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K Ytrehus

Publications and source records attributed to K Ytrehus.

At least 55 records · Page 3Linked to original sources
PubMed1993

Substrate preference of isolated perfused rat hearts during hypothermia and rewarming.

Fatty acid and glucose oxidation rates were measured in isolated rat hearts undergoing hypothermia and rewarming. The hearts were perfused in the Langendorff mode with Krebs-Henseleit bicarbonate buffer containing 11.1 mM glucose plus 0.6 mM albumin-bound oleic acid as energy substrates. The hearts were stabilized at 37 degrees C and thereafter cooled progressively to 15 degrees C over a period of 60 min. The hearts were kept at this temperature for 10 min and then rewarmed to 37 degrees C during the next 30 min. Control hearts were perfused at 37 degrees C throughout the whole perfusion period. Trace amounts of [14C]glucose or [14C]oleic acid were included in the perfusate, and the rate of substrate oxidation was determined on the basis of the radioactive CO2 production. In normothermic hearts steady state oxidation rates of glucose and oleate were found to be 0.17 +/- 0.01 and 0.51 +/- 0.07 mumol min-1 g-1 dry wt, respectively (mean +/- SEM). In response to hypothermia (15 degrees C) glucose oxidation was reduced by 76% (from 0.17 +/- 0.01 to 0.04 +/- 0.01 mumol min-1 g-1 dry wt) and oleate oxidation by 47% (from 0.51 +/- 0.07 to 0.27 +/- 0.02 mumol min-1 g-1 dry wt). Upon rewarming glucose and fatty acid oxidation rates returned to essentially the same values (0.12 +/- 0.02 and 0.45 +/- 0.04 mumol min-1 g-1 dry wt) as those observed under steady state normothermic conditions. The molar ratio between glucose and fatty acid oxidation was, however, significantly (P < 0.05) lower in hypothermic than in normothermic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Oxygen radicals and scavenger enzymes in ischaemia-reperfusion injury of skeletal muscle.

In this study the protective effects of removing oxygen free radicals during ischaemia and reperfusion of skeletal muscle were investigated. The bilateral gracilis muscle model was used in six dogs. Both muscles were made ischaemic for 4 h, followed by reperfusion for 60 min. To remove oxygen free radicals, superoxide dismutase and catalase were given 10 min before ischaemia and during the first 30 min of reperfusion in one muscle; the other muscle served as a control. Muscle blood flow was recorded during the first 35 min of reperfusion. At the end of reperfusion the contents of high-energy phosphates and glycogen were measured. Furthermore, the metabolic burst of leukocytes (chemiluminescence) was determined. Flow as well as creatine phosphate were always highest in the treated muscles as compared with the control muscles (p less than 0.05). Adenosine triphosphate and glycogen were highest in all but one case. Spontaneous leukocyte chemiluminescence was significantly reduced in venous blood from the control muscle and insignificantly reduced in blood from the treated muscle as compared with blood from the aorta. The results are indirect evidence that reactive oxygen metabolites play a role in the genesis of ischaemia-reperfusion injury of skeletal muscle and that treatment with scavenger enzymes may have protective effects.

Animals↗
PubMed1991

An experimental model for the study of transcapillary fluid balance in hypothermia.

Disturbed fluid balance is a significant clinical problem in hypothermia and rewarming. We have therefore investigated whether the transcapillary fluid balance in rats exposed to hypothermia and rewarming could be studied with the use of a wick method. Double nylon wicks were sewn into the abdominal skin and left there for one hour, then removed to double-bottomed conic vials and centrifuged. Wick fluid was collected and colloid osmotic pressure measured. Blood samples were taken simultaneously for measurement of hematocrit, hemoglobin, red cell count and plasma colloid osmotic pressure. This was done at 37 degrees C (prehypothermic), 13 degrees C (hypothermic) and at 30 degrees C (during rewarming). Blood pressure was also recorded. The model provides a good method to investigate the colloid osmotic changes of both plasma and interstitium during hypothermic situations.

Animals↗
PubMed1991

Hemodynamic and metabolic effects of hypothermia and rewarming.

There is a lack of detailed knowledge of the pathophysiologic mechanisms initiated during and after rewarming. To study cardiac function after rewarming from hypothermia sodium pentobarbital anesthetized open chest-dogs were cooled to 25 degrees C and rewarmed. Myocardial blood flow was measured at different temperatures, and blood samples were drawn from the aorta and the coronary sinus for metabolic measurements. Mean aortic blood pressure (AOP) and aortic blood flow were recorded. Compared to precooling, AOP and heart rate were both significantly reduced during hypothermia. During rewarming stroke volume (SV) decreased significantly. At the end of rewarming AOP and SV were significantly lower than before cooling and myocardial blood flow, as well as oxygen and lactate uptake were only 50% of precooling levels. The present study demonstrated that hypothermia and rewarming depress cardiovascular function. Changes in peripheral vascular function, myocardial metabolism and contractility, may lead to the observed reduction in recovery upon rewarming.

Animals↗
PubMed1991

Lipid peroxidation and membrane damage of the heart.

Biological membranes separate the cells from the environment and control flow of molecules and information between the cell and its surroundings. In addition, the cellular energy supply is dependent on membrane functions. The present chapter deals with membrane lipid peroxidation and how this process might influence the physiology and pathophysiology of the myocardium.

Animals↗
PubMed1990

Amelioration of reperfusion injury following hypothermic, ischemic cardioplegia in isolated, infarcted rat hearts.

The left coronary artery was ligated and myocardial infarction developed in 28 rats. Three weeks later, the hearts were excised and mounted in an apparatus for perfusion of non-working isolated hearts (Langendorff). Hypothermic (15 degrees C), ischemic cardioplegia was induced for either 2 or 3 1/2 h followed by reperfusion for 45 min. Half of the hearts were reperfused with an initially gradual rise in temperature and pressure of the perfusion fluid, whereas the other half was reperfused directly with the perfusate at 37 degrees C and 100 cm H2O pressure. The hearts were examined by transmission electron microscopy and randomized for stereological analysis based on point counting on electron micrographs. Cardioplegia of 2 h duration was tolerated better than cardioplegia for 3 1/2 h (interstitial edema; P = 0.03, fraction of altered mitochondria; P = 0.001). Particularly in the hearts undergoing the longest cardioplegia, myocardial injury was less severe following a gentle reperfusion as compared with those exposed to the clinically common abrupt technique (fraction of mitochondria in the myocyte; P = 0.03, fraction of altered mitochondria; P = 0.008). In the interstitium, the luminal area of capillaries was significantly increased and the endothelial swelling less pronounced in the groups undergoing the gentle reperfusion technique, (luminal/endothelial fraction; P = 0.01). The study shows that previously infarcted hearts are susceptible to ischemic damage even after 2 h of regular hypothermic, ischemic cardioplegia and that a gentle reperfusion technique significantly ameliorates reperfusion injury.

Animals↗
PubMed1990

Effects of initial reperfusion temperature and pressure after prolonged cardioplegic ischemic arrest. A metabolic and functional study in rat hearts.

The effects of temperature and pressure during early cardiac reperfusion after 3.5 hours of hypothermic, cardioplegic ischemia were investigated in isolated Langendorff-perfused rat hearts. The hearts were randomized in two groups and subjected to different techniques of reperfusion. The group I hearts were exposed to rapidly rising perfusion pressure and temperature, and in group II slowly rising pressure and temperature were employed. After 60 min of reperfusion, left ventricular developed pressure, coronary flow and tissue content of high-energy phosphates were evaluated. Left ventricular pressure and coronary flow were significantly better preserved in group II. Recovery of adenosine triphosphate and creatine phosphate was significantly lower in group I (5.27 +/- 0.38 and 8.72 +/- 0.62 mumol x g dry weight-1) than in group II (9.31 +/- 0.41 and 14.97 +/- 0.62). The study thus demonstrated that functional recovery, restoration of coronary flow and normalization of high-energy phosphate stores after long periods of hypothermic cardioplegic ischemia can be considerably influenced by the employed reperfusion technique.

Adenosine Triphosphate↗
PubMed1989

Functional impairment in isolated rat hearts induced by activated leukocytes: protective effect of oxygen free radical scavengers.

Ischemia-reperfusion activates polymorphonuclear leukocytes (PMN). Depletion of PMN has been shown to reduce the size of experimental myocardial infarction. We have studied whether PMN activated by phorbol myristate acetate (PMA) would depress function of the isolated rat heart, and if this effect was mediated by oxygen free radicals (OFR). Cells and/or drugs were added to the perfusate into the aortic cannula for 10 min, followed by a 30 min recovery period. Oxygen free radicals formation was verified by chemiluminescence (CL). PMA-activated PMN (n = 13) caused CL response of 27,493 +/- 5113 counts (mean +/- S.E.M.) and reduced left ventricular developed pressure (LVDP) to 30 +/- 9% and coronary flow (CF) to 49 +/- 7% of the baseline value at the end of the observation period. Addition of super-oxide dismutase (SOD) and catalase (CAT) (n = 11) reduced the CL response to 5623 +/- 806 counts, but did not influence either LVDP (36 +/- 15%) or CF (51 +/- 18%). Addition of thiourea (TU) to the activated cell suspension (n = 8) further reduced the CL response (3663 +/- 474 counts), and LVDP was 86 +/- 5% and CF was 87 +/- 3%. When TU + SOD + CAT was mixed with PMN + PMA (n = 11), the CL was almost abolished (117 +/- 21 counts) and LVDP was 73 +/- 8% and CF was 94 +/- 6%. When CF was reduced (n = 7) alike the CF reduction in the hearts receiving PMA + PMA, LVDP was not significantly changed at the end of the observation period (75 +/- 6%). Unactivated PMN (n = 8) caused minor response of LVDP and CF, similar to PMN + PMA + TU and PMN + PMA + SOD + CAT + TU. PMA alone (n = 8) was cardiotoxic and caused changes similar to PMN + PMA. This effect was not inhibited by scavengers (n = 6). The supernatant of the PMN + PMA suspension (n = 7) did not impair cardiac function, suggesting that no free PMA was available after mixing with PMN. We conclude that activated PMN in the coronary circulation depressed cardiac function and increased vascular resistance due to OFR production.

Animals↗
PubMed1988

Oxfenicine-induced accumulation of lipid in the rat myocardium.

Oxfenicine inhibits myocardial metabolism of nonesterified fatty acids (NEFA). The purpose of the present study was to examine the effects of oxfenicine on triglyceride accumulation and the development of histologically visible lipid droplets. The beta-agonist isoproterenol was used to induce elevated arterial NEFA. Four groups of rats were used in the experiment (12 to 14 rats in each group), and each group received two subcutaneous injections, the second injection 25 min after the first, of oxfenicine-isoproterenol, oxfenicine-saline, saline-isoproterenol and saline twice, respectively. One hour after the second injection, the rats were anesthetized, and the hearts from six rats from each group were quickly removed and frozen for later analysis of triglyceride content. From the remaining rats blood samples were drawn for NEFA analysis, and biopsies were taken from the left ventricular wall before the hearts were frozen in liquid nitrogen and prepared for analysis of esters of carnitine and CoA. Quantitative morphometric techniques were used to determine the fractional volume of lipid droplets in myocardial biopsies. Our results show a marked increase in the triglyceride and lipid droplet content in all groups receiving oxfenicine or isoproterenol. The effect was most pronounced after treatment with both drugs. The close association between the increase in triglyceride and lipid droplet supports the notion that the lipid droplets are composed of triglycerides. Our finding that oxfenicine induces lipid droplet accumulation independent of NEFA increase supports the hypothesis that oxfenicine exerts its effect by inhibiting carnitine acyl transferase.

Acyl Coenzyme A↗
PubMed1988

The selenium-deficient rat heart with special reference to tolerance against enzymatically generated oxygen radicals.

The tolerance against two different levels of enzymatically generated oxygen radicals was studied in isolated Langendorff-perfused hearts from selenium (Se)-deficient and control rats. The glutathione peroxidase activity of the Se-deficient hearts was less than 5% of that of the controls. Examination of the ultrastructure was made after random sampling using morphometric methods. Selenium-deficient hearts demonstrated some areas with myocytes with intracellular oedema. Oxygen radicals (hydrogen peroxide and superoxide) were generated by adding xanthine oxidase for 12 min (high dose: 25 U/l; low dose: 12.5 U/l) and hypoxanthine to the buffer of isolated Langendorff-perfused rat hearts. Left ventricle-developed pressure (LVDP) and high-energy phosphates (ATP and CP) were measured. After the low dose of oxygen radicals, LVDP was reduced to 32.7 +/- 6.5% (mean +/- SEM) of initial values in the Se-deficient group, but only to 58.3 +/- 8.4% in the control group (p less than 0.05). After the high dose, LVDP decreased abruptly to zero in both groups. However, ATP content was significantly (p less than 0.05) lower in Se-deficient than in control hearts. Perfusion with oxygen radicals (low dose) resulted in the appearance of mitochondrial damage in both groups, but intracellular oedema was still present only in the Se-deficient hearts. It is concluded that protection against oxygen radicals was reduced in Se-deficient hearts. This was probably due to loss of myocardial glutathione peroxidase activity.

Adenosine Triphosphate↗
PubMed1987

Improved energy preservation following gentle reperfusion after hypothermic, ischemic cardioplegia in infarcted rat hearts.

The influence of temperature and pressure during early reperfusion after 2 h of hypothermic, cardioplegic ischemia was investigated. Adenosine triphosphate (ATP) and creatine-phosphate (CP) were measured after 45-min reperfusion. The experiments were carried out in normal and previously infarcted rat hearts (the left coronary artery having been ligated 3 weeks earlier). Four groups, each containing six hearts, were studied. Group 1 consisted of normal hearts reperfused with an abrupt rise in temperature and pressure, group 2 of normal hearts exposed to slowly rising temperature and pressure, and group 3 and 4 of previously infarcted hearts. Reperfusion procedures in groups 3 and 4 were the same as in group 1 and 2, respectively. The study showed that previously infarcted hearts have a lowered tolerance to ischemia and that the reperfusion technique may influence the preservation of myocardial energetics, although this influence was not statistically significant in normal hearts following only 2 h of ischemia. The gently reperfused infarcted hearts had energy stores equal to the normal hearts after 2 h of ischemia and 45 min of reperfusion, whereas the infarcted hearts reperfused in a rougher mode had significantly lowered values (P less than 0.05 for ATP and P less than 0.01 for CP).

Adenosine Triphosphate↗
PubMed1987

Ultrastructural changes induced in the isolated rat heart by enzymatically generated oxygen radicals.

This study describes the effect of oxygen radicals on the ultrastructure of the isolated Langendorff-perfused rat heart. Oxygen radicals were enzymatically generated by xanthine oxidase (0.025 U/ml) and hypoxanthine (0.96 mM). Hearts were perfusion-fixed for electron microscopy and stereological technique was performed to obtain estimates of volume fractions (Vv) of different tissue components. Perfusion with oxygen radicals resulted in areas with severely damaged myocardial cells. These changes included swelling and cristolysis of mitochondria, disruption of filaments, development of intracellular edema and focal disruption of the sarcolemma. Stereological examination revealed few alterations after 5 min perfusion with oxygen radicals. After 10 min perfusion with oxygen radicals, however, the Vv (myocyte/myocardium) increased from 0.542 +/- 0.042 (mean +/- S.D.) to 0.663 +/- 0.144, and this paralleled the development of Vv (cellular edema/myocyte) being 0.047 +/- 0.028. Vv (capillary wall/capillary) increased from 0.215 +/- 0.046 to 0.411 +/- 0.123 indicating endothelial swelling. Although the mitochondria appeared swollen, Vv (mitochondria/myocyte) remained constant. The effect of a 35 min recovery period on the ultrastructure was minor. The application of SOD and catalase together with xanthine oxidase and hypoxanthine reduced the observed changes significantly, thus proving the participation of oxygen radicals. This study confirms that oxygen radicals can induce major alterations in myocardial ultrastructure.

Animals↗
PubMed1987

Protection by superoxide dismutase and catalase in the isolated rat heart reperfused after prolonged cardioplegia: a combined study of metabolic, functional, and morphometric ultrastructural variables.

To determine the protective effect during ischaemia and reperfusion of removing oxygen radicals two groups of isolated Langendorff perfused rat hearts were arrested with cardioplegic solution at 4 degrees C and kept ischaemic at 15 degrees C for 210 min before being reperfused for 60 min at 37 degrees C. To remove oxygen radicals superoxide dismutase and catalase were added to the cardioplegic solution and to the buffer during the first 30 min of reperfusion in one group, the other group serving as control. At the end of reperfusion the first derivative of left ventricular developed pressure (dP/dt), coronary flow, high energy phosphate concentrations, and ultrastructure were determined. The ultrastructure was examined using a stereological method based on point counting and the results presented as volume fractions (Vv). DP/dt after 60 min of reperfusion was 61.6(5.6)% (mean (SEM)) of the initial values in the control group and 77.6(3.4)% in the superoxide dismutase and catalase supplemented group (p less than 0.05). In the supplemented group coronary flow was significantly higher than in the control group but only in the first part of reperfusion. The concentrations of adenosine triphosphate and creatine phosphate in the control group were 9.9(1.0) and 19.6(1.8) mumol.g-1 dry weight respectively; corresponding values in the supplemented group were 14.4(2.1) and 29.4(3.6) mumol.g-1 dry weight. The morphometric examination of the ultrastructure showed no significant difference in interstitial fluid accumulation evaluated by Vv(myocyte/myocardium) measurements and there was no difference in mitochondrial alteration between the two groups. There was, however, a significant reduction in the volume of cellular oedema (Vv(cell oedema/myocyte)) in the supplemented group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Preservation of high energy phosphates during ischaemic cardiac arrest with glucose.

The possible myocardial protection by glucose-insulin-potassium infusion prior to cardioplegic ischaemic arrest was studied in rats. One group of animals was given intravenous infusions of high concentrations of glucose during 3 days. A control group received the same amount of saline. The isolated hearts were subjected to Langendorff perfusion followed by cardioplegic arrest at 15 degrees C for a period of 2 or 3.5 hours. The hearts were then subjected to reperfusion for a period of 45 min for those sustaining 2 hours of ischaemia and 60 min for those sustaining 3.5 hours of ischaemia. In the hearts that suffered 2 hours of ischaemia there were no differences in myocardial content of high energy phosphate compounds between the pretreated and controls, and there was no evidence of creatine kinase release. In the hearts exposed to 3.5 hours ischaemia, myocardial content of high energy phosphates was significantly higher in the pretreated than in the controls. The release of creatine kinase was also less, but this difference was not significant. The study indicates that preoperative treatment with glucose-insulin-potassium may improve myocardial tolerance to ischaemia.

Animals↗
PubMed1986

Influence of oxygen radicals generated by xanthine oxidase in the isolated perfused rat heart.

To investigate the cardiac effects of enzymatically generated oxygen radicals isolated Langendorff rat heart preparations were perfused with hypoxanthine (0.96 mmol X litre-1) plus xanthine oxidase (0.025 U X ml-1). Oxygen radicals produced an immediate increase in coronary flow. After 10 min a pronounced reduction in contractile performance, as well as in concentrations of high energy phosphates, was seen. Electron microscopical examination showed damage with cellular oedema as a prominent finding. These effects were all effectively reversed by the specific enzymes, superoxide dismutase and catalase, proving that they were due to oxygen radicals.

Animals↗
PubMed1986

Multiple myeloma in central Norway 1981-1982: a randomized clinical trial of 5-drug combination therapy versus standard therapy.

67 previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of combination chemotherapy including vincristine, carmustine, alkylating agents, and prednisone was more effective than conventional therapy with melphalan and prednisone. The treatment groups did not show significant differences with respect to major prognostic factors. With the 2-drug combination therapy and 5-drug combination therapy, 67 and 74% of the patients achieved remission, respectively. Moreover, no significant difference was found between the two treatment schedules in terms of median survival (30+ months). The survival curves for stage III patients treated with the two regimens did not differ significantly. After 12 months, patients who had achieved remission were randomized to have treatment discontinued or to have maintenance treatment. 7 of 15 patients on maintenance therapy relapsed, whereas 9 of 14 patients who had their therapy discontinued relapsed, and the survival of the two groups was similar.

Antineoplastic Combined Chemotherapy Protocols↗