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To ascertain tissue oxygenation during conversion from hypo to hyperdynamic state with vascular volume expansion, venous outflow from a segment of ileum was isolated in anesthetized and pump-ventilated endotoxic dogs to measure gut oxygen uptake (VO2), lactate metabolism, intramucosal PCO2 and tissue PO2 (PtiO2). Tissue PO2 was measured by multipoint surface Mehrdraht Dortmund Oberfläche electrodes placed on mucosal and serosal surfaces of gut. Six dogs were infused with 2 mg.kg-1 E. coli lipopolysaccharide (LPS) in one hour followed by a two hour 0.5 mL.kg-1.min-1 dextran infusion. Two dogs were used as controls and received dextran infusion in order to assess time and hemodilution-dependent effects. LPS infusion resulted in an hypodynamic sepsis with supply limited VO2, increased arterial lactate and increased lactate output by gut. Resuscitation resulted in an hyperdynamic sepsis with improvement of whole-body VO2. In the gut, VO2 remained low and intramucosal PCO2 as well as lactate output remained high, despite increased flow. Gut PtiO2 results suggested blood flow maldistribution with tissue hypoxia in the mucosa despite increased total flow to the gut. Gut VO2, lactate flux, intramucosal PCO2, and tissue PO2 were consistent with regulatory responses that shut down mucosal perfusion and oxygenation in spite of increased blood flow to gut.

Objectives: To determine the oxygen supply (DO2) and uptake (VO2) responses to a 60-min dobutamine infusion in critically ill septic patients without circulatory shock and with normal blood lactate concentrations. Also, to determine whether these responses would predict outcome., Design: Prospective, cohort study., Setting: Five intensive care units in university-affiliated, city hospitals., Patients: Fifty critically ill patients with sepsis syndrome were studied from April 1990 to August 1991., Interventions: Pulmonary artery catheterization; fluid loading if pulmonary artery occlusion pressure was < 10 mm Hg; and 10 micrograms/min/kg dobutamine infusion for 60 mins., Measurements and Main Results: Cardiac index, DO2, VO2, and oxygen extraction ratio were determined immediately before and 1 hr after the onset of the dobutamine test. Using receiver operating characteristic curves, responders to the dobutamine infusion were identified by a > 15% increase in VO2 from the time immediately before to 1 hr after the onset of the dobutamine test. We identified 23 responders and 27 nonresponders. Groups differed significantly in age (responders 46 yrs vs. nonresponders 55 yrs) and associated chronic disease (responders one cancer vs. nonresponders six cancers). Significant changes in responders were: a) cardiac index increased 42.9%; b) systemic vascular resistance decreased 20.7%; and c) DO2 increased 39.1% while VO2 increased 40.8%, with no changes in oxygen extraction or blood lactate concentration. Significant changes in nonresponders were: a) cardiac index increased 14.2%; b) DO2 increased 13.2% and c) oxygen extraction decreased from 0.26 to 0.22. Lactate concentration increased significantly by 25.1% in nonresponders. The mortality rate in responders (8.7%) was significantly less than that rate in nonresponders (44.4%)., Conclusions: Most of these septic patients without shock or hyperlactatemia responded to dobutamine infusion in one of two ways: with little increase in DO2 and no increase in VO2, or with significant increases in both DO2 and VO2. The latter response is typical of healthy volunteers given dobutamine. Because of the calorigenic effect of dobutamine, our results imply nothing about the presence or absence of oxygen supply limitation. Still, patients who had increases in DO2 and VO2 had a much higher survival rate than patients who did not. We speculate that the inability of some patients to respond to dobutamine and the associated higher mortality rate may be related to beta-adrenoreceptor dysfunction.

We investigated the responses of canine coronary rings to endothelium-derived relaxing factor-nitric oxide- (EDRF-NO) dependent agonists and NO synthase (NOS) inhibitors 3 h after endotoxic shock was induced in dogs by lipopolysaccharide infusion (LPS; 2 mg/kg). EDRF-NO-dependent relaxation to thrombin [control maximum response produced after administration of thrombin (Emax) was -85.2 +/- 7.0% of the constrictor response produced by the thromboxane analogue U-46619], acetylcholine (control Emax -88.4 +/- 3.4%), or bradykinin (control Emax -80.5 +/- 2.2%) was not inhibited by LPS (Emax thrombin -75.9 +/- 9.5%; Emax acetylcholine -90.2 +/- 2.4%; Emax bradykinin -91.6 +/- 3.4%). The NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) (10(-6)-3 x 10(-4) M) caused constriction of rings with endothelium (Emax 36.3 +/- 5.6%), an effect that was greater after LPS (Emax 59.2 +/- 4.1%; P < 0.05). D-NMMA had no effect in control, but it increased tension after LPS (Emax 20.8 +/- 9.7%). Contrary to expectations, L- and D-NMMA relaxed endothelium-denuded rings (-30.4 +/- 8.7% L-NMMA; -45.1 +/- 11.7% D-NMMA; P < 0.05). However, neither agent caused relaxation after in vivo LPS (10.2 +/- 3.4% L-NMMA; 8.9 +/- 5.2% D-NMMA). N omega-nitro-L-arginine-methylester (L-NAME) and nitro-L-arginine (10(-6)-3 x 10(-4) M) increased tension (Emax 82.3 +/- 23.9 and 73.1 +/- 8.8%, respectively) but only when endothelium was present, and the increases were no greater in LPS-treated groups than in controls (with LPS: Emax L-NAME 87.3 +/- 16.5%; Emax nitro-L-arginine 65.7 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Two cases are reported of cardiac herniation complicating intrapericardial pneumonectomy in the early postoperative period. Both patients had a radical pneumonectomy for right-sided bronchial carcinoma invading, in one patient, the carina and the superior vena cava. The pericardial defect, made necessary by the surgical procedure, had not been closed in either patient. About two hours after the end of surgery, both patients, lying supine, developed a state of shock, with tachycardia and arterial hypotension. The diagnosis of cardiac herniation was made in both cases on the chest film. Placing the patient on his left side was only partly efficient in one patient, slowing the heart rate from 160 b.min-1 to 120 b.min-1 and increasing the systolic blood pressure (from 60 mmHg to 80 mmHg). Both patients therefore required to be operated on again. In one patient, the heart had completely herniated through the pericardial defect, and had turned to the right side about the vena caval axis; in the other patient, partly improved by being turned to his left, the heart had returned to its normal position. The pericardial defects were closed in both cases with a strip of dura mater previously treated with 2 (ethyl-mercurithiol-5-benzoxazol) carboxylic acid. The immediate postoperative course was uneventful. Unexpected symptoms and sign occurring in the early postoperative period after intrapericardial pneumonectomy must imperatively lead to carrying out a chest X-ray.

Objective: We report a case of corticosteroid-induced myopathy with involvement of respiratory muscles observed in a myasthenic patient., Patient: A 37-years-old woman, under corticosteroid treatment for two years for typical myasthenia gravis was admitted to ICU for acute myasthenic respiratory failure. Weaning from mechanical ventilation remained impossible despite 4 plasma exchanges and azathioprine. The patient exhibited a progressive 12 kg weight loss with muscular weakness and atrophy., Measurements and Results: Peripheral and diaphragmatic electromyography as well as histological study were consistent with a steroid-induced myopathy. Discontinuation of corticosteroid treatment was followed by a rapid weight gain with general improvement and allowed weaning from mechanical ventilation with a complete recovery., Conclusion: This case provides evidence that corticosteroid-induced myopathy may be observed in myasthenia gravis and may involve the respiratory muscles as well as the peripheral musculature.

From previous studies it has been hypothesized that multiple organ failure and high level of mortality, seen in critically ill septic patients, may be due to defective oxygen extraction and tissue hypoxia occurring early in the course of sepsis. Oxygen flux test has been proposed as a method of revealing an occult oxygen debt. We used a one hour dobutamine infusion test, in septic patients, without increase in blood lactate. Fifty patients with sepsis syndrome entered a multicentric prospective study. After fluid loading to increase pulmonary artery occlusion pressure (Paop) to a minimum value of 10 mmHg, all the patients were given 10 mcg/kg.min of dobutamine for one hour. Hemodynamic and metabolic variables were recorded before, HO, and after the test, H1 (cardiac index, Paop, oxygen deliver, DO2, and consumption, VO2, oxygen extraction ratio, (OER), blood lactate). The dobutamine test allowed to identify responders (R) who increased VO2 by more than 15% and non-responders. R and NR differed significantly in mortality (8.5% vs 44.4%). The test has a good predictive value for surviving. Without respect of the result of the test, the patients were randomized in two groups. The group D+ was given conventional therapy and dobutamine at the same rate of infusion for 9 consecutive days and the D- group received only conventional therapy. The RD+ patients improved more rapidly when compared with RD-, NRD+, NRD-. We concluded that a one hour dobutamine test is able to identify R and NR critically ill septic patients. The response is associated with significant difference in outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

High levels of circulating catecholamines associated with heart failure down-regulate cardiac beta-receptors, with a more pronounced effect on beta-1 receptors, leading to impaired inotropic effect. The use of exogenous inotropic agents is therefore a logical therapeutic approach in heart failure. Dobutamine is a synthetic catecholamine that acts on alpha-1, beta-1 and beta-2 adrenergic receptors. In the heart, the stimulation of these receptors produces a relatively strong, additive inotropic effect and a relatively weak chronotropic effect. In the vasculature, alpha-1 agonist activity (vasoconstriction) balances the beta-2 agonist effect (vasodilatation). In clinical use, dobutamine has a rapid onset of action and a short half-life. It increases myocardial contractility, while the reflex reduction in sympathetic tone, in response to augmentation of stroke volume, leads to a decrease in total peripheral resistance. The expected hemodynamic effects are an increase in cardiac output and a decrease in systemic vascular resistance without significant change in arterial pressure or heart rate. In acute cardiac failure state with elevated afterload pressures, resulting from myocardial dysfunction, dobutamine therapy remains, nowadays, the reference.

Myosin light chain kinase, which is located primarily in the soluble fraction of bovine myocardium, has been isolated and purified approximately 1200-fold with 16% yield by a three-step procedure. The approximate content of soluble myosin light chain kinase in heart is calculated to be 0.63 microM. The isolated kinase is active only as a ternary complex consisting of the kinase, calmodulin, and Ca2+; the apparent Kd for calmodulin is 1.3 nM. The enzyme also exhibits a requirement for Mg2+ ions. Myosin light chain kinase is a monomeric enzyme with Mr = 85,000. The enzyme exhibits a Km for ATP of 175 microM, and a K0.5 for the regulatory light chain of cardiac myosin of 21 microM. The optimum pH is 8.1. Kinase activity is specific for the regulatory light chain of myosin. The specific activity of the isolated enzyme (30 nmol 32P/min/mg of protein) is considerably less than and corresponding values reported for the skeletal and smooth muscle light chain kinases. This is probably due to proteolysis during extraction of the myocardium, a phenomenon which has, as yet, proven impossible to eliminate. In contrast to the smooth muscle enzyme (Adelstein, R.S., Conti, M.A., Hathaway, D.R., and Klee, C.B. (1978) J. Biol. Chem. 253, 8347-8350), the cardiac kinase is not phosphorylated by the catalytic subunit of cAMP-dependent protein kinase.

Muscular contraction is triggered by the increase in free calcium concentration and modulated by cyclic nucleotide-dependent phosphorylation. Beside a direct trigger of sarcomeric muscle contraction through binding of troponin C, calcium ions trigger or modulate contractility through calcium-calmodulin-dependent myosin light chain kinases, and increase the rate of relaxation through the calmodulin-dependent phosphorylation of phospholamban, the activator of the cardiac sarcoplasmic reticulum calcium pump. In both cases, a concerted regulation by calcium and cyclic nucleotides is observed. Hyperactivation of the calcium pump is brought about by additional phosphorylation of phospholamban by cAMP-dependent protein kinase. Similarly myofibrillar myosin light chain kinases from smooth and skeletal muscles are substrates of the cAMP-dependent protein kinase. The calmodulin-dependent protein kinases are probably organized into supramolecular regulatory complexes.

Myosin light chain kinase was extracted from bovine aortic muscularis by a low ionic strength buffer containing 50% glycerol. It was purified 130-fold with a 10% yield by anion-exchange chromatography followed by affinity chromatography on calmodulin-Sepharose. The enzyme was 95% calcium/calmodulin-dependent and exhibited a specific activity of 2-6 mumol/min per mg. It phosphorylated the myosin regulatory light chain exclusively. The apparent Kd for calmodulin was 6.3 nM. Upon phosphorylation of the enzyme by the catalytic subunit of cyclic AMP-dependent protein kinase, its affinity for calmodulin decreased 4-fold, without alteration of the V. When examined by SDS-polyacrylamide gel electrophoresis, the purified enzyme was made up of two major peptides (Mr 142 000 and 131 000, respectively), with a minor 80 000 dalton peptide. All these peptides were 32P-labeled after incubation with [gamma-32P]ATP and the catalytic subunit of cyclic AMP-dependent protein kinase. Also, after non-denaturing polyacrylamide gel electrophoresis, they all exhibited myosin light chain kinase activity, suggesting that the 131 000 and 80 000 dalton species are proteolytic products of the native enzyme of Mr 142 000. Vascular smooth muscle myosin light chain kinase is therefore soluble, calcium/calmodulin dependent and phosphorylatable by cyclic AMP-dependent protein kinase with concomitant decrease in its affinity for calmodulin. These features account for the beta-adrenergic relaxation of vascular smooth muscle.

Authors report one case of death caused by anaphylactic collapsus after a fluorescein angiography. They make a review of all the complications described and particularly insist about the anaphylactic reactions. They conclude on the modalities of treatment.

The proteolytic action of a bacterial collagenase on two Bence-Jones k chains has been studied and the localization of the cleavage sites accomplished. The implications of this enzymatic attack are discussed.

Erythrocityc variations of glycolytic intermediates and 2,3-DPG levels in rabbits performing strenuous exercise under hypoxic conditions are correlated with blood pH variations. The hypoxia alone is not able to induce directly an increase of erythrocytic 2,3-DPG level which would facilitate tissue oxygenation.

In order to identify the physiological regulator of calcium dependent myosin light chain kinases of cardiac, skeletal, and smooth muscles, the effects of the three homologous calciproteins, calmodulin, troponin C, and parvalbumin, on the kinases isolated from bovine myocardium, rabbit skeletal muscle, and turkey gizzard were examined. Only calmodulin was effective in stimulating the cardiac, skeletal, or smooth muscle kinase; troponin C and parvalbumin exhibited no activation of any of the three kinases, even when examined at concentrations as high as 10-(5) M. It is concluded that calmodulin is the specific regulator of myosin light chain kinase in cardiac, skeletal, and smooth muscle.