Sodium-calcium balance in coronary angiography. Experimental experience with isotonic iodixanol.
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Animals↗
Biomedical subjects
J O Karlsson
Publications and source records attributed to J O Karlsson.
Long-term storage of tissues by cryopreservation: critical issues.
The technique of cryopreservation (maintenance of biological samples in a state of 'suspended animation' at cryogenic temperatures), its potential use in tissue engineering applications and current obstacles to the development of effective cryopreservation methods for tissues are reviewed. A didactic overview of the principles of cryobiology and the methodology of cryopreservation is given, with emphasis on the processes of injury to cells during freezing and thawing, and how these are related to the physicochemical and biophysical changes occurring during cryopreservation. Critical issues relevant to the application of cryopreservation methods to tissues are then addressed, including heat and mass transfer limitations in these bulk systems, intrinsic differences between isolated and cultured cells, and mechanisms of freezing injury unique to tissue systems.
Animals↗
Fertilization and development of mouse oocytes cryopreserved using a theoretically optimized protocol.
Rational design of a cryopreservation protocol was demonstrated by using theoretical models of the cryopreservation process to develop an optimal freezing protocol for mouse oocytes. A coupled mechanistic model of the processes of freeze-induced cell dehydration and intracellular ice formation was developed, and cryomicroscopical measurements of intracellular ice formation kinetics were used to determine biophysical parameters required by the model, and to test model predictions of the freezing behaviour of mouse oocytes. A simple phenomenological model for oocyte damage resulting from exposure to concentrated electrolyte and cryoprotectant solutions during cryopreservation was obtained by defining a cost function equal to the duration of the freezing protocol. A two-step freezing protocol was theoretically optimized by using a sequential simplex algorithm to minimize the cost function, subject to the constraint that the predicted probability of intracellular ice formation remain below 5%, yielding a putative optimum at the cooling rate B = 0.59 degrees C/min, and plunge temperature Tp = -67 degrees C. By systematically varying B and Tp about these values in experiments with mouse oocytes cryopreserved in 1.5 M dimethyl sulphoxide, the maximal recovery of intact oocytes with a normal morphology (82%) was obtained for B = 0.5 degrees C/min and Tp = -80 degrees C. Further evaluation of the fertilizability and developmental capacity of oocytes cryopreserved using the optimized protocol yielded cleavage to the 2-cell stage in 65% of oocytes inseminated, and blastocyst formation in 50% of these 2-cell embryos.
Animals↗
Calpains in the human lens: relations to membranes and possible role in cataract formation.
Calpains are Ca-activated neutral proteases present in all cells together with an endogenous inhibitor, calpastatin. Proposed substrates are; cytoskeletal proteins like microtubules and actin, protein kinases such as PKC and membrane-bound enzymes like Ca-ATPase and the Ca-channel. In lenses from different species calpains have been detected in decreasing amounts from the epithelium to the cortex to the nucleus. Several substrates for calpain in the lens have been demonstrated: crystallins, vimentin, actin, beaded filaments and MP26 among others. Both studies on animal models and capsulorhexis indicate that calpains are mainly involved in cortical cataract.
Calcium↗
Degradation of fodrin and MAP 2 after neonatal cerebral hypoxic-ischemia.
Neonatal rats were subjected to transient cerebral hypoxic-ischemia (unilateral occlusion of the common carotid artery + 7.70% O2 for 100 min) and allowed to recover for 3 h, 24 h, 2 days or 14 days. Consecutive tissue sections were stained with antibodies against alpha-fodrin, the 150 kDa breakdown product of alpha-fodrin (FBDP, marker of calpain proteolysis) or microtubule associated protein 2 (MAP 2, marker of dendrosomatic neuronal injury). Cortical tissue pieces were subjected to Western blotting using the antibody against the FBDP. Areas with brain injury displayed a distinct loss of MAP 2 which clearly delineated the infarct. FBDP accumulated in injured and borderline regions ipsilaterally and a less conspicuous, transient increase in FBDP also occurred in the contralateral hemisphere, especially in the white matter. A reciprocal staining pattern could be seen in the cerebral cortex, i.e. loss of MAP 2 and accumulation of FBDP, most pronounced 14 days after the insult. Fodrin and MAP 2 are known calpain substrates, and degradation of these proteins preceded neuronal degeneration, indicating that these proteases may be involved in the early events triggering the cascades leading to neuronal death.
Animals↗
Fodrin degradation and subcellular distribution of calpains after neonatal rat cerebral hypoxic-ischemia.
Neonatal rats were subjected to transient cerebral hypoxic-ischemia (unilateral occlusion of the common carotid artery + 7.70% O2 for 100 min). Ipsi-and contralateral parietal cerebral cortex was assayed with Western blotting for fodrin breakdown product (FBDP). Calpain immunoreactivity was assayed in the cytosolic fraction (CF) and the membrane and microsomal fraction (MMF). Calpain immunoreactivity decreased bilaterally in the CF during the insult (62-68% of controls) and remained significantly lower during early recovery, whereas the MMF showed no significant changes. This relative redistribution of calpains coincided with the appearance of FBDP in the left, ipsilateral hemisphere, displaying a significantly higher level of FBDP from immediately after the insult until at least 1 day of recovery (204-292% of controls). No significant changes in FBDP could be detected in the right, contralateral hemisphere, indicating that although redistribution of calpains occurred, hypoxia per se did not suffice to initiate fodrin degradation in this model of neonatal hypoxic-ischemia.
Animals↗
Action of calpastatin in prevention of cardiac L-type Ca2+ channel run-down cannot be mimicked by synthetic calpain inhibitors.
Activity of L-type Ca2+ channels in a membrane patch disappears rapidly when the patch is excised from the cell into an artificial solution. This channel run-down observed in isolated membrane patches can however, be prevented by application of calpastatin, an endogenous protease inhibitor, and ATP. The high specificity of calpastatin for the protease calpain would clearly point to a participation of calpain activity in the run-down of Ca2+ channels. In an attempt to examine a possible involvement of calpain, three synthetic and rather specific calpain inhibitors were substituted for calpastatin. One of these inhibitors chosen for its membrane permeability in addition allowed calpain activity to be inhibited even before patch excision. The potency of these compounds in inhibiting calpain, specifically mu- and m-calpain, was first determined in a biochemical assay and then compared with their efficacy in preventing Ca2+ channel run-down. Surprisingly, calpastatin was least effective in calpain inhibition but by far the most potent in prevention of Ca2+ channel run-down. In addition run-down of Ca2+ channel activity was examined for its reversibility, which would not be expected upon involvement of a proteolytic process. However, Ca2+ channel activity clearly recovered after run-down by application of calpastatin. In contrast, synthetic calpain inhibitors were unable to reverse Ca2+ channel run-down. These results indicate that proteolysis might only be partially responsible for channel run-down and suggest an as yet unidentified function for calpastatin beyond its inhibitory action on calpain in the regulation of Ca2+ channel activity.
Adenosine Triphosphate↗
Effects of manganese dipyridoxyl diphosphate, dipyridoxyl diphosphate--, and manganese chloride on cardiac function. An experimental study in the Langendorff perfused rat heart.
RATIONALE AND OBJECTIVES: Manganese dipyridoxyl diphosphate (MnDPDP) is a promising contrast agent for magnetic resonance imaging of the liver. The authors explored the possibility that high concentrations of MnDPDP may cause manganese ion (Mn++)-induced side effects on cardiac function. METHODS: Potential cardiodepression by MnDPDP, DPDP--, and manganese chloride (MnCl2) (100-3,000 mumol/L) was investigated in the isolated rat heart, with left ventricular developed (systolic--end-diastolic) pressure and heart rate as the primary indices of cardiac function. RESULTS: During 5-minute exposures, 10% and 50% decreases in left ventricular developed pressure were observed for MnDPDP, 250 mumol/L and 1580 mumol/L; DPDP--, less than 100 mumol/L and 1000 mumol/L; MnCl2, 30 mumol/L and 250 mumol/L. Heart rate changes were not observed with MnDPDP. Cardiodepression was reversed within 2 minutes during a 14-minute recovery period for all investigated concentrations of MnDPDP and was less rapid for the highest concentrations of MnCl2. CONCLUSIONS: Manganese dipyridoxyl diphosphate is well tolerated in the rat heart at concentrations as high as 200 to 250 mumol/L and is approximately 10 times less cardiotoxic than MnCl2. Cardiodepressive effects of MnDPDP in the present rat heart model, perfused in the absence of blood and proteins, are related primarily to the release of free Mn++ ions and in part to the simultaneous release of DPDP--.
Animals↗
Genetic differentiation in Fomitopsis pinicola (Schwarts: Fr.) Karst studied by means of arbitrary primed-PCR.
Genetic variation within and among one Finnish and three Swedish populations of Fomitopsis pinicola (Schwarts: Fr.) Karst. were studied by amplifying DNA from haploid isolates originating from single spore cultures using two arbitrary primers. Analysis offspring from single fruit bodies revealed only three pairs of codominant alleles among 42 variable genetic markers, the remaining 38 segregated independently. Genetic similarity was measured in terms of Euclidean distance. Individuals in the Finnish population tended to form a distinct cluster in the principal component analysis. Variation within and among populations/regions was partitioned by Analysis of Molecular Variance-AMOVA. Within population variation accounted for 91.6% of the total genetic variation. The remaining 7.68% was accounted for by variation between the Finnish population and each of the three Swedish ones. Variation among the Swedish populations accounted for only 0.72% of the total variation. Wright's Fst was 0.17 for all four populations and 0.13 for the three Swedish populations. These relatively low values indicate that there is gene flow among all populations or that they are derived from a common ancestral population. The observed pattern of genetic variation is probably the result of effective spore dispersal and the continuous distribution of this common early successional species.
Base Sequence↗
Visipaque is isotonic to human and rat blood plasma.
Even at its highest concentration, 320 mg I/ml, Visipaque - based on the nonionic dimer iodixanol - is isoosmotic to blood plasma, whereas Omnipaque (300 mg I/ml) - based on the nonionic monomer iohexol - has an osmolality of about twice that of the plasma. However, the fact that the solution is isoosmotic to plasma does not necessarily mean that it is isotonic to plasma. An isoosmotic solution can still cause a net movement of water over the plasma membranes of, for example, erythrocytes and endothelial cells. Determination of the tonicity of Visipaque 320 mg I/ml and comparison with that of Omnipaque 300 mg I/ml and hypertonic NaCl have been performed. No change in the water content of human erythrocytes was seen after mixing whole blood 10:1 with either Visipaque 320 mg I/ml or 155 mM NaCl, whereas a significant decrease in water content occurred with Omnipaque 300 mg I/ml and 620 mM NaCl. No difference in the water content of rat erythrocytes was evident after mixing whole blood with Visipaque 320 mg I/ml or isotonic NaCl. However, as with human erythrocytes, a significant decrease in water content occurred after rat blood was mixed with Omnipaque 300 mg I/ml. In conclusion, Visipaque 320 mg I/ml does not cause any net movement of water over the human or the rat erythrocyte plasma membrane, i.e., Visipaque is isotonic to human and rat blood plasma.
Animals↗
Sodium-calcium relationships and cardiac function during coronary bolus perfusion.
The present review deals with the side-effects of contrast media (CM) on cardiac function during coronary angiography. A physiological approach is used to redefine existing concepts of CM osmotoxicity and chemotoxicity in terms of osmolal, ionic and molecular effects. The main idea conveyed is that purely ionic effects are of central importance during and immediately following the transit of a brief coronary bolus. Ionic effects result largely from rapid transient washout of normal extracellular ions, but are also influenced by ions present in the CM. In particular, the calcium (Ca) and sodium (Na) ions controlling cardiac function are easily affected. The myocardial Na-Ca exchange, which is mainly a physiological mechanism for cellular Ca efflux during cardiac relaxation, is therefore highlighted in detail. The importance of avoiding a potential Na-Ca mismatch is shown by examples from basic physiology, cardiac surgery and coronary angiography and by results of experiments with Visipaque. In the isomolal and isotonic CM Visipaque, which is based on the dimer isodixanol (320 mg I/ml), an available osmolal space is filled with an appropriately balanced supplement consisting of NaCl (19mM) and CaCl2 (0.3 mM).
Animals↗
Cardiac effects of iodixanol compared to those of other nonionic and ionic contrast media on the isolated rat heart.
This study was designed to compare the cardiac electrophysiology and mechanical effects of iodixanol to those of iotrolan, iopromide, ioxaglate and diatrizoate. Two consecutive injections of contrast media (CM) (0.3 g I/kg and 0.9 g I/kg b.w.) were given to spontaneously beating, Langendorff-perfused rat hearts. CM were given as a single, short-lasting bolus injection (i.e. over 2 and 5 s). Changes in aortic pressure, left ventricular pressures and ECG were continuously recorded during constant volume perfusion. The nonionic CM had less pronounced effects on aortic pressure than had the ionic media. The peak rate of isovolumetric contraction (LV dP/dt(max)) was slightly decreased by iodixanol and iotrolan, slightly more decreased by iopromide and markedly decreased by ioxaglate and diatrizoate. Similarly, the peak rate of pressure decline (LV dP/dt (min)) was only slightly decreased by iodixanol and iotrolan. Also, the 2 nonionic dimers had the smallest effects on the left ventricular end diastolic pressure (LVEDP) and heart rate. Ioxaglate lengthened the PQ-interval, but less so than diatrizoate. THe QT-interval was only slightly lengthened by iodixanol and iotrolan, as compared to the lenghthening caused by iopromide, ioxaglate and diatrizoate. Single ventricular extrasystoles were seen in all groups. Extrasystoles up to 3 coupled beats were registered after ioxaglate and diatrizoate. No episodes of ventricular fibrillation occurred with any CM. In conclusion, the nonionic dimers, and in particular iodixanol, induce only minor changes in cardiac function, whereas the ionic dimer ioxaglate and the ionic monomer diatrizoate induce pronounced effects.
Animals↗
Effects of iodinated contrast media on peripheral blood flow.
All types of clinically employed iodinated roentgen contrast media (CM) cause vasodilatation after i.a. and i.v. administration, regardless of precise molecular structure. It is now apparent, however, that at iodine concentrations which provide equivalent angiographic contrast, this is significantly less with newer hexa-iodinated dimers, such as iodixanol and iotrolan, than older generations of compounds. The cellular mechanisms that underly the vasodilator effects of CM still remain to be fully elucidated but may include a) effects attributable to hyperosmolality; b) stimulation of the release of endogenous vasoactive mediators; and c) direct relaxant effects upon vascular smooth muscle. This review will discuss the possible contributions of these mechanisms to the vasodilatation observed in the clinical situation.
Animals↗
Angiographic contrast media relax isolated rabbit aorta through an endothelium-independent mechanism that may not depend on the presence of the iodine atom.
Systemically administered iodinated angiographic contrast media evoke vasodilatation through mechanisms that are at present poorly understood. In the current investigation we have evaluated the role of the vascular endothelium in responses to an iso-osmolar formation of the non-ionic dimer iodixanol and a hyperosmolar formulation of the non-ionic monomer iopromide. Isolated rabbit aortic ring preparations with endothelium intact or removed by gentle abrasion were mounted in organ baths containing oxygenated Holman's solution, and cumulative concentration-response curves for relaxation to the contrast media were constructed after pre-constriction by phenylephrine (300 nM) in the presence of indomethacin to inhibit prostaglandin synthesis. Endothelial denudation did not influence the ability of either iodixanol or iopromide to relax the aortic ring preparations. Iopromide was significantly more potent than iodixanol when expressed in terms of iodine concentration (mg I ml-1), but both agents were equipotent when expressed in terms of molarity (mM). We conclude that relaxation of isolated rabbit aortic rings to iodixanol and iopromide under conditions where there is no fluid flow is endothelium-independent, and therefore not mediated by release of the potent endogeneous nitrovasodilator endothelium-derived relaxing factor (EDRF). Furthermore, their relaxant activity under the in vitro experimental conditions employed is attributable to a direct action on vascular smooth muscle by factors in addition to osmolality, and may depend on features that are not specifically associated with the presence of the iodine atom.
Angiography↗
A method for protein assay in Laemmli buffer.
A simple, cheap, and rapid assay for soluble and membrane-bound protein solubilized in Laemmli sodium dodecyl sulfate sample buffer is described. Following the addition of trichloroacetic acid to a final concentration of 24%, the induced turbidity was measured at 570 nm in a microplate reader, after an incubation period of approximately 10-30 min. The assay is suitable for measuring bovine serum albumin at a concentration of 15 to 500 micrograms/ml in Laemmli buffer, corresponding to 2 to 75 micrograms protein per well on the microtiter plate. Other nonproteinaceous macromolecules in the sample may introduce an error.
Animals↗
Calpains in lens epithelium from patients with cataract.
Lens epithelium from patients with cataract was obtained during surgery and frozen. The samples were subjected to SDS-electrophoresis and Western blotting. Calpains were quantified using polyclonal antibodies against m- and mu-Calpain could be detected but not the isoenzyme mu-calpain, indicating that m-calpain is the significant most important calpain in human lens epithelium. Quantification of m-calpain showed no relationship to age or gender, but there were significant differences between different types of cataract.
Adult↗
Effects of odorants on pigment aggregation and cAMP in fish melanophores.
Odor perception within olfactory neuroepithelium and pigment translocation within melanophores both seem to rely on a cAMP-based second messenger system. From studies on cultured frog melanophores, Lerner et al. (Proc. Natl. Acad. Sci. USA 85:261-264, 1988) suggested that some aspect of odor perception may be mediated by a nonspecific mechanism whose signal is transduced by a cAMP-based second messenger system. In the present study, odorants (beta-ionone, benzylaldehyde, cineole, cinnamaldehyde, and octanol), which previously have been shown to stimulate formation of cAMP in the olfactory neuroepithelium, were investigated for possible pigment dispersing and cAMP-increasing effects. Pretreatment of fish melanophores with the adenylate cyclase activator forskolin (1 microM) resulted in an approximately 300% increase in cAMP and an almost complete blockage of noradrenaline-induced pigment aggregation. However, none of the tested odorants were able to increase the cAMP level and only cinnaldehyde and beta-ionone were found to have any pigment dispersing activity.
1-Octanol↗
Mangafodipir (MnDPDP)-and MnCl2-induced endothelium-dependent relaxation in bovine mesenteric arteries.
Mn++ complexed to DPDP (N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate) generic name: mangafodipir), abbreviated MnDPDP, acts as an effective contrast enhancing agent for liver MRI. In clinical trials, a commonly reported side effect after i.v. administration of MnDPDP was facial flushing, most probably due to peripheral vasodilation. The present study was conducted to address possible mechanisms to explain the flushing effect. Nitric oxide is known to be stabilized in the presence of both uncomplexed and complexed Mn++ and this stabilization is probably due to the superoxide-scavenging properties of Mn++. The present study has demonstrated that both MnDPDP and MnCl2 relax phenylephrine precontracted bovine mesenteric artery strips in concentration-dependent manner. It was also found that a concentration of 10 microM MnDPDP, MnEDTA or MnCl2 gave approximately the same relaxation response as 0.1 microM acetylcholine. DPDP and EDTA had no appreciable intrinsic relaxation potential Mn(++)-induced relaxation was abolished when the endothelial layer was removed from the arteries. In addition, the Mn(++)-induced relaxation was attenuated by the nitric oxide synthase inhibitor N-nitro-arginine and the putative superoxide anion generator 6-anilino-5,8-quinolinedione, but not by the cyclooxygenase inhibitor indomethacin. Both N-nitro-arginine and 6-anilino-5,8-quinolinedione were found to induce an endothelium-dependent constriction of the bovine mesenteric artery strips. An approximately 2-fold increase in the intracellular concentration of cyclic GMP was detected after the addition of 10 microM MnDPDP or 0.1 microM acetylcholine. The increase in cyclic GMP coincided with the onset of relaxation and was effectively abolished by pretreatment with N-nitro-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗