A biphasic model for sinusoidal liver perfusion remodeling after outflow obstruction

Liver resection can lead to focal outflow obstruction due to transection of hepatic veins. Outflow obstruction may cause additional damage to the small remnant liver. Drainage of the obstructed territories is reestablished via dilatation of sinusoids. Subsequently, sinusoidal canals are formed draining the blood from the obstructed territory to the neighboring unobstructed territories. We raised the phenomenological hypothesis that the blood pressure gradient is the main driving force for the formation of sinusoidal vascular canals. We generated a biphasic mechanical model to describe this vascular remodeling process in relation to the variable pressure gradient. Therefore, we introduced a transverse isotropic permeability relation as well as an evolutional optimization rule to describe the relationship between pressure gradient and the direction of the sinusoidal blood flow in the fluid phase. As a next step, we developed a framework for the calculation concept including the representation of the governing weak formulations. Then, we examined a representative numerical example with simulation of the blood flow under both conditions, the physiological situation as well as after outflow obstruction. Doing so, we were able to reproduce numerically the experimentally observed process of reestablishing hepatic venous drainage via redirection of blood flow and formation of new vascular structures in respect to the fluid flow. The calculated results support the hypothesis that the reorientation of blood flow mainly depends on the pressure gradient. Further investigations are needed to determine the micromechanical influences on the reorientation of the sinusoids.     

Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure.

To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.     

The erect posture as an aid to the circulation in the feet in the presence of arterial obstruction

When the main artery in the lower limb is occluded and narrow collateral vessels by-passing the obstruction offer the limiting resistance to blood flow, the increase in arterial pressure at the ankle on assuming the erect posture is greater than would be predicted by consideration of the hydrostatic factors. In seven patients with femoral artery occlusion the pressure at the ankle was greater than expected in all and on the average by 8.0 mm. Hg±1.5 S.E. when sitting, (P<0.01) and in the four patients tested, by 12.4 mm. Hg±0.5 S.E. when standing (P<0.01). Rate of blood flow in subdermal tissue of the forefoot estimated by xenon-133 clearance was an average of 21% less when sitting than when supine in five limbs of four normal subjects while in five limbs with occlusion or severe stenosis of the superficial femoral artery the rate of flow was an average of 44% greater.     

A Comparison of Varying alpha-Blockers and Other Pharmacotherapy Options for Lower Urinary Tract Symptoms

alpha(1)-Adrenoceptor antagonists are now well established as the most common treatment for lower urinary tract symptoms (LUTS) suggestive of bladder outflow obstruction associated with benign prostatic hyperplasia. Both alpha(1)-adrenoceptor antagonists and 5alpha-reductase inhibitors are accepted treatments for LUTS, but with finasteride this applies only to patients with clinically enlarged prostates, whereas alpha(1)-adrenoceptor antagonists are considered to be appropriate treatment for all patients, irrespective of prostate size. Systematic analyses of placebo-controlled studies show that commonly used alpha(1)-blockers are significantly superior to placebo in improving urinary flow and reducing symptoms. Efficacy of alpha-blockers appears to be well maintained over time, and there is no evidence of tolerance or tachyphylaxis to alpha(1)-blockade after 6-12 months' usage. Direct comparative trials show that, in the short term, alpha(1)-adrenoceptor antagonists are more effective than finasteride in reducing symptom score. For alpha(1)-adrenoceptor antagonists, the most commonly reported adverse effects are dizziness, asthenia, postural hypotension, and syncope. Alfuzosin has a more pronounced effect on blood pressure than does tamsulosin, especially in elderly patients. Tamsulosin is well tolerated and has minimal effects on blood pressure; tamsulosin 0.4 mg has the lowest potential to reduce blood pressure and causes less symptomatic orthostatic hypotension than terazosin.     

Role of the rise of pressure in the pulmonary artery in the distribution of perfusion and gas exchange in bronchial obstruction

The experiments on the dogs revealed that the damage of lobar bronchus conduction resulted in the decrease of O2 tension in pulmonary venous blood of this lobe. The decrease in the ventilation and blood flow was found in the zone of obstruction by using tracers 133Xe and 99mTc. The pressure rise in the pulmonary artery caused by the spread of bronchial obstruction is one of the factors promoting the redistribution of perfusion into the reserve zones of lungs. The decrease of pressure by the ganglio-blocking preparation results in the increase of arterial hypoxemia.     

Acute increase in anastomotic bronchial blood flow after pulmonary arterial obstruction

We examined the acute changes in anastomotic bronchial blood flow (Qbr) serially for the 1st h after pulmonary arterial obstruction and subsequent reperfusion. We isolated and perfused the pulmonary circulation of the otherwise intact left lower lobe (LLL) with autologous blood in the widely opened chest of anesthetized dogs. Qbr was measured from the amount of blood overflowing from the closed pulmonary vascular circuit and the changes in the lobe weight. The right lung and the test lobe (LLL) were ventilated independently. The LLL, which was in zone 2 (mean pulmonary arterial pressure = 14.8 cm H2O, pulmonary venous pressure = 0, alveolar pressure = 5-15 cmH2O), was weighed continuously. The systemic blood pressure, gases, and acid-base status were kept constant. In control dogs without pulmonary arterial obstruction, the Qbr did not change for 2 h. Five minutes after pulmonary arterial obstruction, there was already a marked increase in Qbr, which then continued to increase for 1 h. After reperfusion, Qbr decreased. The increase in Qbr was greater after complete lobar than sublobar pulmonary arterial obstruction. It was unaltered when the downstream pulmonary venous pressure was increased to match the preobstruction pulmonary microvascular pressure. Thus, in zone 2, reduction in downstream pressure was not responsible for the increase in Qbr; neither was the decrease in alveolar PCO2, since ventilating the lobe with 10% CO2 instead of air did not change the Qbr. These findings suggest that there is an acute increase in Qbr after pulmonary arterial obstruction and that is not due to downstream pressure or local PCO2 changes.     

Wedge pressure in large vs. small pulmonary arteries to detect pulmonary venoconstriction

Pulmonary arterial wedge pressure measures the pressure where blood flow resumes on the venous side. By occlusion of a large artery, the point where blood flow resumes will be in or near the left atrium. However, by occlusion of a small artery, it is possible to shift the point where flow resumes to a more proximal site in the veins and thus measure a pressure within the small veins. Increased pulmonary venous pressure, as a result of partial obstruction in the large veins, may not be detected by wedging a Swan-Ganz catheter in a large artery but may be detected by wedging in a small artery. We demonstrated this phenomenon in open-chest dogs by mechanically obstructing the left lower lobar vein or by infusing histamine to cause a generalized pulmonary venoconstriction. The wedge pressure measured by a 7-F Swan-Ganz catheter, with its balloon inflated in the main left lower lobar artery, nearly equaled left atrial pressure. On the other hand, the wedge pressure measured with a 7-F, 5-F, or a PE-50 catheter advanced into a small artery (without a balloon) was considerably higher than left atrial pressure. These results suggest that high resistance in the pulmonary veins can be demonstrated with the Swan-Ganz catheter by comparing the pressures obtained with the catheter wedged in a small and large artery.     

Increased vascular resistance in paralyzed legs after spinal cord injury is reversible by training.

The purpose of the present study was to determine the effect of a spinal cord injury (SCI) on resting vascular resistance in paralyzed legs in humans. To accomplish this goal, we measured blood pressure and resting flow above and below the lesion (by using venous occlusion plethysmography) in 11 patients with SCI and in 10 healthy controls (C). Relative vascular resistance was calculated as mean arterial pressure in millimeters of mercury divided by the arterial blood flow in milliliters per minute per 100 milliliters of tissue. Arterial blood flow in the sympathetically deprived and paralyzed legs of SCI was significantly lower than leg blood flow in C. Because mean arterial pressure showed no differences between both groups, leg vascular resistance in SCI was significantly higher than in C. Within the SCI group, arterial blood flow was significantly higher and vascular resistance significantly lower in the arms than in the legs. To distinguish between the effect of loss of central neural control vs. deconditioning, a group of nine SCI patients was trained for 6 wk and showed a 30% increase in leg blood flow with unchanged blood pressure levels, indicating a marked reduction in vascular resistance. In conclusion, vascular resistance is increased in the paralyzed legs of individuals with SCI and is reversible by training.     

Effects of arterial pressure on lung capillary pressure and edema after microembolism

The effect of increased arterial pressure (Pa) on microvessel pressure (Pc) and edema following microvascular obstruction (100-micron glass spheres) was examined in the isolated ventilated dog lung lobe pump perfused with blood. Lobar vascular resistance (PVR) increased 2- to 10-fold following emboli when either Pa or flow was held constant. Microbead obstruction increased the ratio of precapillary to total PVR from 0.60 +/- 0.05 to 0.84 +/- 0.02 (SE) or to 0.75 +/- 0.06 (n = 6), as determined by the venous occlusion and the isogravimetric capillary pressure techniques, respectively. Isogravimetric Pc (5.0 +/- 0.7) did not differ from Pc obtained by venous occlusion (3.8 +/- 0.2 Torr, n = 6). After embolism, Pc in constant Pa decreased from 6.2 +/- 0.3 to 4.4 +/- 0.3 Torr (n = 16). In the constant-flow group, embolism doubled Pa while Pc increased only 40% (6.7 +/- 0.6 to 9.2 +/- 1.4 Torr, n = 6) with no greater edema formation than in the constant Pa groups. These data indicate poor transmission of Pa to filtering capillaries. Microembolism, even when accompanied by elevated Pa and increased flow velocity of anticoagulated blood of low leukocyte and platelet counts, caused little edema. Our results suggest that mechanical effects alone of lung microvascular obstruction cause minimal pulmonary edema.     

Development of a twin-flap,porous ceramic mitral valve prosthesis

The pressure drop in most existing cardiac valve prostheses is at least ten times greater than for healthy valves. Steady flow testing indicates that the causes are (i) poor orifice diameter/sewing ring diameter ratio; (ii) occluding mechanism causes obstruction in the region of highest blood velocity. A new mitral prosthesis was constructed to overcome these deficiencies. The significant features are (a) tubular construction to maximize flow area; (b) twin flaps with hinges well above the outlet to minimize obstruction; (c) divergent nozzle to aid pressure recovery. Prostheses were manufactured from porous alumina, promoting firmly anchored, thin tissue growth to reduce haemolysis and thromboembolism. Preliminary trials in mini-pigs show good valve function. The ceramic behaves especially well. Future models will use ceramic flaps to replace the delrin flaps used at present, which encourage fibrin deposits.     

Nifedipine in hypertensive emergencies.

The effects and safety of using oral nifedipine 10-20 mg as acute antihypertensive treatment were studied in a single-blind placebo-controlled study of 25 consecutive patients with very high blood pressure requiring emergency reduction. In addition the effect of this treatment on cerebral blood flow was investigated using xenon-133 in 10 patients randomly allocated to receive oral nifedipine or intravenous clonidine. Whereas placebo did not alter the blood pressure, oral nifedipine significantly reduced the systolic and diastolic blood pressures in all 25 patients (from 221 +/- 22/126 +/- 14 mm Hg to 152 +/- 20/89 +/- 12 mm Hg after 30 minutes, p less than 0.001). Heart rate increased from 74 +/- 11 to 84 +/- 11 beats/minute (p less than 0.01); this effect was inversely related to age (r = -0.65, p less than 0.01). The falls in systolic and diastolic blood pressures were closely related to the blood pressures before treatment ) r = 0.67, p less than 0.001 for systolic, and r = -0.58, p less than 0.01 for diastolic values). No serious unwanted effects were observed. Measurement of cerebral blood flow after nifedipine showed an increase in flow in four out of five patients. Clonidine, by contrast, reduced cerebral blood flow in all patients by up to 28%. Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.     

Neck web and congenital heart defects: a pathogenic association in 45 X-O Turner syndrome?

This study explores the association between neck web and congenital heart disease in patients with Turner syndrome. Of 193 cases with documented 45 X-O karyotype, 106 (55%) had a web neck and 87 (45%) had a normal neck. The incidence of congenital heart disease was significantly different between these two groups, occurring in 30% of those with web neck and 9% of those with normal neck (x2 = 12.82, P less than .0005). The difference was most striking in coarctation of the aorta for which the prevalence was 25% with web neck and 3% with normal neck (X2 = 17.65, P less than .0001). The association between web neck and congenital heart disease suggests a pathogenic relationship exists between the two. The following hypothesis is proposed to explain the association. Increased lymphatic pressure associated with jugular lymphatic sac obstruction distends the thoracic ducts, which compress the ascending aorta altering intracardiac blood flow. Redirection of intracardiac blood flow produces coarctation of the aorta and other defects in the spectrum of left heart obstruction. This proposed mechanism is an example of a teratogenic event remote from the heart, which alters cardiovascular morphology.     

The contribution of prostaglandins to renal blood flow maintenance is determined by the level of activity of the renin-angiotensin system

A growing body of experimental and clinical evidence has led to the formation of the hypothesis that the contribution of intrarenal prostaglandins to the determination of renal blood flow is a function of the level of activity of renin-angiotensin system. The following is a brief review of a portion of the pertinent literature. The focus of this review is the effect of inhibition of prostaglandin synthesis on renal blood flow in diverse conditions characterized by increased activity of the renin-angiotensin system, including reduction of renal arterial pressure, ureteral obstruction, hemorrhage, the hepatorenal syndrome, and sodium depletion. Under these conditions, in contrast to the lack of effect in non-stress conditions, the renin-angiotensin system activity is high, and prostaglandin synthesis inhibition is associated with reductions in renal blood flow.     

Structural adaptation increases predicted perfusion capacity after vessel obstruction in arteriolar arcade network of pig skeletal muscle

Arteriolar arcades provide alternate pathways for blood flow after obstruction of arteries or arterioles such as occurs in stroke and coronary and peripheral vascular disease. When obstruction is prolonged, remaining vessels adjust their diameters chronically in response to altered hemodynamic and metabolic conditions. Here, the effectiveness of arcades in maintaining perfusion both immediately following obstruction and after structural adaptation was examined. Morphometric data from a vascular casting of the pig triceps brachii muscle and published data were used to develop a computational model for the hemodynamics and structural adaptation of the arcade network between two feed artery branches, FA1 and FA2. The predicted total flow to capillaries (Q(TA)) in the region initially supplied by FA2 decreased to 26% of the normal value immediately after FA2 obstruction but was restored to 78% of the normal value after adaptation. After obstruction of 1-10 randomly selected arcade segments, Q(TA) was on average 18% higher in the arcade network than in a corresponding two-tree network without arcades. Structural adaptation increased Q(TA) by an additional 16% in the arcade network but had almost no effect in the two-tree network. These results indicate that arcades can partially maintain blood flow after vascular blockage and that this effect is substantially enhanced by structural adaptation.     

Estimation of airway obstruction using oximeter plethysmograph waveform data

Background

Validated measures to assess the severity of airway obstruction in patients with obstructive airway disease are limited. Changes in the pulse oximeter plethysmograph waveform represent fluctuations in arterial flow. Analysis of these fluctuations might be useful clinically if they represent physiologic perturbations resulting from airway obstruction. We tested the hypothesis that the severity of airway obstruction could be estimated using plethysmograph waveform data.

Methods

Using a closed airway circuit with adjustable inspiratory and expiratory pressure relief valves, airway obstruction was induced in a prospective convenience sample of 31 healthy adult subjects. Maximal change in airway pressure at the mouthpiece was used as a surrogate measure of the degree of obstruction applied. Plethysmograph waveform data and mouthpiece airway pressure were acquired for 60 seconds at increasing levels of inspiratory and expiratory obstruction. At each level of applied obstruction, mean values for maximal change in waveform area under the curve and height as well as maximal change in mouth pressure were calculated for sequential 7.5 second intervals. Correlations of these waveform variables with mouth pressure values were then performed to determine if the magnitude of changes in these variables indicates the severity of airway obstruction.

Results

There were significant relationships between maximal change in area under the curve (P < .0001) or height (P < 0.0001) and mouth pressure.

Conclusion

The findings suggest that mathematic interpretation of plethysmograph waveform data may estimate the severity of airway obstruction and be of clinical utility in objective assessment of patients with obstructive airway diseases.     

Systemic blood flow to the lung after bronchial artery occlusion in anesthetized sheep.

To compare the effectiveness of different embolizing agents in reducing or redistributing bronchial arterial blood flow, we measured systemic blood flow to the right lung and trachea in anesthetized sheep by use of the radioactive microsphere method before and 1 h after occlusion of the bronchoesophageal artery (BEA) as follows: injection of 4 ml ethanol (ETOH) into BEA (group 1, n = 5), injection of approximately 0.5 g polyvinyl alcohol particles (PVA) into BEA (group 2, n = 5), or ligation of BEA (group 3, n = 5). After occlusion, angiography showed complete obstruction of the bronchial vessels. There were no changes in tracheal blood flow in any of the groups. Injection of ETOH produced a 75 +/- 14% (SD) reduction in flow to the middle lobe (P less than 0.02) and a 75 +/- 13% reduction to the caudal lobe (P less than 0.01), whereas injection of PVA produced a smaller reduction in flow to these two lobes (41 +/- 66 and 51 +/- 54%, respectively). After BEA ligation there was a 52 +/- 29% reduction in flow to the middle lobe and a 53 +/- 38% reduction to the caudal lobe (P less than 0.05). This study has significant implications both clinically and experimentally; it illustrates the importance of airway collateral circulation, in that apparently complete radiological obstruction of the BEA does not necessarily mean complete obstruction of systemic blood flow. We also conclude that, in experimental studies in which the role of the bronchial circulation in airway pathophysiology is examined, ETOH is the agent of choice.     

Computational modeling of shear-based hemolysis caused by renal obstruction

As endovascular treatment of abdominal aortic aneurysms (AAAs) gains popularity, it is becoming possible to treat certain challenging aneurysmal anatomies with endografts relying on suprarenal fixation. In such anatomies, the bare struts of the device may be placed across the renal artery ostia, causing partial obstruction to renal artery blood flow. Computational fluid dynamics (CFD) was used to simulate blood flow from the aorta to the renal arteries, utilizing patient-specific boundary conditions, in three patient models and calculate the degree of shear-based blood damage (hemolysis). We used contrast-enhanced computed tomography angiography (CTA) data from three AAA patients who were treated with a novel endograft to build patient-specific models. For each of the three patients, we constructed a baseline model and endoframe model. The baseline model was a direct representation of the patient's 30-day post-operative CTA data. This model was then altered to create the endoframe model, which included a ring of metallic struts across the renal artery ostia. CFD was used to simulate blood flow, utilizing patient-specific boundary conditions. Pressures, flows, shear stresses, and the normalized index of hemolysis (NIH) were quantified for all patients. The overall differences between the baseline and endoframe models for all three patients were minimal, as measured though pressure, volumetric flow, velocity, and shear stress. The average NIH across the three baseline and endoframe models was 0.002 and 0.004, respectively. Results of CFD modeling show that the overall disturbance to flow caused by the presence of the endoframe struts is minimal. The magnitude of the NIH in all models was well below the accepted design and safety threshold for implantable medical devices that interact with blood flow.     

Autoregulation of Brain Circulation in Severe Arterial Hypertension

Cerebral blood flow was studied by the arteriovenous oxygen difference method in patients with severe hypertension and in normotensive controls. The blood pressure was lowered to study the lower limit of autoregulation (the pressure below which cerebral blood flow decreases) and the pressure limit of brain hypoxia. Both limits were shifted upwards in the hypertensive patients, probably as a consequence of hypertrophy of the arteriolar walls. These findings have practical implications for antihypertensive therapy.When the blood pressure was raised some patients showed an upper limit of autoregulation beyond which an increase of cerebral blood flow above the resting value was seen without clinical symptoms. No evidence of vasospasm was found in any patient at high blood pressure. These observations may be of importance for the understanding of the pathogenesis of hypertensive encephalopathy.     

Response of pulmonary circulation to oral pirbuterol in chronic airflow obstruction.

The effects of the oral beta agonist pirbuterol on pulmonary haemodynamics and gas exchange were studied in nine patients with severe irreversible airflow obstruction and moderate arterial hypoxaemia. After administration of 15 mg pirbuterol pulmonary vascular resistance fell by 19% but cardiac output rose by 24%, so that pulmonary arterial pressure showed no significant change. Systemic arterial oxygen pressure fell by 7%, limiting the rise in oxygen delivery to 21%. All changes were significant at the 2% level. These results show that pirbuterol dilates the pulmonary bed at the cost of a slight worsening of gas exchange, which is compensated by an independent rise in blood flow.     

Nonocclusive Hemorrhagic Necrosis of the Intestine

Hemorrhagic intestinal necrosis occurs without demonstrable mechanical obstruction of the mesenteric vascular supply. The etiologic factors include (1) congestive heart failure, (2) cardiac arrhythmia, (3) dehydration, and (4) digitalis therapy with or without digitalis toxicity. All of these factors have been shown to result in a decrease in splanchnic blood flow. The outcome of this disease has invariably been fatal. Early recognition and nonoperative management directed toward increasing splanchnic blood flow are the most significant factors in the survival of patients.