Biomedical subjects

J Lekven

Publications and source records attributed to J Lekven.

At least 55 records · Page 3Linked to original sources

PubMed1986

Is reduced cardiac performance the only mechanism for myocardial infarct size reduction during beta adrenergic blockade?

Equal reductions in heart rate (44 beats X min-1) were obtained in cats by treatment with either the beta blocking agent timolol or alinidine, an agent claimed to cause bradycardia without interfering with beta adrenoceptor function. Infarct size was measured by staining with triphenyltetrazolium-chloride after 5 h of coronary occlusion and related to the area of hypoperfused myocardium as measured by autoradiography. Regional myocardial blood flow was measured by 15 micron radiolabelled microspheres. Compared with the control cats, in whom 87.4 (SEM 2.2)% of hypoperfused myocardium developed into necrosis, timolol reduced infarct size to 65.8 (SEM 2.6)% (p less than 0.001) and alinidine to 76.2 (SEM 3.1)% (p less than 0.01) of the hypoperfused area. Timolol reduced infarct size more than did alinidine (p less than 0.01). Necrosis was more extensive in the endocardium than in the epicardium in all groups. In the subendocardium timolol and alinidine reduced infarct size to the same extent, whereas timolol reduced infarct size more than alinidine in the subepicardium. Although heart rate proved to be the dominant haemodynamic predictor of infarct size, this study indicates that mechanisms other than reduced oxygen demand associated with bradycardia and cardiodepression are operating in the ischaemic myocardium during beta adrenergic blockade.

Animals↗

PubMed1986

Fibre orientation in the left ventricle and its influence on local pressure-length loop analysis in cats.

Deviation from local fibre orientation may seriously affect quantification of myocardial segment work, as measured by implanted ultrasound crystals. Crystal pairs were positioned in mid-wall layers with known directions to the long axis of the heart. One transmitter and four receiving crystals covered a sector on the anterior ventricular wall of 100 degrees. The results show a strong influence of alignment to fibre direction on the pressure-length loop area; the relation followed a cos2 psi function where psi denotes the angle between the crystal pair direction and fibre direction established by microscopy. The angle between the mid-wall muscle fibres on the anterior aspect of the left ventricle and the long axis of the heart varied between 62 degrees and 90 degrees with a mean value of 76 degrees. This study shows that pressure-length loop quantitation depends strongly on crystal alignment to cardiac muscle fibres through which the ultrasound passes.

Animals↗

PubMed1986

Microsphere method in measurement of blood flow to wall layers of small intestine.

Microspheres of 10.90 +/- 0.65 micron (SD) were injected in the superior mesenteric artery of cats and their intramural distribution and diameter in the small intestine were studied microscopically under basal conditions and after vasodilation by isoproterenol. Approximately 2% of the spheres were shunted through the small intestinal vasculature and could be recovered in the liver. Analysis of the tissue distribution suggested that all spheres arrested in villi represented villous blood flow, spheres arrested in the crypt layer represented flow to the crypts, and the majority of microspheres trapped in the submucosa also represented crypt flow. Nutritive blood flow to the submucosa constituted only 1.5% of total intestinal flow. Log-linear analyses identified factors responsible for sphere distribution, including effects of sphere size, isoproterenol treatment, and local blood flow or vascular resistance. Spheres with diameters greater than 11.08 micron had 1.35 times larger odds than smaller spheres to embolize in the muscularis rather than in the mucosa, but no consistent difference between diameter profiles in the crypts and villi was found. With this reservation, 11-micron spheres seem to be appropriate for measuring blood flow to the muscle, crypt, and villous layers of the small intestine.

Animals↗

PubMed1985

Influence of gastric banding on stomach blood supply with or without concurrent splenectomy.

A lethal gastric perforation occurred after a gastric banding procedure, which was complicated with splenectomy. Prompted by this incident, an experimental study was undertaken in which regional blood flow in the stomach was measured in anesthetized cats after gastric banding or splenectomy or both. A fatal course with an extensive ischemic lesion of the stomach near the banding area was seen in all the cats with the combined procedure after 5 to 12 days. Banding alone reduced gastric blood flow within 24 hours, particularly on the greater curvature. Splenectomy also reduced blood flow along the greater curvature within 2 weeks. The combined procedure showed similar flow changes within 24 hours. The implication of these experimental results is that, if the spleen must be removed, the performance of gastric partitioning for morbid obesity should be reconsidered.

Adult↗

PubMed1985

Lipid accumulation in the myocardium during acute regional ischaemia in cats.

Accumulation of lipid material in the myocardium was studied in cat hearts with acute regional ischaemia of 3 h duration. The fractional volume of lipid droplets in cytosol was analysed by electron microscopy of myocardial biopsies using a quantitative stereologic technique. Ischaemic and normally perfused myocardium were identified by fluoresceine injection, and tissue blood flow measurements were performed with labelled microspheres. In normal myocardium only small amounts of lipid droplets were found. A marked accumulation of lipid droplets occurred in borderline tissue between the two types of myocardium, whereas lipid accumulation in ischaemic myocardium was less pronounced. The arterial concentration of nonesterified fatty acids was clearly increased during the 3 h coronary artery occlusion period. Increased triglyceride synthesis from arterial fatty acids, or redistribution of intracellular lipids, are suggested as possible explanations for lipid accumulation during acute myocardial ischaemia.

Acute Disease↗

PubMed1985

Interpretation of myocardial contraction recorded from local segments.

An attempt to quantify the influence of extra-segmental contraction upon external mechanical work of a segment was made in cat hearts. By placing four ultrasound crystals across a borderline between normal and ischaemic myocardium, the pressure-length loop area of segments with different ischaemic contents were recorded. The relation between a normalised segment work index and the amount of ischaemic tissue within the segment showed a negative correlation. Assuming that the contributions to the segment work index from ischaemic and normal tissue coupled in series within the segment add up by cancelling each other, the extra-segmental influence of adjacent fibre contraction could be established. In six cats the extra-segmental influence which affected a typical segment of 10.0 mm corresponded to 1.5 to 3.7 mm of adjacent myocardial musculature on either side of the segment.

Animals↗

PubMed1985

Measurement of local blood flow in acute myocardial infarction: loss of 15-micron microspheres during the first hour.

Distribution of radiolabelled microspheres is widely utilized for determination of regional blood flow in experimental myocardial infarction studies. The purpose of this investigation was evaluation of the microsphere method during 1 h of regional ischaemia. Special attention was focused upon loss of preocclusion microspheres from ischaemic myocardium; mechanisms for loss and blood flow distribution in non-ischaemic left ventricle. Microspheres (15 micron) were injected into the left atrium in nine pentobarbital anaesthetized cats prior to coronary artery occlusion and again after 1 h of occlusion. Preocclusion blood flow estimates were lower in ischaemic compared with non-ischaemic myocardium (1.36 vs. 1.62 cm3 X min-1 X g-1, P = 0.002), corresponding to 16% apparent loss. In endocardial ischaemic tissue, development of oedema could account for the loss. In epicardial ischaemic tissue, oedema was not present and loss was therefore due to migration of microspheres. Epicardial loss increased in proportion to restoration of left ventricular contractility. There was no evidence for significant microsphere loss through lymphatic pathways. In non-ischaemic left ventricular tissue, myocardial blood flow was evenly distributed from apex to base, and also between endocardial and epicardial layers. This study quantitates an important limitation to measurements of local blood flow in ischaemic myocardium by radiolabelled microspheres.

Animals↗

PubMed1985

Myocardial blood flow conditions at re-perfusion following acute ischaemia.

The purpose of this study was to investigate the effect of re-perfusion upon distribution of radioactive microspheres in ischaemic myocardium. Ten anaesthetized cats were given 15-micron microspheres prior to left anterior coronary artery occlusion, at 1 h of occlusion, and after 1 h of subsequent re-perfusion. Pre-occlusion blood flow estimates were lower in tissue which had been ischaemic compared with nonischaemic regions in the same heart (1.44 versus 1.87 ml X min-1 X g-1, p less than 0.001), corresponding to 23% apparent loss. Loss also occurred in ischaemic right ventricular tissue (32%). In left ventricular ischaemic endocardium, apparent loss was due to development of oedema. Oedema was also significant in epicardial ischaemic tissue. Correction for oedema eliminated two-fifths of the loss, while three-fifths was due to physical loss. Oedema increased linearly with the level of re-perfusion. During re-perfusion, myocardial blood flow in previously ischaemic tissue was inhomogeneously distributed and, on average, 28% lower than in non-ischaemic myocardium. The 15-micron spheres appeared to pass through capillaries in the ischaemic subepicardium, but this process was not enhanced by reperfusion.

Animals↗

PubMed1984

Effects of timolol on adenine nucleotide catabolism in cat hearts with acute regional ischaemia.

The effects of the beta-adrenergic blocking agent timolol on cardiac function and adenine nucleotide metabolism were investigated in cats with 45 min of acute ischaemia following coronary occlusion. Regional myocardial blood flow was measured by 15 micron radiolabelled microspheres, and adenine nucleotides and their degradation products were measured by high performance liquid chromatography in 16 tissue regions in each cat. During ischaemia, cats treated with timolol exerted a reduced cardiac performance as judged from reduced heart rate and cardiac contractility; consequently preocclusion tissue blood flow was reduced compared with a control group of cats. The ATP concentration was less severely depleted in ischaemic regions of the left ventricle in cats treated with timolol. The energy charge was reduced to a lesser extent in ischaemic regions, and in intermediate flow ranges the contents of the inosine and hypoxanthine/xanthine were reduced compared with untreated cats. These results indicate that the beta-adrenergic blocking agent timolol might protect the myocardium within a 45 min ischaemic period. The mechanism for this effect is most probably related to the reduction in overall cardiac performance.

Acute Disease↗

PubMed1984

Regional myocardial tissue blood flow during beta-adrenergic blockade in cat hearts with acute ischaemia.

Selective beta 1- or beta 2-adrenergic blockade was achieved by practolol or IPS 339, respectively, in cats with acute ligation of a coronary artery. During blockade, heart rate was kept constant by atrial pacing and blood pressure reduction was prevented by aortic clamping. Regional myocardial blood flow was measured by the distribution of 15 micron labelled microspheres. Practolol slightly reduced epicardial blood flow in ischaemic myocardium, while blood flow in border and normally perfused myocardium remained unchanged. Following IPS 339, myocardial tissue flow increased in normally perfused myocardium, on average by 37% in the endocardium and 30% in the epicardium. No changes occurred in the other regions. The flow changes brought about by IPS 339 were unrelated to haemodynamic changes, and the coronary vascular resistance was reduced. These results are indicative of coronary vasodilation related to beta 2-adrenergic receptor blockade and was confined to well-oxygenated areas surrounding the acutely ischaemic zone.

Adrenergic beta-Antagonists↗

PubMed1984

Gastric blood flow determination: intramural distribution and arteriovenous shunting of microspheres.

Total and regional gastric blood flows were measured in 23 anesthetized cats by labeled 10-micron (range 8-12 microns) and 15-micron (range 12-20 microns) microspheres. Total blood flow correlated closely with the gastric venous outflow. Flow estimates by 10-microns spheres were 2.95% lower than simultaneous 15-micron estimates. Approximately 2% of the 10-micron spheres and 0.1% of the 15-micron spheres were shunted through the gastric vasculature. The diameter distribution of 6,245 embolized spheres, measured by microscopy, corresponded to that of the injectate, except for a lack of the smallest spheres. Within the mucosa, the 10-microns spheres predominantly lodged in the glandular layer, whereas larger spheres gradually lodged more basally; 50% of the 15-microns population appeared in the lamina propria below the gland bases. Vasodilation did not alter the intramucosal distribution. Spheres in the subglandular lamina propria represented blood flow mainly to the glandular layer. It is therefore essential for reliable estimation of blood flow to the glandular layer of the mucosa that the lamina propria is completely included in the specimens. The submucosa contained only 0.5% of the 10-microns and 2.2% of the 15-micron embolized spheres. Spheres of 10.5-17 microns in diameter are considered the most suitable for determination of gastric blood flow.

Animals↗

PubMed1984

Relationship between myocardial adenine nucleotide catabolism and tissue blood flow rate in experimental ischaemia.

A method was developed for tissue preservation and evaluation of the adenine nucleotide metabolism in small samples of myocardium after 45 min of ischaemia. Ischaemia was produced by coronary artery occlusion in anaesthetized cats. Adenine nucleotides and their metabolites were measured by isocratic liquid chromatographic systems which allow quantitative analysis of the nucleotides and their metabolites inosine, hypoxanthine and xanthine in biopsies of 5-20 mg tissue. Regional myocardial blood flow was measured in the tissue surrounding the biopsies by the distribution of 15 micron radiolabelled microspheres. In central ischaemic regions the ATP level was approximately 1 mumol/g wet weight, whereas in normally perfused myocardium the ATP level was approximately 5 mumol/g tissue. In tissue with intermediate flow values, intermediate ATP levels were found. Energy charge, which summarizes all adenine nucleotide concentrations, was reduced from 0.88 to 0.50, and the molar concentrations of inosine, hypoxanthine and xanthine increased in ischaemic tissue. We conclude that this method provides reliable characterization of the local cellular energy status in cat hearts with ischaemic regions.

Adenine Nucleotides↗

PubMed1983

Measurement of cardiac pressure-length loops using an improved sonomicrometer. Accuracy and effect of respiration.

A transit-time sono-micrometer for measurement of myocardial dimensions is described. Crystals of frequencies 1-10 MHz can be used, enabling a large range of distances to be measured. The meter has two channels, operated in sequence to avoid interference between channels. By combining local muscle segment length with the left ventricular pressure in open-chest cats, the pressure-length loop for that segment was continuously displayed. A calibration procedure was developed, permitting calibration to be registered on a recorder and on a storage monitor at any time. Detailed interpretation of loops from normal and ischaemic segments of the left ventricle is presented. Variation of the loop form with respiration is demonstrated, which clearly necessitates a standardized reference point in the respiratory phase for comparing loops from two or more experimental situations.

Animals↗

PubMed1983

Regional myocardial tissue blood flow during sequential beta 1- and beta 2-adrenergic blockade in cat hearts with acute ischaemia.

beta-Adrenergic blockade was imposed on cats with ischaemic regions of the left ventricle produced by coronary artery occlusion. Ten animals first received a beta 1-blocking agent (atenolol) followed by a beta 2-blocking agent (IPS 339). In ten more animals this sequence was reversed. Combined blockade, obtained after both agents were administered, showed clear reduction of tissue blood flow in all areas of the ventricle, except for the central ischaemic zone. The flow reduction could be ascribed to bradycardia and reduced coronary perfusion pressure. By analysing the sequential changes it was evident that blockade of beta 1-adrenergic receptors was responsible for the haemodynamic changes, and the coronary vascular resistance rose so as to match the quantity of blood flow to the functional state of the ventricle. Blockade of beta 2-receptors by IPS 339, however, showed no evidence of coronary vasoconstriction but rather maintained vascular resistance at an unchanged level despite a weak beta 1-adrenergic blocking effect.

Adrenergic beta-Antagonists↗

PubMed1983

Stability of 8-, 15-, and 26-micron microspheres entrapped in feline myocardium.

The stability of 8-, 15-, and 26-micron radioactive microspheres entrapped in ischemic and nonischemic myocardium and possible mechanisms for microsphere loss were investigated. Anesthetized cats were given microspheres prior to left anterior descending coronary artery occlusion (or sham operation) and 8 h later. Eight-micron microspheres, compared with 15-micron spheres, underestimated preocclusion myocardial blood flow in ischemic and nonischemic tissue by 30%. With 26-micron spheres, endocardial-to-epicardial blood flow ratio was 1.28. In nonischemic tissue, no loss of 15- and 26-micron microspheres occurred during 8 h. In ischemic myocardium, however, 15% apparent loss of 15- and 26-micron preocclusion spheres took place. In endocardial ischemic tissue, edema could account for 50% of the 15-micron microsphere loss and almost completely for loss of 26-micron spheres. In epicardial ischemic tissue, microsphere loss was not influenced by edema. We found no hemodynamic variable that could predict the magnitude of microsphere loss. Only weak evidence for migration of 15- and 26-micron microspheres through lymphatic pathways was found. Most likely the spheres migrated through venous pathways to embolize in the lungs. We conclude that 15-micron microspheres provide the most reliable tissue blood flow estimates in normal myocardium, but even for these spheres significant loss occurs during 8 h of ischemia.

Animals↗

PubMed1983

Regional gastric blood flow and acid secretion during histamine H2 receptor blockade in cats.

Experiments were performed in anesthetized cats. Tissue blood flow and cardiac output were measured by means of labeled microspheres. Cimetidine did not affect gastric blood flow at basal conditions. Pentagastrin stimulation more than doubled corpus-fundus mucosal blood flow (MBF). Cimetidine reduced pentagastrin-stimulated corpus-fundus MBF and acid output towards basal level. Recovery of acid secretion after inhibition by a bolus dose of cimetidine occurred without a corresponding restoration of MBF. Neither pentagastrin nor cimetidine significantly altered antrum MBF or muscularis blood flow. The study demonstrates that cimetidine reduces the ratio between pentagastrin-stimulated acid secretion and corpus-fundus MBF by lowering secretion considerably more than the corresponding MBF.

Animals↗

PubMed1982

Effects of timolol on blood flow distribution in the feline myocardium with acute regional ischaemia during controlled haemodynamic conditions.

The beta-adrenergic blocking agent timolol was given to cats with acute coronary artery ligation under controlled haemodynamic conditions. Regional myocardial tissue flow was measured by the distribution of labelled microspheres. Timolol reduced cardiac contractility and left ventricular end-diastolic pressure rose, whereas heart rate and ventricular systolic pressure were kept constant by atrial pacing and aortic clamping. The systolic period increased following timolol administration under these conditions. Myocardial blood flow remained unchanged in central ischaemic and border areas, whereas flow increased both endocardially and epicardially in normally perfused area following timolol administration. Without pacing there was a significant flow reduction in the epicardium of the normally perfused area, compared with the situation where heart rate was constant. Under controlled haemodynamic conditions, therefore, timolol appears to improve coronary perfusion in normal myocardium, whereas blood flow to ischaemic myocardium remains essentially unchanged.

Animals↗

PubMed1982

Temporary intestinal ischaemia induced by proximal mesenteric artery occlusion.

The severity and distribution of small intestinal ischaemia caused by temporary proximal occlusion of the superior mesenteric artery in cats were evaluated by electromagnetic flowmetry and carbonized microspheres. Average mucosal blood flow was reduced from 0.94 to 0.40 ml/min/g. Mucosal flow in the proximal jejunum and distal ileum was even less affected. Ischaemia induced by proximal occlusion of the superior mesenteric artery in cats was not severe enough to provide optimum conditions for intestinal hypoxic radiation protection, nor was such ischaemia evenly distributed along the gut.

Animals↗