Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the influence of glucose infusate administered with insulin and potassium on left ventricular function during 4 h of ischemia, as well as mechanism of action, four groups of intact anesthetized dogs were studied. Acute regional ischemia was induced with a balloon tip catheter in the left anterior descending artery and infusates were begun after 20 min of ischemia. A threefold increase of plasma glucose concentration was associated with improved left ventricular function during ischemia, compared to animals receiving isovolumic saline. There was a significant decline of left ventricular end-diastolic pressure associated with elevation of stroke volume and ejection fraction to control levels, as determined by indicator dilution. In a separate subgroup studied by cineangiography, shortening of the ischemic anterior wall, after an initial decline, was increased in response to glucose but there was no evidence of extension of injury. Ischemic tissue exhibited a smaller gain of water as well as Na+ per gram dry weight as compared to ischemic controls. On precordial electrocardiogram mapping there was a significant decrease in the sigmaST (sum of ST elevation) as well as NST (number of ST segment elevations), but the reduction of R wave amplitude was not different from controls. To further evaluate long-term effects, eight controls and six treated animals underwent myocardial ischemia and were sacrificed after 4 mo. Calculated area and weight of scar, as well as degree of wall thinning, were similar in both groups. The glucose-treated animals had a significant decrease of plasma FFA in contrast to controls which manifested a significant rise. To examine the postulate that the decrease in FFA was important to therapeutic action, a third group was infused with Intralipid (Cutter Laboratories, Inc., Berkeley, Calif.) and heparin, simultaneously with the glucose infusate, to effect an elevation of plasma FFA during ischemia. Changes in myocardial function and electrolyte composition, as well as precordial electrocardiogram mapping, were similar to that of animals receiving glucose alone. Because serum osmolality was increased approximately 40 mosmol during the glucose infusion, the potential role of hyperosmolality was assessed by infusion of 20% mannitol during acute ischemia in a fourth group. After a transient small increase, there was a moderate decline in function by 4 h, suggesting that the response to glucose is not dependent upon extracellular osmolality. Thus, it is concluded that during the initial hours after the onset of myocardial ischemia the glucose infusate improves ventricular performance without evidence of arrhythmia induction or intensification of ischemic injury. Evolution of irreversible necrosis appears to be delayed rather than prevented under the circumstances of this study.
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PMID:Sustained effect of glucose-insulin-potassium on myocardial performance during regional ischemia. Role of free fatty acid and osmolality. 65 87

Three-dimensional myocardial strains in seven isolated, potassium-arrested dog hearts were measured by biplane radiography of 3 transmural columns of 4-6 radiopaque beads implanted in the midanterior left ventricular free wall. Transmural distributions of strain during inflation of a left ventricular balloon to 20-30 mmHg were computed with respect to the zero pressure state. Magnitudes of the 3 principal strains increased in proportion to ventricular volume (0.0088, 0.0037, and -0.0059 ml-1). At a left ventricular pressure of 8 +/- 4 mmHg, mean circumferential (E11) and longitudinal strains (E22) were similar, increasing from epicardium (0.058 +/- 0.055 and 0.036 +/- 0.024) to subendocardium (0.139 +/- 0.102 and 0.120 +/- 0.084) as did the transmural (wall thinning) strain E33 (-0.053 +/- 0.071 to -0.128 +/- 0.083). Negative in-plane shear E12 was small (-0.008 to -0.052), consistent with a left-handed torsion of the left ventricular wall. Mean transverse shear strains E13 and E23 were small (-0.029 to 0.007) but showed considerable variability between hearts. Fiber strain had no significant transmural variation (P = 0.57). The principal axis of greatest strain was close to the fiber orientation on the epicardium (-15 degrees) but closer to the cross-fiber direction near the endocardium (-40 degrees). Therefore, the end-diastolic fiber lengths are maximized on the epicardium and minimized on the endocardium.
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PMID:Transmural distribution of three-dimensional strain in the isolated arrested canine left ventricle. 188 36

The purpose of this animal study was to investigate the histopathologic consequences of esophageal exposure to a variety of medications known to be injurious to the human esophagus. Twenty-four New Zealand white rabbits were utilized. Tablets or control plastic beads were secured to a silk suture thread and positioned in the rabbit esophagus through a proximal esophagostomy and a gastrostomy. Test medications were allowed to dissolve passively on the surface of the esophageal mucosa in the anesthetized rabbits. After 1 hr of drug exposure, the rabbits were killed and the esophagus removed and examined. No gross abnormalities were detected with the exception of a mild degree of erythema at some of the exposure sites. All medications and control beads produced microscopic mucosal changes when compared to suture controls. The beads and test medications caused thinning of the epithelium and increased subepithelial edema (P less than 0.05). Two changes, however, were unique to animals exposed to test medications: fraying and/or splitting of the epithelium and the presence of balloon cells (P less than 0.05). Balloon cells represent damaged squamous epithelial cells recognizable by their distended, globoid shape. The prevalence of balloon cells ranged from 22% to 89% of sites exposed to drug and was most commonly associated with potassium. Of all drugs reported to cause injury to the human esophagus, potassium chloride has been reported to produce the most severe lesions, including esophageal stricture and perforation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Drug-induced esophageal injury. Histopathological study in a rabbit model. 220 88

Periods of preservation for donor corneas, even for short times, are necessary to facilitate optimum conditions in penetrating keratoplasty. However, current techniques for corneal storage at low temperatures may not provide optimal conditions for maintaining tissue integrity. In particular, the ionic composition of the storage medium has received little attention since it has been assumed throughout that the normal complement of ions in tissue culture media will also be suitable for preservation at reduced temperatures. This study extends our previous investigations on the merits of using CPTES (corneal-potassium-TES), a potassium-rich balanced salt solution containing an impermeant anionic pH buffer (TES), as a storage solution specifically designed to prevent the loss of intracellular potassium and minimise endothelial cell swelling during the time that the normal regulatory processes are switched off. The effect of adding the natural polymer chondroitin sulphate (CS) as a colloid osmotic agent to the hyperkalaemic storage medium is now examined. Corneas stored in CPTES containing 2.5% chondroitin sulphate retained a very high level of structural and functional integrity after three, five, and seven days storage at 0 degrees C; furthermore, stromal swelling was restricted to only 21%. All corneas stored in CPTES + 2.5% CS showed active endothelial function by thinning efficiently at rates that were greater than those previously reported for rabbit corneas stored for similar lengths of time in either M-K medium or K-sol. The zwitterionic buffers TES and HEPES were interchangeable in the hyperkalaemic solution and were non-toxic to corneal endothelium at a concentration of 100 mM. These compounds offer excellent pH buffering in bicarbonate-free medium.
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PMID:Hypothermic preservation of corneas in a hyperkalaemic solution (CPTES): II. Extended storage in the presence of chondroitin sulphate. 251 Aug 16

Epicardial wall motion was measured on the left ventricular free wall in six isolated potassium-arrested dog hearts using a biplane video technique. Significant regional variations in epicardial deformations were recorded during static ventricular filling. Epicardial stretches varied linearly with cavity volume, sometimes exceeding 20% at physiological left ventricular end-diastolic pressures. The maximum component of epicardial stretch and the derived wall thinning increased substantially from the base to the apex on both the anterior and the posterior free walls of the left ventricle. In five hearts, the direction of greatest epicardial stretch at moderate and high filling pressures coincided closely with the local epicardial fiber direction, suggesting that the left-handed epicardial fiber helices stretch preferentially during passive filling to maximize end-diastolic fiber lengths. Epicardial rotation was always counterclockwise, consistent with a reduction in the pitch of the fiber helix during filling. These results suggest that, on the epicardial surface, the passive myocardium is anisotropic with respect to the local fiber direction. We suggest that the resulting torsional shear acts to minimize transmural gradients of fiber stretch.
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PMID:Regional left ventricular epicardial deformation in the passive dog heart. 270 34

Preservation solutions for short-term storage of isolated donor corneas for use in penetrating keratoplasty have all been based on tissue culture medium, on the assumption that media designed to maintain the viability of cells at physiological temperatures will also provide suitable conditions for preservation at reduced temperatures. But for hypothermic preservation of some other tissues and organs, when ionic pumps are inhibited, it is unnecessary to support metabolism, and beneficial control of ion and water distribution between intra- and extracellular compartments is achieved by storage in appropriately formulated 'intracellular-type' solutions. We have therefore designed a solution that will restrict ionic imbalances and minimise endothelial cell swelling in corneas during exposure at reduced temperatures. This potassium-rich solution contains the biological pH buffer TES as an impermeant anion and is designated CPTES (corneal-potassium-TES). The structural and functional integrity of rabbit corneas stored at 0 degrees C in CPTES, without the addition of colloid osmotic agents, is compared with that of corneas stored in glutathione bicarbonate Ringers' solution (GBR), an 'extracellular-type' medium formulated for the maintenance of endothelial integrity during in-vitro perfusion at 34 degrees C. Corneas swelled significantly less during storage in CPTES than in GBR and could be stored for five days before reaching the same degree of hydration as corneas stored for only three days in GBR. Gross structural integrity and endothelial ultrastructure were maintained during storage for three and five days in CPTES. The rate of thinning of corneas stored in CPTES was significantly greater than in comparable groups of corneas stored in GBR. However, the efficient dehydration of corneas stored in CPTES was always preceded during perfusion by a brief period of additional swelling which was shown to be an osmotic response during the elution of the buffer compound TES that had permeated the stroma during storage. The omission of calcium or the addition of adenosine and glutathione to the CPTES preservation medium had no detectable effect on the integrity of the endothelium, but the omission of bicarbonate was beneficial, producing significantly higher rates of stromal thinning during normothermic perfusion. Additional benefits for extending storage by including colloid osmotic agents are described in a companion paper.
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PMID:Hypothermic preservation of corneas in a hyperkalaemic solution (CPTES): I. Short-term storage in the absence of colloid osmotic agents. 281 86

Positron emission tomography (PET) with rubidium-82 (82Rb) has been developed to measure regional myocardial perfusion and to detect transient ischemia both in the experimental laboratory and in humans. There are known and separate contaminating effects of the 82Rb signal by disturbances in wall motion, wall thinning, and the partial volume effect that occur during transient ischemia. In nine anesthetized greyhounds, PET with 82Rb (T1/2 = 78 sec) was used to determine the regional myocardial uptake of this cation during a control period that consisted of a mild stenosis of the left anterior descending coronary artery in the absence of ischemia (to limit reactive hyperemia), during 10 min of total occlusion and, finally, at 30 and 60 min of recovery with release of the occlusion but not of the stenosis. Separately, rubidium-81 (81Rb); T1/2 = 4.58 hr) was given as a peripheral intravenous injection 2 hr before the study to allow this long-lived tracer to distribute in the potassium space of the myocardium. Observations during control and ischemia revealed marked decreases in 82Rb uptake (0.84 +/- 0.12 to 0.28 +/- 0.12, p = 0.001) in affected regions and were paralleled by similar decreases in microsphere blood flow (0.88 +/- 0.08 to 0.12 +/- 0.10 ml/min/g, p = 0.003), which gradually recovered by 60 min postischemia. Lesser decreases in 81Rb activity (0.84 +/- 0.11 to 0.76 +/- 0.17, p = 0.83) were observed in the same regions during ischemia, but these were immediately reversible. Separate in vitro postmortem experiments in eight rabbits confirmed a linear relationship between plasma and myocardial activities of stable potassium and 81Rb although there was a greater concentration of 81Rb in the myocardium that in the plasma relative to potassium (y = -3.29 +/- 0.79 x, s.e.e. 1.91, r = 0.95). These studies demonstrate that if 81Rb is given intravenously to distribute into the potassium pool, tomograms of the heart may be recorded to measure the potassium-rich mass of myocardium providing information about the acute effects of wall thinning during ischemia. Rubidium-81 used in this way may be helpful in assessing the effects of wall thinning and/or scar when other tracers are being used to assess perfusion or metabolism.
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PMID:Use of short- and long-lived rubidium tracers for the study of transient ischemia. 349 48

Stunned myocardium can be produced by repeated short episodes of ischemia. Histochemical and ultrastructural abnormalities such as sarcomere lengthening and myofiber thinning have been noted in myocardium soon after the onset of ischemia and have been attributed to the mechanical stretching that occurs during ventricular systole. To test whether mechanical forces alone could produce the residual dysfunction seen in stunned myocardium, regional dyskinesia was produced in open chest dogs by six repeated intracoronary infusions of either potassium chloride, 0.2 mEq/min for 2.5 minutes, or lidocaine, a 10 mg bolus followed by 1 to 3 mg/min for 5 minutes. These dogs were matched with dogs that had six repeated coronary occlusions of 2.5 and 5 minutes' duration, respectively. Regional function was analyzed using fractional systolic shortening and the load-independent end-systolic pressure-length relation. Both potassium chloride and lidocaine produced regional dyskinesia that was similar to the dyskinesia produced by coronary occlusion. Although regional ventricular function after repeated coronary occlusions remained significantly reduced, function returned completely to normal within 5 minutes after the last drug-induced dyskinesia. In conclusion, regional dysfunction produced by potassium chloride and lidocaine does not produce residual dysfunction despite mechanical forces during systole similar to those seen during coronary occlusion.
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PMID:Effect of repeated episodes of drug-induced ventricular dyskinesia on subsequent regional function in the dog: comparison with myocardial stunning produced by repeated coronary occlusions. 358 22

The chronic toxicity of a new topical glucocorticoid, difluprednate (DFBA) was studied in Beagle dogs. DFBA ointment (0.05%) was percutaneously treated to the back of dogs at daily doses of 125, 12.5 and 1.25 micrograms/kg for 6 months. The local effects of DFBA In the treated area, thinning of the skin and inhibition of the fur-growth were observed with scale and erythema. The skin showed histological atrophy of the epidermis, a decrease of the adipose tissue and atrophy of the adnexa. These changes returned to normal after the 2-month withdrawal period. The systemic effects of DFBA In the 125 micrograms/kg group, the following changes were observed, although neither death nor severe symptoms occurred: General observations were seen an increase of water intake and urinary volume. A decrease of lymphocytes and eosinophils, and an increase of neutrophils were observed in the hematological examination. There were high sodium and low potassium levels, and an increase of alkaline phosphatase and gamma-glutamyltranspeptidase activities in the biochemical examination. The organ weights showed a decrease of the thymus, adrenals, prostate and ovaries, and an increase of the liver and kidney. An atrophy of the lymphatic tissues and adrenal cortex, retardation of the sexual maturation, glycogen deposit in the hepatic cells, slight degeneration of the renal tubuli, and slight thinning of the sternum and non-treated skin were noted in the pathological examination. These changes returned to normal after the 2-month withdrawal period. In the 12.5 micrograms/kg group, the atrophic changes in the thymus, adrenal and non-treated skin appeared slight. In the 1.25 micrograms/kg group, no changes were found. Conclusively, all the local and systemic changes observed by DFBA in this study were due to the already known pharmacological effects of glucocorticoids. It is considered that a 12.5 micrograms/kg dosage is similar to a non-effect dose.
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PMID:[Chronic toxicity study on difluprednate in dogs]. 403 1

Adenosine has been reported by several investigators to stimulate corneal deturgescence, but the actual biochemical mechanism of this effect remains unknown. Effects observed include increased magnitude and rate of corneal thinning, increased endothelial fluid transport rate, support of adenosine triphosphate (ATP) levels, stimulation of magnesium activated ATPase (Mg++ATPase) and sodium-potassium activated ATPase (Na+K+ ATPase) activities in endothelium whole cell preparations, but a lack of stimulation of Mg++ATPase and Na+K+ATPase activities in endothelial plasma membrane preparations. This study examined the possibility that adenosine alters the corneal endothelial levels of two biochemical effectors: adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP). Bovine corneal endothelium was studied as fresh tissue and after growth in tissue culture. The samples were processed both at room temperature and in liquid nitrogen. Incubation of fresh and cultured endothelia in media containing adenosine was found to have no effect on the cAMP and cGMP levels regardless of the processing method. The data suggest that cyclic nucleotides do not mediate adenosine-stimulated corneal deturgescence.
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PMID:Null effect of adenosine on cyclic nucleotides of the corneal endothelium: possible implications for adenosine-stimulated corneal deturgescence. 632 99


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