Normovolemic Group Research Articles

Role of albumin-induced volume expansion therapy for cerebral vasospasm in aneurysmal subarachnoid hemorrhage: A systematic review.

This study reviews the effect of albumin-induced volume expansion therapy on symptomatic vasospasm and clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH). Computer searches carried out from the Scopus, Medline, Embase, Web of Science, the Cochrane Library, and Internet documents; hand searching of medical journals; and review of reference lists. Randomized controlled trials (RCT) and observational studies (OSs) comparing albumin therapy in combination or alone with crystalloid therapy for the treatment of cerebral vasospasm in aSAH were included in the study. Risk-of-bias assessment was conducted using ROB2.0 and ROBINS-I tools for RCTs and Oss, respectively. Out of a total of 1078 searches, one RCT (published in two articles) and one observational (retrospective) study were included for final analysis. In RCT, albumin was used for volume expansion therapy with a baseline crystalloid regime and comparison made between hypervolemic and normovolemic groups and it showed no beneficial effects on symptomatic vasospasm and clinical outcomes based on the Glasgow outcome scale. Furthermore, the use of albumin showed a tendency for sodium retention with lowering of glomerular filtration rate, limiting the amount of total fluid required for targeted central venous pressure values, and thereby avoiding fluid overload manifestations. The retrospective study results between albumin versus non-albumin groups (crystalloids only) supported improved outcomes in the former group with lower in-hospital mortality. Cardiorespiratory complications were equivocal in RCT and increased in non-albumin group in the retrospective study. Risk-of-bias assessment analyses revealed "some concerns" in RCT and "serious" limitation in OS due to its retrospective design. Albumin-induced volume expansion therapy for cerebral vasospasm does not have substantiative evidence to improve cerebral vasospasm and clinical outcomes in aSAH. Studies with well-designed RCTs are required to compare the use of albumin for volume expansion therapy versus standard fluid management using crystalloids to mitigate the scarcity of published data.

Hypervolemia suppresses dilutional anaemic injury in a rat model of haemodilution.

Haemodilution leads to complications in clinical practice. It is exactly unknown whether this damage is caused by the fluid or by the stretching of the vascular bed. We aimed to compare two different haemodilution techniques at the same anaemic level. Normovolemic or hypervolemic haemodilution was performed on twelve adult male Wistar rats. In the normovolemic procedure, blood was withdrawn and instantaneously administered with similar amounts of 6% hydroxyethyl starch (HES 130/0.4). Fluid was administered without withdrawing blood in the hypervolemic procedure. In both models, a 25% haematocrit level was targeted and kept at this level for 90 min to deepen the anaemia effect. Besides haemodynamics measurement, renal function (creatinine, blood urea nitrogen) and injury (tissue norepinephrine, malondialdehyde) were evaluated. Also, systemic hypoxia (lactate), oxidative stress (malondialdehyde, ischaemia-modified albumin), inflammation (tumour necrosis factor-alpha [TNF-α]), osmotic stress, adrenal stress (norepinephrine, epinephrine), and vascular stretching (atrial natriuretic peptide [ANP]) were assessed. Arterial pressure in the normovolemic group was lower than in the hypervolemic group. Serum creatinine, blood urea nitrogen, and lactate levels were higher in the normovolemic group. Tissue norepinephrine and malondialdehyde levels were higher in the normovolemic group. Serum ANP, malondialdehyde, ischaemia-modified albumin, free haemoglobin, syndecan-1, and TNF-α were higher in both groups compared to respective baseline. Normovolemic haemodilution may lead to hypoxic kidney injury. The hypervolemic state may be advantageous if fluid is to be administered. Thus, the effect of the fluid itself can be relatively masked.

Abstract 08: Computed Tomography Perfusion Of Cerebral Blood Flow During Open Cardiac Massage For Hypovolemic And Normovolemic Cardiac Arrest In Swine

Introduction: Adequate cerebral blood flow (CBF) during open cardiac massage (OCM) in cardiac arrest is critical for survivors to be neurologically intact. Cerebral perfusion is known to be poor during OCM but has not been quantified using a brain perfusion technique. The aim of this study is to measure CBF in swine undergoing OCM in hypovolemia and normovolemia using computed tomography perfusion (CTP) scanning. Methods: Anesthetized swine underwent instrumentation with right atrial and aortic pressure catheters. A pigtail catheter placed in the ascending aorta was used to administer iodinated contrast and CTP imaging acquired. Brain parenchymal attenuation was measured over time from which CBF (mL/100g of brain) and time to peak (TTP; secs) were derived. Animals were then euthanized exsanguination (hypovolemic group) or potassium chloride injection (normovolemic group). Animals were subject to a clamshell thoracotomy, OCM and repeated CTP. Data pertaining to peak coronary perfusion pressure (pCPP; mmHg) was collected and % CPP >15mmHg (% CPP; secs) calculated post hoc. Results: Normovolemic animals achieved superior pCPP compared to the hypovolemic animals (pCPP: 39.3 vs 12.3, p<0.001; % CPP: 14.5 ± 1.9 vs 30.9 ± 6.5, p<0.001). CTP was successfully performed during OCM generating an attenuation curve (figure). The TTP elongated from spontaneous circulation, normovolemia to hypovolemia (5.7 vs 10.8 vs 14.8, p=0.01). CBF during OCM was similar between hypovolemic and normovolemic groups (7.5 ± 8.1 vs 4.9 ± 6.0, p =0.73) which was lower than baseline values (51.9 ± 12.1, p<0.001). Conclusions: OCM in normovolemia generates superior coronary hemodynamics compared to hypovolemia. Despite this, neither generates adequate CBF as measured by CTP, compared to baseline. To improve the rate of neurologically intact survivors, novel resuscitative techniques need to be investigated that specifically target cerebral perfusion as existing techniques are inadequate.

Characterization of cerebral blood flow during open cardiac massage in swine: Effect of volume status.

Introduction: Patients in cardiac arrest treated with resuscitative thoracotomy and open cardiac massage (OCM) have high rates of mortality with poor neurological outcomes. The aim of this study is to quantitate cerebral perfusion during OCM using computed tomography perfusion (CTP) imaging in a swine model of normo- and hypovolemia. Methods: Anesthetized swine underwent instrumentation with right atrial and aortic pressure catheters. A catheter placed in the ascending aorta was used to administer iodinated contrast and CTP imaging acquired. Cerebral blood flow (CBF; ml/100 g of brain) and time to peak (TTP; s) were measured. Animals were then euthanized by exsanguination (hypovolemic group) or potassium chloride injection (normovolemic group) and subjected to a clamshell thoracotomy, aortic cross clamping, OCM, and repeated CTP. Data pertaining to peak coronary perfusion pressure (pCoPP; mmHg) were collected and % CoPP > 15 mmHg (% CoPP; s) calculated post hoc. Results: Normovolemic animals (n = 5) achieved superior pCoPP compared to the hypovolemic animals (n = 5) pCoPP (39.3 vs. 12.3, p < 0.001) and % CoPP (14.5 ± 1.9 vs. 30.9 ± 6.5, p < 0.001). CTP acquisition was successful and TTP elongated from spontaneous circulation, normovolemia to hypovolemia (5.7 vs. 10.8 vs. 14.8, p = 0.01). CBF during OCM was similar between hypovolemic and normovolemic groups (7.5 ± 8.1 vs. 4.9 ± 6.0, p = 0.73) which was significantly lower than baseline values (51.9 ± 12.1, p < 0.001). Conclusion: OCM in normovolemia generates superior coronary hemodynamics compared to hypovolemia. Despite this, neither generates adequate CBF as measured by CTP, compared to baseline. To improve the rate of neurologically intact survivors, novel resuscitative techniques need to be investigated that specifically target cerebral perfusion as existing techniques are inadequate.

Thiazide-associated hyponatremia in internal medicine patients: analysis of epidemiological and biochemical profiles

Thiazide-associated hyponatremia (TAH) is a clinically important side effect of the therapy with thiazide and thiazide-like diuretics. This study aims to analyze epidemiological, biochemical, and symptomatological profiles (including volume status) of patients admitted with TAH. A retrospective hospital record study was performed. Epidemiological and biochemical parameters and symptoms were compared between the thiazide (n = 143) and non-thiazide (n = 282) groups. Patients in the thiazide group were classified as hypo-, normo-, or hypervolemic. Furthermore, the comparison of epidemiological, biochemical, partially pharmacotherapeutical, and symptomatological parameters between the hypovolemic and normovolemic groups was performed. The thiazide group showed lower s-Na (p = 0.008), s-K (p <0.001), s-Cl (p <0.001), measured s-osmolality (p = 0.021), and eGFR (p <0.001); higher s-urea (p <0.001), s-creatinine (p = 0.023), s-glucose (p <0.001), u-osmolality (p = 0.012), u-Na (p <0.001), u-K (p = 0.023), and u-Cl (p <0.001). Patients using thiazide were older (p <0.001), more likely to be female (p = 0.011), and with symptoms corresponding more to chronic hyponatremia. Compared to the normovolemic group (n = 93; 65%), the hypovolemic patients (n = 47; 32.9%) showed higher s-urea (p = 0.005), s-creatinine (p = 0.045), and s-UA (p = 0.010); lower eGFR (p = 0.032), u-Na (p = 0.015), u-Cl (p = 0.016), anorexia (p <0.001), and a higher frequency of furosemide use (p <0.001). Thiazide use is a crucial etiological cause of hypotonic hyponatremia among internal medicine inpatients, associated with more severe hyponatremia, but with no difference in the in-hospital mortality. Even in hypo-osmolar conditions of TAH, 32.9% of patients exhibited signs of volume depletion. FE-UA did not differ between the hypovolemic and the normovolemic patients in TAH conditions. Anorexia and the combination of thiazide together with furosemide, rather than thiazide use alone, were risk factors for hypovolemic hyponatremia without affecting FE-UA.

Serum ADMA, endothelial dysfunction, and atherosclerosis in hypervolemic hemodialysis patients

Background/aim: Asymmetric dimethyl arginine (ADMA) is a strong predictor of cardiovascular disease and mortality in patients under hemodialysis treatment. We aimed to investigate the relationship among volume status, endothelial dysfunction, and ADMA in hemodialysis patients. Materials and methods: A total of 120 patients with a history of hemodialysis treatment were included. ADMA and CRP were measured. Echocardiographic evaluation and carotid artery intima-media thickness (CIMT) measurements were performed. Patients were divided into two groups according to clinical evaluation, ultrafiltration rate, vena cava inferior diameter (VCI), and cardiothoracic index (CTI); the two groups were hypervolemic and normovolemic. Results: The hypervolemic group included 61 patients while the normovolemic group included 59 patients. CIMT was higher in the hypervolemic group, but this result was not statistically significant (0.95 mm versus 0.85 mm, P = 0.232). There was a statistically significant difference between the hypervolemic and normovolemic groups in terms of ADMA (P < 0.001) (0.69 ± 0.57 μmol/L and 0.41 ± 0.04 μmol/L, respectively). Positive correlations were observed between serum ADMA, VCI, CTI, CRP, CIMT, and cardiac mass (P < 0.001, P = 0.016, P < 0.001, P = 0.006, P = 0.022, respectively), and negative correlations were observed between ADMA and ejection fraction and albumin (P = 0.024, P = 0.024, respectively). In multiple linear regression analysis, ADMA was independently associated with age, systolic blood pressure, CTI, and volume status. Conclusion: ADMA may be a potential determinant of hypervolemia as well as atherosclerosis in patients under hemodialysis treatment.

The effects of hemorrhage on the pharmacokinetics of tranexamic acid in a swine model.

The early use of tranexamic acid (TXA) is strongly advocated in patients who are likely to require massive transfusion to decrease mortality. This study determines the influence of hemorrhage on the pharmacokinetics of TXA in a porcine model. The investigation was a prospective experimental study in Yucatan minipigs. First, in vitro plasma-cell partitioning of TXA was evaluated by inoculating whole blood with known aliquots, centrifuging, and measuring the supernatant with high-performance liquid chromatography with mass spectrometry (HPLC-MS). Then, using in vivo modeling, normovolemic and hypovolemic (35% reduction in blood volume) swine (n = 4 per group) received 1 g of intravenous TXA and had blood sampled at 14 time points over 4 hours to determine baseline clearance via HPLC-MS. Additional swine (n = 4) were hemorrhaged 35% of their blood volume, and TXA was administered as a 15 mg/kg infusion over 10 minutes followed by infusion of 1.875 mg/kg per hour to simulate massive hemorrhage scenario. During the first hour of TXA administration, one total blood volume was hemorrhaged and simultaneously replaced with TXA free blood. Serial blood samples and the hemorrhaged blood were analyzed by HPLC-MS to determine the percentage of dose lost via hemorrhage. Clearance of TXA was diminished in the hypovolemic group compared with the normovolemic group (115 ± 4 vs 70 ± 7 mL/min). Percentage of dose lost via hemorrhage averaged 25%. The lowest measured plasma level during the exchange transfusion was 34 μg/mL. Mean 25% of the present 2017 Joint Trauma System Clinical Practice Guideline dosing of TXA can be lost to hemorrhage if a blood volume is transfused within an hour of initiating therapy. In the case of TXA, which has limited distribution and is administered during active hemorrhage and massive blood transfusions, replacement strategies should be developed and tested to find simple methods of adjusting the current dosing guidelines to maintain therapeutic plasma concentrations. Therapeutic, level II.

Humerus intraosseous administration of epinephrine in normovolemic and hypovolemic porcine model.

Compare the maximum concentration (Cmax), time to maximum concentration (Tmax), mean concentration, rate of return of spontaneous circulation (ROSC), time to ROSC, and odds of ROSC when epinephrine is administered by humerus intraosseous (HIO) compared to intravenous (IV) routes in both a hypovolemic and normovolemic cardiac arrest model. Prospective, between subjects, randomized experimental study. TriService Facility. Twenty-eight adult Yorkshire Swine were randomly assigned to four groups: HIO normovolemia; HIO hypovolemia; IV normovolemia; and IV hypovolemia. Swine were anesthetized. The hypovolemic group was exsanguinated 31 percent of their blood volume. Subjects were placed into arrest. After 2 minutes, cardiopulmonary resuscitation (CPR) was initiated. After another 2 minutes, 1 mg epinephrine was given by IV or HIO routes; blood samples were collected over 4 minutes. Hypovolemic groups received 500 mL of 5 percent albumin following blood sampling. CPR continued until ROSC or for 30 minutes. ROSC, time to ROSC, Cmax, Tmax, mean concentrations over time, odds of ROSC. Cmax was significantly higher, the Tmax, and the time to ROSC were significantly faster in the HIO normovolemic compared to the HIO hypovolemic group (p < 0.05). All seven in the HIO normovolemic group achieved ROSC compared to three of the HIO hypovolemic group. Odds of ROSC were 19.2 times greater in the HIO normovolemic compared the HIO hypovolemic group. The HIO is an effective route in a normovolemic model. However, the findings indicate that sufficient blood volume is essential for ROSC in a hypovolemic scenario.

Detecting hypovolemia in postoperative patients using a discrete Fourier transform

In the present paper, an attempt was made to find waveform-derived variables that would be useful for a more precise diagnosis of hypovolemia. In attempting this, arterial blood pressure graphs of 18 hypovolemic postoperative patients were analysed using a discrete Fourier transform. Using a paired samples t-test, the amplitude of the first harmonic (A1) is shown to be significantly higher in normovolemic cases than in hypovolemic ones (p<0.001). Based on the values of A1, a preliminary study was performed in which an additional group of 14 hypovolemic and 14 normovolemic patients were categorized into hypovolemic and normovolemic groups using logistic regression. The method proved to be successful in identifying hypovolemic patients: the prediction was correct in 80% and wrong only in 20%, indicating that A1 is potentially a useful parameter in detecting hypovolemia.

Low central venous pressure versus acute normovolemic hemodilution versus conventional fluid management for reducing blood loss in radical retropubic prostatectomy: a randomized controlled trial

Objective:To compare acute normovolemic hemodilution versus low central venous pressure strategy versus conventional fluid management in reducing intraoperative estimated blood loss, hematocrit drop and need for blood transfusion in patients undergoing radical retropubic prostatectomy under general anesthesia.Research design and methods:Patients undergoing radical retropubic prostatectomy under general anesthesia were randomized to conventional fluid management, acute normovolemic hemodilution or low central venous pressure (≤5 mmHg). Treatment effects on estimated blood loss and hematocrit change were tested in multivariable regression models accounting for surgeon, prostate size, and all two-way interactions.Results:Ninety-two patients completed the study. Estimated blood loss (mean ± SD) was significantly lower with low central venous pressure (706 ± 362 ml) compared to acute normovolemic hemodilution (1103 ± 635 ml) and conventional (1051 ± 714 ml) groups (p = 0.0134). There was no difference between the groups in need for blood transfusion, or hematocrit drop from preoperative values. The multivariate model predicting estimated blood loss showed a significant effect of treatment (p = 0.0028) and prostate size (p = 0.0323), accounting for surgeon (p = 0.0013). In the model predicting hematocrit change, accounting for surgeon difference (p = 0.0037), the treatment effect depended on prostate size (p = 0.0007) with the slope of low central venous pressure differing from the other two groups. Hematocrit was predicted to drop more with increased prostate size in acute normovolemic hemodilution and conventional groups but not with low central venous pressure.Key limitations:Limitations include the inability to blind providers to group assignment, possible variability between providers in estimation of blood loss, and the relatively small sample size that was not powered to detect differences between the groups in need for blood transfusion.Conclusions:Maintaining low central venous pressure reduced estimated blood loss compared to conventional fluid management and acute normovolemic hemodilution in patients undergoing radical retropubic prostatectomy but there was no difference in allogeneic blood transfusion between the groups.

Bioimpedance-Guided Fluid Management in Hemodialysis Patients

Achieving and maintaining optimal fluid status remains a major challenge in hemodialysis therapy. The aim of this interventional study was to assess the feasibility and clinical consequences of active fluid management guided by bioimpedance spectroscopy in chronic hemodialysis patients. Fluid status was optimized prospectively in 55 chronic hemodialysis patients over 3 months (November 2011 to February 2012). Predialysis fluid overload was measured weekly using the Fresenius Body Composition Monitor. Time-averaged fluid overload was calculated as the average between pre- and postdialysis fluid overload. The study aimed to bring the time-averaged fluid overload of all patients into a target range of 0.5 ± 0.75 L within the first month and maintain optimal fluid status until study end. Postweight was adjusted weekly according to a predefined protocol. Time-averaged fluid overload in the complete study cohort was 0.9 ± 1.6 L at baseline and 0.6 ± 1.1 L at study end. Time-averaged fluid overload decreased by -1.20 ± 1.32 L (P<0.01) in the fluid-overloaded group (n=17), remained unchanged in the normovolemic group (n=26, P=0.59), and increased by 0.59 ± 0.76 L (P=0.02) in the dehydrated group (n=12). Every 1 L change in fluid overload was accompanied by a 9.9 mmHg/L change in predialysis systolic BP (r=0.55, P<0.001). At study end, 76% of all patients were either on time-averaged fluid overload target or at least closer to target than at study start. The number of intradialytic symptoms did not change significantly in any of the subgroups. Active fluid management guided by bioimpedance spectroscopy was associated with an improvement in overall fluid status and BP.

Impact of Volume Status on Blood Pressure and Left Ventricle Structure in Patients Undergoing Chronic Hemodialysis

In this study, we aimed to examine the impact of volume status on blood pressure (BP) and on left ventricular mass index (LVMI) in chronic hemodialysis (HD) patients. This study enrolled 74 patients (F/M: 36/38, mean age 53.5 ± 15.3 years, mean HD time 41.5 ± 41 months) that were on HD treatment for at least 3 months. Demographics, biochemical tests, hemogram and C-reactive protein levels, mean interdialytic weight gain (IDWG), mean percentage of ultrafiltration (UF), and intradialytic complications such as hypotension and cramps were determined. Mean values of predialysis and postdialysis BP measurements were recorded a month before echocardiographic examination. On the day after a midweek dialysis session, 24 h ambulatory BP monitoring (ABPM) and echocardiographic examination were made concurrently. The patients were classified into two groups according to volume status: normovolemic (group 1; 14F/24M, mean age 50 ± 16.7 years, mean dialysis time 47.7 ± 47.7 months) and hypervolemic (group 2; 15F/21M, mean age 57.3 ± 12.7 years, mean dialysis time 34.9 ± 32 months). HD duration, IDWG, UF, and interdialytic complication rates were similar between the two groups (p < 0.05). Eleven patients (28.9%) of group 1 and 8 patients (22.2%) of group 2 showed dipper (p = 0.50). Valvular damage was more common in group 2 (p = 0.002). Whereas 33 patients (91.7%) had left ventricular hypertrophy (LVH) in group 2, 21 patients of the group 1 (55.3%) had LVH (p < 0.001). Although LVMI showed a significant positive correlation with cardiothoracic index, predialysis and postdialysis BP, IDWG, UF, daytime and nighttime BP measurements of 24 h ABPM, a significant negative correlation was seen with Kt/V urea and serum albumin levels. In conclusion, increased IDWG and UF and elevated BP are independent predictors of LVH for HD patients. Increased volume status leads to IDWG and elevated BP and eventually causes severe LVMI increases.

Blood Volume Analysis Can Distinguish True Anemia From Hemodilution in Critically Ill Patients

Peripheral hematocrit (pHct) is traditionally used as a marker for blood loss. In critically ill patients who are fluid resuscitated, pHct may not adequately represent red blood cell volume (RBCV). We hypothesize that the use of pHct alone may overestimate anemia, potentially leading to unnecessary interventions. Patients admitted to the intensive care unit underwent blood volume analysis. Serial blood samples were collected after injection of I-albumin. Samples were then processed by the Blood Volume Analyzer-100. RBCV and total blood volume (TBV) were calculated using the directly measured plasma volume (PV) and pHct. A computed normalized hematocrit (nHct) adjusts pHct to the patient's ideal blood volume. Thirty-six patients (21 men), aged 49.8 years ± 18.4 years, Acute Physiology And Chronic Health Evaluation II score 14.9 ± 8.1, and injury severity score 29.4 ± 12.4 had 84 blood volume analyses performed on 3 consecutive days. Using ratios of TBV compared with ideal TBV, patients were stratified into three separate groups: hypovolemic (16 of 84), normovolemic (23 of 84), and hypervolemic (45 of 84). Mean differences between pHct and nHct in each group were 4.5% ± 3.1% (p≤0.01), 0.0% ± 1.2% (p=0.85), and -6.5% ± 4.1% (p≤0.01), respectively. pHct, when compared with nHct, diagnosed anemia (Hct <30) nearly equal within the hypovolemic and normovolemic groups. However, pHct overdiagnosed anemia in 46.7% of hypervolemic patients. Use of blood volume analysis in critically ill patients may help to distinguish true anemia from hemodilution, potentially preventing unnecessary interventions.

Does Prophylactic Postoperative Hypervolemic Therapy Prevent Cerebral Vasospasm and Improve Clinical Outcome After Aneurysmal Subarachnoid Hemorrhage?

Delayed cerebral vasospasm is a common cause of morbidity and mortality after acute aneurysmal subarachnoid hemorrhage. Hypovolemia and fluid restriction are risk factors for delayed vasospasm; hypervolemic therapeutic approaches are commonly used in patients with subarachnoid hemorrhage to prevent and to treat cerebral vasospasm. To determine if postoperative prophylactic hypervolemic therapy prevents cerebral vasospasm and improves clinical outcome in patients with aneurysmal subarachnoid hemorrhage. The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology. One randomized controlled trial addressed the questions. There was no difference in the incidence of symptomatic cerebral vasospasm (20% each) or clinical outcome at 14 days and 3 months between the hypervolemic and normovolemic groups. Hypervolemic therapy also had no effect on measures of cerebral blood flow. A second quasi-randomized trial reached the same conclusions. Available evidence is insufficient to support use of prophylactic hypervolemic therapy after surgery in patients with aneurysmal subarachnoid hemorrhage. Although completed studies may be insufficiently sensitive (underpowered) to detect a treatment effect, the magnitude of any as yet undetected benefit of prophylactic hypervolemic therapy is likely modest and its risks have not been systematically evaluated.

Effects of diuretic-induced hypovolemia/isosmotic dehydration on cardiorespiratory responses to hyperthermia and its physical treatment in rabbits

Under conditions of heat stress and hyperosmotic dehydration, both animals and humans reduce thermoregulatory evaporation and regulate deep body temperature at elevated levels. Regarding the mechanisms, the main role in producing these thermoregulatory changes during dehydration is attributed to the increased osmolality of body fluids, although the role of the decreased plasma volume without changes in plasma osmolality (hypovolemia/isosmotic dehydration) has not been so far investigated. There are also controversial experimental results regarding the effects of dehydration on heat stress-induced cutaneous vasodilation. Therefore, this paper studied the effects of hypovolemia/isosmotic dehydration on cardiorespiratory responses to hyperthermia and its physical treatment in 17 anaesthetized adult rabbits. The animals were divided into two groups: normovolemic group (NV; n = 10) and hypovolemic group (HV; n = 7). In the HV group, hypovolemia/isosmotic dehydration (decrease in plasma volume by 16.1 ± 1.2%) was induced by furosemide (5 mg kg−1 i.v.) without change in measured plasma Na+ concentration. Hyperthermia (the rise in body temperature (BT) to 42°C by a gradual body surface heating) caused significant increase in minute ventilation (VE) in both groups. However, VE values were significantly higher in the HV rabbits compared to the NV animals despite the lower breathing frequency (p < 0.05). The panting was absent in the HV rabbits at the BT of 42°C, unlike the NV animals. From cardiovascular variables, the vasoconstrictor response in visceral (mesenteric) region during hyperthermia in hypovolemic/isosmotic animals was attenuated (p < 0.05), whereas the heat stress-induced cutaneous vasodilation was not influenced by hypovolemia. Recovery of the BT by body surface cooling was accompanied by further increase in VE in the NV group, whereas VE decreased (p < 0.05) in the HV animals. Cooling led to recovery of the cardiovascular parameters. There were found no significant cardiorespiratory differences between the groups (NV:HV) during cooling. The lower frequency of breathing and attenuation of the mesenteric vasoconstriction during exogenous hyperthermia are present not only during hyperosmotic dehydration induced by water deprivation, but they also occur under conditions of furosemide-induced isosmotic dehydration/hypovolemia in rabbits. The heat stress-induced cutaneous vasodilation regarding its biological importance was not influenced by hypovolemia/isosmotic dehydration. Therefore, it is suggested that hypovolemia alone is sufficient to produce described respiratory, thermoregulatory and cardiovascular changes in dehydrated rabbits during exogenous hyperthermia, whereas hyperosmolality is not a requisite.

Comparison of the Non-Invasive Methods Estimating Dry Weight in Hemodialysis Patients

Background. The treatment of deranged water homeostasis of hemodialysis (HD) patients needs focusing on an accurate assessment of dry weight (DW). However, the correct estimation of postdialysis DW is still a problem. Echocardiography of inferior caval vein diameter (ICVD) was recently considered as a reliable technique to estimate DWs of HD patients, whereas conductivity measurements and biochemical parameters remain controversial. In this study, we aimed to compare the noninvasive methods estimating DW in HD patients. Methods. We enrolled 60 patients: 30 hypervolemic (HV) (12 M, 18 F, with a mean age of 41.9 ± 13.6 years, mean HD duration of 38 ± 45 months) and 30 normovolemic (NV) patients (19 M, 11 F, with a mean age of 42.2 ± 14 years, mean HD duration of 62 ± 51.5 months) according to clinical sign and symptoms as well as the findings on chest x-ray. Furthermore, the DWs of patients were evaluated in post-HD period in terms of echocardiography parameters [ICVD and collapse index (CI) determined by Cheriex], plasma ANP (pANP) levels (RIA), and total body water (TBW) by bioelectrical impedance (BEI). Results. Forty-one of 60 patients had hypervolemic findings (68%) and 19 patients had normovolemia (32%) according to echocardiography parameters. Determination of “hypervolemia” by clinical acumen and pANP levels were not reliable, especially negative predictive values were lower as follows: sensitivity, specificity, positive predictive value, negative predictive values of clinical acumen and pANP levels: 63%, 69%, 87%, 50%, and 67%, 59%, 79%, 43%, respectively. TBW established by BEI did not correlate with ICVD and CI after HD (p > 0.05). The TBW of HV group according to echocardiography parameters was greater than NV group, but the difference was not statistically significant (27.4 ± 6.6 kg versus 26.4 ± 5.8 kg, respectively, p > 0.05). However, there was not any difference in the divided BSA values (1.58 ± 0.2 kg/m2 versus 1.60 ± 0.2 kg/m2, respectively, p > 0.05). Hypertension was seen in 37 (90%) of the echocardiographically hypervolemic patients, and the blood pressure was kept under control by previously given medication in only 7 (19%) patients. After the dry weight of the patients was corrected echocardiographically to normal limits, the blood pressure of 31 patients (86%) was normalized without antihypertensive treatment, but only in 6 patients remained the necessity of antihypertensive treatment. In addition, in 8 of 11 normotensive patients using antihypertensive drugs, assessment of their clinical and radiological findings showed normovolemia but ICVD > 11.5 mm/m2; however, the need for antihypertensive drugs disappeared when the ICVD reduced to 8–11.5/m2. Conclusions. Clinical and radiological assessment, pANP levels, and TBW established by BEI appeared to be less valuable in interpreting DW's of HD patients. In accordance with the literature, echocardiography findings have proven to be reliable, and they are important noninvasive tools that can establish an effective and rational antihypertensive treatment.

Diuretic-induced dehydration/hypovolemia inhibits thermal panting in rabbits

Respiratory and thermoregulatory responses to hyperthermia during isosmotic dehydration/hypovolemia were studied in 17 anaesthetized adult rabbits divided into two groups: normovolemic group (NV; n=10) and hypovolemic group (HV; n=7). Hypovolemia/isosmotic dehydration (a decrease in plasma volume by 16.1+/-1.2%) was induced by furosemide (5 mg kg(-1) i.v.). During hyperthermia (the rise in body temperature to 42 degrees C by a gradual body surface heating), the HV rabbits had lower (P<0.05) respiratory frequency and higher (P<0.05) tidal volume than the NV animals. The panting was absent in the HV rabbits at the BT of 42 degrees C, unlike the NV animals. The lower respiratory frequency and the absence of panting during exogenous hyperthermia in dehydrated animals are present not only during hyperosmotic dehydration induced by water deprivation [Doris, P.A., Baker, M.A., 1981. Hypothalamic control of thermoregulation during dehydration. Brain Res. 206 (1), 219-222], but they also occur in the furosemide-induced isosmotic dehydration/hypovolemia.

Volume Expansion Increases Right Ventricular Infarct Size in Dogs by Reducing Collateral Perfusion

Plasma volume expansion is frequently recommended to correct the low output state resulting from right ventricular (RV) infarction. However, any subsequent increase in pericardial and RV filling pressures from volume expansion could impair RV collateral blood flow. We examined whether volume expansion in dogs before right coronary ligation reduced collateral perfusion and worsened the extent of RV necrosis. Randomized experimental study. Animal research laboratory in university medical center. Forty anesthetized, closed-chest dogs were randomly assigned to normovolemic, pericardium opened (n = 10) or intact (n = 10) groups, and hypervolemic, pericardium opened (n = 10) or intact (n = 10) groups. Hypervolemic animals received 24 mL/kg of 6% hetastarch. All animals underwent 90 min right coronary ligation, followed by 120 min reperfusion. Collateral coronary blood flow (radioactive microspheres) and area of necrosis (An) were determined in the area at risk (Ar). Stroke volume decreased in all groups with ischemia but remained 25 to 40% greater in both hypervolemic groups than in normovolemic animals (p < 0.05). In hypervolemic animals with intact pericardium, RV end-diastolic pressure increased to 10.4 +/- 2.1 mm Hg (mean +/- SD), a value that significantly exceeded those of the other three groups. During RV ischemia, collateral perfusion in the Ar was similar in both normovolemic groups and in hypervolemic animals with opened pericardium (mean range, 12.9 +/- 8.8 to 13.8 +/- 7.6 mL/min/100 g; p = NS), and the An/Ar varied from 11.8 +/- 6.3 to 18.6 +/- 17.4% (p = NS). In contrast, in hypervolemic animals with intact pericardium, collateral perfusion decreased to 7.2 +/- 3.5 mL/min/100 g and the An/Ar was increased to 38.2 +/- 18.6% (p < 0.05 compared with other groups, respectively). Overall, An/Ar was inversely related to collateral blood flow in the Ar (r = -0.46; p < 0.05) and correlated positively with RV end-diastolic pressure (r = 0.61; p < 0.05). Volume expansion preserved stroke volume during RV ischemia, independent of pericardial integrity. However, volume expansion in animals with an intact pericardium increased RV infarct size by twofold to threefold secondary to reduced periischemic collateral perfusion. This detrimental effect of volume expansion on infarct size was prevented by opening the pericardium.

Renal function in the laboratory rat: a student exercise.

Because of the increased concern over use of human body fluids in physiology teaching laboratories, we developed an exercise in renal function that utilizes laboratory rats. The purpose is to demonstrate the role of the kidneys in the homeostatic control of extracellular fluid volume, plasma ionic concentrations, and osmolarity. Three treatment groups are utilized: a volume-expanded (access to 1 g/100 ml sucrose) group, a volume-expanded and salt-loaded (access to 0.9 g/100 ml NaCl) group, and a volume-depleted (water-deprived) group. A normovolemic control group (access to tap water) is also included. Rats are housed individually in metabolic cages that allow accurate measurement of fluid intake and urine output. Blood samples are removed via cardiac puncture. The animals recover from this procedure and can be reutilized within 2-3 wk. When class data are pooled, clear trends are seen that demonstrate the volume-, osmo-, and ionoregulatory abilities of the kidneys.

Systemic hemorrhage augments local O2 extraction in canine intestine

When O2 delivery (QO2) to a tissue is reduced, microvascular adjustments facilitate increases in O2 extraction, thereby delaying the onset of O2 supply-limited metabolism until a critically low QO2 is reached. The present study investigated the contribution of the autonomic nervous system to these adjustments by measuring O2 extraction in isolated intestine. In anesthetized dogs, a 30- to 50-g segment of intestine was vascularly isolated and its QO2 was decreased in stages by reducing the speed of an occlusive pump. In a normovolemic group (n = 11), blood volume was maintained to minimize sympathetic tone while flow to the intestine was reduced. In a hypovolemic group (n = 7), blood volume was removed in stages to augment sympathetic tone as flow to the intestinal segment was simultaneously reduced. A hypovolemic alpha-adrenergic-blocked (alpha-blocked) group (n = 6) was identical to the corresponding alpha-adrenergic intact (alpha-intact) group except that alpha-adrenergic effects were inhibited with phenoxybenzamine (3 mg/kg). The systemic critical O2 extraction ratio in the alpha-blocked group (69 +/- 6%) was less than that in the alpha-intact group (77 +/- 7%; P = 0.05). In the intestine, the critical O2 extraction ratio was significantly poorer in the normovolemic (45 +/- 11%) group than in either hypovolemic group (alpha-intact: 69 +/- 3%, P < 0.00005; alpha-blocked: 62 +/- 9%, P < 0.005). These findings demonstrate that systemic hemorrhage significantly augments critical O2 extraction in intestine during progressive local stagnant hypoxia and suggest that nonadrenergic vasoconstrictor mechanisms may play an important role.