A numerical study of aortic flow stability and comparison with in vivo flow measurements.

The development of an engineering transitional turbulence model and its subsequent evaluation and validation for some diseased cardiovascular flows have been suggestive of its likely utility in normal aortas. The existence of experimental data from human aortas, acquired in the early 1970s with catheter-mounted hot film velocimeters, provided the opportunity to compare the performance of the model on such flows. A generic human aorta, derived from magnetic resonance anatomical and velocity images of a young volunteer, was used as the basis for varying both Reynolds number (Re) and Womersley parameter (α) to match four experimental data points from human ascending aortas, comprising two with disturbed flow and two with apparently undisturbed flow. Trials were made with three different levels of inflow turbulence intensity (Tu) to find if a single level could represent the four different cases with 4000 < Re < 10,000 and 17 < α < 26. A necessary boundary condition includes the inflow "turbulence" level, and convincing results were obtained for all four cases with inflow Tu = 1.0%, providing additional confidence in the application of the transitional model in flows in larger arteries. The Reynolds-averaged Navier-Stokes (RANS)-based shear stress transport (SST) transitional model is capable of capturing the correct flow state in the human aorta when low inflow turbulence intensity (1.0%) is specified.

Oxygen supplementation before or after submaximal exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Evidence for improved exercise tolerance or relief of breathlessness by short term use of oxygen before or after exercise in patients with chronic obstructive pulmonary disease (COPD) is scant, and guidelines for this treatment are lacking despite widespread provision in the UK. METHODS: The effect of oxygenation either before or after exercise on perception of breathlessness and walk distance was studied in a group of patients with moderate to severe COPD (mean forced expiratory volume in 1 second (FEV(1)) 34% of predicted, mean 6 minute walk distance on air 283 m), all of whom desaturated by at least 4% on submaximal exercise. Oxygen (28%) or air was delivered double blind and in random order, either for 5 minutes before a standard 6 minute walk test (n=34) or for 5 minutes following the end of the test (n=18). Exercise tolerance was measured as the distance achieved and breathlessness was assessed using visual analogue scales (VAS) which were scored before and after exercise and during recovery. RESULTS: No increase in mean walk distance after oxygen (288 v 283 m) and no improvement in mean breathlessness scores (58 v 54 mm) or recovery times occurred with oxygen taken either before (177 v 184 seconds) or after exercise (182 v 151 seconds). CONCLUSIONS: This group of patients with COPD derived no physiological or symptomatic benefit from oxygen breathed for short periods before or after submaximal exercise. Domiciliary oxygen should only be prescribed for such patients if they have shown objective evidence of benefit on exercise testing.

Evidence for an influence of mechanical restitution on beat-to-beat variations in haemodynamics during chronic atrial fibrillation in patients.

OBJECTIVE: We tested the hypothesis that beat-to-beat changes in haemodynamics during atrial fibrillation include an effect of each preceding R-R interval through the interval-strength relationship (mechanical restitution). BACKGROUND: The variation in stroke volume and pulse pressure characteristic of atrial fibrillation is usually ascribed to time dependent ventricular filling. METHODS: We measured the maximum rate of rise of left ventricular pressure (LVdP/dtmax), and aortic blood velocity and its integral in patients with atrial fibrillation undergoing cardiac catheterisation. The contractile response of isometric human myocardial trabeculae to sequences of atrial fibrillation was also studied, using the recorded ECGs as stimuli. The trabeculae were obtained from the resected right ventricular outflow tracts of patients with Fallot's tetralogy undergoing operative correction. RESULTS: Beat-to-beat variations in contractile function during atrial fibrillation in the patients were recorded as LVdP/dtmax and left ventricular ejection (ascending aortic) velocity integral (proportional to stroke volume). Both these indices correlated well with the response to the same ECG (R wave) sequences in the isometric model measured as the maximum rate of rise of force, dF/dtmax, r = 0.72 to 0.81, p, 0.0001. When short pre-preceding intervals were excluded (minimizing the effect of post-extrasystolic potentiation), these variables showed a positive curvilinear relationship to preceding interval typical of mechanical restitution. CONCLUSIONS: Mechanical restitution, which causes beat-to-beat changes in inotropic state, accounts in part for the changes in stroke volume in atrial fibrillation.

The value of forced expiratory volume in 1 s in screening subjects with stable COPD for PaO2 < 7.3 kPa qualifying for long-term oxygen therapy.

Guidelines on the management of chronic obstructive pulmonary disease (COPD) issued by the European Respiratory Society (ERS), British Thoracic Society (BTS), American Thoracic Society (ATS), and Department of Health for England and Wales (DoH) suggest differing values of forced expiratory volume in 1 s (FEV1) below which arterial blood gas analysis should be performed to determine the presence of severe hypoxaemia and possible long-term oxygen therapy (LTOT) requirement. This study aimed to determine the value of FEV1 at these different levels in screening for LTOT requirement defined as PaO2 < 7.3 kPa in subjects with stable COPD. Comparative measures were taken against other lung function tests of volume and diffusing capacity. A retrospective analysis of paired lung function and arterial oxygen measurements in 491 subjects was made. The positive and negative predictive values, sensitivity and specificity of FEV1 < 70% predicted (ERS), FEV1 < 50% predicted (ATS), FEV1 < 40% predicted (BTS) and FEV1 < 1.51 (DoH) were determined for fulfilling LTOT criteria (PaO2 < 7.3 kPa). The correlation between lung function variables and PaO2 was established. Logistic regression analysis was used to classify subjects with PaO2 < 7.3 kPa and PaO2 > or = 7.3 kPa. Using FEV1 to screen for LTOT requirement produced a high negative predictive value at all four suggested limits (FEV1 < 70% 100%, FEV1 < 50% 96%, FEV1 < 40% 95%, FEV1 < 1.51 97%). However, the positive predictive values were low (FEV1 < 70% 13%, FEV1 < 50% 16%, FEV1 < 40% 19%, FEV1 < 1.51 15%) as were sensitivities. No single lung function variable was a strong determinant of PaO2. FEV1 % pred (r = 0.40), FVC % pred (r = 0.34) and TLCO % pred (r = 0.27) had the strongest relationships. Logistic regression also placed FEV1 % pred and TLCO % pred as the best predictors of PaO2 < 7.3 kPa. We conclude no lung function variable correlates well with PaO2 in subjects with stable COPD. The best predictor of PaO2 < 7.3 kPa was FEV1 % pred. Whilst a low FEV1 is a poor predictor of LTOT requirement in an individual, PaO2 < 7.3 kPa is only found in subjects with a low FEV1. A high FEV1 may be used to exclude subjects from further investigation for LTOT and prevent unnecessary arterial sampling.

Influence of the geometry of the left main coronary artery bifurcation on the distribution of sudanophilia in the daughter vessels.

The proximal portions of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries are among the sites most predisposed to atherosclerotic disease. This predisposition might be a consequence of their location immediately distal to the left main (LM) coronary artery bifurcation, which may increase the susceptibility of these segments by promoting an adverse fluid dynamic environment within them. The detailed geometry of the bifurcation influences this environment and would therefore affect the susceptibility of the proximal daughter vessels to disease. This hypothesis was tested by examination of the relationship between the geometry of the LM bifurcation and the distribution of sudanophilia in the proximal portions of the LAD and LCx. The geometric parameters at the LM bifurcation, including all three angles and LM length, were obtained from multiangle photographs of 17 vascular casts by use of objective computer-based algorithms. A robust index, the relative proximal involvement (RPI), was developed to measure the localization of disease to the proximal portions of the daughter vessels. The RPI of the LAD segment correlated best with an interaction term that included the planarity of the LM bifurcation and the LCx-LAD branch angle (P = .013). In addition to supporting the concept of geometric risk factors, these observations also suggest that interactions between the hemodynamic influences of multiple geometric variables may play a role in the mediation of tissue susceptibility by geometric factors.

Effects of smoking and clinical status on lung function in human immunodeficiency virus (HIV)-seropositive subjects.

Lung function was measured at 3-month intervals for up to 1 yr in a group of Caucasian HIV-seropositive subjects. The objective was to document any deterioration in lung function and seek correlations between such deterioration and smoking history and Centers for Disease Control (CDC) status. Ninety-nine subjects were studied at enrollment; 43 were followed-up (mean duration 9 +/- 3 months). Ninety-five of the 99 enrolled subjects remained free of HIV-related respiratory disease and were included in the analysis. At enrollment, carbon monoxide diffusing capacity (TLCO) was significantly lower than predicted in non-smokers, smokers and ex-smokers (88, 77 and 88%, respectively, P < 0.001). The TLCO measurements in the smoking group were significantly lower than those of the life-long non-smoking subjects (P < 0.01). Residual volume (RV) was significantly higher than predicted in smokers (111%, P = 0.02). During follow-up, all three groups demonstrated significant declines in TLCO (7%, P = 0.01; 9%, P = 0.005; 13%, P < 0.001, respectively), and increases in RV (9%, P = 0.03; 13.5%, P = 0.02, 22%, P = 0.02, respectively). At enrollment, significantly lower than predicted values of TLCO were observed in groups stratified by CDC criteria: in asymptomatic HIV-seropositive subjects (CDC 11) 89%, P = 0.01; persistent generalized lymphadenopathy (PGL) 84%; AIDS-related complex (ARC) 81%; and in non-pulmonary AIDS (IV C1) 69%, P = 0.0001, respectively. Residual volume was significantly higher than predicted in CDC II (114%, P = 0.05). During follow-up, TLCO fell in groups PGL and ARC by 7 and 9%, respectively, while RV increased in groups CDC II, PGL and ARC by 17, 15 and 8%, respectively. Only the TLCO decline in PGL showed any linkage to clinical deterioration. This study demonstrates deficits at enrollment, and a continuing decline of TLCO and increase in RV in HIV-seropositive subjects without overt lung disease.

Magnitude and time course of acute hypoxic pulmonary vasoconstriction in man.

Acute hypoxic pulmonary vasoconstriction has an established role in the preservation of ventilation-perfusion balance. To further characterize this homeostatic response in man we have attempted to measure both the time course and magnitude of blood flow diversion from single hypoxic lobes. Lobar hypoxia (mean PO2 38 +/- 1.5(SEM)mmHg, mean PCO2 39.9 +/- 0.9 mmHg) was induced by inflating catheter-tip balloons in left upper lobe bronchi during fibreoptic bronchoscopy under local anaesthesia in 8 normal subjects. An index of lobar blood flow was obtained by acquiring dynamic scintigraphic lung images during a continuous intravenous infusion of the short-lived radioisotope krypton-81m dissolved in 5% glucose solution. In 3 subjects blood flow to the occluded lobes was monitored while the lobes were maintained under hyperoxic conditions (mean PO2 127.8 +/- 31.5 mmHg, mean PCO2 40.2 +/- 1.3 mmHg). Under hypoxic conditions the blood flow to the occluded lobes fell to 53% of baseline after 5 min with a mean time constant of 151 +/- 24.8 sec. Under hyperoxic conditions there was no significant change from baseline blood flow. We conclude that this technique has allowed us to monitor both the dynamic and steady state responses of the pulmonary circulation to lobar hypoxia in man.

Regional matching of ventilation and perfusion during lobar bronchial occlusion in man.

1. Ventilation-perfusion balance in the presence of airway obstruction will depend on the efficiency of hypoxic pulmonary vasoconstriction beyond obstructed airways and the matching of redistributed blood flow and ventilation to the rest of the lung. This study investigated the relative importance of these mechanisms in man during experimental bronchial occlusion. 2. The bronchus to the left lower lobe was temporarily occluded with a balloon-tipped catheter during fibreoptic bronchoscopy in eight supine normal volunteers. Respiratory gas tensions were measured within the occluded lobe with a respiratory mass spectrometer. The distribution of ventilation and perfusion was assessed under control conditions and after 5 min of bronchial occlusion by computer analysis of the regional distribution of radioactivity during inhalation of 81mKr gas and following injection of 99mTc-labelled macroaggregated albumin respectively. 3. Respiratory gas partial pressures within the occluded lobes rapidly stabilized at mixed venous gas tensions: PO2 43.4 +/- 2.2 (SEM) mmHg, PCO2 40.2 +/- 1.8 mmHg. During occlusions the arterial oxygen saturation fell from a baseline of 96.3 +/- 0.46% to a nadir of 92.1 +/- 0.43%. Bronchial occlusion produced underventilation in the left lung relative to perfusion, both in the region of the occluded lower lobe and at the lung apex. Relative overventilation occurred in the right lung. 4. It is concluded that arterial hypoxaemia during lobal bronchial occlusion is caused primarily by shunting of mixed venous blood, though the shunt fraction is reduced by approximately 50% by hypoxic pulmonary vasoconstriction. In lung adjacent to obstructed regions reduced compliance may impair ventilation more than perfusion to contribute to hypoxaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of left ventricular contractile behaviour during atrial fibrillation.

OBJECTIVES: The purpose of this study was to explore the physiology underlying the beat-to-beat variations of ventricular function during atrial fibrillation (AF). METHODS: Left ventricular pressure, and its first derivative (LVdP/dtmax, an index of contractility, and aortic blood velocity (and its integral AVI, an ejection index), were recorded using cathetermounted transducers in 15 patients with AF during cardiac catheterisation. Transfer function modelling was used to examine the influence of preceding intervals on LVdP/dtmax, and of LVdP/dtmax on AVI. The technique also allowed simulation of the behaviour of LVdP/dtmax in response to specific manipulations of interval. RESULTS: The variations in LVdP/dtmax recorded from the AF patients were shown to be dependent on up to six preceding intervals; a maximum of 91% of the variation was explicable in this way. The influences of mechanical restitution (MR, the relationship between preceding interval and contractility), postextrasystolic potentiation (PESP, the inverse relationship between pre-preceding interval and contractility) and the decay of that potentiation were all demonstrated. These influences collectively appeared to be powerful determinants of AVI. Simulations of LVdP/dtmax, following single interval perturbations, were entirely consistent with these interval force effects. CONCLUSIONS: The cardiac interval force relationship in man is an important determinant of the beat-to-beat variations of contractile and ejection function during AF: the beat-to-beat variations in contractile (or inotropic) function are independent of changes in ventricular filling or fibre-length.

Collateral ventilation and gas exchange in emphysema.

Resistance to collateral flow of gas is high in the normal human lung but may be lower in emphysema. However, the contribution of collateral ventilation to gas exchange in emphysema remains unclear. This study evaluates the role and magnitude of collateral ventilation between bronchopulmonary segments in six patients with clinical, functional, and computed tomographic evidence of emphysema, compared with our previous findings in 12 normal subjects. To assess collateral flow, a balloon-tipped catheter with a lumen that opened distal to the balloon was inflated in segmental bronchi during fiberoptic bronchoscopy. Respiratory gas tensions were sampled by mass spectrometer from beyond the occlusion via the catheter lumen. Subjects breathed air until occlusion was established and then switched to 79% helium/21% oxygen. The rate of rise of helium concentration was measured within occluded segments and used as an index of collateral ventilation. The mean (+/- SEM) rate of rise of helium concentration was ten times greater in emphysema patients (9.5 +/- 2.7%/min) compared with normal subjects (0.8 +/- 0.3%/min) (p = 0.009). The mean PO2 within occluded segments was similar in normal subjects and emphysema patients: 45.4 +/- 1.8 mm Hg and 44.8 +/- 3.6 mm Hg, respectively. Mean PCO2 within occluded segments was lower in patients (40.1 +/- 1.9 mm Hg) than in normal subjects (46.4 +/- 1.3 mm Hg), probably due to higher regional ventilation-perfusion ratios in emphysema patients rather than collateral ventilation. In emphysema patients there was a positive correlation between rate of rise of helium concentration and final PO2 within an occluded segment (r = 0.73; p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in regional pulmonary blood flow during lobar bronchial occlusion in man.

1. Acute hypoxic pulmonary vasoconstriction is important in the restoration of ventilation-perfusion balance in the presence of regional alveolar hypoventilation. However, the magnitude and time course of this response in man has not been adequately characterized in regions smaller than an entire lung. We have studied the effectiveness of hypoxic vasoconstriction in diverting blood from hypoxic lobes in normal supine subjects, and have documented the redistribution of pulmonary blood flow under these conditions. 2. Lobar hypoxia was induced for 80-300 s by placing occluding balloon-tipped catheters in lobar bronchi during fibreoptic bronchoscopy in 10 normal subjects. Respiratory gas partial pressures within occluded lobes were measured with a mass spectrometer. The percentage reduction in blood flow to the hypoxic lobes was assessed after injection of 99mTc-labelled albumin by gamma-scintigraphy, and compared with a control scan performed 1 week later. A computer program was used to analyse changes in regional pulmonary perfusion. 3. During lobar bronchial occlusion respiratory gas partial pressures rapidly approached reported values for mixed venous partial pressures. After a mean time of occlusion of 3.5 min lobar blood flow was reduced by 47 +/- 5%. During occlusions pulmonary blood flow was not evenly redistributed, but was preferentially redistributed to more cranial lung regions. 4. We conclude that acute hypoxic pulmonary vasoconstriction in occluded lobes is more effective at rapidly diverting pulmonary blood flow away from hypoxic lung regions than has previously been reported in man during unilateral hypoxia of an entire lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of gadolinium on length-dependent force in guinea-pig papillary muscle.

The degree to which stretch-activated channels operate during physiological length changes in multicellular heart preparations, or how much the channels could contribute to length-dependent activation, is not known. We studied the relationship between muscle length and contractile force in guinea-pig papillary muscles superfused with gadolinium chloride (10 microM), a stretch-activated channel blocker, and compared the effects to those with nifedipine (0.25 microM), a calcium channel blocker. Gadolinium reduced contractile force statistically significantly more at the longer muscle lengths than at the short muscle lengths. This did not apply with nifedipine, although a marginally greater effect at longer lengths was perceptible. The results can only partly be explained by gadolinium having a non-specific action via the calcium channel, or Na(+)-Ca2+ exchange, and are consistent with the possibility that stretch-activated channels contribute to length-dependent activation in cardiac muscle, and thus to 'Starling's Law of the Heart'.

Influences of stimulation frequency and temperature on interval-force relationships in guinea-pig papillary muscles.

Relationships between contractile force and the preceding and pre-preceding stimulation intervals were studied in papillary muscles by interposing variable test intervals during steady-state pacing. The strength of test contractions increased exponentially to a maximum as the preceding (test) interval was lengthened. Contractility decreased as an exponential function of pre-preceding interval. At 37 degrees C, the half times for these processes were unaffected by increasing the steady-state frequency from 1 to 3 Hz. At 27 degrees C, the force increase with preceding interval was accelerated and the decay with pre-preceding interval was retarded as the stimulation frequency was increased from 0.33 to 2 Hz. The time-courses of force increase and decay were similar to each other during stimulation at an optimum frequency characteristic for the temperature. Cooling from 37 to 27 degrees C prolonged the half times for force increase and decay by factors of 4.5 and 3 respectively. The slope of the linear relationship between the force of the contraction pre-preceded by the test interval and the immediately subsequent contraction (recirculation fraction) was also halved. These results suggest that high stimulation frequency and low temperature uncouples cellular processes underlying the interval dependence of cardiac contractility. The temperature sensitivities are consistent with these processes being enzymatic. The reduced recirculation fraction provides a mechanism for the lowered threshold frequency for sustained mechanical alternans at 27 degrees C.

The limitations of posterior view ventilation scanning in the diagnosis of pulmonary embolism.

In the diagnosis of pulmonary embolism some centres using 133Xe for comparison with multiple view 99Tcm perfusion images perform only single-breath posterior view ventilation scans. The purpose of this study was to test the reliability of the posterior view ventilation scan in the detection of lobar and segmental defects in ventilation. Occluding balloon catheters were placed in lobar and segmental bronchi during fibreoptic bronchoscopy to produce defects of known anatomical location and size in normal volunteers. Subjects breathed 81Krm/air during the occlusions and images were acquired in the posterior, posterior/oblique and lateral projections. The posterior view images were classified by three experienced nuclear medicine physicians as normal or abnormal. If abnormal, the observers were asked to state which lobe or segment was involved. Segmental defects were missed in 28% of scan readings. Segmental defects were detected but incorrectly sited in 50% of readings and correctly sited in only 22% of readings. The posterior view scan with a defect involving the entire lingula was judged to be normal by all observers. Defects involving the right and left lower lobes were underestimated. We conclude that ventilation scanning techniques that assess the distribution of ventilation in the posterior view alone are unreliable in the detection of segmental and lobar defects, and are likely to increase the false positive rate in the diagnosis of pulmonary embolism.

Obliterative bronchiolitis with atypical features: CT scan and necropsy findings.

We describe the natural history of cryptogenic bronchiolitis obliterans in a patient followed for 24 yrs with serial pulmonary function tests and radiology. Severe, progressive airway obstruction developed, with overinflation but preservation of KCO. There was progressive hypoxaemia, which worsened on exertion; hypercapnoea was modest until late in the illness. Neither bronchodilators nor steroids were effective. The chest radiograph remained normal; CT showed irregular areas of low attenuation peripherally throughout the lungs, with Hounsfield numbers typical of emphysema, but no bullae. Postmortem studies included histology and quantitative studies of a corrosion cast of one lung. They showed marked airway narrowing at all levels, with pruning of peripheral branches, mucus plugging, and some emphysema. The case illustrates that cryptogenic bronchiolitis obliterans may be chronic and difficult to distinguish clinically or by investigation from other forms of chronic obstructive airways disease, particularly emphysema.

Collateral ventilation and gas exchange during airway occlusion in the normal human lung.

The effectiveness of collateral ventilation in maintaining alveolar gas tensions in obstructed lung segments was investigated using fiberoptic bronchoscopy to place an occluding catheter-tip balloon in selected lobar and segmental bronchi in supine normal human subjects. Gas tensions from beyond the occlusion were measured with a respiratory mass spectrometer. Collateral ventilation is known to be minimal between lobes; therefore, values measured in obstructed lobes provide a control. No significant difference was found between the partial pressures of oxygen or carbon dioxide measured in obstructed lobes and in obstructed segments. In both cases respiratory gas tensions approached reported values for mixed venous levels. The time taken to attain a steady state of gas composition in the obstructed lung was rapid (approximately 50 s), and it was no different for lobes and segments. In addition, collateral ventilation was assessed by measuring the amount of helium reaching occluded lobes and segments when subjects breathed a mixture of 21% oxygen and 79% helium. The rate of rise in helium concentration was less than 1%/min in both lobes and segments, a figure that may be explained by delivery of helium in recirculated blood rather than by collateral ventilation. We conclude that intersegmental collateral ventilation has a negligible role in the maintenance of alveolar gas tensions in supine normal humans during tidal breathing.

Effects of nifedipine and low [Ca2+] on mechanical restitution during hypothermia in guinea pig papillary muscles.

Increasing the frequency of steady state stimulation increases the rate of mechanical restitution in hypothermic (27 degrees C) guinea pig papillary muscles. In this paper we have investigated the influences of the calcium antagonist nifedipine and of reduced extracellular calcium concentration on this phenomenon. We found that nifedipine abolished the frequency dependent increase in the restitution rate, which was also sensitive to extracellular [Ca2+]. These findings suggest that the level of intracellular [Ca2+] can influence the rate of restitution. It is implied that this effect is mediated via ICa, the inward calcium current, which makes a larger than normal contribution to direct contractile activation in hypothermic myocardium.

The underestimation of segmental defect size in radionuclide lung scanning.

Criteria used to place ventilation-perfusion lung scans into categories with different probabilities for pulmonary embolism depend largely on the size and anatomical distribution of defects recognized. These criteria assume that actual segmental defects appear segmental on the lung scan. This study examined the accuracy with which four experienced observers were able to estimate the size of defects of known anatomical location and size, using images of segmental defects in ventilation produced with a bronchoscopic technique and 81mKr. Of the 24 segmental defects produced in this study, 17% were interpreted as being < 25% of a segment; 23% were interpreted as being 25%-50% of a segment; 17% were interpreted as 50%-75% of a segment; 40% were interpreted as being 75%-100% of a segment and 4% were interpreted as being > 100% of a segment. Intra- and interobserver agreement as assessed by the Kappa statistic varied with the number of size categories used but was generally poor. Underestimation of defect size observed in this study may explain why many patients with pulmonary embolism do not have high probability scans. We conclude that the subjective impression of the size of a defect on a lung scan is an unreliable indication of a defect's true segmental or subsegmental nature and that scoring systems based on these criteria should be viewed with caution.