Use of intraaortic balloon counterpulsation in patients presenting with cardiogenic shock: observations from the GUSTO-I Study. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries

OBJECTIVES: We sought to examine the use, complications and outcomes with early intraaortic balloon counterpulsation (IABP) in patients presenting with cardiogenic shock complicating acute myocardial infarction and treated with thrombolytic therapy. BACKGROUND: The use of IABP in patients with cardiogenic shock is widely accepted; however, there is a paucity of information on the use of this technique in patients with cardiogenic shock who are treated with thrombolytic therapy. METHODS: Patients who presented within 6 h of chest pain onset were randomized to one of four thrombolytic regimens. Cardiogenic shock was not an exclusion criterion, and data for these patients were prospectively collected. Patients presenting with shock were classified into early IABP (insertion within one calendar day of enrollment) or no IABP (insertion on or after day 2 or never). RESULTS: There were 68 (22%) IABP placements in 310 patients presenting with shock. Early IABP use occurred in 62 patients (20%) and none in 248 (80%). Most IABP use occurred in the United States (59 of 68 IABP placements) involving 32% of U.S. patients presenting with shock. Despite more adverse events in the early IABP group and more episodes of moderate bleeding, this cohort showed a trend toward lower 30-day and 1-year mortality rates. CONCLUSIONS: IABP appears to be underutilized in patients presenting with cardiogenic shock, both within and outside the United States. Early IABP institution is associated with an increased risk of bleeding and adverse events but a trend toward lower 30-day and 1-year all-cause mortality.     

Exercise responses in patients with IDDM

OBJECTIVE: The hemodynamic, respiratory, and metabolic responses to exercise were studied in IDDM patients and control subjects to detect diabetic cardiomyopathy. RESEARCH DESIGN AND METHODS: Eight subjects aged 25-40 years with diabetes of at least 10 years' duration were compared with eight control subjects aged 21-46 years. All subjects underwent a progressive incremental bicycle exercise test with measurement of gas exchange, blood glucose, lactate, fat metabolite, and catecholamine levels and two steady-state exercise tests with measurement of cardiac output by a CO2 rebreathing method. A new first-pass radionuclide method was used to measure cardiac ejection fractions (EFs) at rest, peak exercise, and steady-state exercise. RESULTS: The peak achieved oxygen consumption was similar in the diabetic and control subjects (29.9 [25.1-34.6] and 31.4 [26.9-35.9] ml.min-1.kg-1, respectively; mean [95% CI]). There were no significant differences in heart rate, double product, ventilation, respiratory exchange ratio, or ventilatory equivalents for oxygen and CO2 during the incremental test. Glucose levels were higher in the diabetic subjects, but there were no significant differences in levels of lactate, catecholamines, free fatty acids, glycerol, or beta-hydroxybutyrate. Left ventricular EF fell from rest to peak exercise within the diabetic group (66.0% [59.6-72.4] at rest; 53.6% [45.6-61.6] at peak; P < 0.05) but this did not differ significantly from the control group (58.7% [52.3-65.1] at rest; 60.3% [48.9-71.7] at peak). Right ventricular EFs were similar in each group, and there was no reduction in peak filling rate to suggest diastolic dysfunction. The cardiac output responses to exercise were also similar in the two groups. CONCLUSIONS: There is no evidence of impairment of the exercise response in subjects with long-standing diabetes, and the apparent fall in left ventricular EF at peak exercise could be related to hemodynamic adaptation.     

Excretion of benzoic acid derivatives in urine of sheep given intraruminal infusions of 3-phenylpropionic and cyclohexanecarboxylic acids

The quantitative relationship between the urinary excretion of benzoic acid (BA) and the uptake of 3-phenylpropionic (PPA) and cyclohexanecarboxylic (CHCA) acids was assessed. PPA and CHCA are produced in the rumen by microbial fermentation of lignocellulosic feeds and metabolized, after absorption, to BA which is excreted in the urine mainly as its glycine conjugate hippuric acid (HA). Four sheep nourished by intragastric infusions of all nutrients were given continuous ruminal infusions of PPA (8, 16 or 24 mmol/d) either alone or with CHCA (8 or 16 mmol/d) in a factorial experiment. The treatments were allocated to ten consecutive 6 d periods, with a control being repeated at periods 1, 5 and 10. PPA and CHCA ruminal absorption rates, estimated using the liquid-phase marker Cr-EDTA, were 0.78 (SD 0.29)/h and 0.88 (SD 0.28)/h respectively. For the control, HA excretion was only 0.22 (SD 0.33) mmol/d and free BA was absent. For the other treatments, both HA and free BA were present and HA accounted for 0.85 (SD 0.05) of total BA: The urinary excretion of total BA showed a significant linear correlation (r = 0.997, P < 0.001) with the amounts of PPA and CHCA infused. The urinary recovery of infused PPA and CHCA as total BA was 0.79 (SE 0.01). Faecal excretion of BA and its precursors was negligible. Results of this study show that urinary total BA is a potential estimator of the absorption of PPA + CHCA produced in the rumen.     

Evidence that a GABAA-like receptor is involved in progesterone-induced acrosomal exocytosis in mouse spermatozoa

Endogenous alpha-tocopherol of low density lipoprotein (LDL) particles exposed to ferrylmyoglobin (iron in the form of FeIV = O) vanishes as a function of myoglobin concentration. After alpha-tocopherol depletion, subsequent heavy lipid peroxidation is prevented by caffeic and p-coumaric acids, i.e., phenolic acids present in foods and beverages, by a mechanism involving the one-electron transfer reaction between the phenols and the ferrylmyoglobin, with formation of metmyoglobin and the corresponding phenoxyl radicals from caffeic and p-coumaric acids, as previously discussed. Caffeic acid delays alpha-tocopherol consumption when present before oxidation challenging and restores alpha-tocopherol when added halfway during the reaction. Conversely, p-coumaric acid accelerates the rate of alpha-tocopherol consumption when added either before or during the oxidation reaction. In LDL enriched with alpha-tocopherol, caffeic acid induces an inhibition period of oxidation longer than that expected from the sum of discrete periods characteristic of the phenolic acid and alpha-tocopherol. Surprisingly, p-coumaric acid decreases the peroxidation chain rate. Similar effects of these phenolic acids on alpha-tocopherol consumption were observed in a Triton X-100 micellar system, i.e., in the absence of a peroxidation chain reaction. Results suggest that caffeic acid acts synergistically with alpha-tocopherol, extending the antioxidant capacity of LDL by recycling alpha-tocopherol from the alpha-tocopherol radical (i.e., alpha-tocopheroxyl radical). By contrast, the phenoxyl radical from p-coumaric acid (produced by electron-transfer reaction between phenolic acid and ferrylmyoglobin) oxidizes alpha-tocopherol. However, in spite of alpha-tocopherol consumption, the exchange reaction recycling p-coumaric acid can still afford an antioxidant protection to LDL on basis of the chain-breaking activity of p-coumaric acid. These results emphasize the biological relevance of small structural modifications of phenols on the interaction with alpha-tocopherol in LDL. The significance of these results in the context of atherosclerosis is discussed.     

Activation of transducin guanosine triphosphatase by two proteins of the RGS family

RGS proteins (regulators of G protein signaling) constitute a newly appreciated group of negative regulators of G protein signaling. Several members of this group stimulate the guanosine triphosphatase (GTPase) activity of various G protein alpha-subunits, including the photoreceptor G protein, transducin. In photoreceptor cells transducin GTPase is known to be substantially accelerated by the coordinated action of the gamma-subunit of its effector enzyme, cGMP phosphodiesterase (PDE gamma), and another yet unidentified membrane-associated protein factor. Here we test the possibility that this factor belongs to the RGS family of GTPase stimulators. We report a detailed kinetic analysis of transducin GTPase activation by two members of the RGS family, RGS4 and G alpha interacting protein (GAIP). RGS4, being at least 5-fold more potent than GAIP, stimulates the rate of transducin GTPase by 2 orders of magnitude. Neither RGS4 nor GAIP requires PDE gamma for activating transducin. Rather, PDE gamma causes a partial reversal of transducin GTPase activation by RGS proteins. The effect of PDE gamma is based on a decreased apparent affinity of RGS for the alpha-subunit of transducin. Our observations indicate that GTPase activity of transducin can be activated by at least two distinct mechanisms, one based on the action of RGS proteins alone and another involving the cooperative action of the effector enzyme and another protein.     

Laryngeal sarcomatoid carcinoma: clinical, histological and immunohistochemical study of four cases

A 1488-bp fragment of bovine retina guanylate cyclase B gene encoding the catalytic and dimerizing domains as well as part of the protein kinase domain was expressed in Escherichia coli cells. The expression product was obtained as inclusion bodies and solubilized in 6 M guanidine hydrochloride. The fragment of guanylate cyclase B is a dimer close in catalytic activity to the native enzyme.