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K F Waschke

Publications and source records attributed to K F Waschke.

15 recordsLinked to original sources
PubMed1998

[Partial liquid ventilation].

Partial liquid ventilation (PLV) is a relatively new therapeutic approach to acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). The idea of combining the intrapulmonary application of an oxygen-carrying substance and positive pressure ventilation was introduced by Fuhrman in 1991 and originally called perfluorocarbon-associated gas exchange (PAGE). Nowadays, the technique is mostly known as partial liquid ventilation (PLV). The efficacy of PVL treatment has been demonstrated in numerous animal studies in different models of lung injury. The results of those studies led to multicenter phase I-II studies in patients of all age groups in the United States and Canada. Recently, the first randomized, controlled study in 90 adult patients suffering from ALI and ARDS was completed and first results have been published. Comparison of overall mortality and number of ventilator-free days (VFD's) in a 28-day period showed no differences between PLV and conventionally treated patients. A post-hoc stratification by age (< 55 years) demonstrated a tendency to lower mortality (PLV 25.6%; CMV 36.8%) and a significant increase of VFD (PLV 8.95 days; CMV 4.11 days; p = 0.03) in PLV when compared to conventionally treated patients. Perfluorocarbons (PFCs) are chemically stable and inert. They are mostly eliminated via exhalation (> 99%). The unique physicochemical properties of PFCs permit access to atelectatic, non-ventilated lung areas, enhance gas exchange and decrease inflammation. The dense PFCs prevent the endexpiratory collapse of alveoli and reestablish functional residual capacity (FRC). Comparable to positive endexpiratory pressure (PEEP), these effects have been described as "liquid or fluid PEEP". These properties offer a new approach to the underlying pathophysiology of ALI and ARDS. In addition, the combination with other therapeutic approaches to ALI and ARDS like high-frequency oscillations (HFO), inhaled nitric oxide (NO) therapy, and surfactant replacement can be considered and is already the subject of recent publications. However, combination therapy is still experimental and further investigation is necessary to evaluate efficacy and potential risks. Many questions still exist which need to be answered by experimental as well as human pilot studies. Based on these studies, the results of ongoing human trials can be assessed properly and new multicenter trials can be planned effectively.

Blood Gas Analysis↗
PubMed1998

Artificial oxygen carriers.

The clinical availability of artificial oxygen carriers (AOCs) would result in profound alterations in transfusion medical practice. Rapid progress in the scientific and technological development of AOCs has advanced to a critical stage at which safe and effective alternatives to the transfusion of red blood cells are emerging. Haemoglobin- and perfluorocarbon-based oxygen carriers are under current clinical investigation. Artificial oxygen-carrying solutions, by virtue of their acellular structure, can be used to transport oxygen to ischaemic tissues that cannot otherwise be reached by cellular blood components. Organs awaiting transplantation can be preserved for a long time after perfusion with AOCs and tumour susceptibility to chemo- and radiotherapy is increased. The use of AOCs is therefore not confined to their use as red blood cell substitutes, but may find a wide spectrum of interdisciplinary applications.

Blood Substitutes↗
PubMed1998

Local cerebral blood flow, local cerebral glucose utilization, and flow-metabolism coupling during sevoflurane versus isoflurane anesthesia in rats.

BACKGROUND: Compared to isoflurane, knowledge of local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) during sevoflurane anesthesia is limited. METHODS: LCGU, LCBF, and their overall means were measured in Sprague-Dawley rats (8 groups, n=6 each) during sevoflurane and isoflurane anesthesia, 1 and 2 MAC, and in conscious control animals (2 groups, n=6 each) using the autoradiographic 2-[14C]deoxy-D-glucose and 4-iodo-N-methyl-[14C]antipyrine methods. RESULTS: During anesthesia, mean cerebral glucose utilization was decreased: control, 56+/-5 micronmol x 100 g(-1) x min(-1); 1 MAC isoflurane, 32+/-4 micromol x 100 g(-1) x min(-1) (-43%); 1 MAC sevoflurane, 37+/-5 micromol x 100 g(-1) x min(-1) (-34%); 2 MAC isoflurane, 23+/-3 micromol x 100 g(-1) x min(-1) (-58%); 2 MAC sevoflurane, 23+/-5 micromol x 100 g(-1) x min(-1) (-59%). Local analysis showed a reduction in LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased as follows: control 93+/-8 ml x 100 g(-1) x min(-1); 1 MAC isofurane, 119+/-19 ml x 100 g(-1) x min(-1) (+28%); 1 MAC sevoflurane, 104+/-15 ml x 100 g(-1) x min(-1) (+12%); 2 MAC isoflurane, 149+/-17 ml x 100 g(-1) x min(-1) (+60%); 2 MAC sevoflurane, 118+/-21 ml x 100 g(-1) min(-1) (+27%). LCBF was increased in most brain structures investigated. Correlation coefficients obtained for the relationship between LCGU and LCBF were as follows: control 0.93; 1 MAC isoflurane, 0.89; 2 MAC isoflurane, 0.71; 1 MAC sevoflurane, 0.83; 2 MAC sevoflurane, 0.59). CONCLUSION: Mean and local cerebral blood flows were lower during sevoflurane than during isoflurane anesthesia. This difference cannot be explained by differing changes in glucose utilization because glucose utilization was decreased to the same extent in both groups.

Anesthesia↗
PubMed1997

Isovolemic hemodilution with a bovine hemoglobin-based oxygen carrier: effects on hemodynamics and oxygen transport in comparison with a nonoxygen-carrying volume substitute.

OBJECTIVE: Stroma-free hemoglobin solutions have been shown to maintain oxygen transport in the absence of red blood cells. This study was designed to investigate the impact of such solutions on hemodynamics and oxygen transport during progressive isovolemic hemodilution within and even beyond a clinically relevant range of hematocrit values. DESIGN: Prospective, randomized experimental study comparing a bovine hemoglobin-based oxygen carrier (bHBOC) with a conventional nonoxygen-carrying volume substitute (hydroxyethyl starch [HES]). SETTING: Animal laboratory of a university cardiovascular research center. PARTICIPANTS: Splenectomized full-grown foxhounds, anesthetized with pentobarbital and piritramid. INTERVENTIONS: Twelve splenectomized foxhounds were anesthetized and mechanically ventilated. Catheters were placed for hemodilution, arterial and venous blood sampling, and hemodynamic measurements. The baseline hematocrit (Hct) value was adjusted to 0.35 by an initial isovolemic exchange of blood for identical volumes of HES (10% HES 200/0.5). Thereafter, the hematocrit was progressively reduced by isovolemic hemodilution using either HES (n = 6) or bHBOC (n = 6). MEASUREMENTS AND MAIN RESULTS: Hemodynamic and laboratory parameters of oxygen transport were measured at Hct values of 0.30, 0.20, and 0.10. Oxygen content was directly estimated using an oxygen-specific fuel cell. Arterial oxygen content at an Hct value of 0.10 nearly doubled in bHBOC-treated dogs as compared with HES-diluted animals (p < 0.001). This gain in oxygen-carrying capacity was completely negated by a decrease in cardiac output (-32% Hct 0.35 v Hct 0.30; p < 0.001) immediately on the first infusion of bovine hemoglobin. Thus, oxygen delivery was significantly lower as compared with HES-treated dogs at Hct 0.30 and 0.20, but remained stable at a level of 60% of baseline until Hct was 0.10. Both the pulmonary and the systemic vascular resistances increased. CONCLUSIONS: Isovolemic hemodilution with bHBOC did not improve systemic oxygen delivery in comparison with a nonoxygen-carrying diluent (HES) in a range of Hct values down to 0.10. Unchanged mixed venous lactate levels and stable oxygen consumption indicate sufficiently maintained oxygen delivery. This might become advantageous in patients who are unable to adequately increase cardiac output during hemodilution.

Animals↗
PubMed1997

Flow-independent heterogeneity of brain capillary plasma perfusion after blood exchange with a Newtonian fluid.

Previous studies from our group have indicated a heterogeneity of plasma transit times in brain capillaries. The heterogeneity was decreased with increasing cerebral blood flow during hypercapnia. In the present study, the hypothesis was tested that these apparent changes in microvascular plasma perfusion heterogeneity depend on the existence of red blood cells (RBC). To this end, the blood of anesthetized and paralyzed rats was replaced by a shear rate-independent oxygen-carrying substitute, ultrapurified polymerized bovine hemoglobin (UPBHB). Cerebral blood flow ([14C]iodoantipyrine technique) or microvascular perfusion pattern (intravenous bolus injection of Evans blue and decapitation 3-4 s later) was measured. After exchange transfusion with UPBHB, cerebral blood flow still varied with arterial PCO2, whereas in contrast to the unexchanged condition, the heterogeneity of the intracapillary Evans blue concentration remained unchanged. Compared with the unexchanged normocapnic condition, the heterogeneity of intracapillary dye concentration was decreased by one-quarter. It is concluded that RBC contribute to the microvascular perfusion heterogeneity in the brain.

Animals↗
PubMed1996

Altered expression of Bcl-2, Bcl-X, Bax, and c-Fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats.

Permanent occlusion of the middle cerebral artery in rats was used to assess the effects of focal ischemia on the expression of members of the bcl-2 family which have been implicated in the regulation of programmed cell death. Intraluminal occlusion of one middle cerebral artery for 6 h resulted in histologically detectable brain damage within the ipsilateral caudate putamen, basolateral cortex and parts of the thalamus. In the infarcted basolateral cortex and thalamus fragmentation of DNA was detected in many nuclei using in-situ end-labeling of DNA breaks by terminal transferase, whereas only scattered labeled nuclei were visible in the infarcted caudate putamen. Immunohistochemical analysis revealed activation of c-Fos in the infarcted cortex and thalamus and in the non-infarcted cingulate cortex as has been shown by others. A decrease in immunoreactivity for Bcl-2, and Bcl-X and an increase in immunostaining for Bax was observed exclusively in neurons within the ischemic cortex and thalamus. Within the infarcted caudate putamen, however, protein levels of all bcl-2 family members declined and c-Fos remained absent. By reverse transcription and polymerase chain reaction it was demonstrated that levels of bcl-2 mRNA markedly decreased in the ipsilateral hemisphere, whereas the amount of bax mRNA was elevated. These findings suggest that a shift in the ratio of cell death repressor Bcl-2 to cell death effector Bax and a concomitant activation of c-Fos may contribute to neuronal apoptosis in the infarcted thalamus and cortex.

Animals↗
PubMed1996

Regional heterogeneity of cerebral blood flow response to graded volume-controlled hemorrhage.

OBJECTIVE: Of the animal models of human hemorrhagic shock, the volume-controlled hemorrhage model appears to come closer to the clinical situation than the commonly used pressure-controlled model, since the volume-controlled model allows regulatory adjustment of blood pressure. The effects of volume-controlled hemorrhage on local cerebral blood flow (LCBF) of conscious animals are not known. The present study investigates specific reaction patterns of LCBF in comparison to mean cerebral blood flow (CBF) during graded volume-controlled hemorrhagic shock in conscious rats. METHODS: Conscious, spontaneously breathing, and minimally restrained rats were subjected to different degrees of volume-controlled hemorrhage (taking either 25, 30, 35, or 40 ml arterial blood/kg body weight (b.w.). Thirty minutes after the completion of blood taking, LCBF was determined during hemorrhagic hypovolemia using the autoradiographic iodo (14C) antipyrine method. A group of untreated rats (no hemorrhage) served as controls. LCBF was determined in 34 defined brain structures and mean CBF was calculated. RESULTS: During less severe hemorrhage (25 and 30 ml/kg b.w.) mean CBF was significantly higher than in the control group (+19% and +25%). During severe hemorrhage (35 and 40 ml/kg b.w.) mean CBF remained unchanged compared to the control values, although significant increases in LCBF could be detected in many of the brain structures analyzed (maximum +44%). The mean coefficient of variation of CBF was increased, indicating a larger heterogeneity of LCBF values at shed blood volumes of 35 and 40 ml/kg b.w. CONCLUSIONS: A comprehensive and novel description of the local distribution of CBF during graded volume-controlled hemorrhage in conscious rats shows unexpected increases in LCBF and mean CBF. This "hypovolemic cerebral hyperemia" might be caused by endogenous hemodilution, thus maintaining the blood supply to the brain during hypovolemic shock.

Animals↗
PubMed1996

[Liquid ventilation with perfluorocarbons].

Clark and Gollan demonstrated impressively in 1966 the ability of perfluorchemicals (PFCs) to transport oxygen and to provide gas exchange across the alveolar capillary membrane. PFCs are used for two major medical indications: as artificial blood substitutes and as a medium for liquid ventilation. The PFC perflubron is additionally used as a contrast medium for diagnostic radiologic procedures. For the intravenous application perfluorocarbons have to be emulgated in phospholipids for the intrapulmonary application the sterile pure solution is used. Liquid ventilation can either be performed by a method known as total liquid ventilation (TLV), in which a device is utilised to ventilate with perfluorocarbon the previously perfluorocarbon-filled lung, or as partial liquid ventilation (PLV) in which a conventional mechanical gas ventilator is used to gas ventilate the partially perfluorocarbon-filled lung. A number of studies have demonstrated the efficacy of perfluorocarbon liquid ventilation in improving gas exchange and pulmonary function in a number of animal species in the setting of acute respiratory failure. In 1989 Greenspan reported on the first human liquid ventilation experience in a neonate. More recently human experiences for neonatal, paediatric and adult patients with acute lung injury have been reported. Since 1995 an FDA-approved study to examine the efficacy of PLV in severe respiratory failure in patients of all ages has been undertaken in the United States. The number of PLV-treated patients is still small; if PLV demonstrates its efficacy even in the ongoing human studies, it might be a very effective additional tool for treating severe acute lung injury.

Adult↗
PubMed1996

Coupling between local cerebral blood flow and metabolism after hypertonic/hyperoncotic fluid resuscitation from hemorrhage in conscious rats.

The effects of small volume hypertonic/hyperoncotic fluid resuscitation from hemorrhage on brain metabolism and blood flow were evaluated by autoradiographic techniques with high spatial resolution. The data were compared to fluid resuscitation with a volume equal to shed blood of isotonic 6% hydroxyethyl starch solution (HES) and a control group without hemorrhage and fluid resuscitation (n = 6 in each group). In conscious rats, volume-controlled hemorrhage for 30 min (30 mL/kg body weight, resulting in a blood loss of approximately 50% of the circulating blood volume) was followed by intravenous infusion of a hypertonic/hyperoncotic saline hydroxyethyl starch solution (HTHO; 7.5% saline/10% hydroxyethyl starch, 4.0 mL/kg body weight). Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 34 brain structures 2 h after fluid resuscitation by means of the quantitative autoradiographic iodo [14C]antipyrine and 2-[14C]-deoxy-D-glucose methods. Compared to the untreated control group, LCBF increased significantly in all brain regions analyzed after fluid resuscitation with HTHO (mean, +63%) or HES (mean, +56%). The increases in LCBF after fluid resuscitation were sufficient to restore cerebral oxygen delivery to the level calculated for the untreated control group. LCGU was unchanged after fluid resuscitation. The close relationship between LCGU and LCBF observed in the control group (r = 0.95) was preserved after hemorrhage and fluid resuscitation with HTHO (r = 0.97) and HES (r = 0.96), although the LCBF-to-LCGU ratio was reset to a higher level (1.5 mL/mumol in the control group and 2.7 mL/mumol after fluid resuscitation with HTHO and HES, P < 0.05). We conclude that the increase in LCBF compensates for the reduction of arterial oxygen content to maintain cerebral oxygen delivery. Therefore, "small volume resuscitation" appears to be as effective as resuscitation with large volumes of isotonic HES in meeting the circulatory and metabolic demands of the brain tissue within the first 2 h after fluid resuscitation from hemorrhage.

Animals↗
PubMed1995

[Modified hemoglobins as oxygen transporting blood substitutes ].

Although the attempts to develop an oxygen-carrying alternative to red blood cells (RBC) have spanned the last 100 years, it has proven difficult to develop a clinically useful haemoglobin-based oxygen carrier. Four major problems have been shown to compromise the use of haemoglobin outside the RBC as an oxygen carrier: (1) the increased oxygen affinity due to the loss of 2,3-diphosphoglycerate; (2) dissociation into dimers and monomers with consequent renal and capillary loss of hemoglobin; (3) insufficient concentrations of prepared solutions under iso-oncotic conditions, and thereby reduced oxygen-carrying capacity; and (4) toxicity. Most of these limitations have been overcome by different modifications of haemoglobin, including pyridoxylation, intra- and intermolecular cross-linking, polymerisation, liposome encapsulation, conjugation to inert macromolecules, and genetic engineering. Questions of toxicity are not completely answered at present, especially with regard to renal toxicity, interactions with the nitric oxide system, and antigenicity. Therefore, the issues preventing clinical application are those of safety and not of efficacy of haemoglobin-based RBC substitutes. Potential clinical applications include fluid resuscitation, treatment of anaemia and ischaemia, support in extracorporeal circulation, and organ preservation. Based on promising and reproducible results obtained from animal studies, clinical phase I and II trials with newer haemoglobin solutions have been started in the United States. Substantial knowledge has been gained in the development, production, and evaluation of haemoglobin-based oxygen carriers during the past years. It will probably not take another century before oxygen-carrying RBC substitutes will become available for clinical use.

Animals↗
PubMed1994

Lack of dependence of cerebral blood flow on blood viscosity after blood exchange with a Newtonian O2 carrier.

Whether the increase in cerebral blood flow measured after hemodilution is mediated by a decrease in blood viscosity or in oxygen delivery to the brain is debated. In the present study, blood was replaced by an oxygen-carrying blood substitute, ultrapurified, polymerized, bovine hemoglobin (UPBHB). In contrast to normal blood, UPBHB yields a constant and defined viscosity in the brain circulation, since its viscosity is not dependent on the shear rate. CBF was determined after blood exchange with UPBHB in one group of conscious rats (UPBHB group) and in another group of blood-exchanged conscious rats in which viscosity was increased fourfold by the addition of 2% polyvinylpyrrolidone (PVP), mw 750,000 (UPBHB-PVP group). Local CBF (LCBF) was measured in 34 brain structures by means of the quantitative iodo(14C)antipyrine method. After blood replacement, systemic parameters such as cardiac index, arterial blood pressure, blood gases, and acid-base status were not different between the UPBHB and the UPBHB-PVP groups. In particular, arterial oxygen content was similar in both groups. Compared with a control group without blood exchange, LCBF was increased after blood exchange in the different brain structures by 60-102% (UPBHB group) and by 33-101% (UPBHB-PVP group). Mean CBF was increased by 77% in the UPBHB group and by 69% in the UPBHB-PVP group. No significant differences were observed in the values of LCBF or mean CBF between the UPBHB group and the UPBHB-PVP group. The results show that a fourfold variation in the viscosity of a Newtonian blood substitute does not result in differences in CBF values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Autoradiographic determination of regional cerebral blood flow and metabolism in conscious rats after fluid resuscitation from haemorrhage with a haemoglobin-based oxygen carrier.

The effects of resuscitation fluids on the brain have been investigated in previous studies by global measurements of cerebral blood flow and metabolism. In this study we have examined the effects of a novel haemoglobin-based oxygen carrier on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) after resuscitation from a volume-controlled haemorrhage of 30 min (3.0 ml/100 g body weight) with ultrapurified, polymerized, bovine haemoglobin (UPBHB). LCBF and LCGU were measured in 34 brain structures of conscious rats 2 h after resuscitation using quantitative iodo(14C)antipyrine and 2-(14C)-deoxy-D-glucose methods. The data were compared with a control group without haemorrhage and fluid resuscitation. In the haemorrhage group, LCBF increased after resuscitation by 12-56% in the different brain structures (mean 36%). LCGU changed less (0 to +18%, mean +9%). In the control group there was a close relationship between LCGU and LCBF (r = 0.95). After fluid resuscitation the relationship was preserved (r = 0.95), although it was reset at a higher ratio of LCBF to LCGU (P < 0.05). We conclude that fluid resuscitation of a 30 min volume-controlled haemorrhage using the haemoglobin-based oxygen carrier, UPBHB, induced a moderate degree of heterogeneity in the resulting changes of LCGU and LCBF. Local disturbances of cerebral blood flow or metabolism were not observed.

Animals↗
PubMed1994

Effects of a perfluorocarbon emulsion on regional cerebral blood flow and metabolism after fluid resuscitation from hemorrhage in conscious rats.

Regional cerebral blood flow and metabolism were investigated after addition of a small volume of perfluorocarbon (PFC) emulsion to the resuscitation fluid after hemorrhage. Severe volume-controlled hemorrhage (40 mL/kg body weight (bw) withdrawn over 30 min followed by hypovolemia of 30 min duration) was induced in conscious rats. While breathing 100% oxygen, the intravascular volume was repleted by the infusion of either 6% hydroxyethyl starch (mean mol wt 200,000/0.5; HES) or 6% hydroxyethyl starch plus perflubron (90% wt/vol emulsion of perfluoroctylbromide, 3 mL/kg bw; HES-PFOB). Two hours after fluid resuscitation either iodo[14C]antipyrine or 2[14C]deoxy-D-glucose were infused. Local cerebral blood flow (LCBF) or local cerebral glucose utilization (LCGU) were determined in 34 brain structures using quantitative autoradiography. Local cerebral metabolism was not disturbed in the HES and the HES-PFOB groups after fluid resuscitation, although slight reductions (mean -14%) were measured (HES-PFOB vs HES; P < 0.05). The HES-PFOB group showed LCBF values that were higher in the different brain structures than those of the HES group (mean +30%). A close correlation was found between LCGU and LCBF of the 34 brain structures in both groups (HES: r = 0.96, P < 0.01; HES-PFOB: r = 0.98, P < 0.01), whereas the LCBF-to-LCGU ratio was reset from 2.2 mL/mumol in the HES group to 3.4 mL/mumol in the HES-PFOB group (P < 0.05). The higher blood flows in the HES-PFOB group were sufficient to restore cerebral oxygen delivery to normal levels at a reduced arterial oxygen content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗