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Biomedical subjects

A G Semb

Publications and source records attributed to A G Semb.

At least 19 recordsLinked to original sources
PubMed2006

Clopidogrel increases expression of chemokines in peripheral blood mononuclear cells in patients with coronary artery disease: results of a double-blind placebo-controlled study.

BACKGROUND: Chemokines and platelet activation are both important in atherogenesis. Platelet inhibitors are widely used in coronary artery disease (CAD), and we hypothesized that the platelet inhibitor clopidogrel could modify chemokines in CAD patients. OBJECTIVES: We sought to investigate the effect of clopidogrel on the expression of chemokines and chemokine receptors in peripheral blood mononuclear cells (PBMC) in CAD patients. PATIENTS/METHODS: Thirty-seven patients with stable angina were randomized to clopidogrel (n = 18) or placebo (n = 19). PBMC, blood platelets and plasma were collected at baseline and after 7-10 days in the patients, and in 10 healthy controls. mRNA levels of chemokines and chemokine receptors in PBMC were analyzed by ribonuclease protection assays and real-time reverse transcriptase polymerase chain reaction. Platelet activation was studied by flow cytometry. RESULTS: (i) At baseline, the gene expression of the regulated on activation normally T-cell expressed and secreted (RANTES) chemokines and macrophage inflammatory peptide (MIP)-1beta in PBMC, the expression of CD62P and CD63 on platelets and the levels of platelet-derived microparticles (PMP) were elevated in angina patients comparing healthy controls; (ii) markers of platelet activation were either reduced (CD63) or unchanged (CD62P, PMP, beta-thromboglobulin) during clopidogrel therapy; (iii) in contrast, clopidogrel significantly up-regulated the gene expression of RANTES and MIP-1beta in PBMC, while no changes were found in the placebo group; (iv) a stable adenosine 5'-diphosphate metabolite attenuated the release of MIP-1beta, but not of RANTES, from activated PBMC in vitro. CONCLUSIONS: Even if we do not argue against a beneficial role for clopidogrel in CAD, our findings may suggest potential inflammatory effects of clopidogrel in CAD.

Aged↗
PubMed2006

Increased inflammatory markers in children with familial hypercholesterolaemia.

BACKGROUND: While data are abundant on increased levels of inflammatory markers in adult patients with hypercholesterolaemia, such data in children are limited. Therefore, we sought to investigate the degree and character of inflammation in children with heterozygous familial hypercholesterolaemia (FH) by measuring levels of neopterin, high-sensitivity C-reactive protein (hsCRP), and soluble CD40 ligand (sCD40L). MATERIALS AND METHODS: In the present study, we compared the concentration of inflammatory markers in children suffering from heterozygous FH (n = 207) with those in unaffected siblings (n = 84). Furthermore, we investigated the effect of 2-year treatment with pravastatin (20-40 mg qd) or placebo on plasma levels of those markers. RESULTS: Our main finding was that serum levels of neopterin and hsCRP were significantly higher in FH children compared with healthy siblings, whereas sCD40L was not. Body mass index and high-density lipoprotein cholesterol levels were significant independent predictors of hsCRP and neopterin. Furthermore, pravastatin therapy decreased neopterin, but not hsCRP and sCD40L, in the FH children, but these changes were not different from the placebo group. CONCLUSION: These findings indicate low-grade monocyte/macrophage hyperactivity in the early stages of atherogenesis, but our findings also suggest that inflammation as well as anti-inflammatory effects of statins are less prominent features of atherosclerosis in FH children than in FH adults.

Adolescent↗
PubMed2004

Blood platelet count and reactivity are associated with restenosis 6 months after coronary angioplasty.

OBJECTIVES: Restenosis occurs in 40-50% of patients treated with percutaneous transluminal coronary angioplasty (PTCA). Some data indicate that platelet derived growth factor (PDGF) plays a pathogenetic role. The aims of the present study were to measure the plasma levels of PDGF across the coronary circulation during PTCA and relate them to the development of restenosis. DESIGN AND RESULTS: Blood samples from the aortic root and coronary sinus were drawn simultaneously before, and after completed PTCA in 26 patients. Plasma levels of PDGF and beta-thromboglobulin (BTG), as well as platelet counts were measured. Restenosis was evaluated by quantitative coronary angiography after 6 months. Significant increases both in PDGF and BTG were encountered in the aortic root after PTCA in patients who developed restenosis as compared to patients without restenosis. Patients who developed restenosis also had significantly higher platelet counts compared to those without. CONCLUSION: Increases in plasma PDGF and BTG in the aortic root after PTCA seem to be markers for restenosis 6 months after PTCA. This finding may strengthen the hypothesis that platelets contribute to the process of restenosis.

Age Distribution↗
PubMed2000

Benefits of early lipid-lowering intervention in high-risk patients: the lipid intervention strategies for coronary patients study.

BACKGROUND: There is controversy about whether lipid-lowering pharmacotherapy should be initiated immediately after an acute coronary event or only after diet and lifestyle changes have proved inadequate. OBJECTIVE: This study, known as the Lipid Intervention Strategies for Coronary Patients Study, compared the efficacy of immediate versus deferred simvastatin treatment in conjunction with dietary advice about reducing lipid levels in hypercholesterolemic patients with acute coronary syndromes. METHODS: This randomized, open-label, parallel-group study included 151 hypercholesterolemic (low-density lipoprotein cholesterol [LDL-C] >3.0 mmol/L) men and women aged 35 to 75 years. Within 4 days of diagnosis of acute myocardial infarction (MI) or unstable angina pectoris, all patients received dietary advice from a specially trained nurse. Subsequently, patients were randomized to 2 treatment groups: 1 group received immediate treatment with simvastatin 40 mg/d; patients in the other group received simvastatin 40 mg/d after 3 months only if their LDL-C remained >3.0 mmol/L. RESULTS: The immediate-simvastatin group (n = 73) and the deferred-simvastatin group (n = 78) were balanced with respect to baseline characteristics. Of the 151 patients, 25% were women, 25% had concomitant hypertension, and 75% had a diagnosis of MI on enrollment. At 3 months, 90% of the patients receiving dietary advice plus immediate simvastatin treatment had achieved the recommended European target LDL-C level of <3.0 mmol/L, compared with 7% of those treated with diet alone. By 6 months, when 92% of the study participants were receiving simvastatin 40 mg/d, the proportion of patients achieving target LDL-C levels was 92% in the group that received immediate simvastatin therapy and 81% in the group that received deferred simvastatin therapy. The reductions in LDL-C (42%-48%) were considered to be clinically comparable between the 2 groups at 12 months. CONCLUSIONS: On the basis of these results, we concluded that few patients with hypercholesterolemia and acute coronary syndromes reach the recommended European target LDL-C level of <3.0 mmol/L with dietary advice alone. However, early treatment with simvastatin 40 mg/d combined with dietary advice and follow-up at a dedicated outpatient clinic specializing in coronary heart disease resulted in 9 out of 10 patients reaching a recommended target LDL-C level of <3.0 mmol/L. Initiation of simvastatin therapy while a patient is hospitalized may increase the likelihood of the patient's lipid levels being managed according to current recommendations after he or she is discharged.

Adult↗
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↗
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↗
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↗
PubMed1993

Measurements of leukotrienes in human plasma by solid phase extraction and high performance liquid chromatography.

Leukotrienes (LTs) are biologically active compounds derived from lipoxygenase catalyzed metabolism of arachidonic acid in mammalian tissues. The present report describes a simple method for extraction and isolation of dihydroxy-LTs; LTB4, LTB5 and the peptido-LTs; LTC4, LTD4 and LTE4 from human plasma, using a pretreatment cartridge which utilizes both hydrophobic and ion-exchange interactions. 5 ml acidified plasma or acetate buffer containing commercially available LT standards were passed through the cartridges under suction, and the absorbed LTs were subsequently eluted in a stepwise manner with acetate buffer containing increasing amounts of methanol. The eluted LTs were analyzed by reversed-phase high performance liquid chromatography (HPLC) on octadecylsilyl (ODS)-silica, using a Waters HPLC unit. Both with plasma and acetate buffer the present methodology resulted in good separation of the LTs with a total run-time of less than 32 min. Recovery of dihydroxy-LTs was approximately 80% (range 73-82%) both when the standards were dissolved in plasma and in acetate buffer. Recovery of the peptido-LTs was, however somewhat lower (47-50%). It should be noted that the present method has the advantage that exposure to chemicals of high toxicity is avoided.

Chemical Phenomena↗
PubMed1991

Cardiac surgery and distribution of the leukocyte L1 protein-calprotectin.

Activated polymorphonuclear leukocytes (PMN) secrete lysosomal enzymes, eicosanoids and toxic oxygen metabolites. In cardiac surgery patients, we measured arterial plasma levels of PMN and L1 (calprotectin), a prominent granulocyte protein, during cardiopulmonary bypass (CPB). The myocardial arterio-venous gradients were evaluated during reperfusion after cold cardioplegic arrest (n = 10). The arterial plasma concentration of L1 increased during CPB from 344 +/- 71 micrograms/l (mean +/- SD) preoperatively to 5221 +/- 1267 micrograms/l at the end of CPB (P less than 0.001). Simultaneously, the number of circulating PMN also increased (from 4.4 +/- 0.4 x 10(9)/l to 9.1 +/- 1.2 x 10(9)/l (P less than 0.05)). There was a positive correlation between the mean number of circulating PMN and the plasma level of L1 at all sampling times during CPB (r = 0.93, P less than 0.05). A coronary sequestration of both L1 (P less than 0.006) and PMN (P less than 0.002) was found after 5 min reperfusion. This was not present at 15 and 30 min reperfusion. The coronary entrapment of L1 and PMN did not covary significantly, and was unrelated to both the time of cardioplegic arrest and the arterial levels of L1 and PMN. In conclusion, the increased plasma concentrations of PMN and L1 during CPB and the coronary sequestration of both PMN and L1 may be factors in the pathogenesis of reperfusion injury of the myocardium.

Adult↗
PubMed1991

Oxygen free radical-induced injury in isolated rat hearts: effects of ibuprofen and BW 755c.

Inhibitors of the arachidonic acid metabolism (AA) as well as scavengers of oxygen free radicals (OFR) have been shown to reduce myocardial infarct size. We investigated the effects of two inhibitors of AA metabolism on the cardiac effects of OFR. Isolated rat hearts were retrogradely perfused for 10 min with buffer containing hypoxanthine (HX, 1 mmol l-1) and xanthine oxidase (XOD: 24 U l-1) alone (n = 11), or with the addition of ibuprofen (IBU) (n = 6) (a cyclooxygenase inhibitor) or BW 755C (n = 6) (a dual inhibitor of cyclo-oxygenase and lipoxygenase). The hearts were observed for 30 min thereafter (total observation time 40 min). Left-ventricular pressures were measured by a balloon in the left ventricle. HX + XOD significantly reduced left-ventricular developed pressure (LVDP) and coronary flow (CF), but not heart rate. The reduction of LVDP and CF was not significantly ameliorated by the addition of IBU (7.6 x 10(-4) mol l-1) or BW 755C (2 x 10(-3) mmol l-1). OFR increased left-ventricular end-diastolic pressure (LVEDP) from (mean +/- SEM) 0 to 22 +/- 4 mmHg (10 min) and 30 +/- 5 mmHg (40 min). Upon addition of IBU, LVEDP increased from 0 to 24 +/- 8 mmHg and 17 +/- 6 mmHg at 10 and 40 min respectively. The addition of BW 755C almost completely inhibited the increase in LVEDP (1 +/- 1 mmHg and 3 +/- 3 mmHg at 10 min and 40 min). In conclusion, except for inhibition of OFR-induced diastolic dysfunction by BW 755C, neither BW 755C nor IBU appear to inhibit cardiac injury induced by OFR.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1990

[Ergotamine induced ischemia].

Drugs containing ergotamine are commonly used in the treatment of migraine. Hypersensitivity to these drugs may be triggered off even with intake of recommended doses, inducing peripheral ischemia. Contributing factors to ergotism are concurrent fever, liver disease and drugs such as erythromycin or propranolol. We present a case history and different methods of treatment.

Ergotamine↗
PubMed1990

Oxygen free radical producing leukocytes cause functional depression of isolated rat hearts: role of leukotrienes.

Polymorphonuclear granulocytes PMN) are suggested mediators of myocardial ischemia-reperfusion injury. We have previously shown that activated PMN producing oxygen free radicals (OFR) in the coronary circulation are cardiodepressive. OFR may induce lipid peroxidation and production of eicosanoids. We have investigated the influence of cyclo-oxygenase and lipoxygenase inhibitors on the effects of activated, OFR producing PMN in the Langedorff rat heart model. Left ventricular developed pressure (LVDP) was measured by a balloon in the left ventricle. Human PMN and drugs were given into the aortic cannula for 10 min and the hearts were observed for 30 min thereafter. After infusion for 5 min OFR production in the cellular infusate was measured at the level of the aortic cannula by a chemiluminescence (CL) technique. Phorbol 12-myristate 13-acetate (PMA)-activated PMN (n = 8), produced a CL response of 27649 +/- 11048 counts (mean +/- S.E.M.), and reduced coronary flow (CF) to 53 +/- 6% (mean +/- S.E.M.) and LVDP to 38 +/- 9% of baseline values at the end of the observation period. Ibuprofen (n = 6), a cyclooxygenase (CO) inhibitor, neither influenced the CL response (31915 +/- 7563) of activated PMN, nor the reduction of CF and LVDP at this time. Although both BW 755C (n = 7), a dual inhibitor of CO and lipoxygenase (LO) (CF:90 +/- 4%, LVDP:99 +/- 6%) and diethylcarbamazine (DCM) (n = 8), a LO inhibitor (CF:88 +/- 11%, LVDP:87 +/- 4%), significantly inhibited the cardiodepressive effects of activated PMN. BW 755C alone abolished the CL response (431 +/- 158 counts), whereas DCM had no effect on CL (30105 +/- 1698 counts).(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1990

Granulocyte and eicosanoid gradients across the coronary circulation during myocardial reperfusion in cardiac surgery.

Polymorphonuclear granulocytes (PMN) and eicosanoids such as leukotrienes have been suggested as possible mediators of myocardial ischemia-reperfusion injury. We have investigated the gradients of PMN, 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) and leukotriene B4 (LTB4) across the coronary circulation during myocardial reperfusion after cold, cardioplegic arrest in cardiac surgery. Baseline values in arterial blood were 4.4 +/- 0.4 x 10(9)/l, 59 +/- 6 pg/ml and 149 +/- 27 pg/ml (mean +/- SEM) for PMN, 6-keto-PGF1 alpha and LTB4, respectively. They were significantly elevated during cardiopulmonary bypass (CPB). There was a positive correlation between the number of circulating PMN and LTB4 at all sample times during cardiopulmonary bypass (P less than 0.05). At 5 min reperfusion (CPB time: 122 +/- 8 min) PMN, 6-keto-PGF1 alpha and LTB4 were 6.2 +/- 0.5 x 10(9)/l, 696 +/- 117 pg/ml and 280 +/- 60 pg/ml, respectively. The PMN in coronary sinus blood were significantly lower (P less than 0.001) than in arterial blood at 5 min reperfusion, but not at 15 and 30 min. The concentrations of 6-keto-PGF1 alpha and LTB4 were significantly elevated in coronary sinus blood as compared to arterial blood after reperfusion for 5 min (P less than 0.05). Thereafter, no significant gradients were found across the heart, except at 30 min reperfusion when LTB4 was significantly lower in coronary sinus blood. Neither PMN sequestration nor 6-keto-PGF1 alpha and LTB4 production were significantly correlated to aortic cross clamp time.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Coronary trapping of a complement activation product (C3a des-Arg) during myocardial reperfusion in open-heart surgery.

Accumulation of complement factors has been found to occur in the myocardium after infarction. We studied the possibility that the complement activation product C3a des-Arg is trapped within the coronary circulation during reperfusion of the ischemic myocardium. In 11 patients undergoing routine coronary artery bypass grafting, arterial blood was sampled before, during and after cardiopulmonary bypass. Blood was drawn from the coronary sinus concomitantly with arterial blood sampling 5 and 30 min after release of the aortic cross-clamp (n = 10). From a preoperative value of 92 +/- 13 ng/ml, C3a des-Arg rose during CPB to a maximum of 1816 +/- 393 at the end of CPB. Following reperfusion for 5 min, C3a des-Arg was 1284 +/- 232 ng/ml in arterial and 1106 +/- 100 in coronary sinus blood, a significant difference (p less than 0.05). The amount of C3a des-Arg trapped in the heart at 5-min reperfusion showed positive correlation with its arterial concentration (p less than 0.05). No significant difference was found after 30 min of reperfusion. Complement activation products trapped in the heart in the early reperfusion period may play a pathogenetic role in myocardial ischemia-reperfusion injury.

Cardiopulmonary Bypass↗
PubMed1989

[Poisoning by phenylpropanolamine (Rinexin)--an alpha adrenergic receptor agonist].

The incidence of suicide is increasing, the most common form being intoxication by drugs. It is well known that young cocaine abusers, with no cardiovascular disease, may suffer from acute chest pain due to arterial coronary spasm or myocardial infarction. Adrenoceptor stimulating drugs will give the same symptoms and should be considered as a possible cause of the pain in young intoxicated patients with no history of drug abuse or cardiovascular disease. A case is presented.

Adult↗
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↗
PubMed1989

Oxygen free radicals decrease survival time of isolated rat hearts.

Effects of oxygen free radicals (OFR), enzymatically generated in the coronary circulation, were studied in isolated rat hearts retrogradely perfused with Krebs-Ringer solution. Control hearts (n = 6) functioned adequately for at least 5 hours. When rat hearts (n = 6) received xanthine oxidase (XOD) and hypoxanthine (HX) in order to generate OFR, survival time was reduced to 31 +/- 0.4 min (mean +/- SEM). Infusion of XOD (n = 8) or HX (n = 5) alone also reduced cardiac survival time, to 32 +/- 6 min and 139 +/- 23 min, respectively. When allopurinol (an inhibitor of XOD) was given together with XOD (n = 6), survival time (277 +/- 30 min) was similar to the control value. The production of OFR did not result in depressed coronary flow or heart rate, but reduced the aortic pulse pressure. OFR thus can depress cardiac function and may ultimately cause cardiac arrest.

Animals↗