Phytochemical Composition and Antitumor Activities of New Salad Greens: Rucola (Diplotaxis tenuifolia) and Corn Salad (Valerianella locusta).

D. tenuifolia and V. locusta, two greens, were analyzed for active compounds and antitumor actions on colorectal cancer cells. Phenolics were determined by UHPLC-Orbitrap-MS; carotenoids and glucosinolates by HPLC-MS; and sterols and fatty acids by gas-liquid chromatography (GLC). For antitumor effects, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) tests were run on HT-29 colorectal cancer cells, and in CCD-18 untransformed enterocyte cells. Six main carotenoids were identified in both vegetables, while total carotenoids accounted for 3520 and 2970 µg · g(-1) dry weight in D. tenuifolia and V. locusta, respectively. Six phenolics were detected in D. tenuifolia (68,600 µg · g(-1) dry weight) and five in V. locusta (139,000 µg · g(-1) dry weight). Three glucosinolates (GSL) were found in D. tenuifolia (1960 µg · g(-1) dry wt. total). Low-polarity extracts from V. locusta and D. tenuifolia showed IC50 ~ 150 and ~200 µg · mL(-1) on HT-29 cells, while both plants lacked actions on CCD-18 cells. V. locusta inhibited HT-29 cancer cells viability more efficiently than D. tenuiofolia, but induced less cytotoxicity. This work highlights the importance of functional foods for colorectal cancer prevention.

Sedimentary environmental quality of a biosphere reserve estuary in southwestern Iberian Peninsula.

The Huelva estuary is formed by the common mouths of the Odiel and Tinto Rivers, and inside this ecosystem is the biosphere reserve of the Odiel saltmarshes. This ecosystem has been historically affected by acid mine drainage (AMD) and by releases of pollutants from five phosphoric acid industrial plants and phosphogypsum (PG) waste stacks located in the area. This study carried out a comprehensive assessment of the environmental impact of the biosphere reserve of the Odiel saltmarshes. To this end, it was necessary to find a suitable sedimentary background (Piedras River in our case). To quantify this impact, several pollution indexes were used. According to the values reached by the indexes, this impact was classified as "serious" pollution for most trace elements, excepting the deepest layers, and "low-moderate" pollution for the 238U-series radionuclides, while no pollution for the 232Th-series and 40K radionuclides was found as expected.

Guidelines for inhaled sedation in the ICU.

INTRODUCTION AND OBJECTIVES: Sedation is used in intensive care units (ICU) to improve comfort and tolerance during mechanical ventilation, invasive interventions, and nursing care. In recent years, the use of inhalation anaesthetics for this purpose has increased. Our objective was to obtain and summarise the best evidence on inhaled sedation in adult patients in the ICU, and use this to help physicians choose the most appropriate approach in terms of the impact of sedation on clinical outcomes and the risk-benefit of the chosen strategy. METHODOLOGY: Given the overall lack of literature and scientific evidence on various aspects of inhaled sedation in the ICU, we decided to use a Delphi method to achieve consensus among a group of 17 expert panellists. The processes was conducted over a 12-month period between 2022 and 2023, and followed the recommendations of the CREDES guidelines. RESULTS: The results of the Delphi survey form the basis of these 39 recommendations - 23 with a strong consensus and 15 with a weak consensus. CONCLUSION: The use of inhaled sedation in the ICU is a reliable and appropriate option in a wide variety of clinical scenarios. However, there are numerous aspects of the technique that require further study.

Spatiotemporal evolution of U and Th isotopes in a mine effluent highly polluted by Acid Mine Drainage (AMD).

The spatiotemporal evolution of both U and Th isotopes in a mine effluent highly polluted by acid mine drainage (AMD) was evaluated. The acidic tributary, which born from the outflows of an abandoned sulfide mine, flows into the Odiel River. AMD comprises an important source of natural radionuclides, presenting concentrations of 238U and 232Th, two and four orders of magnitude higher, respectively, than the background values of surface continental waters. These natural radionuclides behave conservatively along the mine effluent (pH < 2.5) throughout the hydrological year. Under AMD conditions uranium is in the hexavalent state U(VI) and the main dissolved species are uranyl sulfate complexes. The polluted tributary has a significant impact on the Odiel River acidifying its waters during the low flow season and increasing up to one order of magnitude the activity concentrations of U and Th isotopes. U presented a conservative behavior in the Odiel River during the low flow season (pH ≈ 3), however it is removed from the liquid phase in the wet season (pH ≈ 6), probably due its coprecipitation/adsorption onto Al-phases. Th shows a high sensitivity to small increases of pH, and it is strongly coprecipitated/adsorbed with or onto Fe-oxyhydroxydizes in the river.

Behaviour of heavy metals and natural radionuclides in the mixing of phosphogypsum leachates with seawater.

Phosphogypsum (PG) is disposed worldwide in large stacks usually placed in coastal zones, as in the case of Huelva (SW of Spain), where around 100 Mt of PG are stored on the salt marshes of the Tinto River estuary covering a surface of about 1000 ha. This management generates the weathering of PG, and due to its high acidity (pH ≈ 2) and pollutant load can provoke significant emissions into their surroundings. In this work were evaluated by laboratory experiments the effects of pH increase in the behaviour of heavy metals and natural radionuclides during the mixing of phosphogypsum leachates with seawater. The acidic phosphogypsum leachates showed concentrations of heavy metals from two to three orders of magnitude higher than natural continental waters, and natural radionuclides (U-isotopes and 210Po) from four to five orders of magnitude higher than unperturbed aquatic systems. Major elements and some heavy metals as Mn, Ni, Cd, As, Sb and Co showed a conservative behaviour during the neutralisation of the leachates with seawater, remaining in the liquid phase, while other ones as Al, Fe, Cr, Zn, Cu, Pb precipitated and/or were adsorbed onto the solid phase. The U-isotopes and 210Po showed a clear non-conservative behaviour probably due to coprecipitation/adsorption processes onto the formed precipitates, but while 210Po reached a total removal at pH ≈ 7, U- isotopes after a total removal at pH ≈ 5 returned into the liquid phase due to redissolution/desorption processes at near neutral pH. The formed precipitates, mainly composed by iron phosphates particles, showed heavy metal and natural radionuclide concentrations from one to three orders of magnitude higher than unperturbed soils. All these facts demonstrate the serious environmental impact produced by the PG stacks into their surroundings and the urgency of effective restoration measures.

Radon transport events associated with the impact of a NORM repository in the SW of Europe.

Two radon measurement stations located to the north and south of a NORM (Naturally Occurring Radioactive Materials) repository of phosphogypsum (southwest of Europe) were used to monitor radon behavior during 2018. The stations are located at opposing sides of the repository, one in Huelva City to the north and other one in a rural area to the south. This setup aimed to identify the influence of the NORM repository on each station and use radon levels as a marker of atmospheric transport in the local area. To achieve this, a comparison was carried out with other coastal stations in the south of Spain, finding higher average concentrations in Huelva City, ~3.3 Bq m-3. Hierarchical clustering was applied to identify days with different radon patterns at each Huelva station, detecting possible local radon transport events from the repository. Three events were investigated with WRF (Weather Research and Forecasting) and FLEXPART-WRF (FLEXible PARTicle dispersion model). It was found that both sampling sites required atmospheric stagnant conditions to reach high radon concentration. However, under these conditions the urban station showed high radon regardless of wind direction while the rural station also required radon transport from the repository, either directly or indirectly.

Arsenic removal procedure for the electrolyte from a hydro-pyrometallurgical complex.

Commercial copper (Cu) is obtained by a hydro-pyrometallurgical process, where the Cu anodes obtained in the furnaces (Cu > 99.5%) are enriched up to 99.99% in "cathodes" by electrorefining at an electrolysis plant. During this process, some impurities accumulate in the electrolyte, mainly arsenic (As), which decrease the quality of the Cu cathode. For this reason, the electrolyte is sent to an electrolyte cleaning plant (ECP) for its purification. Electrolyte sludge (ES) is produced in the last stage of purification and is recirculated back to the furnace due to the high Cu content. This recirculation involves a severe problem of As accumulation in the industrial process. The objective of this work was to develop a procedure to fully dissolve the ES, removing the As and recovering its Cu content. The ES dissolution process was optimised (dissolution efficiency > 99%) in H2SO4 (1.4 M)/HNO3 (1.8 M) medium using a 1:20 g mL-1 solid-to-liquid ratio. As was removed from the ES solution by its precipitation as iron (III) arsenate, with high efficiency (more than 70%). After As removal, the Cu can be precipitated as copper sulphate, which is used in several applications.

Influence of the accumulation chamber insertion depth to measure surface radon exhalation rates.

A common method to measure radon exhalation rates relies on the accumulation chamber technique. Usually, this approach only considers one-dimensional gas transport within the soil that neglects lateral diffusion. However, this lateral transport could reduce the reliability of the method. In this work, several cylindrical-shaped accumulation chambers were built with different heights to test if the insertion depth of the chamber into the soil improves the reliability of the method and, in that case, if it could limit the radon lateral diffusion effects. To check this hypothesis in laboratory, two reference exhalation boxes were manufactured using phosphogypsum from a repository located nearby the city of Huelva, in the southwest of Spain. Laboratory experiments showed that insertion depth had a deep impact in reducing the effective decay constant of the system, extending the interval where the linear fitting can be applied, and consistently obtaining reliable exhalation measurements once a minimum insertion depth is employed. Field experiments carried out in the phosphogypsum repository showed that increasing the insertion depth could reduce the influence of external effects, increasing the repeatability of the method. These experiments provided a method to obtain consistent radon exhalation measurements over the phosphogypsum repository.

Radiological and physico-chemical characterization of materials from phosphoric acid production plant to assess the workers radiological risks.

The industry devoted to the production of phosphoric acid by using as raw material sedimentary phosphate rock (PR) is considered as a NORM activity (Naturally Occurring Radioactive Materials), due to the high levels of U-series radionuclides contained in this ore, which are 1-2 orders of magnitude higher than those in unperturbed soils. This fact allowed us to develop a deep characterization of the raw materials, wastes, main intermediate materials, and final products obtained at a typical phosphoric acid factory. The elemental composition (major, minor and trace elements), radionuclide concentrations, grain size distribution, mineralogy and micro-structural composition were analyzed. The aim of this characterization was to obtain information for operators and maintenance personnel involved in clean-up and waste management operations. The highest concentrations of some heavy metals and radionuclide activity concentrations were found in the "scales" (or internal incrustations)from the pipes that carry either phosphoric acid (PA) or the phosphogypsum waste (PG). The highest concentrations where found for 226Ra and 40K,with values up to 9 and 5 Bq g-1, respectively. In addition, high concentrations of many toxic heavy metals and trace elements, such as Cd, Cr, Ni, Sr, Y, V, Zn, Th, and U, were found in some sludge samples. The shielding effect of the containers/vessels/pipes has an essential role in the measured external dose in the intermediate products. The radiological implications of natural radionuclides with higher activity showed that if the maximum particulate matter concentration established in the Spanish regulation is verified, and taking into account the most conservative scenario, the annual limit of 1 mSv y-1 is not exceeded.

Early steroid withdrawal in pediatric renal transplantation at a single center: preliminary report.

Steroids have been a cornerstone in renal transplant immunosuppression despite cardiovascular risk and growth impairment in children. New immunosuppressive drugs have allowed early withdrawal or even complete avoidance of steroids. To evaluate a new immunosuppressive protocol with early withdrawal of steroids in a pediatric renal transplant population, we initiated a prospective study in recipients >1 year old who showed low immunologic risk was started. Group A (n = 12) received decreasing doses of steroids until day posttransplant 7 under a regimen of Tacrolimus (FK) and mycophenolate mofetil (MMF). Group B (n = 11) were controls treated with steroids, cyclosporine and azathioprine. In both groups, induction therapy included basiliximab. We evaluated anthropometric and biochemical variables, acute rejection episodes (ARE), and cytomegalovirus (CMV) infection. Mean values and variations for continuous variables were calculated at months 1 and 3 for comparison at the same time using student's t-test and regresion analysis. We obtained mean values at months 1, 3, and 6 for groups A and B of creatinine clearance (mL/min): 86.2 versus 107.4; 76.9 versus 96.6; 73.3 versus 97.9 (P < .05); hematocrit (%) was 27.4 versus 31.8; 29.3 versus 33.9; 32.9 versus 34.3% (P < .05); total cholesterol (mg/dL), 148 versus 195, 139 versus 85, 142 versus 174 (P < .05); creatinine clearance decreased in both groups during follow-up with a smaller slope among group A (P < .05). No differences were observed between the groups in Z height, diastolic and systolic blood pressures at 6 months of follow-up. Serum total cholesterol mean levels at months 1, 3, and 6 were significantly lower among the group withdrawn from steroids (P < .05). Plasma bicarbonate levels were lower among group A than B; there was no difference in blood glucose levels. No AREs and no difference in CMV infections were observed. In conclusion, early withdrawal of steroids with FK and MMF was not associated with a higher incidence of either ARE or CMV infection. Lower levels of cholesterol could imply a reduced cardiovascular risk. Longer follow-up is needed to evaluate the impact of this therapy on renal function and linear growth.

Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue-type plasminogen activator in dogs.

Localized thrombosis was produced in the left anterior descending (LAD) coronary artery of open chest dogs by constricting a segment so as to produce greater than 90% stenosis (reducing blood flow to 40 +/- 10% of baseline), and placing a thrombus in the segment immediately proximal to the stenosis by inducing endothelial cell injury and instilling a mixture of blood and thrombin. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 15-30 micrograms/kg per min for 30 or 60 min in eight dogs induced coronary artery reperfusion within 23 +/- 7 min (mean +/- SD), but reocclusion occurred despite heparin anticoagulation in all but one of these dogs within 7 +/- 5 min. Intravenous injection of 0.8 mg/kg of the F(ab')2 fragment of a monoclonal antibody (7E3) directed against the platelet GPIIb/IIIa receptor, prevented reocclusion in 10/10 dogs during an observation period of 2 h (P less than 0.001 vs. rt-PA alone). The antibody abolished ADP-induced platelet aggregation and markedly prolonged the bleeding time. Intravenous aspirin or dipyridamole prevented reocclusion for 1 h or more in only 2/7 and 1/6 dogs, respectively. We conclude that the monoclonal antibody is very effective in preventing reocclusion after successful thrombolysis of occluded coronary arteries with rt-PA.

Regulation of cardiac hypertrophy in vivo by the stress-activated protein kinases/c-Jun NH(2)-terminal kinases.

Cardiac hypertrophy often presages the development of heart failure. Numerous cytosolic signaling pathways have been implicated in the hypertrophic response in cardiomyocytes in culture, but their roles in the hypertrophic response to physiologically relevant stimuli in vivo is unclear. We previously reported that adenovirus-mediated gene transfer of SEK-1(KR), a dominant inhibitory mutant of the immediate upstream activator of the stress-activated protein kinases (SAPKs), abrogates the hypertrophic response of neonatal rat cardiomyocytes to endothelin-1 in culture. We now report that gene transfer of SEK-1(KR) to the adult rat heart blocks SAPK activation by pressure overload, demonstrating that the activity of cytosolic signaling pathways can be inhibited by gene transfer of loss-of-function mutants in vivo. Furthermore, gene transfer of SEK-1(KR) inhibited pressure overload-induced cardiac hypertrophy, as determined by echocardiography and several postmortem measures including left ventricular (LV) wall thickness, the ratio of LV weight to body weight, cardiomyocyte diameter, and inhibition of atrial natriuretic factor expression. Our data suggest that the SAPKs are critical regulators of cardiac hypertrophy in vivo, and therefore may serve as novel drug targets in the treatment of hypertrophy and heart failure.

Clinical protocol for the management of malignant hyperthermia. / Protocolo clínico asistencial de manejo de la hipertermia maligna.

Malignant hyperthermia is a hypermetabolic syndrome that appears in susceptible patients after exposure to certain anaesthetic drugs (succinylcholine, inhalation anaesthetics). Its incidence in Spain is 1 in 40,000 adults, with a 10% mortality rate. It is induced by an abnormal regulation of the ryanodine receptors, producing a massive release of calcium from the sarcoplasmic reticulum in the striate muscle. Clinical manifestations include: CO2 increase, tachycardia, haemodynamic instability, metabolic and respiratory acidosis, profuse sweating, hyperpyrexia, CPK increase, myoglobinuria, kidney failure, disseminated intravascular coagulation (DIC), and ending in cardiac arrest. Dantrolene sodium is a ryanodine receptor antagonist, and inhibits the release of intracellular calcium. Definitive diagnosis is achieved by the exposure of muscle fibres to caffeine and halothane. Protocols can help guarantee a reliable and secure management when this severe event occurs.

Purification process for MUFA- and PUFA-based monoacylglycerols from edible oils.

Important health benefits have been attributed to monoacylglycerols (MAGs) due to their various physiological functions, owing to which they become candidates for use as functional foods in order to prevent the onset of certain diseases such as colon cancer. In this work, six edible oils, namely: olive, linseed, sunflower, evening primrose, DHASCO® and ARASCO® have been processed to obtain different MUFA- and PUFA- based MAGs. First, the oils were hydrolyzed by means of an enzymatic process using porcine pancreatic lipase and then the reaction products were fractionated by using a liquid chromatography column containing silica gel as stationary phase in order to purify the MAGs-enriched fraction. A second chromatography process was performed using silver nitrate coated silica gel as stationary phase, in order to obtain the different MUFA- and PUFA-based MAGs from the corresponding oils. Overall, MAGs based on oleic, linoleic, α-linolenic, γ-linolenic, arachidonic and docosahexaenoic acids have been isolated in high yields and purities (92.6, 97.4, 95.3, 90.9, 100 and 95.3% purity, respectively). Positional distribution was determined by means of 1H NMR, which revealed a mix of 1(3) and 2-MAGs in variable proportions in the different MAGs.

Gamma-linolenic acid from Cape Verdian Boraginaceae.

The distribution of gamma-linolenic acid (GLA) was studied in the seed oil of six Cape Verdian Boraginaceae. The GLA ranges from trace levels in the three Heliotropum surveyed to 22.2% on saponifiable oil in Echium stenosiphon. All Echium species had GLA percentages in their seed oil around 20%. Echium seeds yield saponifiable oil from 15.8% (E. stenosiphon) to 17.3% (E. hypertropicum).

The power-velocity integral at the vena contracta: A new method for direct quantification of regurgitant volume flow.

BACKGROUND: Noninvasive quantification of regurgitation is limited because Doppler measures velocity, not flow. Because backscattered Doppler power is proportional to sonified blood volume, power times velocity should be proportional to flow rate. Early studies, however, suggested that this held only for laminar flow, not for regurgitant jets, in which turbulence and fluid entrainment augment scatter. We therefore hypothesized that this Doppler power principle can be applied at the proximal vena contracta, where flow is laminar before entrainment, so that the power-times-velocity integral should vary linearly with flow rate and its time integral with stroke volume (SV). METHODS AND RESULTS: This was tested in vitro with steady and pulsatile flow through 0.07- to 0.8-cm(2) orifices and in 36 hemodynamic stages in vivo, replacing the left atrium with a rigid chamber and column for direct visual recording of mitral regurgitant SV (MRSV). In 12 patients, MRSV was compared with MRI mitral inflow minus aortic outflow and in 11 patients with 3D echo left ventricular ejection volume-Doppler aortic forward SV. Vena contracta power in the narrow high-velocity spectrum from a broad measuring beam was calibrated against that from a narrow reference beam of known area. Calculated and actual flow rates and SV correlated well in vitro (r=0.99, 0.99; error=-1.6+/-2.5 mL/s, -2. 4+/-2.9 mL), in vivo (MRSV: r=0.98, error=0.04+/-0.87 mL), and in patients (MRSV: r=0.98, error=-2.8+/-4.5 mL). CONCLUSIONS: The power-velocity integral at the vena contracta provides an accurate direct measurement of regurgitant flow, overcoming the limitations of existing Doppler techniques.

Design of a new surgical approach for ventricular remodeling to relieve ischemic mitral regurgitation: insights from 3-dimensional echocardiography.

BACKGROUND: Mechanistic insights from 3D echocardiography (echo) can guide therapy. In particular, ischemic mitral regurgitation (MR) is difficult to repair, often persisting despite annular reduction. We hypothesized that (1) in a chronic infarct model of progressive MR, regurgitation parallels 3D changes in the geometry of mitral leaflet attachments, causing increased leaflet tethering and restricting closure; therefore, (2) MR can be reduced by restoring tethering geometry toward normal, using a new ventricular remodeling approach based on 3D echo findings. METHODS AND RESULTS: We studied 10 sheep by 3D echo just after circumflex marginal ligation and 8 weeks later. MR, at first absent, became moderate as the left ventricle (LV) dilated and the papillary muscles shifted posteriorly and mediolaterally, increasing the leaflet tethering distance from papillary muscle tips to the anterior mitral annulus (P<0.0001). To counteract these shifts, the LV was remodeled by plication of the infarct region to reduce myocardial bulging, without muscle excision or cardiopulmonary bypass. Immediately and up to 2 months after plication, MR was reduced to trace-to-mild as tethering distance was decreased (P<0.0001). LV ejection fraction, global LV end-systolic volume, and mitral annular area were relatively unchanged. By multiple regression, the only independent predictor of MR was tethering distance (r(2)=0.81). CONCLUSIONS: Ischemic MR in this model relates strongly to changes in 3D mitral leaflet attachment geometry. These insights from quantitative 3D echo allowed us to design an effective LV remodeling approach to reduce MR by relieving tethering.

Paradoxic decrease in ischemic mitral regurgitation with papillary muscle dysfunction: insights from three-dimensional and contrast echocardiography with strain rate measurement.

BACKGROUND: Ischemic mitral regurgitation (MR) was first ascribed to papillary muscle (PM) contractile dysfunction. Current theories include apical leaflet tethering caused by left ventricular (LV) distortion, but PM dysfunction is still postulated and commonly diagnosed. PM contraction, however, parallels apical tethering, suggesting the hypothesis that PM contractile dysfunction can actually diminish MR due to ischemic distortion of the inferior base alone. METHODS AND RESULTS: We therefore occluded the proximal circumflex circulation in 7 sheep while maintaining PM perfusion, confirmed by contrast echocardiography. By 3D echocardiography, we measured the tethering distance between the ischemic medial PM tip and anterior annulus and LV ejection volume to give MR (by subtracting flowmeter LV outflow). In 6 sheep without initial MR, inferior ischemia alone produced PM tip retraction with restricted leaflet closure and mild-to-moderate MR (regurgitant fraction, 25.2+/-2.8%). Adding PM ischemia consistently decreased MR and tethering distance (5.2+/-0.3 to 1.4+/-0.3 mL; +3.8+/-0.5 mm to -2.2+/-0.7 mm axially relative to baseline; P<0.001) as PM strain rate decreased from +0.78+/-0.07 per second (contraction) to -0.42+/-0.06 per second (elongation, P<0.001) and leaflet tenting decreased. In one sheep, prolapse and MR resolved with inferior ischemia and recurred with PM ischemia. CONCLUSIONS: PM contractile dysfunction can paradoxically decrease MR from inferobasal ischemia by reducing leaflet tethering to improve coaptation. This emphasizes the role of geometric factors in ischemic MR mechanism and potential therapy.

Chordal cutting: a new therapeutic approach for ischemic mitral regurgitation.

BACKGROUND: Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Because such MR is related to increased leaflet tethering by displaced attachments to the papillary muscles (PMs), it is incompletely treated by annular reduction. We therefore addressed the hypothesis that such MR can be reduced by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. This was tested in 8 mitral valves: a porcine in vitro pilot with PM displacement and 7 sheep with acute inferobasal infarcts studied in vivo with three-dimensional (3D) echo to quantify MR in relation to 3D valve geometry. METHODS AND RESULTS: In all 8 valves, PM displacement restricted leaflet closure, with anterior leaflet angulation at the basal chord insertion, and mild-to-moderate MR. Cutting the 2 central basal chordae reversed this without prolapse. In vivo, MR increased from 0.8+/-0.2 to 7.1+/-0.5 mL/beat after infarction and then decreased to 0.9+/-0.1 mL/beat with chordal cutting (P<0.0001); this paralleled changes in the 3D leaflet area required to cover the orifice as dictated by chordal tethering (r(2)=0.76). CONCLUSIONS: Cutting a minimum number of basal chordae can improve coaptation and reduce ischemic MR. Such an approach also suggests the potential for future minimally invasive implementation.

Prostacyclin and pathogenesis of hemodynamic abnormalities of diabetic ketoacidosis in rats.

The pathogenesis of the hemodynamic abnormalities of diabetic ketoacidosis (DKA) is not well understood. Previous studies suggest that prostacyclin (PGI2) production by adipose tissue is increased in DKA. We investigated the role of PGI2 in the pathogenesis of the reduced vascular resistance in DKA. Rats with streptozocin-induced DKA were anesthetized with pentobarbital sodium, and flow was measured with an electromagnetic probe on the infradiaphragmatic aorta. The plasma level of 6-keto-PGF1 alpha (stable derivative of PGI2) was higher (mean +/- SE 0.91 +/- 0.05 ng/ml) and vascular resistance lower (4.9 +/- 0.2 mmHg.ml-1.min-1.100 g-1 [resistance units, RU]) in 67 rats with DKA than in 21 normal rats (0.34 +/- 0.03 ng/ml, P less than .01, and 9.0 +/- 0.7 RU, P less than .01, respectively). Inhibition of cyclooxygenase activity with either indomethacin or meclofenamic acid reduced the plasma 6-keto-PGF1 alpha level but failed to raise vascular resistance. Infusions of PGI2 in rats with DKA demonstrated that the vasculature was responsive to PGI2. Inhibition of cyclooxygenase activity not only reduced PGI2 production but also suppressed renin release. When the effects of the renin-angiotensin system were excluded by bilateral nephrectomy, indomethacin caused a significant increase (P less than .05) in vascular resistance. Thus, the failure of cyclooxygenase inhibitors to raise vascular resistance in DKA was a result of concurrent suppression of vasodilator (PGI2) and vasoconstrictor (renin-angiotensin system) mechanisms that are activated in DKA. Insulin administration increased vascular resistance (P less than .01) and decreased the level of plasma 6-keto-PGF1 alpha (P less than .01). Combined administration of PGI2 and insulin did not alter vascular resistance, suggesting that the increase in vascular resistance with insulin was predominantly due to the reduction of circulating PGI2. Thus, vascular resistance is decreased in DKA primarily as a result of the vasodilator effects of PGI2 produced by adipose tissue. The activation of the renin-angiotensin system represents a partial compensation. The increase in PGI2 production may contribute to the hypotension and mortality of DKA.