Effects of triiodothyronine supplementation after myocardial ischemia

Women who had experienced an infant or fetal death responded to an open-ended question on the 1988 National Maternal and Infant Health Survey about their perinatal experience. A qualitative analysis of the 413 responses identified six major themes, including need for further information, problems with the mourning process, and unresolved questions about the cause of the death. Implications of the findings for health care practice are discussed.     

Increased in vitro phosphorylation of rat liver nucleolar proteins following triiodothyronine administration

It has been shown that triiodothyronine (Ta) administration to thyroidectomized rats induces an increase in the in vitro net 32P uptake into liver nucleolar proteins. Such an increase depends on a stimulation of the nucleolus-associated protein kinase activity and not on a lower dephosphorylation rate.     

DNA synthesis in isolated mitochondria: effect of thyroidectomy and of triiodothyronine administration in vivo

The incorporation was studied of labelled deoxy-ribonucleosides triphosphates into acid-insoluble material by isolated liver mitochondria, obtained from either normal young male rats, or thyroidectomized at weaning, or thyroidectomized and then treated with triiodothyronine (T3). The incorporation extents in normal animals decreased with the age starting from the weaning until the 210th day. Thyroidectomy reduced the incorporation extent to about 70% of the values observed in normal animals. During the T3 treatment of thyroidectomized rats a sharp increase of incorporation was observed one day after the first administration, followed by a decrease from the 1st to the 3rd day; successively the incorporation extent remained unchanged until the 12th day. Finally, evidence was provided that T3 doses used were thyreomimetic and definitely lower than the thyreotoxic ones.     

Changes in myocardial metallothionein on isoproterenol-induced myocardial injury

The amounts of myocardial metallothionein (MT) and heavy metal (Zn, Cu) levels during the early stage of the experimental myocardial infarction model induced by isoproterenol (Isp) administration were measured by an atomic absorption spectrophotometry. MT was measured by the Cd-hem method. Myocardial infarction was induced by the administration of 75 mg/kg i.p. of Isp to rats weighing 270 +/- 10 g. Thirty minutes after Isp injection, Zn and Cu levels began to decrease and 12 h later, reached the minimal values compared with the control value. The level of MT began to increase 3 h after the Isp injection and reached the maximal value at 12 h, although MT remained undetectable in the control myocardial tissue by the Cd-hem method. MT levels in the liver increased and total Zn and Cu were elevated compared with the control value 12 h after Isp administration. These results suggest that MT is produced in the myocardium after Isp administration, and that the roles of MT in the heart and the liver are different. It was thought that a rise in MT was induced for the protection of the myocardial cells to injury.     

Effect of glucose administration on contusion volume after moderate cortical impact injury in rats

Previous studies had shown that pre- and postinjury glucose administration increased brain injury caused by a mild cortical impact injury only when the traumatic injury was complicated by a secondary ischemic insult. The purpose of this study was to examine the effect of pre- and postinjury glucose administration on a more severe cortical impact injury, where primary ischemia occurs at the site of the impact. Long Evans rats who were fasted overnight and anesthetized with isoflurane were subjected to a 5-m/sec, 2.5-mm impact injury. The animals were randomly assigned one of the following treatments: (1) 2.2 g/kg glucose in 4 ml of saline, 20 min prior to injury; (2) 2.0 g/kg glucose in 4 ml of saline, 20 min after injury; or (3) 4 ml of saline either 20 min before injury or 20 min after the injury. At 2 weeks, the animals were sacrificed and the brains were examined for contusion volume and for neuronal loss in CA1 and CA3 regions of the hippocampus. Contusion volume was increased from a median value of 23 mm3 in the saline-infused animals to 34 mm3 in the preimpact glucose infusion animals (p=0.005). Postimpact glucose infusion had no effect on contusion volume. Neuron density in CA1 and CA3 regions of the hippocampus was similar in all three treatment groups. These studies support the hypothesis that glucose administration adversely affects experimental traumatic brain injury in those circumstances where the trauma is complicated by primary cerebral ischemia, such as around cortical contusions.     

Effects of triiodothyronine (T3) supplementation upon ozone-induced lung injury

Ozone exposure results in an acute decrease in the serum levels of thyroid hormones; the physiologic sequelae of this are unclear. Whereas thyroid hormone supplementation appears to benefit pulmonary function in septic, oxyradical models of injury, thyroid hormone increases ozone toxicity. We demonstrated an increase in metabolic rate and pulmonary injury in lungs from ozone exposed, T3 treated animals. This was evidenced by an increase in pulmonary weight gain, vascular perfusion pressure, and decrease in compliance in the supplemented animals. However, an increase in alkane generation, as an index of lipid peroxidation, was not seen in the ozone exposed, hormonally treated animals. This suggests that although thyroid hormone supplementation increases metabolic rate and ozone toxicity, an increased rate of lipid peroxidation plays a minimal role.     

Perindopril effects on angiotensin I elimination in lung after experimental myocardial injury induced by intracoronary microembolization in rats

The objective of the study was to determine whether angiotensin (Ang) I elimination in lung circulation depends on the degree of myocardial damage with and without early long-term perindopril treatment in a rat model of myocardial injury induced by intracoronary microembolization. Twenty-one days after surgery, steady-state arterial [125I]-Ang I and [125I]-Ang II blood concentrations were measured after high-performance liquid chromatography separation during i.v. infusion of [125I]-Ang I in three groups of male Wistar conscious rats: (a) sham-operated rats receiving saline (sham group, n = 6); (b) rats after coronary microembolization receiving saline (saline group, n = 7); and (c) rats after coronary microembolization receiving perindopril (2 mg/kg/day; from days 2-20 after embolization; perindopril group, n = 6). Ang I clearance and the Ang I-to-Ang II concentration ratio (R) were estimated. The embolization per se resulted in focal fibrosis, appearance of hypertrophic and dystrophic cardiac myocytes, and was accompanied by increased Ang I clearance (1,479 vs. 314 ml/min in sham group), 1.8-fold decreased [125I]-Ang II arterial level, and decreased R (0.5 vs. 1.2 in sham group; p < 0.05). Only Ang I concentrations and R were correlated with number of scars (r = -0.77; p < 0.05; and r = -0.82; p < 0.01, respectively). Captopril bolus (1 mg/kg, i.v.) caused similar reduction in [125I]-Ang II blood concentration in both sham and saline groups, but a significant increase of [125I]-Ang I blood concentration was detected in the sham group only. Thus in rats with coronary microembolization, a higher proportion of Ang I in lung circulation is eliminated by pathways independent of angiotensin-converting enzyme. In the perindopril group, a reduced number of scars (seven vs. 17 per slice in the saline group; p < 0.05), density of dystrophic and hypertrophic cardiac myocytes, and increased content of cell glycogen were observed. It was accompanied by normalized arterial [125I]-Ang I concentration, Ang I clearance, and R; [125I]-Ang II concentration tended to that in sham group. Only in the sham and perindopril groups was there significant correlation between Ang I and Ang II concentrations. The clear relation between number of scars per slice and R (r = -0.83; p < 0.01) was observed in all rats with embolized coronary vessels (saline and perindopril groups together). In conclusion, in this experimental, model Ang I elimination in the lung circulation was directly related to the degree of myocardial damage. Early perindopril treatment prevented maladaptive changes in Ang I processing and led to significant reduction of the undesirable aftereffects of myocardial tissue damage. Our data demonstrate the cardioprotective action of perindopril based on its beneficial influence on the renin-angiotensin system disturbances.     

Effect of chronic neutral endopeptidase inhibition on cardiac hypertrophy after experimental myocardial infarction

BACKGROUND: The purposes of the present study were to attempt to replicate a previous finding of increased cerebrospinal fluid (CSF) neuronal cell adhesion molecule (N-CAM) in schizophrenia, and to assess whether the increases could be related to medication, clinical state effects, or brain structural measures. METHODS: CSF N-CAM was measured by the Western blot technique in 45 DSM-III-R diagnosed male schizophrenic patients both on and off haloperidol treatment and in 20 healthy male control subjects. RESULTS: CSF N-CAM was significantly increased in schizophrenic patients, with no overlap in the ranges, when compared to controls. There were no significant effects of medication or exacerbation on CSF N-CAM. No associations with measures of brain structure were found. CONCLUSIONS: Because N-CAM levels were not shown to be different on and off treatment or in exacerbated versus nonexacerbated patients, the higher levels seen in schizophrenic patients may be inherent to the disorder and possibly related to neurodevelopment.     

Nonsurgical infarctectomy in acute experimental myocardial infarction

This study examines whether a catheter mounted left intraventricular balloon may prevent left ventricular (LV) dysfunction following acute experimental myocardial infarction. In 10 anesthetized pigs, multiple coronary arterial ligations were applied around the apex of the heart. LV end-diastolic pressure (LVEDP), aortic flow (AF), and LV long and short axis fractional shortening (FS) were measured before and at 15 min intervals after ligations. At the 60th min after ligation, the LV long axis FS and AF decreased by 7.2 +/- 2.6% (p < 0.05) and 13.25 +/- 2.68% (p < 0.01), respectively, and the LVEDP increased by 4.3 +/- 1.1 mm Hg (p < 0.01) while no change was noted in the LV short axis FS. An intraventricular catheter mounted nonpulsating balloon was positioned over the endocardium of the infarcted area at the LV apex. Inflation of the nonpulsating balloon to an optimal volume, which was found to be equal to 8-10% of the LV end-diastolic volume, resulted in a reduction (by 3.8 +/- 1.2 mm Hg, p < 0.01) of the already increased LVEDP and in an increase (by 6.6 +/- 2.1%, p < 0.05) in the LV short axis FS while no statistically significant change was noted in the AF and LV long axis FS. It is concluded that an intraventricular catheter mounted balloon patch positioned over the endocardium of the infarcted area may ameliorate early LV dysfunction, possibly by interfering with the functional geometry of the LV contraction.     

Effect of cyclic GMP reduction on regional myocardial mechanics and metabolism in experimental left ventricular hypertrophy

We tested the hypotheses that decreased myocardial cyclic GMP levels produced by intracoronary injection of methylene blue would increase local myocardial work and O2 consumption while decreasing intracellular cyclic GMP and that the relation between work, O2 consumption, and cyclic GMP may be altered in left ventricular hypertrophy (LVH) produced by aortic valve plication. In 8 control and 8 LVH open-chest anesthetized dogs, 1 mg/kg/min methylene blue was infused into the left anterior descending coronary artery (LAD); the circumflex region (CFX) served as control area. Regional work was calculated as the integrated product of force (miniature transducer) and segment shortening (sonomicrometry). Regional myocardial O2 consumption was calculated from flow measurements (radioactive microspheres), and regional O2 saturations (microspectrophotometry). A radioimmunoassay was used to determine intracellular level of cyclic GMP in the myocardium. Global hemodynamics and blood gases were unchanged by methylene blue in both control and LVH animals. Intracoronary methylene blue increased regional work from 762 +/- 129 to 1,451 +/- 307 g center dot mm/min in controls and from 912 +/- 173 to 1581 +/- 253 g center dot mm/min in the LVH groups. No significant changes in CFX regional work were observed. Regional blood flow, O2 extraction, and O2 consumption remained unchanged after injection of methylene blue in both control and LVH animals. The basal levels of cyclic GMP in the LVH group were fivefold higher than that in controls. In both groups, cyclic GMP levels were significantly decreased by methylene blue and to a greater extent in the LVH animals (from 6.16 +/- 1.2 to 3.34 +/- 0.44 pmol/g) than in the control animals (from 1.32 +/- 0.20 to 1.09 +/- 0.19 pmol/g). Therefore, intracoronary methylene blue increased regional myocardial work equally in control and LVH hearts without affecting regional metabolism (i.e., increased efficiency). For the same increased mechanical function, the hypertrophic myocardium exhibited a greater reduction in cyclic GMP pool size.     

Surfactant administration reduces testicular ischemia-reperfusion injury

PURPOSE: The mechanism of testicular ischemia-reperfusion injury has not been well delineated. We determined the efficacy of a biocompatible surfactant (tetronic 1107) to reduce tissue injury and evaluated cell membrane integrity as reflected by calcium ion permeability in an in vivo animal model of testicular ischemia-reperfusion. MATERIALS AND METHODS: Three groups of male Sprague-Dawley rats (6 per group) were studied. Group 1 was the nonoperative control, and groups 2 and 3 underwent 4 hours of unilateral testicular ischemia followed by 4 hours of reperfusion. Ten minutes after reperfusion 0.4 ml. saline was administered intravenously to group 2 and 180 mg./kg. surfactant tetronic 1107 to group 3. 99mTechnetium pyrophosphate was used to monitor calcium ion uptake by the ipsilateral and contralateral testicles. Both testicles were also examined histologically. RESULTS: The surfactant treated animals had markedly diminished hemorrhagic discoloration and vascular congestion compared to saline treated animals. These results were confirmed microscopically with improved nuclear chromicity and disarray of germ cell layers of the seminiferous tubules. The surfactant treated group also had a statistically significant (p <0.05) reduction in radiotracer uptake compared to the saline treated animals, confirming a reduction in calcium ion permeability. CONCLUSIONS: The results of this study suggest that tetronic 1107 is effective in reducing tissue damage in a testicular ischemia-reperfusion animal model.     

Chronic, post-injury administration of D-cycloserine, an NMDA partial agonist, enhances cognitive performance following experimental brain injury

The purpose of this study was to determine the effect of augmenting NMDA receptor activation on cognitive deficits produced by traumatic brain injury (TBI). Specifically, D-cycloserine (DCS), a partial agonist of the NMDA-associated glycine site, was tested as a potential cognitive enhancer. Rats were injured using lateral fluid percussion TBI (2.8 +/- .10 atm). On days 1-15 post-injury, animals were injected (i.p.) with vehicle (n = 8), 10 mg/kg (n = 9), or 30 mg/kg (n = 8) of DCS. Sham-injured animals treated with either vehicle (n = 8) or 30 mg/kg of DCS (n = 8) were used for comparison. On days 11-15 post-injury, cognitive function was assessed using the Morris water maze (MWM). Results indicate that the 30 mg/kg dose of DCS significantly attenuated memory deficits as compared to injured vehicle-treated animals (P < 0.01). Analysis also revealed that performance of the injured-DCS (30 mg/kg) group was not significantly different from sham-injured animals treated with vehicle (P > 0.10). In contrast, the 10 mg/kg dose of DCS was ineffective in reducing injury-induced memory deficits. DCS (30 mg/kg) also significantly improved the spatial memory of sham-injured animals when compared with sham-injured animals treated with vehicle (P < 0.05). In conclusion, chronic, post-injury enhancement of the NMDA receptor is an effective strategy for ameliorating TBI-associated cognitive deficits.     

Liberation of thyreotropin, thyroxine and triiodothyronine in the controllable and uncontrollable stress and after administration of naloxone in rats

The aim of this study was to investigate whether controllable stress, in which the animal can avoid a stressor, and uncontrollable stress, in which the animal can not avoid its influence change the activity of the endocrine pituitary-thyroid axis and whether these changes are modified by naloxone--the antagonist of opioid receptors. The experiments were carried out on rats using electric foot shock as a stressor and the concentration of thyreotropin, thyroxine and triiodothyronine in the blood was determined with radioimmunoassay. The uncontrollable stress caused the inhibition of secretion of the hormones mentioned above, but the controllable stress did not influence their secretion. Naloxone administered centrally to lateral ventricle of the brain decreased the inhibitional influence on the pituitary-thyroid axis. The obtained results suggest that change of pituitary-thyroid axis activity during the stress depends not only on the stressor but also on the animal's abilities to control that stressor.     

Inhibition of experimental neointimal hyperplasia and thrombosis depends on the type of vascular injury and the site of drug administration

BACKGROUND: Heparin inhibits vascular smooth muscle cell proliferation in tissue culture and limits neointimal hyperplasia after experimental arterial injury but has been ineffective in reducing clinical restenosis. We examined how this discrepancy might reflect suboptimal drug-tissue interactions and/or differences in the vascular response to injury. METHODS AND RESULTS: Intravenous infusion was compared with local administration of heparin to injured rabbit iliac arteries either from drug-impregnated polymeric controlled release matrices in the perivascular space or from drug-releasing endovascular stents. Occlusive thrombosis, seen in 42% of control stent-bearing arteries, and partial thrombosis were virtually eliminated by heparin delivery from any route. Intimal area 14 days after balloon withdrawal denudation alone was reduced to an equal extent by continuous systemic heparin or by perivascular heparin for the first 3 days. In contrast, endovascular stents produced more exuberant neointimal hyperplasia, the inhibition of which required continuous rather than only early heparin administration. Neither perivascular delivery limited to the first 3 days nor stent-based delivery reduced neointimal hyperplasia as effectively. CONCLUSIONS: The antiproliferative and antithrombotic effects of heparin differ markedly, depending on the type of arterial injury and the mode of drug administration. Different forms of injury may require different therapies, and complications of arterial intervention such as excessive neointimal hyperplasia and thrombosis may demand alternate therapeutic regimens. Duration, dose, and site of delivery rather than frank resistance to therapy may explain why experimentally effective antiproliferative and antithrombotic agents fail clinically.     

Expression of tenascin in mesangial injury in experimental glomerulonephritis

The resistance to torsional load was measured in a human cadaver model of a surgical neck fracture. Ten fresh-frozen human cadaver shoulders were thawed, dissected free of soft tissue attachments, and analyzed with dual energy x-ray absorptiometry to establish bone mineral density. Osteotomies were fixed with figure-of-eight wire alone and figure-of-eight wire supplemented with intramedullary Enders rods. Intramedullary Enders rods improved the mean maximum load by 1.5 times (p < 0.05). No statistically significant correlation was found between mean maximum load and bone mineral density.