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K Rakusan

Publications and source records attributed to K Rakusan.

At least 55 records · Page 3Linked to original sources
PubMed1992

Morphometry of human coronary capillaries during normal growth and the effect of age in left ventricular pressure-overload hypertrophy.

BACKGROUND: In adults, acquired pressure-overload left ventricular hypertrophy can result in myocardial ischemia, which may be due in part to insufficient capillary growth during development of hypertrophy. The coronary microvascular response to congenital pressure-overload hypertrophy in children has not been previously characterized. METHODS AND RESULTS: Average capillary density and heterogeneity of capillary spacing were measured in 63 postmortem human hearts with left ventricular hypertrophy and control hearts without heart disease. Pathology specimens were chosen that had left ventricular hypertrophy caused by 1) congenital isolated aortic valve stenosis in infants less than 1 year old at death, children 9-14 years old, and adults 15-30 years old; 2) congenital isolated coarctation of the aorta in adults 15-39 years old; and 3) acquired aortic stenosis in adults 51-86 years old. Major findings of the study were: 1) Human left ventricular capillary density and heterogeneity of capillary spacing are similar to other mammalian species. 2) Capillary density is higher in infants (3,315 +/- 85 capillaries per square millimeter), decreases with increasing heart weight during normal growth in early childhood (children, 2,388 +/- 75 capillaries per square millimeter, p less than 0.05), and thereafter remains relatively constant. 3) Capillary density with left ventricular hypertrophy is dependent on the age of onset. Congenital aortic stenosis and coarctation are characterized by an increase in capillary supply proportional to myocyte volume, maintaining capillary density similar to control hearts. Adults with acquired aortic stenosis have decreased capillary density (1,671 +/- 66 capillaries per square millimeter, p less than 0.01 versus control). CONCLUSIONS: Pressure-overload left ventricular hypertrophy in children demonstrates proportional capillary angiogenesis, whereas in adults, hypertrophy appears to be associated with failure of compensatory angiogenesis.

Adolescent↗
PubMed1992

Capillary geometrical changes with fiber shortening in rat myocardium.

Capillary-to-fiber geometrical relations constitute an integral component of peripheral gas exchange. Determination of capillary length and surface area density necessitates quantification of capillary orientation (i.e., tortuosity and branching). In skeletal muscle, capillary tortuosity increases in a curvilinear fashion at reduced sarcomere length, and this compensates for decreased capillary density as fiber cross-sectional area increases. To investigate these relations in myocardium, rat hearts were glutaraldehyde perfusion-fixed in calcium- or barium-induced "systole" to provide varying degrees of fiber shortening. Morphometric techniques were used to analyze capillary geometry in subepicardium (EPI) and subendocardium (ENDO) using 1-micron sections cut transverse and longitudinal to the muscle fiber axis. Capillary density on transverse and longitudinal sections, capillary diameter, fiber cross-sectional area, and sarcomere length were determined in each region. Capillary surface density was computed, and values were related to sarcomere length and compared with published data for diastolic hearts. Sarcomere length in systole ranged from 2.06 +/- 0.03 to 1.35 +/- 0.02 microns (EPI) and from 1.93 +/- 0.04 to 1.44 +/- 0.04 microns (ENDO). Fiber cross-sectional area (EPI, 344 +/- 13 microns2; ENDO, 343 +/- 12 microns2) was significantly larger, and capillary density on transverse sections was significantly smaller (EPI, 4,105 +/- 318 mm-2; ENDO, 4,145 +/- 267 mm-2) than in hearts arrested in diastole. Compared with skeletal muscle, capillary tortuosity was substantially less increased by fiber shortening. Capillary tortuosity and branching did not differ between EPI and ENDO and contributed a maximum of 33% (range, 13-33%) to capillary length density and surface area at a sarcomere length of 1.45 +/- 0.04 microns. Compared with diastolic hearts, capillary length density decreased on average by 19.6% (EPI) and 17.7% (ENDO); similarly, capillary surface density decreased 19.9% (EPI) and 13.7% (ENDO). We conclude that, with fiber shortening in the heart, fiber cross-sectional area increases and capillary numerical density decreases as predicted from reduced sarcomere length. Combined with the minimal geometrical changes of the capillary bed at shorter fiber lengths, this results in a lower capillary length and surface area per fiber volume in systole. Consequently, the structural potential for O2 diffusion into myocytes is determined, in part, by fiber length.

Animals↗
PubMed1992

Microvascular geometry of the rat heart. Arteriolar and venular capillary regions.

The importance of realistic data regarding microvascular geometry for the understanding of oxygen transport to tissue cannot be underestimated. The purpose of the present investigation was therefore to determine the pattern of capillarization in rat myocardium. The histochemical method used in this study was novel in that it allowed for the discrimination of arteriolar capillary (AC) and venular capillary (VC) regions on the basis of color. Our preeminent finding was that systematic differences exist in microvascular geometry from arteriolar to venular capillary regions in normal rat myocardium. Specifically, VC regions are characterized by greater capillary density; more uniform capillary spacing; shorter segment lengths; and increased capillary diameter. These differences translate to significantly greater capillary length, surface and volume densities on the venular side of the capillary bed. In the face of lower PO2 values towards venules, this distinctive geometry would serve to provide advantageous geometric conditions for oxygen diffusion.

Animals↗
PubMed1991

Geometry of capillary networks in hypertrophied rat heart.

Capillary geometry was examined in normal and hypertrophic myocardium. Hypertrophy was induced by aortic constriction in neonatal rats. Morphometric data were obtained from tissue sections exposed to a staining technique that distinguished the arteriolar and venular portions of capillaries by color. In sham-operated controls, the theoretical tissue region supplied by a single capillary decreased from the arteriolar to venular side (499 +/- 3 microns 2 and 456 +/- 5 microns 2, P less than 0.05; mean +/- SE) of capillaries. In hypertrophy, only arteriolar capillary tissue regions increased in size, thus enlarging the difference between arteriolar and venular ends (547 +/- 6 microns 2 and 464 +/- 5 microns 2, P less than 0.01). Intercapillary distances, measured at various levels along the capillary path length, decreased in a stepwise manner in both normal and hypertrophic hearts. In hypertrophic hearts, mean capillary path length was significantly longer than in controls, but the total length of the individual capillary nets was reduced. In both groups, arteriolar capillary segment length was longer (P less than 0.01) than venular capillary segment length. Given that PO2 values are lower on the venular side of capillaries, this spatially distinctive geometry in normal myocardium: smaller domains, shorter intercapillary distances and segment lengths, would provide favorable geometric conditions for oxygen diffusion. In hypertrophy, average intercapillary distance increased, and the distinction between arteriolar and venular portions of capillaries was further exacerbated.

Animals↗
PubMed1991

Geometry of capillary networks in volume overloaded rat heart.

Volume overload cardiac hypertrophy was induced in male Sprague-Dawley rats by experimental aortocaval fistula. This procedure resulted in considerable increases in left ventricular mass (70%) by 21-23 days. Our objective was to study the effect of volume overload on the geometry of coronary capillaries in the left ventricular midmyocardium. Tissue sections were stained according to a protocol that distinguished arteriolar (AC) and venular (VC) capillary regions by color. Morphometric data were then collected and compared between AC and VC regions. In sham-operated controls (CON; n = 8), the tissue area (capillary domain) supplied by a single capillary decreased from AC to VC regions (AC = 505 +/- 5 microns 2: VC = 452 +/- 7 microns 2; P less than 0.01; mean +/- SE). In volume overloaded hearts (VOL; n = 8), only VC domain areas were reduced from control values (P less than 0.01) and the differences between AC and VC regions were preserved (AC = 480 +/- 5 microns 2; VC = 395 +/- 6 microns 2; P less than 0.01). Minimal capillary length was significantly longer in volume overloaded hearts (VOL = 723 +/- 18; CON = 581 +/- 20 microns; P less than 0.01). In the control group, AC segment length was longer than VC segment length (AC = 93 +/- 2 microns: VC = 74 +/- 2 microns; P less than 0.01). In volume overload, AC segment length was also longer than VC segment length, but the divergence between AC and VC regions was increased (AC = 108 +/- 3 microns; VC = 71 +/- 2 microns; P less than 0.01). These changes in capillary geometry may be secondary to specific changes in the arrangement and dimension of myocytes in the left ventricular wall following volume overload hypertrophy.

Animals↗
PubMed1991

An in oculo model for quantitation of vascular growth in the rat heart.

STUDY OBJECTIVE: The aim was to describe, both qualitatively and quantitatively, vascularisation in an in oculo model that may prove useful for studying neovascularisation in the myocardium. DESIGN: Whole hearts from 13-14 d rat fetuses were implanted into the anterior chamber of host Sprague Dawley rats. Implant growth was monitored and at 3 months postimplantation grafts were recovered. EXPERIMENTAL MATERIAL: Fixed tissue sections were histologically characterised with light and electron microscopy and morphometrically analysed using image analysis. MEASUREMENTS AND MAIN RESULTS: At two weeks, 92% of implanted hearts were beating. At 1 month, well vascularised implants that were beating were slightly larger than those not beating, at 16.0(SD 1.0) v. 12.3(2.0)mm2. By 2 months, beating implants were significantly (p less than 0.05) larger than non-beating implants, at 23.5(3.0) v. 12.4(1.7)mm2. In non-beating implants, the larger the extent of vascularisation, the larger the implant size. Histologically, well vascularised beating implants showed normal adult cardiac myocyte structure, with normal appearing sarcomeres and intercalated discs, but no preferential fibre orientation. The amount of area occupied by muscle and connective tissue varied between implants. Implant vasculature, including arterioles and capillaries, appeared normal. The percentage of vascular area was consistent between grafts. A small percentage of total area was occupied by lymphocytes. CONCLUSIONS: This investigation indicates that sufficient vascularisation is important for growth of grafts, provides for the first time quantitative morphometric data characterising the in oculo cardiac implant model, and reports baseline data that will be useful for comparison to myocardium treated with putative angiogenic factors in the future.

Animals↗
PubMed1991

Spatial relationship between cardiac mast cells and coronary capillaries in neonatal rats with cardiomegaly.

Density of cardiac mast cells and their localization with respect to coronary capillaries was studied in two experimental situations. First, cardiac hypertrophy produced by aortic constriction in 5-day-old rats was studied. Left ventricular weight increased more than twofold in this experimental situation, while the increases in total capillary length and total number of cardiac mast cells were much smaller, resulting in decreased densities of both tissue components. In the second series of experiments, localization of cardiac mast cells at two distinct portions of coronary capillaries was studied in normal hearts of adult rats. Differential histochemical staining enabled us to distinguish between the portions of capillaries close to arterioles and portions on the venular side. The number of mast cells close to arteriolar portions of coronary capillaries was significantly higher than one would expect in the case of their even distribution along the capillary wall. The relationship between the mast cells and formation of new capillaries is discussed.

Animals↗
PubMed1991

Computed myocardial PO2 histograms: effects of various geometrical and functional conditions.

A model of myocardial oxygenation was developed that allows calculation of Po2 histograms under varying conditions. The model consists of parallel tissue cylinders with varying radii, simulating the heterogeneity of capillary spacing, in agreement with our previous experimental results. The facilitated diffusion of O2 by myoglobin, an additional resistance to diffusion at the capillary level, and the Michaelis-Menten type of O2 consumption were also incorporated. The shape of the histograms depends on input data. When no additional barrier to O2 transport is included, the histograms resemble those obtained with Po2 surface electrodes, and they are strongly dependent on heterogeneity in capillary spacing and capillary blood flow. On the other hand, an inclusion of an additional capillary barrier combined with the Michaelis-Menten type of O2 consumption can generate Po2 histograms similar to those derived from myoglobin cryospectroscopy. In this case, the Po2 histograms are relatively independent of heterogeneity of capillary spacing and blood flow. The facilitation of O2 diffusion by myoglobin has only a modest effect on the form of the histograms in all situations considered.

Animals↗
PubMed1991

Remodeling of myocyte dimensions in hypertrophic and atrophic rat hearts.

Changes in hemodynamic load cause alterations in cardiac myocyte size, with regional variations in myocyte size distribution possible within the ventricular wall. We studied regional changes in cellular dimensions and their distribution in two models of cardiac hypertrophy and in cardiac atrophy in the rat. Combined volume-pressure overload was produced by 3,3',5-triiodo-L-thyronine (T3) treatment; atrophy was produced by heterotopic isotransplantation. Our previous data from long-term pressure overload after aortic constriction were used for comparison. Isolated ventricular myocytes were obtained after in vitro coronary perfusion with collagenase. Cell volume and its distribution were determined; cell length was directly measured by image analysis, and cross-sectional area was estimated from the cell volume/cell length ratio, assuming a cylindrical model. Myocyte hypertrophy resulting from hyperthyroidism and aortic constriction was primarily due to increased cross-sectional area. In both cases, the relative response was greater in the right ventricle than in the left ventricle. Within the left ventricle, epimyocardial myocytes enlarged the most. Aortic constriction and T3 treatment predominantly increased the size of smaller myocytes. Heterogeneity in myocyte size increased after constriction but remained relatively unaffected after T3 treatment. Atrophy of left ventricular myocytes was due to a proportional decrease in cell length and cross-sectional area, with the greatest decrease in the left ventricular endomyocardium. Atrophy predominantly affected larger myocytes, resulting in a more homogeneous overall population of smaller myocytes. We conclude that various alterations in load lead to diverse remodeling in the myocyte population throughout the ventricular wall. In general, smaller myocytes show the highest growth potential, whereas larger myocytes exhibit the highest potential to atrophy.

Animals↗
PubMed1991

Capillarization of the hypertrophic heart: discrepancy of the results obtained by the triangulation and domain methods.

The geometry of capillary networks was examined in pressure-overloaded hypertrophic rat myocardium. All hearts were exposed to a staining protocol that distinguished the arteriolar (AC) and venular (VC) regions of capillaries. In control hearts, the triangulation method (one-dimensional distance between neighboring capillaries) and the domain method (two-dimensional area surrounding capillaries) exhibited similar results, showing increased capillarization for the venular region of capillaries networks. In hypertrophic hearts, the triangulation method did not demonstrate differences between arteriolar and venular capillaries (AC = 27.2 +/- 0.4 microns, VC = 27.0 +/- 0.2 microns, p = 0.56). However, the domain method still detected smaller tissue supply regions for venular capillaries (AC = 547 +/- 6 microns 2, VC = 464 +/- 5 microns 2, p less than 0.01). To resolve this discrepancy in hypertrophic heart, we have measured capillary spacing from longitudinal sections at discrete intervals along the A-V path length. These results indicate a stepwise decrease in intercapillary distance from arteriole to venule for both groups, which would support results obtained by the domain method. A possible explanation for the discrepancy between these two methods, specific to hypertrophic heart, may be changes in the clustering patterns of arteriolar and venular capillaries.

Animals↗
PubMed1991

Development of the coronary vasculature in hypoxic fetal rats treated with a purified perfluorocarbon emulsion.

OBJECTIVE: To quantitatively define the coronary vascular bed in the 21-day-old rat fetus with gestational normoxia and hypoxia; to determine if maternal supplemental oxygen and/or oxygen-carrying perfluorocarbons (PFCs) influence development of coronary vessels; and to compare the results using purified and unpurified PFC treatment. DESIGN: Unilateral uterine artery ligation was introduced on gestational day 17 in pregnant animals. Control fetuses were from unligated uterine horns. Experimental intervention occurred during gestational days 17 to 21, with fetuses recovered on day 21. Developing coronary vessels were analyzed quantitatively via light microscopy. ANIMALS: Pregnant Sprague Dawley rats. INTERVENTIONS: Following ligation, pregnant rats received no further treatment, supplemental oxygen inhalation alone, or daily intravenous purified PFC treatment, with or without supplemental oxygen. MAIN RESULTS: Hypoxia caused an increase in resorptions (P less than 0.001), and decreased fetal body weight (P less than 0.001) and heart weight (P less than 0.05). Although the area occupied by developing coronary vessels (sinusoids) was substantially increased, maturation was unchanged. Oxygen supplementation alone did not appreciably influence fetal resorptions or body weight in ligated horns, but did increase fetal heart weight. Sinusoidal area decreased (P less than 0.01), with no effect on sinusoidal maturity. Purified PFC treatment did not alter maternal weight gain or fetal body weight, and moderately decreased resorptions in ligated horns. Fetal heart weight was augmented with purified perflurochemical, while unpurified perfluorochemical treatment diminished heart weight. Both PFC emulsions substantially decreased sinusoidal area. CONCLUSIONS: Perflurocarbon treatment associated with supplemental oxygen is capable of improving the hypoxic effects on fetal heart and coronary vessel development if the emulsion used is appropriately purified.

Animals↗
PubMed1990

Morphometry of the small arteries and arterioles in the rat heart: effects of chronic hypertension and exercise.

STUDY OBJECTIVE: The aim of the study was to characterise small coronary arteries and arterioles quantitatively in rat left ventricle and septum under various experimental conditions. DESIGN: Morphometric analysis of resistance vessels was carried out in rats divided into four experimental groups: (1) control animals sedentary; (2) control animals exercised (moderate swimming); (3) renal hypertensive animals sedentary; (4) renal hypertensive rats exercised. Hypertensive animals received the two kidney/one clip Goldblatt procedure; control animals were sham operated. SUBJECTS: Experimental animals were 28 female Sprague-Dawley rats. MEASUREMENTS AND RESULTS: In hypertensive rats, there was a significant increase in left ventricular mass and a reduced coronary reserve. Morphometric analysis of 10,000 resistance vessels in the coronary bed showed that cardiac hypertrophy in hypertensive rats was characterised by increased wall thickness in arterioles and small arteries and an increased lumen to wall ratio, particularly in vessels of 30-100 microns size. The number of capillary profiles per arteriole in cross section was also decreased in the hypertensive rat. Chronic exercise increased the number of capillaries per arteriole in controls but not in hypertensive rats. Swimming did not affect the architecture of the resistance vessels. CONCLUSIONS: Chronic renal hypertension, but not swimming, produces subtle but significant changes in structure of coronary resistance vessels.

Animals↗
PubMed1990

Mast cells in the rat heart during normal growth and in cardiac hypertrophy.

Mast cells in rat hearts were studied quantitatively during normal postnatal growth and in two types of cardiac hypertrophy. Normally, cardiac mast cell density in 11-12-day-old animals is very low, but increases markedly in the following 2-3 weeks to its highest values, with a subsequent decline toward adult values. At the peak of mast cell density, the percentage of mast cells in close proximity to capillaries is also highest. In adult animals, mast cell counts are significantly higher in the right ventricle than in the left. This relation is preserved even when the right ventricle is hypertrophic, as in rats born at simulated high altitude. Chronic hypertension and swimming have little effect on the mast cell density in rat hearts. Conspicuous changes in the mast cell density at the time of capillary proliferation seem to indicate a special role played by these cells in the formation of new vessels.

Altitude↗
PubMed1990

Functional and morphological characteristics of compensated and decompensated cardiac hypertrophy in dogs with chronic infrarenal aorto-caval fistulas.

The relation between cardiac hypertrophy, shunt size, myocardial contractility, capillary density, adrenergic responsiveness, and neurohumoral stimulation was evaluated in dogs with compensated and decompensated cardiac hypertrophy caused by an infrarenal aorto-caval shunt. Shunt size varied from 5 to 35 mm2 due to an inability to create a uniform size. Dogs that developed heart failure within 4 months had 25 +/- 2 mm2 shunts, whereas those that developed it after 4 months had 19 +/- 3 mm2 shunts; those that did not develop heart failure had 10 +/- 1 mm2 shunts. Hypertrophy developed at the same rate in all the dogs that developed heart failure, which occurred at a critical heart weight (hypertrophy) for a given load (shunt size). In the dogs with heart failure there was a decrease in myocardial contractility (tension = 5.7 +/- 0.6 vs. 7.3 +/- 0.3 g/mm2, p less than 0.05), a decrease in adrenergic responsiveness (maximal heart rate with isoproterenol = 203 +/- 7 vs. 249 +/- 5 beats/min, p less than 0.01), an increase in circulating neurohormones, and a decrease in urinary sodium excretion (0.4 +/- 0.1 vs. 5.0 +/- 1.3 meq/3 hr, p less than 0.01). None of these abnormalities occurred in dogs with compensated hypertrophy. There were no differences in cardiac capillary density between the control dogs and the dogs with compensated cardiac hypertrophy or heart failure. Thus, it would appear that if heart failure is to develop after an initial toleration of a sudden volume overload, it will develop at a given combination of cardiac hypertrophy and volume overload, with cardiac hypertrophy developing at the same rate in all cases. In this model, once heart failure develops, myocardial contractility and cardiac adrenergic responsiveness are decreased and there is pronounced neurohumoral activation. All these changes are absent in hearts with compensated hypertrophy.

Adaptation, Physiological↗