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Norway↗
Biomedical subjects
J Lekven
Publications and source records attributed to J Lekven.
Transmural heterogeneity of postjunctional alpha 2 adrenergic coronary vasoconstriction in hypoperfused cat left ventricle.
OBJECTIVE: The aim was to analyse the influence of coronary postjunctional alpha 1 and alpha 2 adrenergic vasoconstriction in hypoperfused myocardium with special emphasis on transmural distribution of blood flow. METHODS: The left coronary artery was hypoperfused by means of a clamped shunt line. Sequential selective postjunctional alpha 1 (doxazosin) and alpha 2 (SK&F 104078) adrenergic antagonism was established following beta adrenergic antagonism with propranolol. Regional myocardial blood flow was measured with radiolabelled microspheres during equal coronary perfusion pressures. Experimental subjects were nine pentobarbitone anaesthetised open chest cats. RESULTS: Left coronary hypoperfusion decreased endocardial blood flow, whereas epicardial flow was unaltered. In this situation alpha 1 adrenergic antagonism did not affect myocardial blood flow. Subsequent alpha 2 antagonism impaired endocardial blood flow, whereas epicardial blood flow was augmented. Mean coronary vascular resistance declined following combined alpha 1 and alpha 2 adrenergic antagonism. CONCLUSIONS: Coronary alpha adrenergic vasoconstriction is localised mainly epicardially in hypoperfused myocardium and counteracts endocardial hypoperfusion distal to a fixed coronary stenosis. Furthermore, this vasoconstriction is of the postjunctional alpha 2 adrenergic subtype.
Adrenergic alpha-Antagonists↗
Compensatory subendocardial hyperkinesis in the cat is abolished during coronary insufficiency outside an acutely ischaemic region.
OBJECTIVE: The aims were to determine (1) whether acute coronary occlusion provoked uniform hyperkinesis in remote non-ischaemic myocardium, and (2) how subsequent coronary stenosis affected such hyperkinesis. METHODS: Two pairs of ultrasonic crystals were placed in the anterior left ventricular midwall of nine pentobarbitone anaesthetised open chest cats. One pair (longitudinal) ran parallel to subendocardial fibres; the other pair (circumferential) was aligned with subepicardial and mid-myocardial fibres. Following circumflex coronary occlusion, subsequent hypoperfusion of the anterior wall was established by controlled constriction of a shunt line from the right subclavian artery to the left main coronary artery in two discrete steps. RESULTS: Following circumflex occlusion maximum systolic shortening of segments aligned to subendocardial fibres increased from 6.7(SEM 0.9)% to 11.5(1.4)% (p less than 0.001), whereas circumferential segment shortening was unchanged, at 12.2(0.8)% v 14.1(1.1)%. During mild shunt stenosis [delta P = 42(2) mm Hg] subendocardial tissue blood flow in the anterior wall decreased by 42(10)% (p less than 0.001), and longitudinal segment shortening decreased from 11.5(1.4)% to 6.9(1.1)% (p less than 0.001). Corresponding shortening of circumferential segments did not change. During severe shunt stenosis [delta P = 52(3) mm Hg] subendocardial tissue blood flow decreased further, and shortening of longitudinal segments approached zero value (p less than 0.001). CONCLUSIONS: Compensatory hyperkinesis of remote non-ischaemic myocardium following an acute coronary occlusion may depend mostly on augmented subendocardial contraction.
Animals↗
Coronary artery stenosis provokes non-uniformity of two-dimensional deformation in the anterior wall of the feline left ventricle.
The effect of coronary stenosis on the uniformity of local left ventricular contraction was studied in 11 open-chest cats. Coronary artery stenosis was established by controlled constriction of a shunt line from the right subclavian artery to the left main coronary artery. Two pairs of ultrasonic crystals were placed in the midwall of the anterior left ventricular wall; one pair, circumferential (Circ), aligned with midwall and subepicardial fibres; the other, longitudinal (Long), aligned with subendocardial fibres. Three steps of coronary perfusion pressure (poststenotic) were studied; open shunt line (140 +/- 4 mmHg), light stenosis (94 +/- 2 mmHg), and severe stenosis (70 +/- 3 mmHg). Subendocardial tissue blood flow showed the most pronounced reduction (from 1.87 +/- 0.11 to 1.43 +/- 0.10 and 0.86 +/- 0.12 ml min-1 g-1, respectively) with coronary stenosis whereas subepicardial flow remained unchanged. Maximal systolic shortening deteriorated for both segments. However, it was most pronounced for longitudinal segments. Duration of shortening decreased in longitudinal segments during severe stenosis to 62% of duration with open shunt (P less than 0.05), but was unchanged in circumferential segments. Long/Circ ratio of maximal systolic shortening declined by 50% (P less than 0.05) with reduction of coronary perfusion pressure. The reduced uniformity of segment shortening, caused by a marked reduction of longitudinal segment shortening, may support the notion that the longitudinal segment reflects performance of subendocardial fibres. This study demonstrates local non-uniformity of two-dimensional deformation during coronary artery stenosis and subendocardial hypoperfusion.
Animals↗
Compensatory regional contraction following coronary artery occlusion depends on subendocardial hyperaemia and hyperkinesis.
The effects of circumflex coronary artery occlusion on regional myocardial performance and blood flow in the left ventricular anterior wall was studied, using 16 thoracotomized pentobarbital-anaesthetized cats. Two pairs of ultrasonic crystals were placed in the midwall; one segment (longitudinal) parallel to the subendocardial fibres, the other (circumferential) being aligned to the fibres of the outer half-layer. A shunt line from the right subclavian artery to the main left coronary artery was unrestricted in eight cats (Group A) and clamped in another eight cats (Group B) until coronary perfusion pressure was clearly reduced with only a minor reduction in shunt flow, but without changes in global cardiac function. After circumflex coronary occlusion hyperkinesis was most pronounced in segments parallel to subendocardial fibres (longitudinal), also validated as a marked leftward shift in the end-systolic pressure-length relation of these segments. Such a shift may indicate decreased regional afterloading along the cardiac major axis. Hyperkinesis of longitudinal segments was attenuated in Group B where a fixed shunt stenosis hampered subendocardial and mid-myocardial hyperaemia. The lesser hyperkinesis of Group B was associated with decreased left ventricular systolic pressure and cardiac output. Thus, impaired compensatory contraction outside an acute ischaemic region was produced by a significant coronary stenosis which precluded the subendocardial hyperaemia and hyperkinesis of that region.
Animals↗
Postjunctional alpha-adrenergic stimulation of inotropy in hypoperfused myocardium outside an acute infarct.
The functional significance of myocardial postjunctional alpha-adrenergic support of inotropy in the vicinity of an acute regional ischemic zone was addressed in pentobarbital-anesthetized, beta-adrenergic blocked cats with circumflex coronary artery occlusion. Regional myocardial performance was measured by ultrasonic crystals in the anterior wall perfused by the left anterior descending coronary artery (LAD) before and during postjunctional alpha-adrenergic antagonism (SK&F 104078 2 mg/kg). A group with unrestricted flow in the LAD (control group) was compared with a group perfused below the autoregulatory pressure range (stenosis group). End-systolic pressure-length relations during dynamic after-load elevation were calculated for assessment of regional contractility. Regional myocardial blood flow (RMBF) was measured by radioactive microspheres. SK&F 104078 did not alter regional myocardial shortening or the slope of end-systolic pressure-length relations in the control group. In the stenosis group, however, alpha-adrenergic antagonism produced significant deterioration of shortening as well as consistent reduction of the slope of the end-systolic pressure-length relations (p < 0.05). As a reflection of reduced demands for perfusion, impairment of midmyocardial and endocardial blood flow occurred in the stenosis group (p < 0.05). These findings imply a negative inotropic effect of SK&F 104078 in metabolically vasodilated myocardium in the vicinity of an acute ischemic region.
Adrenergic alpha-Agonists↗
Alpha-adrenergic vasoconstriction in normal and hypoperfused myocardium during sympathetic nerve stimulation.
Coronary vasoconstriction mediated by postjunctional alpha 1- and alpha 2-adrenergic receptors was studied in normally perfused (control group) and left coronary hypoperfused (stenosis group) hearts of vagotomized, beta-blocked (propranolol) cats. Cardiac sympathetic nerve stimulation was combined with alpha 1- and subsequent alpha 2-adrenergic antagonism (doxazosin and SK&F 104078). Coronary perfusion pressure and heart rate were kept constant within groups; regional myocardial blood flow and cardiac output were obtained by means of microspheres with concomitant measurement of left ventricular myocardial oxygen consumption (MVO2). alpha 1-Adrenergic antagonism alone did not significantly alter blood flow in any wall layer in either group. Subsequent alpha 2-adrenergic antagonism increased epicardial as well as composite transmural flow in the stenosis group (P < 0.025). The inverse correlation between coronary resistance and MVO2 vanished in the stenosis group following alpha 1- and alpha 2-adrenergic antagonism. Maximal first derivative of the left ventricular pressure-time relation (dP/dt) and cardiac output were reduced simultaneously (P < 0.001). Hence, the significance of alpha 1- and alpha 2-adrenergic stimulation of inotropy and cardiac performance are augmented by myocardial hypoperfusion. Furthermore, alpha 2-adrenergic receptors are responsible for epicardial vasoconstriction in hypoperfused myocardium.
Adrenergic alpha-Agonists↗
Effect of afterload and beta-adrenergic blockade on nonischemic myocardial contraction pattern.
We studied how changes in afterload affect regional contraction in the anterior wall of the left ventricular after circumflex coronary arterial (CFX) occlusion and subsequent beta-adrenergic blockade in pentobarbital sodium-anesthetized cats. Regional function was determined by orthogonal sonomicrometry. CFX occlusion produced nonuniform hyperkinesis in the nonischemic anterior wall; shortening of circumferential segments increased from 10.1 to 14.1% (P < 0.001), whereas shortening of longitudinal segments increased from 3.0 to 9.6% (P < 0.001). Hyperkinesis of longitudinal segments was influenced neither by changes in afterload over a pressure range of +/- 30 mmHg nor by beta-adrenergic blockade, indicating that hyperkinesis of longitudinal segments does not rely on increased inotropic state or resistance to ventricular emptying. Hyperkinesis of longitudinal segments occurred at end-diastolic lengths equal to preocclusion conditions, whereas hyperkinesis of circumferential segments was dependent on activation of the Frank-Starling mechanism. Furthermore, shortening of circumferential segments decreased with increments in afterload, particularly after CFX occlusion and subsequent beta-adrenergic blockade. In conclusion, CFX occlusion alters the contraction pattern of the nonischemic anterior wall. The postocclusion contraction is sensitive to increased afterload in the cardiac minor axis direction. These initial alterations may well direct the following remodeling process in infarcted hearts.
Adrenergic beta-Antagonists↗
Myocardial adenine nucleotide depletion within 1 h of acute coronary artery occlusion.
In anaesthetized open-chest casts with occlusion of the left anterior descending coronary artery (LAD), adenine nucleotides and degradation products were studied in small myocardial tissue samples (10-20 mg) with high-pressure liquid chromatography, and tissue blood flow was measured with radioactive microspheres 5, 10, 20, 40, and 60 min after LAD occlusion. There was a rapid and parallel decrease of myocardial ATP and accumulation of adenosine, inosine, hypoxanthine, and xanthine both in epicardial and endocardial half-layers of the ischaemic myocardium within the first 20 min of coronary occlusion. After 40 and 60 min, myocardial ATP content decreased and degradation products accumulated further in the endocardium but stabilized epicardially. Analysis of covariance showed that the slightly higher blood flow in ischaemic epicardial layers, did not explain the transmural difference in ATP content after 40 and 60 min. Adenosine decreased after 40 min of ischaemia in both wall layers reaching negligible amounts after 60 min. It is concluded that breakdown of energy stores is less severe in epicardial than in endocardial wall layers during the first hour after acute coronary occlusion in the cat heart. This transmural difference cannot be explained entirely by less severe epicardial ischaemia. Therefore, transmural heterogeneity in metabolic function during severe ischaemia may also be important.
Adenine Nucleotides↗
Effects of intramedullary reaming and nailing on blood flow in rat femora.
The right femur in 40 rats was reamed, and in 40 others it was additionally nailed. Analysis of bone blood flow was performed by the distribution of radiolabeled microspheres at different postoperative time intervals. Blood-flow measurements were accompanied by analyses of hydroxyproline and calcium contents. Immediately after reaming, the blood flow of the diaphyseal part of the femur was reduced to approximately one third of that of the intact femur, whereas the contents of hydroxyproline and calcium were reduced by 10 percent. Within 1 week, the blood flow was normal. This study provides evidence that the presence of a nail does not interfere with the restoration of bone blood flow. Restoration of blood flow in bone apparently is a rapid process. The replacement of hydroxyproline and calcium contents seemed to be linked to flow, as no increase in these constituents were found until the blood flow had approximated the level of the intact femur.
Animals↗
Non-uniform and non-linear end systolic pressure-length relations at low left ventricular pressures in anaesthetised cats.
STUDY OBJECTIVE: The aims were (1) to establish a basis for measurements of regional inotropy using the slope (E) of the linear part of the end systolic pressure-length relation; (2) to investigate the range of end systolic pressure where linearity is valid, and particularly its lower pressure limit, called turning point pressure; (3) to determine whether local myocardial inotropy measured by normalised slope, E(n), varies with segment orientation DESIGN: Pressure and two cross oriented segment lengths were measured in the left ventricle. One pair of crystals measured a longitudinal segment, aligned with anterior midwall fibre direction; another pair measured a transverse segment, aligned with endocardial and epicardial fibre direction. Temporary obstruction of the inferior caval vein and descending aorta were performed to produce a wide pressure range of end systolic pressure-length relations during basal as well as high inotropic states (isoprenaline). SUBJECTS: Seven open chest cats anaesthetised with sodium pentobarbitone and nitrous oxide were used. MEASUREMENTS AND MAIN RESULTS - Turning point pressure for longitudinal segments showed lower values than for transverse segments (p less than 0.05). With isoprenaline, turning point pressure increased for all transverse segments, at 103(SEM 8) v 153(19) mm Hg (p less than 0.05), whereas no change occurred for longitudinal segments, at 82(4) v 87(7) mm Hg. In the basal state, E(n) showed lower values in all longitudinal segments compared to transverse segments, except for one pair. E(n) of all segments increased during isoprenaline infusion, except in one segment where no change occurred. CONCLUSIONS - There is a lower limit for linearity of end systolic pressure-length relations; this is affected by segment orientation as well as by the inotropic state of the heart. E(n) as a measure of regional inotropy varies with segment orientation, but offers a local measure of changes in inotropic state.
Anesthesia, General↗
Blood flow regulation during acute regional ischemia in feline hearts: importance of postjunctional alpha 1- and alpha 2-adrenoceptors.
Influence of postjunctional alpha 1- and subsequent alpha 2-adrenergic antagonism on myocardial blood flow was measured in a group of anesthetized cats with acute occlusion of the left anterior descending coronary artery (LAD) and a control group (n = 10 for both). The relatively selective postjunctional alpha 1-(doxazosin) and alpha 2-adrenergic (SK&F 104078) antagonists were applied after beta-adrenergic blockade (propranolol). Regional myocardial blood flow was obtained with radiolabeled microspheres. Major hemodynamic determinants for perfusion were kept constant both within and between groups by right atrial pacing and aortic obstruction. Mean coronary resistance in nonischemic myocardium was permanently lower in the occlusion group as compared with controls (p less than 0.01). Subsequent alpha 2-adrenergic antagonism reduced mean coronary resistance in controls only (p less than 0.05). Cardiac output (CO) and dP/dt was reduced in LAD-occluded hearts after alpha 2-adrenergic blockade (p less than 0.01, p less than 0.05). The study demonstrates the significance of postjunctional alpha 2-adrenergic-mediated vasoconstriction in well-perfused myocardium of control hearts, whereas such vasoconstriction was deteriorated in LAD-occluded hearts. A role for myocardial alpha 2-adrenoceptors for maintenance of global cardiac function in acute regional ischemia was also indicated.
Adrenergic alpha-Antagonists↗
Transmural fibre direction in the anterior wall of the feline left ventricle: theoretical considerations with regard to uniformity of contraction.
Previous studies of non-uniform performance of a myocardial region have indicated that measurement of local contraction is vectorial. Myocardial performance in one direction mainly, but not exclusively, depends on performance of the wall fibres in this same direction irrespective of wall depth. In this study we therefore determined fibre direction across the anterior wall of the left ventricle in twelve cats. Based on the fibre configuration a simple model is developed to analyse and predict the degree of uniformity of contraction. Fibre direction shifted continuously across the wall, from almost alignment with global apex-to-base axis in the endocardium (90 degrees), to close to the equatorial direction (0 degrees) in the midwall, and finally to about -50 degrees in the epicardial layer. The model predicts less uniformity with reduction of preload, and in the event of subendocardial ischaemia, which fits well with experimental data. Analysis of uniformity based on the integrated vectorial contribution of all myocardial layers thus provides a way to quantify regional uniformity/non-uniformity as a regulatory mechanism of cardiac function.
Animals↗
Dyssynchrony of segment shortening in the anterior wall of the feline left ventricle.
Non-uniformity of regional contraction may be both spatial and temporal. This study was undertaken to deal with the temporal aspects of shortening and to quantify non-uniformity with regard to timing. Nine cats were anaesthetized and artificially ventilated. Two pairs of ultrasonic crystals were situated in the anterior midwall of the left ventricle to measure regional shortening. One pair, longitudinal segment, was oriented to align with midwall fibres. The other pair, transverse segment, was placed perpendicular to the first one. Registrations in control state, during caval occlusion, and during aortic constriction were carried out with and without isoprenaline infusion. Cyclic events were analysed in terms of phase angle, 0-2 pi representing one heart cycle. Transverse segments showed marked shift of duration of shortening, from 1.19 pi +/- 0.06 pi (mean +/- SEM) in the control state to 0.40 pi +/- 0.14 pi during caval occlusion with isoprenaline infusion. Duration of shortening of longitudinal segments showed less prominent shift with mean values between 1.38 pi and 1.11 pi. Regional uniformity of timing, expressed as synchronization index, varied markedly with interventions (P less than 0.0005). Dyssynchrony was most prominent during caval occlusion with mean values less than 0.6. A simple model of force generation for the two segments visualizes that segment shortening of the transverse segment is of shorter duration than the longitudinal segment and a common mechanism for temporal and spatial non-uniformity within a region could be elaborated. This study quantifies both the time course of shortening and temporal non-uniformity of two cross-oriented segments within the same myocardial region.
Animals↗
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↗
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↗
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↗
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↗