EDRF inhibition attenuates the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs.

At birth, pulmonary vasodilation occurs during rhythmic distension of the lungs and oxygenation. Inhibition of prostaglandin synthesis prevents pulmonary vasodilation during rhythmic distension of the lungs but not during oxygenation. Because endothelium-derived relaxing factor (EDRF) modulates pulmonary vascular tone at birth, at rest, and during hypoxia in older animals, we hypothesized that EDRF may modulate pulmonary vascular tone during oxygenation in fetal lambs. We studied the responses to N omega-nitro-L-arginine, a competitive inhibitor of EDRF synthesis, in nine near-term fetal lambs and to drug vehicle in six of these lambs and the subsequent responses to in utero ventilation with 95% O2 in these fetal lambs. In all fetal lambs, prostaglandin synthesis was prevented by meclofenamate. N omega-nitro-L-arginine increased pulmonary and systemic arterial pressures by 28% (P < 0.05) and 31% (P < 0.05), respectively, and decreased pulmonary blood flow by 83% (P < 0.05). In the controls, ventilation with 95% O2 increased pulmonary blood flow by 1,050% (P = 0.05) without changing pressures, thereby decreasing pulmonary vascular resistance by 88% (P = 0.05). During N omega-nitro-L-arginine infusion, ventilation with 95% O2 increased pulmonary blood flow by 162% (P = 0.05) and decreased pulmonary vascular resistance by 74% (P = 0.05). This suggests that EDRF may play an important role in modulating resting pulmonary vascular tone in fetal lambs and in the vasodilatory response to ventilation with O2 in utero.     

Optimization of shunt placement for the Norwood surgery using multi-domain modeling

An idealized systemic-to-pulmonary shunt anatomy is parameterized and coupled to a closed loop, lumped parameter network (LPN) in a multidomain model of the Norwood surgical anatomy. The LPN approach is essential for obtaining information on global changes in cardiac output and oxygen delivery resulting from changes in local geometry and physiology. The LPN is fully coupled to a custom 3D finite element solver using a semi-implicit approach to model the heart and downstream circulation. This closed loop multidomain model is then integrated with a fully automated derivative-free optimization algorithm to obtain optimal shunt geometries with variable parameters of shunt diameter, anastomosis location, and angles. Three objective functions: (1) systemic; (2) coronary; and (3) combined systemic and coronary oxygen deliveries are maximized. Results show that a smaller shunt diameter with a distal shunt-brachiocephalic anastomosis is optimal for systemic oxygen delivery, whereas a more proximal anastomosis is optimal for coronary oxygen delivery and a shunt between these two anatomies is optimal for both systemic and coronary oxygen deliveries. Results are used to quantify the origin of blood flow going through the shunt and its relationship with shunt geometry. Results show that coronary artery flow is directly related to shunt position.     

Tissue oxygenation in septic respiratory failure

The relationships between tissue oxygenation and the different haemodynamic and respiratory parameters were studied in 20 patients with ARDS of septic origin. Good regressions were found between O2 delivery and cardiac index (r = 0.8507), O2 delivery and systemic vascular resistance (r = -0.7051), O2 extraction ratio and mixed venous O2 saturation (r = 0.8978), O2 consumption and cardiac index (r = 0.6593), O2 consumption and systemic vascular resistance (r = -0.6548), and O2 consumption and mixed venous O2 saturation (r = -0.7068). The correlation among the parameters of tissue oxygenation was more expressed between O2 extraction ratio and O2 consumption (r = 0.7285), than between O2 delivery and O2 consumption (r = 0.6095). A better result was achieved by multiple regression analysis, where the multiple r was 0.9748 between O2 consumption and O2 delivery + O2 extraction ratio, whereas the other variables did not increase the multiple r significantly. These regressions also proved the relationship following from the Fick equation, that is O2 consumption is the result of O2 delivery multiplied with the O2 extraction ratio.     

Upstream pressure for systemic to pulmonary flow from bronchial circulation in dogs

Systemic to pulmonary flow from bronchial circulation, important in perfusing potentially ischemic regions distal to pulmonary vascular obstructions, depends on driving pressure between an upstream site in intrathoracic systemic arterial network and pulmonary vascular bed. The reported increase of pulmonary infarctions in heart failure may be due to a reduction of this driving pressure. We measured upstream element for driving pressure for systemic to pulmonary flow from bronchial circulation by raising pulmonary venous pressure (Ppv) until the systemic to pulmonary flow from bronchial circulation ceased. We assumed that this was the same as upstream pressure when there was flow. Systemic to pulmonary flow from bronchial circulation was measured in left lower lobes (LLL) of 21 anesthetized open-chest dogs from volume of blood that overflowed from pump-perfused (90-110 ml/min) pulmonary vascular circuit of LLL and was corrected by any changes of LLL fluid volume (wt). Systemic to pulmonary flow from bronchial circulation upstream pressure was linearly related to systemic arterial pressure (slope = 0.24, R = 0.845). Increasing Ppv caused a progressive reduction of systemic to pulmonary flow from bronchial circulation, which stopped when Ppv was 44 +/- 6 cmH2O and pulmonary arterial pressure was 46 +/- 7 cmH2O. A further increase in Ppv reversed systemic to pulmonary flow from bronchial circulation with blood flowing back into the dog. When net systemic to pulmonary flow from bronchial circulation by the overflow and weight change technique was zero a small bidirectional flow (3.7 +/- 2.9 ml.min-1 X 100 g dry lobe wt-1) was detected by dispersion of tagged red blood cells that had been injected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen transport during steady-state submaximal exercise in chronic hypoxia

Arterial O2 delivery during short-term submaximal exercise falls on arrival at high altitude but thereafter remains constant. As arterial O2 content increases with acclimatization, blood flow falls. We evaluated several factors that could influence O2 delivery during more prolonged submaximal exercise after acclimatization at 4,300 m. Seven men (23 +/- 2 yr) performed 45 min of steady-state submaximal exercise at sea level (barometric pressure 751 Torr), on acute ascent to 4,300 m (barometric pressure 463 Torr), and after 21 days of residence at altitude. The O2 uptake (VO2) was constant during exercise, 51 +/- 1% of maximal VO2 at sea level, and 65 +/- 2% VO2 at 4,300 m. After acclimatization, exercise cardiac output decreased 25 +/- 3% compared with arrival and leg blood flow decreased 18 +/- 3% (P less than 0.05), with no change in the percentage of cardiac output to the leg. Hemoglobin concentration and arterial O2 saturation increased, but total body and leg O2 delivery remained unchanged. After acclimatization, a reduction in plasma volume was offset by an increase in erythrocyte volume, and total blood volume did not change. Mean systemic arterial pressure, systemic vascular resistance, and leg vascular resistance were all greater after acclimatization (P less than 0.05). Mean plasma norepinephrine levels also increased during exercise in a parallel fashion with increased vascular resistance. Thus we conclude that both total body and leg O2 delivery decrease after arrival at 4,300 m and remain unchanged with acclimatization as a result of a parallel fall in both cardiac output and leg blood flow and an increase in arterial O2 content.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet-activating factor modulates pulmonary vasomotor tone in the perinatal lamb

Eight near-term fetal lambs were studiedacutely in utero to determine role of platelet-activating factor (PAF)in the regulation of vasomotor tone in systemic and pulmonarycirculations in the immediate perinatal period. Four fetal lambs werestudied predelivery and 2 h postdelivery to determine circulating PAFlevels. Aortic and pulmonary arterial pressures and cardiac output weremeasured continuously, and systemic and pulmonary vascular resistances were calculated. Left pulmonary arterial blood flow was also measured in four fetal lambs. After delivery and oxygenation, circulating PAFlevels fell significantly. When WEB-2170, a specific PAF-receptor antagonist, was infused to block effect of endogenous PAF in the eightnear-term fetal lambs, systemic vascular resistance fell 30% butpulmonary vascular resistance fell dramatically by 68%. Specificity of WEB-2170 was tested in juvenile lambs and was found tobe very specific in lowering vasomotor tone only when tone was elevatedby action of PAF. Our data show that endogenous PAF levels in the fetuscontribute to maintain a high basal systemic and pulmonary vasomotortone and that a normal fall in circulating PAF levels after birth andoxygenation may facilitate fall in pulmonary vascular resistance atbirth.

     

Potent effects of aerosol compared with intravenous treprostinil on the pulmonary circulation.

Inhaled vasodilator therapy for pulmonary hypertension may decrease the systemic side effects commonly observed with systemic administration. Inhaled medications only reach ventilated areas of the lung, so local vasodilation may improve ventilation-perfusion matching and oxygenation. We compared the effects of intravenous vs. aerosolized treprostinil on pulmonary and systemic hemodynamics in an unanesthetized sheep model of sustained acute pulmonary hypertension. Acute, stable pulmonary hypertension was induced in instrumented unanesthetized sheep by infusing a PGH(2) analog, U-44069. The sheep were then administered identical doses of treprostinil either intravenously or by aerosol. Systemic and pulmonary hemodynamics were recorded during each administration. Both intravenous and aerosol delivery of treprostinil reduced pulmonary vascular resistance and pulmonary arterial pressure, but the effect was significantly greater with aerosol delivery (P < 0.05). Aerosol delivery of treprostinil had minimal effects on systemic hemodynamics, whereas intravenous delivery increased heart rate and cardiac output and decreased left atrial pressure and systemic blood pressure. Aerosol delivery of the prostacyclin analog treprostinil has a greater vasodilatory effect in the lung with minimal alterations in systemic hemodynamics compared with intravenous delivery of the drug. We speculate that this may result from treprostinil stimulated production of vasodilatory mediators from pulmonary epithelium.     

Effects of respiratory muscle unloading on leg muscle oxygenation and blood volume during high-intensity exercise in chronic heart failure

Blood flow requirements of the respiratory muscles (RM) increase markedly during exercise in chronic heart failure (CHF). We reasoned that if the RM could subtract a fraction of the limited cardiac output (QT) from the peripheral muscles, RM unloading would improve locomotor muscle perfusion. Nine patients with CHF (left ventricle ejection fraction = 26 +/- 7%) undertook constant-work rate tests (70-80% peak) receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxy-hemoglobyn, oxi-Hb ([O2Hb]), tissue oxygenation index, and total Hb ([HbTOT], an index of local blood volume) in the vastus lateralis were measured by near infrared spectroscopy. In addition, QT was monitored by impedance cardiography and arterial O2 saturation by pulse oximetry (SpO2). There were significant improvements in exercise tolerance (Tlim) with PAV. Blood lactate, leg effort/Tlim and dyspnea/Tlim were lower with PAV compared with sham ventilation (P < 0.05). There were no significant effects of RM unloading on systemic O2 delivery as QT and SpO2 at submaximal exercise and at Tlim did not differ between PAV and sham ventilation (P > 0.05). Unloaded breathing, however, was related to enhanced leg muscle oxygenation and local blood volume compared with sham, i.e., higher Delta[O2Hb]% and Delta[HbTOT]%, respectively (P < 0.05). We conclude that RM unloading had beneficial effects on the oxygenation status and blood volume of the exercising muscles at similar systemic O2 delivery in patients with advanced CHF. These data suggest that blood flow was redistributed from respiratory to locomotor muscles during unloaded breathing.     

Evaluation of the efficacy of extracorporeal membrane oxygenation of animals with acute respiratory insufficiency

The efficiency of extracorporeal membrane oxygenation was studied for 2-3 hours in experiments on dogs with severe ventilatory respiratory failure. Extracorporeal oxygenation led to the decrease in arterial hypoxaemia and hypercapnia in animals. However, the variables did not reach the initial levels and were closer to normal values during veno-venous and not veno-arterial perfusion. During extracorporeal membrane oxygenation total systemic blood flow exceeded the initial level irrespective of the means of perfusion and total oxygen transport did not decline lower than the initial level. At the same time during veno-arterial perfusion oxygen delivery provided by the cardiac output decreased almost two-fold by the second hour of perfusion. This might be the reason for inadequate oxygen delivery to the brain and heart. 67% and 71% of animals survived after veno-arterial and veno-venous perfusion, respectively.     

Hemodynamic effects of postpulmonary administration of prostaglandin D2 in fetal animals

Dose-response relationships in pulmonary vascular resistance (PVR), mean systemic arterial pressure (SAP), and heart rate (HR) to left atrial administration of prostaglandin D2 (PGD2) were determined in five fetal lambs. Fetuses were delivered by cesarean section from chloralose anesthetized ewes with the umbilical circulation maintained intact. Fetuses were prevented from breathing thus maintaining pulmonary vascular tone in the elevated fetal state. Blood was withdrawn from the inferior vena cava and pumped at constant flow into the lower left lobe of the fetal lung. Postpulmonary infusions of PGD2 brought about dose-dependent decreases in pulmonary vascular resistance. Heart rate tended to increase in fetal lambs. Mean systemic arterial pressure increased in the fetal lambs at all doses tested except for the largest dose (44.14 micrograms/kg X min), which produced slight hypotension. These data demonstrate that exposure to the systemic circulation prior to entering the pulmonary vasculature does not alter the preferential dilator action of PGD2 on fetal pulmonary vessels nor does it produce significant systemic hypotension.     

Multiscale modelling in biofluidynamics: application to reconstructive paediatric cardiac surgery

Multiscale computing is a challenging area even in biomechanics. Application of such a methodology to quantitatively compare postoperative hemodynamics in congenital heart diseases is very promising. In the treatment of hypoplastic left heart syndrome, which is a congenital heart disease where the left ventricle is missing or very small, the necessity to feed the pulmonary and systemic circulations is obtained with an interposition shunt. Two main options are available and differ from the sites of anastomoses: (i) the systemic-to-pulmonary conduit (Blalock-Taussig shunt known as the Norwood Operation (NO)) connecting the innominate artery (NO-BT) or the aorta (NO-CS) to the right pulmonary artery and (ii) the right ventricle to pulmonary artery shunt (known as Sano operation (SO)). The proposition that the SO is superior to the NO remains controversial. 3-D computer models of the NO (NO-BT and NO-CS) and SO were developed and investigated using the finite volume method. Conduits of 3, 3.5 and 4 mm were used in the NO models, whereas conduits of 4, 5 and 6 mm were used in the SO model. The hydraulic nets (lumped resistances, compliances, inertances and elastances) which represent the systemic, coronary and pulmonary circulations and the heart were identical in the two models. A multiscale approach was adopted to couple the 3-D models with the circulation net. Computer simulation results were compared with post-operative catheterization data. Results showed that (i) there is a good correlation between predicted and observed data: higher aortic diastolic pressure, decreased pulmonary arterial pressure, lower pulmonary-to-systemic flow ratio and higher coronary perfusion pressure in SO; (ii) there is a minimal regurgitant flow in the SO conduit. The close correlation between predicted and observed clinical data supports the use of mathematical modelling, with a mandatory multiscale approach, in the design and assessment of surgical procedures.     

Atrial septostomy benefits severe pulmonary hypertension patients by increase of left ventricular preload reserve

At present, it is unknown why patients suffering from severe pulmonary hypertension (PH) benefit from atrial septostomy (AS). Suggested mechanisms include enhanced filling of the left ventricle, reduction of right ventricular preload, increased oxygen availability in the peripheral tissue, or a combination. A multiscale computational model of the cardiovascular system was used to assess the effects of AS in PH. Our model simulates beat-to-beat dynamics of the four cardiac chambers with valves and the systemic and pulmonary circulations, including an atrial septal defect (ASD). Oxygen saturation was computed for each model compartment. The acute effect of AS on systemic flow and oxygen delivery in PH was assessed by a series of simulations with combinations of different ASD diameters, pulmonary flows, and degrees of PH. In addition, blood pressures at rest and during exercise were compared between circulations with PH before and after AS. If PH did not result in a right atrial pressure exceeding the left one, AS caused a left-to-right shunt flow that resulted in decreased oxygenation and a further increase of right ventricular pump load. Only in the case of severe PH a right-to-left shunt flow occurred during exercise, which improved left ventricular preload reserve and maintained blood pressure but did not improve oxygenation. AS only improves symptoms of right heart failure in patients with severe PH if net right-to-left shunt flow occurs during exercise. This flow enhances left ventricular filling, allows blood pressure maintenance, but does not increase oxygen availability in the peripheral tissue.     

Increased vasoreactivity and chronic pulmonary hypertension following thoracic irradiation in sheep

Six chronically catheterized sheep were exposed to 1,500-rad whole-lung irradiation and followed for a four-week period. Pulmonary arterial, left atrial and systemic arterial pressures, cardiac output, arterial blood gases, and pH were measured at base line and biweekly following radiation. Pulmonary vasoreactivity to 12% O2, 100% O2, and an analogue of prostaglandin H2 (PGH2-A) was also assessed. Five nonirradiated sheep served as controls. By the 2nd wk following irradiation, pulmonary vascular resistance had doubled. Final pulmonary arterial pressure was increased 50% over the base-line value (base line = 14 +/- 1 cm H2O; final 22 +/- 2; mean +/- SE; P less than 0.05). Arterial PO2 was decreased to approximately 70 Torr throughout the study. In addition, pulmonary vasoreactivity to PGH2-A, but not to breathing 12 or 100% O2, was significantly increased above base line in the irradiated animals (P less than 0.05). Morphometric techniques applied to the lungs in which the pulmonary arterial circulation was distended with barium gelatin mixture, showed extension of muscle into the distal intra-acinar arteries, and a reduction in both the external diameter and the number of barium-filled peripheral arteries in the irradiated animals. Thus thoracic irradiation results in functional and structural changes of chronic pulmonary hypertension and increased pulmonary vasoreactivity to PGH2-A. The structural changes in the peripheral pulmonary arterial bed may contribute to the increased pulmonary vascular reactivity following thoracic irradiation.     

Vascular resistance and vasoactivity of gills and pulmonary artery of the salamander,Ambystoma tigrinum

Summary In order to understand the blood flow patterns and their regulation in the gills and pulmonary artery ofAmbystoma tigrinum, the vascular resistance and vasoactivity of the two major branchial perfusion pathways and a vascular plexus in the pulmonary artery were investigated using an isolated-tissue perfusion method. Acetylcholine and epinephrine were both pressor agents in all three vascular segments. Angiotensin II also constricted the branchial respiratory vasculature. Norephinephrine was primarily a vasodilator in the branchial respiratory vasculature, however, it had no effect on the shunt vessels of the gill or the pulmonary arterial plexus. Both gill circulations were insensitive to alterations in CO₂ and pH. Anoxia produced a slight vasodilation of the branchial respiratory vessels but had no effect on the shunt vasculature. Mild hypoxia had no effect on either branchial circulations. The results suggest that: (1) blood flow through the respiratory section of the gill may vary between 8 and 47% of total gill flow, (2) the major perfusion pathway to the lung is probably from the efferent artery of the third gill through the ductus arteriosus and then into the pulmonary artery, (3) O₂, CO₂ and pH exert no local control of branchial perfusion, (4) both cholinergic and adrenergic regulation of branchial and proximal pulmonary arterial vascular resistance is possible, (5) a rise in circulating norepinephrine should increase blood flow to the respiratory section of the gill.Abbreviations AII angiotensin II - ACh acetylcholine - EPi epinephrine - NE norepinephrine     

Decreased O2 consumption and cardiac output during normobaric hyperoxia in conscious dogs

Recent reports indicate that under certain restricted conditions hyperoxia may decrease tissue O2 consumption. However, this effect has not been established for whole body O2 consumption in the intact healthy conscious state. The goal of the present study was to document the effect of hyperoxia on resting whole body O2 consumption and hemodynamics under these latter more general physiological conditions. The inspired gas was delivered by mask to six fasted resting conscious dogs and alternated hourly between air and O2-enriched air (hyperoxia) for 5 h, while hemodynamics and blood gas data were obtained every 20 min. Compared with air breathing, hyperoxia increased the mean arterial O2 tension from 95 to 475 Torr and decreased heart rate, cardiac output, pulmonary vascular resistance, and right and left ventricular work rates and thus, presumably, myocardial O2 consumption. Hyperoxia also increased systemic vascular resistance and right atrial pressure but did not change stroke volume or systemic arterial pressure. The increase in arterial O2 content during hyperoxia was counterbalanced by the decrease in cardiac output, so that O2 delivery was unchanged by hyperoxia. Surprisingly, hyperoxia decreased the arterial-to-mixed venous difference in O2 content; this decrease together with the decrease in cardiac output produced a decrease in resting whole body O2 consumption from 5.88 +/- 0.68 to 4.80 +/- 0.62 ml O2.min-1.kg-1 (P = 0.0002). It is concluded that under physiological conditions normobaric hyperoxia may decrease metabolic rate in addition to cardiac output, which may have important implications for the metabolic regulation of O2 utilization as well as for the medical and nonmedical uses of O2.     

A computational framework for adjusting flow during peripheral extracorporeal membrane oxygenation to reduce differential hypoxia

Peripheral veno-arterial extra corporeal membrane oxygenation (VA-ECMO) is an established technique for short-to-medium support of patients with severe cardiac failure. However, in patients with concomitant respiratory failure, the residual native circulation will provide deoxygenated blood to the upper body, and may cause differential hypoxemia of the heart and brain. In this paper, we present a general computational framework for the identification of differential hypoxemia risk in VA-ECMO patients. A range of different VA-ECMO patient scenarios for a patient-specific geometry and vascular resistance were simulated using transient computational fluid dynamics simulations, representing a clinically relevant range of values of stroke volume and ECMO flow. For this patient, regardless of ECMO flow rate, left ventricular stroke volumes greater than 28 mL resulted in all aortic arch branch vessels being perfused by poorly-oxygenated systemic blood sourced from the lungs. The brachiocephalic artery perfusion was almost entirely derived from blood from the left ventricle in all scenarios except for those with stroke volumes less than 5 mL. Our model therefore predicted a strong risk of differential hypoxemia in nearly all situations with some residual cardiac function for this combination of patient geometry and vascular resistance. This simulation highlights the potential value of modelling for optimising ECMO design and procedures, and for the practical utility for personalised approaches in the clinical use of ECMO.     

Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF

Endothelin (ET) contributes to the increased systemic vascular resistance and elevated cardiac filling pressures seen in congestive heart failure (CHF). We investigated to what extent ET-mediated vasoconstriction in CHF occurs through an endocrine action of elevated plasma ET or by an autocrine/paracrine mechanism related to induction of vascular ET gene expression. Three weeks of pacing (225 beats/min) induced a marked release of ET-1 from the pulmonary circulation with a sixfold elevation of arterial plasma ET in CHF pigs compared with sham-operated pigs. Arterial plasma ET was the strongest and only independent predictor of systemic vascular resistance. In contrast, vascular preproET-1 and ET-receptor mRNA expression were unaltered or decreased in CHF pigs and did not correlate with indexes of vascular tone. However, myocardial preproET-1 mRNA expression increased twofold in CHF pigs. PreproET-2 and preproET-3 mRNAs were not detectable in cardiovascular tissues. In conclusion, plasma ET was markedly increased because of an augmented release from the pulmonary circulation during CHF, and arterial plasma ET correlated with systemic vascular resistance. The absence of ET induction in the peripheral vasculature suggests that ET increases vascular tone during CHF by an endocrine, not an autocrine/paracrine, mechanism.     

Umbilical cord compression produces pulmonary hypertension in newborn lambs: a model to study the pathophysiology of persistent pulmonary hypertension in the newborn

We investigated the effects of chronic intrauterine hypoxaemia produced by prolonged partial umbilical cord compression on the circulation shortly after birth in lambs. Vascular catheters were inserted in 10 fetal sheep at 120 to 130 days gestation to measure descending aortic blood gases, arterial pH, and arterial O2 saturation. An inflatable silicone rubber balloon cuff was also placed around the umbilical cord. After recovery and the return of descending aortic blood gases to the normal range, the balloon was gradually inflated, decreasing the PaO2 from 21.2 +/- 3.6 to 17.5 +/- 1.3 mm Hg and the arterial O2 saturation from 57.1 +/- 9.2% to 37.2% +/- 5.2. After 14.3 +/- 3.7 days of partial umbilical cord compression, the lambs were delivered by Caesarean section, instrumented to measure systemic and pulmonary arterial, right atrial and pulmonary arterial wedge pressures, pulmonary and systemic blood flows, and mechanically ventilated. Five normal lambs were also studied. From 60 to 120 min after delivery, when compared to normal lambs, the umbilical compression lambs had an increased pulmonary arterial pressure (P less than 0.05) pulmonary vascular resistance (P less than 0.05), and right atrial pressure (P less than 0.05) with similar arterial blood gases. In both groups, hypoxic ventilation produced an increase in pulmonary arterial pressure (P less than 0.05) which on return to room air ventilation decreased to baseline in the normal lambs but not in the umbilical cord compression lambs (P less than 0.05). Prolonged partial umbilical cord compression produces chronic fetal hypoxaemia and pulmonary arterial hypertension after birth. This may represent a model to study the pathophysiology of persistent pulmonary hypertension syndrome.     

Multiscale modeling of the cardiovascular system: application to the study of pulmonary and coronary perfusions in the univentricular circulation

The objective of this study is to compare the coronary and pulmonary blood flow dynamics resulting from two configurations of systemic-to-pulmonary artery shunts currently utilized during the Norwood procedure: the central (CS) and modified Blalock Taussig (MBTS) shunts. A lumped parameter model of the neonatal cardiovascular circulation and detailed 3-D models of the shunt based on the finite volume method were constructed. Shunt sizes of 3, 3.5 and 4 mm were considered. A multiscale approach was adopted to prescribe appropriate and realistic boundary conditions for the 3-D models of the Norwood circulation. Results showed that the average shunt flow rate is higher for the CS option than for the MBTS and that pulmonary flow increases with shunt size for both options. Cardiac output is higher for the CS option for all shunt sizes. Flow distribution between the left and the right pulmonary arteries is not completely balanced, although for the CS option the discrepancy is low (50-51% of the pulmonary flow to the right lung) while for the MBTS it is more pronounced with larger shunt sizes (51-54% to the left lung). The CS option favors perfusion to the right lung while the MBTS favors the left. In the CS option, a smaller percentage of aortic flow is distributed to the coronary circulation, while that percentage rises for the MBTS. These findings may have important implications for coronary blood flow and ventricular function.     

The aetiology of hypoxaemia in chickens selected for rapid growth

In comparison to other classes of chickens, broilers selected for rapid growth tend to be hypoxaemic, and many develop congestive heart failure (CHF). In order to explain the physiological mechanisms associated with hypoxaemia in fast-growing broiler chickens (Gallus gallus), this study examined several basic physiological parameters including the blood gas profile in arterial [left atrial (LA)] and mixed venous [right atrial (RA)] blood, systemic oxygen extraction ratio, and intrapulmonary shunt fraction. These parameters were further studied in the context of blood flow in the pulmonary circulation, structural characteristics of the lungs, and cardiac function [measured as cardiac index (CI)]. Overall, broilers had lower arterial and mixed venous blood pO(2) levels and higher pCO(2) levels compared to leghorns. The cardiac index was lower in fast-growing and CHF broilers compared to leghorn chickens or feed-restricted broilers. Systemic oxygen extraction ratio (ER) and intrapulmonary shunt fraction were significantly higher in fast-growing broilers and birds with CHF (all P<0.01). Lungs of all broilers, but not leghorns, contained ectopic, irregular nodular formations located within air spaces. Broilers with clinical signs of hypoxaemia revealed the highest number of these formations in their lung. Taken together, the present findings indicate that key factors associated with the development of hypoxaemia in fast-growing broilers include: (1) high demand for oxygen as evidenced by high oxygen ER; (2) inadequate cardiac output (CO) to fulfill the higher oxygen demands, leading to severe depletion of O(2) in mixed venous blood; and (3) elevated intrapulmonary shunt fraction and possibly dead space associated with specific pathological and anatomical characteristics within the lung.