ABSTRACT
Ischemic changes in excised rat myocardium were followed by series of T1 or T2 measurements from 1 to 60 min after isolated perfusion cessation, and the influence of manganese enhancement was investigated. An inverse Laplace transformation (ILT) of T1 or T2 data was used to resolve the number, time constants, and fractions of tissue water components in a continuous distribution. For T1 distributions, one single tissue component approximately 900 ms was significantly shortened and dispersed by manganese enhancement (25 and 200 microM MnCl2). For T2 distributions, three tissue components (approximately 30, approximately 100, and approximately 350 ms) were obtained initially. The two shortest components merged after approximately 10 min to one component (approximately 40 ms). Both T1 and T2 tissue components became shorter with time. In particular, the T2 distribution dynamics might be compatible with complex sequential changes in tissue water fractions during ischemia.
Subject(s)
Body Water/metabolism , Magnetic Resonance Spectroscopy , Myocardial Ischemia/metabolism , Myocardium/metabolism , Algorithms , Animals , Chlorides/pharmacokinetics , Extracellular Fluid/metabolism , Heart Ventricles/metabolism , Intracellular Fluid/metabolism , Male , Manganese Compounds/pharmacokinetics , Rats , Rats, Wistar , Time FactorsABSTRACT
Water compartments were identified and equilibrium water exchange was studied in excised rat myocardium enriched with intracellular manganese (Mn(2+)). Standard relaxographic measurements were supplemented with diffusion-T(2) and T(1)-T(2) correlation measurements. In nonenriched myocardium, one T(1) component (800 ms) and three T(2) components (32, 120, and 350 ms) were identified. The correlation measurements revealed fast- and slow-diffusing water fractions with mean diffusion coefficients of 1.2 x 10(-5) and 3.0 x 10(-5) cm(2) s(-1). The two shortest T(2) components, which had different diffusivities, both originated from water in intracellular compartments. A component with longer relaxation time (T(1) approximately equal 2200 ms; T(2) approximately equal 1200 ms), originating from extra-tissue water, was also observed. The presence of this component may lead to erroneous estimations of water exchange rates from multiexponential relaxographic analyses of excised tissues. The tissue T(1) value is strongly reduced with increasing enrichment of Mn(2+), and eventually a second tissue T(1) component emerges, indicating a shift in the equilibrium water exchange between intra- and extracellular compartments from the fast-exchange limit to the slow-exchange regime. Using a two-site water exchange analysis, the lifetime of intracellular water, T(ic), was found to be 475 ms, with a fraction, p(ic), of 0.71.
Subject(s)
Magnetic Resonance Spectroscopy/methods , Myocardium/metabolism , Water/metabolism , Animals , Extracellular Fluid/metabolism , Intracellular Fluid/metabolism , Male , Manganese/analysis , Rats , Rats, WistarSubject(s)
Antineoplastic Agents/pharmacology , Edetic Acid/analogs & derivatives , Pyridoxal Phosphate/analogs & derivatives , Superoxide Dismutase/metabolism , Biomimetic Materials/pharmacology , Contrast Media/pharmacology , Edetic Acid/pharmacology , Hydrogen Peroxide/metabolism , Pyridoxal Phosphate/pharmacologyABSTRACT
We have used combined D-T1 and T1-T2 correlation experiments to explore water compartments in rat heart tissue (myocardium). The results show that two main compartments can be identified, which we assign to extracellular (ec) and intracellular (ic) water. The exchange rate of water across the cell membrane was found to be on the order of 0.1 Hz. In addition, the T1-T2 correlation measurements indicate that the ic compartment contain two T2 populations.
Subject(s)
Body Water/chemistry , Magnetic Resonance Spectroscopy/methods , Myocardium/chemistry , Animals , Body Fluid Compartments , Cell Membrane Permeability , Porosity , RatsABSTRACT
OBJECTIVES: Manganese ions (Mn) enter cardiomyocytes via calcium (Ca) channels and enhance relaxation intracellularly. To prevent negative inotropy, new Mn-releasing contrast agents have been supplemented with high Ca. The study aim was to investigate how this affects cardiac function and magnetic resonance efficacy. MATERIALS AND METHODS: MnCl2 based contrast agents, manganese and manganese-calcium (Ca:Mn 10:1), were infused during 4 repeated washin-washout sequences in perfused guinea pig hearts. [Mn] were 10, 50, 100 and 500 microM. RESULTS: During washin, manganese depressed left ventricular developed pressure (LVDP) by 4, 9, 17, and 53% whereas manganese-calcium increased LVDP by 13, 18, 25, and 56%. After experiments, tissue Mn contents (nmol/g dry wt) were control <40, manganese 3720, and manganese-calcium 1620. T1 was reduced by 85-92% in Mn-enriched hearts. CONCLUSIONS: High Ca supplements to Mn-releasing contrast agents may be counterproductive by inducing a strong positive inotropic response and by reducing the magnetic resonance efficacy.
Subject(s)
Calcium/pharmacokinetics , Chlorides/pharmacokinetics , Contrast Media/pharmacokinetics , Heart/drug effects , Magnetic Resonance Imaging , Manganese Compounds/pharmacokinetics , Adenosine Triphosphate/analysis , Animals , Calcium/metabolism , Calcium Gluconate/administration & dosage , Calcium Gluconate/chemistry , Chlorides/administration & dosage , Chlorides/chemistry , Contrast Media/chemistry , Guinea Pigs , Heart/physiology , Heart Ventricles/drug effects , Magnetic Resonance Imaging/methods , Manganese/administration & dosage , Manganese/analysis , Manganese/chemistry , Manganese Compounds/administration & dosage , Manganese Compounds/chemistry , Myocardial Contraction/drug effects , Myocardium/chemistry , Myocardium/metabolism , Perfusion , Phosphocreatine/analysis , ProtonsABSTRACT
The efficacy of manganese ions (Mn2+) as intracellular (ic) contrast agents was assessed in rat myocardium. T1 and T2 and Mn content were measured in ventricular tissue excised from isolated perfused hearts in which a 5-min wash-in with 0, 30, 100, 300, or 1000 microM of Mn dipyridoxyl diphosphate (MnDPDP) was followed by a 15-min wash-out to remove extracellular (ec) Mn2+. An inversion recovery (IR) analysis at 20 MHz revealed two T1 components: an ic and short T1-1 (650-251 ms), and an ec and longer T1-2 (2712-1042 ms). Intensities were about 68% and 32%, respectively. Tissue Mn content correlated particularly well with ic R1-1. A two-site water-exchange analysis of T1 data documented slow water exchange with ic and ec lifetimes of 11.3 s and 7.5 s, respectively, and no differences between apparent and intrinsic relaxation parameters. Ic relaxivity induced by Mn2+ ions in ic water was as high as 56 (s mM)(-1), about 8 times and 36 times higher than with Mn2+ aqua ions and MnDPDP, respectively, in vitro. This value is as high as any reported to date for any synthetic protein-bound metal chelate. The increased rotational correlation time (tauR) between proton and electron (Mn2+) spins, and maintained inner-sphere water access, might make ic Mn2+ ions and Mn2+ -ion-releasing contrast media surprisingly effective for T1-weighted imaging.
Subject(s)
Contrast Media/pharmacokinetics , Manganese/pharmacokinetics , Myocardium/metabolism , Analysis of Variance , Animals , Contrast Media/administration & dosage , Freeze Drying , Heart/drug effects , Heart Ventricles/drug effects , Heart Ventricles/metabolism , In Vitro Techniques , Least-Squares Analysis , Male , Manganese/administration & dosage , Rats , Rats, WistarABSTRACT
The role of oxidative stress in clinical cardiology is still controversial. The aims of the present study were to examine if minor ischaemic episodes as may occur during elective percutaneous coronary intervention (PCI) induce oxidative stress and, eventually, if oxygen stress correlates with myocardial injury. Thirty eight and nine patients underwent PCI and diagnostic coronary angiography, respectively. Peripheral blood was sampled at different time points for plasma analyses of: 8-iso-PGF2alpha (free radical-mediated oxidative stress); 15-keto-dihydro-PGF2alpha (cyclooxygenase-mediated inflammation); troponin-T (myocardial injury); hsCRP, vitamin A and vitamin E; and, total antioxidants status (TAS). In both groups 8-iso-PGF2alpha increased transiently by approximately 80% (p < 0.001) during the procedure. There was a minor troponin-T release (p < 0.001) after PCI, but no correlation with 8-iso-PGF2alpha. Troponin-T did not increase after angiography. 15-keto-dihydro-PGF2alpha decreased by 50% after ended procedure, but increased by 100% after 24 h compared to baseline. hsCRP increased significantly (p < 0.001) from baseline to the next day in the PCI-group, but not in the angiography group. Vitamins and TAS decreased slightly after the procedures. It is concluded that a moderate oxidative stress was induced by both elective PCI and coronary angiography but that no correlation was found between oxidative stress and myocardial injury in this setting. This indicates that other mechanisms than ischaemia-reperfusion episodes caused an elevation in plasma isoprostane such like the injury at a vascular site mutual for both procedures. A secondary finding from the study was elevated markers of early inflammatory response, not only after PCI, but also after angiography.
Subject(s)
Angioplasty, Balloon, Coronary , Biomarkers/blood , Dinoprost/analogs & derivatives , Myocardial Infarction/therapy , Oxidative Stress , Adult , Aged , Aged, 80 and over , Angioplasty, Balloon, Laser-Assisted , Antioxidants/metabolism , C-Reactive Protein/metabolism , Coronary Angiography , Dinoprost/blood , Female , Humans , Male , Middle Aged , Troponin T/blood , Vitamin A/blood , Vitamin E/bloodABSTRACT
Paramagnetic manganese (Mn) ions (Mn(2+)) are taken up into cardiomyocytes where they are retained for hours. Mn content and relaxation parameters, T(1) and T(2), were measured in right plus left ventricular myocardium excised from isolated perfused rat hearts. In the experiments 5 min wash-in of MnCl(2) were followed by 15 min wash-out to remove extracellular (ec) Mn(2+) MnCl(2), 25 and 100 micro M, elevated tissue Mn content to six and 12 times the level of control (0 micro M MnCl(2)). Variations in perfusate calcium (Ca(2+)) during wash-in of MnCl(2) and experiments including nifedipine showed that myocardial slow Ca(2+) channels are the main pathway for Mn(2+) uptake and that Mn(2+) acts as a pure Ca(2+) competitor and a preferred substrate for slow Ca(2+) channel entry. Inversion recovery analysis at 20 MHz revealed two components for longitudinal relaxation: a short T(1 - 1) and a longer T(1 - 2). Approximate values for control and Mn-treated hearts were in the range 600-125 ms for T(1 - 1) and 2200-750 ms for T(1 - 2). The population fractions were about 59 and 41% for the short and the long component, respectively. The intracellular (ic) R(1 - 1) and R(2 - 1) correlated best with tissue Mn content. Applying two-site exchange analyses on the obtained T(1) data yielded results in parallel to, but also differing from, results reported with an ec contrast agent. The calculated lifetime of ic water (tau(ic)) of about 10 s is compatible with a slow water exchange in the present excised cardiac tissue. The longitudinal relaxivity of Mn ions in ic water [60 (s mM)(-1)] was about one order of magnitude higher than that of MnCl(2) in water in vitro [6.9 (s mM)(-1)], indicating that ic Mn-protein binding is an important potentiating factor in relaxation enhancement.