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G Valen

Publications and source records attributed to G Valen.

At least 55 records · Page 3Linked to original sources
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

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)↗
PubMed1996

Preconditioning improves cardiac function after global ischemia, but not after cold cardioplegia.

BACKGROUND: Ischemic preconditioning reduces infarct size and cardiac dysfunction during reperfusion. Preconditioning may offer myocardial protection in open heart operations. METHODS: The effect of preconditioning before ischemia and cardioplegia was investigated in Langendorff-perfused rat hearts in the following groups. First, group 1 received two episodes of 3-minute ischemia and 5-minute reperfusion before 25 minutes of global (37 degrees C) ischemia and 60 minutes of reperfusion. Group 2 served as ischemic controls to group 1. Groups 3, 5, and 7 were preconditioned as described, before 3.5, 4, or 5 hours of cold (6 degrees to 8 degrees C) St. Thomas' II cardioplegia and 1 hour of reperfusion (37 degrees C). Groups 4, 6, and 8 were cardioplegic controls to groups 3, 5, and 7 (n = 17 in groups 1 and 2, and n = 10 in groups 3 to 8). RESULTS: Preconditioning before warm ischemia attenuated the ischemia-induced increase of left ventricular end-diastolic pressure (3 +/- 1 versus 17 +/- 4 mm Hg; p < 0.01) (mean +/- standard error of the mean), the reduction of coronary flow (14 +/- 1 versus 9 +/- 0.5 mL/min; p < 0.001) and heart rate (252 +/- 19 versus 198 +/- 18 beats/min; p < 0.04), and the incidence of ventricular fibrillation (2 of 17 versus 10 of 17 hearts; p < 0.04) at the start of reperfusion. However, preconditioning did not influence postischemic cardiac function or the release of lactate dehydrogenase in any of the cardioplegia groups. CONCLUSIONS: Ischemic preconditioning improved post-ischemic cardiac function after warm global ischemia, but did not protect cold cardioplegic hearts, perhaps because of the time span used.

Animals↗
PubMed1996

Effects of a novel low-molecular weight antioxidant on cardiac injury induced by hydrogen peroxide.

H290/51, an indenoindole derivative, is a novel low-molecular weight (287.8) inhibitor of lipid peroxidation. Its effect on cardiac injury induced by exogenous reactive oxygen intermediates (ROI) was investigated. ROI were generated by adding H2O2 (180 mu M) to the perfusate of isolated rat hearts (Langendorff model, n = 9) for 10 min. H2O2 reduced left ventricular developed pressure (LVDP = left ventricular systolic pressure -- left ventricular end-diastolic pressure) from 90 +/- 6 to a minimum of 25 +/- 2 mmHg (mean +/- SEM) after 10 min (p < 0.001), elevated left ventricular end-diastolic pressure (LVEDP) from 0 to 32 +/- 7 mmHg after 20 min (p < 0.0001), and increased coronary flow (CF). Lactate dehydrogenase (LDH) release in the coronary effluent and thiobarbituric acid-reactive substances (TBARS) in cardiac tissue increased (TBARS from 0.6 +/- 0.04 to 3.1 +/- 0.4 nmol/g tissue after 10 min of H2O2 administration, p < 0.001). Addition of H290/51 (1 mu M, n = 12) from the start of H2O2 exposure, attenuated the H2O2-induced increase of LVEDP (9 +/- 3 mmHg at 20 min, p < 0.006) and reduced the release of LDH (p < 0.02 at 30 min). LVDP was not significantly influenced. The increase of TBARS was abolished by H290/51 (p < 0.001). In conclusion, H290/51 inhibited lipid peroxidation, and attenuated functional and biochemical injury induced by H2O2 exposure.

Animals↗
PubMed1996

Perfusing isolated rat hearts with hydrogen peroxide: an experimental model of cardiac dysfunction caused by reactive oxygen species.

A model of cardiac dysfunction induced by reactive oxygen species (ROS) was established by adding hydrogen peroxide (H2O2) to the perfusate of isolated, Langendorff-perfused rat hearts, and the mechanism of functional injury was investigated. The following groups were included: 1 (n = 7), control perfusion; 2 (n = 11), perfusion with H2O2 (180 mumol 1(-1) for 10 min followed by recovery for 50 min; 3 (n = 4), control perfusion with N-acetylcysteine (NAC, 100 mumol 1(-1); 4 (n = 7), perfusion with H2O2 and NAC; 5 (n = 4), control perfusion with thiourea (15 mmol 1(-1), 6 (n = 7), H2O2 and thiourea together; 7 (n = 4), control perfusion with catalase (150 U ml-1); 8 (n = 7), catalase and H2O2, 9 (n = 4), control perfusion with deferoxamine (5 mmol 1(-1); and 10 (n = 7), deferoxamine and H2O2. coronary flow (CF), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and heart rate (HR) were measured. All values are mean +/- SEM. When given alone, catalase, thiourea, NAC and deferoxamine did not influence left ventricular pressures, but NAC, catalase and thiourea increased CF. H2O2 increased CF (maximum 146 +/- 6% of baseline value after 5 min, p < 0.001 compared to group 1), decreased LVDP (minimum 14 +/- 5% of baseline value after 10 min, p < 0.0004), and increased LVEDP (from 0 mmHg to a maximum of 54 +/- 7 mmHg after 5 min recovery, p < 0.0003). All these changes gradually reversed during recovery. Catalase and thiourea both inhibited the H2O2-induced effects, but catalase inhibition was more complete. Neither NAC nor deferoxamine had any effect on H2O2-induced cardiac dysfunction. In conclusion, H2O2 perfusion is a convenient and reversible model of ROS-induced functional injury to isolated rat hearts. H2O2, rather than the hydroxyl radical, seems to be the main injurious ROS in this model.

Animals↗
PubMed1996

The effect of exogenous adenosine on functional injury caused by hydrogen peroxide in the isolated rat heart.

Adenosine is an endogenous cardioprotective substance. The present study examines whether exogenous adenosine attenuates cardiac injury induced by oxidative stress. Rat hearts (Langendorff model) were perfused with H2O2 (180 microM) for 10 min, then recovered for 60 min (n = 10). In other groups adenosine 55 microM, 11 0 microM, or 220 microM (n = 10 in each) was given in addition to H2O2 throughout perfusion. Control perfusion with Krebs Henseleit only (n = 7), adenosine 110 microM throughout perfusion (n = 7), and adenosine 110 microM as an intervention (n = 7) was performed. The hearts were paced at 320 beats/min. Left ventricular systolic (LVSP) and end-diastolic (LVEDP) pressures were measured together with coronary flow (CF), and left ventricular developed pressure (LVDP = LVSP - LVEDP) was calculated. H2O2 decreased LVSP from 105 +/- 8 to 60 +/- 5 mmHg (mean +/- SEM) after 10 min infusion (p < 0.008). Adenosine did not attenuate the decrease of LVSP. LVEDP increased from 0 to 59 +/- 10 mmHg (p < 0.004) and 62 +/- 11 mmHg 5 and 15 min after end of infusion of H2O2, respectively. Neither 55 microM nor 220 microM adenosine inhibited the H2O2-induced increase of LVEDP. Adenosine 110 microM attenuated the increase after 15 (15 +/- 4 mmHg, p < 0.004) and 25 min observation (26 +/- 7 mmHg, p < 0.012). Adenosine did not attenuate the reduction of LVDP. CF initially increased during infusion of H2O2, thereafter decreased. Hearts given adenosine had higher basal CF, and CF did not increase after H2O2. Control perfusion with adenosine, given throughout perfusion or as an intervention, increased CF and tended to increase LVSP. In summary, adenosine did not inhibit H2O2-induced depression of contractility or reduction of CF. One concentration of adenosine (110 microM) attenuated H2O2-induced impairment of relaxation. Exogenous adenosine does not have an important influence on functional injury caused by exogenous oxidants.

Adenosine↗
PubMed1995

The effects of exogenous histamine in isolated rat hearts.

The role of histamine in cardiac physiology and pathophysiology is not clarified, but is dependent on species. The effects of exogenous histamine in Langendorff-perfused rat hearts were investigated. 1 mM, 100, 10, 1 and 0.1 microM of histamine (n = 7 each) as 15 min infusions were employed in a dose-response study, and compared to control perfused hearts (n = 7). In another experimental series, 100 microM histamine (n = 15) was added during reperfusion after 25 min global ischemia, and compared to control ischemia-reperfusion (n = 15). The maximal response to histamine in the dose-response study (100 microM) was an increase of left ventricular developed pressure to 126 +/- 8% of initial value (mean +/- SEM, p < 0.04), and increase of coronary flow to 152+6% (p < 0.02) after 5 min infusion. 100 microM histamine did not significantly influence heart rate or rhythm. The lowest concentration (0.1 microM) did not have effects cardiac performance. Reperfusion with histamine for 2 min after ischemia reduced left ventricular developed pressure to 68 +/- 10% of initial value versus 116+17% in ischemic controls (p < 0.05), and increased left ventricular end-diastolic pressure to 24 +/- 8 mmHg compared to 6 +/- 2 mmHg in controls (p < 0.04). Left ventricular pressures were similar in hearts reperfused with histamine and in ischemic controls for the rest of the observation. Coronary flow increased during reperfusion in hearts given histamine. Histamine had a dose-dependent positive inotropic and vasodilatory effect in isolated rat hearts. Exogenous histamine had only minor effects on post-ischemic cardiac function.

Animals↗
PubMed1995

Cardiac release of histamine after ventricular fibrillation and defibrillation during insertion of implantable cardioverter defibrillators (ICD).

Histamine has inotropic, chronotropic, arrhythmogenic, and vasoactive effects, and is released from the heart in ischaemia-reperfusion injury. The effect of ventricular fibrillation (VF) and defibrillation (DEF) on histamine release was investigated in 9 anaesthetized patients undergoing transvenous implantation of ICD. Concomitant arterial and coronary sinus (CS) blood samples were drawn before induction of VF (duration 20 seconds), immediately after, and 2 and 5 min after DEF (18-24 Joules). Basal arterial histamine was 2.5 +/- 6 nmol/l, and did not increase after VF. The histamine level in CS was 1.1 +/- 0.2 nmol/l before VF (p < 0.008 compared to arterial), and increased to 2.5 +/- 0.6 nmol/l immediately after (p < 0.045 compared to basal), to 3 +/- 1.1 nmol/l 2 min after (p < 0.45), and to 2.4 +/- 0.8 nmol/l 5 min after VF. In the basal state there was an uptake of histamine across the coronary circulation. After VF/DEF the level of histamine increased in coronary venous blood, suggesting cardiac release of histamine.

Aged↗
PubMed1994

Release of von Willebrand factor by cardiopulmonary bypass, but not by cardioplegia in open heart surgery.

von Willebrand Factor (vWF) is released from endothelial cells. Increased vWF in the coronary circulation during cardiac surgery could be a potential indicator of coronary endothelial injury or stimulation, and thus a possible tool to evaluate regimens of myocardial protection. Release of vWF was investigated in 12 patients undergoing coronary artery bypass surgery with cardiopulmonary bypass (CPB). Concomitant samples of arterial and coronary sinus blood for measurement of vWF (antigen method) were drawn before start of CPB and 1, 4, 10 and 30 min after release of the aortic cross clamp. Additional arterial samples were drawn pre-, per-, and postoperatively. Preoperative arterial vWF was 1.58 +/- 0.59 IU/ml (mean +/- SD), and increased during CPB (highest level 2.37 +/- 0.76 IU/ml, p < 0.0026). No difference between arterial and coronary sinus vWF levels was found. Arterial vWF increased further the first postoperative day (3.96 +/- 0.92 IU/ml, p < 0.0026). In conclusion, systemic vWF is increased during CPB, and may be a possible marker of endothelial injury/activation to evaluate deleterious effects of different equipment for CPB. Reperfusion of the ischaemic, cardioplegic heart did not release vWF in the coronary circulation.

Aged↗
PubMed1994

Open heart surgery increases the levels of histamine in arterial and coronary sinus blood.

The possible release of histamine into the coronary circulation during reperfusion of the cold, cardioplegic heart was investigated during open heart surgery in 13 patients (cardioplegic arrest 54 (35-120 min) (median (range)), cardiopulmonary bypass (CPB) 96 (65-360) min. Samples were drawn concomitantly from coronary sinus and arterial blood before cardioplegia and during myocardial reperfusion for measurement of histamine (radioenzymatic method). Additional arterial samples were drawn pre-, per- and postoperatively. CPB induced a sustained increase in arterial histamine (from 4.02 +/- 2.71 nmol/l preoperatively (mean +/- SD) to maximum 16.31 +/- 7.12 nmol/l, p < 0.009). Immediately before cardioplegia histamine levels were higher in arterial than coronary sinus blood (9.24 +/- 4.85 versus 4.04 +/- 2.07 nmol/l, p < 0.002). During myocardial reperfusion coronary sinus histamine increased to levels similar to that of arterial blood. In conclusion, histamine is released during CPB. Before cardioplegic arrest, there is a net uptake of histamine by the heart, which is abolished during reperfusion, possibly due to increased cardiac release of histamine.

Aged↗
PubMed1994

Fibrinolysis during cardiac surgery. Release of tissue plasminogen activator in arterial and coronary sinus blood.

Endothelial release of tissue plasminogen activator (t-PA) may initiate fibrinolysis. Fibrinolysis and coagulation were investigated in 12 patients undergoing elective coronary artery bypass surgery. Cardiopulmonary bypass (CPB) was 108 +/- 7 min (mean +/- SEM), the time of cold, crystalloid, retrograde cardioplegia 53 +/- 5 min. Arterial and coronary sinus blood were sampled concomitantly before cardioplegia and after release of the aortic cross-clamp, for measurement of t-PA antigen (Ag) and activity, plasminogen activator inhibitor (PAI-1) Ag and activity, t-PA/PAI-1 complex, single chain urokinase (sc-uPA) and urokinase (uPA) plasminogen activators, the fibrin split product D-dimer, thrombin-antithrombin complex (TAT), and the prothrombin split product F 1 + 2. Cardiopulmonary bypass significantly increased t-PA Ag and activity, t-PA/PAI complex, D-dimer, TAT, and F 1 + 2, and decreased PAI-1 Ag and activity in arterial blood; uPA and sc-uPA were unchanged. The tissue plasminogen activator antigen was higher in coronary sinus than arterial blood after 1 (39 +/- 5 vs 24 +/- 4 ng/ml, P < 0.003), 4 (P < 0.003), and 10 min (P < 0.004) reperfusion. Tissue plasminogen activator activity and t-PA/PAI complex increased, PAI-1 activity decreased, while all other parameters were unchanged across the coronary circulation. In conclusion, CPB induces fibrinolysis and coagulation. Cold cardioplegia induces t-PA release in the coronary circulation, denoting a postischemic antithrombotic function of the coronary endothelium. Tissue plasminogen activator may be used to evaluate endothelial stimulation or injury induced by CPB, or by different regimens of myocardial protection.

Aged↗
PubMed1994

Histamine release and its effects in ischaemia-reperfusion injury of the isolated rat heart.

Histamine is released from the heart during ischaemia-reperfusion injury. As histamine has cardiac effects, we investigated the role of histamine in ischaemia-reperfusion injury of isolated rat hearts. A Langendorff-model with 30 min global (37 degrees C) ischaemia followed by 60 min reperfusion was employed. The effects of ischaemia alone (n = 10, group 1.1 + n = 10, group 2.1, 2 different series), and ischaemia with H1- and H2-receptor blockade with cimetidine (10 microM, n = 10), chlorpheniramine (10 microM, n = 8), terfenadine (10 microM, n = 8), and promethazin (10 microM, n = 9), or both cimetidine and chlorpheniramine (n = 8), were studied. Histamine was measured in the coronary effluent and cardiac tissue of group 1.1. Release of histamine increased from 6.5 +/- 1 pmol min-1 before ischaemia to 19 +/- 3 pmol min-1 at the start of reperfusion. Ischaemia decreased left ventricular developed pressure to 18 +/- 11% (1.1) and 50 +/- 11% (2.1) of initial value (mean +/- SEM) at the start of reperfusion. Left ventricular end-diastolic pressure increased from 0 to 79 +/- 8 mmHg (1.1) and 39 +/- 9 (2.1) mmHg, while left ventricular systolic pressure was unchanged (101 +/- 12% in 1.1 and 101 +/- 10% in 2.1). Severe arrhythmias were induced in 90 (1.1) and 30 (2.1)% of the hearts, while coronary flow decreased during reperfusion. H2-blockade did not modify the changes in left ventricular pressures, coronary flow, or heart rate induced by ischaemia. Three different H1-blockers increased left ventricular systolic pressure, inhibited the decrease of developed pressure, attenuated the increase of end-diastolic pressure, and totally inhibited reperfusion arrhythmias. The effect of both blockers together was similar to that of H1-blockers alone. Coronary flow was increased during reperfusion in two of the groups with H1-blocker compared with ischaemic controls. Increased release of histamine from ischaemic-reperfused rat hearts concurred with depression of left ventricular function and arrhythmias during early reperfusion. Cardiac dysfunction during reperfusion was attenuated by three different H1-receptor blockers.

Animals↗
PubMed1993

Reactive oxygen intermediates and ischemia-reperfusion injury release tissue plasminogen activator from isolated rat hearts.

Tissue plasminogen activator (t-PA) is a marker of endothelial cell injury or activation. The release of t-PA from isolated rat hearts (Langendorff model) subjected to ischemia-reperfusion or reactive oxygen intermediates (ROI) generated by H2O2 was investigated. H2O2 (200 microM) increased t-PA activity in the coronary effluent to 305 +/- 84% of initial value (mean +/- SEM, p < 0.04 vs controls) at the end of a 10 min intervention. The hydroxyl radical scavenger thiourea (10 mM) only partially inhibited the increase (175 +/- 27%, p < 0.01 compared to controls). 20 min normothermic ischemia increased t-PA activity to 416 +/- 108% (p < 0.005 compared to controls) at the start of reperfusion. In conclusion, cardiac injury by ischemia-reperfusion or ROI increases release of t-PA.

Animals↗
PubMed1993

Toxic oxygen metabolites and ischemia-reperfusion increase histamine synthesis and release in the isolated rat heart.

Histamine is synthetized in the heart, and released by ischemia-reperfusion injury in several species. Histamine has arrhythmogenic, chronotropic, inotropic and vasoactive effects. Cardiac histamine release during ischemia-reperfusion may be mediated by toxic oxygen metabolites. We studied the effect of ischemia-reperfusion and toxic oxygen metabolites on release and synthesis of histamine in the isolated rat heart (Langendorff model). The following groups were included: I, (n = 10) control perfusion for 60 min; II, (n = 7) H2O2 (200 microM) was given for 10 min followed by 50 min recovery; III, (n = 7) thiourea (15 mM) was given in addition to H2O2; IV, (n = 7) thiourea given alone; V, (n = 7) catalase (150 U/ml) plus H2O2; VI, (n = 7) 20 min ischemia followed by 40 min reperfusion. The contents of histamine in the coronary effluent and in cardiac tissue were measured repeatedly (radioenzymatic method). Ischemia-reperfusion and toxic oxygen metabolites increased release of histamine in the coronary effluent. Concomitantly the histamine contents in cardiac tissue increased, indicating increased synthesis of histamine.

Animals↗
PubMed1993

Release of histamine from isolated rat hearts during reperfusion is not dependent on length of ischemic insult, or contents of histamine in cardiac tissue.

Release of histamine (H) by ischemia-reperfusion injury was investigated in isolated rat hearts (Langendorff model). The effect of 10, 15, 20, 25, 30, 40 and 60 min ischemia (n = 10 each) on H in the coronary effluent and in cardiac tissue was studied after 4 min reperfusion. Release of creatine kinase and lactate dehydrogenase in the coronary effluent increased with time of ischemia. Tissue H increased from 95 +/- 10 ng/g rat heart (mean +/- SEM) before ischemia to max 148 +/- 10 ng/g after 20 min ischemia (p < 0.002), and increased also after 15 (p < 0.01), 25 (p < 0.01), and 30 min (p < 0.045). H in the coronary effluent increased after 15 (from 16 +/- 3 to 26 +/- 2 pmol/min, p < 0.044), 30 (26 +/- 6 pmol/min, p < 0.027), and 60 min ischemia (47 +/- 6 pmol/min, p < 0.0044). Release of H during ischemia-reperfusion is neither dependent on the severity of the ischemic insult, nor on the level of tissue H.

Animals↗
PubMed1993

Inhibition of lipoxygenase and cyclooxygenase augments cardiac injury by H2O2.

The role of arachidonic acid metabolites in the cardiac effects of toxic oxygen metabolites (TOM) was investigated in buffer-perfused rat hearts (Langendorff model). Hydrogen peroxide (H2O2, 200 microM) was given for 10 min to generate TOM, followed by 30 min recovery. H2O2 reduced left ventricular developed pressure (LVDP), increased left ventricular end-diastolic pressure (LVEDP), and increased coronary flow (CF). The hydroxyl radical scavenger thiourea inhibited the H2O2-induced effects. Perfusion with three lipoxygenase inhibitors, AA861, BWA4C, and diethylcarbamazine, in addition to H2O2, augmented the decrease of LVDP and the increase of LVEDP induced by H2O2. The cyclooxygenase inhibitor indomethacin had the same effects. The H2O2-induced increase in CF was not influenced by diethylcarbamazine, but inhibited by all other drugs. Control perfusion with drugs alone did not influence cardiac function. In conclusion, inhibition of lipoxygenase and cyclooxygenase augmented the depression of cardiac function induced by TOM. Leukotrienes and prostanoids appear to be protective against H2O2-induced cardiac injury.

Animals↗