Computer studies of systemic and regional blood flow mechanisms during cardiopulmonary resuscitation

Based on the new concept that intrathoracic and abdominal pressure variations cause blood flow in most of the cardiopulmonary resuscitation (CPR) techniques, two mathematical models were developed to explore related mechanisms of blood flow. The models were based on a representation of the cardiovascular system by resistive, capacitive and inductive elements, and the existence of venous and cardiac unidirectional valves. Cyclic intrathoracic and abdominal pressure variations were simulated by modulating the pressure within the corresponding vessels. It was found that blood flow during CPR is highly dependent on venous valving and aortic valve competence. The systemic blood flow was calculated to be between 10 and 20 per cent of its normal value. The maximum flow under a cyclic pressure of 50 mmHg was 663 m/min⁻¹, which was achieved with a pulse rate of 115 cycles per min and a duty cycle (ratio of artificial systole to cycle duration) of 58 per cent. The coronary blood flow was found to occur only during artificial diastole and was actually reversed during the compression phase. The systemic blood flow increased when pressure variations were delivered to the chest alone or when some phase lag was introduced between the thoracic and abdominal pressure waves. The mathematical model presented provided a tool to study the effect of thoracic and abdominal pressure waves on the circulation in CPR. The information derived from the model can be used to design better methods for CPR.     

Cyclic fluctuations in the cardiac performance of the isolated Langendorff‐perfused mouse heart: pyruvate abolishes the fluctuations and has an anti‐ischaemic effect

During the development of a Langendorff preparation of isolated mouse hearts, hitherto undescribed cyclic fluctuations in left ventricular pressure and coronary flow were independently observed in three laboratories. Isolated mouse hearts were perfused with crystalloid glucose‐containing Krebs–Hensleit buffer in a constant pressure model, and left ventricular pressures were measured via an intraventricular balloon catheter. After acquiring technical skill in preparing the mouse hearts, the perfusionists observed that fluctuations in cardiac performance with a cycle period lasting 5–10 min occurred shortly after initiation of perfusion. Each fluctuation cycle consisted of a phase of increase and a phase of decrease. Synchronized with the fluctuations in left ventricular pressure, increases and decreases in dP/dt max took place. Analogous fluctuations in coronary flow occurred, with onset 1–2 min later than changes in left ventricular systolic pressure. In some preparations a gradual ST‐segment elevation was seen on the electrocardiogram during the systolic pressure increase phase. The amplitude of the fluctuations could be augmented by increasing the perfusion pressure, and reduced, but not abolished, by lowering the pressure. Changes in buffer calcium, magnesium, or sodium concentration did not alter the fluctuations, nor did any change of anaesthetics, mouse strain, or left ventricular drainage. Altering the perfusion mode from constant pressure to constant flow did not prevent the occurrence of the cyclic fluctuations. The hearts became stable and the fluctuations disappeared when the buffer was supplemented with 2 mm pyruvate. In the present study, pyruvate given throughout stabilization and reperfusion also markedly attenuated the ischaemic insult, as evidenced by the delayed ischaemic contracture and a reduced magnitude of ischaemic contracture. A cardioprotective effect was only visible at early reperfusion, did not affect the final functional recovery. In conclusion, a phenomenon of cyclic fluctuations in left ventricular pressure followed by fluctuations in coronary flow was observed in isolated mouse hearts. These could be abolished by adding 2 mm pyruvate to the perfusion buffer. Pyruvate in the buffer also markedly attenuated the post‐ischaemic deterioration of cardiac performance seen in this mouse model.     

Cyclic fluctuations in the cardiac performance of the isolated Langendorff-perfused mouse heart: pyruvate abolishes the fluctuations and has an anti-ischaemic effect

During the development of a Langendorff preparation of isolated mouse hearts, hitherto undescribed cyclic fluctuations in left ventricular pressure and coronary flow were independently observed in three laboratories. Isolated mouse hearts were perfused with crystalloid glucose-containing Krebs-Hensleit buffer in a constant pressure model, and left ventricular pressures were measured via an intraventricular balloon catheter. After acquiring technical skill in preparing the mouse hearts, the perfusionists observed that fluctuations in cardiac performance with a cycle period lasting 5-10 min occurred shortly after initiation of perfusion. Each fluctuation cycle consisted of a phase of increase and a phase of decrease. Synchronized with the fluctuations in left ventricular pressure, increases and decreases in dP/dt max took place. Analogous fluctuations in coronary flow occurred, with onset 1-2 min later than changes in left ventricular systolic pressure. In some preparations a gradual ST-segment elevation was seen on the electrocardiogram during the systolic pressure increase phase. The amplitude of the fluctuations could be augmented by increasing the perfusion pressure, and reduced, but not abolished, by lowering the pressure. Changes in buffer calcium, magnesium, or sodium concentration did not alter the fluctuations, nor did any change of anaesthetics, mouse strain, or left ventricular drainage. Altering the perfusion mode from constant pressure to constant flow did not prevent the occurrence of the cyclic fluctuations. The hearts became stable and the fluctuations disappeared when the buffer was supplemented with 2 mm pyruvate. In the present study, pyruvate given throughout stabilization and reperfusion also markedly attenuated the ischaemic insult, as evidenced by the delayed ischaemic contracture and a reduced magnitude of ischaemic contracture. A cardioprotective effect was only visible at early reperfusion, did not affect the final functional recovery. In conclusion, a phenomenon of cyclic fluctuations in left ventricular pressure followed by fluctuations in coronary flow was observed in isolated mouse hearts. These could be abolished by adding 2 mm pyruvate to the perfusion buffer. Pyruvate in the buffer also markedly attenuated the post-ischaemic deterioration of cardiac performance seen in this mouse model.     

Pressures generated by ribcage and abdominal compressions during cardiopulmonary resuscitation

When the ribcage and abdomen are compressed during cardiopulmonary resuscitation (CPR), the effect on intrathoracic pressure, and therefore on haemodynamics, cannot be quantitatively predicted without a physiologically based mathematical model of chest wall dynamics. Using such a model, we compared model simulations of pleural P_pl and abdominal P_ab pressures with those from dog experiments in which the compression of the ribcage was delayed from 0 to 500 ms after compression of the abdomen. Integrals of P_pl and transdiaphragmatic pressure, P_di=P_ab−P_pl, over their positive and negative values during a cycle were chosen as indices of driving pressures for cardiac output. Both from the model output and experimental data, we found that the positive p_pl integral PPI tends to increase with a longer delay between ribcage and abdominal compressions. The negative P_pl integral NPI, however, tends to decrease according to the model predictions and data. Furthermore, the positive and negative integrals of P_dl also tend to change with delay time in the opposite way, as shown by both the model simulations and the experiments. Our results show that chest wall tissues modify the externally applied pressures, thereby not allowing us to use the externally applied pressure sources directly as the driving pressure of the cardiovascular system under study. The optimal conditions for haemodynamics during CPR require a compromise between the positive and negative integral indices. Prediction of the optimal haemodynamics from externally applied pressures requires the coupling of appropriate physiological models of chest wall dynamics and haemodynamics.     

Non-blood contacting electro-hydraulic artificial myocardium (EHAM) improves the myocardial tissue perfusion.

Artificial heart (AH) and ventricular assist devices (VAD) are widely used in the clinical setting to assist severe heart failure patients. The concept of direct cardiac compression (DCC) has been in use for several decades and has advantages over intravascular VAD. The process involves compressing the dysfunctional heart from its epicardial surface to avoid the thromboembolic events and decrease the complications and mortality. An Electro-hydraulic Artificial Myocardium (EHAM) system was designed and fabricated by Tohoku University. This system may assist cardiac contraction and create pulsatile blood flow. The aim of this study was to clearly define the hemodynamic efficiency of the EHAM system in myocardial tissue perfusion during its application in acute animal experiment. Eight healthy adult goats were used; left lateral thoracotomy was performed and the chest was opened by the resection of the 4th and 5th ribs. Hemodynamic parameters including ECG, blood pressure and cardiac output were continuously monitored. Myocardial tissue perfusion was measured by using Omega flow laser fiber attached to the surface of the heart. During the EHAM compression, and increase in blood pressure and myocardial tissue perfusion was observed in all animals when compared with pre-assisted mode. To conclude, EHAM effectively improves myocardial tissue perfusion and increases the pressure on the initiation of direct cardiac compression immediately. Thus it can be a potentially valuable adjunct in the management of severe heart failure.     

"Stolen" blood flow: effect of an open arterial filter purge line in a simulated neonatal CPB model

The purpose of this study was to evaluate the effect of different flow rates and pressures on the degree of shunting of blood flow by the arterial filter purge line in a simulated neonatal cardiopulmonary bypass circuit. The circuit was primed with heparinized bovine blood (hematocrit 24%) and postfilter pressure was varied from 60-180 mm Hg (20 mm Hg increments) using a Hoffman clamp. Trials were conducted at flow rates ranging from 200-600 ml/min (100 ml/min increments). During trials conducted at a postfilter pressure of 60 mm Hg, 42.6% of blood flow was shunted through the purge line at a flow rate of 200 ml/min, whereas only 12.8% of flow was diverted at a flow rate 600 ml/min. During trials conducted at a postfilter pressure of 180 mm Hg, 82.8% of blood flow at 200 ml/min and 25.9% of blood flow at 600 ml/min was diverted through the open arterial purge line. The results of this study confirm that a significant amount of flow is diverted away from the patient when the arterial purge line is open. Shunting of blood flow through the arterial purge line could result in less effective tissue perfusion, particularly at low flow rates and high postfilter pressures. To minimize hypoperfusion injury, a flow probe (distal to the arterial filter) may be used to monitor real-time arterial flow in the setting of an open arterial filter purge line.     

Towards optimum chest compression performance during constant peak displacement cardiopulmonary resuscitation

The aim of this study is to determine the conditions necessary to achieve optimum chest compression (CC) performance during constant peak displacement cardiopulmonary resuscitation (CPR). This was accomplished by first performing a sensitivity analysis on a theoretical constant peak displacement CPR CC model to identify the parameters with the highest sensitivity. Next, the most sensitive parameters were then optimized for net sternum-to-spine compression depth, using a two-variable non-linear least squares method. The theoretical CC model was found to be most sensitive to: thoracic stiffness, maximum sternal displacement, CC rate, and back support stiffness. Based on a two-variable, non-linear least squares analysis to optimize the model for the net sternum-to-spine compression depth during constant peak displacement CPR, it was found that the optimum ranges for the CC rate and back support stiffness are between 40–120 cpm and 241.0–1198.5 Ncm⁻¹, respectively. Clinically, this suggests that current ERC guidelines for the CC rate during peak displacement CPR are appropriate; however, practitioners should be aware that the stiffness of the back support surfaces found in many hospitals may be sub-optimal and should consider using a backboard or a concrete floor to enhance CPR effectiveness.     

Intrinsic Regulation of Blood Flow in Adipose Tissue

Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called auto regulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an auto regulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g·min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue. Following total ischemia all experiments showed a period with reactive hyperemia, and both duration of hyperemia and excess flow was related to the duration of the ischemia. This response therefore seems more resistant to the experimental procedure, while auto regulation of blood flow to lowered pressure is more susceptible to surgical exposure of the tissue. During elevation of arterial perfusion pressure blood flow in the isolated tissue showed a transient increase and then almost returned to the level during normotension, indicating an elevated vascular resistance. Raising of venous pressure elicited vasoconstriction with pronounced flow reduction. These two reactions may be important for local regulation of blood flow in subcutaneous tissue during orthostatic changes in arterial and venous pressure. It is concluded that the response in adipose tissue to changes in arterial pressure (auto regulation), venous pressure and total ischemia appear to be elicited by different mechanisms.     

呼吸机潮气量和高压报警值参数设置在心肺复苏中的应用

目的:探讨呼吸机潮气量（VT）和高压报警值参数设置在心肺复苏（CPR）中的应用效果。方法:94例心搏骤停需实施心肺复苏治疗的患者作为研究对象,根据不同呼吸机潮气量和高压报警值参数设置,将所有纳入对象随机分为观察组和对照组,各47例。观察组呼吸机潮气量和高压报警值参数分别设置为6~7 mL/kg和60 cmH2O,对照组呼吸机潮气量和高压报警值参数分别设置为8~12 mL/kg和40 cmH2O,对比分析两组患者CPR治疗成功率、治疗过程中不同时间点乳酸水平、动脉血气［pH、氧饱和度（SaO2）、血氧分压（PaO2）、血二氧化碳分压（PaCO2）、碳酸氢根（HCO3-）］水平以及治疗后吸气峰压（PIP）水平、治疗后复苏即刻及复苏24 h后神经功能评分。结果:观察组患者CPR成功率为65.96%,显著优于对照组的42.55%（[χ2]=5.187, P=0.023）;观察组CPR后患者10、30 min时间点pH、PaO2、PaCO2及乳酸水平均显著低于对照组（P<0.05）,SaO2、HCO3-显著高于对照组（P<0.05）;观察组患者CPR后PIP、复苏时间显著低于对照组（P<0.05）;复苏24 h后,观察组患者格拉斯哥昏迷评分和急性生理与慢性健康评分增加程度显著高于对照组（P<0.05）。结论:呼吸机采取低潮气量、上调高压报警值参数,可有效改善心搏骤停患者动脉血气指标,增加患者CPR成功率,缓解患者神经功能损伤,且未增加CPR后并发症发生风险。     

Metabolic and physical changes during calcium paradox induced in the rat heart

Early changes in metabolic and physical properties were determined in rat hearts during calcium paradox. Calcium paradox was induced under constant perfusion pressure (60 mmHg) or constant coronary flow rate (9.8 ml/min). Within 30 s after calcium repletion, in either case, NADH increased, despite a decrease in ATP and increases in ADP and AMP. Surface spectrophotometry showed a deoxygenation of the myoglobin, thereby indicating myocardial oxygen depletion. These changes were predominant under conditions of constant pressure perfusion. In association with a rapid development of contracture, there were also a reduction in coronary flow (18%) in constant pressure perfusion, and an increase in perfusion pressure (208%) under constant flow perfusion. Thus, tissue deoxygenation has to be given due attention in the early development of calcium paradox, particularly in case of a constant pressure perfusion. Under constant flow perfusion, the physical stress due to high pressure perfusion against contracture may play an important role in the development of calcium paradox. This may be the first reported evidence for tissue anoxia in calcium paradox.     

Metabolic and physical changes during calcium paradox induced in the rat heart.

Early changes in metabolic and physical properties were determined in rat hearts during calcium paradox. Calcium paradox was induced under constant perfusion pressure (60 mmHg) or constant coronary flow rate (9.8 ml/min). Within 30 s after calcium repletion, in either case, NADH increased, despite a decrease in ATP and increases in ADP and AMP. Surface spectrophotometry showed a deoxygenation of the myoglobin, thereby indicating myocardial oxygen depletion. These changes were predominant under conditions of constant pressure perfusion. In association with a rapid development of contracture, there were also a reduction in coronary flow (18%) in constant pressure perfusion, and an increase in perfusion pressure (208%) under constant flow perfusion. Thus, tissue deoxygenation has to be given due attention in the early development of calcium paradox, particularly in case of a constant pressure perfusion. Under constant flow perfusion, the physical stress due to high pressure perfusion against contracture may play an important role in the development of calcium paradox. This may be the first reported evidence for tissue anoxia in calcium paradox.     

Coronary hemodynamics during hemopump left-intraventricular assistance.

Hemopump left intraventricular pumping (HP) can permit percutaneous transluminal angioplasty (PTCA) in high-risk patients. Benefits may be related to left ventricular unloading or myocardial perfusion improvement, or both. Direct ultrasonic measurements of coronary blood flow were made in the dilated vessel after a successful PTCA in five patients. A 3 Fr intracoronary Doppler catheter was placed in the coronary artery to measure flow velocities (maximal or diastolic velocity; minimum or systolic velocity and mean velocity). A SwanGanz catheter was used to measure the cardiac index and pulmonary capillary wedge pressure. Mean aortic pressures were monitored through an 8 Fr guiding catheter. Measurements were made after a 5-min period of minimal speed (T0) of the HP to avoid retrograde regurgitation through the turbine; during the increase from minimum to maximal speed (T1); after a 5-min period of maximal HP flow (3l/min) (T2) and after HP was pulled back (T3). From T0 to T2, cardiac index rose from 1.93 +/- 0.38 to 3.26 +/- 0.35 l/min/m2 and capillary wedge pressure decreased from 18 +/- 6 to 13 +/- 5 mmHg (p less than 0.05); from T2 to T3, cardiac index decreased to 2.4 +/- 0.4 while capillary wedge pressure increased to 17 +/- 5 (p less than 0.05). Mean arterial pressure and heart rate did not change significantly throughout the study. When the hemopump flow was raised to high speed, coronary blood flow increased immediately but returned shortly to baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular resistance of intestine, muscle and skin during blood pressure oscillation.

After the blood supply to the head was surgically limited to one common carotid artery in rabbits, the artery was compressed by exertion of stepwise elevated side pressure on a segment of the artery. Systemic arterial pressure rose and began to oscillate when the side pressure was increased to 50 to 60 mmHg. The oscillations were regular and occurred at a rate of 3 to 4 per minute with a wave height of 15 to 45 mmHg. Concomitant with systemic pressure oscillations, and in near synchrony were undulations in the perfusion pressures recorded during constant flow from the vascularly isolated abdominal skin, skeletal muscle and small intestine. With the graded elevation of side pressure on the common carotid artery, mean systemic pressure and perfusion pressure showed a nearly exponential relation. The ratio between the two variables was slightly less than one below the systemic pressure of 120 mmHg and rapidly increased above this level. At ratios greater than one, the peripheral resistance undulations in the isolated areas gave a larger minimum and maximum, a sharper contour and, particularly in the skin, a phase lag in the period of the wave form when compared to the systemic pressure oscillations. These observations highlight the differences in response characteristics of peripheral resistance vessels and those of cardiac output and different consecutive parts of the systemic arteries during periods of intense sympathetic activation.     

Local regulation of subcutaneous blood flow and capillary filtration in limbs with occlusive arterial disease. Studies before and after arterial reconstruction

The aim of the study was to examine the local blood flow regulation and the capillary filtration rate in patients with occlusive arterial disease before and after arterial reconstructive surgery. Fourty-seven normal subjects and 99 patients were studied. Subcutaneous blood flow was measured on the forefoot by the local 133Xenon method. Forefoot arterial blood pressure was measured indirectly by cuff and strain-gauge technique. Capillary filtration rate was measured by strain-gauge plethysmography on the forefoot. The arterial and venous pressures of the forefoot were changed by elevating or lowering the foot in relation to heart level. In normal limbs autoregulation was demonstrated during elevation of the limb when blood flow remained almost constant despite the reduction in arterial and perfusion pressures. The local vasoconstrictor response to increased venous transmural pressure was demonstrated when the limb was lowered and blood flow decreased about 30% despite a constant perfusion pressure. In limbs with occlusive arterial disease both local blood flow regulation mechanisms became progressively more abnormal the severe the symptoms and the lower the distal blood pressure. Estimations of the changes in local vascular resistance suggested that the abnormalities in blood flow regulation in all but the severest cases are the result of changes in local perfusion pressure rather than the result of inability of the arteriolar smooth muscle to dilate and constrict in response to changes in arterial and venous pressures. After arterial reconstruction the two mechanisms generally normalized within about a week. However, disturbances occurred in some cases in the early postoperative period, possibly as the result of postoperative pain and stress. Postreconstructive hyperaemia developed in most limbs despite the early normalization of local blood flow regulation. Compared with normal limbs, the forefoot capillary filtration rate was reduced in limbs with occlusive arterial disease. In the early postoperative period the filtration rate remained reduced, but it increased to normal values within three months. Postreconstructive oedema developed independently of the normalization of blood flow regulation, and almost exclusively after femoro-distal by-pass surgery. The study supports the hypothesis that the postreconstructive oedema is a lymphoedema due to surgical trauma, rather than the result of microvascular derangement.     

Resetting of the pressure range for blood flow autoregulation in the rat kidney

Both a myogenic response and the tubuloglomerular feedback control mechanism seem to be involved in autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF). Earlier experiments have shown that clamping of renal arterial perfusion pressure, below the autoregulatory range, reduces single-nephron GFR, and that this low value is maintained during the first 10-15 min after release of the clamp. It was also found that the tubuloglomerular feedback mechanism in the early declamp phase was strongly activated to reduce GFR. These findings can not be easily understood with the current knowledge of autoregulation, but would suggest a resetting of RBF and GFR autoregulation to a new level. To test this, left renal arterial perfusion pressure was reduced from 100 to 60 mmHg during 20 min with and without angiotensin converting enzyme inhibition (0.5 mg i.v. enalapril). Renal blood flow was measured with laser-Doppler flowmetry. When arterial perfusion pressure was reduced from 100 to 60 mmHg for 20 min, RBF was reduced to 77% of control and remained at this low level during the first minutes of declamp. In this situation there was an autoregulation to a new level. Renal blood flow was then slowly normalized (16.1 min). In the enalapril-treated animals RBF was only reduced to 85% during the 20 min of clamping and returned immediately to the control level at declamp. Thus, these experiments demonstrate that if renal blood flow is decreased by reducing the perfusion pressure below the normal autoregulatory range the pressure range for blood flow autoregulation resets to a lower level and that this change is mediated via the renin-angiotensin system.     

Contribution of myocardial contractility to myocardial perfusion.

Myocardial contractility in open-chest anesthetized (sodium pentobarbital) dogs was varied while ventricular pressure, coronary perfusion pressure, and coronary tone were held constant. Under those conditions, changes in regional blood flow should reflect changes only in intramyocardial compression related to the altered inotropic state. Increasing contractility with isoproterenol caused flow to decrease in the outer myocardial layers without change at the subendocardium. When contractility was decreased with pentobarbital, flow at the subendocardium was increased with little change in the outer layers. By manipulating perfusion pressure in the latter experiments it was demonstrated that subendocardial compression was falling from a starting value that was somewhat above peak ventricular pressure.     

Breath hold diving: In vivo model of the brain survival response in man?

Breath hold divers are faced with two main physiological challenges: pressure induced compression and extended time without breathing, exposing them to extremes of hypoxia/hypercapnia. Current world records are 214 m for depth and 11:35 min for duration. Hypoxic loss of consciousness is frequently observed during competitions. The major physiological components of the diving response that occurs during breath holding are peripheral vasoconstriction, bradycardia, decreased cardiac output, increased cerebral and myocardial blood flow, increased blood pressure, splenic contraction and preserved O(2) delivery to the brain and the heart. Sympathetic nervous activity is exceptionally engaged at the end of voluntary breath holds. We hypothesize that these adaptations to extended cessation of breathing ending with extreme hypoxia can be used as a model of brain survival response during conditions involving profound brain deoxygenation and in some instances reduced brain perfusion.     

Optimization of dynamic culture conditions: effects on biosynthetic activities of chondrocytes grown in collagen sponges

Application of mechanical stimulation, using dynamic bioreactors, is considered an effective strategy to enhance cellular behavior in load-bearing tissues. In this study, two types of perfusion mode (direct and free flow) are investigated in terms of the biosynthetic activities of chondrocytes grown in collagen sponges by assessment of cell proliferation rate, matrix production, and tissue morphology. Effects of the duration of preculture and dynamic conditioning are further determined. Our results have demonstrated that both bovine and human-derived chondrocytes demonstrate a dose-dependent response to flow rate (0-1 mL/min) in terms of cell number and glycosaminoglycan (GAG) content. This may reflect the weak adhesion of cells to the sponge scaffolds and the immature state of the constructs even after 3 weeks of proliferative culture. Our studies define an optimal flow rate between 0.1 and 0.3 mL/min for direct perfusion and free flow bioreactors. Using fresh bovine chondrocytes and a lower flow rate of 0.1 mL/min, a comparison was made between free flow system and direct perfusion system. In the free flow bioreactor, no cell loss was observed and higher GAG production was measured compared with static cultured controls. However, as with direct perfusion, the enhancement effect of free flow perfusion was strongly dependent on the maturation and organization of the constructs before the stimulation. To address the maturation of the matrix, preculture periods were varied before mechanical conditioning. An increase in culture duration of 18 days before mechanical conditioning resulted in enhanced GAG production compared with controls. Interestingly, additional enhancement was found in specimens that were further subjected to a prolonged duration of perfusion (63% increase after an additional 4 days of perfusion) after prematuration. The free flow system has an advantage over the direct perfusion system, especially when using sponge scaffolds, which have lower mechanical properties; however, mass transfer of nutrients is still more optimal throughout the scaffolds in a direct perfusion system as demonstrated by histological analysis.     

Blood Flow and Oxygen Extraction in the Cat Uvea at Normal and High Intraocular Pressures

The rate of blood flow through the uvea and the arterio-venous O₂ difference across the uveal tract were determined in cats. The normal rate of blood flow was 1.14 ± 0.23 ml/min and the normal a-v O₂ difference was 1.02 ± 0.16 volume per cent. The O₂ extraction was 8.0 ± 0.6 μl NTP/min. The arterial O₂ saturation, P_o2, P_co2, and pH were 95.6 ± 0.3 per cent, 93 ± 3 mm Hg, 25.8 ± 1.0 mm Hg, and 7.44 ± 0.01 units, respectively. An artificial rise in eye pressure reduced the rate of uveal blood flow and increased the a-v O₂ difference. The O₂ extraction was relatively constant at blood flow rates above 0.3–0.5 ml/min. At lower flow rates the O₂ extraction decreased in spite of a high venous O₂ concentration. Blood collected from the choroidal veins had a slightly higher O₂ concentration than blood collected from the intrascleral venous plexus. A reduction in uveal blood flow, produced by a reduction in the mean arterial blood pressure, reduced the O₂ content both in blood collected from the choroid and in blood leaving the anterior uvea. The results suggest that at low perfusion pressures there is anoxia in some tissue supplied by the uveal vessels, in spite of a relatively well oxygenated venous blood.     

Evaluation of Mechanisms of Postflight Orthostatic Intolerance with a Simple Cardiovascular System Model

A significant fraction of astronauts experience postflight orthostatic intolerance (POI) during 10-min stand tests conducted on landing day. The average time that nonfinishers can stand is about 7 min. This phenomenon, including the delay in occurrence of presyncope, was studied with a five-compartment model of the cardiovascular system incorporating compartments for the heart/lungs, systemic arteries and cephalic, central, and caudal veins. The model included 28 independent parameters, including factors characterizing cardiac performance, vascular resistance, intrathoracic pressure, nonlinear venous compliance and circulating blood volume, and 13 dependent parameters, including cardiac output and cardiac and vascular compartment pressures and volumes. First, a sensitivity analysis of hemodynamic indicators of presyncope to independent parameters was performed. Results demonstrated that both cardiac output and arterial pressure were most sensitive to volume-related parameters, particularly total blood volume, and less sensitive to peripheral resistance. Next, a simulated postflight stand test confirmed that fluid loss due to capillary filtration, particularly from the caudal region where transmural pressure is high during standing, is a plausible mechanism of POI that also explains the delayed onset of symptoms in most astronauts. An accumulated drop in arterial pressure sufficient to compromise cerebral perfusion and, therefore, cause syncope was reached in about 7 min with a fluid loss of 280 mL. Finally, additional simulations showed that a 75% increase in peripheral resistance, similar to finishers of stand tests, was insufficient to overcome the loss of circulating fluid associated with capillary filtration, and extended the time that the modeled astronaut could stand by only about 1 min. It is therefore concluded that capillary filtration may play a key role in producing POI and that development of countermeasures should perhaps focus on reducing postflight capillary permeability or on stimulating volume-compensating mechanisms.