Rise In Hematocrit Research Articles

Ebola and hantaviruses.

Hantavirus pulmonary syndrome (HPS) and Ebola hemorrhagic fever are acute diseases with high mortality rates in humans caused by negative-stranded RNA viruses for which we have no vaccines. These viruses present two very different profiles when their ecology, history, and status as emerging pathogens are considered. This paper will discuss the dynamics of the discovery and emergence of these two viruses in recent epidemics — HPS in the United States and Ebola hemorrhagic fever in Africa — and summarize what is known about these dangerous viruses. Our laboratory became involved with hantaviruses in the summer of 1993 soon after patients began to present in the southwestern United States with an acute febrile disease associated with rapid progression of pulmonary failure and, at times, rapid recovery. The disease, which had a mortality rate of about 50%, began with a prodromal phase, typically lasting 3 or 4 days, characterized by fever, myalgia and malaise. The development of dyspnea signalled the onset of severe pulmonary edema. As fluid entered the lungs, the blood picture changed: there was hemoconcentration with rise in hematocrit; immunoblasts were present, thrombocytopenia and other changes were seen. The Special Pathogens Branch (SPB) of the National Center for Infectious Diseases (NCID) became involved, not because of any preconceived notion about the nature of the etiologic agent, but rather as part of a coordinated effort mounted by NCID, Centers for Disease Control and Prevention (CDC), as well as other federal, state, and local health agencies, to deal with the outbreak. Many CDC staff were involved in this investigation, both in Atlanta and in the field. CDC adopted a policy of testing for virtually every agent that could be imagined as being in any way associated with this disease. Help was sought from investigators outside CDC if they had particular expertise that …

Kinetics of reticulocyte maturity fractions and indices and iron status during therapy with epoetin beta (recombinant human erythropoietin) in cardiac surgery patients

We evaluated the changes in reticulocyte maturity fractions and indices, as measured by flow cytometry, during preoperative treatment with recombinant human erythropoietin (epoetin beta) in cardiac surgery patients. A total of 72 patients was enrolled in this double-blind, randomized, placebo-controlled clinical trial and assigned to the two treatment groups (5 x 500 U/kg bodyweight epoetin beta or placebo intravenously over 14 days preoperatively). Therapy with epoetin beta produced continuous increases in hematocrit/hemoglobin, in the most mature fraction of reticulocytes (LR), and in reticulocyte count. In the first treatment week there were parallel increases in the fraction of most immature reticulocytes (HR) and in the reticulocyte mean cell volume. During the second week of treatment the reticulocyte mean cell hemoglobin content (CHr) decreased, but CHr was independent of all iron parameters, affecting neither the reticulocyte fractions nor the hematocrit/hemoglobin increase. The total preoperative rise in hematocrit correlated with the rises in LR fraction (P = 0.0270) and reticulocyte count (P = 0.0486) during the first week of treatment. Whereas in the epoetin beta patients the preoperative change in HR fraction showed negative correlations with transferrin saturation at baseline (P = 0.0058) and with the preoperative change in iron (P = 0.0113), the preoperative change in the LR fraction correlated positively with transferrin at baseline (P = 0.0115). Postoperatively, the reticulocyte parameters revealed that the onset of increased stimulation of erythropoiesis did not occur in the placebo patients until the second postoperative day, whereas erythropoietic activity in the epoetin beta patients was much higher during the postoperative period as well, as a result of the preoperative stimulation of erythropoiesis. The reticulocyte parameters measured by flow cytometry permitted an objective analysis of erythropoietic activity during treatment with epoetin beta and in all patients postoperatively. Further studies in various types of epoetin beta therapy are needed in order to clarify the value of these reticulocyte parameters for identification of iron deficiency and optimization of epoetin beta treatment regimen.

Danazol for paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal stem-cell disorder in which blood cells lack complement inhibiting membrane proteins, and become susceptible to complement-mediated injury, leading to chronic intravascular hemolysis and pancytopenia. Glucocorticoids have been a mainstay of therapy. For patients refractory to glucocorticoids and requiring blood transfusions, an alternative therapy is needed. We studied danazol therapy in 5 patients refractory to other treatments. Four of the 5 benefited, showing rise in hematocrit and eventual cessation of transfusion requirements. Remissions lasted ≥2 years in 3 and 10 years in 1 patient. Danazol was well-tolerated without serious side effects. Danazol appears to be a good alternative treatment in PNH. Am. J. Hematol. 54:149–154, 1997 © 1997 Wiley-Liss, Inc.

Sustained systemic arterial hypertension induced by extended hypobaric hypoxia

Regular administration of recombinant erythropoietin (EPO) is frequently complicated by a rise in arterial blood pressure. We therefore asked if prolonged stimulation of endogenous EPO production has the same effect. To this end, male Sprague-Dawley rats were placed in a hypobaric chamber (390 mm Hg) for 24 days. The control (NL) group was placed in the chamber at normobaric condition. The animals were then removed from the chamber and monitored through day 108. Plasma EPO peaked within 24 hours and returned to baseline by day 7 and remained so thereafter. Hematocrit rose steadily during the hypoxic phase and declined steadily during the normobaric phase, reaching the baseline on day 45. This was accompanied by parallel changes in erythrocyte mass and blood volume. The rise in hematocrit during hypoxia was accompanied by a parallel rise in blood pressure which peaked on day 24. Despite the restoration of normal hematocrit, erythrocyte mass and blood volume following resumption of normoxia, blood pressure remained elevated throughout the observation period. To dissect the role of hypoxia from that of the associated rise in hematocrit, the experiments were repeated using a group of rats whose hematocrits were kept constant by repeated phlebotomies. These animals exhibited a sustained rise in blood pressure identical to that found in the original group. Thus, prolonged hypobaric hypoxia leads to a severe hematocrit-independent systemic hypertension (HTN) that persists long after the restoration of normoxia. Given the transient nature of the rise in its plasma concentration, endogenous EPO does not appear to play a role in the genesis of the observed systemic HTN. The authors believe that this animal model can be used for future studies of the mechanism, consequences and treatment of acquired HTN.

Haemorheological Consequences of Chronic Cigarette Smoking

Smoking is a universally accepted major cardiovascular risk factor, but the mechanisms by which it promotes ischaemic vascular disease are not fully understood. The changes that chronic smoking exerts on the flow properties of blood might contribute to an explanation. It is well documented that smoking leads to a rise in haematocrit. It also alters the rheological behaviour of red blood cells and increases both plasma viscosity and fibrinogen levels. Finally, it increases the total white cell count and modifies leukocyte function. Together these changes cumulate in a significant deterioration of the flow properties of blood, as evidenced by a steep increase in whole blood viscosity. Alterations of blood rheology in turn can promote atherothrombogenesis in several ways. It seems possible, therefore, that one mechanism by which smoking increases the risk of vascular diseases operates through its complex effects on blood rheology.

Treatment with recombinant human erythropoietin induces a moderate rise in hematocrit and thrombin antithrombin in healthy subjects

Recombinant human erythropoietin (EPO) therapy in uremic patients raises the hematocrit (Hct) and increases physical exercise capacity (1,2) and quality of life (1). In general, partial correction of anemia to subnormal levels in uremic patients has proven to be safe with few serious adverse effects apart from hypertension (3). Ever since the advent of EPO the prospect of abuse of the hormone by sportsmen has been subject to scrutiny. Both maximal oxygen uptake and endurance capacity are increased after EPO treatment in healthy subjects (4). Moreover, EPO treatment in healthy subjects has been found to induce an accentuated blood pressure reaction after submaximal exercise (5). Previous studies have shown that extreme physical exertion can predispose to an increased intravascular coagulation (6). Moreover there is a significantly increased risk of thrombosis in patients with myeloproliferative disorders, particularly in polycythemia vera (7). An enhanced risk of cardiovascular events may therefore arise should sportsmen abuse EPO as a blood doping agent. The aim of this study was to examine the effects of an EPO-induced increase in Hct on the coagulation system in healthy subjects.

Open heart surgery without homologous blood transfusion and subsequent use of recombinant erythropoietin to treat postoperative anemia

SummaryThe purpose of our study was to assess the effect of administration of erythropoietin on postoperative anemia in patients with congenital heart disease who had undergone open heart surgery without the use of homologous blood. One intravenous and one subcutaneous dose of 300 units of erythropoietin per kg body weight was given to 10 patients at a mean of five (3–8) days after surgery. Another group of 10 patients, who had undergone open heart surgery but were not given erythropoietin postoperatively, were used as controls. There was a significant fall in all patients in hemoglobin from 13.6±1.3 gm/dl prior to surgery to 9.8±1.6 gm/dl after surgery. In patients treated with erythropoietin, there was an immediate significant rise in hemoglobin and hematocrit. Hemoglobin rose by 14% on the seventh day after treatment (the twelfth day after surgery) and by 25% on the tenth day after treatment (the fifteenth day after surgery). It had increased by only 8% 15 days after surgery in the controls. These findings suggest a beneficial effect of administration of recombinant erythropoietin on postoperative anemia in children who had undergone open heart surgery without the use of homologous blood.

Anti-N<sub>form</sub> Antibody in Hemodialysis Patients

The anti-Nform antibody is produced by dialysis patients following reuse of dialyzers sterilized with formaldehyde and it has been implicated as a cause of hemolytic anemia. Formaldehyde is one of the common disinfectants used for reprocessing capillary hemodialyzers. The safety of formaldehyde and the clinical significance of anti-Nform antibody need further evaluation. Amongst 45 patients practising dialyzer reuse, anti-Nform antibody was detected in 5 (11.1%), but not amongst 111 patients not reusing their dialyzer (p < 0.005). The presence of anti-Nform was not related to the sex, or duration of dialysis with positive anti-Nform antibody. Direct Coombs' test was positive amongst 80% of all tested patients with anti-Nform antibody, and in 38% of patients reusing dialyzers but without anti-Nform antibody. No tests of hemolysis (including direct Coombs' test) discriminated between anti-Nform antibody-positive and -negative patients, nor between anti-Nform antibody patients with and without overt hemolysis. The best diagnostic test for hemolysis in anti-Nform antibody-positive patients was hematocrit rise after cessation of dialyzer reuse. It appears that despite the induction of anti-Nform antibody, hemolysis is rarely a serious consequence of dialyzer reuse.

Middle cerebral artery velocity changes during transfusion in sickle cell anemia.

Sickle cell disease is associated with cerebral hyperemia, which is therapeutically reduced by transfusion; however, the process of transfusion-induced cerebral perfusion changes has heretofore not been observed. We document the acute changes of intracranial arterial velocity in 10 patients (7 with strokes, 3 without) undergoing transfusion therapy using transcranial Doppler ultrasonography. Middle cerebral artery velocities were bilaterally measured every 30 minutes for the duration of transfusion (4 to 5 hours). Regional cerebral blood flow was quantified in 5 of these patients before the transfusion and 24 hours later by the 133Xe technique. Velocities in stroke-associated vessels (64.33 +/- 18.65 cm/s; n = 6) were significantly lower than in uninfarcted territories (99.54 +/- 27.39 cm/s; n = 13), and both types of vessels showed a robust reduction of blood flow velocities during transfusion. The rates of reduction were not significantly different as a function of prior stroke but did correlate with pretransfusion velocities and with the rise in hematocrit (multiple r = .887, P < .001). These reductions occurred rapidly within the first 3 hours of transfusion. Velocities attained at the end of transfusion were maintained in the hour after transfusion and the next day. We conclude that transfusion induces rapid changes in cerebral hemodynamics that are related to pretransfusion velocities and a rise in hematocrit. Transcranial Doppler provides a safe, simple, and noninvasive technique of monitoring these changes and may provide a means of making therapeutic decisions regarding transfusion therapy in patients with sickle cell anemia.

Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin.

To investigate the effect of recombinant human erythropoietin (rh-EPO) on the hypothalamo-pituitary-gonadal axis in end-stage renal failure, plasma luteinizing hormone (LH) concentration release was assessed by frequent blood sampling (every 10 min), both during an 8-h baseline period and after stimulation with an iv bolus of gonadotropin-releasing hormone (GnRH). Seven adult hemodialyzed men were studied before and after partial correction of anemia by rh-EPO treatment. LH was determined by an in vitro Leydig cell bioassay (bio-LH) and a highly sensitive immunoradiometric assay. Pulsatile bio-LH secretion and clearance characteristics were assessed by multiple-parameter deconvolution analysis. Although the rh-EPO treatment did not lead to a change in average concentrations of plasma bio-LH, the mass of hormone released per secretory burst more than doubled, and the estimated bio-LH production rate increased from 8.8 +/- 2.3 to 15.6 +/- 5.2 IU/L per hour (P = 0.05). The lack of change in mean plasma bio-LH is explained by a simultaneous decrease in plasma half-life from 106 +/- 27 to 67 +/- 19 min (P < 0.02). The decrease in the plasma half-life of bio-LH was closely associated with the rise in hematocrit, suggesting an effect of the increased red blood cell mass on LH distribution space and elimination kinetics. As a consequence of the changes in hormone kinetics, the incremental amplitudes of the plasma concentration pulses of bio-LH increased from 112 to 121% of nadir levels (P < 0.05), resulting in a more distinctly pulsatile pattern of hormone signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythropoietin Treatment in Peritoneal Dialysis Patients

The availability of recombinant EPO has greatly improved the lives of patients with end-stage renal disease. Knowledge is still accumulating regarding the use and effects of EPO in patients on PD, and several critical questions remain to be answered: 1. At what hematocrit level and when in the predialysis or dialysis course should EPO be started in PD patients? Recent studies by Golper suggest that the concomitant initiation of EPO and PD results in an increased hematocrit response compared to starting EPO after PD has been initiated for some time (63). 2. What is the best route of administration of EPO in PD patients? It is apparent that i.v., SC, and IP EPO can be effective in this population if utilized properly. The goal should be to tailor the route to the needs of the patient. Perhaps the daily SC route, for example, might be best for minimizing hypertension because of the slow, steady rise of hematocrit, while the IP route would be best tolerated by children (33,64). 3. What should the target hematocrit level be? This may vary depending on which organ function is being assessed. For the whole patient data are not currently available on appropriate hematocrit targets to maximize oxygen utilization, but near normal levels have recently been reported to be safe and beneficial (65-67). 4. What are the end-organ effects of anemia and its correction in PD patients? There is a dearth of information in this area for PD as well as HD patients. Additional research of this kind will increase our understanding of the pathophysiology of anemia as well as uremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of erythrocyte mass on arterial blood pressure in dialysis patients receiving maintenance erythropoietin therapy.

Treatment of renal anemia with recombinant human erythropoietin (rEPO) frequently raises arterial blood pressure. The objective of this study was to determine whether this is a direct effect of rEPO or a consequence of the expansion of erythrocyte mass. Twenty-three chronic hemodialysis patients receiving maintenance rEPO therapy who had uncontrolled anemia due to iron deficiency were studied. It was anticipated that repletion of iron stores with iv iron dextran would restore rEPO responsiveness, leading to a gradual rise in hematocrit to the target values (0.30 to 0.33). The effect of the increase in hematocrit on arterial blood pressure could then be dissected from the direct effect of rEPO in patients receiving constant doses of rEPO throughout the study period. To this end, arterial blood pressure, iron indices, hematocrit, and measures of fluid balance were monitored at baseline and for a 10-wk period after iron repletion. In eight patients, the hematocrit transiently rose above 0.33, triggering a reduction in rEPO dosage. In the remaining 15 patients, rEPO dosage was held constant during the study period. In this subgroup, repletion of iron stores led to a rise in hematocrit from 0.25 +/- 0.04 to 0.32 +/- 0.04 (P < 0.001) within 4 wk. Despite the significant rise in hematocrit, both systolic and diastolic blood pressure values remained virtually unchanged. Likewise, body weight and interdialytic fluid gain were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in hemorheology with fetal intravascular transfusion

OBJECTIVE: Our aim was to determine the changes in fetal hemorheologic parameters caused by fetal intravascular transfusion for alloimmune anemia. STUDY DESIGN: Fetal blood samples were collected before and after 95 fetal transfusions in 31 women. Fetal hematocrit, whole-blood viscosity at a variety of shear rates, plasma viscosity, fetal fibrinogen, and fetal plasma proteins were measured. RESULTS: Fetal whole-blood viscosity increased, sometimes massively, with transfusion. The rise in viscosity was principally dependent on the rise in hematocrit, with a linear rise in hematocrit producing a linear rise in the logarithm of whole-blood viscosity, but was also affected by the amount of adult plasma proteins present in the donor blood. CONCLUSIONS: Rises in fetal whole-blood viscosity during transfusion can be minimized by using donor blood that has been serum depleted to a high hematocrit (>90%) and by restricting the end hematocrit to 50% to 55%. (AM J OBSTET GYNECOL 1994;170:726-32.)

Erythropoietin enhances recovery from cisplatin-induced acute renal failure

Acute renal failure (ARF) is associated with erythropoietin (EPO) deficiency anemia. The present study was designed to determine whether the course of ARF can be altered by preventing EPO deficiency and the associated anemia. Sprague-Dawley rats were injected with a single dose of cisplatin (CP), 7 mg/kg intraperitoneally, and randomized into recombinant EPO-treated (EPO), placebo-treated (control), recombinant EPO-treated pair-fed (EPO-PF), and EPO-treated anemic (EPO-anemic) groups. They were then treated with daily injections of recombinant EPO, 100 U/kg, or placebo for 9 days. Animals in the EPO-anemic group received daily phlebotomies gauged to maintain hematocrits equal to those in the control group. Rats in the EPO-PF group were pair fed with the controls. The control and EPO-anemic groups showed a fall, whereas the EPO and EPO-PF groups showed a rise in hematocrit on day 9. Although blood volume on day 9 was significantly greater in the EPO group than in either the EPO-anemic group or the control group, it was comparable in the latter groups. An equally severe reduction in creatinine clearance (CCr) was found in all groups on day 4. However, measurements of CCr and inulin clearance on day 9 revealed a significantly greater functional recovery in the EPO, EPO-PF, and EPO-anemic groups than in the controls. The enhanced functional recovery with EPO administration was accompanied by an increased tubular regeneration and [3H]thymidine incorporation in the cortical tissue. No significant difference was found in either cortical tissue iron content or arterial blood pressure in the study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible mechanisms of sudden death and hemoconcentration induced by endothelin-1 and big endothelin-1 in mice.

We investigated the profiles of sudden death and hemoconcentration induced by endothelin-1 (ET-1) and big endothelin-1 (big ET-1) in mice using various compounds as pharmacological tools. In ET-1-induced sudden death (5 nmol/kg, i.v.), pretreatment with the Ca(2+)-channel blockers, diltiazem, nifedipine or verapamil at a dose of 2 mg/kg, i.v. significantly inhibited the mortality and prolonged the latency to death. These Ca(2+)-channel blockers, however, failed to inhibit the rise in hematocrit (Ht), namely hemoconcentration, induced by ET-1 (2.5 nmol/kg). A beta-adrenoceptor agonist, isoproterenol (1 mg/kg) tended to prolong the latency, whereas, a beta-adrenoceptor blocker, propranolol (2 mg/kg), and an alpha- and beta-adrenoceptor blocker, labetalol (5 mg/kg), aggravated the sudden death. Esculetin (10 mg/kg) and fenbufen (10 mg/kg), which are enzyme inhibitors in the arachidonate cascade, prevented only the hemoconcentration. Anti-arrhythmic drugs, lidocaine (1 mg/kg) and disopyramide (20 mg/kg) did not improve any parameters. Big ET-1 also caused sudden death (20 and 25 nmol/kg, i.v.) and hemoconcentration (10 nmol/kg, i.v.). Of several proteinase inhibitors, only a metalloproteinase inhibitor, phosphoramidon (2 mg/kg i.v.), prevented the sudden death and the hemoconcentration induced by big ET-1 but not by ET-1. Ca(2+)-channel blockers exerted their protective effects only when a lower dose of big ET-1 was employed. These results indicate that the sudden death caused by both peptide is mainly due to myocardial ischemia and respiratory disorder, and that hemoconcentration caused by them is due to their vasoconstrictor action but to their effects on the vascular permeability via secondary endogenous factors.

Endogenous angiotensin II modulates the effect of atrial natriuretic peptide on extracellular fluid partition.

Atrial natriuretic peptide (ANP) has been shown to promote a fluid shift from the intravascular toward the interstitial compartment and to interact with the renin-angiotensin system at the renal as well as the extrarenal level. In the present studies, the interaction between the renin-angiotensin system and the effects of ANP infusion (100 ng.kg-1 x min-1 for 45 min) on arterial pressure and hematocrit were assessed in bilaterally nephrectomized, anesthetized rats. In a first series of experiments, suppression of angiotensin II generation was achieved by chronic (10 days) treatment by the angiotensin-converting-enzyme inhibitor (ACEI) captopril in rats maintained on a low-sodium diet. ACEI pretreatment prevented the rise in hematocrit associated with ANP infusion (+2.1 +/- 0.1 vs. +5.8 +/- 0.2%, P < 0.05), without influencing the effect of ANP on arterial pressure. In ACEI-pretreated rats, acute administration of angiotensin II at a subpressor dose (2.5 ng.kg-1 x min-1) restored the ANP-induced increase in hematocrit. In a second series of experiments, acute blockade of the renin-angiotensin system was obtained by the ACEI enalaprilat or the nonpeptide angiotensin II receptor antagonist losartan (both 1 mg/kg i.v. bolus). In the presence of either enalaprilat or losartan, the ANP-induced increase in hematocrit was similarly prevented. These results indicate that the effect of ANP on vascular permeability is modulated by endogenous angiotensin II, possibly due to distinct influences of the two peptides at the level of pre- and postcapillary resistances.

Erythropoietin in pregnancies complicated by severe anemia of renal failure

Recombinant human erythropoietin has been approved for treatment of the anemia of renal failure since 1989, yet data regarding the safety and efficacy of this drug in pregnancy are limited. We used recombinant human erythropoietin to treat the anemia of renal disease in three pregnant women.Nadir hematocrit values before initiation of erythropoietin were 19-23%. Erythropoietin, 50-160 U/kg/week subcutaneously, was begun at 14-26 weeks' gestation. Initially, the rise in hematocrit averaged 0.6-2% each week, with peak values of 26.7-32%. Iron supplementation was given simultaneously. Maternal and neonatal outcomes were favorable despite the development of preeclampsia or worsening renal function requiring early delivery.In this small series, erythropoietin begun during the second trimester in a dose of about 100 U/kg/week, in conjunction with orally administered iron, appeared to be effective in treating the anemia of renal failure during pregnancy. Additional experience is needed to evaluate the safety of this medication during pregnancy.

Spleen emptying and venous hematocrit in humans during exercise

The spleen may release pooled erythrocytes to the general circulation during strenuous conditions such as heavy exercise. Most of our knowledge of this reservoir function of the spleen derives from animal studies, and the splenic contribution to the circulating blood volume in humans has been regarded as unimportant. We recorded the erythrocyte content in the human spleen during graded bicycle exercise to maximal working capacity. In five normal adults 99mTc-labeled autologous erythrocytes were injected intravenously, and the subjects were placed on bicycles with the back against a gamma camera focusing on the spleen. During increasing exercise the splenic erythrocyte content decreased linearly, and at maximal work load it had been reduced to a mean of 34.2% (range 44-26%) of the initial count rate at supine rest. Concomitantly norepinephrine and epinephrine in plasma increased gradually, whereas neuropeptide Y increased only at maximal exercise. A rise in hematocrit from a mean of 44.6 to 48 was observed, but the autotransfusion of erythrocytes from the spleen only partly explains the rise in hematocrit during physical activity.

Diminished cardiac contractile response to burn injury in aged guinea pigs.

Previous studies have shown that regulation of the cardiovascular system progressively deteriorates with adult aging, limiting cardiovascular adaptive mechanisms to stress such as aerobic exercise or trauma. This present study examined cardiac contractile performance as a function of adult aging in a guinea pig model and secondarily examined the effects of adult aging on cardiac contractile responses to burn injury. In a total of 39 adult and 49 senescent animals, a cutaneous full-thickness burn comprising 45% of the total body surface area was obtained using a template device (Walker model); a sham burn was produced in 38 adult and 35 senescent animals by immersion in room temperature water. Adult aging altered cardiac contraction and relaxation as indicated by significantly lower left ventricular pressure and +/- dP/dt max, as well as diminished left ventricular responsiveness to increases in preload, perfusate calcium, isoproterenol, and calcium channel blockade. Burn injury caused significant hypotension, hypothermia, and a rise in hematocrit regardless of age. Cardiac contractile dysfunction occurred in all hearts after burn injury regardless of age, as indicated by a rightward and downward shift of left ventricular function curves for both burn groups compared with their respective controls. The failure of increasing perfusate calcium to overcome burn-mediated contractile deficits in both age groups suggested that burn injury disrupts sarcolemma-bound calcium. The burn-induced decrease in negative inotropic potency of a calcium channel blocker suggests that burn injury specifically targets the calcium slow channel of the sarcolemma.(ABSTRACT TRUNCATED AT 250 WORDS)

Morning increase in whole blood viscosity: a consequence of a homeostatic nocturnal haemodynamic pattern.

In a series of studies, we have shown that in non-human primates there is a consistent overnight fall in cardiac output and central venous pressure, and a rise in total peripheral resistance. This haemodynamic pattern is associated with a higher haematocrit level in the morning suggesting that these changes in the circulation are homeostatic adjustments to a nighttime fall in plasma volume. The present study was designed to test the hypothesis that in the morning whole blood viscosity also is higher. Whole blood viscosity was measured at shear rates of 450, 225, 90, 45, and 22.5 s-1 in each of six monkeys, on four occasions, at 2-week intervals, at 17.00 and 09.00 h the next morning. The average haematocrit was 4.2% higher in the morning than in the previous evening (P < 0.01). Viscosity decreased monotonically at progressively higher shear rates but was always significantly higher in the morning than in the evening (P < 0.01 at all shear rates). When viscosity was adjusted by covarying for haematocrit level, the morning/evening differences became non-significant. However, the morning/evening differences in linear trend of shear stress as a function of shear rate persisted. These findings add further support to our hypothesis that the nocturnal haemodynamic pattern in non-human primates is related to a reduction in plasma volume, and they also suggest that the morning rise in haematocrit is a major contributing factor to the elevated viscosity.