Regional Pulmonary Blood Flow Research Articles

Pulmonary Perfused Blood Volume with Dual-Energy CT as Surrogate for Pulmonary Perfusion Assessed with Dynamic Multidetector CT

To compare measurements of regional pulmonary perfused blood volume (PBV) and pulmonary blood flow (PBF) obtained with computed tomography (CT) in two pig models. The institutional animal care and use committee approved all animal studies. CT-derived PBF and PBV were determined in four anesthetized, mechanically ventilated, supine swine by using two methods for creating pulmonary parenchymal perfusion heterogeneity. Two animals were examined after sequentially moving a pulmonary arterial balloon catheter from a distal to a central location, and two others were examined over a range of static airway pressures, which varied the extents of regional PBF. Lung sections were divided into blocks and Pearson correlation coefficients calculated to compare matching regions between the two methods. CT-derived PBF, CT-derived PBV, and their associated coefficients of variation (CV) were closely correlated on a region-by-region basis in both the balloon occlusion (Pearson R = 0.91 and 0.73 for animals 1 and 2, respectively; Pearson R = 0.98 and 0.87 for comparison of normalized mean and CV for animals 1 and 2, respectively) and lung inflation studies (Pearson R = 0.94 and 0.74 for animals 3 and 4, respectively; Pearson R = 0.94 and 0.69 for normalized mean and CV for animals 3 and 4, respectively). When accounting for region-based effects, correlations remained highly significant at the P < .001 level. CT-derived PBV heterogeneity is a suitable surrogate for CT-derived PBF heterogeneity.

Regional pulmonary blood flow in the lung of the chicken

It is known that alterations in respiratory gases in birds can cause a nonhomogenous redistribution of pulmonary blood flow between the 2 separate gas-exchanging regions of the avian lung, the paleopulmo (PALEO) and neopulmo (NEO); however, the effect of alterations in respired gas content on the distribution of pulmonary blood flow in birds, such as the chicken, that possess a highly developed NEO is not known. This study used a colorimetric microsphere method to determine the effects of hypoxia and hypercapnia on the relative distribution of pulmonary blood flow in anesthetized chickens (Gallus domesticus) during control (normoxic) and experimental (hypoxic or hypercapnic) conditions, where the relative regional distribution of blood flow in the lung is expressed as the ratio NEO/PALEO. Administration of a hypoxic gas mixture (16.0% O(2)) produced a 13.4% increase in NEO/PALEO, and, administration of a hypercapnic gas mixture (5.0% CO(2)) resulted in a 27.8% increase in NEO/PALEO. Our results are consistent with a mechanism in which the regional redistribution of pulmonary blood flow is mediated by local intrapulmonary factors.

Quantification of Systemic-to-Pulmonary Artery Collateral Flow

Abnormal vascular connections between systemic arteries and the pulmonary vascular bed—systemic-to-pulmonary collateral (SPC) vessels—manifest in patients with a variety of congenital and acquired heart disease. These vessels, which originate from branches off the brachiocephalic arteries, chest wall arteries, and the descending aorta, vary markedly in size, number, course, and distribution. Although the precise mechanisms that lead to development of SPCs are incompletely understood, hypoxemia, diminished global or regional pulmonary blood flow, and nonpulsatile flow in the pulmonary arteries are some of the commonly cited contributors.1 Indeed, SPCs are frequently encountered in patients with cardiac anomalies that include ≥1 of these abnormalities such as severe forms of tetralogy of Fallot and functional single ventricle (FSV). In the latter group, the clinical importance of SPCs and their optimal management have been topics of intense debate for >2 decades.2–6 Article see p 218 The physiology of SPC flow involves both beneficial and deleterious effects.1,2 SPCs can augment blood flow to hypoperfused lung segments, improve gas exchange, and potentially inhibit the development of pulmonary arteriovenous malformations in patients in whom hepatic venous flow does not reach the pulmonary circulation. In contrast, like other shunts, SPC flow is inherently inefficient because relatively highly oxygenated blood returns to the pulmonary circulation and potentially competes with the more efficient antegrade flow to the lungs through the native pulmonary arteries. Consequently, SPC flow results in volume load on the FSV, which can lead to ventricular dilatation and dysfunction, atrioventricular valve regurgitation, and heart failure symptoms. Other deleterious effects of excessive SPCs include flow energy loss,7 exuberant blood flow returning through the pulmonary veins to the surgical field during cardiopulmonary bypass, respiratory distress, pulmonary hypertension, and hemoptysis.8 In patients with FSV, the hemodynamic burden from SPCs has been the topic …

Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction without affecting endogenous pulmonary nitric oxide production

Hypercapnic acidosis often occurs in critically ill patients and during protective mechanical ventilation; however, the effect of hypercapnic acidosis on endogenous nitric oxide (NO) production and hypoxic pulmonary vasoconstriction (HPV) presents conflicting results. The aim of this study is to test the hypothesis that hypercapnic acidosis augments HPV without changing endogenous NO production in both hyperoxic and hypoxic lung regions in pigs. Sixteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Eight pigs received 10% carbon dioxide (CO(2)) inhalation to both lung regions (hypercapnia group), and eight pigs formed the control group. NO concentration in exhaled air (ENO), nitric oxide synthase (NOS) activity, cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. There were no differences between the groups for ENO, Ca(2+)-independent or Ca(2+)-dependent NOS activity, or cGMP in hypoxic or hyperoxic lung regions. Relative perfusion to LLL (Q (LLL)/Q (T)) was reduced similarly in both groups when LLL hypoxia was induced. During the first 90 min of hypercapnia, Q (LLL)/Q (T) increased from 6% (1%) [mean (standard deviation, SD)] to 9% (2%) (p < 0.01), and then decreased to the same level as the control group, where Q (LLL)/Q (T) remained unchanged. Cardiac output increased during hypercapnia (p < 0.01), resulting in increased oxygen delivery (p < 0.01), despite decreased PaO(2) (p < 0.01)(.) Hypercapnic acidosis does not potentiate HPV, but rather transiently weakens HPV, and does not affect endogenous NO production in either hypoxic or hyperoxic lung regions.

Effects of Acute Cigarette Smoke Exposure on Regional Pulmonary Blood Flow

Effects of Acute Cigarette Smoke Exposure on Regional Pulmonary Blood Flow

The changes of pulmonary blood flow in non-ventilated lung during one lung ventilation

A pulmonary artery catheter placement is necessary for intrapulmonary shunt fraction evaluation. The purpose of this study was to investigate the feasibility for detecting the changes of regional pulmonary blood flow in non-ventilated lung by transesophageal echocardiography (TEE) during one-lung ventilation (OLV). 22 adult patients for selective thoracic surgery were enrolled in the study. Doppler flow patterns in left upper pulmonary vein (LUPV) were obtained by TEE before switching to right OLV and every 5 min in 30 min OLV period. Systolic peak velocity (Vs), diastolic peak velocity (Vd) and velocity time integral (VTI) were measured respectively. The VTI of LUPV blood flow pattern decreased significantly 5 min after right OLV. The percent of changes in LUPV blood flow decreased rapidly by 78.4 and 67.7% at OLV 5 min and 10 min, respectively. Then it slowly decreased by 60% at OLV 30 min. Provides an alternative method to measure the changes of pulmonary blood flow during OLV. The percent changes of regional pulmonary blood flow decreased immediately after OLV, and decreased by 60% at 30 min OLV.

Posttraumatic Lung Injury After Pulmonary Contusion and Fat Embolism: Factors Determining Abnormal Gas Exchange

The objective was to investigate changes in pulmonary blood flow after lung contusion and fat embolism. Eighteen mongrel dogs were randomly assigned to three groups: fat embolism alone (n = 7); moderate unilateral pulmonary contusion followed by fat embolism (n = 6); and severe unilateral pulmonary contusion followed by fat embolism (n = 5). Fat embolism was produced by intramedullary reaming of left femur and tibia followed by canal pressurization using bone cement. Outcome measures were systemic blood pressure, pulmonary artery pressure, pulmonary artery occluded pressure, cardiac output (CO), and partial pressures of arterial and mixed venous oxygen (Pao2, PvO2). Samples were taken from contused and noncontused contralateral lung to calculate regional pulmonary blood flow. After the fat embolism, pulmonary artery pressure and pulmonary vascular resistance increased significantly (p < 0.05) in all groups, whereas Pao2 decreased in groups 2 and 3 and at 30 minutes in group 1. CO decreased significantly in group 3. Group 3 also demonstrated a greater initial decrease in Pao2 and PvO2 from baseline and a larger increase in pulmonary vascular resistance. In those animals that underwent contusion, regional pulmonary blood flow was not found to be different between contused and noncontused lung segments. After contusion, flow decreased significantly in contused and noncontused segments in group 3 only. Gas exchange deteriorates because of decreased CO. For any preexisting intrapulmonary shunt, the decrease of PvO2 will cause worsening of Pao2.

Pulmonary Endarterectomy Improves Dyspnea by the Relief of Dead Space Ventilation

In chronic thromboembolic pulmonary hypertension (CTEPH), dyspnea is considered to be related to increased dead space ventilation caused by vascular obstruction. Pulmonary endarterectomy releases the thromboembolic obstruction, thereby improving regional pulmonary blood flow. We hypothesized that pulmonary endarterectomy reduces dead space ventilation and that this reduction contributes to attenuation of dyspnea symptoms. In this follow-up study we assessed dead space ventilation, hemodynamic severity of disease, and symptomatic dyspnea in 54 consecutive CTEPH patients, before and 1 year after pulmonary endarterectomy. Dead space ventilation was calculated using the Bohr-Enghoff equation. Dyspnea was assessed by Borg scores and the New York Heart Association functional classification. Preoperatively, dead space ventilation was increased (0.40 +/- 0.07) and correlated with severity of disease (mean pulmonary artery pressure: r = 0.49, p < 0.001; total pulmonary resistance: r = 0.53, p < 0.001), and resting (r = 0.35, p < 0.05) and post-exercise Borg dyspnea scores (r = 0.44, p < 0.01). Postoperatively, dead space ventilation (0.33 +/- 0.08, p < 0.001) and dyspnea symptoms decreased significantly. Changes in symptomatic dyspnea were independently associated with changes in pulmonary hemodynamics and absolute dead space. Dead space ventilation in CTEPH is increased and correlates significantly with hemodynamic severity of disease and dyspnea symptoms. Pulmonary endarterectomy decreases dead space ventilation. The induced change in dead space upon surgical removal of chronic thromboembolism contributes to the postoperative recovery of symptomatic dyspnea.

The effect of left heart bypass on pulmonary blood flow and arterial oxygenation during one-lung ventilation in patients undergoing descending thoracic aortic surgery

To study the effect of left heart bypass (LHB) on regional pulmonary blood flow and arterial oxygenation during one-lung ventilation (OLV). Prospective, observational study Operating room 14 ASA physical status II and III patients scheduled to undergo descending thoracic or thoracoabdominal aortic surgery using LHB. Parameters studied during OLV with 100% oxygen before and during LHB mean arterial pressure, heart rate, pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac index, cardiac output, arterial oxygen tension (PaO(2)), mixed venous oxygen pressure, alveolar arterial oxygen difference (P((A-a)O2)), and right upper pulmonary venous flow (RUPVF). Right upper pulmonary venous flow was measured using transesophageal echocardiography. With the transition to OLV, there was a significant decrease in PaO(2) and a significant increase in P((A-a)O2). However once LHB was initiated, these values improved significantly (P = 0.0007 and 0.0004, respectively) with the simultaneous increase in RUPVF (P = 0.0018). LHB improved pulmonary blood flow to the dependent lung and arterial oxygenation during OLV in descending thoracic aortic surgery.

Effects of posture on regional pulmonary blood flow in rats as measured by PET

Using small animal PET with (68)Ga-radiolabeled human albumin microspheres (Ga-68-microspheres), we investigated the effect of posture on regional pulmonary blood flow (PBF) in normal rats. This in vivo method is noninvasive and quantitative, and it allows for repeated longitudinal measurements. The purpose of the experiment was to quantify spatial differences in PBF in small animals in different postures. Two studies were performed in anesthetized, spontaneously breathing Wistar rats. Study 1 was designed to determine PBF in the prone and supine positions. Ga-68-microspheres were given to five prone and eight supine animals. We found that PBF increased in dorsal regions of supine animals (0.75) more than in prone animals (0.70; P = 0.037), according to a steeper vertical gradient of flow in supine than in prone animals. No differences in spatial heterogeneity were detected. Study 2 was designed to determine the effects of tissue distribution on PBF measurements. Because microspheres remained fixed in the lung, PET was performed on animals in the position in which they received Ga-68-microsphere injections and thereafter in the opposite posture. The distribution of PBF showed a preference for dorsal regions in both positions, but the distribution was dependent on the position during administration of the microspheres. We conclude that PET using Ga-68-microspheres can detect and quantify regional PBF in animals as small as the rat. PBF distributions differed between the prone and supine postures and were influenced by the distribution of lung tissue within the thorax.

Regional pulmonary blood flow: Comparison of dynamic contrast‐enhanced MR perfusion and phase‐contrast MR

Regional pulmonary blood flow can be assessed using both dynamic contrast-enhanced (DCE) MR and phase-contrast (PC) MR. These methods provide somewhat complementary information: DCE MR can assess flow over the entire lung while PC MR can detect rapid changes in flow to a targeted region. Although both methods are considered accurate, one may be more feasible than the other depending on pathology, patient condition, and availability of an intravenous route. The objective of this study was to establish a consensus between the two methods by comparing paired DCE MR and PC MR measurements of relative blood flow in Yorkshire piglets (N = 5, age = 7 days, weight = 3.3 +/- 0.6 kg) under various physiological states including regional lung collapse. A strong correlation (R(2) = 0.71, P < 0.01) was observed between the methods. In conclusion, DCE MR and PC MR provide a consistent measure of changes in regional pulmonary blood flow.

Association between reduced pulmonary diffusing capacity and cardiac autonomic dysfunction in Type 1 diabetes

In Type 1 diabetes mellitus (DM), it has been suggested that autonomic nervous system dysfunction (NAD) impairs lung diffusion capacity. Heart rate variability (HRV), a measure of cardiac autonomic function, is a sensitive method of detecting NAD. To our knowledge, no previous study has assessed whether cardiac sympatho-vagal balance is associated with lung diffusion capacity in diabetes. Twenty Type 1 DM patients without pulmonary abnormalities and systemic NAD underwent measurement of lung diffusion capacity for carbon monoxide (DLCO) by single-breath method and assessment of cardiac autonomic function by HRV analysis on 24-h electrocardiographic Holter recordings. Standard respiratory function tests and peripheral autonomic tests were normal in all patients. DLCO was lower than normal reference values in six patients (30%). DLCO correlated significantly with most HRV variables, independent of the clinical and laboratory variables. The strongest correlation was found with standard deviation of all RR intervals (SDNN; r = 0.62, P = 0.003) in the time domain and low frequency (LF) power (r = 0.73, P < 0.001) in the frequency domain. In Type 1 diabetes, a significant association exists between cardiac NAD and reduced DLCO in the absence of clinical respiratory and autonomic abnormalities. Thus, NAD may be involved in the early reduction of DLCO in these patients, possibly through abnormalities in the regulation of pulmonary blood flow at the microvascular level.

Regional Pulmonary Blood Flow in Humans and Dogs by 4D Computed Tomography

Pulmonary vascular control mechanisms are complex and likely to differ between species. We wish to quantify regional perfusion and the effects of gravity using computed tomography. Sequential density measurements following the administration of a bolus of iodinated contrast medium were acquired from four healthy human subjects and four dogs. In humans, perfusion (Q) was linear throughout most of the range of vertical height, with an overall gradient of -2.6% cm(-1). However, when perfusion was normalized to "tissue" density (blood plus tissue: sQt), maximum perfusion occurred around the mid-range of vertical height, being 9% (range 1-22%) greater than either the dorsal or ventral extreme. Within discrete transverse axial sections, concentric zones of perfusion centered on blood vessels were demonstrated. The relationship between sQt and vertical height in dogs was distinctly linear, with a gradient of -7.2% cm(-1). In dogs, the median gradient of Q was -13.6% cm(-1) (range -9.7 to -17.1%). Differences in regional pulmonary perfusion, particularly the vertical gradient observed in humans and dogs, may in part reflect anatomic differences between the symmetric dichotomous branching structure of the human pulmonary vasculature and the more asymmetrical structure found in dogs.

Rebuttal from Dr. Glenny

POINT-COUNTERPOINTRebuttal from Dr. GlennyPublished Online:01 May 2008https://doi.org/10.1152/japplphysiol.01092.2007cMoreSectionsPDF (56 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Drs. Hughes and West (6) argue convincingly that a vertical gradient of perfusion exists in human lungs. We agree completely and have never stated otherwise. The controversy, however, is about whether gravity is the most important determinant of regional pulmonary blood flow. They reason that gravity must be the single most important determinant of regional perfusion because numerous prior studies have observed a gradient vertical. This logic parallels the argument that the sun revolves around the earth because it is repeatedly seen traversing from one horizon to the other. While the observation is consistent with the hypothesis, it is not sufficient proof. When it was discovered that the earth spins about its axis, prior observations were not invalidated but rather reinterpreted. The realization that blood flow within horizontal planes is present, well structured, and stable over time, suggests a reinterpretation of prior studies of pulmonary blood flow distribution.None of the studies cited in their Point (6) can determine if gravity is the most important determinant of regional pulmonary blood flow. To settle this issue, high spatial resolution measurements of perfusion must be obtained under varying conditions of posture or gravity while tracking the same lung regions across conditions. Although this kind of study is not currently possible in humans, the requisite study has been performed in baboons (2). The baboon is a biped that has similar lung anatomy, muscularization of pulmonary vessels, hydrostatic gradients, and pulmonary arterial pressures found in humans and therefore meets the criteria set by Drs. Hughes and West (4, 6). Baboons were studied in the upright, supine, prone, and head-down postures. Blood flow to each lung region was described by its vertical position in the lung and a structural component that remained stable across changes in posture. Vertical gradients of perfusion were observed in all postures, corroborating prior observations in humans (5, 8). Multiple stepwise linear regression was used to estimate the relative importance of the gravitational and structural components of blood flow. As expected, gravity had its largest influence in the upright posture. However, structure was more than twice as important as gravity in determining regional pulmonary blood flow (59 vs. 25%).The perspective that the geometry of the vascular tree is more important than gravity in determining regional blood flow requires that other concepts of the gravitational model be reconsidered. While the zones of the lung must exist due to physical laws, they do not need to be vertically stacked in the lung (3). The fractal model predicts that all three zones can exist within the same horizontal plane. The concept that the shared effects of gravity cause matching of regional ventilation and perfusion, however, cannot explain efficient gas exchange in the face of large heterogeneities of ventilation (1) and perfusion within isogravitational planes or during sustained microgravity (7).REFERENCES1 Altemeier WA, McKinney S, Glenny RW. Fractal nature of regional ventilation distribution. J Appl Physiol 88: 1551–1557, 2000.Link | ISI | Google Scholar2 Glenny RW, Bernard S, Robertson HT, Hlastala MP. Gravity is an important but secondary determinant of regional pulmonary blood flow in upright primates. J Appl Physiol 86: 623–632, 1999.Link | ISI | Google Scholar3 Glenny RW, Robertson HT. Regional differences in the lung. In: Complexity in Structure and Function of the Lung, edited by Hlastala MP and Robertson HT. New York: Marcel Dekker, 1998, p. 461–481.Google Scholar4 Hughes JM. Pulmonary blood flow distribution in exercising and in resting horses. J Appl Physiol 81: 1049–1050, 1996.Link | ISI | Google Scholar5 Hughes JM, Glazier JB, Maloney JE, West JB. Effect of lung volume on the distribution of pulmonary blood flow in man. Respir Physiol 4: 58–72, 1968.Crossref | Google Scholar6 Hughes JM, West JB. Counterpoint: Gravity is not the major factor determining the distribution of blood flow in the healthy human lung. J Appl Physiol; doi:10.1152/japplphysiol.01092.2007a.Link | ISI | Google Scholar7 Prisk GK, Guy HJ, Elliott AR, West JB. Inhomogeneity of pulmonary perfusion during sustained microgravity on SLS-1. J Appl Physiol 76: 1730–1738, 1994.Link | ISI | Google Scholar8 West JB, Dollery CT. Distribution of blood flow and ventilation-perfusion ratio in the lung, measured with radioactive carbon dioxide. J Appl Physiol 15: 405–410, 1960.Link | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Collections More from this issue > Volume 104Issue 5May 2008Pages 1535-1536 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.01092.2007cHistory Published online 1 May 2008 Published in print 1 May 2008 Metrics

A New Method to Estimate Regional Pulmonary Blood Flow Using Transesophageal Echocardiography

We report a novel method to estimate regional blood flow in the atelectatic lung using transesophageal echocardiography in an experimental dog model. To verify the efficacy of the method, we investigated the ability of this experimental model to detect changes in regional pulmonary blood flow. Fourteen anesthetized and ventilated mongrel dogs were randomized into an isoproterenol group (n = 7) or a dopamine group (n = 7). To produce an atelectatic lesion, 60 mL/kg of saline was infused into the left pleural space. The velocity time integral (VTI) derived from pulse Doppler was evaluated as an index of blood flow in the atelectatic lesion. To investigate the response of the method to changes in blood flow, the VTI and the shunt fraction (Qs/Qt) were measured during systemic administration of isoproterenol 0.05 microg x kg(-1) x min(-1) (as a pulmonary vasodilator) and dopamine 10 microg x kg(-1) x min(-1) (as a pulmonary vasoconstrictor). Both VTI and Qs/Qt were increased significantly by isoproterenol administration. There was a significant correlation between the percentage changes of VTI and Qs/Qt with isoproterenol administration (r2 = 0.50, P < 0.001). Both VTI and Qs/Qt were unchanged during administration of dopamine. Transesophageal echocardiography may be useful in detecting changes in regional pulmonary blood flow in an atelectatic lesion.

Interpretation of the echocardiographic pressure gradient across a pulmonary artery band in the setting of a univentricular heart

Pulmonary artery (PA) banding has been established as a palliative surgical technique for congenital heart defects for over 50 years [1]. With the advent of earlier corrective surgery, the indications for PA banding have changed over time [2, 3]. Currently these include: (a) limitation of pulmonary blood flow in the setting of an excessive left-toright shunt; (b) regulation of pulmonary blood flow in the univentricular circulation; and (c) a training procedure for the left ventricle prior to conversion to the systemic pumping chamber (late presentation of D-transposition of the great arteries, or prior to a double-switch procedure with L-transposition).

Spatial and Temporal Heterogeneity of Regional Pulmonary Blood Flow in Piglets

Regional pulmonary blood flow (PBF) in adult animals varies over space and time, following a fractal pattern. We hypothesized that PBF would follow a fractal pattern in young animals. Five, two-week old piglets were sedated and mechanically ventilated. After stabilization, fluorescent microspheres were injected via the right atrium at baseline and then again at 5, 20, 20.5, 40 and 60 min. The lungs were subsequently excised, dried, inflated, and cored into 0.12-cm3 pieces (mean n=561+/-106 per animal) with the spatial coordinates recorded for each piece. Regional PBF was spatially and temporally heterogeneous with a spatial coefficient of variation of 43.3+/-7.9% and a temporal coefficient of variation of 14.3+/-0.4%. PBF followed a fractal pattern with a fractal dimension of 1.20+/-0.06 at 20 min, remaining stable throughout the experiment. PBF decreased with distance from the hilum but did not follow a lobar pattern. Temporal heterogeneity did not significantly increase with time but low flow regions demonstrated the greatest temporal variability throughout the study. Hence, PBF in young piglets was characterized both spatial and temporal heterogeneity.

Sporadic coordinated shifts of regional ventilation and perfusion in juvenile pigs with normal gas exchange

Repeated high-resolution measurements of both regional pulmonary ventilation and regional blood flow (r ) have revealed that approximately 6 to 10% of the summed spatial and temporal heterogeneity can be attributed to spontaneous temporal variability. To test the hypothesis that the spontaneous temporal shifts of r and r are coordinated, 12 anaesthetized juvenile pigs had pairs of colours of aerosol and intravenous fluorescent microspheres (FMS) administered simultaneously at 20 min intervals to mark r and r . The animals were killed, the lungs inflated, air-dried and cut into approximately 2 cm(3) cubes. The concentrations of FMS colours from each cube, representing r and r at every 20 min interval, were measured with a fluorescence spectrophotometer. The correlation between per-piece temporal shifts in r and r , calculated as the mean within-piece covariance, was positive (P < 0.001) for every temporally adjacent pair of measurements in every animal, although there were large differences in the magnitude of the mean temporal covariance among animals. The individual cubes with the most positive temporal covariance across all measurement periods usually demonstrated a large single-interval coordinated shift of r and r , with average temporal covariance observed at the other intervals. The largest between-interval shifts in r and r included equal proportions of coordinated increases and coordinated decreases. High-resolution measurements of r and r acquired over 20 min intervals reveal that the overall positive correlation between temporal changes in r and r is driven by relatively infrequent large-magnitude changes within small regions of the lung.

Endothelial Dysfunction in Heart Failure and Ischemic Heart Disease: Rationale for the Clinical use of Mononitrates

The clinical observation that heart failure can progress independently of the patient's hemodynamic status has focused interest on new, potential mechanisms underlying the progression of cardiac insufficiency It has been shown that in both ischemic and non-ischemic heart failure, endothelial dysfunction and reduced bioavailability of NO can contribute to the process of left ventricular remodelling. The endothelial dysfunction contributes to increasing peripheral vascular resistance, limiting blood flow to skeletal muscles, particularly during exercise, and compromising the regulation of pulmonary blood flow, leading to a flow-perfusion mismatch. The nitroderivates are a heterogeneous class of compounds that have in common their pharmacodynamic action, which is mediated through the production of NO. Isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5-MN) are the two main metabolites of isosorbide dinitrate (ISDN) and both act on the smooth muscle cells of vessel walls, causing generalized peripheral vasodilation, which is more marked in the venous system, reduced venous return to the heart and a reduction in peripheral resistance. The shorter half-life of IS-2-MN compared to that of IS-5-MN allows greater fluctuation of the blood levels of the drug; it can, therefore, be hypothesized that tolerance would develop more slowly. In the light of the important role of oxidative stress in the progression of heart failure, reduced occupation of the receptors for NO by IS-2-MN could have important implications for the bioavailability of the sulphydryl groups otherwise involved in the denitrification of the organic nitrates.

Regional pulmonary blood flow in dogs by 4D-X-ray CT

ECG-triggered computed tomography (CT) was used during passage of iodinated contrast to determine regional pulmonary blood flow (PBF) in anesthetized prone/supine dogs. PBF was evaluated as a function of height within the lung (supine and prone) as a function of various normalization methods: raw unit volume data (PBFraw) or PBF normalized to regional fraction air (PBFair), fractional non-air (PBFgm), or relative number of alveoli (PBFalv). The coefficient of variation of PBFraw, PBFair, PBFalv, and PBFgm ranged between 30 and 50% in both lungs and both body postures. The position of maximal flow along the height of the lung (MFP) was calculated for PBFraw, PBFair, PBFalv, and PBFgm. Only PBFgm showed a significantly different MFP height supine vs. prone (whole lung: 2.60 +/- 1.08 cm supine vs. 5.08 +/- 1.61 cm prone, P < 0.01). Mean slopes (ml/min/gm water content/cm) of PBFgm were steeper supine vs. prone in the right (RL) but not left lung (LL) (RL: -0.65 +/- 0.29 supine vs. -0.26 +/- 0.25 prone, P < 0.02; LL: -0.47 +/- 0.21 supine vs. -0.32 +/- 0.26 prone, P > 0.10). Mean slopes of PBFgm vs. vertical lung height were not different prone vs. supine above this vertical height of MFP (VMFP), but PBFgm slopes were steeper in the supine position below the VMFP in the RL. We conclude that PBFgm distribution was posture dependent in RL but not LL. Support of the heart may play a role. We demonstrate that normalization factors can lead to differing attributions of gravitational effects on PBF heterogeneity.