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PubMed1998

Oviposition attraction and repellency of Aedes aegypti (Diptera: Culicidae) to waters from conspecific larvae subjected to crowding, confinement, starvation, or infection.

As the biomass of Aedes aegypti (L.) larvae increased in relation to the volume of rearing waters, oviposition attraction of these waters to conspecific, gravid females first rose to a peak and then declined. Further increases in biomass rendered waters strongly repellent. Comparable responses were elicited by a decrease in the volume of rearing waters or an increase in the relative size or number of mosquito larvae. Low volumes of water reduced oviposition attraction and increased repellency, whereas larger volumes increased attraction. Excessively large volumes diluted attraction to neutrality. Constraints imposed by the physical dimensions of the larval environment which interfered with the normal postural movements and behaviors of the larvae also induced repellency, independent of rearing volume. Titration of repellent waters revealed that infection with the digenean Plagiorchis elegans (Rudolphi) generated the most powerful repellent effect, whereas crowding or starvation induced significantly weaker responses. At no time did dilution of repellent waters restore attractive properties. Repellents, even at minute concentrations, overrode attractants. The density-dependent action of oviposition attractants and repellents may help to maintain larval populations near optimal levels through their influence on recruitment. Oviposition repellency induced by sublethal infections with P. elegans may maintain population levels below the carrying capacity of the environment. Persistence of oviposition attraction and repellency varied inversely with temperature. The magnitude of the repellent effect induced by larvae appears to be a good indicator of their probability of survival and may be of selective significance. Repellency may deflect ovipositing females away from sites close to human habitation and may lead to new, and perhaps more effective, method, to control mosquitoes and the diseases they transmit.

Aedes↗
PubMed2000

Pathophysiology of anaemia: focus on the heart and blood vessels.

The amount of oxygen delivered to an organ depends on three factors: blood flow and its distribution; the oxygen-carrying capacity of the blood, i.e. haemoglobin concentration; and oxygen extraction. Non-haemodynamic and haemodynamic mechanisms operate to compensate for anaemia. Non-haemodynamic mechanisms include increased erythropoietin production to stimulate erythropoiesis, and increased oxygen extraction (displacement of the haemoglobin oxygen dissociation curve). This decreased affinity of oxygen for haemoglobin is mediated by increased 2,3-diphosphoglycerate concentrations. Increased cardiac output is the main haemodynamic factor, mediated by lower afterload, increased preload, and positive inotropic and chronotropic effects. Decreased afterload is due to vasodilatation and reduced vascular resistance as a consequence of lower blood viscosity, hypoxia-induced vasodilatation, and enhanced nitric oxide activity. Vasodilatation also involves recruitment of microvessels and, in the case of chronic anaemia, stimulation of angiogenesis. With decreased afterload, the venous return (preload) and left ventricular (LV) filling increase, leading to increased LV end-diastolic volume and maintenance of a high stroke volume and high stroke work. High stroke work is also due to enhanced LV contractility attributed to increased concentrations of catecholamines and non-catecholamine inotropic factors. In addition, heart rate is increased in anaemia, due to hypoxia-stimulated chemoreceptors and increased sympathetic activity. In the long term, these haemodynamic alterations lead to gradual development of cardiac enlargement and LV hypertrophy (LVH). The LVH is eccentric, characterized by increased LV internal dimensions and a normal ratio of wall thickness to cavity diameter, as occurs in other forms of volume overload. When anaemia-related LVH develops in an otherwise 'healthy' humoral environment, the lesions are reversible and the type of LVH is primarily physiological and is not associated with impaired diastolic function. In the absence of underlying cardiovascular disorders, severe anaemia (Haemoglobin concentration < 4-5 g/dl) leads to congestive heart failure. In the presence of heart disease, especially coronary artery disease, anaemia intensifies angina and contributes to a high incidence of cardiovascular complications. In end-stage renal disease (ESRD), LVH is influenced by many other factors, leading to intense interstitial fibrosis, to alterations in diastolic function, and usually to poor reversibility. The chronic increase in cardiac output contributes to arterial remodelling of central elastic arteries such as the aorta and common carotid artery. This remodelling consists principally of arterial enlargement and compensatory arterial intima--media thickening. In ESRD, these geometric changes are accompanied by arterial stiffening. The principal consequences of arterial alterations are increased systolic pressure and high inertia due to higher blood mass in the dilated arterial system. These alterations contribute to the development of LVH and abnormal coronary perfusion.

Anemia↗
PubMed1998

The effects of increased doses of bovine hemoglobin on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery.

UNLABELLED: In two consecutive studies (Study A and Study B), we evaluated the effects of increasing doses of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After the induction of anesthesia and the exchange of 1 L of blood for 1 L of lactated Ringer's solution, 24 patients (12 in each study) were randomly assigned to receive, within 30 min, a predetermined volume of either HBOC-201 or 6% hydroxyethyl starch (Study A 6.9 mL/kg; Study B 9.2 mL/kg). Monitored variables included systemic and pulmonary arterial pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic (SVRI) and pulmonary (PVRI) vascular resistance indices, oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER). In both studies, the infusion of HBOC-201 was associated with increases in SVRI (Study A 121%; Study B 71%) and PVRI (Study A 70%; Study B 53%) and with a decrease in CI (29% both studies). Hemodilution with HBOC-201 maintained the arterial oxygen content at levels higher than hemodilution with hydroxyethyl starch, but the advantage of a greater oxygen-carrying capacity was offset by the increase in SVRI, with a resulting net decrease in both CI and DO2I (Study A 30%; Study B 28%); VO2I was maintained by increased O2ER. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch. IMPLICATIONS: Bovine hemoglobin in doses ranging between 55 and 97 g of hemoglobin increased vascular resistance and decreased cardiac output in anesthetized surgical patients. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch.

Aged↗
PubMed2002

Preserved gastric tonometric variables in cardiac surgical patients administered intravenous perflubron emulsion.

UNLABELLED: Low gastric intramucosal pH (pHi) and an increased gastric-arterial PCO2 difference (CO2 gap) are markers of tissue hypoperfusion. Perfluorocarbons (PFCs) have a large oxygen-carrying capacity and release oxygen when encountering low tissue oxygen tension. Nine cardiac surgical patients instrumented for gastric tonometry were enrolled as part of a multicenter, randomized, single-blinded study of a PFC emulsion (perflubron emulsion [Oxygent]). Patients were randomized to receive PFC (n = 4) or placebo (n = 5) after intraoperative autologous blood harvesting by acute normovolemic hemodilution. At baseline there were no intergroup differences in tonometric-, hemodynamic-, or oxygen delivery-derived variables, e.g., Control group (pHi, 7.37 +/- 0.06; CO2 gap, 6.4 +/- 1.3 mm Hg) versus PFC group (pHi, 7.38 +/- 0.06; CO2 gap, 6.7 +/- 1.5 mm Hg). After acute normovolemic hemodilution, pHi was significantly lower (P < 0.01) in the Control group (7.22 +/- 0.25) than in the PFC group (7.44 +/- 0.25), and CO2 gap was significantly higher (P < 0.001) in the Control group (23.4 +/- 5.1 mm Hg) than in the PFC group (1.8 +/- 0.8 mm Hg). These differences in tonometric variables persisted during surgery. The PFC group showed a significantly (P < 0.007) shorter time to first bowel movement postoperatively (2.0 +/- 0.8 vs 5.4 +/- 1.6 days). Time to consumption of solid food was also shorter in the PFC group and almost achieved statistical significance (P = 0.056). IMPLICATIONS: This study suggests that the administration of perflubron emulsion prevents gastrointestinal tract ischemia in cardiac surgical patients and may preserve postoperative gastrointestinal tract function.

Aged↗
PubMed1996

Circulatory effects of hypoxia, acute normovolemic hemodilution, and their combination in anesthetized pigs.

BACKGROUND: Because hemodilution decreases the oxygen-carrying capacity of blood, it was hypothesized that severe hemodilution would decrease the tolerance to alveolar hypoxia. METHODS: Hemodynamics, oxygen transport, and blood lactate concentrations were compared in ten pigs with normal hematocrit (33 +/- 4%), and ten hemodiluted pigs (hematocrit 11 +/- 1%; mean +/- SD) anesthetized with ketamine-fentanyl-pancuronium during stepwise decreases in inspired oxygen fraction (FIO2; 1.0, 0.35, 0.21, 0.15, 0.10, 0.05). RESULTS: Median systemic oxygen delivery (DO2SY) became critical (the DO2SY value when arterial lactate exceeded 2.0 mmol.l-1) at 10.4 ml.kg-1.min-1 (range 6.9-16.1) in hemodiluted animals and at 11.8 ml.kg-1.min-1 (5.9-32.2) in animals with normal hematocrits (NS). The relationship between mixed venous oxygen saturation and arterial lactate values was less consistent and median critical mixed venous oxygen saturation was higher (P < 0.05) in the hemodiluted group (35%, range 21-64), than in animals with normal hematocrits (21%, 7-68%). In animals with normal hematocrit, decreasing FIO2 from 1.0 to 0.10 resulted in a decrease in DO2SY from 26.3 +/- 9.1 to 9.3 +/- 3.9 ml.kg-1.min-1 (P < 0.01). Cardiac output did not change, systemic oxygen extraction ratio increased from 0.23 +/- 0.08 to 0.68 +/- 0.13 (P < 0.01), and arterial lactate from 0.9 +/- 0.2 to 3.4 +/- 3.0 mmol.l-1 (P < 0.05). Cardiac venous blood flow, as measured by retrograde thermodilution, increased from 5.7 +/- 2.9 to 12.6 +/- 5.7 ml.kg-1.min-1 (P < 0.01). When FIO2 was reduced to 0.05, three animals became hypotensive and died. In the second group, hemodilution increased cardiac output and systemic oxygen extraction ratio (P < 0.01). Cardiac venous blood flow increased from 4.1 +/- 1.7 to 9.8 +/- 5.1 ml.kg-1.min-1 (P < 0.01), and cardiac venous oxygen saturation from 22 +/- 5 to 41 +/- 10% (P < 0.01). During the subsequent hypoxia, cardiac output and DO2SY were maintained until FIO2 = 0.15 (DO2SY = 10.1 +/- 3.3 ml.kg-1.min-1). Cardiac venous blood flow was then 18.5 +/- 10.7 ml.kg-1.min-1 (P < 0.01), but in spite of this, myocardial lactate production occurred. At FIO2 = 0.10 (DO2SY = 7.7 +/- 3.0 ml.kg-1.min-1), arterial lactate concentration increased to 8.5 +/- 2.3 mmol.l-1 (P < 0.01), and most animals became hypotensive. All hemodiluted animals died when FIO2 was decreased to 0.05 (P < 0.01 when compared to animals with normal hematocrit). CONCLUSIONS: Systemic and myocardial lactate production occurred at similar systemic oxygen delivery rates in hemodiluted and nonhemodiluted animals. Mixed venous oxygen saturation may be a less reliable indicator of inadequate oxygen delivery during hemodilution.

Anesthesia↗
PubMed1996

Protective effect of stroma-free methemoglobin during cyanide poisoning in dogs.

BACKGROUND: During fire exposure, cyanide toxicity can block aerobic metabolism. Oxygen and sodium thiosulfate are accepted therapy. However, nitrite-induced methemoglobinemia, which avidly binds cyanide, decreases oxygen-carrying capacity that is already reduced by the presence of carboxyhemoglobin (inhalation of carbon monoxide in smoke). This study tested whether exogenous stroma-free methemoglobin (SFmetHb) can prevent depression of hemodynamics and metabolism during canine cyanide poisoning. METHODS: In 10 dogs (weighing 18.8 +/- 3.5 kg) anesthetized with chloralose-urethane and mechanically ventilated with air, baseline hemodynamic and metabolic measurements were made. Then, 137 +/- 31 ml of 12 g% SFmetHb was infused into five dogs (SFmetHb group). Finally, the SFmetHb group and the control group (n = 5, no SFmetHb) received an intravenous potassium cyanide infusion (0.072 mg.kg-1.min-1) for 20 min. Oxygen consumption (VO2) was measured with a Datex Deltatrac (Datex Instruments, Helsinki, Finland) metabolic monitor and cardiac output (QT) was measured by pulmonary artery thermodilution. RESULTS: From baseline to cyanide infusion in the control group, QT decreased significantly (p < 0.05) from 2.9 +/- 0.8 to 1.5 +/- 0.4 l/min, mixed venous PCO2 (PvCO2) tended to decrease from 35 +/- 4 to 23 +/- 2 mmHg, PvO2 increased from 43 +/- 4 to 62 +/- 8 mmHg, VO2 decreased from 93 +/- 8 to 64 +/- 19 ml/min, and lactate increased from 2.3 +/- 0.5 to 7.1 +/- 0.7 mM. In the SFmetHb group, cyanide infusion did not significantly change these variables. From baseline to infused cyanide, the increases in blood cyanide (4.8 +/- 1.0 to 452 +/- 97 microM) and plasma thiocyanate cyanide (18 +/- 5 to 65 +/- 22 microM) in the SFmetHb group were significantly greater than those increases in the control group. SFmetHb itself caused no physiologic changes, except small decreases in heart rate and PvO2. Peak SFmetHb reached 7.7 +/- 1.0% of total hemoglobin. CONCLUSIONS: Prophylactic intravenous SFmetHb preserved cardiovascular and metabolic function in dogs exposed to significant intravenous cyanide. Blood concentrations of cyanide, and its metabolite, thiocyanate, revealed that SFmetHb trapped significant cyanide in blood before tissue penetration.

Animals↗
PubMed2001

Efficacy of acute normovolemic hemodilution assessed as a function of fraction of blood volume lost.

BACKGROUND: It has been recommended that intraoperative acute normovolemic hemodilution (ANH) be considered for patients expected to experience surgical blood loss of 20% or more of their blood volume. Previous mathematical analyses have not evaluated the potential efficacy of ANH in terms of fraction of blood volume lost. Since decrease of oxygen-carrying capacity is a function of erythrocyte loss relative to blood volume, the purpose of this analysis was to provide an assessment of ANH applicable to all blood volumes and to determine whether this recommendation is appropriate. METHODS: Equations were developed to describe the fractional blood volume loss (blood volume loss/blood volume; VReM/VBld) required to reduce hematocrit below a "trigger" hematocrit with maintenance of isovolemia. This is also the minimum fractional blood volume loss required for initial erythrocyte savings by any conservation technique. Equations were also developed to describe the fractional surgical blood volume loss for which ANH will obviate the need for transfusion of erythrocytes from any source other than those removed by ANH, and the fractional surgical blood volume loss required for ANH to save a defined volume of erythrocytes. RESULTS: Acute normovolemic hemodilution can extend the allowable fractional surgical blood loss before erythrocyte transfusion is required. The VRem/VBld required to initiate erythrocyte savings is approximately 0.5-0.9. The efficacy of ANH in terms of erythrocytes saved cannot be expressed as a function of the fractional blood volume lost alone. To save 1 unit of erythrocytes requires a fractional surgical blood loss of approximately 0.7-1.2 for the usual surgical patient when the transfusion trigger hematocrit is 0.18-0.21. CONCLUSIONS: This analysis suggests that surgical blood loss should be 0.50 or more for ANH to begin to "save" erythrocytes and 0.70 or more of the patient's blood volume for ANH to save 1 unit erythrocytes, for the usual surgical patient with an initial hematocrit of 0.32-0.36 and a transfusion "trigger" hematocrit (the value at which transfusion is initiated) of 0.18-0.21.

Blood Loss, Surgical↗
PubMed1997

Superiority of blood over saline resuscitation from hemorrhagic shock: a 31P magnetic resonance spectroscopy study.

OBJECTIVE: To study the relation between blood and saline administration, postresuscitation hematocrit (Hct) level, and metabolic recovery after hemorrhagic shock. SUMMARY BACKGROUND DATA: It is generally believed that crystalloid can be substituted, in whole or in part, for blood during resuscitation of hemorrhagic shock. This is based on the belief that Hct can be safely reduced but should not fall below a critical level. METHODS: Male rats weighing 200 g were subjected to an isobaric hemorrhagic shock at a mean arterial pressure of 30 mmHg for 14 minutes, after which they were randomized to one of three resuscitation regimens. Control group (n = 36) were resuscitated by return of all shed blood. Mid-Hct (n = 39) and low-Hct (n = 60) groups were depleted of one third and one half of their circulating blood volumes, respectively, and were resuscitated with three times that volume of normal saline. Skeletal muscle intracellular energetics and pH were measured serially using 31P magnetic resonance spectroscopy at baseline, during shock, and after resuscitation. Arterial blood was sampled at the same time points. The number of surviving animals in each group at 24 hours was recorded. RESULTS: After resuscitation, surviving rats in the low-Hct group demonstrated a greater consumption of high-energy phosphocreatine stores than did the other groups (control = 0.479 +/- 0.003, mid-Hct = 0.465 +/- 0.004, low-Hct = 0.457 +/- 0.007, mean +/- standard error of the mean; p < 0.01 low-Hct vs. other groups by analysis of variance). The rats that received saline resuscitation developed a relative intracellular acidosis (control = 7.29 +/- 0.02, mid-Hct = 7.25 +/- 0.02, low-Hct = 7.23 +/- 0.02; p < 0.05 controls vs. other groups by analysis of variance). At 24 hours, the death rates were significantly different among the groups: control = 1 of 36 rats (2.8%), mid-Hct = 6 of 39 (15.4%), and low-Hct = 14 of 60 (23.3%) (p < 0.05 by chi square analysis). CONCLUSION: The oxygen-carrying capacity of resuscitation fluid has an important impact on intracellular metabolism and outcome.

Animals↗
PubMed2004

Blood substitutes.

PURPOSE OF REVIEW: Risk of disease transmission and limitations in the ability to transfuse in the prehospital or combat setting have stimulated research in the field of oxygen therapeutics. Several products have completed safety trials and are presently undergoing investigation for their efficacy. In the near future, the clinician will likely employ these products in the management of a variety of patient populations. Though similar in their oxygen carrying capacity, each agent possesses distinct physiologic effects. Understanding of the benefits and shortcomings of the various compounds is essential in order to optimally utilize them in various clinical settings. This review provides an overview of recent developments in the field of oxygen therapeutics and highlights results of clinical trials. RECENT FINDINGS: Modified hemoglobin solutions of human or bovine origin and perfluorochemical-based emulsions are in advanced stages of clinical testing. Bovine hemoglobin-based solutions have been associated with vascular reactivity, methemoglobin formation and development of antibodies. Larger safety trials are necessary before they can find widespread use. Polymerized human hemoglobin solutions have a favorable safety profile in early trials and have been effective as a resuscitation fluid in circumstances when red cells may be unavailable. Unfortunately, outdated human blood, the substrate for this product, is itself in short supply. Perfluorocarbons similarly reduce the need for allogeneic transfusion, but the need for high-inspired oxygen levels currently limits use. Recombinant, polymer-encapsulated and additional forms of chemically modified hemoglobins are being developed and are undergoing testing in animal models SUMMARY: Oxygen carriers offer a viable alternative to allogeneic transfusion. All oxygen therapeutic agents are not clinically equivalent. Optimal utilization requires a thorough understanding of the therapeutic potentials and adverse effects of the solution being considered for use.

Journal Article↗
PubMed1982

Hemoglobin solution in the treatment of hemorrhagic shock.

The major physiological effects of hemorrhage are hypovolemia and anemia. The administration of an oxygen-carrying plasma expander, such as crystalline hemoglobin solution (CHb), can restore both of these deficits while avoiding many of the logistical problems entailed in the use of blood. The authors have used Chb to treat severe hypovolemia and anemia in separate canine models and found it to be highly effective. CHb acts as a colloid plasma expander to resuscitate intravascular volume in hypovolemia and supplements oxygen-carrying capacity in anemia. CHb can support oxygen transport essentially in the absence of red blood cells. Hemodynamic responses to low P50 CHb, however, suggest that oxygen offloading at the tissue level is compromised by the high oxygen affinity of unmodified CHb. Whereas such oxygen offloading deficits may be compensated for in the chronic situation, they may be of crucial importance in severe trauma where oxygen transport is often limited by arterial desaturation, low cardiac output, maldistribution of perfusion and interstitial water overload. The development of a lower-affinity CHb is, therefore, of the essence.

Animals↗
PubMed1990

Cardiovascular and metabolic response to red blood cell transfusion in critically ill volume-resuscitated nonsurgical patients.

We examined the cardiovascular and metabolic response to RBC transfusion in patients with circulatory shock after volume resuscitation. Data were analyzed from 36 transfusions in 32 patients who were undergoing continuous hemodynamic monitoring. Transfusions were administered for moderate to severe anemia, mean Hgb 8.3 g/dl. The diagnosis were sepsis (19/36), cardiogenic shock (14/36), connective tissue disease (2/36), and severe hypocalcemia (1/36). Benefit from transfusion was defined as an improvement in tissue oxygen utilization (increased oxygen consumption [VO2] or decreased lactate), a decrease in myocardial VO2 (MAP x HR), or a decrease in myocardial work (left ventricular work index). Mean transfusion volume was 577 ml over 4.5 h. Hgb and oxygen delivery (DO2) increased by 27% and 28%, respectively, while pulmonary artery wedge pressure and cardiac index were unchanged. No significant change was noted in VO2, or lactate, after augmentation of red cell mass. An increase occurred in myocardial work indices and MAP x HR. No changes were identified when subgroups were analyzed based on diagnosis, pretransfusion Hgb, lactate, or VO2 levels. We conclude that selective increase in DO2 by augmentation of RBC mass and oxygen-carrying capacity did not improve the shock state in these volume-resuscitated patients, regardless of the etiology of the shock.

Adolescent↗
PubMed1995

Oxygen transport and cardiovascular effects of resuscitation from severe hemorrhagic shock using hemoglobin solutions.

OBJECTIVE: To test the short-term efficacy of three hemoglobin solutions in restoring cardiac output, intravascular pressures, oxygen transport (DO2), and oxygen consumption (VO2) after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Beagle dogs. INTERVENTIONS: After anesthesia and instrumentation, hemorrhagic shock was induced for 2 hrs by blood withdrawal to maintain systolic blood pressure at 50 mm Hg. Resuscitation then occurred with one of four different resuscitation fluids. One group of dogs was not resuscitated. Survival rate was monitored for 8 days. MEASUREMENTS AND MAIN RESULTS: In 33 beagle dogs, cardiovascular variables (DO2 and VO2) were compared after resuscitation with 8% stroma-free hemoglobin, 4% or 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP44 and PHP88, respectively), or autologous whole blood. The dogs were anesthetized, paralyzed, mechanically ventilated (FIO2 of 0.21), and instrumented with arterial and pulmonary artery catheters. An average of 63% of estimated blood volume was removed to maintain systolic blood pressure at 50 mm Hg for 2 hrs. The dogs then were either not resuscitated (n = 4) or resuscitated with 8% stroma-free hemoglobin (n = 7), PHP44 (n = 6), PHP88 (n = 8), or whole blood (n = 8), with a volume equivalent to the withdrawn blood. Cardiovascular variables, DO2, VO2, oxygen extraction ratios, and blood concentrations of lactic acid and catecholamines were determined before, and for < or = 6 hrs after, resuscitation from hemorrhagic shock. Blood smears were microscopically examined. In addition, the survival rate was monitored for 8 days after resuscitation. By 2 hrs of hemorrhagic shock, there was a large decrease in DO2 (p < .05) and an increase in oxygen extraction ratio from 0.27 to 0.70 (p < .05). There was a 3.5-fold increase in lactate concentrations and a 25-fold increase in catecholamine concentrations as compared with preshock values. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. After resuscitation with whole blood, all cardiovascular and oxygen transport variables returned to approximately prehemorrhage values and remained so throughout the measurement period. After resuscitation with any hemoglobin solution, DO2 returned transiently to control values. However, recovery of DO2 was short-lived in all hemoglobin solution groups, and, by 4 hrs postresuscitation in all groups, DO2 was less than the DO2 of the dogs receiving whole blood (p < .05). These changes were associated with decreases in total hemoglobin concentrations compared with the values immediately before resuscitation (p < .05). In addition, with resuscitation using the PHP solutions, blood smears demonstrated aggregation of red blood cells and platelets. On day 8 after hemorrhagic shock, the survival rate was 100% for whole blood and PHP44, 86% for 8% stroma-free hemoglobin, and 33% for PHP88. CONCLUSIONS: Resuscitation from severe hemorrhagic shock with 8% stroma-free hemoglobin, PHP44, or PHP88 is equally effective in restoring cardiac index and vascular pressures as using whole blood. However, resuscitation with the three hemoglobin solutions only transiently restored DO2 after hemorrhagic shock. The subsequent reduction of DO2 compared with the DO2 value using whole blood was due mostly to hemodilution. With the two PHP solutions, formation of red blood cell aggregates probably resulted in sequestration of red cell mass and additional loss of oxygen carrying capacity.

Animals↗
PubMed1996

Role of endothelin in the cardiovascular effects of diaspirin crosslinked and stroma reduced hemoglobin.

OBJECTIVES: Diaspirin crosslinked hemoglobin is a resuscitative solution with excellent oxygen-carrying capacity. Diaspirin crosslinked hemoglobin produces an immediate increase in blood pressure and marked regional circulatory changes in rats and pigs. Our objective was to determine the role of endothelin in the cardiovascular actions of diaspirin crosslinked hemoglobin (modified) and (unmodified) stroma reduced hemoglobin solutions. DESIGN: Prospective, randomized comparison of cardiovascular effects of diaspirin crosslinked and stroma reduced hemoglobin in control rats and in rats pretreated with cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), an endothelin-A receptor antagonist. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Modified, highly purified, and heat pasteurized (diaspirin crosslinked) and unmodified (stroma reduced) hemoglobin in control (untreated) and BQ-123 (5 mg/kg/hr iv)-treated rats. MEASUREMENTS AND MAIN RESULTS: Infusion of stroma reduced hemoglobin (400 mg/kg iv) in control rats produced an increase in blood pressure (43%) and total peripheral resistance (65%) without any change in heart rate, cardiac output, and stroke volume. Stroma reduced hemoglobin decreased blood flow to the kidneys and liver, increased blood flow to the heart, and had no effect on blood flow to the brain, gastrointestinal tract, spleen, musculoskeletal system, skin, and mesentery and pancreas. Infusion of stroma reduced hemoglobin in rats treated with BQ-123 (5 mg/kg/hr iv) increased the blood pressure to a similar degree when compared with control rats, but the increase in total peripheral resistance was significantly attenuated. The stroma reduced hemoglobin-induced decrease in blood flow to the kidneys and liver was significantly attenuated in BQ-123-treated rats as compared with control rats. However, the stroma reduced hemoglobin-induced increase in blood flow to the heart of BQ-123-treated rats was similar to the increase in control rats. Infusion of diaspirin crosslinked hemoglobin (400 mg/kg iv) produced increases in blood pressure (81%), cardiac output (36%), stroke volume (30%), and total peripheral vascular resistance (45%), along with increases in blood flow to the heart, spleen, gastrointestinal tract, and skin of control rats. The blood flows to the brain, kidneys, liver, musculoskeletal system, and mesentery and pancreas were not altered by diaspirin crosslinked hemoglobin in control rats. The increases in blood pressure, cardiac output, stroke volume, and total peripheral vascular resistance by diaspirin crosslinked hemoglobin were significantly blocked in BQ-123-treated rats as compared with control rats. The increases in blood flow to the heart, spleen, and skin by diaspirin crosslinked hemoglobin were significantly blocked in BQ-123-treated rats as compared with control rats. Diaspirin crosslinked hemoglobin produced an increase in the blood flow to the brain and a decrease in blood flow to the kidney and musculoskeletal system of BQ-123-treated rats as compared with control rats. Blood plasma endothelin-1-like immunoreactivity was found to be significantly increased after treatment with diaspirin crosslinked hemoglobin or stroma reduced hemoglobin. CONCLUSIONS: The endothelin-A receptor antagonist, BQ-123, could attenuate the systemic hemodynamic and regional circulatory effects of diaspirin crosslinked hemoglobin and stroma reduced hemoglobin. However, the increase in blood flow to the heart induced by stroma reduced hemoglobin could not be attenuated by BQ-123.

Animals↗
PubMed1996

Regional blood flow alterations after bovine fumaryl beta beta-crosslinked hemoglobin transfusion and nitric oxide synthase inhibition.

OBJECTIVES: a) To determine whether isovolemic exchange transfusion with cell-free, bovine fumaryl beta beta-crosslinked hemoglobin results in a different pattern of regional blood flow distribution than transfusion with a poor oxygen-carrying, colloidal solution. b) Because of potential nitric oxide scavenging by plasma-based hemoglobin, to determine whether blood flow differences are reduced after nitric oxide synthase inhibition. DESIGN: A prospective, randomized design with repeated blood flow measurements within groups. SETTING: Experimental physiology laboratory in a university medical center. SUBJECTS: Pentobarbital-anesthetized female cats. INTERVENTIONS: Three groups of eight cats were studied: a) a control group with no transfusion (hematocrit of 32%); b) an anemia group in which exchange transfusion with an albumin-containing solution reduced hematocrit to 18% over a 40- to 50-min period; and c) a group in which cell-free hemoglobin was exchanged transfused to reduce hematocrit to 18%, without a proportional reduction in oxygen-carrying capacity. Bovine hemoglobin was covalently crosslinked intramolecularly between the 81-lysine residues on the beta-subunits to stabilize the tetramer. Regional blood flow was measured by the radiolabeled microsphere technique before transfusion and at 10, 100, and 180 mins from the start of transfusion. At 190 mins, N omega-nitro-L-arginine methyl ester (L-NAME; 10mg/kg) was infused to inhibit nitric oxide synthase and blood flow was measured 30 mins later. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure was unchanged in the control and albumin-transfused groups. However, mean arterial pressure increased rapidly in the hemoglobin-transfused group. With hemoglobin transfusion, there were marked reductions in blood flow to the intestines, kidneys and adrenal glands. Administration of L-NAME after hemoglobin transfusion failed to increase arterial pressure or cause further reductions in intestinal, renal, or adrenal blood flow. Administration of L-NAME to the control and albumin-transfused groups increased arterial pressure and reduced intestinal, renal, and adrenal blood flows to values attained with hemoglobin transfusion. In contrast, in skeletal muscle and left ventricle, blood flow rates increased in the albumin-transfused group and were greater than those values found in the control group and hemoglobin-transfused group. The greater flow in the albumin-transfused group persisted after L-NAME administration. There was no difference in renal sodium, potassium, or osmolar excretion, or in urine flow between groups. CONCLUSIONS: Transfusion with cell-free, bovine crosslinked hemoglobin in cats can selective reductions in blood flow in the intestines, kidneys, and adrenal glands without evidence of renal dysfunction by a mechanism consistent with nitric oxide scavenging. In skeletal and cardiac muscle, the increase in blood flow persisted after nitric oxide inhibition in the albumin group relative to the hemoglobin-transfused group at equivalent hematocrit values. This finding is consistent with compensatory vasoconstriction with hemoglobin transfusion due to improved oxygenation by this oxygen carrier.

Animals↗
PubMed1997

Prolonged extracorporeal life support (ECLS) for varicella pneumonia.

OBJECTIVE: To review the institutional experience of a national tertiary referral center for extracorporeal life support (ECLS) in severe varicella pneumonia. DATA SOURCES: Hospital records and ECLS flow sheets. STUDY SELECTION: All pediatric (nonneonatal) and adult patients who were treated for varicella pneumonia with ECLS at the University of Michigan Medical Center between 1986 and 1995. DATA EXTRACTION: Diagnosis of varicella pneumonia was made by history of recent exposure to chickenpox, progressive dyspnea, fever, a characteristic diffuse, vesicular rash, and a supporting chest roentgenogram. Indications for ECLS included a shunt fraction of > 30% or PaO2/FlO2 ratio of < 80 despite maximal conventional therapy, which included aggressive diuresis, blood transfusions to optimize oxygen-carrying capacity, pressure-controlled/inverse-ratio ventilation, and intermittent prone positioning. DATA SYNTHESIS: Between 1986 and 1995, 191 patients were referred for ECLS. Among these patients, there were 51 (27%) cases of viral pneumonia, of which nine cases were due to acute varicella-zoster infection. Intravenous acyclovir was administered to eight of the nine patients. Of the nine patients, two patients improved using conventional ventilator management, and seven patients underwent ECLS. Overall survival on ECLS was 71% (5/7). The mean (+/-SD) alveolar-arterial oxygen gradient and PaO2/FlO2 ratio were 533 +/- 101 torr (71.3 +/- 13.5 kPa) and 67 +/- 24, respectively. The median duration of mechanical ventilation before ECLS and the subsequent duration of ECLS were 4 and 12.8 days, respectively. One of the deaths was from progressive right heart failure secondary to pulmonary hypertension and the other death was from overwhelming Pseudomonas sepsis. CONCLUSIONS: Early recognition of imminent pulmonary failure and rapid institution of ECLS are critical in the successful management of severe, life-threatening varicella pneumonia.

Acyclovir↗
PubMed1997

Using pulse oximetry in the home.

As complex patients require more sophisticated nursing care and equipment to stay at home, home care nurses must be able to make detailed, objective assessments. Pulse oximetry provides a tool to objectively assess oxygenation in the home. This article reviews how pulse oximetry works, how to interpret the results based on the patient's blood oxygen-carrying capacity, and technical aspects of using pulse oximetry in the home, including sources of inaccuracy in measurements and basic troubleshooting. These pulse oximetry principles are applied in the home care setting in three case studies.

Adult↗
PubMed2000

Noninvasive assessment of cerebral oxygenation during acclimation to hypobaric hypoxia.

Factors regulating cerebral tissue PO2 (PtO2) are complex. With the increased use of clinical PtO2 monitors, it has become important to elucidate these mechanisms. The authors are investigating a new methodology (electron paramagnetic resonance oximetry) for use in monitoring cerebral PtO2 in awake animals over time courses of weeks. The authors used this to study cerebral PtO2 in rats during chronic acclimation to hypoxia predicting that such acclimation would cause an increase in PtO2 because of increases that occur in capillary density and oxygen carrying capacity. The average PtO2 between 7 and 21 days was increased by 228% over controls.

Acclimatization↗
PubMed1994

A retrospective analysis of plate contouring in the tibia using the conventional 4.5 (narrow) dynamic compression plate.

Plate contouring is an essential part of plate osteosynthesis. Its safety and technical ease is dependent on plate factors (material and design) and the complexity of the contouring. Our purpose was to determine the range of plate contouring; estimate the strain on the plate from the radius of curvature in the area of contouring; and determine whether shaped plates had a reduction in their load carrying capacity. A retrospective analysis of 500 radiographed tibias that had undergone osteosynthesis with the conventional dynamic compression plate was conducted to evaluate the radius of curvature and degree of bend in the plates, and to determine whether plates were bent at screw holes. Contouring of the plate to fit the bone was done by the surgeon at the time of application. Postoperative radiographs were evaluated. We found that (a) the shorter the length of plate contoured, the greater the strain; (b) plates were bent at screw holes, and these tended to be the areas of highest strain; (c) the range of plate strain was 0.6-16% (average 1.6%); and (d) plates were bent from 10 to 90 degrees (average 20 degrees).

Biophysical Phenomena↗