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P Mendes

Publications and source records attributed to P Mendes.

8 recordsLinked to original sources
PubMed1992

Channelling can decrease pool size.

It is widely considered that a possible advantage of metabolite channelling, in which a product of an enzyme is transferred to the next enzyme in a metabolic pathway without being released to the 'bulk' solution, is that channelling can decrease the steady-state concentrations of 'pool' intermediates. This then spares the limited solvent capacity of the cell, and reduces the loss of pathway flux due to leakage or instability of the free intermediate. Recently, however, based on simulations of a particular model of a 'dynamic' channel, Cornish-Bowden ["Failure of channelling to maintain low concentrations of metabolic intermediates" (1991) Eur. J. Biochem. 195, 103-108] has argued that this is not in fact the case; his simulations indicated that the channel was rather ineffective at decreasing the concentration of the pool intermediate, and in some cases actually increased it. However, although his simulations were restricted to very specific thermodynamic and kinetic parameters, he generalised his conclusions, arguing that "channelling has no effect on the free concentration of a channelled intermediate in a pathway". By showing that, for a number of kinetic cases, the concentration of the pool intermediate did decrease substantially with increased channelling, we demonstrate here that the conclusion of Cornish-Bowden is not correct. In particular, if the reaction catalysed by the enzymes forming the channel has an equilibrium constant K higher than 1, and if the enzyme removing the product of the channel reaction is kinetically competent, channelling in the model system studied by Cornish-Bowden (1991) can decrease the steady-state concentration of the pool by a factor of 1000, independently of the mechanism of the terminal reaction and under conditions of essentially constant overall flux. If the channel is a 'static' channel, the decrease in the pool can be to arbitrarily low levels. This conclusion also holds for a system in which other reactions may consume the pool intermediate. Thus, channelling can maintain metabolite concentrations at low levels.

Catalysis↗
PubMed1992

Pressure-flow relationships of the pulmonary circulation during endotoxin infusion in intact dogs.

BACKGROUND AND METHODS: We aimed to characterize the effects of an endotoxin insult (Escherichia coli 0127:B8) on the relationships between pulmonary vascular pressure and flow in intact dogs. To achieve this goal, multipoint plots of total pressure gradient, arterial pressure gradient, and venous pressure gradient vs. flow were generated by graded inflation of a right atrial balloon, which was used to vary flow. The partitioning of the total pressure decrease across the pulmonary vasculature (total pressure gradient = pulmonary arterial pressure-pulmonary artery occlusion pressure [PAOP]) into gradients across pulmonary arterial (arterial pressure gradient = pulmonary arterial pressure--effective capillary pressure) and pulmonary venous (venous pressure gradient = effective capillary pressure--PAOP) regions was assessed by a waveform mathematical analysis of the pulmonary arterial pressure profile during arterial occlusion, with computation of both PAOP and effective pulmonary capillary pressures. Slopes and extrapolated pressure intercepts from linear regression fits to the pulmonary vascular pressure/flow plots were determined in seven dogs after a 2-hr endotoxic infusion interval and were compared with the corresponding values that characterized a similar group of sham-operated dogs. RESULTS: Under normal conditions, the extrapolated pressure intercept for pulmonary arterial pressure gradient was virtually 0 mm Hg; for total pulmonary arterial pressure gradient and pulmonary venous pressure gradient, the mean extrapolated pressure intercepts were substantially positive: 2.4 +/- 0.2 and 2.1 +/- 0.3 mm Hg, respectively. Endotoxin infusion at 0.25 micrograms/kg/min significantly increased the pressure intercepts from 2.4 to 8.7 and from 2.1 to 8.3 mm Hg of total pressure gradient and venous pressure gradient vs. flow, respectively. This infusion produced a minor, nonsignificant change in the intercept of arterial pressure gradient vs. flow, whereas it increased its slope significantly (p less than .05) from 0.036 to 0.081 mm Hg/mL/min/kg. CONCLUSIONS: These data suggest that endotoxin's effects on vascular resistance are exerted at two different loci such that these effects are additive. These endotoxin-induced effects consisted of increased vascular resistance of the arterial segment and appearance of a Starling resistor at the venous side of the pulmonary circulation, which acted as the relevant back-pressure to flow.

Animals↗
PubMed1992

Effect of positive end-expiratory pressure on pulmonary vascular pressure-flow characteristics in canine endotoxin shock.

The vascular pulmonary pressure-flow (P-Q degree) relationships were studied in anesthetized dogs in order to characterize the distribution of total resistance in the pulmonary bed with respect to incremental resistance and critical closure prior to and after endotoxin insult. Incremental resistance was computed as the slope of the P-Q degree relation, whereas critical closure was referred to as the extrapolated pressure intercept at zero flow. P-Q degree coordinates were obtained by varying Q degree through graded inflation of right atrial balloon. The gradients across the arterial segment (Pa = Ppa - Pc) and across the venous segment (Pv = Pc - Pw) of the pulmonary vasculature were defined by the computation of effective capillary pressure (Pc) obtained from the analysis of the transient decay of pulmonary artery pressure (Ppa) toward wedge pressure (Pw) after arterial occlusion. Six group E dogs were infused with endotoxin at a rate of 0.25 microgram/kg min, while six additional animals served as control (group C). Endotoxin induced increases in flow resistance from 0.056 to 0.096 mm Hg/ml/min/kg due to arterial vasoconstriction and increases in critical closure from 2.3 to 8.4 mm Hg due to a venous waterfall. Before and after endotoxin insult, we assessed effects of each of three levels of static lung inflation (PEEP) on P-Q degree relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Lung fluid dynamics and supply dependency of oxygen uptake during experimental endotoxic shock and volume resuscitation.

BACKGROUND AND METHODS: We studied the effect of volume resuscitation on lung fluid balance and systemic oxygen extraction during septic shock in eight anesthetized dogs. Sepsis was induced using a 2-hr continuous infusion of Escherichia coli endotoxin at 0.25 micrograms/min.kg. Relationships between oxygen uptake (VO2) and oxygen supply (DO2) were performed acutely during stepwise controlled decrements in cardiac output by progressive inflation of an intracardiac balloon. At each stage, DO2 and corresponding VO2 were measured independently and the individual critical DO2 level was referred to as the point below which the relationship held. The slope of such a constructed relationship was defined as the maximal oxygen extraction ratio. Lung fluid balance was assessed by measurements of extravascular lung water. All values were studied at baseline, after endotoxin insult, and after reversing hypotension by a 10% dextran infusion. RESULTS: Endotoxin infusion led to a shock state that associated hypotension (from 135 to 63 mm Hg) with increases in blood lactate (from 0.53 to 3.9 mmol/L). The mean critical DO2 and maximal oxygen extraction ratio were significantly altered from 7.9 to 17.8 mL/min.kg and from 0.81 to 0.38, respectively. After reversing hypotension by 28 mL/kg colloid infusion, the critical DO2 (11.4 mL/min.kg) and maximal oxygen extraction ratio (0.48) were significantly improved. However, restoration of normal values required a state of fluid overload by further dextran infusion (8 mL/kg). At the end of the fluid challenge, extravascular lung water significantly increased from 6.4 to 17.4 mL/kg. CONCLUSIONS: These data suggest that volume loading may reverse endotoxin-induced peripheral perfusion abnormalities. However, substantial pulmonary edema may occur, possibly jeopardizing the beneficial effects of fluid expansion.

Animals↗
PubMed1990

Pharmacokinetics of cefodizime during continuous ambulatory peritoneal dialysis.

In a single-dose open cross-over trial we studied the pharmacokinetics of cefodizime 1 g in four uraemic patients treated by continuous ambulatory peritoneal dialysis (CAPD). Cefodizime was administered, successively with a wash out, (a) iv over 3 min and (b) by intraperitoneal (ip) administration together with the dialysate fluid (2 litres). Concentrations of cefodizime were measured by HPLC in blood and dialysate samples collected during an 8-h dwell period and in additional dialysate samples collected up to 48 h after drug administration. The mean (relative) total clearances following the iv and ip administration were 23 and 31 ml/min, respectively, and the terminal half-lives 5.5 and 6.7 h, respectively. Following iv administration, the peritoneal clearance was approximately 0.5 ml/min. After ip administration high concentrations of cefodizime were measured in the dialysate throughout the dwell period and systemic availability was good (80%) but variable.

Adult↗
PubMed1990

Accuracy in early prediction of prognosis of patients with septic shock by analysis of simple indices: prospective study.

In 26 consecutive septic shock patients, we analyzed the clinical, hemodynamic, and metabolic data before and during volume infusion to test their circulatory reserve in response to fluid repletion. These patients were investigated to identify early variables that could predict outcome. There were 15 survivors (group A) and 11 nonsurvivors (group B). As a mean, group A patients were hemodynamically evaluated 2.3 h after onset of the sepsis syndrome, whereas group B patients underwent cardiac catheterization after a 12-h interval. At the initial evaluation, both groups demonstrated similarly decreased mean arterial pressure, mean heart rate, and mean cardiac filling pressure. Only group A patients evidenced elevated cardiac index (CI) (greater than 4 L/min.m2) associated with low systemic vascular resistance index (less than 7400 dyne.sec/cm5.m2), which is generally recognized as hyperdynamic cardiac state. However, none of the initial cardiovascular variables could serve as a predictor for survival. Fluid challenge increased left ventricular preload from 6 to 12.4 and from 7.8 to 12.7 mm Hg in group A and group B, respectively. The increases were associated with significant increases in CI from 4.4 to 6.9 and from 3 to 3.8 L/min.m2. However, at the end of fluid challenge, only group A patients exhibited normal cardiac response, as evidenced by the change in left ventricular stroke work index (LVSWI) for a given increase in the pulmonary capillary wedge pressure (WP) that was referred to as left cardiac preload.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Pathogenesis and management of acute pulmonary embolism.

Pulmonary embolism can produce severe cardiopulmonary dysfunction characterized by pulmonary artery hypertension, right ventricular failure, and hypoxemia. The search for the source of a pulmonary embolus, by exploration of the veins of the lower limbs and the inferior vena cava should be systematically carried out in all cases of pulmonary embolus which are not immediately life-threatening to the patient. The treatment of deep vein thrombosis associated with pulmonary embolism with thrombolytic agents has been proposed and utilized for approximately 20 years. Although superior results have been claimed with thrombolytic agents, the use of this type of treatment remains limited to massive or sub-massive pulmonary embolism. Fibrinolytic agents with high specificity for fibrin in the thrombi and little systemic activation of the fibrinolytic system have been developed and tested in preliminary clinical trials of patients with acute pulmonary embolism. The largest published experience available has been with recombinant tissue plasminogen activator (rtPA). The acylated streptokinase-plasminogen complex (APSAC) and pro-urokinase also gave promising results. All these agents were accompanied by unexpectedly high incidence of systemic activation of the fibrinolytic system and by hemorrhagic complications with frequencies similar to those that follows the use of first generation products (urokinase and streptokinase). Hence, their superior clinical efficacy must be clearly proven before they are substituted for a more widely available and less expensive drug, such as streptokinase.

Acute Disease↗