Biomedical subjects

Márk Kollai

Publications and source records attributed to Márk Kollai.

At least 19 recordsLinked to original sources

PubMed2006

Human heart mitochondria do not produce physiologically relevant quantities of nitric oxide.

Previous studies raised the possibility that nitric oxide synthase is present in heart mitochondria (mtNOS) and the existence of such an enzyme became generally accepted. However, original experimental evidence is rather scarce and positive identification of the enzyme is lacking. We aimed to detect an NOS protein in human and mouse heart mitochondria and to measure the level of NO released from the organelles. Western blotting with 7 different anti-NOS antibodies failed to detect a NOS-like protein in mitochondria. Immunoprecipitation or substrate-affinity purification of the samples concentrated NOS in control preparations but not in mitochondria. Release of NO from live respiring human mitochondria was below 2 ppb after 45 min of incubation. In a bioassay system, mitochondrial suspension failed to cause vasodilation of human mammary artery segments. These results indicate that mitochondria do not produce physiologically relevant quantities of NO in the heart and are unlikely to have any physiological importance as NO donors, nor do they contain a recognizable mtNOS enzyme.

Animals↗

PubMed2006

Mitochondria produce reactive nitrogen species via an arginine-independent pathway.

We measured the contribution of mitochondrial nitric oxide synthase (mtNOS) and respiratory chain enzymes to reactive nitrogen species (RNS) production. Diaminofluorescein (DAF) was applied for the assessment of RNS production in isolated mouse brain, heart and liver mitochondria and also in a cultured neuroblastoma cell line by confocal microscopy and flow cytometry. Mitochondria produced RNS, which was inhibited by catalysts of peroxynitrite decomposition but not by nitric oxide (NO) synthase inhibitors. Disrupting the organelles or withdrawing respiratory substrates markedly reduced RNS production. Inhibition of complex I abolished the DAF signal, which was restored by complex II substrates. Inhibition of the respiratory complexes downstream from the ubiquinone/ubiquinol cycle or dissipating the proton gradient had no effect on DAF fluorescence. We conclude that mitochondria from brain, heart and liver are capable of significant RNS production via the respiratory chain rather than through an arginine-dependent mtNOS.

Animals↗

PubMed2005

Graft derived cells with double nuclei in the penumbral region of experimental brain trauma.

Recent in vitro studies showed that stem cells might fuse with mature cells or each other; however, there is no in vivo evidence for this phenomenon in the cerebral cortex. Our goal was to find evidence for cell fusion in a model of traumatic brain injury followed by grafting of embryonic cortical cells. Cold lesion protocol was applied to induce lesion of the motor cortex in adult male rats. Six days later we grafted a suspension of freshly isolated rat brain cortical cells of early embryonic stage (E14) into the penumbra area of the lesion. The grafted cell nuclei were labelled with bromodeoxyuridine (BrDU). Six days after transplantation 4,328 BrDU positive cells were observed in nine animals. 89.5% of these cells had cytoplasmic staining probably representing dead or phagocyted grafted cells. Ten percent of surviving BrDU positive cells had only one BrDU positive nucleus and negative cytoplasm, while 0.5% had two distinct nuclei, one was unlabelled and one was BrDU positive. These cells were similar in appearance and size to the astrocytes in the vicinity and expressed the astocyte specific glial fibrillaly acidic protein. Thus, these cells showed a possible sign of cell fusion in the penumbral region of the injured brain.

Animals↗

PubMed2005

Gender differences in the endotoxin-induced inflammatory and vascular responses: potential role of poly(ADP-ribose) polymerase activation.

Activation of poly(ADP-ribose) polymerase (PARP) is an important factor in the pathogenesis of various cardiovascular and inflammatory diseases. Here, we report that the gender-specific inflammatory response is preferentially down-regulated by PARP in male animals. Female mice produce less tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha in response to systemic inflammation induced by endotoxin than male mice and are resistant to endotoxin-induced mortality. Pharmacological inhibition of PARP is effective in reducing inflammatory mediator production and mortality in male, but not in female, mice. Ovariectomy partially reverses the protection seen in female mice. Endotoxin-induced PARP activation in circulating leukocytes is reduced in male, but not female, animals by pharmacological PARP inhibition, as shown by flow cytometry. Pretreatment of male mice with 17-beta-estradiol prevents endotoxin-induced hepatic injury and reduces poly(ADP-ribosyl)ation in vivo. In male, but not female, animals, endotoxin induces an impairment of the endothelium-dependent relaxant responses, which is prevented by PARP inhibition. In vitro oxidant-induced PARP activation is reduced in cultured cells placed in female rat serum compared with male serum. Estrogen does not directly inhibit the enzymatic activity of PARP in vitro. However, PARP and estrogen receptor alpha form a complex, which binds to DNA in vitro, and the DNA binding of this complex is enhanced by estrogen. Thus, estrogen may anchor PARP to estrogen receptor alpha and to the DNA and prevent its recognition of DNA strand breaks and hence its activation. In conclusion, the gender difference in the inflammatory response shows preferential modulation by PARP in male animals.

Angiotensin II↗

PubMed2005

The novel red-fluorescent probe DAR-4M measures reactive nitrogen species rather than NO.

INTRODUCTION: Several fluorescent probes were designed for the measurement of nitric oxide (NO), however, questions arose regarding their specificity and sensitivity in biological samples. In the present study we tested the reaction of a novel rhodamine-based chromophore diaminorhodamine-4M (DAR-4M) with NO and other reactive nitrogen and oxygen species. METHODS: We performed fluorometry in 96-well plates in a cell-free buffer with similar ion concentrations as the cytoplasm. Dose-response curves were generated using various NO donors and reactive nitrogen and oxygen species. The effects were compared between the red-fluorescent DAR-4M and its green-fluorescent counterpart 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM). RESULTS: DAR-4M had a markedly higher fluorescence yield to NO donors than DAF-FM, while both probes had a comparable threshold of sensitivity (in the range of 0.1 mM nitroprusside). Both dyes reacted with various NO donors in a dose-dependent manner, while superoxide, hydrogen peroxide, peroxynitrite, or nitroxyl failed to change the fluorescence intensity of the probes. DAR-4M was potentiated in the presence of peroxynitrite to react with low levels of NO donors in a similar manner to DAF-FM. DISCUSSION: We conclude that DAR-4M is a suitable red-fluorescent probe for the qualitative assessment of reactive nitrogen species production, but not specific for NO. Quantitative comparisons among samples is inappropriate since the fluorescent yield is affected by the presence of other oxidants in the sample.

Artifacts↗

PubMed2005

Mitochondrial NO and reactive nitrogen species production: does mtNOS exist?

It is more than 10 years now that mitochondria are suspected to be sources of nitric oxide (NO). This hypothesis is intriguing since NO has multiple targets within the organelle and it is even suggested that mitochondria are the primary targets of NO in the cell. Most remarkably, nanomolar concentrations of NO can inhibit mitochondrial respiration, so even a small amount of NO in the mitochondrial matrix may regulate ATP synthesis. Therefore, the idea that mitochondria themselves are capable of NO production is an important concept in several physiological and pathological mechanisms. However, this field of research generates surprisingly few original papers and the published studies contain conflicting results. The reliability of the results is frequently questioned since they are seldom reproduced by independent investigators. Until 2003, all papers published in this field showed affirmative results but since then several studies directly challenged the existence of a mitochondrial nitric oxide synthase. The present review aims to summarize the most recent developments in mitochondrial NO production, highlights a few unsolved questions, and proposes new directions for future work in this research area.

Animals↗

PubMed2005

[Investigation of cerebral autoregulation in Parkinson's disease--a transcranial Doppler study].

BACKGROUND AND PURPOSE: The frequent orthostatic intolerance in Parkinson's disease could be the consequence of cardiovascular autonomic failure and/or a damaged cerebral autoregulation (AR). To clarify this question the regulation of cerebral circulation was investigated by polygraphic method. METHODS: On a tilt table simultaneous and continuous registrations were made of MCA velocity (V(MCA)) by transcranial Doppler, arterial blood pressure by non-invasive method, and end-tidal CO2, in supine and in tilted positions of 10 degrees, 30 degrees, 70 degrees grades. The cerebral autoregulation was characterized by the slope of the curve of the arterial blood pressure at the level of the Willis-circle (BP(W) as MCA perfusion pressure) plotted against the MCA velocity, achieved by linear regression (y = ax + b function, a=AR, or index of autoregulation). PATIENTS: The data of 17 parkinsonian patients (PP) and eight age-matched controls (C) were analyzed. RESULTS: The decrease of blood pressure in parkinsonian patients was significantly lower than in the controls when supine position was restored from 70 degrees (deltaABP 70 degrees - 0 degree pp = -3.1 +/- 7.5 Hgmm; deltaABP 70 degrees - 0(C) degrees = -11.1 +/- 7.3 Hgmm; p < 0.05), which suggests a damage to the sympathetic cardiovascular system. A disturbance of the cerebral autoregulation in patients was suggested by a 'progressively decreasing MCA average velocity (V(MCA)) during graded tilt, which was significant at 70 degrees (deltaV(ACM) = 9.8 +/- 8.82% cms(-1); p(C-PP) P 0.5), and by a higher slope of pressure-velocity curve (AR(C) = 0.143 +/- .125% cms(-1)/Hgmm; AR(PP) = 0.38 +/- 0.25% cms(-1)/Hgmm; p(C-PP) < 0.05). CONCLUSIONS: The results show that the cerebral blood flow of patients is more dependent on perfusion pressure compared to healthy controls. The disturbance of the sympathetic cardiovascular system and of cerebral autoregulation could be the consequence of a damage to the postganglionic structures in Parkinson's disease. These results could explain the frequent orthostatic intolerance of patients even with normal blood pressure.

Aged↗

PubMed2005

Reduced baroreceptor sensitivity and elasticity of the carotid artery in a preeclamptic patient.

Baroreflex sensitivity, distensibility coefficient, and intima-media thickness (IMT) of the common carotid artery were determined in a preeclamptic patient during 1st and 3rd trimesters as well as after childbirth. From the beginning of her pregnancy, baroreflex sensitivity and distensibility coefficient of the carotid artery exhibited a parallel decline, whereas the IMT increased as compared with normotensive pregnancies. The values of all parameters examined returned to their initial levels after 14 weeks of delivery. These results suggest that augmented IMT and carotid stiffness coupled to baroreceptor dysfunction may have contributed to the perturbation of blood pressure control in our preeclamptic patient.

Adult↗

PubMed2005

Poly(ADP-ribose) polymerase regulates myocardial calcium handling in doxorubicin-induced heart failure.

Reactive oxygen and nitrogen species are overproduced in the cardiovascular system in response to the exposure to doxorubicin, a cardiotoxic anticancer compound. Oxidant-induced cell injury involves the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) and pharmacological inhibition of PARP has recently been shown to improve myocardial contractility in doxorubicin-induced heart failure models. The current investigation, by utilizing an isolated perfused heart system capable of beat-to-beat intracellular calcium recording, addressed the following questions: (1) is intracellular calcium handling altered in hearts of rats after 6-week doxorubicin treatment, under baseline conditions, and in response to oxidative stress induced by hydrogen peroxide exposure in vitro; and (2) does pharmacological inhibition of PARP with the phenanthridinone-based PARP inhibitor PJ34 affect the changes in myocardial mechanical performance and calcium handling in doxorubicin-treated hearts under normal conditions and in response to oxidative stress. The results showed a marked elevation in intracellular calcium in the doxorubicin-treated hearts which was normalized by pharmacological inhibition of PARP. PARP inhibition also prevented the myocardial contractile disturbances and calcium overload that developed in response to hydrogen peroxide in the doxorubicin-treated hearts. We conclude that PARP activation contributes to the development of the disturbances in cellular calcium handling that develop in the myocardium in response to prolonged doxorubicin exposure.

Animals↗

PubMed2005

Opposite changes in carotid versus aortic stiffness during healthy human pregnancy.

Systemic arterial compliance has been known to increase during healthy pregnancy, whereas, recently, the carotid artery has been reported to stiffen. To clarify this controversy, we simultaneously measured aortic PWV (pulse wave velocity) and carotid artery elastic parameters in a cohort of pregnant women. Twelve normotensive pregnant women were studied longitudinally during the three trimesters of pregnancy (T1, T2 and T3 respectively) and 12 weeks PP (postpartum). Carotid artery diastolic diameter and pulsatile distension was measured by an echo-wall tracking method and carotid pulse pressure by applanation tonometry. Carotid strain, compliance, distensibility coefficient, stiffness index beta, Einc (incremental elastic modulus) and augmentation index were calculated. Aortic PWV was determined to estimate aortic distensibility. All carotid artery elastic parameters indicated significant stiffening from T1 to T3 (1.8+/-0.2 versus 2.9+/-0.3 mmHg for Einc), which was reversed after delivery (2.3+/-0.2 mmHg). Aortic PWV decreased during pregnancy (6.2+/-0.2 versus 5.4+/-0.2 m/s) and increased in the PP period (6.7+/-0.2 m/s). No correlation was found between changes in carotid artery elastic parameters and changes in aortic PWV either from T1 to T3 or from T3 to PP. The carotid artery exhibits regionally specific stiffening during pregnancy, which appears to represent a qualitatively different change in arterial elastic behaviour.

Adult↗

PubMed2005

Experimental orthostasis elicits sustained hypertension, which can be prevented by sympathetic blockade in the rat.

Incidence of orthostatic hypertension is estimated at 5% but is even more prevalent in borderline hypertension and autonomic neuropathies. The aim of this study was to develop a potential model to investigate orthostatic hypertension. We used normotensive and hypertensive Wistar rats to analyze responses and diurnal variations of arterial blood pressure, heart rate, temperature, and locomotor activity by telemetry. Orthostatic tests were carried out during 45 degrees head-up tilt (R, repeated 3 times for 5 minutes; or S, sustained for 120 minutes). Hypertension was induced by blockade of nitric oxide synthesis. In normotensives, horizontal control blood pressure was R115.4 +/- 1.4/S113.7 +/- 1.6 mm Hg and heart rate R386.4 +/- 7.0/S377.9 +/- 8.8 bpm. Head-up tilt increased blood pressure by R4.5/S8.4 mm Hg, including a 3.8 mm Hg hydrostatic component. The sustained hypertensive response was prevented by prazosin (10 mg/kgbw) and augmented by a subanesthetic dose of chloralose (26 mg/kgbw). In NO-deprived hypertension, horizontal control blood pressure and heart rate were R138.4 +/- 2.6/S140.3 +/- 2.7 mm Hg and R342.1 +/- 12.0/S346.0 +/- 8.3 bpm, respectively. Tilt increased blood pressure further by R4.2/S9.4 mm Hg. In both normo- and hypertensives, variables exhibited similar diurnal rhythms except for nighttime locomotor activity, reduced from 3.7 +/- 0.4 to 2.8 +/- 0.3 counts/s. These data demonstrate that conscious rats respond to sustained orthostasis with hypertension, probably as a result of increased sympathetic output. Decreasing stress using a subanesthetic dose of chloralose increased this response, reducing the inhibitory effect on hypertensive responses.

Animals↗

PubMed2004

Poly(ADP-Ribose) polymerase promotes cardiac remodeling, contractile failure, and translocation of apoptosis-inducing factor in a murine experimental model of aortic banding and heart failure.

Oxidant stress-induced activation of poly(ADP-ribose) polymerase (PARP) plays a role in the pathogenesis of various cardiovascular diseases. We have now investigated the role of PARP in the process of cardiac remodeling and heart failure in a mouse model of heart failure induced by transverse aortic constriction (banding). The catalytic activity of PARP was inhibited by the potent isoindolinone-based PARP inhibitor INO-1001 or by PARP-1 genetic deficiency. PARP inhibition prevented the pressure overload-induced decrease in cardiac contractile function, despite the pressure gradient between both carotid arteries being comparable in the two experimental groups. The development of hypertrophy, the formation of collagen in the hearts, and the mitochondrial-to-nuclear translocation of the cell death factor apoptosis-inducing factor (AIF) were attenuated by PARP inhibition. The ability of the inhibitor to block the catalytic activity of PARP was confirmed by immunohistochemical detection of poly(ADP-ribose), the product of the enzyme in the heart. Plasma levels of INO-1001, as measured at the end of the experiments, were in the concentration range sufficient to block the oxidant-mediated activation of PARP in murine cardiac myocytes in vitro. Myocardial hypertrophy and AIF translocation was also reduced in PARP-1-deficient mice undergoing aortic banding, compared with their wild-type counterparts. Overall, the current results demonstrate the importance of poly(ADP-ribos)ylation in the pathogenesis of banding-induced heart failure.

Animals↗

PubMed2004

Restoration of the endothelial function in the aortic rings of apolipoprotein E deficient mice by pharmacological inhibition of the nuclear enzyme poly(ADP-ribose) polymerase.

Oxidant-mediated activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) plays a role in the development of endothelial dysfunction and the pathogenesis of various cardiovascular diseases. The aim of the current study was to investigate whether activation of PARP contributes to the development of endothelial dysfunction in the apolipoprotein E (ApoE) deficient mice. We tested whether PARP inhibition prevents the development of endothelial dysfunction and whether it restores function in vessels with established endothelial dysfunction. ApoE deficient mice were kept on high-fat diet for 12 weeks with and without INO-1001 treatment. Chronic treatment with the PARP inhibitor INO-100 reduced the degree of the endothelial dysfunction (the ability of the vessel to relax to acetylcholine) in the thoracic aortae of ApoE deficient mice. In addition, in vitro incubation of vessels from ApoE deficient mice with established endothelial dysfunction with the PARP inhibitor acutely improved the ability of the rings to relax to acetylcholine. We conclude that the early atherosclerotic functional alterations that develop in the endothelium of the ApoE deficient mice are, at least in part, reversible, and are dependent on the activation of the nuclear enzyme PARP in the endothelial cells.

Acetylcholine↗

PubMed2004

Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure.

Aging is associated with profound changes in the structure and function of the heart. A fundamental understanding of these processes, using relevant animal models, is required for effective prevention and treatment of cardiovascular disease in the elderly. Here, we studied cardiac performance in 4- to 5-mo-old (young) and 24- to 26-mo-old (old) Fischer 344 male rats using the Millar pressure-volume (P-V) conductance catheter system. We evaluated systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (+dP/dt), and its relation to end-diastolic volume (+dP/dt-EDV) as well as the time constant of left ventricular pressure decay, as an index of relaxation. The slope of the end-diastolic P-V relation (EDPVR), an index of left ventricular stiffness, was also calculated. Aging was associated with decrease in left ventricular systolic pressure, +dP/dt, maximal slope of the diastolic pressure decrement, +dP/dt-EDV, PRSW, ejection fraction, stroke volume, cardiac and stroke work indexes, and efficiency. In contrast, total peripheral resistance, left ventricular end-diastolic volume, left ventricular end-diastolic pressure, and EDPVR were greater in aging than in young animals. Taken together, these data suggest that advanced aging is characterized by decreased systolic performance accompanied by delayed relaxation and increased diastolic stiffness of the heart in male Fischer 344 rats. P-V analysis is a sensitive method to determine cardiac function in rats.

Aging↗

PubMed2004

A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging.

Increased production of reactive oxygen and nitrogen species has recently been implicated in the pathogenesis of cardiac and endothelial dysfunction associated with atherosclerosis, hypertension, and aging. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP), which in turn contributes to cardiac and vascular dysfunction in various pathophysiological conditions including diabetes, reperfusion injury, circulatory shock, and aging. Here, we investigated the effect of a new PARP inhibitor, INO-1001, on cardiac and endothelial dysfunction associated with advanced aging using Millar's new Aria pressure-volume conductance system and isolated aortic rings. Young adult (3 months old) and aging (24 months old) Fischer rats were treated for 2 months with vehicle, or the potent PARP inhibitor INO-1001. In the vehicle-treated aging animals, there was a marked reduction of both systolic and diastolic cardiac function and loss of endothelial relaxant responsiveness of aortic rings to acetylcholine. Treatment with INO-1001 improved cardiac performance in aging animals and also acetylcholine-induced, nitric oxide-mediated vascular relaxation. Thus, pharmacological inhibition of PARP may represent a novel approach to improve cardiac and vascular dysfunction associated with aging.

Aging↗

PubMed2004

Effects of poly(ADP-ribose) polymerase inhibition on inflammatory cell migration in a murine model of asthma.

BACKGROUND: Poly(ADP-ribose) polymerase-1 (PARP-1), a monomeric nuclear enzyme present in eukaryotes, plays a role in cell death, inflammatory mediator expression, and mononuclear cell recruitment in various experimental models of inflammation and reperfusion injury. Part of the molecular mechanism of this function involves the regulation of cytokine and chemokine production. Since chemokines are principal regulators of mononuclear and polymorphonuclear cell trafficking in asthma, we investigated the possibility whether PARP modulates chemokine production and cell recruitment in a murine model of asthma. MATERIAL/METHODS: We studied ovalbumin-sensitized mice challenged with a single dose of ovalbumin. RESULTS: PARP inhibition with the phenanthridinone-based PARP inhibitor PJ34 suppressed inflammatory cell migration. These effects were associated with downregulation of the CC chemokine MIP-1alpha, but not the CXC chemokine MIP-2. The production of TNF- alpha and IL-12, but not IL-5 or IL-13, was also suppressed by PARP inhibition. CONCLUSIONS: Our results demonstrate the pathogenetic role of PARP activation in a murine model of asthma. PARP selectively regulates the production of certain chemokines and cytokines in this experimental model, which may be responsible for some of the observed protective effects seen in the current murine asthma model.

Animals↗

PubMed2004

Lack of mitochondrial nitric oxide production in the mouse brain.

Based on our initial finding that the nitric oxide (NO) sensitive fluorochrome diaminofluorescein (DAF) was localized to mitochondria in cultured primary neurons, we investigated whether brain mitochondria produce NO through a mitochondrial NO synthase (mtNOS) enzyme. Isolated brain mitochondria were loaded with DAF and subjected to flow cytometry analysis. Neither the application of NOS inhibitors nor the genetic disruption of either NOS gene diminished the DAF-fluorescence. However, peroxynitrite scavengers reduced the mitochondrial DAF fluorescence, indicating that the DAF signal is not specific to NO. Chemiluminescence detection in the head space gas and a Clark-type NO-sensitive electrode in the solution failed to detect NO release in brain mitochondria. NOS activity in mitochondria was only 1% of the whole brain NOS activity level, which may be attributed to extramitochondrial contamination. Extensive immunoblotting and immunoprecipitation experiments failed to show the presence of endothelial, neuronal, or inducible NOS in mouse brain mitochondria using a variety of primary antibodies. Arginine, calmodulin or 2,5-ADP affinity purification protocols successfully concentrated eNOS and nNOS from full brain tissue but failed to show any signal in mitochondria. We conclude that mouse brain mitochondria do not contain NOS isoforms, nor do they produce NO through a NOS-dependent mechanism.

Animals↗

PubMed2003

Time related changes in calcium handling in the isolated ischemic and reperfused rat heart.

The main aim of this study was to assess the kinetics of intracellular free calcium (Ca(2+)i) handling by isolated rat hearts rendered ischemic for 30 min followed by 30 min of reperfusion analyzing the upstroke and downslope of the Ca(2+)i transient. Changes in mechanical performance and degradation of membrane phospholipids--estimated by tissue arachidonic acid content--were correlated with Ca(2+)i levels of the heart. The fluorescence ratio technique was applied to estimate Ca(2+)i. The disappearance of mechanical activity of the heart preceded that of the Ca(2+)i transient in the first 2 min of ischemia. The slope of upstroke of the Ca(2+)i transient, reflecting Ca2+ release, decreased by 60%, while the duration of the downslope of the transient, reflecting Ca2+ sequestration, expressed a significant prolongation (105 +/- 17 vs. 149 +/- 39 msec) during the first 3 min of ischemia. At about 20 min of ischemia end-diastolic pressure expressed a 3.5-fold increase (contracture) when the fluorescence ratio showed a 2-fold elevation. Reperfusion was accompanied with a further precipitous increase in end-diastolic pressure, while resting Ca(2+)i remained at end-ischemic levels. Increases in the arachidonic acid (AA) content of the ischemic and postischemic hearts were proportional to Ca(2+)i levels. In summary, the present findings indicate that both calcium release and removal are hampered during the early phase of ischemia. Moreover, a critical level of Ca(2+)i and a critical duration of ischemia may exist to provoke contracture of the heart. Upon reperfusion the hearts show membrane phospholipid degradation and signs of stunning exemplified by elevated AA levels, partial recovery of Ca(2+)i handling and sustained depression of mechanical performance.

Animals↗