Cyclosporin A does not enhance the development of transplant vasculopathy: experimental study in a rat cardiac transplant model.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H G Olbrich
Publications and source records attributed to H G Olbrich.
Angiotensin II type 1 receptor blockade after cardiac transplantation reduced the incidence and severity of transplant vasculopathy in an animal-based study.
Explore the source record for details and available documents.
Angiotensin Receptor Antagonists↗
[Epidemiology-etiology of dilated cardiomyopathy].
Among the cardiomyopathies,--dilated cardiomyopathy (dcm), hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy--, dcm is the most frequent entity. Its prevalence in the United States amounts to 36 cases per 100,000 inhabitants, men being almost 3-fold more involved than women. The etiology of dcm is very heterogenous; 50% of the cases are due to idiopathic dcm whereas the other half comprises a broad spectrum of various etiologies such as myocarditis, ischemic heart disease, peripartal cardiomyopathy, hypertension, HIV infection, toxic cardiomyopathy and others. In 20 to 30% of the cases of idiopathic dcm a genetic transmission of the disease has been found. Another 20 to 30% of idiopathic dcm are associated with inflammatory and immunological phenomena. Infectious myocarditis with enteroviruses, especially with coxsackie-virus type B has been suggested to be an important trigger for an immune-mediated dcm. In both, familiar dcm and infection with coxsackie-virus B, an impairment of constituents of the myocardial cytoskeleton has been shown. This is regarded as a possible pathogenetic mechanism in the development of dcm.
Adult↗
Do vascular compartments differ in the development of chronic rejection? AT(1) blocker candesartan versus Ace blocker enalapril in an experimental heart transplant model.
BACKGROUND: Accelerated coronary artery disease (ACAD), a serious consequence after heart transplantation, is characterized by diffuse, concentric myointimal proliferation in the arteries. Increasing evidence supports the existence of a local renin-angiotensin system and the role of angiotensin-II in smooth muscle cell proliferation. We investigated the effect of angiotensin-II blocker candesartan and angiotensin-converting enzyme (ACE) inhibitor enalapril on experimental ACAD in a rat model. METHODS: After heterotopic cardiac transplantation (Fisher to Lewis), recipients received 20 mg/kg/day candesartan or 40 mg/kg/day enalapril per os. Two groups of animals received additional pre-treatment with candesartan or enalapril 7 days before transplantation, and treatment was continued after grafting. All study groups including the controls received 3 mg/kg/day of sub-cutaneous cyclosporine for immunosuppression. A syngeneic group (Lewis to Lewis), serving as extra control, did not receive any treatment. Eighty days after grafting, we assessed the extent of ACAD in large and small arteries, using digitizing morphometry and expressed as mean vascular occlusion (MVO). RESULTS: In enalapril and candesartan pre- and post-treated animals, we observed significant reduction of MVO of intramyocardial arteries compared with the cyclosporine group (p < 0.005), to levels similar to the syngeneic transplants. MVO of epicardial arteries in enalapril and candesartan pre- or posttreated animals did not significantly differ from cyclosporine controls (p > 0.05). CONCLUSION: Our results support the hypothesis of 2 proliferative compartments in the development of ACAD, with differing receptor or enzyme distribution: the compartment of small, intramyocardial arteries in which ACAD can be reduced by ACE or AT(1) blockade, and that of large, epicardial arteries in which inhibition fails.
Angiotensin Receptor Antagonists↗
Extension of generator longevity by use of high impedance ventricular leads.
The resistance of a pacing lead negatively correlates to current consumption. A prospective, randomized trial was conducted to evaluate the effect of a high impedance ventricular lead (CapSure Z) on generator longevity compared to a conventional lead (CapSure SP) eighty-nine patients were included in the study (51 male, 37 female, age 70.0+/-10.3 years). Forty-six patients received a CapSure SP lead (5024 bipolar), and 43 patients received a CapSure Z lead (5034 bipolar) in a randomized fashion. Follow-up data collected at 5 days, 3, 6, and 12 months postimplant included: lead impedance, pacing and sensing thresholds, impulse energy, and estimated time to replacement. All parameters were collected via pacemaker telemetry; the time to replacement was calculated automatically by a programmed algorithm of the pacemaker. There was no difference in the performance of the atrial lead when a dual chamber device was indicated. The CapSure Z leads displayed statistically significant higher impedance values than the CapSure SP lead in all follow-up periods. There was no significant difference in lead related complications. No significant differences were observed between pacing and sensing thresholds in both groups. The CapSure Z leads provided a significant reduction in current drain, resulting in a reduction of mean energy consumption at the 12-month follow-up from 10.4+/-5.0 microJ in the CapSure SP group to 6.6+/-1.4 microJ in the CapSure Z group (median from 9.9 microJ to 6.9 microJ, respectively), providing an estimated increase in mean longevity of more than 1 year from 81.1+/-23.5 months in the CapSure SP group to 94.5+/-13.4 months in the CapSure Z group (median: 76.5 months to 95.0 months, respectively). The use of a high resistance lead for ventricular pacing appears to result in a clinically relevant extension of generator longevity.
Aged↗
Vitamins C and E protect isolated cardiomyocytes against oxidative damage.
There is considerable evidence that oxygen free radicals are involved in reperfusion injury of ischemic myocardium. Epidemiologic studies showed an inverse correlation between plasma levels of alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) and mortality from ischemic heart disease. The present study examines the influence of both vitamins on the toxic effects of singlet oxygen on isolated rat cardiomyocytes. Freshly isolated cardiomyocytes from adult rats were exposed to singlet oxygen which was generated by photoactivation of the photosensitive dye rose bengal (10(-7) M). This procedure induced irreversible hypercontracture in about 95% of rod-shaped cardiomyocytes within 15 min after onset of photoactivation of rose bengal. Pretreatment with vitamin C (10(-5) to 10(-2) M) or E (10(-6) to 10(-3) M) reduced the number of hypercontracted cells after exposure to singlet oxygen in a concentration-dependent manner. Simultaneous application of both vitamins (vitamin E 10(-6) M plus vitamin C 10(-5) M or vitamin E 10(-5) M plus vitamin C 10(-4) M) revealed a marked overadditive protective effect against oxidative damage as compared with the single application of each vitamin. Our data show that alpha-tocopherol and ascorbic acid exert direct protective actions on isolated cardiomyocytes against oxidative damage and provide an overadditive effect if administered simultaneously.
Animals↗
New approach in the therapy of chronic rejection? ACE- and AT1-blocker reduce the development of chronic rejection after cardiac transplantation in a rat model.
BACKGROUND: Angiotensin II is one of the most potent mitogens of smooth muscle cell proliferation and plays a central role in the development of accelerated coronary artery disease (ACAD), which remains a serious consequence after heart transplantation and limits long-term survival. We investigated the effect of an angiotensin-II blocker, Losartan (angiotensin II Type 1 [AT(1)]-blocker), and an angiotensin-converting enzyme (ACE) inhibitor, Enalapril, on experimental ACAD in a rat cardiac transplant model (Fisher to Lewis). METHODS: After grafting, recipients were treated with 10 mg/kg/day per os Losartan or 40 mg/kg/day per os Enalapril. Two groups of animals received additional pre-treatment with Losartan or Enalapril 7 days before transplantation. All study groups, including the control group, received immunosuppression with cyclosporine (3 mg/kg/day sub-cutaneously). We assessed the extent of ACAD of large and small arteries 80 days after grafting using digitizing morphometry. RESULTS: We observed significant reduction of neointimal proliferation in small arteries in Losartan pre- and post-treated and in Enalapril pre-treated recipients compared with the cyclosporine-treated group (p < 0.05). In epicardial arteries, Enalapril pre- and post-treatment as well as Losartan post-treatment significantly reduced neointimal formation compared with the control group. Reduction of neointima by Enalapril post-treatment in small arteries and Losartan pre-treatment in large arteries trended toward but failed statistical significance. CONCLUSIONS: Our results suggest the important role of the renin-angiotensin system in neointimal proliferation, which can be reduced equally with ACE inhibitors or the angiotensin-II blocker. Therefore AT(1) blockade with Losartan is a useful therapeutic strategy for inhibition of ACAD after cardiac transplantation.
Angiotensin II↗
Effects of lovastatin and pravastatin on the survival of hamsters with inherited cardiomyopathy.
Cardiomyopathic hamsters develop heart disease early in life, which leads to congestive heart failure and death as these hamsters age. Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to reduce ubiquinone concentrations and to deteriorate myocardial function in humans and in experimental animals. HMG-CoA reductase inhibitors differ regarding their ability to penetrate extrahepatic tissues. As a consequence, lovastatin inhibits cholesterol biosynthesis at least 100-fold more effectively than pravastatin in extrahepatic cells. We examined the effect of lovastatin and pravastatin (approximately 10 mg per kilogram of body weight and per day mixed in the diet) compared with controls on the lifespan of cardiomyopathic hamsters (BIO 8262 strain) in the heart-failure period. In male hamsters, neither lovastatin nor pravastatin significantly affected survival. In female hamsters, lovastatin reduced median survival time from 89 days (control animals) to 30 days (P <.05); pravastatin (median survival, 115 days) had no statistically significant effect. We conclude that lovastatin, but not pravastatin, at a daily dose of 10 mg per kilogram of body weight significantly increases the mortality of cardiomyopathic hamsters. This effect may be the result of inhibition of myocardial ubiquinone supply.
Administration, Oral↗
Glimepiride (Hoe490) inhibits the rilmakalim induced decrease in intracellular free calcium and contraction of isolated heart muscle cells from guinea pigs to a lesser extent than glibenclamide.
Glibenclamide is a potent inhibitor of the ATP-dependent potassium channel. Opening of the ATP-dependent potassium channel is regarded as a mechanism of ischemic preconditioning. This in vitro study examines the influence of glibenclamide and glimepiride, a new sulfonylurea, on the negative inotropic action of the potassium channel opener rilmakalim in isolated ventricular myocytes. Cardiac myocytes were isolated from adult guinea pig hearts by collagenase perfusion and incubated with rilmakalim (concentration range 0.1-12.0 microM), glibenclamide (concentration range 0.03-3.0 microM) plus rilmakalim (3.0 or 7.5 microM), and glimepiride (0.03-9.0 microM) plus rilmakalim (3.0 or 7.5 microM) and paced by electrical field stimulation. Contractility of the myocytes was evaluated by digital image analysis, intracellular free calcium was determined by means of fura-2 fluorescence measurements, and cell viability was assessed morphologically as well as by measurement of lactate dehydrogenase activity. Rilmakalim reduced the systolic intracellular free calcium and contractility of ventricular myocytes in a concentration dependent manner. This effect was antagonized by glibenclamide at lower concentrations (0.3 microM) than glimepiride (3.0 microM). The smaller antagonistic action of glimepiride on the negative inotropic effect of rilmakalim as compared with glibenclamide most likely reflects a less potent inhibition of ATP-dependent potassium channels by glimepiride.
Adenosine Triphosphate↗
Extracellular matrix structure after heart transplantation.
Following heart transplantation remodeling of the donor heart causes changes in the extracellular myocardial matrix. We investigated 20 right ventricular endomyocardial biopsies taken 17+/-4 days (group I, n=9) and 63+/-13 days (group II, n=11) after heart transplantation from 16 patients transplanted for end-stage cardiomyopathy (15 dilated/1 ischemic). Immunohistochemical staining for collagen I, collagen III, collagen IV, and fibronectin was used. Evaluation was performed at a magnification of 400x using a computer-assisted image analyzing system measuring the relative area stained by the immunoperoxidase method, the number of cells in the given area, and the total area. Collagen I per cell was 13.9+/-5.9 microm2 in group I and increased significantly 66+/-13 days after heart transplantation in the perimysium around the myocardial cells as well as in the endocardium to 49.9+/-15.1 microm2 (P<0.05). No quantitative change in collagen III was noted (75.7+/-12.4 versus 75.5+/-16.0 microm2 n.s.). Collagen IV was found in the perimysial, in the capillary bed and in the vascular network. Significant quantitative change in the amount of collagen IV was not found (64.1+/-12.6 versus 61.0+/-8.9 microm2). Fibronectin was found in the entire perimysial extracellular matrix and in the endocardium in relationship with collagen I and III. An increased amount of fibronectin from 87.09+/-9.9 microm2 (group I) to 140.8+/-17.9 microm2 (group II, P<0.05) was found. The cell area and cell diameters were not significantly different (group I; cell area 772+/-227 microm2, diameter 31.3 microm; group II; cell area 776+/-224 microm2, diameter 31.4 microm). It is concluded that remodeling of the donor heart after transplantation is characterized by a specific increase in collagen I and fibronectin, whereas a change in other collagen subtypes was not observed.
Analysis of Variance↗
Lipoprotein(a) stimulates growth of human mesangial cells and induces activation of phospholipase C via pertussis toxin-sensitive G proteins.
BACKGROUND: Renal disease is commonly associated with hyperlipidemia and correlates with glomerular accumulation of atherogenic lipoproteins, for example, lipoprotein(a) [Lp(a)], and mesangial hypercellularity. Specific binding of Lp(a) to mesangial cells and induction of c-myc and c-fos expression has been demonstrated. Therefore, in this study, we investigated a possible growth stimulatory effect and mode of action of Lp(a) in human mesangial cells. METHODS: Lp(a) was purified from the regenerate fluid of a dextran sulfate column-based low-density lipoprotein apheresis system. Human mesangial cells were isolated by a sequential sieving technique from patients undergoing tumor nephrectomy. DNA synthesis was measured by [3H]-thymidine incorporation. The intracellular calcium concentration ([Ca2+]i) was determined by Fura 2-fluorescence, and inositol 1,4,5-trisphosphate (1,4,5-IP3) concentration was measured by a radioreceptor assay. RESULTS: The data show that Lp(a) bound to the cells with a Kd of 17.0 micrograms/ml and increased DNA synthesis and cell proliferation. Lp(a) caused a rapid increase in 1,4,5-IP3 and [Ca2+]i via a pertussis toxin-sensitive mechanism. The phospholipase C (PLC) inhibitor U73122 abolished Lp(a)-induced cell proliferation. In contrast, vasopressin-induced increase in 1,4,5-IP3 and [Ca2+]i was pertussis toxin insensitive. CONCLUSION: This study revealed that Lp(a) stimulates growth of human mesangial cells. Lp(a)-induced signaling involves binding to a receptor and stimulation of PLC via Gi proteins. Stimulation of PLC appears to be essential for the growth stimulatory effect of Lp(a). Whether these effects of Lp(a) contribute to the pathophysiology of renal disease needs to be determined.
Blood Proteins↗
Prognostic significance of coronary flow reserve on left ventricular ejection fraction in cardiac transplant recipients.
BACKGROUND: Cardiac allograft vasculopathy is a common phenomenon in epicardial and microvascular vessels. Intramyocardial vessel disease may lead to small, stellate infarcts. The present study tested the impact of microvascular vasomotor function on changes in left ventricular systolic function in the long-term follow-up after cardiac transplantation. METHODS: Seventeen consecutive cardiac transplant patients, 40+/-21 months after cardiac transplantation, without angiographically visible cardiac allograft vasculopathy and without episodes of acute rejection were included in the study. Coronary microvascular reactivity was assessed by the endothelium-dependent stimulus acetylcholine (50 microg i.c.) and by the endothelium-independent stimulus dipyridamole (0.56 mg/kg i.v.) utilizing an Doppler catheter. Radionuclide ventriculography was performed at the time of coronary flow measurement and repeated 2 years later to correlate changes in left ventricular ejection fraction with the coronary flow reserve measurement 2 years previously. RESULTS: There was a statistically significant correlation between endothelium- independent coronary flow reserve to dipyridamole and changes in ejection fraction at rest (r=0.59; P < 0.01) and during exercise (r=0.48; P < 0.05). Twenty-four months later, patients with a coronary flow reserve to dipyridamole < 2.5 showed a significant decline in ejection fraction during exercise (-7 +/- 5%) compared to patients with a coronary flow reserve > 2.5 (1.1+/-5%; P=0.003). Coronary flow reserve to acetylcholine was not correlated with a reduced ejection fraction during exercise. CONCLUSIONS: Endothelium-independent microvascular dysfunction has prognostic importance for deterioration of left ventricular function in cardiac transplant recipients without angiographically visible coronary artery stenoses. These results reinforce the concept that microvascular and epicardial vessel disease after transplantation are two distinct entities with different functional consequences.
Adolescent↗
Soluble interleukin-2-receptor levels as a marker of coronary microvascular dysfunction after heart transplantation.
BACKGROUND: Immunologic mechanisms operating in a milieu of nonimmunologic risk factors constitute the principal stimuli that result in progressive cardiac allograft vasculopathy. Interleukin-2 has a central role in the development of cell-mediated immunity and is a key factor in the induction of a complex network of cytokines. On exposure to cytokines, endothelial cells can undergo profound alterations of vasomotor function. In this study we characterized the relationship between coronary microvascular function and soluble interleukin-2 receptor (sIL-2R) levels after human heart transplantation. METHODS: We studied 15 heart transplant recipients after an average follow-up time of 39+/-22 months. We measured coronary artery blood flow in an endothelium-dependent manner with acetylcholine (50 microg) and in an endothelium-independent manner with dipyridamole (0.56 mg/kg) by intracoronary Doppler catheter. Blood samples from the superior vena cava were drawn 3 to 12 months after transplantation (early value) and at time of the coronary artery flow measurement (present value). Coronary artery flow reserve was correlated to sIL-2R levels, which were determined by use of an enzyme-linked immunoabsorbent assay. RESULTS: We found a significant inverse correlation between impaired endothelium-mediated (p = 0.03) but not endothelium-independent relaxation of the coronary microvasculature and elevated sIL-2R levels. In heart transplant recipients without acute rejection or an infection episode, an sIL-2R-level of more than 800 U/ml was defined as a cutpoint, indicating disturbed endothelium-dependent microvascular function. Additionally, there was a conspicuous trend toward an inverse correlation between early elevated sIL-2R-levels and endothelium-dependent microvascular dysfunction (p = 0.06). CONCLUSIONS: The results of this study demonstrate the utility of sIL-2R, an index of immunologic activity, to be used as a marker and predictor of impaired endothelial microvascular function in heart transplant recipients. These observations support the hypothesis that after heart transplantation endothelial dysfunction in the microcirculation is an immunologic phenomenon.
Adult↗
Effects of beta-adrenoceptor blockade on beta-adrenergic signal transduction in cardiomyopathic hamster (BIO 8262) hearts.
In myopathic BIO 8262-hamsters beta1-adrenergic stimulation of cardiac adenylyl cyclase has been found to be markedly reduced compared to that of healthy controls. In order to test the hypothesis that the functional uncoupling of beta1-adrenoceptors in diseased hamster hearts is due to agonist-dependent desensitization, we investigated the effects of prolonged treatment with beta-adrenoceptor antagonists on cardiac beta-adrenergic signaling. Groups of hamsters aged 240 days received either drinking water, or drinking water containing metoprolol (10 or 100 mg/kg/day) or propranolol (4 or 40 mg/kg/day). After 4 weeks' treatment animals were killed and heart ventricles were prepared for determination of beta1- and beta2-adrenoceptor densities and their functional contribution to stimulation of adenylyl cyclase. Markers of myocardial hypertrophy, i.e. absolute and relative ventricular weight and 5-nucleotidase activity, were not affected by the different treatment regimens. Neither absolute densities nor relative proportions of beta-adrenoceptor subtypes differed between untreated and treated hamster groups. Metoprolol had no effects on the functional efficacy of beta1- and beta2-adrenoceptors. Hamsters treated with high dose propranolol showed unchanged beta1-adrenoceptor function but reduced beta2-adrenergic stimulation of adenylyl cyclase. The findings of the present study demonstrate that the disturbed coupling of cardiac beta1-adrenoceptors to adenylyl cyclase cannot be reversed by in vivo treatment with beta-adrenoceptor antagonists and, therefore, is unlikely to be due to agonist-dependent desensitization.
5'-Nucleotidase↗
Variations of segmental endothelium-dependent and endothelium-independent vasomotor tone after cardiac transplantation (qualitative changes in endothelial function).
Endothelial dysfunction is a common phenomenon after cardiac transplantation. However, qualitative differences in endothelial vasoregulation at different coronary segments and at different postoperative times have rarely been explored. To uncover the functional variations of endothelium responses we infused the endothelium-dependent vasodilator acetyl-choline (50 micrograms) followed by the endothelium-independent vasodilator 3-morpholinosydnonimine (SIN-1) (1 mg; 16 patients) or nitroglycerin (0.3 mg; 14 patients) sequentially into the left coronary artery. We investigated the responses of 120 nonstenotic coronary segments (proximal and distal left anterior descending and right circumflex coronary arteries) in 30 patients with quantitative angiography (group 1: 13 patients, 12 +/- 1 months after cardiac transplantation; group 2: 17 patients, 55 +/- 3 months after cardiac transplantation). Continuous-flow measurement was performed to exclude significant reduction of microvascular response influencing epicardial dilation. Five responses to acetylcholine administration followed by nitrates were observed. On the one end of the spectrum, segments dilate to acetylcholine administration with no further dilation to exogenous nitric oxide, indicating completely preserved endothelial function. On the other end, segments constrict to acetylcholine with no change after endogenous nitric oxide, reflecting a defective endothelial and defective smooth muscle function. The different patterns of coronary vasomotor lone responses to endogenous nitric oxide followed by exogenous nitric oxide represent different degrees of endothelial function after cardiac transplantation. In addition, the functional assessment of endothelial integrity shows qualitative time-dependent differences between proximal and distal coronary parts. The existence of coronary segments with functioning endothelium indicates that the latter is not diffusely disturbed in all cardiac transplant recipients and that the endothelial damage is perhaps not irreversibly lost.
Acetylcholine↗
Cardiac microvascular vasomotor response as a prognostic marker of left ventricular function in cardiac transplant recipients.
Explore the source record for details and available documents.
Adult↗
Time course of endothelial function in epicardial conduit coronary arteries and in the microcirculation in the long-term follow-up after cardiac transplantation.
BACKGROUND: Endothelial dysfunction has been reported in epicardial conduit coronary arteries and in the microcirculation after cardiac transplantation. It has been assumed that endothelial dysfunction may precede hemodynamically relevant transplant vasculopathy. In this study the long-term course of endothelial function was investigated in conduit coronary arteries and in the microcirculation after cardiac transplantation. METHODS: Patients were stratified according to time after transplantation (group I, up to 2 years after transplantation; group II, 2 to 4 years after transplantation; group III, more than 4 years after transplantation). Changes of the diameter of proximal, mid and distal segments of the left anterior descending coronary artery and the circumflex branch of the left coronary artery were investigated after endothelium-dependent and endothelium-independent stimulation with acetylcholine (ACh, 50 and 100 micrograms i.c.) and nitroglycerin 0.3 mg i.c. Coronary flow changes were assessed endothelium-dependently (ACh 50 and 100 micrograms i.c.) and endothelium-independently (dipyridamole 0.56 mg/kg i.v.) utilizing an 8 F Judkins-style Doppler catheter. RESULTS: Application of 50 micrograms/100 micrograms ACh resulted in a reduction of coronary artery diameter in proximal, mid and distal vascular segments of the left anterior descending coronary artery and the circumflex branch of the left coronary artery. The vasoconstrictive effect did not differ significantly between groups I,II and III. Nitroglycerin 0.3 mg i.c. increased coronary artery diameters in groups I, II and III. ACh (50 micrograms/100 micrograms) increased coronary flow index by 217 +/- 70%/236 +/- 110% (P < 0.05 vs. baseline) in group I, 113 +/- 26%/77 +/- 22% (P < 0.05 vs. baseline) in group II and 108 +/- 26%/109 +/- 21% (P < 0.05 vs. baseline) in group III. Dipyridamole increased coronary flow index by 296 +/- 78% (P < 0.05 vs. baseline) in group I, by 63 +/- 16% (P < 0.05 vs. baseline and vs. group I) in group II and by 113 +/- 30% (P < 0.05 vs. baseline and vs. group I) in group III. CONCLUSION: A constant vasosonstrictor response to ACh was observed in epicardial coronary arteries after cardiac transplantation indicating endothelial dysfunction independent of the time course. Endothelial dysfunction in these vessels may not be an early indicator of hemodynamically relevant transplant vasculopathy. Endothelium-dependent and endothelium-independent flow reserves decreased 2 years after transplantation and remained constant thereafter.
Acetylcholine↗
Protective action of hydroxyethyl rutosides on singlet oxygen challenged cardiomyocytes.
1. The effect of a standardized mixture of beta-hydroxyethyl rutosides against oxidative damage in singlet oxygen-challenged isolated cardiac myocytes from adult rats was investigated. The morphology of the myocytes was evaluated as an indicator for cell viability (elongated, rod shaped cells vs. hypercontracted, rounded cells). The determination of the production of thiobarbituric acid reactive substances served as an indicator for lipid peroxidation. 2. Exposure to singlet oxygen which was generated by photo-excitation of rose bengal (10(-7) M) reduced the number of rod shaped (vital) cardiomyocytes by 78.5 +/- 2.5% and increased the production of thiobarbituric acid reactive substances by 1180 +/- 150% in comparison to incubation with control buffer. 3. Coincubation of the cells with beta-hydroxyethyl rutosides (concentration range: 6.7 pg ml-1 to 670 micrograms ml-1) increased the number of rod shape cardiomyocytes after exposure to singlet oxygen in a dose-dependent bell-shaped manner. A significant protective effect was observed at beta-hydroxyethyl rutosides concentrations ranging from 0.67 ng ml-1 to 67 ng ml-1. 4. In spite of their protective action, beta-hydroxyethyl rutosides did not reduce the accumulation of thiobarbituric acid reactive substances, used as an indicator for lipid peroxidation. 5. The data suggest that beta-hydroxyethyl rutosides exert a protective action against oxygen radical-induced damage of cardiac myocytes at very low concentrations without interfering with lipid peroxidation.
Animals↗