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Biomedical subjects

K Rakusan

Publications and source records attributed to K Rakusan.

At least 19 recordsLinked to original sources
PubMed2001

Effect of anemia on cardiac function, microvascular structure, and capillary hematocrit in rat hearts.

The effect of anemia on the coronary microcirculation was studied in young male rats. Chronic anemia resulted in increased left ventricular end-diastolic pressure and decreased functional reserve. Cardiac mass in anemic animals increased by 25%. Capillary and arteriolar densities in these hearts remained unchanged, indicating angiogenesis in this experimental situation (estimated aggregate capillary length in the left ventricle of anemic hearts was 3.06 km compared with 2.35 km in control hearts). Capillary hematocrit was decreased in chronic anemia less than systemic hematocrit: from 25 to 18% in anemia versus 45 to 28% in controls. Capillary hematocrit and red blood cell spacing were also studied after acute blood withdrawal. Here, capillary hematocrit was preserved even more: 22 versus 24% in systemic hematocrit. Finally, the same was studied in isolated hearts perfused with solutions of various hematocrits. After perfusion with low-hematocrit solution (14%), the capillary hematocrit (24%) was even higher than the perfusate hematocrit! In conclusion, we found evidence of angiogenesis in cardiomegaly induced by chronic anemia. Microvascular growth was accompanied by advantageous regulation of red blood cell spacing within these vessels. This was even more pronounced during acute hemodilution and in isolated perfused hearts.

Anemia↗
PubMed2001

Cardiac function, microvascular structure, and capillary hematocrit in hearts of polycythemic rats.

The effect of polycythemia on the coronary microcirculation was studied in young male rats. Two experimental models of polycythemia were employed: cobalt-induced polycythemia, which mimics hypoxia-induced changes, and erythropoietin-induced polycythemia, which circumvents these changes. In both models, baseline left ventricular function was normal, whereas maximal systolic and developed pressures were decreased. In cobalt-treated rats the left ventricular functional reserve was also compromised. Morphometric analysis of the left ventricle confirmed previously described improved geometric conditions for oxygen supply at the distal portions of capillaries (smaller domain areas and shorter capillary segments). In cobalt-treated but not in erythropoietin-treated rats, increased capillary angiogenesis was also detected. In the hearts from rats with both types of polycythemia, a small but significant increase in the formation of arterioles was found. Capillary linear hematocrit was within the normal range in both types of polycythemia despite sizeable increases in systemic hematocrit. Significant differences in red blood cell distribution within capillaries were found between proximal and distal portions in all experimental groups.

Animals↗
PubMed2000

The effect of treatment with low dose ACE inhibitor and/or diuretic on coronary microvasculature in stroke-prone spontaneously hypertensive rats.

Angiotensin II is considered to have angiogenic properties. Nevertheless, several authors reported an increase in coronary capillary density after treatment with ACE inhibitors. The aim of the present study was to evaluate the effect of treatment with low doses of ACE inhibitor perindopril, low doses of the diuretic indapamide, or a combination of the two on microvascular structure in hearts from stroke-prone spontaneously hypertensive rats (SHR-sp). Young adult male SHR treated with indapamide (0.24 mg/kg/day), perindopril (0.76 mg/kg/day), or both were compared with untreated animals after 8 or 14 weeks of treatment. Survival of SHR-sp was significantly increased after treatment. Only perindopril alone or in combination with indapamide significantly decreased blood pressure and cardiac mass. Treatment also significantly increased capillary and myocyte densities but arteriolar density tended to decrease. External and internal diameters significantly increased in treated animals while arteriolar thickness remained the same. Thus, thickness in vessels of the same size was the greatest in untreated animals, followed by indapamide- and perindopril-treated rats with the thinnest walls in rats with combined treatment, and the treatment resulted in a significant increase in the lumen to wall ratio. Capillary and arteriolar growth responses in treated animals seem to indicate that the two are independently regulated processes. Treatment with indapamide alone at this dosage did not significantly influence most responses but in combination with perindopril it strengthened the effect of perindopril.

Angiotensin II↗
PubMed1999

Effects of chronic heparin administration on coronary vascular adaptation to hypertension and ventricular hypertrophy in sheep.

BACKGROUND: Hypertension decreases myocardial perfusion capacity in adults for several reasons, including insufficient coronary angiogenesis with left ventricular (LV) hypertrophy, arteriolar hypertrophy, and altered vasomotion. Heparin influences growth factors that promote angiogenesis and vasodilation and inhibit arteriolar wall thickening. METHODS AND RESULTS: Adult sheep were given heparin 200 U/kg body wt SC twice daily throughout 6 weeks of LV and coronary hypertension from a progressively constricted ascending aortic band (n=14). They were compared with untreated sheep with (n=13) and without (n=13) aortic stenosis. After 6 weeks, maximum myocardial perfusion was measured during adenosine infusion in the conscious state by the microsphere method. Sheep with aortic stenosis had less maximum coronary flow per gram, less conductance reserve, and thicker arteriolar walls in the LV and nonhypertrophied right ventricle. Capillary density decreased in the LV endomyocardium and remained unchanged in the right ventricle. Heparin-treated sheep had significant partial normalization of coronary conductance reserve and maximum perfusion in both ventricles and capillary density in the LV endomyocardium. Arteriolar wall thickness was unchanged. Compared with untreated sheep with aortic stenosis, in heparin-treated sheep LV FGF-2 protein increased 2-fold, whereas FGF-2 mRNA remained unchanged. VEGF mRNA and protein increased 3-fold and 1.4-fold, respectively, whereas TGF-beta(1) mRNA declined 3-fold. CONCLUSIONS: Heparin administration during LV hypertension increases heparin-binding angiogenic factors FGF-2 and VEGF in the LV and ameliorates decreases in LV perfusion capacity and capillary density.

Adaptation, Physiological↗
PubMed1998

Pressure overload induced in newborn rats: effects on left ventricular growth, morphology, and function.

Gradual pressure overload was induced by abdominal aortic constriction in male rats on postnatal d 6 (AC6) or 2 (AC2). At the age of 8 wk, the systemic blood pressure was measured, and the contractile performance of the left ventricle (LV) was assessed after acute ligation of the ascending aorta in open chest anesthetized animals. The LV free wall was used for the determination of collagen concentration and morphometric analysis of cardiac myocytes and capillaries. Aortic constriction resulted in LV hypertrophy, which was more pronounced in AC2 (by 71%) as compared with AC6 (by 34%) groups and correlated closely with the degree of pressure overload (r = 0.88 and 0.80, respectively). The right ventricular weight was increased by 13% in the AC2 group only. Contractile performance of the LV of aortic constricted rats was significantly higher before as well as after the acute load, but the average functional reserve was unchanged in both experimental groups. Although the maximum value of the rate of pressure development increased linearly with the degree of ventricular hypertrophy in the AC6 group (r = 0.82), a negative correlation was observed in the AC2 animals (r = -0.61). The density of myocytes was decreased, and the calculated average myocyte cross-sectional area was increased in aortic constricted rats, but the coronary capillary density and myocardial concentration of collagen remained constant. Thus, in spite of the larger cardiac growth response in the younger age group, the capillary proliferation and collagen formation were proportional to the ventricular hypertrophy. Therefore, the degrees of overload and hypertrophy do not seem to be limiting factors. Pressure overload induced in newborn rats can be a useful model for the study of mechanisms that control either the growth and differentiation of myocardium soon after birth, as well as the transition from compensated to decompensated hypertrophy at later stages.

Animals↗
PubMed1997

Transplantation-induced atrophy of normal and hypertrophic rat hearts: effect on cardiac myocytes and capillaries.

Changes in tissue structure of hearts undergoing atrophy following heterotopic isotransplantation were studied. Both normal and hypertrophic hearts were used, originating from male and female rats. Aortic constriction produced in newborn rats, resulted in an 86 and 155% increase of left ventricular mass in male and female rats, respectively. On day 50, control and experimental animals were killed, half of their hearts were analysed morphometrically, while remaining hearts were transplanted into the abdominal cavity of recipient rats. Transplantation resulted in significantly decreased cardiac mass in control hearts (approximately 50% decrease compared to values at transplantation), and an even more pronounced decrease in hypertrophic hearts. Cardiac hypertrophy was characterized by significant decreases in capillary and myocyte densities. While myocyte density simply reflected changes in cell size, evidence for additional capillary growth was found (the aggregate length of capillaries per left ventricle increased by 57-88%). Cardiac atrophy resulted in increased capillary density, despite evidence of some capillary involution in transplanted hearts (aggregate length of capillaries decreased by 30-35% and 52-64% for transplants of normal and of hypertrophic hearts, respectively). Myocyte density increased due to a proportional decrease in the size of cardiac myocytes. In transplanted hearts, an increasing number of myocytes containing nuclei located close to the nearest capillary, suggests that changes in myocyte size are not symmetrical. The present study demonstrated the remarkable plasticity of the heart in neonatal animals; they were capable of large increases and decreases in cardiac mass within a few weeks, with more pronounced changes in female rats. These changes were accompanied by changes in myocardial structure, indicating some capillary growth in cardiac hypertrophy, and involution of coronary capillaries in cardiac atrophy.

Animals↗
PubMed1997

Early and late effect of neonatal hypo- and hyperthyroidism on coronary capillary geometry and long-term heart function in rat.

OBJECTIVE: The aim of the present study was two-fold: (1) to examine the effect of hyper- and hypothyroidism on the developing coronary capillary network in neonatal rats, and (2) to determine in adult rats that had re-established euthyroid status whether long-term changes in capillary geometry or cardiac function had been induced by either neonatal thyroid condition. METHOD: Two-day-old rats were treated every other day for 12 or 28 days with either 3,3'5-triiodo-l-thyronine or 0.05% 6-n-propylthiouracil. After this time, treatment was stopped and in two-thirds of the rats morphometric examination of capillary geometry and immunohistochemical detection of proliferating cell nuclear antigen (PCNA) expression in endothelial cell nuclei were conducted. Remaining rats were weaned and grew to 80 days of age, at which time persistent changes in capillary geometry, PCNA expression, and cardiac function were assessed. RESULTS: Neonatal hyperthyroidism induced cardiomegaly (P < 0.01), whereas neonatal hypothyroidism attenuated cardiac growth (P < 0.01). Capillary numerical density, capillary segment lengths and PCNA-labelling analysis indicated marked capillary growth in hyperthyroid rats (P < 0.05), but attenuated capillary growth in hypothyroid rats. The elicited capillary growth response appeared to be more dependent on altered tissue maturation than on cardiac growth rate. After discontinuing treatment both neonatal thyroid conditions induced a deficit in left ventricular growth (P < 0.01). Furthermore, neonatal hyperthyroidism appeared to inhibit subsequent capillary growth in distal regions of the capillary bed in addition to inducing lasting positive chronotropic and inotropic effects on cardiac function (P < 0.05). Neonatal hypothyroidism did not produce any lasting changes in capillarization or in cardiac function. CONCLUSIONS: Results suggest that neonatal thyroid status influences early growth and development of the coronary capillary network, possibly by regulating tissue maturation, as well as inducing lasting effects on subsequent cardiac and capillary growth and heart function.

Aging↗
PubMed1997

The role of diltiazem in treating hypertension and coronary artery disease: new approaches to preventing first events.

OBJECTIVE: To review the role of diltiazem in treating and preventing a group of cardiovascular diseases, including painful and silent cardiac ischemia, stroke, nonfatal myocardial infarction and sudden cardiac death, by modulating certain physiological causes that they appear to share. DATA SOURCES: A MEDLINE search was conducted for all clinical articles on the use of diltiazem for hypertension and coronary artery disease. When clinical data were not available, basic research findings were reviewed. DATA EXTRACTION AND SYNTHESIS: Because many cardiovascular events show a marked daily periodicity--which appears to coincide with circadian peaks in the ability of platelets to aggregate, sympathetic activity, coronary tone, blood pressure, heart rate and hematocrit, and a trough in fibrinolytic activity--the impact of diltizazem on these physiological changes was assessed. CONCLUSIONS: Diltiazem influences many of these events by increasing myocardial bloodflow, and reducing myocardial oxygen demand and cardiac workload. However, it differs from other calcium antagonists in its mild negative inotropic and moderate negative dromotropic effects, without apparent stimulation of cardiac performance or contractility. In addition, it inhibits platelet aggregation, decreases catecholamine release, diminishes coronary tone and blocks the vasoconstrictive actions of endothelin-1. This appears to translate into a beneficial effect on ischemia, thrombolysis, arrhythmias, infarct parameters, atherosclerosis and hypertension. Diltiazem has a relatively favourable safety and tolerability profile, and is available in a once-daily dosage form. The most common adverse effects are related to vasodilation (eg, edema and headache), and the most frequent serious adverse event is atrioventricular block, which occurs rarely. In summary, diltiazem appears to be well suited to preventing the first occurrence of cardiovascular events and may even have a role in preventing certain types of secondary events. The data accumulated so far indicate the need for a large scale random clinical trial addressing these outcomes.

Arrhythmias, Cardiac↗
PubMed1996

Transmural channels can protect ischemic tissue. Assessment of long-term myocardial response to laser- and needle-made channels.

BACKGROUND: We previously found that transmural laser channels failed to acutely increase myocardial blood flow. Nevertheless, this method is being used to treat patients with coronary artery disease who are unable to undergo angioplasty or bypass graft surgery and in cases in which previous surgery has failed. To reconcile the lack of an acute increase in blood flow with beneficial effects claimed in patients, our hypothesis was that the channel-making process might, over time, stimulate a protective effect, possibly by the growth of new vessels linking channels to the existing circulation. We tested this hypothesis in rat hearts, which have little native collateral circulation. METHODS AND RESULTS: We made six transmural channels in the left ventricle of each heart using a 400-micrometer-diameter optic fiber coupled to a holmium:yttrium-aluminum-garnet laser or a 400-micrometer-diameter syringe needle. Two months after the channels were made, rats were randomized to either an infarct-size study or analysis of myocardial capillary density. We challenged any induced protective mechanism by acutely occluding the left coronary artery for 90 minutes, followed by 4.5 hours of reperfusion. The artery was then reoccluded, and pigment was injected into the circulation to delineate tissue perfused by the occluded vessel and to detect perfusion via the channels. We used triphenyltetrazolium staining to determine the amount of muscle necrosis and the location of muscle protection. Infarct size in needle-treated hearts was smaller than in controls (15 +/- 6% versus 40 +/- 3% of the left ventricle, P<.01). Infarct size in laser-treated hearts (27 +/- 5%) did not differ significantly from controls; however, all eight laser-treated hearts showed evidence of muscle protection in areas adjacent to channels. We found that the laser-made channels were associated with more fibrosis than the needle-made channels (mean width of fibrosis 430 +/- 50 versus 180 +/- 30 micrometer, P<.0001), and, in tissue remote from channels, fibrosis was increased more in laser-treated hearts (3.6 +/- 0.3%) versus both control (2.5 +/- 0.2%) and needle-treated (2.5 +/- 0.3%) hearts (P<.05). In addition, muscle disarray was seen adjacent to channel-associated fibrosis. We observed injected pigment within fibrosis associated with the channels and in surrounding myocardium. We also found vessels that appeared to be connected to channels; however, there was no overall increase in capillary density. CONCLUSIONS: We were able to protect the heart against coronary artery occlusion by making transmural channels 2 months before occlusion. Channels created by a needle provided greater protection than channels created by a laser, probably because they caused less initial injury. Our results are consistent with the concept that the channels were able to provide blood flow to the tissue directly from the ventricular cavity; however, we cannot rule out the possibility that other mechanisms of protection may be involved.

Animals↗
PubMed1996

Red blood cell spacing in rat coronary capillaries during the cardiac cycle.

Theoretical studies have demonstrated a pronounced effect of red blood cell (RBC) spacing on tissue oxygen supply. Our objective was to collect data regarding RBC spacing and related linear capillary hematocrit (Hct) in rat coronary capillaries, from two distinct locations within the capillary bed (proximal and distal portions), in the subendo- and midmyocardium, during systole and diastole. Hearts were rapidly frozen in situ, and tissue sections were stained in order to distinguish capillaries in proximal and distal portions of the capillary bed, as well as the RBCs within them. Morphometric data were compared according to capillary type, cardiac region, and cardiac phase. Distal portions of the capillary bed had a significantly greater capillary Hct (p < 0.001) and significantly lower RBC spacing values (P < 0.01), compared to proximal portions, irrespective of cardiac phase or region. There was a greater frequency of RBC spacing values equal to O microns in systole compared to diastole (P < 0.001) and a greater frequency of RBC spacing values greater than 40 microns in proximal portions of the capillary bed compared to distal portions (P < 0.001). These results suggest that intracapillary resistance to O2 transport is reduced, and O2 carrying capacity of the blood increased, in distal portions of the capillary bed, where PO2 in the blood is lower.

Animals↗
PubMed1996

Short- and long-term effects of neonatal hypo- and hyperthyroidism on coronary arterioles in rat.

Neonatal hypo- and hyperthyroid effects on coronary arteriolar geometry were examined in newborn male Sprague-Dawley rats treated for 12 or 28 days with either triiodothyronine or propylthiouracil. Long-term effects were assessed in weaned rats 52 days after stopping treatment. Influence of both neonatal conditions was more pronounced after 28 days. Neonatal hyperthyroidism induced cardiac hypertrophy; neonatal hypothyroidism attenuated cardiac growth. Hyperthyroid rats had similar arteriolar and capillary numerical densities and arteriolar length density but significantly greater (P < 0.05) total arteriolar length than control. Hypothyroid rats had similar arteriolar numerical and length densities, greater capillary numerical density (P < 0.05), but markedly lower total arteriolar length (P < 0.01) than control. Results suggest that neonatal hyperthyroidism stimulates arteriolar and capillary growth, whereas neonatal hypothyroidism attenuates arteriolar but not capillary growth. After cessation of treatment, total arteriolar length in previously hyperthyroid rats did not change despite increased cardiac mass, whereas previously hypothyroid rats demonstrated marked increases in both cardiac mass and total arteriolar length (P < 0.01). These results indicate a lasting inhibitory effect of early hyperthyroidism on subsequent arteriolar growth.

Animals↗
PubMed1996

The effect of AT1 receptor antagonist on chronic cardiac response to coronary artery ligation in rats.

OBJECTIVE: The aim was to study the effect of the AT1 receptor antagonist losartan on hemodynamic and morphometric changes following experimental infarction. METHODS: Experimental infarction was produced in adult male rats by ligating the coronary artery. Treatment with losartan was compared to untreated controls, in rats with experimental infarction and sham-operated animals. RESULTS: Infarcted hearts were characterized by significant decreases in left ventricular developed pressure, as well as positive and negative (dP/dt)max, whereas left ventricular end-diastolic pressure (LVEDP), relaxation constant tau and right ventricular systolic pressure (RVSP) significantly increased. Treatment with losartan decreased the LVEDP, the relaxation constant tau and RVSP in the infarcted hearts. Right ventricular weight significantly increased in rats with infarction; this was attenuated by losartan. Infarct size was not significantly influenced by losartan treatment. Morphometric data revealed decreased capillary supply in infarcted hearts, especially in regions close to infarction; the decrease was less pronounced after losartan treatment. Capillary density in near infarct region decreased from 2826/mm2 to 1471/mm2 in untreated animals but in the treated animals it decreased from 2982/mm2 to only 2037/mm2. Simultaneous significant decrease in myocyte-to-capillary ratio in treated animals compared to untreated rats (0.87 to 0.67) seems to indicate formation of new capillary channels after losartan treatment. LVEDP was dependent on the size of infarction in untreated but not in treated animals. A close correlation between LVEDP and capillary density was found. CONCLUSIONS: Decreased ventricular contractility, prolonged relaxation and decreased coronary capillary density in rat experimental cardiac infarction confirm and amplify previous reports dealing with this experimental model. Moreover, we have found evidence of improved hemodynamics and coronary angiogenesis after losartan treatment.

Angiotensin I↗