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Biomedical subjects

E Hexeberg

Publications and source records attributed to E Hexeberg.

At least 37 records · Page 2Linked to original sources

Changes in myocardial contraction pattern during initial reperfusion.

The characteristics of hypercontraction during initial reperfusion were studied in 10 pentobarbitone-anesthetized cats. The left anterior descending coronary artery was occluded for 10 min followed by 1 h of reperfusion, and regional function was assessed by two cross-oriented pairs of sonomicrometers placed in the left ventricular anterior wall. At 1 min of reperfusion (hyperfunctional phase) there was an uniform contraction pattern with 90% recovery of ejection shortening in both circumferential and longitudinal segments. During initial hypercontraction, end-diastolic segment lengths remained unchanged, whereas end-systolic segment lengths decreased transiently. Inotropic stimulation during reperfusion in four additional animals also affected end-systolic lengths more than end-diastolic lengths. This suggests that the initial hyperfunctional phase is due to an inotropic stimulation of the stunned myocardium, most probably caused by intracellular Ca2+ overload. At 5 min of reperfusion a nonuniform contraction pattern had developed with 68% recovery of shortening in circumferential segments vs. 25% in longitudinal segments. The decreased performance in longitudinal segments was paralleled by a delayed start of contraction as well as a decreased velocity of contraction. Because longitudinal segment shortening is a sensitive parameter of subendocardial performance, our results indicate a brief transmural hypercontraction followed by increasing dysfunction (stunning) in the subendocardial layer.

Animals↗

Cholesterol induced lipid accumulation in myocardial cells of rats.

OBJECTIVE: The aim was to investigate whether cholesterol feeding of rats for only 10 d would result in lipid accumulation in myocardial cells and a change in the peroxisomal beta oxidation in the heart compared to the hearts of rats on standard feeds. METHODS: Eight rats received a cholesterol diet (2%) and eight rats received a standard diet for 10 d. Lipids were measured in serum, liver, and heart. Palmitoyl-CoA hydrolase and fatty acyl-CoA oxidase were determined in total homogenate of hearts. The fractional volume of lipid droplets in myocardial cells was calculated from micrographs at a magnification of x9600 obtained by electron microscopy. RESULTS: The fractional volume of lipid droplets in the cardiomyocytes increased from 0.109(SEM 0.019)% to 0.259(0.037)%, (p < 0.003), as a result of cholesterol feeding. Cholesterol and triglycerides in the heart measured by biochemical methods increased by 13% and 24%, respectively. There was no difference in palmitoyl-CoA hydrolase or fatty acyl-CoA oxidase in the hearts of the cholesterol fed group compared to the control group, suggesting an unaltered peroxisomal beta oxidation of fatty acids in the myocardium. The serum triglycerides and serum phospholipids were reduced in the cholesterol fed rats (p < 0.05 and p < 0.001, respectively). Rats fed cholesterol diet showed a reduced ratio of HDL cholesterol to total cholesterol in serum, together with an increased liver weight and relative liver weight compared to the control rats. The addition of cholesterol to the diet increased liver cholesterol to 21.0(1.6) mumol.g-1 wet weight compared to 5.87(0.93) mumol.g-1 in the controls on standard diet (p < 0.0001). Cholesterol feeding had no effect on the hepatic level of phospholipids, but the liver triglycerides tended to increase from 23.3(9.5) mumol.g-1 wet weight to 53.3(6.3) mumol.g-1. CONCLUSIONS: Lipid accumulation in the myocardial cells was shown by morphometry after 10 d of cholesterol feeding, without any visible damage to the tissue.

Acyl-CoA Oxidase↗

Beta-adrenergic blockade improves uniformity of local contraction in the anterior wall of feline left ventricles.

Uniformity of myocardial contraction has been put forward as an important regulatory mechanism of myocardial contraction, and we have previously demonstrated reduced uniformity of local myocardial contraction in the midwall of left ventricles during preload reduction combined with increased inotropy. The aim of the present study was to explore the isolated inotropic influence on uniformity of contraction, keeping loading conditions constant. Segment performance was measured by implanted piezo-electric crystals in ten open-chest, anaesthetized cats. One crystal pair, circumferential segment, aligned with midwall and epicardial fibres, whereas another perpendicular segment, longitudinal, ran close to endocardial fibre direction. Maximal systolic shortening of longitudinal segments remained unchanged following inotropic interventions, isoprenaline and timolol, whereas circumferential segments revealed reduced performance with timolol (8.4 +/- 1.0% compared with 14.0 +/- 1.3% during control; P < 0.001). In the control state the longitudinal-to-circumferential ratio (LONG/CIRC) a quantitative measure of uniformity, was 0.32 +/- 0.08. No change in uniformity occurred during isoprenaline infusion (0.32 +/- 0.11) but during beta-adrenergic blockade with timolol a clearly higher LONG/CIRC ratio was observed (0.56 +/- 0.06, P < 0.005). Myocardial tissue blood flow measurement by radioactive microspheres showed a shift in transmural distribution with interventions so that subepicardial blood flow was markedly reduced during beta-adrenergic blockade. The direction of subepicardial fibres approximates our circumferential segments. Thus, there may well exist a relationship between segmental shortening and perfusion. In conclusion, circumferential segments were most influenced by changes in inotropy in contrast to previous observations where pronounced changes in longitudinal segments with loading occur. Furthermore, this study demonstrates that reduced inotropy with timolol helped uniform local contraction as estimated by the increased LONG/CIRC ratio, a transition that could improve contraction efficacy.

Adrenergic beta-Antagonists↗

Non-uniformity of two-dimensional myocardial deformation in response to chronotropic and inotropic stimulation in cats.

The degree of uniformity of myocardial deformation for cross-oriented segments in the anterior wall of the left ventricle is influenced both by loading conditions and by infusion of isoprenaline. The aim of this study was to clarify the chronotropic influence (atrial pacing) compared to the combined inotropic and chronotropic effects of isoprenaline on uniformity of contraction. In eight open-chest pentobarbitone-anaesthetized cats segment performance was measured by orthogonal sonomicrometry. Heart rate (HR) increased from control state, 199 +/- 5 (mean +/- SEM) beats min-1, to 224 +/- 6 and 227 +/- 7 beats min-1 during atrial pacing and isoprenaline infusion, respectively (P < 0.0005). Circumferential segment shortening remained unchanged during pacing but increased with isoprenaline (P < 0.0005). Longitudinal segments showed reduced shortening during pacing (P < 0.05), whereas shortening during isoprenaline infusion did not differ from control shortening. The ratio between shortening of longitudinal and circumferential segments, long/circ ratio, changed from 0.52 +/- 0.13 in the control state to 0.36 +/- 0.10 during pacing and 0.39 +/- 0.11 with isoprenaline (P < 0.05). End-systolic pressure-length relations were unchanged by atrial pacing but showed leftward shifts during isoprenaline infusion. Myocardial tissue blood flow (microspheres) was unchanged during interventions. We conclude that both atrial pacing and isoprenaline infusion lead to a more non-uniform deformation in the anterior wall. However, non-uniformity during atrial pacing was primarily related to reduced longitudinal shortening whereas the non-uniformity during isoprenaline infusion was due to increased circumferential shortening.

Animals↗

The influence of afterload on uniformity of segment shortening in feline left ventricles. Importance of cross-fibre contraction.

Previous studies have shown that the combined increase of preload and afterload leads to a more uniform wall contraction. As our previous information with a stable afterloaded situation showed considerable increase of left ventricular end-diastolic pressure, we have as yet no information of how afterload per se effects uniformity of segment shortening. We therefore analysed maximal systolic shortening of cross-oriented segments for three consecutive beats during abrupt elevation of afterload in 12 open-chest cats. Peak left ventricular systolic pressure increased during the three beats from 154 +/- 5 mmHg (mean +/- SEM) to 167 +/- 5 mmHg and 186 +/- 5 mmHg. Left ventricular end-diastolic pressure remained unchanged. Maximal systolic shortening was reduced for both segments with increasing afterload, in longitudinal segment (LONG) from 7.6 +/- 1.1 to 6.1 +/- 1.0% (P < 0.005), and more pronounced for circumferential segments (CIRC) from 12.2 +/- 0.7 to 8.3 +/- 0.9% (P < 0.0005). Uniformity of maximal systolic shortening, LONG/CIRC, increased from 0.63 +/- 0.08 in the first beat to 0.73 +/- 0.10 and 0.82 +/- 0.12 in the following beats (P < 0.02). We conclude that uniformity of contraction for cross-oriented segments in the anterior left ventricular wall is increased during increased afterload. We propose that this can be explained by reduction of the effect of cross-fibre contraction with increasing afterload.

Analysis of Variance↗

Non-uniform recovery of performance in stunned myocardium evaluated by two-dimensional sonomicrometry.

The objective of the present study was to assess the uniformity of contraction in reperfused myocardium. Regional function was measured by two pairs of piezo-electric crystals oriented in the circumferential and longitudinal axis of the left ventricular anterior midwall in 10 open-chest pentobarbitone-anaesthetized cats. The left anterior descending coronary artery was occluded for 10 min followed by 60 min of reperfusion. Myocardial blood flow was measured four times by radioactive labelled microspheres: at pre-occlusion, occlusion and after 30 and 60 min of reperfusion. There was a severe and transmural homogenous ischaemia during coronary occlusion. The recovery of ejection shortening was on average 76% at 30 min and 77% at 60 min of reperfusion in circumferential segments versus 25 and 44% in longitudinal segments (P < 0.05). Diastolic function was deranged in longitudinal segments; at 60 min of reperfusion the end diastolic pressure-length relation was still shifted rightwards in longitudinal segments, whereas it was normalized in circumferential segments. In conclusion, systolic and diastolic dysfunction in stunned myocardium were more severe in the longitudinal axis than in the circumferential axis of the feline heart. This indicates that stunning was more pronounced in longitudinally oriented sub-endocardial fibres which were reflected by the longitudinal segment, despite transmural homogenous ischaemia during coronary artery occlusion.

Animals↗

[Working conditions of medical students--medical students and research].

A questionnaire survey was conducted among 33 medical students (22 men and 11 women) working as part or full-time research trainees at the University of Bergen in 1990, in order to examine various aspects of their working conditions. Most trainees (81%) experienced a well-organized initial research project, and 85% were quite content with their personal supervision. The students "defined" two hours per week as an "adequate amount" of supervision. A higher percentage of the male trainees were first author of scientific publications, while a higher percentage of the females felt that they had learned something from their scientific training. Surprisingly perhaps, relatively more of the female wished to do research full time in the future. 94% of the research trainees recommended other medical students to participate in research training programmes during their student career.

Education, Medical, Continuing↗

[Research interest and recruitment potential--medical students and research].

A questionnaire survey on scientific interest among 324 medical students at the University of Bergen in 1990 showed that 14% of the students had already participated in medical research programmes (10% still research trainees). In addition, 45% had considered starting working as a research trainee while a student. Many were discouraged, however, by the problem of finding a suitable supervisor. Relatively more of the male students expressed considerable interest in science (32 versus 22% of the females). The medical students already recruited to scientific work stressed the importance of scientific experience for their future career. The faculty has recently made participation in research projects compulsory. The personal supervision during this short period (6-8 weeks) will probably have major impact on the interest in research and the recruitment of future medical research trainees.

Education, Medical, Continuing↗

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↗

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↗

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↗