Blood osmolality during in vivo changes of CO2 pressure

In 16 experiments male subjects, age 22.4 +/- 0.5 (SE) yr, inspired CO2 for 15 min (8% end-tidal CO2) or hyperventilated for 30 min (2.5% end-tidal CO2). Osmolality (Osm) and acid-base status of arterialized venous blood were determined at short intervals until 30 min after hypo- and hypercapnia, respectively. During hypocapnia [CO2 partial pressure (PCO2) -2.31 +/- 0.32 kPa (-17.4 Torr), pH + 0.19 units], Osm decreased by 3.9 +/- 0.3 mosmol/kg H2O; during hypercapnia [PCO2 + 2.10 +/- 0.28 kPa (+15.8 Torr), pH -0.12 units], Osm increased by 5.8 +/- 0.7 mosmol/kg H2O. Presentation of the data in Osm-PCO2 or Osm-pH diagrams yields hysteresis loops probably caused by exchange between blood and tissues. The dependence of Osm on PCO2 must result mainly from CO2 buffering and therefore from the formation of bicarbonate. In spite of the different buffer capacities in various body compartments, water exchange allows rapid restoration of osmotic equilibrium throughout the organism. Thus delta Osm/delta pH during a PCO2 jump largely depends on the mean buffer capacity of the whole body. The high estimated buffer value during hypercapnia (38 mmol/kg H2O) compared with hypocapnia (19 mmol/kg H2O) seems to result from very strong muscle buffering during moderate acidosis.     

Cerebral blood flow during orthostasis: role of arterial CO2

Reductions in end-tidal Pco(2) (Pet(CO(2))) during upright posture have been suggested to be the result of hyperventilation and the cause of decreases in cerebral blood flow (CBF). The goal of this study was to determine whether decreases in Pet(CO(2)) reflected decreases in arterial Pco(2) (Pa(CO(2))) and their relation to increases in alveolar ventilation (Va) and decreases in CBF. Fifteen healthy subjects (10 women and 5 men) were subjected to a 10-min head-up tilt (HUT) protocol. Pa(CO(2)), Va, and cerebral flow velocity (CFV) in the middle and anterior cerebral arteries were examined. In 12 subjects who completed the protocol, reductions in Pet(CO(2)) and Pa(CO(2)) (-1.7 +/- 0.5 and -1.1 +/- 0.4 mmHg, P < 0.05) during minute 1 of HUT were associated with a significant increase in Va (+0.7 +/- 0.3 l/min, P < 0.05). However, further decreases in Pa(CO(2)) (-0.5 +/- 0.5 mmHg, P < 0.05), from minute 1 to the last minute of HUT, occurred even though Va did not change significantly (-0.2 +/- 0.3 l/min, P = not significant). Similarly, CFV in the middle and anterior cerebral arteries decreased (-7 +/- 2 and -8 +/- 2%, P < 0.05) from minute 1 to the last minute of HUT, despite minimal changes in Pa(CO(2)). These data suggest that decreases in Pet(CO(2)) and Pa(CO(2)) during upright posture are not solely due to increased Va but could be due to ventilation-perfusion mismatch or a redistribution of CO(2) stores. Furthermore, the reduction in Pa(CO(2)) did not fully explain the decrease in CFV throughout HUT. These data suggest that factors in addition to a reduction in Pa(CO(2)) play a role in the CBF response to orthostatic stress.     

Contribution of arterial Windkessel in low-frequency cerebral hemodynamics during transient changes in blood pressure

The Windkessel properties of the vasculature are known to play a significant role in buffering arterial pulsations, but their potential importance in dampening low-frequency fluctuations in cerebral blood flow has not been clearly examined. In this study, we quantitatively assessed the contribution of arterial Windkessel (peripheral compliance and resistance) in the dynamic cerebral blood flow response to relatively large and acute changes in blood pressure. Middle cerebral artery flow velocity (MCA(V); transcranial Doppler) and arterial blood pressure were recorded from 14 healthy subjects. Low-pass-filtered pressure-flow responses (<0.15 Hz) during transient hypertension (intravenous phenylephrine) and hypotension (intravenous sodium nitroprusside) were fitted to a two-element Windkessel model. The Windkessel model was found to provide a superior goodness of fit to the MCA(V) responses during both hypertension and hypotension (R2 = 0.89 ± 0.03 and 0.85 ± 0.05, respectively), with a significant improvement in adjusted coefficients of determination (P < 0.005) compared with the single-resistance model (R2 = 0.62 ± 0.06 and 0.61 ± 0.08, respectively). No differences were found between the two interventions in the Windkessel capacitive and resistive gains, suggesting similar vascular properties during pressure rise and fall episodes. The results highlight that low-frequency cerebral hemodynamic responses to transient hypertension and hypotension may include a significant contribution from the mechanical properties of vasculature and, thus, cannot solely be attributed to the active control of vascular tone by cerebral autoregulation. The arterial Windkessel should be regarded as an important element of dynamic cerebral blood flow modulation during large and acute blood pressure perturbation.     

Pulsatile pressure and flow in arterial stenoses simulated in a mathematical model

This paper presents the detailed pulsatile pressure and flow velocity patterns inside an axis symmetric stenosis model with 75% constriction. The pressure and velocities have been calculated by solving the Navier-Stokes equations by the finite element method, the velocity profile in a straight tube caused by a pulsating driving pressure has been calculated first and then used as a boundary condition for the stenosis calculations. The results of the mathematical simulations of the stenosis model have been obtained in terms of velocity vectors, streamlines and isobars at 16 different instances in time, each 15 degrees apart during a cardiac cycle. The calculated velocity field shows that a vortex is developed at the wall distal to the stenosis as the velocity decreases from the peak systolic value. At the site of the vortex, a local pressure minimum is found due to the conversion of pressure to kinetic energy. When the flow is reversed, the reversal occurs first along the wall, thus forcing the vortex toward the the centre of the tube. As the reverse flow velocity increases, a vortex is also developed at the proximal site of the stenosis.     

Pulsatile pressure and flow in an arterial aneurysm simulated in a mathematical model

The pressure and flow patterns within arterial aneurysms are little known. In the present work the equations describing pulsatile flow, the Navier-Stokes equations, are solved numerically using the finite element method with a computer. The solutions of the Navier-Stokes equations are obtained at 24 points in time during the cardiac cycle. At selected instants in time, the solutions are presented as velocity vectors, streamlines and isobars. The results demonstrate a vortex formation during most of the cycle. The pressure within the aneurysm is nearly constant. At the downstream end of the expansion,high pressure gradients are found.     

Two-breath CO(2) test detects altered dynamic cerebrovascular autoregulation and CO(2) responsiveness with changes in arterial P(CO(2))

The new two-breath CO(2) method was employed to test the hypotheses that small alterations in arterial P(CO(2)) had an impact on the magnitude and dynamic response time of the CO(2) effect on cerebrovascular resistance (CVRi) and the dynamic autoregulatory response to fluctuations in arterial pressure. During a 10-min protocol, eight subjects inspired two breaths from a bag with elevated P(CO(2)), four different times, while end-tidal P(CO(2)) was maintained at three levels: hypocapnia (LoCO(2), 8 mmHg below resting values), normocapnia, and hypercapnia (HiCO(2), 8 mmHg above resting values). Continuous measurements were made of mean blood pressure corrected to the level of the middle cerebral artery (BP(MCA)), P(CO(2)) (estimated from expired CO(2)), and mean flow velocity (MFV, of the middle cerebral artery by Doppler ultrasound), with CVRi = BP(MCA)/MFV. Data were processed by a system identification technique (autoregressive moving average analysis) with gain and dynamic response time of adaptation estimated from the theoretical step responses. Consistent with our hypotheses, the magnitude of the P(CO(2))-CVRi response was reduced from LoCO(2) to HiCO(2) [from -0.04 (SD 0.02) to -0.01 (SD 0.01) (mmHg x cm(-1) x s) x mmHg Pco(2)(-1)] and the time to reach 95% of the step plateau increased from 12.0 +/- 4.9 to 20.5 +/- 10.6 s. Dynamic autoregulation was impaired with elevated P(CO(2)), as indicated by a reduction in gain from LoCO(2) to HiCO(2) [from 0.021 +/- 0.012 to 0.007 +/- 0.004 (mmHg x cm(-1) x s) x mmHg BP(MCA)(-1)], and time to reach 95% increased from 3.7 +/- 2.8 to 20.0 +/- 9.6 s. The two-breath technique detected dependence of the cerebrovascular CO(2) response on P(CO(2)) and changes in dynamic autoregulation with only small deviations in estimated arterial P(CO(2)).     

Temporal pattern of arterial CO2 partial pressure during exercise in humans

The major objective of this study was to test the hypothesis that arterial CO2 partial pressure (PaCO2) does not change in transitions from rest to steady-state exercise and between two levels of exercise. Nine young adults exercised on a treadmill or a bicycle (sit or supine) for 5 min at a mild work load (heart rate = 90 beats X min-1) and then 3 min at a moderate work load (heart rate = 150 beats X min-1). In some studies the moderate work load preceded the mild work load. Arterial blood was sampled from a catheterized artery. During all exercise tasks isocapnia was not strictly maintained (F greater than 4.0, P less than 0.001). For example, a 1-to 2-Torr hypocapnia was the dominant trend during the first 15-45 s after increasing treadmill speed, and a transient hypercapnia was most prevalent when treadmill speed was decreased. During steady-state exercise PaCO2 did not deviate by more than 1-3 Torr from PaCO2 during any resting posture, and PaCO2 differences between exercise intensities and conditions did not exceed 1-2 Torr. A mouthpiece-breathing valve system was not used in most studies, but when this system was used, it did not consistently affect exercise PaCO2. Increasing inspired O2 to 40% likewise did not consistently alter exercise PaCO2. Failure to maintain isocapnia throughout exercise indicates that the matching of alveolar ventilation (VA) to lung CO2 delivery is not exquisitely precise. Accordingly it is inappropriate to base theories of the exercise hyperpnea on the heretofore contention of precise matching.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transport of macromolecules in arterial wallin vivo: A mathematical model and analytical solutions

A mathematical model has been developed to simulatein vivo transmural accumulation of an intravenously injected tracer in the aortic wall of experimental animals. Parameters have been included to represent the following processes that affect tracer distribution: permeation of the blood-tissue interface, diffusion through the layers of the artery wall,convective solute drag through the same, and degradation. Of particular interest for thein vivo situation situation is the inclusion of boundary conditions that account for the variation in the plasma concentration of injected tracer as a function of time. Two analytical solutions are presented. The first describes a system in which two boundaries must be delineated; it pertains if the tracer is allowed to circulate until it enters the avascular media of the artery wall both across its luminal boundary and from the capillaries in its outer layer. The second applies to shorter duration experiments in which entry across only the luminal boundary is considered. A limiting case of the solution for short circulation times is presented, compared with a previously published solution, and examined for its potential utility in parameter estimation. Because of its treatment of time-dependent boundary conditions, the model has unique application toin vivo experiments related to macromolecular transport in atherosclerosis that may otherwise elude proper interpretation. This work was supported by National Institutes of Health Grants HL-29582 and HL-07242.     

Periodic hemodynamics in skeletal muscle during local arterial pressure reduction.

The time-dependent features of red blood cell flow were evaluated with laser-Doppler flowmetry (LDF) in the left gastrocnemius muscle of 31 anesthetized New Zealand White rabbits during stepwise arterial occlusion. During the control period with a median femoral pressure of 72 mmHg, 29 animals showed minor irregular fluctuations in LDF blood flow, and only two animals displayed periodic variations of blood flow. Lowering femoral arterial pressure induced maximal periodic blood flow variations at a median pressure of 35 mmHg in all animals with a median frequency of 1.5 cycles/min (termed "slow-wave flow motion"). The median amplitude was 48% of the corresponding average flow. These slow waves disappeared at a median femoral pressure of 20 mmHg. The median LDF flow value was 4.00 arbitrary units (AU) at control pressure and 2.05 AU at maximum slow-wave flow motion. When slow-wave flow motion was seen at several pressure levels, their frequency was identical, which supports the local pacemaker concept. This study promotes a novel concept for the role and physiological significance of periodic hemodynamics in that it is a condition not characteristic for normal control situations but is activated below a specific local arterial blood pressure and flow threshold, which is known to be the lower end of autoregulation in the microcirculation of rabbit skeletal muscle. This also suggests that slow-wave flow motion is primarily under local control mechanisms.     

Resonance in a mathematical model of baroreflex control: arterial blood pressure waves accompanying postural stress

A mathematical model of the arterial baroreflex was developed and used to assess the stability of the reflex and its potential role in producing the low-frequency arterial blood pressure oscillations called Mayer waves that are commonly seen in humans and animals in response to decreased central blood volume. The model consists of an arrangement of discrete-time filters derived from published physiological studies, which is reduced to a numerical expression for the baroreflex open-loop frequency response. Model stability was assessed for two states: normal and decreased central blood volume. The state of decreased central blood volume was simulated by decreasing baroreflex parasympathetic heart rate gain and by increasing baroreflex sympathetic vaso/venomotor gains as occurs with the unloading of cardiopulmonary baroreceptors. For the normal state, the feedback system was stable by the Nyquist criterion (gain margin = 0.6), but in the hypovolemic state, the gain margin was small (0.07), and the closed-loop frequency response exhibited a sharp peak (gain of 11) at 0.07 Hz, the same frequency as that observed for arterial pressure fluctuations in a group of healthy standing subjects. These findings support the theory that stresses affecting central blood volume, including upright posture, can reduce the stability of the normally stable arterial baroreflex feedback, leading to resonance and low-frequency blood pressure waves.     

A simple mathematical model of the interaction between intracranial pressure and cerebral hemodynamics

Ursino, Mauro, and Carlo Alberto Lodi. A simplemathematical model of the interaction between intracranial pressure andcerebral hemodynamics. J. Appl.Physiol. 82(4): 1256-1269, 1997.A simplemathematical model of intracranial pressure (ICP) dynamics oriented toclinical practice is presented. It includes the hemodynamics of thearterial-arteriolar cerebrovascular bed, cerebrospinal fluid (CSF)production and reabsorption processes, the nonlinear pressure-volumerelationship of the craniospinal compartment, and a Starling resistormechanism for the cerebral veins. Moreover, arterioles are controlledby cerebral autoregulation mechanisms, which are simulated by means ofa time constant and a sigmoidal static characteristic. The model isused to simulate interactions between ICP, cerebral blood volume, andautoregulation. Three different related phenomena are analyzed: thegeneration of plateau waves, the effect of acute arterial hypotensionon ICP, and the role of cerebral hemodynamics during pressure-volume index (PVI) tests. Simulation results suggest the following:1) ICP dynamics may become unstablein patients with elevated CSF outflow resistance and decreasedintracranial compliance, provided cerebral autoregulation is efficient.Instability manifests itself with the occurrence of self-sustainedplateau waves. 2) Moderate acutearterial hypotension may have completely different effects on ICP,depending on the value of model parameters. If physiological compensatory mechanisms (CSF circulation and intracranial storage capacity) are efficient, acute hypotension has only negligible effectson ICP and cerebral blood flow (CBF). If these compensatory mechanismsare poor, even modest hypotension may induce a large transient increasein ICP and a significant transient reduction in CBF, with risks ofsecondary brain damage. 3) The ICPresponse to a bolus injection (PVI test) is sharply affected, viacerebral blood volume changes, by cerebral hemodynamics andautoregulation. We suggest that PVI tests may be used to extractinformation not only on intracranial compliance and CSF circulation,but also on the status of mechanisms controlling CBF.

     

The pulmonary hemodynamics changes under experimental myocardial ischemia in rabbits following increased arterial pressure

In acute experiments in anesthetized rabbits, changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the infusion of adrenaline and phenylephrine. The pulmonary artery pressure was increased following infusion of these drugs; however, it decreased to normal level in the condition of myocardial ischemia. Meanwhile the pulmonary vascular resistance was elevated to the same level in both cases. Following adrenaline infusion, the pulmonary artery blood flow and venous return increased and, in the condition of myocardial ischemia, they decreased to normal level, but the left atrial pressure was decreased. Following phenylephrine infusion, the pulmonary artery blood flow and venous return did not change and, in the condition of myocardial ischemia, these parameters decreased lower than normal level but the left atrial pressure was elevated. Thus we concluded that equal values of the pulmonary artery pressure in both cases were caused by changes of different character in the left atrial pressure. The differences of the changes character and values of the pulmonary artery flow under experimental myocardial ischemia following the infusion of adrenaline and phenylephrine were caused by different shifts of the venous return.     

Effects of transient intrathoracic pressure changes (hiccups) on systemic arterial pressure

Mathew, Oommen P. Effects of transient intrathoracicpressure changes (hiccups) on systemic arterial pressure.J. Appl. Physiol. 83(2): 371-375, 1997.The purpose of the study was to determine the effect oftransient changes in intrathoracic pressure on systemic arterialpressure by utilizing hiccups as a tool. Values of systolic anddiastolic pressures before, during, and after hiccups were determinedin 10 intubated preterm infants. Early-systolic hiccups decreasedsystolic blood pressure significantly (P < 0.05) compared with control(39.38 ± 2.72 vs. 46.46 ± 3.41 mmHg) and posthiccups values,whereas no significant change in systolic blood pressure occurredduring late-systolic hiccups. Diastolic pressure immediately after thehiccups remained unchanged during both early- and late-systolichiccups. In contrast, diastolic pressure decreased significantly(P < 0.05) when hiccups occurred during diastole (both early and late). Systolic pressures of the succeeding cardiac cycle remained unchanged after early-diastolic hiccups, whereas they decreased after late-diastolic hiccups. Theseresults indicate that transient decreases in intrathoracic pressurereduce systemic arterial pressure primarily through an increase in thevolume of the thoracic aorta. A reduction in stroke volume appears tocontribute to the reduction in systolic pressure.

     

A mathematical model of maternal vascular growth and remodeling and changes in maternal hemodynamics in uncomplicated pregnancy

The maternal vasculature undergoes tremendous growth and remodeling (G&R) that enables a?>?15-fold increase in blood flow through the uterine vasculature from conception to term. Hemodynamic metrics (e.g., uterine artery pulsatility index, UA-PI) are useful for the prognosis of pregnancy complications; however, improved characterization of the maternal hemodynamics is necessary to improve prognosis. The goal of this paper is to develop a mathematical framework to characterize maternal vascular G&R and hemodynamics in uncomplicated human pregnancies. A validated 1D model of the human vascular tree from the literature was adapted and inlet blood flow waveforms at the ascending aorta at 4 week increments from 0 to 40 weeks of gestation were prescribed. Peripheral resistances of each terminal vessel were adjusted to achieve target flow rates and mean arterial pressure at each gestational age. Vessel growth was governed by wall shear stress (and axial lengthening in uterine vessels), and changes in vessel distensibility were related to vessel growth. Uterine artery velocity waveforms generated from this model closely resembled ultrasound results from the literature. The literature UA-PI values changed significantly across gestation, increasing in the first month of gestation, then dramatically decreasing from 4 to 20 weeks. Our results captured well the time-course of vessel geometry, material properties, and UA-PI. This 1D fluid-G&R model captured the salient hemodynamic features across a broad range of clinical reports and across gestation for uncomplicated human pregnancy. While results capture available data well, this study highlights significant gaps in available data required to better understand vascular remodeling in pregnancy.