Biomedical subjects
Publications and source records attributed to A Carpi.
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The potential additive protective effect provided by nifedipine to the University of Alabama Hospitals cardioplegia solution (ACS) was assessed with the use of a guinea pig heart-lung model of cardiopulmonary bypass and ischemic arrest. The addition of nifedipine consistently enhanced the protective properties of ACS infused at 37 degrees C; functional recovery was similar to that observed with cold ACS. Despite the additional protection under normothermic conditions, nifedipine did not improve recovery after infusion at 4 degrees C. The abolition by hypothermia of the protective effects of nifedipine suggests a similarity in action between nifedipine and hypothermic protection. The interaction between ACS and nifedipine was studied on bovine coronary arteries in vitro. Nifedipine caused a marked reduction in the coronary vasoconstricting effect of ACS, both under normothermic and hypothermic conditions. The use of nifedipine in cardioplegia may provide additional protection when uneven distribution of the cardioplegic solution is expected and hypothermic protection is unreliable.
Cold cardioplegia is currently the method of choice for providing myocardial protection during open-heart surgical procedures. Two components of protection, perfusion cooling and pharmacological cardiac arrest, were investigated in the guinea pig heart-lung model. The effects of two cardioplegic solutions, the University of Alabama Hospital solution and the St. Thomas' Hospital solution, and a control perfusate were compared. The results confirmed the efficacy of hypothermia as a protective agent and the additional protection afforded by pharmacological cardioplegia. Infusion temperature critically influenced the cardioprotective action of the Alabama solution: Striking protection was afforded only under hypothermic conditions, whereas myocardial damage was exacerbated by the infusion at 37 degrees C. The St. Thomas' Hospital solution provided substantial protection independent of infusion temperature. Thus, the safety margin of the Alabama solution was narrower than that of the St. Thomas' solution. It is suggested that the difference between the two cardioplegic solutions partially depends on their coronary vasoactivity, since the administration of the Alabama solution at 37 degrees C increased coronary perfusion pressure. It would seem worthwhile to use a temperature-independent cardioplegic solution devoid of coronary vasoconstricting action.
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Concentrations of prolactin, follicle stimulating hormone, luteinising hormone and growth hormone were measured simultaneously in the serum and cerebrospinal fluid of 57 patients affected by neurologic disease without any pituitary or diencephalic involvement. Prolactin secretion was stimulated in another group of 12 patients using sulpiride or metoclopramide, and the hormone concentration was measured simultaneously in serum and in CSF during the test. Basal studies showed that the concentrations of prolactin, FSH, LH and GH in serum and in CSF were directly correlated (p varying from less than 0.001 to less than 0.05). A negative correlation was found between the molecular weight of hormones reported in this and in other studies and the natural logarithm of the CSF/serum hormone concentration ratios. During prolactin stimulation the correlation between serum and CSF concentration was maintained, nevertheless a higher increase of prolactin in blood than in CSF was observed. This last finding suggests that other mechanisms in addition to filtration from blood into CSF can be responsible for the presence of adenohypophyseal hormones in CSF.
An accurate and close follow-up of serum levels of thyroid hormones and various muscle markers (myoglobin, creatine kinase and its isoenzymes CK-MB and CK-BB, lactic dehydrogenase, alpha-hydroxybutyric dehydrogenase, etc.) was carried out in 10 hypothyroid patients on replacement therapy. The main muscle markers, creatine kinase and myoglobin, were elevated respectively in 9 and 6 subjects. In 1 male significant CK-MB traces were measured, while in 1 woman significant CK-BB amounts were assayed. Significant correlations between patients' thyroid hormones and the levels of the muscle parameters were found. The rate of normalization of thyroid hormones and muscle markers in relation to replacement therapy was also studied. Myoglobin and creatine kinase have proved to be the best indicators of the hypothyroid myopathy, since they are sensitive for the early detection of muscle involvement due to the metabolic disorder and are closely correlated to the metabolic conditions of patients.
We describe here a new method for the direct measurement of the conversion rate of T4 to T3 in man. The metabolic study was performed in 23 subjects: 13 healthy controls, 7 T4-treated hypothyroids, and 3 sick euthyroid patients. The experimental protocol involved the simultaneous iv bolus injection of [125I]T4 and [131I]T3, and the use of Sephadex G-25 column chromatography to determine the plasma concentrations of [125I]T4, [131I]T3, and [125I]T3 newly formed through 5'-monodeiodination of labeled T4 in the peripheral tissues. The T4 and T3 kinetic parameters were determined by noncompartmental analysis. The conversion rate of T4 to T3 was computed by a method based on the precursor-product relationship, using the [131I]T3 disappearance curve for correcting the concentrations of newly formed [125I]T3 (convolution method). The conversion rate of T4 to T3 was 0.2541 +/- 0.0125 (mean +/- SEM) in the control group and was significantly reduced (0.1283 +/- 0.0204; P less than 0.001) in the sick euthyroid patients, while it was slightly, though not significantly, increased in the T4-treated patients (0.2932 +/- 0.0220). A close agreement was found between the values for the conversion rate obtained by the convolution approach and those derived from the ratio between the serum concentrations of [125I]T3 and [125I]T4 at equilibrium. The conversion rates obtained by the convolution approach were also in good agreement with the values estimated from the molar ratio between the turnover rates of T3 and T4. In the control group, 72.0 +/- 3.6% of the circulating T3 was produced by 5'-monodeiodination of T4 in the peripheral tissues, and 28.0 +/- 3.6% of the circulating T3 derived from direct thyroidal secretion. The sick euthyroid patients showed a significantly smaller proportion of circulating T3 deriving from peripheral conversion of T4 (52.5 +/- 3.9%; P less than 0.025).
Near infrared spectra (700-930 nm) were recorded from the head of anesthetized rats before and after blood substitution with a fluorocarbon emulsion. A large band, centered at 850 nm and characteristic of oxidized cytochrome a, a3, was evidenced in hemoglobin-free living animals. Variations in the amplitude of this absorption band were observed under different respiratory conditions.
Ultrastructural changes of the myocardium and the coronary arterial endothelium were studied following cold perfusion with two different cardioplegic solutions (CPS) (the University of Alabama and the St. Thomas Hospital solutions), and with Krebs' solution as a control (CS). Guinea pig heart-lung preparations (HLP) were subjected to cardiac arrest by perfusion under CPS or CS (4 ml/Kg/min. X 4 min.). The duration of the cardiac arrest was 60 minutes, and additional amounts of cold solution were perfused after the first 30 minutes. In a second experimental group, HLP were reperfused with blood following 60 minutes of cardioplegic arrest, and maintained under full activity for the next 30 minutes. At the end of the study, specimens of coronary artery and myocardium were obtained and observed by Scanning (SEM) and Trasmission (TEM) electron microscopy. All the specimens were compared with additional specimens obtained from control hearts not subjected to cardiac arrest. The myocardial ultrastructure of hearts arrested with CPS was well preserved, whereas severe myocardial damage, consisting in the absence of glycogen granules, intracellular edema and myofibrillar contraction, was following CS-induced cardiac arrest. In contrast, perfusion with the St. Thomas CPS produced severe vascular damage, characterized by interruption of the endothelial layer, and bulging of endothelial cells into the lumen; no vascular changes were observed following cardiac arrest with CS or Alabama CPS. We conclude that the damage to the coronary arterial endothelium is not related to cardiac arrest, or to perfusion with cristalloid solution, or to myocardial damage, but appears to depend on the composition of the CPS.
Serum concentrations of TSH, TT4, TT3 and rT3 were monitored for one month after excision of ten autonomous thyroid adenomas which had suppressed TSH secretion. Basal serum TSH levels start to increase between 30 hr and 20 days after surgery reaching normal and steady levels by the 24 day. Serum TT3 concentrations rapidly decrease in the first 20 hr to values near the lower limit of the normal range. Thereafter TT3 levels change little until pituitary TSH secretion recovers. Serum TT4 levels also fall, but much more slowly than TT3. Rising TSH levels stimulate residual extranodular thyroid tissue secretion of both TT3 and TT4. However, serum TT3 levels rise more rapidly than TT4 levels. Preoperative serum concentrations of both TT4 and TT3 are related directly to the time required until the beginning of the postoperative rise in TSH levels, and inversely with the maximal postoperative serum TSH concentration achieved. Throughout the study period, for all patients, serum TSH concentrations were inversely related to serum TT4 concentrations. These data suggest that, although the time required until the onset of recovery of TSH secretion is directly related to preoperative levels of TT4 and TT3, the regulation of postoperative TSH levels is dependent upon serum TT4 levels. Also, the serum TT3 levels constant at the lower limit of the normal range before recovery of TSH secretion, and the preferential rise in serum TT3 concentrations associated with rising TSH secretion, may prevent or abbreviate temporary postoperative hypothyroidism.
The effects of two cardioplegic solutions (CPSs) on isolated, superfused, bovine coronary arteries were compared with those produced by changes in composition of standard Krebs medium. High potassium, low sodium content or the addition of albumin produced vasoconstriction; high magnesium, high glucose content or the addition of mannitol led to vasodilatation. In most cases hypothermia slightly reduced vasoconstriction and enhanced vasodilatation. The action of the two CPSs is the result of the interaction of these basic effects. The results suggest that the vasomotor reactions of coronary arteries to CPS may affect the delivery of the CPS to the myocardium and exert a critical influence on successful cardioplegia.
Near-infrared 700-950 absorbance of some chromophores has been measured in different biological tissues, in particular rat and rabbit brain, to assess value of this noninvasive technique for monitoring of the regional functional state. Experiments carried out under different induced circulatory conditions confirmed the possibility of obtaining information on local blood content and hemoglobin oxygenation level as well as an indication of redox state of cytochrome c oxidase, the enzymatic complex that catalyzes about 95% of cellular oxygen consumption. The near IR spectral data were correlated with the result of independent simultaneous measurements of circulatory function: blood pressure, local blood flow, and local blood volume.
Continuous measurements of local blood flow were performed by means of short pulse heated miniature thermistors. Results obtained in rat cerebral cortex or skeletal muscle show good stability of the recordings and the sensitivity of the system to phasic changes in local blood flow. Experiments on perfused rabbit kidney support the possibility of using this method for quantitative measurements.
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Triiodothyronine (T3) kinetic studies were carried out using 126I-T3 and the single injection technique in eight clinically euthyroid patients with autonomous thyroid nodules and the metabolic results were compared to those obtained in a group of 12 healthy control subjects. Plasma labeled T3 concentration was measured by a chromatographic method based on the extraction of the hormone on Sephadex G-25 columns, followed by its elution with a specific anti-T3 antiserum. The analysis of the experimental plasma disappearance curves of the labeled hormone was performed using the noncompartmental method. The results obtained showed a significantly increased metabolic clearance rate of T3 in the patients with autonomous thyroid nodules, as compared to the control group. On the average, the T3 production rates were increased more significantly than the corresponding circulating levels of the hormone, therefore, suggesting that the significant TSH inhibition observed in the euthyroid patients with autonomous thyroid nodules could be related with an increased peripheral utilization of triiodothyronine.
The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.
PRA, AII CR, AII E and cardiac output have been measured in 9 normals and in 22 hypertensives: 8 with URD, 12 with BRD and 2 with MHY. PRA, as well as AII E, shows the highest values in BRD and MHY patients. AII CR is directly correlated with blood pressure levels in URD and BRD patients (p less than 0.05 and p less than 0.001, respectively). A significant positive correlation is found between AII E and TPR (within each group of patients and among all subjects) and between PRA and TPR within the hypertensive patients. These data suggest that peripheral handling of AII is involved in the control of blood pressure in the patients studied.