Hyaline membrane disease, alkali, and intraventricular haemorrhage.
The relation between intraventricular haemorrhage (IVH) and hyaline membrane disease (HMD) was studied in singletons that came to necropsy at Hammersmith Hospital over the years 1966-73. The incidence of IVH in singleton live births was 3-22/1000 and of HMD 4-44/1000. Although the high figures were partily due to the large number of low birthweight infants born at this hospital, the incidence of IVH in babies weighing 1001-1500 g was three times as great as that reported in the 1658 British Perinatal Mortality Survey. Most IVH deaths were in babies with HMD, but the higher frequency of IVH was not associated with any prolongation of survival time of babies who died with HMD as compared with the 1958 survey. IVH was seen frequently at gestations of up to 36 weeks in babies with HMD but was rare above 30 weeks' gestation in babies without HMD. This indicated that factors associated with HMD must cause most cases of IVH seen at gestations above 30 weeks. Comparison of clinical details in infants with HMD who died with or without IVH (at gestations of 30-37 weeks) showed no significant differences between the groups other than a high incidence of fits and greater use of alkali therapy in the babies with IVH. During the 12 hours when most alkali therapy was given, babies dying with IVD received a mean total alkali dosage of 10-21 mmol/kg and those dying without IVH 6-34 mmol/kg (P less than 0-001). There was no difference in severity of hypoxia or of metabolic acidosis between the 2 groups. Babies who died with HMD and germinal layer haemorrhage (GLH) without IVH had received significantly more alkali than those who died with HMD alone, whereas survivors of severe respiratory distress syndrome had received lower alkali doses than other groups. It is suggested that the greatly increased death rate from IVH in babies with HMD indicates some alteration of management of HMD (since 1958) as a causative factor. Liberal use of hypertonic alkali solutions is the common factor which distinguishes babies dying with GLH and IVH from other groups of babies with HMD. Although the causal nature of this association remains unproved, it seems justifiable to lrge caution in alkali usage. (+info)
Modeling the effects of proteins on pH in plasma.
Stewart's model of plasma acid-base balance (Can. J. Physiol. Pharmacol. 61: 1444-1461, 1983) has three weaknesses in the treatment of weak acids: 1) the combination of all weak acids into one entity, 2) inappropriate chemistry for the protein combination with H+, and 3) undocumented values for the dissociation parameters. The present study models serum albumin acid-base properties by fixed negative charges and the association of H+ with the imidazole side chain of histidine. This model has three parameters: 1) the net negative fixed charge (21 eq/mol), 2) the number of histidine residues (16/mol), and 3) the association constant for the imidazole side chain (1.77 x 10(-7) eq/l), all determined from published values. The model was compared with that of Figge, Mydosh, and Fencl (J. Lab. Clin. Med. 120: 713-719, 1992) and with the pH data of Figge, Rossing, and Fencl (J. Lab. Clin. Med. 117: 453-467, 1991). The predictions of pH were excellent, comparable to those found by Figge, Mydosh, and Fencl. The model has the advantages that its structure and parameter values are supported by the literature and that the acid-base effects of factors modifying protein can be investigated. (+info)
Cardiovascular and catecholamine responses during endovascular and conventional abdominal aortic aneurysm repair.
OBJECTIVES: To compare changes in plasma catecholamines, acid-base status and cardiovascular dynamics in patients undergoing endovascular or conventional infrarenal abdominal aortic aneurysm (AAA) repair under standard general anaesthesia. DESIGN: Prospective cohort study. MATERIALS: 30 patients scheduled for elective infrarenal AAA repair. METHODS: Plasma epinephrine and norepinephrine concentrations, acid-base status and cardiovascular measurement were compared before surgery, and 5 min after aortic clamping and clamp release (conventional group) or occlusion and release (endovascular group) in patients undergoing endovascular (n = 15) or conventional AAA repair (n = 15). RESULTS: Arterial pH (p < 0.005) and base deficit (p < 0.05) increased, and plasma bicarbonate decreased (p < 0.005) during aortic cross-clamping in the conventional group. pH decreased further (p < 0.005), and base deficit and pCO2 increased (both p < 0.005) after clamp release. These changes were significantly greater than during endovascular repair, in whom within-group changes were not statistically significant. Values were similar in the two groups 30 min after reperfusion. Plasma epinephrine concentrations increased during conventional surgery (p < 0.05) and were greater than in the endovascular group (p < 0.05). Plasma norepinephrine concentrations increased during surgery in both groups but the changes were not statistically significant. CONCLUSIONS: Plasma catecholamine concentrations, changes in cardiovascular variables and acid-base status were increased during conventional compared with endovascular AAA repair. (+info)
Benzodiazepine localisation at the lipid-water interface: effect of membrane composition and drug chemical structure.
The effect of membrane chemical composition and drug chemical structure on the localisation of several benzodiazepines (BZDs) (DZ, diazepam; CZ, clonazepam; CX, chlordiazepoxide) within model membranes was investigated. We used a spectrophotometric method presented in a previous paper (B.A. Garcia, M.A. Perillo, Biochim. Biophys. Acta 1324 (1997) 76-84) based on the study of BZD acid-base equilibrium. 'Intrinsic pK' values (pKi) were calculated according to the theory of M.S. Fernandez and P. Fromherz (J. Phys. Chem. 81 (1977) 1755-1761). Homogeneous media of known dielectric constant (dioxane 0-80% v/v in water) were used to construct a curve of DeltapKi (pKi-pKw) vs. dielectric constant (D) where DeltapKi values obtained in lipidic dispersions were interpolated. In heterogeneous media consisting of aqueous dispersions of Triton X-100 micelles we determined the relative localisation depth of BZDs according to their DTriton values (36, 37 and 62 for DZ, CX and CZ respectively) taking into account that lower D values correspond to deeper localisation. pKi determined in dispersions of dipalmitoylphosphatidylcholine (dpPC) and egg phosphatidylcholine (egg-PC) mixed multilamellar vesicles showed that, when cholesterol content increased from 0 to 20 mole%, D values decreased (from 59 to 40) in dpPC vesicles and increased (from 51 to 72) in egg-PC vesicles, indicating a tendency of BZDs to penetrate deeper into less ordered interfaces. These results should be considered to understand the non-specific pharmacological effects of BZDs as well as to evaluate the actual relevance of their pharmacological concentrations. (+info)
Changes in ionized calcium concentrations and acid-base status during abdominal aortic vascular surgery.
Abdominal aortic surgery may produce significant haemodynamic instability (from a combination of factors: hypovolaemia, acid-base disturbances, vasoactive metabolite release from ischaemic tissues and hypocalcaemia). Calcium is often given after aortic unclamping to attenuate this instability. We studied 20 patients undergoing elective abdominal aortic surgery and observed a triphasic change in ionized calcium concentrations and acid-base status. Initially, during the cross-clamp period (when patients were cardiovascularly stable), ionized calcium concentrations decreased significantly (mean 1.06 (SD 0.08) to 0.91 (0.13) mmol litre-1; P < 0.01), while a significant metabolic acidosis developed (pH 7.38 (0.05) to 7.30 (0.05); P < 0.05). Second, release of the aortic cross-clamp resulted in further acidosis (pH 7.27 (0.05) (P < 0.05) mixed respiratory and metabolic) with a decrease in mean arterial pressure, with no change in ionized calcium concentrations. The third phase was associated with spontaneous restoration of acid-base status and ionized calcium concentrations to normal over 2 h. There was no correlation between units of blood given, volume of blood lost, fluid volume given or duration of aortic cross-clamping and degree of ionized hypocalcaemia. We conclude that ionized hypocalcaemia occurred during the cross-clamp period of aortic surgery, was unrelated to the volume of blood given and did not appear to be responsible for the changes in arterial pressure during surgery. (+info)
Regulation of thick ascending limb ion transporter abundance in response to altered acid/base intake.
Changes in ammonium excretion with acid/base perturbations are dependent on changes in medullary ammonium accumulation mediated by active NH4+ absorption by the medullary thick ascending limb. To investigate whether alterations in the abundance of medullary thick ascending limb ion transporters, namely the apical Na+/K+(NH4+)/2Cl- -cotransporter (BSC-1), the apical Na+/H+ -exchanger (NHE3), and the Na+/K+ -ATPase alpha1-subunit, may be responsible in part for altered medullary ammonium accumulation, semiquantitative immunoblotting studies were performed using homogenates from the inner stripe of the rat renal outer medulla. After 7 d of NH4Cl (7.2 mmol/220 g body wt per d) loading (associated with increased medullary ammonium accumulation), neither BSC-1 nor Na+/K+ -ATPase protein expression was altered, but NHE3 protein abundance was significantly increased. On the other hand, both BSC-1 and Na+/K+ -ATPase protein abundance was increased significantly in rats fed NaHCO3 (7.2 mmol/220 g body wt per d) for 7 d. Rats fed a high-NaCl diet (7.7 mEq Na+/220 g body wt per d) for 5 d also showed marked increases in both BSC-1 and Na+/K+ -ATPase expression. The expression level of NHE3 protein did not change with either NaHCO3 or high NaCl intake. None of these three transporters showed a significant difference in abundance between the groups fed equimolar (7.2 mmol/220 g body wt per d for 7 d) NaHCO3 or NaCl. It is concluded that outer medullary BSC-1 and Na+/K+ -ATPase alpha1-subunit protein abundance is increased by chronic Na+ loading but not by acid/base perturbations and that outer medullary NHE3 protein abundance is increased by chronic NH4Cl loading. (+info)
VCO2 and VE kinetics during moderate- and heavy-intensity exercise after acetazolamide administration.
The effect of carbonic anhydrase inhibition with acetazolamide (Acz) on CO2 output (VCO2) and ventilation (VE) kinetics was examined during moderate- and heavy-intensity exercise. Seven men [24 +/- 1 (SE) yr] performed cycling exercise during control (Con) and Acz (10 mg/kg body wt iv) sessions. Each subject performed step transitions (6 min) in work rate from 0 to 100 W [below ventilatory threshold (VET)]. VE and gas exchange were measured breath by breath. The time constant (tau) was determined for exercise VET by using a three-component model (fit from the start of exercise). VCO2 kinetics were slower in Acz (VET, MRT = 75 +/- 10 s) than Con (VET, MRT = 54 +/- 7 s). During VET kinetics were faster in Acz (MRT = 85 +/- 17 s) than Con (MRT = 106 +/- 16 s). Carbonic anhydrase inhibition slowed VCO2 kinetics during both moderate- and heavy-intensity exercise, demonstrating impaired CO2 elimination in the nonsteady state of exercise. The slowed VE kinetics in Acz during exercise +info)
Acid-base disturbance during hemorrhage in rats: significant role of strong inorganic ions.
The present study tests the hypothesis that changes in the strong inorganic ion concentrations contribute significantly to the acid-base disturbance that develops during hemorrhage in the arterial plasma of rats in addition to lactate concentration ([Lac-]) increase. The physicochemical origins for this acid-base disorder were studied during acute, graded hemorrhage (10, 20, and 30% loss of blood volume) in three groups of rats: conscious, anesthetized with ketamine, and anesthetized with urethan. The results support the hypothesis examined: strong-ion difference (SID) decreased in the arterial plasma of all groups studied because of an early imbalance in the main strong inorganic ions during initial hemorrhagic phase. Moreover, changes in plasma [Lac-] contributed to SID decrease in a later hemorrhagic phase (after 10% hemorrhage in urethan-anesthetized, after 20% hemorrhage in ketamine-anesthetized, and after 30% hemorrhage in conscious group). Inorganic ion changes were due to both dilution of the vascular compartment and ion exchange with extravascular space and red blood cells, as compensation for blood volume depletion and hypocapnia. Nevertheless, anesthetized rats were less able than conscious rats to preserve normal arterial pH during hemorrhage, mainly because of an impaired peripheral tissue condition and incomplete ventilatory compensation. (+info)