Biomedical subjects

J Lekven

Publications and source records attributed to J Lekven.

At least 37 records · Page 2Linked to original sources

PubMed1991

Tissue reaction to polypropylene mesh: a study of oedema, blood flow, and inflammation in the abdominal wall.

The purpose of the present work was to study the tissue reaction to polypropylene mesh (Marlex) implanted in three different layers of the abdominal wall, comparable to common clinical practices. The reaction to mesh was compared in terms of tissue oedema, blood flow, and histological appearance in rats. When mesh was placed between muscle layers, blood flow in the abdominal wall was high during the first 4 days after implantation but similar to flow in nonoperated rats 14 and 140 days after implantation. When mesh was placed under skin or on the peritoneum, there was no hyperaemia early after implantation, and flow rate was clearly lower than in non-operated controls 140 days after implantation. The operative procedure produced increased tissue water content, declining from the 1st to the 14th day after operation. Mesh induced additional oedema in adjacent muscle tissue irrespective of localization of the implant (p less than 0.01, vs. sham). Except when separated by peritoneum, mesh caused hyperaemia in muscle tissue in direct contact with mesh the 1st and the 4th day after implantation. After 14 and 140 days no mesh-induced hyperaemia was present. The inflammatory response to mesh was similar in the peritoneum and between muscles, less pronounced in the subcutis. It was characterized by the accumulation of macrophages and the formation of inflammatory granulation tissue in the subacute phase, later followed by the formation of fibrous tissue around mesh fibres. This study suggests that mesh implants should be placed in apposition to muscles in order to obtain well-vascularized healing.

Abdominal Muscles↗

PubMed1991

Source of information in heart research 1978 and 1988.

Several regulatory provisions have been introduced during the last decade that might interfere with the conduct of experimental medical science. In order to study their impact on the source of information within one major field, heart research, a total of 3579 abstracts from the 1978 and 1988 Scientific Sessions of the American Heart Association were analysed with respect to their source of information. There was no change in overall fractions of classical patient studies (45%) or experimental animal studies (30%) for the 2 years although regulations have been introduced in both areas. There was no evidence that the volume of circulatory physiology, a subset that extensively utilizes animal experimentation, declined relative to other subsets of the composite information base. The fraction of cell culture studies clearly rose over the period at the expense of in vitro laboratory studies but not as replacement for animal experimentation. Particularly tight regulations on experiments with selected species apparently explains why dogs and cats are less frequently used relative to rats, rabbits, ferrets and pigs which represent the alternatives. Nevertheless, the absolute number of dog studies doubled over the 10-year period and this species still remains the most widely used experimental model in heart research. The study does not reveal directly what is actually performed within the research community but rather identifies the source of information for those studies that are considered to bring about pertinent new information in modern heart research.

American Heart Association↗

PubMed1991

Myocardial contractile performance during acute coronary occlusion with special emphasis on nonoccluded regions.

Ischaemia of the left ventricle caused by coronary artery occlusion generally leads to less changes in overall ventricular performance than would be expected from the amount of ischaemic, noncontracting tissue. Ischaemic myocardium shows elongation of segment lengths and paradoxial movement during contraction of the left ventricle. Compensation for the loss of contractile tissue is most likely related to increased performance of the nonischaemic myocardium and the most likely mechanisms involved are discussed. The effect of increased preload, brought about by increased left ventricular end-diastolic pressure following coronary occlusion, on nonischaemic parts appear to be the most important mechanism of compensation.

Adaptation, Physiological↗

PubMed1990

Gradual reduction of coronary perfusion pressure in cats: changes in transmural distribution of blood flow.

We evaluated a model for regional myocardial hypoperfusion in cats with an extracorporeal shunt line to the left main coronary artery, and investigated the effects of reduced coronary perfusion pressure on the transmural distribution of left ventricular blood flow measured with radioactive microspheres. Shunt establishment did not alter cardiac function, myocardial tissue blood flow, or its transmural distribution. An artificial shunt stenosis, which clearly reduced coronary perfusion pressure without changing cardiac function, caused reduced endocardial blood flow, slight flow reduction in mid-myocardium, and no flow change in the epicardium. When a severe stenosis was applied, causing increased end-diastolic pressure and reduced shunt flow, endocardial and mid-myocardial flow further decreased whereas epicardial blood flow remained essentially unchanged. These results demonstrate a transmural profile of the coronary autoregulation capacity.

Animals↗

PubMed1990

Regional perfusion in hearts with acute coronary artery occlusion and subsequent beta 2- and alpha 1-adrenergic blockade.

Blockade of cardiac adrenoceptor subtypes, coronary or myocardial, might elicit compensatory interaction from remaining unblocked subtypes. An attempt to explore this interplay was made by studying regional myocardial blood flow alterations associated with beta 2-adrenergic blockade followed by alpha 1-adrenergic blockade in anaesthetized cats with acute coronary occlusion. In order to maintain constant needs for perfusion, atrial pacing was established and the aortic blood pressure was kept constant. In myocardium remote from the ischaemic region, beta 2-adrenergic blockade produced higher endocardial blood flow whereas no flow changes were observed close to the ischaemic region. With subsequent alpha 1-adrenergic blockade, blood flow increased endocardially in non-ischaemic regions, but remained unchanged in epicardial tissue. Control experiments without coronary ligation revealed no increase in left ventricular oxygen consumption during the experiments and support the theory that the observed blood flow increase in the coronary ligation group, following drug interventions, was not caused by increased cardiac work. This study indicates that combined beta 2- and alpha 1-adrenergic blockade alters the balance between receptor subtypes. Unopposed beta 1-mediated vasodilation is the most likely candidate to explain why endocardial flow was increased.

Adrenergic alpha-Antagonists↗

PubMed1990

Distribution of cardiac output during pentobarbital versus midazolam/fentanyl/fluanisone anaesthesia in the rat.

Differences in effects on central haemodynamics, organ blood flow, and serum corticosterone were studied in 11 rats anaesthetized with midazolam/fentanyl/fluanisone (MFF) and 11 other rats anaesthetized with sodium pentobarbital. Compared with pentobarbital, MFF reduced aortic blood pressure by 25%, increased heart rate by 20%, and increased cardiac output by 80%. Unlike most tissues, MFF produced a fivefold increase in blood flow to skeletal muscle, and decreased adrenal blood flow compared to pentobarbital anaesthesia. Initial serum corticosterone levels were lower in rats given MFF anaesthesia, indicating better stress protection. This study also indicates that MFF anaesthesia is preferable to pentobarbital because tissue perfusion generally was better preserved.

Anesthesia↗

PubMed1990

Acute erosions of the gastric mucosa in burned rats: effect of gastric acidity and fluid replacement.

Early changes in the morphology of the gastric mucosa after the skin had been burned were studied using a standardised model in rats. A full thickness burn was inflicted by exposing about 20% of the total body surface area to hot water (99 degrees C) for 10 s. Intragastric acidity was kept at pH 1.0 or pH 7.4 in six experimental groups of eight rats. Rats were subjected to burns with the stomach irrigated at pH 1.0 or pH 7.4. Parallel groups received fluid replacement with a solution of human albumin, and two uninjured groups served as controls. Lesions of the gastric mucosa were measured by planimetry of photographs, and light microscopy was used for histological examination. At an intragastric pH of 1.0, the burned rats developed mucosal erosions covering an average of 13% of the total glandular mucosa; the remaining groups had only minimal mucosal lesions. Erosions of the gastric mucosa after the skin had been burned could be prevented in two ways--either by establishing an alkaline (pH 7.4) milieu in the gastric lumen, or by replacing sufficient fluid to maintain aortic blood pressure at the pre-experiment level. Fluid replacement prevented mucosal erosions even if the intragastric pH was kept at 1.0. Thus both luminal acidity and local tissue blood flow are possible mechanisms for gastric epithelial damage following burns of the skin.

Acute Disease↗

PubMed1989

Embryonic versus adult myocardium: adenine nucleotide degradation during ischemia.

Neonatal myocardium demonstrates better recovery from ischemia than does adult tissue. We tested the hypothesis that developmental differences in adenine nucleotide degradation might facilitate recovery by quantitating depletion of high-energy phosphates in nine-day-old embryonic (n = 9) and 15-month-old adult (n = 14) chicken hearts at 15-, 30-, 45-, and 60-minute intervals of normothermic ischemia in vitro. Nucleotides adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate and nucleosides adenosine, inosine, hypoxanthine, and xanthine were determined by high-performance liquid chromatography. Several observations in metabolite degradative response to ischemia were noted. The embryonic myocardium maintained higher adenosine triphosphate and adenosine monophosphate levels over the course of the investigation than did mature myocardium. Moreover, the adult group showed an increase in diffusible nucleoside pool metabolites. Relative immaturity of enzymes responsible for nucleotide degradation may facilitate postischemic recovery by preserving nondiffusible high-energy phosphate precursors to participate in salvage resynthesis of adenosine triphosphate.

Adenine Nucleotides↗

PubMed1989

Does alpha 1-adrenergic blockade influence regional blood flow regulation in hearts with coronary artery occlusion?

The effects of selective alpha 1-adrenergic blockade with doxazosin on regional myocardial tissue blood flow was studied in anaesthetized cats with acute coronary artery occlusion. Reflex tachycardia was prevented by selective beta 1-adrenergic blockade with atenolol and coronary perfusion pressure was kept constant by partial stenosis of the descending aorta. Administration of atenolol reduced cardiac mechanical work-load by its negative inotropic and chronotropic effects, and reduced myocardial tissue blood flow in normally perfused myocardium. This reduction was most pronounced in the endocardial half-layer of the myocardium adjacent to the ischaemic region. Administration of doxazosin in this situation clearly reduced peak systolic and coronary perfusion pressure. But when coronary perfusion pressure was raised to pre-administration values, measurements of regional blood flow revealed no changes either in ischaemic or non-ischaemic myocardium. Also, there was no sign of redistribution of blood flow between endocardial and epicardial tissue in any area. This study, therefore, indicates that alpha 1-adrenoceptors play a minor role in the regulation of coronary blood flow in normal myocardium as well as ischaemic myocardium.

Animals↗

PubMed1989

Nonuniform shortening of the anterior wall of feline left ventricles.

Recorded performance of segments between implanted ultrasonic crystals placed at midwall position of the left ventricle reportedly depends almost exclusively on midwall function and alignment with fibers. Accordingly, one would expect the ratio between performance of a segment perpendicular to midwall fiber direction (transverse) and a parallel segment (longitudinal) to be constant and independent of changes in preload, afterload, and the inotropic state. We tested this hypothesis by implanting cross-oriented crystal pairs in nine open-chest cats and studied their performance during preload and afterload changes with and without isoproterenol infusion. Fiber orientation across the ventricular wall was determined by serial histological sectioning. The ratio between performance of transverse and longitudinal segments (trans/long) changed with interventions. Increased end-diastolic pressure leads to increased segment performances as well as trans/long. Inotropic stimulation produced increased sensitivity to preload changes both for individual segment performances and for trans/long. These results suggest that longitudinal segments represent the function of midwall fibers, whereas transverse segments may well represent the function of sub-endocardial fibers, which run closer to this orientation. Thus trans/long provides a way to quantify nonuniformity of local myocardial contraction.

Animals↗

PubMed1988

Myocardial oxygen use during epinephrine administration to ischemically injured canine hearts.

The rationale for inotropic support by epinephrine during cardiac surgery and the early postoperative period was examined in 11 dogs after 20 minutes of normothermic ischemia and 1 hour of reperfusion. Ischemia reduced myocardial adenosine 5'-triphosphate (ATP) content by 37%. Left ventricular performance was assessed from pressure-dimension loops generated by minor-axis-diameter crystals for a range of controlled loading as high as end-diastolic pressures of 15 mm Hg. Myocardial oxygen consumption was determined at 6-9 steady-state steps throughout this range, including those at basal conditions of the empty beating ventricle. The hearts were artificially paced at 160 beats/min. Higher oxygen consumption with epinephrine (0.5 microgram/min/kg) administration was demonstrated at all levels of left ventricular performance and at all end-diastolic lengths. Several mechanisms for higher oxygen cost for similar external work performances have been suggested. From this study, it appears that increased uptake of free fatty acids, which increased threefold during epinephrine infusion, contributes to less efficient use of oxygen for mechanical work. We conclude that the use of inotropic support in ischemically injured hearts for reasons other than overt heart failure is not well based because myocardial oxygen consumption increases even when greater work is performed at lower end-diastolic dimensions.

Animals↗

PubMed1988

Myocardial reperfusion injury. Role of myocardial hypoxanthine and xanthine in free radical-mediated reperfusion injury.

The aim of this study was to differentiate myocardial reperfusion injury from that of ischemia. We assessed the role of the myocardial adenosine 5'-triphosphate (ATP) catabolites, hypoxanthine and xanthine, generated during ischemia and the early phase of reperfusion, in reperfusion injury by modulating adenosine transport and metabolism with specific metabolic inhibitors. This was followed by intracoronary infusion of exogenous hypoxanthine and xanthine. Twenty-four dogs instrumented with minor-axis piezoelectric crystals and intraventricular pressure transducers were subjected to 30 minutes of normothermic global myocardial ischemia and 60 minutes of reperfusion. In Group 1 (n = 7), normal saline was infused into the cardiopulmonary bypass reservior before ischemia and before reperfusion. Saline solution containing 25 microM p-nitrobenzylthioinosine (NBMPR) and 100 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was infused in Group 2 (n = 10) dogs. Group 3 (n = 7) dogs were treated exactly like those in Group 2 except, at the end of the ischemic period and immediately before releasing the cross-clamp, a solution of EHNA-NBMPR containing 100 microM hypoxanthine and 100 microM xanthine was infused into the aortic root. Left ventricular performance and myocardial adenine nucleotide pool intermediates were determined before and after ischemia. ATP was depleted by about 50% (p less than 0.05 vs. preischemia) in all groups after 30 minutes of ischemia. Inosine was the major ATP catabolite (9.29 +/- 1.2 nmol/mg protein) in Group 1, while adenosine (9.91 +/- 0.7 nmol/mg protein) was the major metabolite in EHNA-NBMPR-treated dogs (Groups 2 and 3). Hypoxanthine levels were fivefold more in Group 1 compared with Groups 2 and 3 (p less than 0.05). Left ventricular performance in Group 1 decreased from 76.8 +/- 7.6 to 42.9 +/- 9.8 and 52.3 +/- 8.4 dynes/cm2 x 10(3) (p less than 0.05), while myocardial ATP decreased from 30.9 +/- 2.2 to 17.2 +/- 1.0 and 16.5 +/- 1.0 nmol/mg protein during 30 and 60 minutes of reperfusion, respectively (p less than 0.05 vs. preischemia). Ventricular function in Group 2 dogs completely recovered within 30 minutes of reperfusion, and myocardial ATP recovered to the preischemic level at 60 minutes of reperfusion. In Group 3, left ventricular performance was depressed by 39% and 30% during 30 and 60 minutes of reperfusion (p less than 0.05), respectively, and myocardial ATP did not recover during reperfusion despite a significant intramyocardial adenosine accumulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine↗

PubMed1987

Controlled bending instability in the healing of diaphyseal osteotomies in the rat femur.

Ninety-six rats underwent a midshaft transverse osteotomy followed by osteosynthesis with an intramedullary nail, so that the effect of bending instability on time to union and on the mechanical properties of experimental diaphyseal fracture could be evaluated. Rotation was reduced by cementing both nail ends to the bone. Rigid nails made of stainless steel were used on one group and flexible nails made of polyacetal resin were used on another group. Serial radiographs were evaluated at 4-6-week intervals. Twelve animals with either nail type were killed at 4, 8, 16, and 24 weeks. Both femora were mechanically tested and the callus diameters were measured. There was no significant difference in time to union between the two groups. The cross-sectional area of callus was significantly higher at 8 and 16 weeks in femora with flexible nails. The strength, toughness, and resilience of the bone increased in this group until 24 weeks. Between 16 and 24 weeks, these parameters did not improve in femora with rigid nails. Poorer mechanical properties in femora with steel nails are interpreted as an effect of stress protection of the bone. This study, therefore, indicates that flexible nails prevent stress protection effects without delaying union.

Acetals↗

PubMed1987

Gastric epithelial restitution at low luminal pH during influence of pentagastrin or cimetidine in the cat.

This study examines restitution of the gastric surface epithelium at luminal pH 1 after damage to the gastric mucosa by instillation of 2 M NaCl for 10 min. After mucosal damage, potential difference decreased to zero and H+ back-diffusion increased. Gastric blood flow increased after exposure to 2 M NaCl, irrespective of the secretory state of mucosa. Neither pentagastrin nor cimetidine showed any protective effect against mucosal damage produced by 2 M NaCl. Ninety minutes after mucosal exposure to 2 M NaCl there was an almost complete restitution of the gastric surface epithelium in pentagastrin-stimulated and cimetidine-treated animals, whereas about 15% of the gastric surface still showed damage in animals in which acid secretion was not interfered with. These findings show that restitution of the surface epithelium, in vivo, is a rapid and resistant process even at a very low luminal pH. The secretory state of mucosa may have some influence on this process.

Animals↗

PubMed1987

Local myocardial function following coronary occlusion in cats. Effect on non-ischaemic regions.

The mechanical function and perfusion in ischaemic and non-ischaemic myocardium after coronary occlusion was studied in 10 cats using pressure-length loop analysis and radiolabelled microspheres. Measurements in three regions--ischaemic, adjacent normal and remote normal myocardium--all showed different responses to coronary occlusion. In the ischaemic region loop area, segment shortening and tissue flow were markedly reduced. In the adjacent normal region, both loop area and segment shortening as well as flow increased. In the remote normal region, neither loop area, segment shortening nor flow showed consistent changes. End-diastolic segment length increased in all regions, most in the ischaemic region and least in the remote region. The increased end-diastolic segment length in all regions after coronary occlusion indicates activation of the Frank-Starling mechanism as an attempt to maintain stroke volume. However, the end-diastolic segment length did not increase uniformly for all normal myocardium: it depended on the proximity to the ischaemic region. Increased contractile function in the adjacent normal myocardium due to non-uniform distribution of the Frank-Starling effect is the most likely mechanism behind the left ventricle's ability to partially compensate for loss of contractile mass during acute regional ischaemia in anaesthetized cats.

Animals↗

PubMed1987

Regional blood flow and acid secretion associated with damage and restitution of the gastric surface epithelium in cats.

The gastric mucosa of anesthetized cats was exposed to 2 M NaCl for 10 min. After returning to gastric perfusion with 150 mM NaCl and pH 7.40, with and without pentagastrin stimulation, transmucosal potential difference decreased to zero and then gradually increased to approximately half the original value during the following 90 min. H+ secretion decreased and remained close to zero after exposure to 2 M NaCl in nonstimulated cats, whereas pentagastrin-stimulated secretion gradually increased to nearly half the preexposure level. Mucosal blood flow increased, and the vascular resistance decreased in the posterior wall of the stomach corresponding to epithelial damage, as observed by light microscopy after 15 min. Blood flow during pentagastrin stimulation was initially high in fundus and corpus and did not increase further after exposure to 2 M NaCl, but showed similar changes as without pentagastrin in the antrum. Epithelial restitution occurred within 90 min during both nonstimulated conditions and pentagastrin stimulation. In control animals subjected to 150 mM NaCl there were no changes in transmucosal potential difference, H+ secretion, or blood flow throughout the experiment and epithelial damage was not found. In conclusion, damage caused by 2 M NaCl to the gastric surface epithelium was associated with decreased acid secretion and increased mucosal blood flow. These factors may contribute to creating favorable conditions for the epithelial restitution, indicated by restoration of transmucosal potential difference and observed by light microscopy.

Animals↗

PubMed1987

Anesthetic interaction in cardiovascular research models: effects of xylazine and pentobarbital in cats.

The effects of xylazine given to cats before anesthetization was induced with pentobarbital were determined. Cardiac hemodynamic variables and regional blood flow rates in the heart and other organs were measured, using radiolabeled microspheres. Two groups, each of 10 cats, were included in the study: one group (group 1) was anesthetized with pentobarbital given intraperitoneally and subsequently given xylazine; the other group (group 2) was first given 1 mg of xylazine/kg, IM, and then anesthetized with pentobarbital given IV. Anesthesia was maintained in both groups with nitrous oxide. The preanesthetic administration of xylazine decreased the amount of pentobarbital used for surgical anesthesia by approximately 50%. It also resulted in decreased heart rate, cardiac contractility, and cardiac output and increased left ventricular end-diastolic pressure, compared with those values in cats given pentobarbital (group 1). After the latter cats (anesthetized with pentobarbital) were given xylazine, heart rate, cardiac contractility, and cardiac output decreased and left ventricular end-diastolic pressure increased to values similar to those found in group 2 (given xylazine before anesthetization). Myocardial tissue blood flow rates in the left and right ventricles were lower in the cats of group 2. In group 1 cats, myocardial blood flow rates decreased when xylazine was subsequently added. Blood flow rates in the kidneys and gastrointestinal tract were generally decreased by xylazine. Xylazine profoundly changed cardiac hemodynamic function and perfusion in the heart, as well as several other organ systems, because of marked cardiodepression.

Animals↗

PubMed1986

Cellular lipid accumulation in different regions of myocardial infarcts in cats during beta adrenergic blockade with timolol.

The effects of non-selective beta adrenergic blockade on intracellular lipid accumulation in hearts with acute ischaemia were studied by electron microscopy of myocardial biopsy specimens using quantitative stereological techniques. Pentobarbital anaesthetised cats with coronary ligation were divided into eight controls and eight cats treated with timolol intravenously just before ligation. Biopsy specimens were collected from ischaemic, borderline, and normally perfused myocardium, defined by an in vivo injection of fluorescein and verified by regional myocardial blood flow measurements with 15 microns radiolabelled microspheres. During a 3 h occlusion period timolol treated cats had a lower heart rate, left ventricular dP/dt, and plasma free fatty acid concentration. In control cats the cytosolic volume fraction of lipids was 0.71 X 10(-3) in non-ischaemic myocardium, 2.63 X 10(-3) in central ischaemic tissue, and 6.53 X 10(-3) in borderline tissue. Timolol reduced the appreciable lipid accumulation in borderline tissue by 24% (to 4.97 X 10(-3)) compared with controls, whereas accumulation in central ischaemic tissue was not affected. Thus timolol diminished lipid accumulation in borderline myocardial tissue. The mechanism is most likely related to reduced ischaemic intensity and better preserved metabolic function.

Animals↗