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J Vaage

Publications and source records attributed to J Vaage.

At least 55 records · Page 3Linked to original sources
PubMed1998

Simultaneous antegrade and retrograde delivery of continuous warm blood cardioplegia after global ischemia.

OBJECTIVE: Simultaneous delivery of antegrade and retrograde cardioplegia may provide a more homogeneous distribution of cardioplegic solution. It may, however, increase myocardial edema and postcardioplegic myocardial injury. The purpose of this study was to compare simultaneous antegrade-retrograde cardioplegia with antegrade cardioplegia. METHODS: After 30 minutes of warm, "unprotected," global ischemia, pigs were given warm, continuous blood cardioplegia for 45 minutes (antegrade group, n = 8 and simultaneous antegrade-retrograde group, n = 9). All pigs were weaned from cardiopulmonary bypass 45 to 60 minutes after aortic unclamping. Indices of left ventricular function were measured after another 30 minutes with the conductance catheter technique and pressure-volume loops. RESULTS: Global left ventricular function, evaluated by preload recruitable stroke work, decreased from baseline values of 126 (102 to 150) (mean [90% confidence limits]) (antegrade) and 122 (116 to 127) erg/ml x 10(3) (simultaneous) to 75 (61 to 89) (p = 0.004) and 95 (79 to 112) erg/ml x 10(3) (p = 0.02), respectively. End-diastolic pressure-volume relation increased from 0.25 (0.21 to 0.28) (antegrade) and 0.30 (0.25 to 0.35) mm Hg/ml (simultaneous) to 0.60 (0.41 to 0.79) (p = 0.009) and 0.53 (0.35 to 0.71) mm Hg/ml (p = 0.02), respectively. The time constant of left ventricular pressure relaxation was unchanged. No intergroup difference was observed in preload recruitable stroke work, preload recruitable stroke work area, end-diastolic pressure volume relation, or stiffness constant. Plasma levels of troponin T increased without any difference between groups. Myocardial water content was increased in the simultaneous group (81.1% [80.7% to 81.5%]) versus the antegrade group (80.1% [79.6% to 80.7%], p = 0.01). CONCLUSION: Despite a small increase in myocardial water content induced by simultaneous blood cardioplegia, no impairment of postcardioplegic cardiac function was observed compared with antegrade cardioplegia.

Animals↗
PubMed1998

Measurements of plasma glutaredoxin and thioredoxin in healthy volunteers and during open-heart surgery.

Thioredoxin (Trx) and glutaredoxin (Grx) are both multifunctional redox-active proteins. In this study, Grx was identified in human plasma by immunoaffinity purification. The affinity-purified material from human plasma displayed a band of 12 kDa identical to recombinant human Grx by Western blotting and its glutathione-dependent reducing activity of beta-hydroxyethyl disulfide. Competitive enzyme-linked immunosorbent assays (ELISA) showed that plasma levels (mean +/- SD) of Grx and Trx in healthy volunteers (n = 41) were 456 +/- 284 ng/ml and 28.5 +/- 12.6 ng/ml, respectively. In cardiac surgical patients (n = 17), plasma Grx levels did not significantly change during cardiopulmonary bypass (CPB). In contrast, Trx levels in arterial plasma measured by sandwich ELISA and corrected for hemolysis were elevated during reperfusion of the postcardioplegic heart (p = .0001 at maximum), whereas by competitive ELISA Trx increased during surgical preparation for CPB, but decreased during CPB. When recombinant Trx was oxidized, immunoreactive Trx levels were decreased by competitive ELISA but not changed by sandwich ELISA. These results suggest that oxidized Trx is released into plasma during CPB. There was no significant difference in Trx and Grx levels between arterial and intracoronarial plasma samples, indicating no specific release by the post-cardioplegic heart. Trx and Grx may be important components in the plasma defense against oxidative stress.

Adult↗
PubMed1998

Effects of a novel, low-molecular weight inhibitor of lipid peroxidation on ischemia-reperfusion injury in isolated rat hearts and in cultured cardiomyocytes.

We investigated the effect of H290/51, a novel, low-molecular-weight inhibitor of lipid peroxidation, on cardiac ischemia-reperfusion injury. Lactate dehydrogenase (LD) release from cultured cardiomyocytes exposed to 1 h hypoxia and 4 h reoxygenation was measured after pretreatment with different concentrations of H290/51. In another series, Langendorff-perfused rat hearts were exposed to 30 min global ischemia and 60 min reperfusion (n=minimum 10 in each group): 1. Control ischemia-reperfusion. 2. Vehicle throughout the experiment. 3. Vehicle during stabilization, and H290/51 (10(-6) mol/l) during reperfusion. 4. H290/51 throughout the experiments. During reoxygenation of isolated cardiomyocytes, H290/51 dose dependently inhibited LD release with an pIC50 value of 7.2+/-0.4 (mean+/-SEM), with 10(-6) mol/l as the lowest efficient concentration. In isolated hearts ischemia-reperfusion induced severe reperfusion arrhythmias, reduced left ventricular developed pressure (LVDP) and coronary flow (CF), and increased LV end-diastolic pressure (LVEDP). LD activity in the effluent increased. H290/51 throughout perfusion (group 4) reduced the occurrence of severe reperfusion arrhythmias (p < .0001), attenuated the decrease of LVDP (p < .008), and CF (p < .006), the increase of LVEDP (p < .008), and the release of LD (p < .002). Tissue contents of thiobarbituric acid-reactive substances did not increase during reperfusion in controls, but was reduced in group 4 (p < .004). H290/51 given only during reperfusion (group 3) tended to improve cardiac function, but significantly so only for increase of CF (p < .01). The lipid peroxidation inhibitor H290/51 attenuated cardiac injury induced by ischemia-reperfusion.

Animals↗
PubMed1998

Preconditioning with hydrogen peroxide (H2O2) or ischemia in H2O2-induced cardiac dysfunction.

The possible cardioprotective effects of preconditioning by ischaemia (IPC) or a low dose of H2O2 (HPC) prior to a high dose of H2O2 was investigated. Langendorff-perfused rat hearts (n = 10 in each group) were subjected to 10 min of 140 micromol/L H2O2 and 30 min recovery after either (1) control perfusion, (2) 20 micromol/L H2O2 for 10 min, recovery 10 min, or (3) 2 x 2 min global ischaemia and 5 min reperfusion. 140 micromol/L H2O2 increased left ventricular end-diastolic pressure from 0 to 68+/-8 mmHg in controls (mean+/-SEM), which was attenuated by IPC (46+/-9 mmHg, p<0.001) and HPC (18+/-4 mmHg, p < 0.001 compared to controls, p < 0.01 compared to IPC). HPC, but not IPC, improved coronary flow (p < 0.02) and left ventricular developed pressure (p < 0.001) during recovery. Troponin T release was similar in all groups. Tissue thiobarbituric acid reactive substances, antioxidant capacity, catalase, and glutathione peroxidase were not influenced by 140 micromol/L H2O2. H2O2 decreased the level of tissue glutathione. This reduction was augmented by HPC (p <0.02) and attenuated by IPC (p < 0.02). H2O2 increased superoxide dismutase (p < 0.04). The increase was attenuated by IPC (p < 0.05), but not influenced by HPC. HPC efficiently protected cardiac function in H2O2-induced cardiac injury, while IPC had only a small protective effect. The functional protection cannot be explained by reduction of irreversible injury, attenuation of lipid peroxidation, or modification of tissue antioxidant parameters.

Animals↗
PubMed1997

Oxidative stress and release of tissue plasminogen activator in isolated rat hearts.

UNLABELLED: To evaluate the potential of tissue plasminogen activator (t-PA) as a marker of endothelial activation or injury, the dose-response relationship between reactive oxygen intermediates and t-PA release was investigated in isolated rat hearts. After stabilization the hearts were perfused for 10 minutes with different concentrations of hydrogen peroxide (H2O2) (0 (control perfusion), 20, 40, 80, 120, 160, or 200 microM) (n = 8 hearts/group), followed by 30 minutes recovery. Higher concentrations than 80 microM induced cardiac dysfunction and a dose-dependent release of lactate dehydrogenase, indicating myocyte injury. H2O2-concentrations of 80 microM and more caused a significant, but temporary t-PA release. Peak t-PA release occurred more rapidly with higher concentrations, but otherwise there was no difference dependent on the H2O2-dose. The effects of H2O2 (120 or 200 microM) on t-PA release were also compared to the effects of bradykinin. Both were given for 10 minutes as above, and the procedure was repeated after 10 minutes recovery. Bradykinin (50 or 500 nM) released t-PA with the same magnitude, but with peak values occurring earlier than t-PA release induced by H2O2. Bradykinin, but not H2O2, induced t-PA release during the second exposure, suggesting different mechanisms of release. IN CONCLUSION: Perfusion with H2O2 leads to a dose-dependent myocardial injury in isolated rat hearts. H2O2 also causes an acute t-PA release without dose-dependency, suggesting an all or nothing response of the endothelium. t-PA may be used as an indicator of, but cannot quantify endothelial activation or injury.

Animals↗
PubMed1997

Exogenous reactive oxygen species deplete the isolated rat heart of antioxidants.

The effects of reactive oxygen species (ROS) on myocardial antioxidants and on the activity of oxidative mitochondrial enzymes were investigated in the following groups of isolated, perfused rat hearts. I: After stabilization the hearts freeze clamped in liquid nitrogen (n = 7). II: Hearts frozen after stabilization and perfusion for 10 min with xanthine oxidase (XO) (25 U/l) and hypoxanthine (HX) (1 mM) as a ROS-producing system (n = 7). III: Like group II, but recovered for 30 min after perfusion with XO + HX (n = 9). IV: The hearts were perfused and freeze-clamped as in group III, but without XO + HX (n = 7). XO + HX reduced left ventricular developed pressure and coronary flow to approximately 50% of the baseline value. Myocardial content of hydrogen peroxide (H2O2) and malondialdehyde (MDA) increased at the end of XO + HX perfusion, indicating that generation of ROS and lipid peroxidation occurred. Levels of H2O2 and MDA normalized during recovery. Superoxide dismutase, reduced glutathione and alpha-tocopherol were all reduced after ROS-induced injury. ROS did not significantly influence the tissue content of coenzyme Q10 (neither total, oxidized, nor reduced), cytochrome c oxidase, and succinate cytochrome c reductase. The present findings indicate that the reduced contractile function was not correlated to reduced activity of the mitochondrial electron transport chain. ROS depleted the myocardium of antioxidants, leaving the heart more sensitive to the action of oxidative injury.

Animals↗
PubMed1997

Ventilation by external high-frequency oscillations improves cardiac function after coronary artery bypass grafting.

OBJECTIVE: To compare the effects of ventilation with intermittent positive pressure and external high frequency oscillation by the Hayek Oscillator during the first 5 h after coronary artery bypass grafting. METHODS: Eleven patients were randomized to intermittent positive pressure ventilation throughout the observation period (5 h), while 13 patients were initially ventilated with intermittent positive pressure ventilation, then by external high-frequency oscillations for 4 h, changing to positive pressure ventilation for the last hour. RESULTS: Cardiac index, stroke volume index, right ventricular stroke work index, right ventricular end-diastolic volume index and mixed venous oxygen saturation were significantly increased during ventilation with external high-frequency oscillations, and arteriovenous oxygen content difference was significantly reduced. There were no significant inter- or intragroup differences in fluid accumulation, mean arterial blood pressure, arterial blood gases, pulmonary artery pressure, central venous pressure, pulmonary capillary wedge pressure, heart rate, systemic vascular resistance index, pulmonary vascular resistance index, intrapulmonary shunt fraction, right ventricular ejection fraction, right ventricular end-systolic volume index and left ventricular stroke work index. CONCLUSIONS: Ventilation by external high-frequency oscillations increases cardiac index and improves tissue perfusion. The increased pumping of the heart is probably caused by changes of the intracardiac pressure-volume relationship. The Hayek Oscillator may have distinct cardiovascular benefits as ventilatory assistance in postoperative cardiac surgical patients.

Aged↗
PubMed1997

Tumour uptake of doxorubicin in polyethylene glycol-coated liposomes and therapeutic effect against a xenografted human pancreatic carcinoma.

This study tested the therapeutic efficacy of doxorubicin hydrochloride in two formulations: free in saline suspension and encapsulated in polyethylene glycol-coated, long-circulating liposomes. The drug formulations at a dose level of 3 mg doxorubicin per kg body weight were injected intravenously to treat the human pancreatic carcinoma AsPC-1, implanted s.c. into nude Swiss mice. Liposome-encapsulated doxorubicin was significantly more effective in inhibiting tumour growth and in effecting cures, and had only minor systemic toxic side-effects, indicated by a transient weight loss. Confocal laser scanning microscopy was used to determine the tumour uptake and the clearance of doxorubicin in the free and in the liposomal forms. The liposome-encapsulated doxorubicin entered the tumour in greater quantity, and remained in the tumour longer, than the free drug. The liposome formulation produced a sixfold or greater increase in doxorubicin at the disease site. It is probable that increased penetration into the tumour, and long presence with slow drug release from liposomes in the tumour, account for the enhanced therapeutic effect when the drug was encapsulated in polyethylene glycol-coated liposomes.

Adenocarcinoma↗
PubMed1997

Can reactive oxygen species precondition the isolated rat heart against arrhythmias and stunning?

Ischaemic preconditioning has cardioprotective effects. Reactive oxygen species may be possible mediators. The present study investigated whether low doses of exogenous hydrogen peroxide could mimic preconditioning in isolated, Langendorff-perfused rat hearts. Hearts were subjected to two episodes of 3 min global ischaemia and 5 min reperfusion (n = 17), or were given 10 (n = 15), 20 (n = 10), 30 (n = 20), 40 (n = 18), 80 (n = 17) or 160 microM (n = 10) hydrogen peroxide for 10 min, followed by 10 min recovery, before 25 min global ischaemia and 60 min reperfusion, and compared with ischaemic controls of matching perfusion time (n = 17 and n = 23). Cardiac performance was assessed by heart rate, left ventricular systolic, end-diastolic and developed pressures, and coronary flow. Severe reperfusion arrhythmias occurred frequently in control hearts, and was attenuated by ischaemic preconditioning. All hearts pretreated with 160 microM hydrogen peroxide had severe arrhythmias throughout reperfusion, while these were not seen in any heart perfused with 20 microM hydrogen peroxide (P < 0.01 compared to controls). Ischaemia and reperfusion induced a minor decrease in heart rate, left ventricular systolic and developed pressures, and increased end-diastolic pressure. Ischaemic preconditioning attenuated the decrease of heart rate and the increase of end-diastolic pressure, and increased coronary flow, while hydrogen peroxide did not significantly attenuate these changes. In conclusion, a low dose of exogenous hydrogen peroxide before global ischaemia inhibited severe reperfusion arrhythmias, but had no other protective effects. The present work does not suggest that reactive oxygen species are important mediators of the preconditioning effects on stunning and arrhythmias in the rat heart.

Animals↗
PubMed1997

Preconditioning the globally ischaemic, isolated rat heart: the impact of the preconditioning model on post-ischaemic systolic and diastolic function.

In studies of preconditioning, a variety of models have been used. The aim of the present study was to find the optimal preconditioning model for preservation of cardiac function during reperfusion of globally ischaemic, Langendorff-perfused rat hearts. Cardiac function was assessed by the occurrence of severe reperfusion arrhythmias (ventricular fibrillation or asystolia), heart rate (HR), left ventricular systolic (LVSP), end diastolic (LVEDP), and developed pressures (LVDP = LVSP - LVEDP), as well as coronary flow (CF). Series 1 (n = 17) in each group: control perfusion for 20 min without preconditioning or 2 episodes of 2, 3, 4, or 5 min of ischaemia, each followed by 5 min reperfusion, before 25 min ischaemia and 60 min reperfusion. Preconditioning reduced the incidence of reperfusion arrhythmias, attenuated the reperfusion-induced increase of LVEDP, and increased CF, but did not influence LVSP, LVDP, or rate x pressure-product (RPP = LVSP x HR) during reperfusion. The greatest effect was found by 2 min ischaemia and 5 min reperfusion. In series 2 (n = 17 in each group) control perfusion for 7 or 28 min, or preconditioning with 1-4 episodes of 2 min ischaemia and 5 min reperfusion before 35 min ischaemia and 60 min reperfusion were compared. Reduction of severe reperfusion arrhythmias and LVEDP elevation, as well as improvement of CF, LVDP, and HR in preconditioned hearts were observed in series 2. Optimal cardioprotection was achieved by only one episode of preconditioning. In conclusion, preconditioning before global ischaemia improved cardiac function during reperfusion of isolated rat hearts. The most marked effects were reduction of severe reperfusion arrhythmias and attenuation of diastolic dysfunction. Although all preconditioning models employed were cardioprotective, 1 episode of 2 min ischaemia provided optimal protection.

Animals↗
PubMed1997

Release of creatine kinase, troponin-T, and tissue plasminogen activator in arterial and coronary venous blood during coronary artery bypass surgery.

Tissue plasminogen activator (t-PA) as a possible marker of endothelial injury during elective coronary artery bypass surgery was studied. T-PA antigen and activity were measured in arterial and coronary venous plasma in 14 patients, and compared to the markers of myocyte injury creatine kinase (CK-MB) and troponin-T (TnT). Cardiopulmonary bypass (CPB) lasted 86 (55-107) min, and aortic cross-clamping (cold, crystalloid cardioplegia) lasted 41 (25-62) min (median (central 90% percentile)). Blood flow in the great cardiac vein was measured by retrograde thermodilution, and increased from 49 (27-90) ml/min before CPB to a maximum of 92 (55-125) ml/min 40 min after declamping (not significant). CK-MB, TnT, and t-PA antigen and activity all increased during CPB, and were significantly higher in coronary sinus than arterial plasma after declamping the aorta. Net cardiac release ([coronary sinus-arterial concentration] x coronary flow) of TnT increased after the aorta was declamped, and was higher in the seven patients with the longest cross-clamping time than in the seven with the shortest time (p < 0.01). Cardiac release of CK-MB and t-PA antigen also increased after declamping, but with no significant difference between long and short cross-clamp times. t-PA activity, however, increased more in the patients with the longest cross-clamp times (p < 0.008). In conclusion, CK-MB, TnT and t-PA were released from the postcardioplegic heart. Release of t-PA indicates that postcardioplegic coronary endothelial activation or injury occurred t-PA activity as well as TnT increased more in patients with long times of cross-clamping, indicating that t-PA activity may be a possible marker of postcardioplegic endothelial injury or activation.

Aged↗
PubMed1997

Release of markers of myocardial and endothelial injury following cold cardioplegic arrest in pigs.

Cold cardioplegic arrest causes reperfusion injury to both endothelium and myocardium. We investigated release of troponin-T (TnT), tissue plasminogen activator activity (t-PA) and histamine (HA) from the heart before and after 2h of cold crystalloid cardioplegia in eight Swedish landrace pigs. Coronary sinus blood flow was measured in an external shunt between the coronary sinus and the right atrium. TnT, t-PA and HA were measured concomitantly in arterial and coronary sinus plasma, and the cardiac release was calculated. Cardiac release of TnT increased from 18 (15-25) micrograms/min (median (central 90% percentile)) before cold cardioplegia to maximum 281 (132-510) micrograms/min 30 min after aortic declamping (p < 0.02 vs initial value). t-PA rose from -4 (-52-34) to maximum 249 (75-691) IU/min 2 min after declamping (p < 0.01) and thereafter returned to baseline levels. The net cardiac release of HA was 72 (-80-1321) nmol/min before cardioplegia, rising to 234 (-188-524) after 2 min of reperfusion (p < 0.02) and returning to baseline after 30 minutes. We conclude that the porcine heart releases t-PA, Tn-T and HA during postcardioplegic reperfusion. The differing kinetics of their release may indicate different affection of the myocardium and the endothelium. Tn-T, t-PA and HA are potential markers of myocardial and endothelial injury in the porcine heart.

Animals↗
PubMed1996

Systemic release of thrombomodulin, but not from the cardioplegic, reperfused heart during open heart surgery.

Thrombomodulin is a potential marker of endothelial injury. Plasma thrombomodulin was measured in concomitant arterial and coronary sinus samples in 9 patients undergoing elective coronary artery bypass surgery with cardiopulmonary bypass (CPB, 88 +/- 14 min) (mean +/- SD) and cold, crystalloid, antegrade cardioplegia (44 +/- 14 min). Arterial thrombomodulin was 17 +/- 6 ng/ml before surgery, and decreased to 10 +/- 5 ng/ml after heparinization (p < 0.008 compared to initial value). During CPB thrombomodulin increased, with a maximal level of 23 +/- 7 ng/ml (p < 0.008 vs initial value) 40 min after aortic declamping. No difference between arterial and coronary sinus concentrations was detected during reperfusion of the heart. In conclusion, plasma thrombomodulin is decreased by heparin, and increased during CPB. Consequently, thrombomodulin may be used to evaluate endothelial injury during CPB. However, as there is no specific intracoronary release of thrombomodulin during reperfusion, thrombomodulin is not a suitable marker of coronary endothelial injury after cardioplegia.

Aged↗
PubMed1996

Release of tissue plasminogen activator during reperfusion after different times of ischaemia in isolated, perfused rat hearts.

Tissue plasminogen activator (t-PA) is a potential marker of endothelial cell activation or injury. The relationship between duration of ischaemia and release of t-PA during reperfusion was investigated in isolated rat hearts exposed to either 5, 10, 20, 30, 40, or 60 min of global, normothermic ischaemia followed by 30 min of reperfusion (n = 8 in each group). t-PA activity was measured (chromogenic peptide substrate assay) in the effluent before ischaemia, and after 2.5, 5, 7.5, 10, 20, and 30 min of reperfusion. Release of lactate dehydrogenase (LD), a marker of myocyte injury, was measured before ischaemia and after 5 min reperfusion. Left ventricular pressures were measured by a balloon in the left ventricle. Ischaemia for 20 min or less had only minor effects on cardiac function. Thirty min or more of ischaemia induced ventricular fibrillation during reperfusion in most hearts. After ischaemia t-PA outflow increased, but without any significant difference between groups. Peak release occurred after either 2.5 or 5 min of reperfusion. After 10 min reperfusion the release was not different from the basal value. In contrast, postischaemic release of LD correlated to the length of ischaemia. To conclude, t-PA release from the ischaemic-reperfused rat heart is independent of the length of ischaemia. Thus the potential of t-PA to quantify endothelial injury appears to be limited.

Animals↗
PubMed1996

The role of nitric oxide in the cardiac effects of hydrogen peroxide.

Oxidative stress mediated by hydrogen peroxide (H2O2) increases coronary flow (CF) in Langendorff-perfused rat hearts. We investigated the possible role of nitric oxide (NO) in H2O2-induced vasodilation. A dose-response study was conducted to find a concentration of H2O2 which increased CF without influencing left ventricular developed (LVDP) or end-diastolic (LVEDP) pressures. 80(n = 10), 100 (n = 7), 120 (n = 7), 140 (n = 7), 160 (n = 7), and 180 (n = 10) microM H2O2 was infused for 10 min, followed by recovery for 50 min. 80 microM H2O2 increased CF to a maximum of 143 +/- 4 (mean +/- S.E.M) percent of initial value after 15 min observation (p < 0.001 compared to buffer only), with no effect on LVDP or LVEDP. Another series of hearts were perfused with N-nitro-L-Arginine methylester (L-NAME, 1 mM), methylene blue (MB, 50 microM), or haemoglobin (Hb, 10 microM), without (n = 7 in each) or with (n = 10 in each) 80 microM H2O2 for 10 min. L-NAME, MB, and Hb alone increased CF, but attenuated the H2O2-induced increase of CF.LVDP was depressed when L-NAME, MB or Hb were given in conjunction with 80 microM H2O2. In summary, H2O2 concentration-dependently increased LVEDP and depressed LVDP. The H2O2-induced increase of CF was independent of concentration. Inhibition of NO synthesis, action, or soluble guanylate cyclase attenuated the H2O2-induced increase of CF, and depressed LVDP when given together with H2O2. H2O2 induces a NO-dependent vasodilation, and inhibition of NO is detrimental to left ventricular function after H2O2-mediated oxidative stress.

Animals↗
PubMed1996

Cardiac injury by activated leukocytes: effect of cyclooxygenase and lipoxygenase inhibition evaluated by electron microscopical morphometry.

Leukocytes can take part in an inflammatory response in the heart after myocardial infarction or cardio-thoracic surgery. To investigate the injurious mechanism of activated polymorphonuclear leukocytes (PMN), isolated rat hearts were perfused with phorbol 12-myristate 13-acetate (PMA) activated PMN (3 x 10(6)/ml) alone for 10 min, in combination with a mixture of oxygen free radical scavengers (superoxide dismutase+catalase+thiourea) or in combination with ibuprofen (IBU), a cyclooxygenase inhibitor or diethylcarbamazine (DCM), a lipoxygenase inhibitor or BW 755C, a dual inhibitor of cyclooxygenase and lipoxygenase and an oxygen free radical scavenger. After 30 min of recovery, the hearts were perfusion-fixed with glutaraldehyde for electron microscopical examination. Based on examination of 25 micrographs per heart obtained by a random sampling procedure and on morphometric methods, volume fractions (Vv) of mitochondria (mito), altered mitochondria (alt mito), myofilament, and cellular edema were measured as fractions of myocyte volume. The most important finding was that Vv(alt mito/myocyte) was 0.09 +/- 0.16 and 0.02 +/- 0.04 in the hearts receiving PMN+PMA alone and when scavengers were added, respectively, whilst no changes in mitochondrial ultrastructure was observed after addition of IBU, BW 755C or DCM. Vv(mito/myocyte) was for PMN+PMA alone: 0.33 +/- 0.04, +scavengers: 0.29 +/- 0.02 +IBU:0.29 +/- 0.02, +BW 755C: 0.23 +/- 0.03*, +DCM: 0.28 +/- 0.02 (mean +/- S.D., *P < 0.05 compared to PMN+PMA). Capillary wall volume (cap wall) as a fraction of the whole capillary was also quantified. Vv(cap wall/cap) was for PMN+PMA alone: 0.26 +/- 0.06, +scavengers: 0.22 +/- 0.03, +IBU: 0.19 +/- 0.04*, +BW755C: 0.21 +/- 0.03, +DCM: 0.15 +/- 0.04* (*P < 0.05). These results further strengthen the notion that activated PMN are intravascularly active. In addition to exerting a cardiodepressive effect the present study shows that activated PMN can induce structural changes in the heart through the combined action of oxygen free radicals and arachidonic acid metabolites.

Animals↗
PubMed1996

Activity of histamine metabolizing and catabolizing enzymes during reperfusion of isolated, globally ischemic rat hearts.

Myocardial ischemia-reperfusion injury increases both tissue levels and release of histamine. To study the possible effects of ischemia-reperfusion on histamine metabolism tissue activities of histidine decarboxylase (HDC), histamine N-methyl transferase (HNMT) and diamine oxidase (DAO) were investigated in isolated rat hearts subjected to either 20 min global ischemia and 40 min reperfusion (n = 10) or control perfusion (n = 8). Histamine in the coronary effluent increased from 21 +/- 4 nmol/min (mean +/- SEM) before ischemia to 55 +/- 5 and 50 +/- 7 nmol/min after 4 and 10 min reperfusion (p < 0.004 and p < 0.004). Tissue HDC activity did not change during observation in any group. HNMT activity was unchanged in controls, but increased from 0.37 +/- 0.04 to 0.84 +/- 0.18 and 0.96 +/- 0.22 pmol methylhistamine/mg protein hour after 4 and 10 min reperfusion (p < 0.008 and p < 0.01). DAO decreased similarly in controls and ischemic-reperfused hearts during observation. In conclusion, the previously observed increase of tissue histamine during reperfusion cannot be explained by increased histamine synthesis or decreased histamine catabolism.

Amine Oxidase (Copper-Containing)↗