Morphology of the elastic pulmonary arteries in pulmonary hypertension: a quantitative study.

Recent studies of intravascular ultrasound of the pulmonary arteries suggest that the technique can detect intimal and medial thickening in patients with pulmonary hypertension, potentially providing a method of assessing severity of pulmonary vascular disease in life. A major drawback of the technique is that only the elastic pulmonary arteries are accessible to current ultrasound catheters. The aim of this study was to determine whether morphological changes in vessels accessible to intravascular imaging reflect severity of pulmonary vascular disease and are of a sufficient degree to be detectable by current ultrasound catheters. Morphometric studies of the elastic pulmonary arteries were performed in specimens of lungs from 24 patients who had died with pulmonary hypertension (aged 3 weeks-9 years) and compared with measurements from infants who had died from sudden infant death syndrome. Morphological changes evident in the elastic pulmonary arteries in pulmonary hypertension included luminal dilation and medial thickening but these changes were too variable to be predictive of the severity of peripheral pulmonary vascular disease. Intimal thickening and atherosclerosis were present only in those with advanced pulmonary hypertensive disease. The changes of medial thickening and luminal dilation, nonetheless, are too variable to be predictive of the severity of peripheral pulmonary vascular disease. Thus, imaging by intravascular ultrasound may help confirm advanced pulmonary vascular disease, but is unlikely to differentiate less severe pulmonary vascular disease when the patient may still potentially be operable.     

A method for quantitative estimation of mast cells in the bone marrow of the rat

Observations of thick smears of marrow obtained from the femur, tibia, humerus,sternum, and ribs (in rats), showed that in the first three bones, the number ofmast cells was much higher than in the latter two bones.

A method for the quantitative estimation of the total number of nucleated cellsand of mast cells in the bone marrow of rats is presented. The method involves dilution of the marrow, in a red cell pipet, with a 1:50,000 solution of toluidine bluein 3 per cent acetic acid. This method confirmed the results of mast-cell distribution obtained in the study of marrow smears.

     

Qualitative and quantitative observations of smoking-induced morphologic changes in muscular pulmonary arteries]

Light microscopy, transmission electron microscopy, image processing and morphometric technique were applied to analyze the morphologic changes in the muscular pulmonary arteries from the rats after exposure to smoking. The results showed that the pronounced muscularization of the small pulmonary arteries. significant reduction of the intraacinar arteries, intimal and medical thickening that was significantly associated with the cellular elements and extracellular matrix, and the smooth muscle cells proliferated and migrated from the media to intima of artery, the cell shape modified and increased in rough endoplasmic reticulum also were found. Although the functional significance of these findings is unknown, they might play an important role in smoke-induced occurrence and development of pulmonary hypertension and cor pulmonale.     

Euhydric hypercapnia increases vasoreactivity of rat pulmonary arteries via HCO3- transport and depolarisation

OBJECTIVE: To examine whether altered PCO2 or HCO3- at normal pH potentiate agonist-induced vasoconstriction of small pulmonary arteries, and if so to determine the mechanism. METHODS: Small intrapulmonary arteries (IPA) from rats were mounted on a myograph and PGF2alpha (3 microM)-induced tension recorded before and 40 min after replacing normal bath solution (5% CO2, 24 mM [HCO3-], pH 7.4) with one containing either normal [HCO3-] (24 mM) gassed with 10% CO2 (pH 7.12; hypercapnic acidosis) or high [HCO3-] (48 mM) gassed with 10% CO2 (pH 7.4; euhydric hypercapnia). RESULTS: Hypercapnic acidosis had no significant effect on the response of IPA to PGF2alpha. Euhydric hypercapnia however caused a substantial approximately 5.5-fold potentiation of the response (n=17, p<0.001) in the majority of preparations, whilst 20% of IPA (11 of 58) developed a slow spontaneous vasoconstriction after approximately 20 min. No equivalent responses to euhydric hypercapnia were observed in either mesenteric or renal arteries. Both the potentiation of PGF2alpha-induced vasoconstriction and the spontaneous vasoconstriction in IPA were inhibited by the L-type channel blocker diltiazem (10 microM). The potentiation was also suppressed by DIDS, an inhibitor of anion transporters, removal of extracellular Na+, and anthracene-9-carboxylic acid (A9C; 200 microM), reported to inhibit Ca2+-activated Cl- channels. Inhibition of nitric oxide synthase with L-NAME (100 microM) did not prevent potentiation. Depolarisation with 20 mM [K+] mimicked the effect of euhydric hypercapnia in that it also potentiated the response to PGF(2alpha) (>sixfold, n=6). CONCLUSIONS: Euhydric hypercapnia increases vasoreactivity of IPA, but not mesenteric or renal arteries, via a mechanism involving Na+-dependent HCO3- transport, activation of Ca2+-dependent Cl- channels, and subsequent depolarisation. These results may have consequences for patients with CO2-retaining chronic respiratory disease where plasma [HCO3-] is raised following renal compensation, and could explain the increased propensity to pulmonary hypertension and increased mortality in such patients.     

Cellular mechanisms of hypoxia-induced contraction in human and rat pulmonary arteries

The effect of hypoxia was investigated in human (HPA) and rat (RPA) pulmonary arteries. Hypoxia-induced contraction was 95 ± 8.7% and 9.3 ± 4.8% of the control response to K⁺-rich (80 mM) solution in HPA and RPA, respectively (n = 10). When RPA strips were precontracted with phorbol 12,13 dibutyrate (0.2 μM), hypoxia elicited a larger contraction (105 ± 13.4% of the control response, n = 8). In both types of artery, hypoxia-induced contraction was dependent on the extracellular calcium concentration (66 ± 8.4% and 40 ± 14.4%, reduction for 1.25 mM Ca^{2 +} in HPA and RPA, respectively, n = 6) and was inhibited by verapamil (0.05–10 μM) and nifedipine (0.05–1 μM). Glibenclamide (5–10 μM) increased the amplitude of hypoxia-induced contraction (+ 42 ± 5.3%, n = 5). Hypoxia-induced contraction was blocked by cromakalim (1 μM) and this effect was reversed by glibenclamide (5 μM). This contraction was also inhibited by iodoacetic acid (250 μM). In β-escin skinned pulmonary arterial strips, hypoxia had no effect on the calcium concentrationtension relationship. These results suggest that the O₂ sensor in the pulmonary artery is located on the vascular smooth muscle plasmalemma. Hypoxia-induced contraction is dependent on calcium influx through voltage sensitive calcium channels. Its amplitude is modulated by the functioning of potassium channels.     

Tissue remodeling of rat pulmonary arteries in recovery from hypoxic hypertension

The reversibility of tissue remodeling is of general interest to medicine. Pulmonary arterial tissue remodeling during hypertension induced by hypoxic breathing is well known, but little has been said about the recovery of the arterial wall when the blood pressure is lowered again. We hypothesize that tissue recovery is a function of the oxygen concentration, blood pressure, location on the vascular tree, and time. We measured the changes of blood pressure, vessel lumen, vessel wall thicknesses, and opening angle of each segment of the blood vessel at its zero-stress state after step changes of the oxygen concentration in the breathing gas. The zero-stress state of each vessel is emphasized because it is important to the analysis of stress and strain and in morphometry. Experimental results are presented as histories of tissue parameters after step changes of the oxygen level. Tissue characteristics are examined under the hypothesis that they are linearly related to changes in the local blood pressure. Under this linearity hypothesis, each aspect of the tissue change can be expressed as a convolution integral of the blood pressure history with a kernel called the indicial response function. It is shown the indicial response function for rising blood pressure is different from that for falling blood pressure. This difference represents a major nonlinearity of the tissue remodeling process of the blood vessels.     

Balloon pulmonary valvuloplasty in infants: a quantitative analysis of pulmonary valve-anulus-trunk structure.

OBJECTIVES. The present study was designed to establish possible predictors of unfavorable outcome in infants with pulmonary valve stenosis. BACKGROUND. Balloon pulmonary valvuloplasty is the treatment of choice for typical pulmonary valve stenosis. Patients with dysplastic valves may be less suitable candidates for this procedure because they have morphologic abnormalities of the complex valve-anulus-trunk that cause the obstructive phenomenon. METHODS. Twenty-five children (mean age +/- SD 1.1 +/- 0.7 years) with normal anulus diameter underwent balloon pulmonary valvuloplasty using a balloon/anulus ratio of 1.2 +/- 0.11. From the lateral view of a right ventricular angiogram, the following variables were quantified and scored: A, supravalvular narrowing; B, texture of the valve surface; C, diastolic deformity of the Valsalva sinuses; D, trunk/anulus ratio; E, systolic valve motion; and F, presence of a contrast jet. Paired t test, stepwise multivariate correlation with "dummy" variable methods were applied for both hemodynamic and valve-anulus-trunk determinations. RESULTS. The right ventricular-pulmonary artery gradient decreased from 66 +/- 21 (range 40 to 120) to 24 +/- 11 (range 10 to 50) mm Hg (p less than 0.001), whereas the right ventricular systolic pressure decreased from 89 +/- 20 (range 60 to 130) to 48 +/- 15 (range 30 to 80) mm Hg (p less than 0.001). Only variables A, B and D had significant influence in a percent reduction in right ventricular pulmonary artery gradient (R2 0.94, SEE 5.7; p less than 0.001). A score greater than or equal to greater than 4 obtained by adding the values from these three variables was correlated with poor outcome. CONCLUSIONS. These data show that there is an adequate relation between scores and outcome. We conclude that children less than 2 years old with pulmonary valve stenosis and a score greater than or equal to 4 should not be candidates for balloon pulmonary valvuloplasty.     

Normal values of the growth of the pulmonary arteries in children. An angiography study

Systolic and diastolic diameters of the pulmonary artery anulus (PA-A), pulmonary artery sinus (PA-S), pulmonary artery trunc (PA-St), as well as those of the right and left pulmonary arteries (RPA, LPA) were measured from cineangiograms of 51 infants, children and adolescents without heart disease (n = 16) or with cardiovascular malformations which had no hemodynamic relevance (n = 35). The following diagnostic categories were included in the normal group: pulmonary stenosis (n = 16), bicuspid aortic valve (n = 4) or subvalvular aortic stenosis (n = 2), all with a systolic gradient lower than 15 mm Hg, aberrant innominate artery (n = 5), small PDA (n = 3) or small VSD (n = 2) and patients with Kawasaki disease without coronary aneurysms (n = 3). The patients were sedated and studied in a fasting state and in the supine position. Angiocardiographies were performed in the right ventricle or/and in the pulmonary artery. A grid or the known diameter of the catheter was used for calibration purposes. The corresponding systolic and diastolic diameter values were averaged in order to obtain a mean diameter of each vascular segment. All measurements were correlated with the body length and the body surface area (BSA). A root exponential function [square root of y = a(1 - e-bx) + c] was used, the regressions coefficients of which can be explained by physiological means. In this function c2 is the theoretical minimal diameter and (a + c)2 the theoretical maximal diameter of a cardiovascular structure; in this way the growth of the cardiovascular dimensions could be well defined mathematically and correlated strongly (r = 0.99) with body length and BSA. Different exponents were found for the pulmonary artery anulus, sinus, trunc as well as right and left pulmonary arteries. All the diameters showed a systolic increase between 8 to 10% above diastolic measurements. The anulus had an average diameter 16% smaller than the sinus and 9% than the distal region of the pulmonary artery; the right pulmonary artery was 7% larger than the left. A limitation of the study was that the diameters were measured in single projections only, necessitating the assumption of a circular cross section of the cardiovascular structures. The angiographically determined PA-A was larger than those of formaldehyd-fixed hearts. This finding indicates that the fixation method may alter the anatomic structures probably due to shrinkage process. PA-S measurements were closest to echocardiographic diameters measured by other authors.     

A 2-D/3-D model-based method to quantify the complexity of microvasculature imaged by in vivo multiphoton microscopy

This paper presents model-based information-theoretic methods to quantify the complexity of tumor microvasculature, taking into account shape, textural, and structural irregularities. The proposed techniques are completely automated, and are applicable to optical slices (3-D) or projection images (2-D). Improvements upon the prior literature include: (i) measuring local (vessel segment) as well as global (entire image) vascular complexity without requiring explicit segmentation or tracing; (ii) focusing on the vessel boundaries in the complexity estimate; and (iii) added robustness to image artifacts common to tumor microvasculature images. Vessels are modeled using a family of super-Gaussian functions that are based on the superquadric modeling primitive common in computer vision. The superquadric generalizes a simple ellipsoid by including shape parameters that allow it to approximate a cylinder with elliptical cross-sections (generalized cylinder). The super-Gaussian is obtained by composing a superquadric with an exponential function giving a form that is similar to a standard Gaussian function but with the ability to produce level sets that approximate generalized cylinders. Importantly, the super-Gaussian is continuous and differentiable so it can be fit to image data using robust non-linear regression. This fitting enables quantification of the intrinsic complexity of vessel data vis-a-vis the super-Gaussian model within a minimum message length (MML) framework. The resulting measures are expressed in units of information (bits). Synthetic and real-data examples are provided to illustrate the proposed measures.