation for the HbO₂ saturation curves was used to analyze the % HbO₂ and PO₂ data pairs. For each value of suffusion solution PCO₂, P₅₀ was determined and yielded values of 25 ± 3, 30 ± 3, and 41 ± 4 mm Hg for solution PCO₂'s of 10, 32, and 75 mm Hg, respectively. The in vivo values are qualitatively in agreement with predictions from published HbO₂ saturation curves, although the predicted P₅₀ during suffusion with the hypocapnic solution (PCO₂ = 10 mm Hg) was somewhat higher than expected. The sustained vasodilation produced by adenosine did not in itself lead to a statistically significant change in P₅₀ between normal and dilated arterioles. A pronounced longitudinal decrease in PO₂ from large to small arterioles with an accompanying fall in % HbO₂ was observed in all experiments. This longitudinal gradient in arteriolar oxygen content confirms and extends the previous reports of a progressive decline in precapillary PO₂. In addition, evidence is presented which suggests the existence of a precapillary longitudinal gradient in PCO₂.     

Effect of venous and lymphatic congestion on lymph capillary pressure of the skin in healthy volunteers and patients with lymph edema

The aim of the present study was to assess the influence of venous and lymphatic congestion on lymph capillary pressure (LCP) in the skin of the foot dorsum of healthy volunteers and of patients with lymph edema. LCP was measured at the foot dorsum of 12 patients with lymph edema and 18 healthy volunteers using the servo-nulling technique. Glass micropipettes (7-9 microm) were inserted under microscopic control into lymphatic microvessels visualized by fluorescence microlymphography before and during venous congestion. Venous and lymphatic congestion was attained by cuff compression (50 mm Hg) at the thigh level. Simultaneously, the capillary filtration rate was measured using strain gauge plethysmography. The mean LCP in patients with lymph edema increased significantly (p < 0.05) during congestion (15.7 +/- 8.8 mm Hg) compared to the control value (12.2 +/- 8.9 mm Hg). The corresponding values of LCP in healthy volunteers were 4.3 +/- 2.6 mm Hg during congestion and 2.6 +/- 2.8 mm Hg during control conditions (p < 0.01). The mean increase in LCP in patients with lymph edema was 3.4 +/- 4.1 mm Hg, and 1.7 +/- 2.0 mm Hg in healthy volunteers (NS). The maximum spread of the lymph capillary network in patients increased from 13.9 +/- 6.8 mm before congestion to 18.8 +/- 8.2 mm during thigh compression (p < 0.05). No increase could be observed in healthy subjects. In summary, venous and lymphatic congestion by cuff compression at the thigh level results in a significant increase in LCP in healthy volunteers as well as in patients with lymph edema. The increased spread of the contrast medium in the superficial microlymphatics in lymph edema patients indicates a compensatory mechanism for lymphatic drainage during congestion of the veins and lymph collectors of the leg.     

Association of Capillary Density and Function Measures With Blood Pressure,Fasting Plasma Glucose,and Insulin Sensitivity

J Clin Hypertens (Greenwich). 2010;12:125–135. ^©2009 Wiley Periodicals, Inc. The pathophysiology underlying the association between hypertension and insulin resistance remains unclear. The study purpose was to determine whether reduced capillary density and/or function underlie, and may therefore explain, this association. The study was conducted on 115 black and non-black participants aged 18 to 55 years: 91 with normal blood pressure (systolic blood pressure [SBP] <130 mm Hg) and 24 with mild blood pressure elevation (SBP 130–159 mm Hg). Capillary density and function were quantified using direct capillaroscopy measures. Insulin sensitivity (IS) was estimated using the Quantitative Insulin Sensitivity Check Index (QUICKI). Endothelial function (EF) was measured using strain-gauge plethysmography. Data were analyzed by linear regression adjusted for age, sex, race, and body mass index (BMI). After adjustment for BMI, capillary density and function measures were significant predictors of SBP ( P<.01), fasting plasma glucose (P=.012, P=.03, and P=.004, respectively), and EF (P=.033, P=.001, and P=.009, respectively). However, none of the capillary measures were significant predictors of fasting insulin or IS. These capillaroscopy data demonstrated an association with SBP but not insulin resistance, suggesting that capillary measures are unlikely to explain the association between hypertension and insulin resistance, at least with modest degrees of blood pressure elevation.     

An implantable colloid osmometer. Measurements in subcutis and skeletal muscle of rats.

An implantable colloid osmometer has been developed for measurement of interstitial fluid colloid osmotic pressure (COP_i). Amicon hollow fibres with a cutoff at MW 10,000 were used as a semipermeable membrane. The osmometer has a length of 10–15 mm, an outer diameter of 0.35 mm, and is connected to a pressure transducer via a PE 20 catheter. The equlibration time was about 10 min. In vitro comparison to an ordinary membrane osmometer showed a coefficient of correlation of 0.99. When the osmometer is implanted in tissue, the pressure transducer read the sum of -COP_i (COP measured as a negative hydrostatic pressure, but defined as positive) and interstitial fluid hydrostatic pressure (P_i, positive or negative). In other words, the sum of the “interstitial Starling pressures” is measured directly. After perforation of the membrane, only P_i will be recorded. With intact membrane, implantation in rat subcutis (18 measurements in 8 rats) gave an average pressure of −10.8 (SD, 1.4) mm Hg. In skeletal muscle (17 measurements in 7 rats), the average pressure was −8.6 (SD, 2.1) mm Hg. With perforated membrane, pressures between −1 and 0 were obtained in both tissues, giving a COP_i of about 10 mm Hg in subcutis and 8 mm Hg in muscle. An increased pressure (less negative) could be recorded continuously or by reimplantation, while furosemide diuresis reduced the pressure.     

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.     

Effects of Omapatrilat in Low,Normal, and High Renin Experimental Hypertension

Combined inhibition of neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) produces cardiovascular effects greater than those elicited by selective inhibition of either enzyme alone. Dual metalloprotease inhibitors are single molecules that inhibit both NEP and ACE and produce cardiovascular effects in animal models similar to those elicited by the combination of NEP and ACE inhibitors. The purpose of this study was to determined the duration of antihypertensive activity of the dual metalloprotease inhibitor omapatrilat in rodent models of hypertension. Omapatrilat inhibited NEP (K_i = 9 nmol/L) and ACE (K_i = 6 nmol/L) activities in vitro and inhibited the pressor response to angiotensin I in rats after intravenous administration with a potency and duration of action similar to those of the long acting ACE inhibitor fosinoprilat. After single dose administration, omapatrilat lowered mean arterial blood pressure (aortic catheter) in sodium depleted spontaneously hypertensive rats (high renin model) from 148 ± 5 to 106 ± 3 mm Hg (baseline to 24 h), in deoxycorticosterone acetate–salt hypertensive rats (low renin) from 167 ± 4 to 141 ± 5 mm Hg and in spontaneously hypertensive rats (normal renin) from 162 ± 4 to 138 ± 3 mm Hg (P < .05 at 24 h v vehicle in all models). After oral administration, omapatrilat (100 μmol/kg/day) persistently lowered systolic blood pressure (tail cuff) in spontaneously hypertensive rats during 11 days of treatment; at 24 h after dosing on day 12, mean arterial pressure (aortic catheter) was lower (P < .05) in the group receiving omapatrilat (133 ± 5 mm Hg) than in the group receiving vehicle (149 ± 2 mm Hg). The results indicate that omapatrilat is a potent dual metalloprotease inhibitor of NEP and ACE with long lasting, oral antihypertensive effects in low, normal, and high renin models of hypertension. Omapatrilat has the potential to be an effective, broad spectrum antihypertensive agent.     

Fructose feeding increases insulin resistance but not blood pressure in Sprague-Dawley rats

Fructose feeding has been widely reported to cause hypertension in rats, as assessed indirectly by tail cuff plethysmography. Because there are potentially significant drawbacks associated with plethysmography, we determined whether blood pressure changes could be detected by long-term monitoring with telemetry in age-matched male Sprague-Dawley rats fed either a normal or high-fructose diet for 8 weeks. Fasting plasma glucose (171+/-10 versus 120+/-10 mg/dL), plasma insulin (1.8+/-0.5 versus 0.7+/-0.1 microg/L), and plasma triglycerides (39+/-2 versus 30+/-2 mg/dL) were modestly but significantly elevated in fructose-fed animals. Using the hyperinsulinemic euglycemic clamp technique, the rate of glucose infusion necessary to maintain equivalent plasma glucose was significantly reduced in fructose-fed compared with control animals (22.9+/-3.6 versus 41.5+/-2.9 mg/kg per minute; P<0.05). However, mean arterial pressure (24-hour) did not change in the fructose-fed animals over the 8-week period (111+/-1 versus 114+/-2 mm Hg; week 0 versus 8), nor was it different from that in control animals (109+/-2 mm Hg). Conversely, systolic blood pressure measured by tail cuff plethysmography at the end of the 8-week period was significantly greater in fructose-fed versus control animals (162+/-5 versus 139+/-1 mm Hg; P<0.001). Together, these data demonstrate that long-term fructose feeding induces mild insulin resistance but does not elevate blood pressure. We propose that previous reports of fructose-induced hypertension reflect a heightened stress response by fructose-fed rats associated with restraint and tail cuff inflation.     

Effect of the diphosphonate ethane-I-hydroxy-I, I-diphosphonate (EHDP) on hemoglobin oxygen affinity of diabetic and healthy subjects.

In order to study the effect of prolonged elevation of plasma inorganic phosphate (P₁) on red cell metabolism and function, oxyhemolobin dissociation curves (ODC) from zero to full saturation were performed on whole blood from 14 insulintreated, nonacidotic diabetics and 5 healthy volunteers following oral administration of disodium ethane-l-hydroxy-l, l-diphosphonate (EHDP; 20 mg kg^?1 day^?1 or placebo for 28 days. EHDP significantly increased mean P_i (diabetics, 1.18 to 1.67 mmol/liter; P < 0.001; controls 1.14 to 1.69 mmol/liter; P < 0.005 and P₅₀ at in vivo pH of the ODC (diabetics, 25.6 to 26.7 mm Hg, P < 0.025; controls, 27.6 to 29.5 mm Hg, P < 0.02). P_i and P₅₀ were correlated in both diabetics (r = 0.58, P < 0.01) and controls (r = 0.69, P < 0.05). Mean P₅₀ in diabetics was significantly lower than normal in spite of normal red cell 2,3-diphosphoglycerate (2,3-DPG) (diabetics, 15.2μmol/g of Hb; controls, 14.3 μmol/g of Hb). 2,3-DPG increased when the diabetics were on EHDP (15.2 to 16.3 μmol/g of Hb, P < 0.005), while no significant changes occurred in hemoglobin concentration, oxygen saturation, or blood pH. The study emphasizes the importance of P_i on red cell function and indicates that an elevation of P_i tends to counteract the defect in oxygen-release capacity of the red cells in diabetic subjects.     

Interstitial colloid osmotic and hydrostatic pressures in subcutaneous tissue of human thorax

Interstitial colloid osmotic pressure (π_i) of human subcutaneous tissue was measured simultaneously by three different techniques: in fluid collected by implanted nylon wicks or empty wick catheters, and by implantable colloid osmometers. Hydrostatic pressure in interstitial fluid (P_i) was measured by wick catheters and by wick-in-needle technique. The implantations were done at heart level on the side of the thorax in 15 healthy male subjects. They were divided in two groups, one for a direct comparison of the methods and one for a further investigation on the effect of suction in empty wick catheters. In nylon wicks implanted for 60 min, π_i averaged about 16 mm Hg in both groups. In fluid sampled with empty wick catheters, a suction pressure of ?10 cm H₂O, and 60-min implantation time, the mean π_i was 10.5 and 12.9 mm Hg in the first and second group, respectively. Two factors contributed to lowering of π_i in empty wick catheters: dilution of the samples by saline contained in the wick catheter before implantation, and a π_i-lowering effect of suction. Measurements with implantable colloid osmometers averaged 9.8 mm Hg. Mean implantation time was 30 min. However, the π_i value was positively correlated to implantation time and linear extrapolation to 60 min gives π_i values similar to implanted nylon wicks. We therefore conclude that the three methods give the same π_i in the same area of human subcutaneous tissue provided equal implantation time and little or no suction in empty wick catheters. P_i was ?0.2 mm Hg with both wick catheter and wick-in-needle technique.     

Response of canine ileocolonic sphincter to intraluminal acetic acid and colonic distension

The aim was to determine the effect of intraluminal acetic acid and proximal colonic distension on canine ileocolonic sphincter pressure, ileal motility, and coloileal reflux. In six conscious dogs with an isolated ileocolonic loop, basal pressure of the ileocolonic sphincter was similar during ileal perfusion with 100 mM acetic acid at 1 ml/min (mean±sem=18±0.4 mm Hg) and with saline (18±0.5 mm Hg;P=0.81). Discrete clustered ileal contractions were more frequent with acetic acid, however, and when they propagated across the sphincter, sphincter pressure increased from 18±0.4 mm Hg to 36±1.3 mm Hg (P=0.002). Sphincter pressure was also greater during colonic perfusion with acetic acid (32±0.7 mm Hg) than during ileal perfusion with acetic acid or saline (P<0.017). Moreover, sphincter pressure gradually increased as the colon was distended with saline (slope=0.8 mm Hg/cm H₂O,P<0.017) or acetic acid (slope=0.5 mm Hg/cm H₂O,P<0.017), but the increase did not prevent coloileal reflux. In conclusion, ileal clustered contractions, colonic perfusion of acetic acid, and colonic distension all increased canine ileocolonic sphincter pressure.     

Influence of vascular muscle tone upon isogravimetric capillary pressure

Isogravimetric capillary pressure (P_ci) was determined in vitro in the perfused, skinned dog forearm preparation. Two procedures were employed. In one, arterial pressure was lowered before venous pressure was elevated (A, V sequence). In the second procedure, venous pressure was elevated before arterial pressure was lowered (V,A sequence). If the composition of the blood perfusing the preparation remains constant, the capillary pressure determined by both procedures should be equal. However, it was found that the A,V sequence resulted in a lower estimate of P_ci and a higher value for venous resistance than did the V,A sequence. A deliberate filtration of 2–5 g of fluid elevated the mean P_ci values but did not abolish the A,V and V,A difference. Addition of KCN to relax smooth muscle, yielded a single P_ci value for both the A,V and V,A sequences. This value was higher than the values obtained prior to KCN treatment. Moreover, A,V and V,A KCN isogravimetric sequences exhibited no differences in venous resistance or venous pressure at comparable levels of flow, whereas differences were present before treatment with KCN. Therefore, it was concluded that the double set of data in the untreated state was due to the presence of active and/or myogenic postcapillary smooth muscle. Because of the influence of venous smooth muscle, most estimates of P_ci underestimate plasma colloid osmotic pressure. Moreover, calculations of venous resistance employing this P_ci would be underestimated, since these calculations involve P_ci.     

Limb venous compliance responses to lower body negative pressure in humans with high blood pressure

This study tested the hypothesis that limb venous responses to baroreceptor unloading are altered in individuals with high blood pressure (HBP) compared with normotensive (NT) controls. Calf venous compliance was assessed in 20 subjects with prehypertension and stage-1 hypertension (mean arterial pressure, MAP: 104±1?mm?Hg) and 13 NT controls (MAP: 86±2?mm?Hg) at baseline and during lower body negative pressure (LBNP), using venous occlusion plethysmography. Baroreflex sensitivity (BRS) was measured using the sequence technique and total peripheral resistance (TPR) was estimated from finger plethysmography. Baseline venous compliance was not different between groups, but the HBP group had lower baseline lnBRS (2.22±0.14 vs 2.7±0.18?ms?mm?Hg(-1)) and greater baseline TPR (3828±138 vs 3250±111?dyn?sec(-1)?cm(-5)?m(2), P<0.05). Calf venous compliance was reduced in response to LBNP only in the NT group (P<0.05). The HBP group had a greater increase in TPR (ΔTPR) compared with the NT group (+1649±335 vs +718±196?dyn?sec(-1)?cm(-5)?m(2), P<0.05). In conclusion, the early stages of hypertension are characterized by an attenuated venoconstrictor response to baroreceptor unloading, which may compensate for an exaggerated vasoconstrictor response and protect against further increases in blood pressure.     

Influence of venous pressure on plasma-lymph transport in the dog's paw: Convective and dissipative mechanisms

Studies were carried out to evaluate convective and dissipative (diffusion and vesicular) components of blood-lymph transport of large molecules in the dog's paw. Steady-state lymph flow rates (L) and lymph/plasma concentration ratios (R) were measured for six plasma proteins and for exogenous Dextran (MW 110,000). Measurements were made under control conditions and at two to four elevated levels of venous pressure (PV). Below 45 mm Hg, L increased linearly with PV, and R fell progressively, but less than in proportion to flow: the product LR (clearance) increased. Above 45 mm Hg, there was a time-dependent increase in R at constant or increasing L, which was greater for larger molecules and indicated an alteration of permeability. From values of L and R obtained for the normal permeability state, solvent drag coefficients (σ_f) and permeability surface area products (PS) were calculated according to the principles of irreversible thermodynamics and hydrodynamics. Values obtained for σ_f ranged from 0.82 for serum albumin to 0.95 for Dextran 110. At control levels of lymph flow, convection (solvent drag) accounted for about 30% of the total flux of albumin into lymph. With elevation of venous pressure, the contribution of convective flux increased.     

The effects of enoximone (MDL-17043) on forearm venous circulation in healthy volunteers and patients with heart failure

Summary The effect of intravenous enoximone on forearm venous circulation was studied in ten healthy volunteers (group A) and in ten patients with NYHA class III–IV congestive heart failure (group B). Distensibility of the forearm capacitance vessels was assessed from pressure-volume curves by venous occlusion plethysmography using a mercury-in-rubber strain gauge. Three recordings each at 3-min intervals were obtained before the infusion and again 20 min after completion of the infusion. Venous volume changes (VV) at congesting pressures of 10, 20, and 30 mmHg before and after enoximone were compared. Forearm muscle blood flow was also measured by venous occlusion plethysmography; electrocardiogram, heart rate, and cuff blood pressure were recorded throughout. Enoximone at a dose of 1 mg/kg body weight was infused over 10 min through a peripheral vein in group A and via a central line in group B. In group A, the effect of the injection vehicle was also assessed.VV₁₀, VV₂₀, and VV₃₀ did not differ from baseline values after enoximone in both groups A and B. The vehicle caused a small but significant degree of venoconstriction in group A (VV₂₀, 2.64±0.9 to 2.48±0.83 ml/100 ml,P<0.05; VV₃₀, 3.47±1.27 to 3.33±1.20 ml/100 ml,P<0.05), which could be explained by an acute response to local pain from the infusion. This effect was not evident following enoximone, perhaps as a result of its counterbalancing vasodilating action to venoconstriction induced by acute pain. Muscle blood flow increased in both groups (group A, 3.05±0.33 to 4.62±1.32 ml/100 ml/min,P<0.01; group B, 2.33±0.93 to 3.13±0.95 ml/100 ml/min,P<0.02) after enoximone and did not change in group A after vehicle (3.08±1.50 to 2.73±0.87,P—not significant).It is concluded that enoximone at the dose studied does not exert appreciable effects on the forearm venous system in normal subjects or in patients with heart failure.     

Radionuclide analysis of the forearm venous pressure-volume relationship: response to nitroglycerin

By means of equilibrium radionuclide forearm venous occlusion plethysmography, we studied 12 adult men without heart failure. By using stepwise increases in venous occlusion pressure (0, 10, 20, and 30 mm Hg), we found that the relationship between venous cuff pressure and forearm radionuclide volume was consistently linear (r greater than 0.985). When sublingual nitroglycerin (NTG) was administered (0.8 mg), the venous pressure-volume relationship was consistently shifted rightward (reducing the slope and increasing the intercept). This resulted in large increases in venous capacitance, as shown by other workers using alternative techniques. Increased venous distensibility due to NTG was caused by an entire shift of the venous pressure-volume relationship rather than increased capacitance at one occlusion pressure. Equilibrium radionuclide venous occlusion plethysmography is a sensitive way to characterize venous pressure-volume relations. In addition, by using radionuclide blood pool component imaging to evaluate venous compliance, concern over fluid transudation seen with standard strain gauge venous plethysmographic techniques can be ignored, particularly at higher occlusion pressures.     

Transcapillary protein leakage and fluid movement: Effect of venous pressure

The effect of elevating venous pressure (ΔP_v) on the transcapillary escape of albumin (Q_T) in control and papverinized gracilis muscles perfused at constant flow was determined by means of direct monitoring of the rate of accumulation of tissue ¹²⁵I-labeled albumin radioactivity. Simultaneously, transcapillary fluid movement (FM) was assessed volumetrically. Under control isovolumetric conditions, Q_T = 2.25 mg/min · 100 g. In addition to causing an FM of 0.03 ml/min · 100 g · mm Hg, increasing P_v enhanced Q_T by 0.06 mg/min · 100 g · mm Hg. Papverinization itself decreased Q_T to 2.0 mg/min · 100 g and affected FM only slightly. However, the superposition of P_v elevation caused a FM of 0.008 ml/min · 100 g · mm Hg and resulted in Q_T increasing by 0.29 mg/min · 100 g · mm Hg. The results of this study indicate that Q_T is sensitive to changes in microvascular hemodynamics, and thus changes in microvascular pressure may affect FM in two ways, first by increasing the transcapillary pressure gradient and second by augmenting Q_T which may superimpose an oncotic adjunct to FM.     

Diastolic myocardial wall stiffness of the left ventricle in chronic pressure overload

Five dogs were instrumented with a left ventricular (LV) micromanometer,pairs of ultrasonic crystals to measure L V short axis and LV wall thickness and an inflatable cuff around the ascendingaorta. Wall stress, midwall strain and strain rate were calculatedat rest, after acute pressure elevation, and one, two and threeweeks as well as 24 h after release of aortic constriction.Myocardial wall stiffness and viscosity were determined froma viscoelastic stress-strain model. Reference values at zeropressure were determined in all five dogs. LV end-diastolic pressure increased from 7 mm Hg at rest to25 mm Hg after acute pressure elevation, to 18 mm Hg after twoweeks and decreased to 16 mm Hg after three weeks of pressureelevation, and 11 mm Hg at release of aortic constriction. LV peak systolic pressure increased from 140 mm Hg at rest to218 mm Hg after acute pressure elevation, to 227 mm Hg afterthree weeks of pressure elevation and returned to normal (143mm Hg) after cuff release. Diastolic myocardial wall stiffnessshowed no change from 23 at rest to 19 after acute pressureelevation, but increased to 47 after one and 81 after two weeks,and it decreased to 50 after three weeks and 45 after cuff release.Myocardial viscosity increased from 0.1 at rest to 3.0 afteracute pressure elevation and remained elevated during chronicpressure elevation. The reference values at zero filling pressureshowed an increase in LV short axis (creep) from 25.6 mm atrest to a maximum of 28.9 mm after one and two weeks of pressureelevation and then decreased to 27.0 mm after three weeks. LVwall thickness at zero pressure increased from 12.8 mm at restto 13.7 mm after three weeks of pressure elevation and remainedelevated after cuff release (13.8 mm). Thus, diastolic myocardial wall stiffness increased during theinitial stages of chronic pressure overload during ventriculardilatation, but decreased when dilatation regressed and concentrichypertrophy developed. Myocardial viscosity was increased duringboth acute and chronic pressure overload. It is suggested thatthe early increase in myocardial stiffness may be more importantlyrelated to ventricular dilatation with creep than to wall hypertrophyper se.