Muscle dysfunction during exercise of a single skeletal muscle in rats with congestive heart failure is not associated with reduced muscle blood supply.

AIM: Inadequate muscle blood flow is a possible explanation for reduced fatigue resistance in patients with congestive heart failure (CHF). METHODS: In rats with post-infarction CHF we electrically stimulated the soleus muscle (SOL) in situ with intact blood supply. Contractile properties, blood flow, high-energy phosphates and metabolites were measured during 30 min of intermittent stimulation, and in addition capillarization of SOL was recorded. RESULTS: During stimulation, SOL contracted more slowly in rats with CHF compared with sham-operated rats. However, the blood flow in SOL was unaltered and capillary density was maintained in CHF rats. Further, the content of ATP, ADP, AMP, NAD, CrP, P(i) and lactate in SOL was not different between the groups. CONCLUSION: The cause of contractile dysfunction in a single exercising skeletal muscle in rats with CHF cannot be explained simply by reduced blood supply. In addition, absence of changes in high-energy phosphates and metabolites indicate that the oxidative metabolism of SOL is intact in rats with CHF.

Human cytokines modulate arterial vascular tone via endothelial receptors.

Only a few cytokines have been tested for their possible role in modulating vascular function. Moreover, no direct effect of cytokines on vascular tone has yet been thoroughly studied. We therefore examined whether a wide range of well-defined cytokines could directly affect vascular tone in isolated human arterial and venous segments from various organs. We found that the cytokines stem cell factor (maximal response with 1 mM), granulocyte colony-stimulating factor (0, 1 mM) and erythropoietin (1 mM) relaxed, while tumor necrosis factor alpha (0.1 mM), interleukin (IL) 6 (10 mM) and IL-10 (0.1 mM) induced contraction of arterial but not of venous segments. The cytokines (maximal concentration tested was 1 mM) IL-3, IL-5, IL-13, macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor had no apparent effects on either arterial or venous tone. These vascular effects were endothelium-dependent as denuded arteries did not respond to any cytokine, and inhibition of nitric oxide synthase or endothelin receptor A abrogated the cytokine-induced changes in vascular tone. With immunohistochemistry we found receptors for the active cytokines on the arterial endothelium. In conclusion, several cytokines may modulate arterial vascular tone via endothelium-dependent mechanisms. Therefore cytokines might significantly modify blood supply to inflamed or ischemic tissues with elevated local concentrations of cytokines.

Effect of particles on sheep lung hemodynamics parallels depletion and recovery of intravascular macrophages.

We previously showed in newborn lambs that the pulmonary hemodynamic responses to foreign particulate matter (liposomes; Monastral blue) developed in parallel with the maturation of the pulmonary intravascular macrophage system. We now report our use of the liposome-encapsulated heavy-metal-chelating agent dichloromethylene diphosphonate to deplete the intravascular macrophages of small lambs. Functionally and by quantitative histology, we depleted the vast majority of the intravascular macrophages (71% by Monastral blue particle retention, n = 22; 77% by histology; n = 2). Depletion success increased to > 90% as we optimized the liposome-depletion regime. Recovery of the lung hemodynamic response began within 3 days. By 2 wk, the functional responses had fully recovered (n = 8), and, according to quantitative histology, the macrophage population (n = 2) had recovered 65%. Macrophage depletion in lambs is relatively inexpensive and easy to achieve. It is a safe procedure and is followed by full recovery in approximately 2 wk, provided that an aseptic technique is used to prevent bacteremia.

Distribution of ouabain-binding sites along the dog nephron.

To quantify the relative amount of ouabain bound to different segments of the nephron after in vivo injection of the drug, an autoradiographic (ARG) study was carried out. After intrarenal injection of [3H]ouabain (120 nmol kg-1 body wt, 0.9-1.2 Ci mol-1) to intact kidneys of three anaesthetized dogs, 69-89% of renal Na,K-ATPase activity was inhibited. Sodium reabsorption decreased by 21-54%. Sections for ARG were obtained from tissue slices frozen in liquid Freon, freeze-dried and embedded in resin. Almost no loss of activity occurred during processing and background activity was negligible after 23-36 days' exposure. The density of [3H]ouabain grains per mu 2 of tubular walls was 3.8 times higher over medullary ascending limbs of Henle's loop (MAL) and distal cortical tubules (DT) as compared to proximal tubules (PT). In terms of tubular length, the grain density of MAL exceeded that of PT by merely 35% since the cross-sectional area of the MAL was only 25% of that of PT. In DT, grain density in terms of tubular length was lower than in PT by 10%. Based on previous estimate of the absolute ouabain-binding capacity in MAL of 60 fmol mm-1 tubule, the ouabain-binding capacity in PT and DT would equal 45 and 40 fmol mm-1, respectively. From composite microphotographs, the relative volume of PT was estimated to be 42% of the total renal volume. This means that 47% of the total renal ouabain-binding sites are localized to PT, whereas MAL and DT together contain 51%.

Interstitial fluid pressure in the isolated perfused rabbit lung.

Interstitial fluid pressure was measured in nine isolated perfused rabbit lungs with the servonull micropipette method. Bevelled glass micropipettes, with tip diameter 2-6 micrometers (o.d.) were inserted 2-6 mm into the left lung. At alveolar pressures of 3 to 5 cm H2O we found mean interstitial fluid pressures of 1.0 (SD 1.0) and 1.6 (SD 1.0) cm H2O relative to pleural pressure in the upper (n = 19) and lower (n = 21) lobes respectively. The vertical distance between the measuring sites in the upper and lower lobes was about 3 cm. Net filtration caused by elevated left atrial pressure caused practically no change in interstitial fluid pressure. Increased alveolar pressure either increased or decreased interstitial fluid pressure. The measured pressures probably represent interstitial fluid pressure in alveolar junctions or in the interstitium around small pulmonary arteries or veins. We conclude that interstitial fluid pressure in these sites is between alveolar and pleural pressure, and that it is only moderately affected by changes in alveolar pressure. The interstitial compliance appears to be high and there seem to be little or no vertical gradients in interstitial fluid pressure within the lung.

Vascular resistance in atelectatic lungs: effects of inhalation anesthetics.

We have investigated the relative contribution of mechanical obstruction and hypoxia-induced vasoconstriction to the increased pulmonary vascular resistance (PVR) in atelectatic lungs. For this purpose we have utilized the previous observation that inhalation anesthetics inhibit the vasoconstrictor response to pulmonary hypoxia. The effects of halothane, enflurane and ether on PVR in atelectatic lungs have been explored. Two pairs of isolated rat lungs were perfused in series at constant flow. One of the preparations was made atelectatic by airway occlusion subsequent to ventilation with a high PO2 gas (95% O2). Ventilation of the other preparation continued with hypoxic gas (2% O2), resulting in a gradual increase in PVR in both preparations. When maximum PVR was reached, one of the above inhalation anesthetics was administered to the atelectatic lungs via the ventilated lung preparation. This caused a dose-dependent, reversible reduction of PVR. The same effect was observed when pulmonary arterial PO2 was increased (greater than 66.5 kPa). Histological examination revealed that two out of four preparations were completely atelectatic 1 h after airway occlusion, whereas atelectasis was nearly complete in the other two. In two groups, airways were occluded for 1 h. In the first group PVR increased to 163% (median) above baseline level, as found during ventilation with high PO2. High arterial PO2 reduced PVR in the atelectatic lungs to 50% (median) above baseline, whereas papaverine induced a further PVR reduction, to 7% (median) above baseline. In the other group, papaverine was given before airway occlusion, and PVR increased to 10% (median) above baseline. Comparison of the two groups shows that mechanical obstruction accounts for about 6% (10/163) of the overall rise in PVR during atelectasis.

Qualitative and quantitative studies of the capillary structure in the rete mirabile of the eel, Anguilla vulgaris L.

The capillaries of the counter-current capillary organ, rete mirabile, have been studied by light microscopy and electron microscopy. The vasculature of this rete was found to have a cross-sectional area of about 5.25 mm2, and it consisted of 34,000 efferent (=arterial) and 22,000 afferent (=venous) capillaries. The total surface area was the same for the two types of capillaries. The capillary endothelial cells showed numerous pinocytotic vesicles, scattered giant vacuoles and cytoplasmic extrusions (microvilli) at the luminal surface. The majority of the intercellular junctions appeared to have patent gaps with a width of 110-120 A. The arterial capillaries appeared in many ways to be morphologically similar to skeletal muscle capillaries of mammals, whereas the fenestrated venous capillaries resembled those in the intestinal mucosa of mammals. Measurements of the ionic composition of the rete tissue indicated that the endothelial cells contained much less K+ than other cells, the rete containing approximately equimolar amounts of K+ and Na+. The functional significance of the structural and chemical observations are discussed.