Biomedical subjects

M Borgers

Publications and source records attributed to M Borgers.

At least 91 records · Page 5Linked to original sources

PubMed1994

Histopathological characterization of photochemical damage in nervous tissue.

This paper discusses histological and ultrastructural changes produced by dye-sensitized photoreactions in the central and peripheral nervous system. Particular attention has been given to morphological outcome in experimental models which reproduce widespread clinical pathologies, e.g. stroke, spinal cord injury and peripheral neuropathy. Evaluation of structural alterations may not only help to characterize the evolution of these disease processes but also allow us to study possibilities of therapeutic intervention.

Animals↗

PubMed1993

A new model of photochemically induced acute and reversible demyelination in the peripheral nervous system.

Acute photochemical demyelination accompanied by minor axonal degeneration was produced in rat sciatic nerve after topical application of the photosensitive dye Rose Bengal and focal illumination with cold light. Animals were sacrificed at different time periods after challenge and the exposed nerves prepared for light microscopic and ultrastructural evaluation. Important structural changes were already observed at 4-6 h. These included endoneurial swelling, diapedesis of neutrophils and monocytes, vacuolization and vesicularization of Schwann cell cytoplasm, lamellar separation of myelin sheaths, disintegration of axonal microtubules, and accumulation of vesicular material and mitochondria in the axoplasm. Disrupted myelin fragments were phagocytosed by macrophages which penetrated Schwann tubes at Day 3. Schwann cells proliferated and started to enwrap denuded segments of the axon. They were surrounded by redundant basal lamina, thrown into deep folds. Axons remained partly hypertrophic and contained many neurofilaments. A minority showed signs of degeneration. At Days 5-7 denudation was almost complete in the light-exposed nerve area but also in small distal nerve fascicles. After 1 month, axons in the illuminated area and distal to it were completely remyelinated although they had thinner sheaths. Exposure to increased light intensity resulted in deeper lesions and more extended anterograde damage, which also recovered within 1 month. All animals showed rapid functional deterioration which correlated with the severity and extent of structural damage. Recovery was slow and also depended on the degree of histologic damage. Neither control nerves nor sham-exposed nerves revealed signs of structural or functional changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

R56865, a Na(+)- and Ca(2+)-overload inhibitor, reduces myocardial ischemia-reperfusion injury in blood-perfused rabbit hearts.

The cardioprotective effects of R56865 were studied in isolated rabbit hearts, blood-perfused with a support rabbit system. The effect on ischemic injury was evaluated by comparing myocardial contracture and contents of ATP catabolites and of lactate during 60 min of normothermic ischemia in untreated hearts (group I) and in hearts treated with 0.63 mg/kg of R56865 starting 20 min before ischemia (group II; n = 5 in each group). R56865 delayed the onset, and decreased the extent of ischemic contracture, but had no effect on the myocardial content of ATP, of its catabolites of lactate. The effect on reperfusion injury was studied by monitoring left ventricular function during 80-min reperfusion after the 60-min ischemia in three groups (n = 6 in each): an untreated group (group I) and two groups treated with R56865 given either before (group II) or after ischemia (group III). Ultrastructural changes and cellular calcium distribution after reperfusion were also studied. R56865 improved the recovery of function and prevented contracture during reperfusion. Left ventricular end-diastolic pressure was 13.2 +/- 2.8 mmHg in group II and 31.3 +/- 8.1 mmHg in group III vs 45.0 +/- 2.6 mmHg in group I (P < 0.0001 for II vs I; P > 0.05 for III vs I). Left ventricular developed pressure, maximum dP/dt and minimum dP/dt recovered to 71.0 +/- 5.4%, 98.9 +/- 6.1%, 85.3 +/- 4.8% of baseline values, respectively, in group II, to 64.5 +/- 3.0% (P > 0.05), 76.8 +/- 3.0%, 70.2 +/- 4.0% in group III, vs 52.0 +/- 6.5%, 58.9 +/- 6.9% and 53.6 +/- 5.8% in untreated hearts (P < 0.05 for II or III vs I). Coronary flow was 24.5 +/- 2.2 ml/min and 19.8 +/- 1.8 ml/min in groups II and III vs 14.8 +/- 0.7 ml/min (P < 0.05) in the untreated group. On histology the myocardium in hearts treated either before or after ischemia was well protected and calcium distribution was almost normal after reperfusion, while in untreated hearts, most of the myocardium displayed irreversible damage accompanied by massive intracellular calcium accumulation. We conclude that R56865 could attenuate Ca(2+)-overload, thereby reducing myocardial ischemia-reperfusion injury after an extended period of ischemia.

Animals↗

PubMed1993

Distribution of calcium in a subset of chronic hibernating myocardium in man.

The structural correlates of 'chronic hibernating myocardium' in man consist of myocardial cells which transformed from a functional state (rich in contractile material) to a surviving state (poor in contractile material, rich in glycogen). Since the calcium-handling organelles such as SR, sarcolemma and mitochondria underwent structural changes in cells so affected, the distribution of calcium was investigated in biopsies obtained from 'hibernating' areas. The material was processed for microscopic localization of total calcium (laser microprobe mass analysis, LAMMA) and of exchangeable calcium (phosphate-pyroantimonate precipitation method, PPA). Subcellular distribution of total calcium as assessed by LAMMA revealed that in the structurally affected cells the areas in which sarcomeres were replaced by glycogen contained significantly more calcium than all other areas probed such as mitochondria, remaining sarcomeres at the cell periphery and subcellular areas of normally structured cells. Calcium precipitate, obtained after PPA assessment, was localized at the sarcolemma but was virtually absent in the mitochondria of affected cells. The high calcium content in the myolytic areas of affected cells most probably belongs to a pool of bound calcium. The observations that calcium is retained at the sarcolemma and that mitochondria are devoid of precipitate favour the hypothesis that cells structurally affected as such are not ischaemic and are still able to regulate their calcium homeostasis.

Calcium↗

PubMed1993

Photochemically-induced cerebral infarction in the rat: comparison of NMR imaging and histologic changes.

The evolution of a photochemically induced cerebral thrombotic infarction was followed in rats during the first week after the insult by means of NMR imaging and histology. Heavily T2-weighted images provided an excellent lesion detection and a high specificity for the discrimination of different histological abnormalities. The T2-weighted images showed a brain lesion evolving during the first 24 h from a homogeneous hyperintense area, histologically corresponding to diffuse vasogenic and cytotoxic oedema with concomitant neuronal necrosis, to an iso-intense area with a hyperintense seam, which microscopically correlated with increased vascular permeability at the periphery of the lesion. The hyperintense seam was observed up to day 7, but at that time coincided with gliomesodermal repair reaction which could be verified histochemically and ultrastructurally. It may be concluded that NMR-micro-imaging at a moderately high field, enables early detection and adequate follow-up of small cerebral infarctions in rats.

Animals↗

PubMed1993

Inhibition of sodium and calcium overload pathology in the myocardium: a new cytoprotective principle.

Ca2+ overload is known to play a major role in cell dysfunctioning in ischaemia/reperfusion and in cardiac glycoside intoxication. Suppression of Ca2+ overload or its consequences may therefore improve cellular function in these pathological conditions. Recent evidence suggests that Ca2+ overload occurs secondary to Na+ overload. Both depressed efflux and increased influx mechanisms have been mentioned as factors contributing to Na+ load. Prevention of this initial Na+ overload, without interfering with the normal Na+ current during the action potential, may therefore represent a novel pharmacological approach in the management of Ca2+ overload. The new cardioprotective drug R 56865 potently protects the heart against Ca2+ overload: ischaemia induced and ouabain induced arrhythmias and cell death are prevented in the absence of negative inotropism (no L-type Ca2+ channel blockade). At least three interactions at the cellular level may be held responsible for protection in these conditions. First, excessive Na+ entry into myocardial cells due to non-inactivating Na+ channels in depolarised cells is inhibited at concentrations that do not affect action potential configuration or contractile force. This leads to prevention of Na+ overload and subsequent Ca2+ overload and cell death. Second, R 56865 inhibits the transient inward current in Ca(2+)-(over)loaded cells, thus effectively preventing after-depolarisations and triggered propagated contractions. It has been proposed that R 56865, independent of its action on Na+ loading, might reduce oscillatory Ca2+ release from the intracellular Ca2+ stores, without interfering with the normal release mechanisms. Third, the drug attenuates K+ efflux in Na+ and Ca2+ loaded cells. In this way, R 56865 may contribute to prevention of action potential shortening and inhomogeneous repolarisation.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzothiazoles↗

PubMed1993

Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function.

BACKGROUND: Studies done in potential donors for heart transplantation and in experimental animals have suggested that brain death can have major histopathological and functional effects on the myocardium. METHODS AND RESULTS: We developed experimental models of brain death using dogs to study the hemodynamic and catecholamine changes, the extent of myocardial structural damage, and the recovery potential of donor hearts obtained from brain-dead donors. Brain death was caused by increasing the intracranial pressure (ICP) suddenly or gradually by injecting saline in an epidural Foley catheter. In a first series of experiments, dogs given a sudden rise in ICP (n = 5) showed a hyperdynamic response and a 1,000-fold increase in the level of epinephrine after brain death. Histology revealed 93 +/- 2% of the myocardium to be severely ischemic. Dogs given a gradual rise in ICP (n = 6) showed a lesser hyperdynamic response, almost 200-fold increase in the level of epinephrine after brain death, and mild ischemic damage to the myocardium (23 +/- 1%). In a second series, hearts obtained from brain-dead and non-brain-dead donors were transplanted in recipients, and the weaning and recovery potential were studied. All four recipients with hearts from non-brain-dead donors were weaned with good functional recovery. Also, all four recipients with hearts from brain-dead dogs given a gradual rise in ICP were weaned with only moderate functional recovery. However, only two of four recipients with hearts from donors given a sudden rise in ICP were weaned and showed poor functional recovery. CONCLUSIONS: Our results indicate that a sudden rise in ICP can cause irreversible myocardial damage.

Animals↗

PubMed1993

Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium.

BACKGROUND: Even in the absence of a previous myocardial infarction, patients with coronary artery disease often present with chronic regional wall motion abnormalities that are reversible spontaneously or after coronary revascularization. In these patients, regional dysfunction has been proposed to result either from prolonged postischemic dysfunction (myocardial "stunning") or from adaptation to chronic hypoperfusion (myocardial "hibernation"). This study examines which of these two mechanisms is responsible for the chronic regional dysfunction often detected in patients with angina and noninfarcted collateral-dependent myocardium. METHODS AND RESULTS: Twenty-six anginal patients (19 men; mean age, 60 +/- 9 years old) with chronic occlusion of a major coronary artery but without previous infarction were studied. Positron emission tomography was performed to measure absolute regional myocardial blood flow with 13N-ammonia at rest (n = 26) and after intravenous dipyridamole (n = 11). The kinetics of 18F-deoxyglucose and 11C-acetate were measured to calculate the rate of exogenous glucose uptake and the regional oxidative metabolism (n = 15). Global and regional left ventricular function was evaluated by contrast ventriculography at baseline (n = 26) and after revascularization (n = 12). Transmural myocardial biopsies from the collateral-dependent area were obtained in seven patients during bypass surgery and analyzed by optical and electron microscopy. According to resting regional wall motion, patients were separated into groups with and without dysfunction of the collateral-dependent segments. In patients with normal wall motion (n = 9), regional myocardial blood flow, oxidative metabolism, and glucose uptake were similar among collateral-dependent and remote segments. By contrast, in patients with regional dysfunction (n = 17), collateral-dependent segments had lower myocardial blood flow (77 +/- 25 versus 95 +/- 27 mL.min-1.100 g-1, p < 0.001), smaller k values (slope of 11C clearance reflecting oxidative metabolism, 0.049 +/- 0.015 versus 0.068 +/- 0.020 min-1, p < 0.001) and higher glucose uptake (relative 18F-deoxyglucose-to-flow ratio of 1.9 +/- 1.6 versus 1.2 +/- 0.2, p < 0.05) compared with remote segments. However, myocardial blood flow and k values were similar among collateral-dependent segments of patients with and without segmental dysfunction. After intravenous dipyridamole, collateral-dependent myocardial blood flow increased from 78 +/- 5 to 238 +/- 54 mL.min-1.100 g-1 in three patients with normal wall motion and from 88 +/- 17 to only 112 +/- 44 mL.min-1.100 g-1 in eight patients with regional dysfunction. There was a significant (r = -0.85, p < 0.001) inverse correlation between wall motion abnormality and collateral flow reserve. Analysis of the tissue samples obtained at the time of bypass surgery showed profound structural changes in dysfunctioning collateral-dependent areas, including cellular swelling, loss of myofibrillar content, and accumulation of glycogen. Despite these alterations, the regional wall motion score improved significantly in the patients studied before and after revascularization (from 3.8 +/- 1.3 to 0.8 +/- 0.9, p < 0.005). CONCLUSIONS: In a subgroup of patients with noninfarcted collateral-dependent myocardium, immature or insufficiently developed collaterals do not provide adequate flow reserve. Despite nearly normal resting flow and oxygen consumption, these collateral-dependent segments exhibit chronically depressed wall motion and demonstrate marked ultrastructural alterations on morphological analysis. We propose that these alterations result from repeated episodes of ischemia as opposed to chronic hypoperfusion and represent the flow, metabolic, and morphological correlates of myocardial "hibernation."

Aged↗

PubMed1993

Possible neuroprotective properties of flunarizine infused after asphyxia in fetal lambs are not explained by effects on cerebral blood flow or systemic blood pressure.

Neuroprotective properties of the calcium channel blocker flunarizine have been reported after hypoxic-ischemic insults in immature, infant, and adult rats. However, its effect on fetal regional cerebral blood flow (rCBF) and systemic blood pressure after severe asphyxia is not known. In 15 fetal lambs (3 to 5 d after surgery; gestational age at the experiment, 123.2 +/- 2.5 d), arterial oxygen content was progressively reduced to 30% by restriction of uterine blood flow with an inflatable balloon occluder around the maternal common internal iliac artery. The rCBF was measured with radioactive microspheres at baseline condition, after 1 h of severe asphyxia, and at 30 and 120 min in the recovery phase. Immediately after the end of the occlusion period, fetuses randomly received either flunarizine or its solvent (0.5 mg/kg estimated fetal weight). No differences in rCBF changes between groups were observed during and after asphyxia. Changes in arterial blood pressure or fetal heart rate due to flunarizine could not be demonstrated either. Only five fetuses (33%) survived this degree of asphyxia longer than 24 h: four of the flunarizine-treated group and one of the control group. It is unlikely that this possible protective property of the drug is caused by its influence on rCBF, arterial blood pressure, or fetal heart rate in the phase immediately after asphyxia.

Acid-Base Imbalance↗

PubMed1993

Influence of superoxide dismutase on reperfusion injury in donor hearts preserved with Bretschneider-HTK cardioplegic solution.

The ability of superoxide dismutase to prevent reperfusion injury after long-term cold storage of donor hearts was evaluated in canine hearts. Whole blood reperfusion was performed using a 'support animal'. Twelve dog hearts were arrested by a single dose of Bretschneider cardioplegic solution and stored cold (0.5 degrees C) for 24 h. Thereafter they were reperfused for 60 min without (n = 6) or with (n = 6) superoxide dismutase treatment. Myocardial tissue biopsies were taken for determination of high-energy phosphates before explantation, after the preservation period and during reperfusion. Early reperfusion in both groups resulted in an initial recovery of high-energy phosphates and was followed by a decrease during the subsequent reperfusion phase. The latter was associated with the appearance of left ventricular contracture, and cessation of heart beat. Electron microscopic examination of the myocardial tissues after reperfusion revealed a severe reperfusion injury in both groups. It is concluded, that in donor hearts preserved with Bretschneider solution, reperfusion injury cannot be prevented by administration via the perfusate of superoxide dismutase.

Animals↗

PubMed1993

Learning performance at different time periods after hypoxia in infant rats.

Infant rats were exposed to hypoxia. At different time periods after the hypoxic aggression the animals were subjected to a one-way active avoidance task consisting of 3 daily training sessions. Learning performance of hypoxic rats, expressed as the number of avoidances per 10 trials, was significantly decreased in all the sessions at posthypoxic day 35 (P < 0.001). The rate to which learning behaviour was affected by hypoxia was comparable among all 3 sessions in both groups. Histological evaluation of hippocampus and cortex at day 7 and day 35 after hypoxic exposure, did not reveal detectable structural changes. It can be concluded from this study that hypoxia, induced in 21 day old rats leads to learning performance deficits in the adult animal.

Animals↗

PubMed1992

Synaptic plasticity in rat hippocampus associated with learning.

Rats subjected to a one-way active avoidance task consisting of 3 daily training sessions, showed obvious shape changes in dendritic spines of the hippocampal supragranular molecular layer. Performance, expressed as the number of avoidances per 10 trials, significantly improved in the second and third session (P < 0.001). In trained animals, at the end of the third session, the amount of perforated concave synapses significantly increased as compared to untrained controls (P < 0.05). When compared with a group of sham-shocked rats, the increase was less pronounced. The length of the postsynaptic density in both, perforated and non-perforated synapses, significantly increased in comparison with untrained control and sham-shocked animals (perforated: P < 0.005; non-perforated: P < 0.05). The results are indicative for the existence of synaptic remodeling and turnover in rats subjected to one-way active avoidance training.

Animals↗

PubMed1992

Protection of human, rat, and guinea-pig atrial muscle by mioflazine, lidoflazine, and verapamil against the destructive effects of high concentrations of Ca2+.

In right atrial trabeculae from humans and in left atria from rat and guinea-pig hearts, the protective effects of mioflazine, lidoflazine, and verapamil against the accumulation of cellular calcium were investigated. Two consecutive, cumulative increases in the extracellular calcium concentration, [Ca2+]o (1-25 mmol/l), were induced, in between which the muscles were exposed for at least 30 minutes to solvent or drug. When using solvent in the 30-minute interval, the force of contraction was much lower during the second Ca2+ challenge, while the aftercontractions and the increase in passive tension at high [Ca2+]o tended to be larger. These signs of functional impairment were prevented by exposure to mioflazine or lidoflazine (3 mumol/l each) but not to verapamil (3 mumol/l). Muscles were fixed with glutaraldehyde at the end of the second Ca2+ challenge for morphological and cytochemical examination. After solvent treatment, more than half of the cells were severely damaged, showing cellular edema, contraction-band necrosis, mitochondrial swelling, and nuclear pyknosis; the sarcolemma was devoid of calcium deposits, damaged mitochondria contained either large deposits of calcium or flocculent densities, and in some cells, the cytoplasm was filled with calcium deposits. Following exposure to mioflazine and lidoflazine, but not to verapamil, the number of intact cells after the second Ca2+ challenge was not different from time-matched controls (80-90%). Furthermore, the shifts in cellular calcium distribution were prevented with mioflazine and lidoflazine, whereas verapamil was less effective. There were no species differences with respect to either morphological or contractile changes. In conclusion, exposure of atria to high [Ca2+]o induced similar ultrastructural and cytochemical changes as seen after ischemia-reperfusion induced damage. Indeed, under the mentioned conditions the sarcolemma lost its capacity to exclude Ca2+ after a challenge with high [Ca2+]o and allowed excessive Ca2+ entry. The pathway for this extra Ca2+ remains to be elucidated. L-type calcium channels are probably not involved, since verapamil cannot prevent the Ca2+ overload.

Animals↗

PubMed1992

Microwave-enhanced silver staining of degenerating neuronal processes.

A simple and rapid method for light and electron microscopic visualization of degenerating neuronal processes and axon terminals is described. Hundred-micrometer vibratome sections of perfusion-fixed rat brain were incubated briefly in a 5% silver nitrate solution in a conventional microwave oven. After a rinse in 1% acetic acid, the sections were silver enhanced. Differentiation and counterstaining was done respectively in ethanol 100% and cresyl violet. In the light microscope, degenerating neuronal processes appeared as black dots against a clear background. Areas of calcification were also positively stained. The presence of silver deposits in degenerating presynaptic terminals and dendrites was confirmed ultrastructurally.

Animals↗

PubMed1992

Species differences in adenosine metabolic sites in the heart.

5'-Nucleotidase and purine nucleoside phosphorylase, two key enzymes in nucleoside metabolism, have been localized electronmicroscopically in left ventricular myocardium of the human, dog, pig, rabbit, guinea pig and rat. Ectonucleotidase activity was present in all species at the plasma membrane of pericytes. Reactive endothelial cells in the microcirculatory bed were restricted to those covering resistance arterioles. Cardiomyocytes were reactive only in the rat. Purine nucleoside phosphorylase was localized uniformly in the vascular endothelium of all species. The strongest activity was seen in the pericytes of guinea pig, rat and dog. Pericytes of rabbit and pig were virtually unreactive, whereas a minority of cells in human samples were positive. Cardiomyocytes were unreactive in all species. These variations in the distribution pattern of adenosine metabolic sites may have definite consequences for disposal and recovery of adenylates and their breakdown products in ischaemia and for the effects to be expected from interference with nucleoside transport inhibition.

5'-Nucleotidase↗

PubMed1992

The course of vasospasm following subarachnoid haemorrhage in rats. A vertebrobasilar angiographic study.

The course of vasospasm following subarachnoid haemorrhage in rats was studied using vertebrobasilar angiography. Wistar and Sprague Dawley rats were compared with respect to vasospastic response after bleeding. A more pronounced vasospasm was found in Sprague Dawley rats. In order to avoid a possible toxic effect on the contrast medium, only one angiogram per animal was initially performed. However, a comparison with the results obtained in a separate series of non-challenged animals demonstrated a difficulty due to high variability in basilar artery size in the latter group. Therefore, vasospasm can be more readily shown if multiple angiograms are used in the same animal so that the vasospasm can be expressed as a percentage of the initial diameter of the basilar artery. It was found that multiple angiograms are well tolerated when non-ionic contrast media are used.

Animals↗

PubMed1992

Haemodynamic, intracranial pressure and electrocardiographic changes following subarachnoid haemorrhage in rats.

Experimental induction of subarachnoid haemorrhage in rats resulted in acute haemodynamic changes. Heart rate decreased concomitantly with a rise in arterial blood pressure. Intracranial pressure increased and consequently cerebral perfusion pressure dropped. These changes as well as the observed electrocardiographic (ECG) changes were comparable to those reported in patients. Apart from blood also saline, when introduced into the cisterna magna, was able to elicit such abnormalities. The haemodynamic and electrocardiographic changes, which result from subarachnoid haemorrhage, may even become aggravated, when repetitive injections of blood or saline are given into the cisterna magna and when cerebral angiography is performed prior to induction of the subarachnoid haemorrhage. Chronic intracranial pressure monitoring during the 48 hours following subarachnoid haemorrhage revealed no significant rise in pressure. A thorough control of the experimental conditions is thus of utmost importance in order to give a valid interpretation of the observed anomalies.

Animals↗

PubMed1992

Lysophosphatidylcholine-induced Ca(2+)-overload in isolated cardiomyocytes and effect of cytoprotective drugs.

It has been previously demonstrated that lysophosphatides accumulate rapidly in ischaemic tissue, and may play a key role in the genesis of ischaemia-reperfusion injury. The present study investigated the effects of exogenously added lysophosphatidylcholine (1-20 microM) on single isolated cardiomyocytes from adult rabbit hearts. Quiescent cells exposed to > or = 8 microM lysophosphatidylcholine dose-dependently displayed irreversible hypercontraction, whereas after 60 min at 3 microM lysophosphatidylcholine, most cells remained rod-shaped (87.2 +/- 2.0%, mean +/- S.E.M.). However, when combined with electrical field stimulation (1 Hz), exposure to 3 microM lysophosphatidylcholine resulted in irreversible hypercontracture of most cells after 60 min: only 27.5 +/- 7.5% of the cells remained rod-shaped. Contracture depended upon the presence of extracellular Ca2+, and coincided with a significant rise in the median intracellular free Ca2+ level from 72.2 to 352.1 nM (P = 0.0001), suggesting intracellular Ca(2+)-overload. Pretreatment with 10(-6) M flunarizine or R 56865 significantly reduced the fraction of damaged cells when exposed to 3 microM lysophosphatidylcholine and electrical stimulation: 78.3 +/- 12.2% and 56.3 +/- 13.1% respectively of the cells remained rod-shaped. No protection was observed when quiescent cells were exposed to 10 microM lysophosphatidylcholine. Cytochemical localization of Ca2+ showed that lysophosphatidylcholine induced a loss of sarcolemma-bound Ca2+ precipitate and an accumulation of Ca2+ clusters in mitochondria of damaged cells in a dose and time dependent way. These results suggest that lysophosphatidylcholine induces functional and structural damage (Ca(2+)-overload) in isolated cardiomyocytes and that this can be prevented by cytoprotective drugs.

Animals↗