Polymer structure and solubility of deoxyhemoglobin S in the presence of high concentrations of volume-excluding 70-kDa dextran. Effects of non-s hemoglobins and inhibitors.
Earlier observations indicated that volume exclusion by admixed non-hemoglobin macromolecules lowered the polymer solubility ("Csat") of deoxyhemoglobin (Hb) S, presumably by increasing its activity. In view of the potential usefulness of these observations for in vitro studies of sickling-related polymerization, we examined the ultrastructure, solubility behavior, and phase distributions of deoxygenated mixtures of Hb S with 70-kDa dextran, a relatively inert, low ionic strength space-filling macromolecule. Increasing admixture of dextran progressively lowered the Csat of deoxyHb S. With 12 g/dl dextran, a 5-fold decrease in apparent Csat ("dextran-Csat") was obtained together with acceptable sensitivity and proportionality with the standard Csat when assessing the effects of non-S Hb admixtures (A, C, and F) or polymerization inhibitors (alkylureas or phenylalanine). The volume fraction of dextran excluding Hb was 70-75% of total deoxyHb-dextran (12 g/dl) volumes. Electron microscopy showed polymer fibers and fiber-to-crystal transitions indistinguishable from those formed without dextran. Thus when Hb quantities are limited, as with genetically engineered recombinant Hbs or transgenic sickle mice, the dextran-Csat provides convenient and reliable screening of effects of Hb S modifications on polymerization under near-physiological conditions, avoiding problems of high ionic strength. (+info)
Resetting of exaggerated tubuloglomerular feedback activity in acutely volume-expanded young SHR.
One purpose of the present study was to evaluate the ability of 7-wk-old spontaneously hypertensive rats (SHR) to reset tubuloglomerular feedback (TGF) activity in response to acute volume expansion (VE). Second, we evaluated the contribution of ANG II, via its action on AT1 receptors, to TGF control of glomerular function during VE. TGF was assessed by micropuncture methods and proximal tubular stop-flow pressure (SFP) determinations in SHR, Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD). During euvolemia SHR exhibited enhanced TGF activity. In the same animals acute VE was achieved by infusion of saline (5 ml. h-1. 100 g body wt-1). VE led to resetting of TGF in all three strains. Maximal SFP responses, elicited by a 30-40 nl/min loop of Henle perfusion rate, decreased from 19 to 12 mmHg in SHR and, on average, from 11 to 5 mmHg in WKY and SD (P < 0.001). Tubular flow rate producing a half-maximal response (turning point) shifted to higher flow rates during VE, from 12 to 14 nl/min in SHR and from 15 to 19 nl/min in WKY. Administration of the AT1 receptor blocker candesartan (0.05 mg/kg iv) during sustained VE decreased TGF-mediated reductions in SFP in SHR and slightly increased the turning point in WKY. Nevertheless, other parameters of TGF activity were unaffected by AT1 receptor blockade. In conclusion, young SHR possess the ability to reset TGF activity in response to VE to a degree similar to compensatory adjustments in WKY. However, TGF remains enhanced in SHR during VE. ANG II and its action on AT1 receptors are in part responsible for the exaggerated SFP responses in young SHR during VE. (+info)
Influence of right atrial pressure on the cardiac pacemaker response to vagal stimulation.
We have recently shown that the intrinsic rate response to an increase in right atrial pressure is augmented when cardiac muscarinic receptors are activated. This present study examines the cardiac pacemaker response to vagal stimulation at different values of right atrial pressure in isolated rat right atrium and in the rabbit heart in situ. In the rat atrium, when pressure was raised in steps from 2 to 10 mmHg, there was a progressive reduction in the response to vagal stimulation [40.5 +/- 7.2% reduction (mean +/- SE) at 8 mmHg, P < 0.01], which was independent of the level of vagal bradycardia, that persisted in the presence of the beta-adrenergic agonist isoproterenol. In barbiturate-anesthetized rabbits with cervical vagi cut and beta-adrenergic blockade, raising right atrial pressure approximately 2.5 mmHg by blood volume expansion reduced the bradycardia elicited by electrical stimulation of the peripheral end of the right vagus nerve (9.1 +/- 1.1% reduction, P < 0.0001). These results demonstrate that vagal bradycardia is modulated by the level of right atrial pressure and suggest that normally right atrial pressure may interact with cardiac vagal activity in the control of heart rate. (+info)
Effect of 20% in vitro haemodilution with warmed buffered salt solution and cerebrospinal fluid on coagulation.
We have conducted an in vitro coagulation study consisting of two separate groups of 20 subjects using the thrombelastograph. In the first group, haemodilution was performed with a physiological balanced salt solution similar to plasma, with the exception of calcium, and buffered to a normal pH (Plasmalyte B) at 37 degrees C on blood obtained from consenting volunteers. In the second group, a protein-poor body fluid (cerebrospinal fluid (CSF)) obtained from parturient patients undergoing spinal anaesthesia for Caesarean section was used as the diluent. There were statistically significant differences between the warmed Plasmalyte B treated samples and their untreated controls for all variables measured by the thrombelastograph, except for maximum amplitude, and between the CSF treated samples and their untreated controls for all variables. We conclude that electrolyte and acid-base composition of the diluent fluid had no effect on the observation that crystalloid haemodilution produces hypercoagulability. The marked increase in coagulability produced by addition of CSF cannot be explained on a simple haemodilution basis and confirms previous suggestions of the presence of a procoagulant factor in CSF. (+info)
Pseudo-proteinuria following gelofusine infusion.
Transient massive proteinuria following cardiopulmonary bypass surgery was observed. It was characterized and attributed to post-operative gelofusine infusion. Gelofusine was found to interfere with dye binding but not immunochemical assays of proteinuria. Proteinuria following gelofusine infusion may not reflect underlying glomerular pathology. (+info)
Effect of intravenous saline, albumin, or hydroxyethylstarch on blood volume during combined ultrafiltration and hemodialysis.
It is generally advocated to use saline or albumin infusions during symptomatic hypotension during dialysis. However, because of their side effects and/or costs, they are of limited use. Hydroxyethylstarch (HES), a synthetic colloid with a long-standing volume effect, is used in the management of hypovolemia. In this study, the efficacy of three fluids (isotonic saline [0.9%], albumin [20%], and HES [10%]) was assessed during three treatment sessions with combined ultrafiltration and hemodialysis, which differed in the type of fluid given intravenously. Changes in relative blood volume (BV), systolic BP (SBP), and vascular reactivity (venous tone [VT]) were compared. An intravenous infusion of 100 ml of fluid was given when the decrease in BV versus baseline was more than 10% as measured by a continuous optical reflection method. The ultrafiltration was continued. BV decreased significantly versus baseline independent of the intravenous fluid administration in all three treatment sessions. However, when we compared BV values at the end of the dialysis session with those at the time of infusion, BV continued to decrease significantly with saline (change in BV -4.56 +/- 2.75%; P < 0.05) and albumin (change in BV -2.13 +/- 2.51%; P < 0.05), but not with HES (change in BV -0.15 +/- 2.17%; NS). Between albumin and HES there were no significant differences in changes in BV (NS), whereas between HES and saline (P < 0.05) and between albumin and saline (P < 0.05) the differences in BV changes were significant. SBP remained unchanged within each session. Although SBP tended to decrease more with saline compared to albumin and HES, the difference was not significant. The higher decrease in BV and SBP with saline was counterbalanced by a significantly higher increase in VT, while VT remained unchanged in the other two sessions. It is concluded that HES is a promising fluid in preserving blood volume, comparable to albumin, but superior to saline. (+info)
Plasma volume expansion with solutions of hemoglobin, albumin, and Ringer lactate in sheep.
We have measured plasma volume expansion (Evans blue and hematocrit changes) and hemodynamic responses in conscious hemorrhaged and normovolemic splenectomized sheep after a 30-min infusion of either 20 ml/kg of diaspirin cross-linked hemoglobin (DCLHb), 20 ml/kg of human albumin (Alb), or 60 ml/kg of a solution of Ringer lactate (RL). All regimens expanded blood volume and increased blood pressure and cardiac output after hemorrhage. However, only 15 +/- 3% of the infused volume of RL was evident as intravascular expansion 10-min postinfusion, compared with 67 +/- 16% and 139 +/- 139% for Alb and DCLHb, respectively. DCLHb infusions were associated with higher blood pressures and lower cardiac outputs compared with RL and Alb infusions, but the increased oxygen content of blood with DCLHb resulted in systemic delivery of oxygen similar to that of the other infusions. These differences in hemodynamics and vascular volume continued for 6 h, and at 24 h vascular volume and all hemodynamics were similar in all three groups. The better volume expansion with DCLHb may be due to greater mobilization of endogenous interstitial protein or reduced transcapillary loss as total intravascular endogenous plasma protein increased after infusion of DCLHb, whereas there was an apparent loss of endogenous intravascular protein after infusions of Alb and RL. Vasoconstriction by DCLHb is one mechanism that could lower blood-to-tissue transport of fluid and protein. In addition to its oxygen-carrying capacity and vasoactivity, DCLHb is associated with volume expansion properties out of proportion to its colloid osmotic pressure. (+info)
Thrombelastogram reveals hypercoagulability after administration of gelatin solution.
We have compared the effects of gelatin, low molecular weight hydroxyethyl starch (HES) or albumin on tests of haemostasis and on the thrombelastogram in 42 ASA I patients undergoing total hip or knee replacement. Patients were allocated randomly to receive one of the three blood substitutes to obtain moderate intraoperative haemodilution. Blood loss and packed red cell infusion was the same in each group. A greater amount of gelatin was given (1.5 times the measured blood loss) because of its shorter half-life. There was a statistically significant but clinically negligible decrease in platelets count, prothrombin time and fibrinogen, and an increase in bleeding time in all groups. Platelets were slightly but significantly lower after HES. Haemodilution was comparable between groups. TEG showed a state of hypercoagulability in the gelatin group with a significant decrease in r, r + k and an increase in alpha angle. (+info)