Muscle blood flow response to contraction: influence of venous pressure.

The skeletal muscle pump is thought to be at least partially responsible for the immediate muscle hyperemia seen with exercise. We hypothesized that increases in venous pressure within the muscle would enhance the effectiveness of the muscle pump and yield greater postcontraction hyperemia. In nine anesthetized beagle dogs, arterial inflow and venous outflow of a single hindlimb were measured with ultrasonic transit-time flow probes in response to 1-s tetanic contractions evoked by electrical stimulation of the sciatic nerve. Venous pressure in the hindlimb was manipulated by tilting the upright dogs to a 30 degrees angle in the head-up or head-down positions. The volume of venous blood expelled during contractions was 2.2 +/- 0.2, 1.6 +/- 0.2, and 1.4 +/- 0.2 ml with the head-up, horizontal, and head-down positions, respectively. Although altering hindlimb venous pressure influenced venous expulsion during contraction, the increase in arterial inflow was similar regardless of position. Moreover, the volume of blood expelled was a small fraction of the cumulative arterial volume after the contraction. These results suggest that the muscle pump is not a major contributor to the hyperemic response to skeletal muscle contraction.     

The relationship of umbilical glucose uptake to uterine blood flow

In 30 experiments performed on 5 pregnant sheep, the rate of glucose transfer from the placenta to fetus via the umbilical circulation was measured while varying uterine blood flow by means of a cuff-type occluder and while maintaining a constant maternal glucose concentration by means of a 'glucose clamp'. Over the range of uterine blood flows obtained, there was no significant effect on the simultaneously measured umbilical blood flow. Fetal glucose uptake and arterial glucose concentration remained normal as the uterine blood flow rate decreased from 600 to 300 ml per min per kg of fetus. At blood flow rates less than 300 ml.min-1.kg-1, the fetal glucose uptake decreased and became negative in one instance while the arterial glucose concentration became variable and markedly increased in 2 animals. This increase in fetal glucose concentration was associated with a decrease in the uterine oxygen delivery rate, a decrease in fetal oxygen content and a decrease in fetal oxygen uptake. These observations support the concept that fetal glucose metabolism is altered by severe hypoxia and demonstrate that there is little effect of uterine blood flow on fetal glucose uptake in the normal physiological range.     

Localized real time blood flow measurements

A novel method for real time, localized, flow measurements is applied to blood flow in human fingers. Results for arterial and venous flow in normal subjects and patients with abnormal blood circulation are presented. Effects of blood flow regulation by the autonomic nervous system have been observed. Stricture of the digital arteries could be clearly demonstrated in a patient with Raynaud's phenomenon. Experimental signals due to pulsatile flow in a model system can be simulated in a quantitative way. The calibration, however, depends on the actual spin-spin relaxation time and the shape of the pulsatile flow vs. time curve. Due to these limitations, the volume flow rate can be measured with a relative error of approximately +/- 25%.     

The relationship between the longitudinal pressure gradient and the blood flow velocity in the canine superior vena cava

In the superior vena cava of anaesthetized open chest dogs the axial pressure gradient (delta P) was measured simultaneously with the blood flow velocity (V) under a variety of preload conditions. Both delta P and V curves showed distinct systolic and diastolic waves. Peak delta P ranged between 26 and 93 P/cm (0.2-0.7 mm Hg/cm) and V varied between 0.095 and 0.19 m/s. Peak systolic delta P, but not peak diastolic delta P was significantly linearly correlated to respectively peak systolic V and peak diastolic V. The shape of delta P and V curves corresponded fairly well but variations of delta P preceded the variations of V. Both the shape correspondence and the phase lag between delta P and V were evaluated by means of the normalized cross-correlation technique. During volume expansion the shape correspondence improved and the phase lag decreased. It is concluded that the transient vena caval blood velocity variations are directly related to the pulsatile axial pressure gradient.     

Role of potassium in regulating blood flow and blood pressure

Unlike sodium, potassium is vasoactive; for example, when infused into the arterial supply of a vascular bed, blood flow increases. The vasodilation results from hyperpolarization of the vascular smooth muscle cell subsequent to potassium stimulation by the ion of the electrogenic Na+-K+ pump and/or activating the inwardly rectifying Kir channels. In the case of skeletal muscle and brain, the increased flow sustains the augmented metabolic needs of the tissues. Potassium ions are also released by the endothelial cells in response to neurohumoral mediators and physical forces (such as shear stress) and contribute to the endothelium-dependent relaxations, being a component of endothelium-derived hyperpolarization factor-mediated responses. Dietary supplementation of potassium can lower blood pressure in normal and some hypertensive patients. Again, in contrast to NaCl restriction, the response to potassium supplementation is slow to appear, taking approximately 4 wk. Such supplementation reduces the need for antihypertensive medication. "Salt-sensitive" hypertension responds particularly well, perhaps, in part, because supplementation with potassium increases the urinary excretion of sodium chloride. Potassium supplementation may even reduce organ system complications (e.g., stroke).     

Digital defects induced by vasodilating agents: relationship to reduction in uteroplacental blood flow

The effects of nifedipine (40-100 mumol/kg), nitrendipine (40 and 80 mumol/kg), hydralazine (381 and 763 mumol/kg), felodipine (12 mumol/kg), and the pharmacologically inactive first-step metabolite of felodipine, H152/37 (80 mumol/kg) were studied in rabbits (New Zeeland White) after oral administration on day 16 of gestation. The vasodilating drugs--nifedipine, nitrendipine, felodipine, and hydralazine--all induced digital defects in the fetuses. The defects consisted of a reduction, absence, or abnormal structure of the distal phalanx of especially the fourth digit on the hind paw(s). Histologically, a disturbed differentiation of the cartilage, and secondarily also of the ossification centre and joint structure of the distal phalanx, was observed. In contrast, no digital abnormalities were observed after administration of vehicle or H152/37. The findings that vasodilators with different structures, like dihydropyridines and hydralazine, induced the same type of digital defects strongly suggest that the observed phalangeal defects are secondary to pharmacological action, and not related to chemical structure. A decrease in uteroplacental blood flow, caused by excessive hypotension, is discussed as the most probable mechanism underlying the observed defects.     

Effects of pleural pressure and abdominal pressure on diaphragmatic blood flow

Alveolar transfer of prostaglandin E2 (PGE2) was characterized in isolated perfused guinea pig lungs (n = 19) by measuring radioactivity appearing in the venous effluent during 30 min after intratracheal instillation of [3H]PGE2, [14C]-mannitol, and [125I]iodoantipyrine. Recovery of lipid-soluble [125I]iodoantipyrine [91 +/- 3% (SE)] after 30 min was used to estimate total 3H and 14C delivered to the exchanging region of lung at time 0. In seven control lungs, 58 +/- 4% of [14C]mannitol and 16 +/- 4% of [3H]PGE2 was retained 10 min after instillation. Neither perfusion with diphloretin phosphate (10 micrograms/ml; n = 4) nor hypothermia (5 degrees C; n = 5) significantly affected the amount of [14C]mannitol retained; however, [3H]PGE2 remaining in these lungs increased significantly to 36 +/- 4 and 53 +/- 2%, respectively. Addition of unlabeled PGE2 (200 micrograms) to the instilled solution (n = 3) increased retention of both [14C]mannitol (80 +/- 3%) and [3H]PGE2 (65 +/- 4%). Alveolar transfer of [3H]PGE2 was calculated as the difference in percent retention of [14C]mannitol and [3H]PGE2 and normalized to that of [14C]mannitol. After 10 min, alveolar transfer of [3H]PGE2 was 71 +/- 8% in control lungs but was decreased to 26 +/- 7, 10 +/- 5, and 19 +/- 6% by diphloretin phosphate, hypothermia, or unlabeled PGE2, respectively. These data suggest that alveolar clearance of PGE2 involves a saturable drug- and temperature-sensitive process.     

Effects of airway pressure on bronchial blood flow

We studied the effects of increased airway pressure caused by increasing levels of positive end-expiratory pressure (PEEP) on bronchial arterial pressure-flow relationships. In eight alpha-chloralose-anesthetized mechanically ventilated sheep (23-27 kg), the common bronchial artery, the bronchial branch of the bronchoesophageal artery, was cannulated and perfused with a pump. The control bronchial blood flow (avg 12 +/- 1 ml/min or 0.48 ml X min-1 X kg-1) was set to maintain mean bronchial arterial pressure equal to systemic blood pressure. Pressure-flow curves of the bronchial circulation were measured by making step changes in bronchial blood flow, and changes in these curves were analyzed with measurements of the pressure at zero flow and the slope of the linearized curve. The zero-flow pressure represents the effective downstream pressure, and the slope represents the resistance through the bronchial vasculature. At a constant bronchial arterial pressure of 100 mmHg, an 8 mmHg increase in mean airway pressure caused a 40% reduction in bronchial blood flow. Under constant flow conditions, increases in mean airway pressure with the application of PEEP caused substantial increases in bronchial arterial pressure, averaging 4.6 mmHg for every millimeters of mercury increase in mean airway pressure. However, bronchial arterial pressure at zero flow increased approximately one-for-one with increases in mean airway pressure. Thus the acute sensitivity of the bronchial artery to changes in mean airway pressure results primarily from changes in bronchovascular resistance and not downstream pressure.     

A simple coronary blood flow model to study the collateral flow index

Biomechanics and Modeling in Mechanobiology - In this work, we present a novel modeling framework to investigate the effects of collateral circulation into the coronary blood flow physiology. A...     

Cerebral blood flow velocity response to induced and spontaneous sudden changes in arterial blood pressure

The influence of different types of maneuvers that can induce sudden changes of arterial blood pressure (ABP) on the cerebral blood flow velocity (CBFV) response was studied in 56 normal subjects (mean age 62 yr, range 23-80). ABP was recorded in the finger with a Finapres device, and bilateral recordings of CBFV were performed with Doppler ultrasound of the middle cerebral arteries. Recordings were performed at rest (baseline) and during the thigh cuff test, lower body negative pressure, cold pressor test, hand grip, and Valsalva maneuver. From baseline recordings, positive and negative spontaneous transients were also selected. Stability of PCO2 was monitored with transcutaneous measurements. Dynamic autoregulatory index (ARI), impulse, and step responses were obtained for 1-min segments of data for the eight conditions by fitting a mathematical model to the ABP-CBFV baseline and transient data (Aaslid's model) and by the Wiener-Laguerre moving-average method. Impulse responses were similar for the right- and left-side recordings, and their temporal pattern was not influenced by type of maneuver. Step responses showed a sudden rise at time 0 and then started to fall back to their original level, indicating an active autoregulation. ARI was also independent of the type of maneuver, giving an overall mean of 4.7 +/- 2.9 (n = 602 recordings). Amplitudes of the impulse and step responses, however, were significantly influenced by type of maneuver and were highly correlated with the resistance-area product before the sudden change in ABP (r = -0.93, P < 0.0004). These results suggest that amplitude of the CBFV step response is sensitive to the point of operation of the instantaneous ABP-CBFV relationship, which can be shifted by different maneuvers. Various degrees of sympathetic nervous system activation resulting from different ABP-stimulating maneuvers were not reflected by CBFV dynamic autoregulatory responses within the physiological range of ABP.     

An instrument to evaluate the time dependent flow properties of blood at moderate shear rates

The rheology of blood is characterized by shear thinning, viscoelasticity, and thixotropy. Its rheological evaluation is usually accomplished using a torque balance technique during rotational viscometry. Because a stable torque balance does not develop instantly, studies of thixotropy and viscoelasticity of blood have usually been carried out only at low shear rate where their development is slow enough to be monitored accurately. The torque balance technique may be converted from static to dynamic by incorporating the rate of change of sensing system angular momentum. We have modified our Couette viscometer, adding a computer-controlled stepping motor and a second digital voltmeter. The latter is used to determine the angular position of the sensing system every 25 or 50 msec. The new approach allows rapid observation of the development and disappearance of shear stress, enabling us to examine the transient behavior of blood at moderate shear rate (1 to 100 inverse seconds). The transient flow behavior of blood at moderate shear rate is most easily compared directly with the behavior of Newtonian fluids. We present information about the response of our system using a torque balance observation rate of 20 per second. Blood's viscoelasticity is observed to fall substantially as shear rate rises, while its thixotropic transient excess stress rises steadily with increasing shear rate.