Simple model of pulmonary hypertension secondary to left heart pressure overload induced by partial intravascular occlusion of the ascending aorta.

Pulmonary hypertension is a group of diseases characterized by elevated pulmonary artery pressure and pulmonary vascular resistance with significant morbidity and mortality. The most prevalent type is pulmonary hypertension secondary to left heart disease (PH-LHD). The available experimental models of PH-LHD use partial pulmonary clamping by technically nontrivial open-chest surgery with lengthy recovery. We present a simple model in which the reduction of the cross-sectional area of the ascending aorta is achieved not by external clamping but by partial intravascular obstruction without opening the chest. In anesthetized rats, a blind polyethylene tubing was advanced from the right carotid artery to just above the aortic valve. The procedure is quick and easy to learn. Three weeks after the procedure, left heart pressure overload was confirmed by measuring left ventricular end-diastolic pressure by puncture (1.3 ± 0.2 vs. 0.4 ± 0.3 mmHg in controls, mean ± SD, P < 0.0001). The presence of pulmonary hypertension was documented by measuring pulmonary artery pressure by catheterization (22.3 ± 2.3 vs. 16.9 ± 2.7 mmHg, P = 0.0282) and by detecting right ventricular hypertrophy and increased muscularization of peripheral pulmonary vessels. Contributions of a precapillary vascular segment and vasoconstriction to the increased pulmonary vascular resistance were demonstrated, respectively, by arterial occlusion technique and by normalization of resistance by a vasodilator, sodium nitroprusside, in isolated lungs. These changes were comparable, but not additive, to those induced by an established pulmonary hypertension model, chronic hypoxic exposure. Intravascular partial aortic obstruction offers an easy model of pulmonary hypertension induced by left heart disease that has a vasoconstrictor and precapillary component.NEW & NOTEWORTHY We present a new, simple model of a clinically important type of pulmonary hypertension, that induced by left heart failure. Left ventricular pressure overload is induced in rats by inserting a blinded cannula into the ascending aorta via carotid artery access. This partial intravascular aortic obstruction, which does not require opening of the chest and prolonged recovery, causes pulmonary hypertension, which has a precapillary and vasoconstrictor as well as a vascular remodeling component.

Recovery from hypoxic pulmonary hypertension in rats.

To characterize the time frame of changes in pulmonary arterial pressure, right ventricular hypertrophy and morphology of small pulmonary arteries male Wistar rats were exposed to isobaric hypoxia (3 weeks, F1O2 0.1) and then let to recover on air for 1 or 5 weeks. Normoxic animals (group N) served as controls. Mean pulmonary arterial pressure (PAP), ratio of the weight of the right heart ventricle to the sum of the weights of the left ventricle and septum (RV/LV+S) and percentage of double laminated pulmonary vessels ( % DL) were measured at the end of hypoxic exposure (group H), after 1 or 5 weeks of recovery (groups 1R and 5R), and in controls kept in air (group N). Three weeks in hypoxia resulted in increase in PAP, RV/LV+S and % DL. After 1 week of recovery RV/LV+S normalized, PAP decreased, while % DL did not change. After 5 weeks in air PAP returned to control values and % DL diminished significantly but did not normalize. Our results suggest that recovery depends on the degree of HPH and that knowledge of the time-frame of recovery is important for future studies in our rat model.

Volumetry of the human amygdala - an anatomical study.

A striking feature of the studies that have addressed the measurement of the amygdala is the wide range of volumes encountered, with reports of volumes ranging from 1 to almost 4 cm(3). Another striking feature is the number of discrepancies in the landmarks adopted for manual tracing in magnetic resonance imaging (MRI). The goal of our study was to assess the anatomical volume of the amygdala on the basis of its cytoarchitecture while comparing the differences in age and sex. This study was performed on 21 normal male brains (mean age of 56.8 years) and 9 normal female brains (mean age of 61.2 years). The volume of the amygdala was measured by planimetry of Nissl-stained serial sections using ImageJ software. To address the complexity of the amygdala, we elected to use two types of amygdalar measurement that differ mainly in the definition of anterior pole boundaries. The average size of the classic amygdala was 1.24 cm(3) (S.D.=0.14), while the average size of the amygdala with wider borders was 1.63 cm(3) (S.D.=0.2). No interhemispheric or intersexual differences were observed for either type of amygdalar measurement. Neither sex revealed any statistically important relationship between volume of the amygdala and age. Our study was concerned exclusively with the anatomical volume of the amygdala rather than the MRI volume. Nevertheless, our results may have important implications for MRI studies because as of yet there is no gold standard for manual volumetry of the amygdala.

Prevention of mast cell degranulation by disodium cromoglycate delayed the regression of hypoxic pulmonary hypertension in rats.

BACKGROUND: Pulmonary vascular remodeling induced by chronic hypoxia regresses after return to normoxia. This regression is associated with an increased amount of collagenase in pulmonary mast cells and increased collagenolytic and elastolytic activity in the lung tissue. OBJECTIVE: The role of lung mast cells during recovery from chronic hypoxia was tested by the inhibition of their degranulation by disodium cromoglycate (DSCG). METHODS: Male Wistar rats (n = 46) were exposed to isobaric hypoxia (3 weeks, F(i)O(2) 0.1). Thirteen of them were tested immediately at the end of exposure, 17 were treated with DSCG during the first 4 days of recovery and tested on the 5th or 14th day of recovery, 16 untreated animals were measured at the same time intervals. These groups were compared with 12 animals kept in normoxia. The rats were anesthetized (Thiopental) and their pulmonary arterial blood pressure (PAP), cardiac output and heart weight were tested, as well as the collagen composition of the walls of the peripheral pulmonary arteries. RESULTS: DSCG applied during the first 4 days of recovery from chronic hypoxia blocked the decrease in PAP during the early phase of recovery and had no influence on PAP at a later phase. DSCG administration prevents collagen splitting in peripheral pulmonary vessels at the early phase of recovery. PAP and right ventricle hypertrophy were normalized after 14 days of return to normoxia. CONCLUSIONS: Mast cell degranulation plays a role in the regression of pulmonary hypertension during the early phase of recovery from chronic hypoxia.

[Mast cells--a new view of the old acquaintances]. / Zírné bunky--nový pohled na staré známé.

Mast cells are well known as the producers of histamine and major effectors of type 1 hypersensitivity. They play however an important role in many other physiological and pathological processes. Lesser-known is their role in the processes such as a termination of pregnancy and initiation of delivery. The mast cells are considered as the modulators of endocrine signals on the local reactions in uterus. Many substances produced by the mast cells have the angiogenic effects known primarily for their role in tumour growth, but they influence also embryonal and postnatal growth or process of wound healing. Mast cells also participate in a number of compensatory reactions in the tissue response to the mechanical load, hypoxia or inflammation (airway remodelling in asthma, remodelling of pulmonary vessels in chronic hypoxia, myocardial hypertrophy, liver cirrhosis, chronic pancreatitis). This review describes recent concepts of their role in labour, non-cancerous angiogenesis and remodelling of pulmonary vasculature during chronic hypoxia.

The effect of exposure to hypoxia on superoxide formation by alveolar macrophages is indirect.

AIMS: To elucidate the role of alveolar macrophages (AM) in the pathogenesis of hypoxic pulmonary hypertension (HPH), we tested the effects of sustained hypoxia on AM polarization and on the formation of superoxide by AM in vivo and in vitro. MAIN METHODS: Rat AM were obtained by bronchoalveolar lavage. 4-day exposure to hypoxia (10% O2) was carried out in vivo (rats in isobaric hypoxic chamber, controls kept in air) or in vitro (control AM in 21% O2 and 5% CO2). Superoxide production was measured by luminol-orthovanadate chemiluminescence, AM polarization was detected immunocytochemically. To ascertain the effect of substances contained in the alveolar environment, we cultivated cells also in the presence of non-cellular components of the bronchoalveolar lavage fluid (BALF) either from controls or from rats exposed to 4 days of hypoxia. KEY FINDINGS: In vivo, but not in vitro, hypoxia increased AM superoxide production. Both types of hypoxia polarized AM into M2 (pro-proliferative) type. While the presence of control BALF attenuated superoxide production in AM cultivated in normoxia, BALF from the hypoxia-exposed rats had no effect. In AM cultivated in hypoxia, superoxide production was not altered by control BALF and elevated by BALF obtained from hypoxic rats. SIGNIFICANCE: Hypoxia does not influence superoxide production by AM directly but rather by modulating their milieu and their sensitivity to external influences.

Prevention of mast cell degranulation by disodium cromoglycate attenuates the development of hypoxic pulmonary hypertension in rats exposed to chronic hypoxia.

BACKGROUND: Chronic hypoxia induces lung vascular remodeling, which results in pulmonary hypertension. Vascular remodeling is associated with collagenolysis and activation of matrix metalloproteinases (MMPs). One of the possible sources of MMPs in hypoxic lung are mast cells. OBJECTIVE: The role of lung mast cell collagenolytic activity in hypoxic pulmonary hypertension was tested by the inhibitor of mast cell degranulation disodium cromoglycate (DSCG). METHODS: Rats were treated with DSCG in an early or later phase of isobaric hypoxia. Control groups were exposed to hypoxia only or to normoxia. Lung hemodynamics, muscularization and collagen metabolism in the walls of peripheral pulmonary vessels in the lungs were measured. RESULTS: DSCG applied at an early phase of exposure to hypoxia reduced the development of pulmonary hypertension, inhibited muscularization in peripheral pulmonary arteries and decreased the amount of collagen cleavage fragments in prealveolar vessels. CONCLUSIONS: Mast cell degranulation plays a role in the initiation of hypoxic pulmonary vascular remodeling.