H. Krieter

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. It is concluded that blood viscosity is less important to CBF than hitherto postulated.

Intestinal ischaemia during cardiac arrest and resuscitation: comparative analysis of extracellular metabolites by microdialysis

Intestinal ischaemia is a major complication of shock syndromes causing translocation of bacteria and endotoxins and multiple organ failure in intensive care patients. The present study was designed to use microdialysis as a tool to monitor intestinal ischaemia after cardiac arrest and resuscitation in pigs. For this purpose, microdialysis probes were implanted in pig jejunal wall, peritoneum, skeletal muscle and brain, and interstitial fluid was obtained during circulatory arrest (induced by ventricular fibrillation) and after return of spontaneous circulation (ROSC). Cardiac arrest for 4 min caused a prolonged (60 min) reduction of blood flow in jejunal wall, muscle and brain as determined by the ethanol technique. This was accompanied by cellular damage in heart muscle and brain as indicated by increased levels of troponin-I and protein S-100, respectively. Plasma levels of glucose, lactate and choline were increased at 15-60 min following cardiac arrest. In contrast, cardiac arrest induced a rapid but variable decrease of interstitial glucose levels in all monitored organs; this decrease was followed by an increase over baseline during reperfusion. In the intestine, lactate, glutamate and choline levels were increased during ischaemia and reperfusion for 60-120 min; intestinal and peritoneal samples yielded parallel changes of lactate levels. Brain and muscle samples showed similar changes as in intestinum and peritoneum except for glutamate, which was increased in brain but not in muscle. We conclude that intestinal ischaemia occurs as a consequence of cardiac arrest and resuscitation and can be monitored by in vivo microdialysis. Comparative analysis by multi-site microdialysis reveals that the intestine is equally or even more sensitive to ischaemia than brain or muscle.

Measurement of liver blood flow using oxygen-15 labelled water and dynamic positron emission tomography: Limitations of model description

To date no satisfactory method has been available for the quantitative in vivo measurement of the complex hepatic blood flow. In this study two modelling approaches are proposed for the analysis of liver blood flow using positron emission tomography (PET). Five experiments were performed on three foxhounds. The anaesthetised dogs were each given an intravenous bolus injection of oxygen-15 labelled water, and their livers were then scanned using PET. Radioactivity in the blood from the aorta and portal vein was measured directly and simultaneously using closed external circuits. Time-activity curves were constructed from sequential PET data. Data analysis was performed by assuming that water behaves as a freely diffusible tracer and adapting the standard one-compartment blood flow model to describe the dual blood supply of the liver. Two particular modelling approaches were investigated: the dual-input model used both directly measured input functions (i.e. using the hepatic artery and the portal vein input, determined from the radioactivity detected in the aorta and portal vein respectively) whereas the single-input model used only the measured arterial curve and predicted the corresponding portal input function. Hepatic arterial flow, portal flow and blood volume were fitted from the PET data in several regions of the liver. The resulting estimates were then compared with reference blood flow measurements, obtained using a standard microsphere technique. The microspheres were injected in a separate experiment on the same dogs immediately prior to PET scanning. Whilst neither the single- nor the dual-input models accurately reproduced the arterial reference flow values, the flow values from the single-input model were closer to the microsphere flow values. The proposed single-input model would be a good approximation for liver blood flow measurements in man. The observed discrepancies between the PET and microsphere flow values may be due to the inherent temporal and spatial heterogeneity of liver blood flow. The results presented suggest that adaptation of the standard one-compartment blood flow model to describe the dual blood supply of the liver is limited and other flow tracers have to be considered for quantitative PET measurements in the liver.

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.

Accuracy and precision of three different methods to determine Pco2 (Paco2 vs. Petco2 vs. Ptcco2) during interhospital ground transport of critically ill and ventilated adults.

BACKGROUND Interhospital transportation of critically ill and mechanically ventilated patients represents a common, yet difficult problem. Three different methods to determine Pco2 during transport are available: arterial blood gas analysis (Paco2), end-tidal (Petco2) and transcutaneous (Ptcco2) measurement. The aim of the present study is to analyze accuracy and precision of those different methods simultaneously in critically ill and ventilated adults during interhospital transport. METHODS Patients scheduled for interhospital transport were investigated after approval of the local ethics committee in the prospective study. Pco2 was determined five times in each patient during the transport simultaneously by (1) arterial blood gas analysis (Paco2[Immediate Response Mobile Analyzer, IRMA]), (2) end-tidal (Petco2), and (3) transcutaneous (Ptcco2) measurements. The results were compared with an in-hospital reference measurement performed by an ABL 625 blood gas analyzer (Paco2[ABL625]). For statistical analysis the Bland-Altman method was used. A p < 0.05 was considered statistically significant. RESULTS One hundred seventy data sets (Paco2[IRMA], Paco2[ABL625], Petco2, Ptcco2) were obtained in 34 patients (61 years +/- 16 years old; 19 male patients, 15 female patients). The mean Paco2(ABL625) was 43.2 mm Hg +/- 8.8 mm Hg ranging from 24.9 mm Hg to 72.4 mm Hg. Bland-Altman analysis revealed a bias and precision of -0.6 mm Hg +/- 2.5 mm Hg for the arterial blood gas analysis with the mobile IRMA device and -0.6 mm Hg +/- 7.5 mm Hg for the transcutaneous measurement (p > 0.05). Bias and precision (-5.3 mm Hg +/- 6.1 mm Hg) of endexpiratory CO2-measurement differed significantly (p < 0.003) when compared with the reference. CONCLUSIONS During interhospital transport Paco2(IRMA) and Ptcco2 provide the best accuracy when compared with the reference measurement. Patients who either require a tight control of Pco2 or endured lengthy transportation could benefit greatly from the combination of expiratory capnography with mobile arterial blood gas analysis or the transcutaneous measurement of Pco2.

Hypertonic-Hyperoncotic Solutions Reduce the Release of Cardiac Troponin I and S-100 After Successful Cardiopulmonary Resuscitation in Pigs

UNLABELLED In some patients, cardiopulmonary resuscitation (CPR) can revive spontaneous circulation (ROSC). However, neurological outcome often remains poor. Hypertonic-hyperoncotic solutions (HHS) have been shown to improve microvascular conductivity after regional and global ischemia. We investigated the effect of infusion of HHS in a porcine CPR model. Cardiac arrest was induced by ventricular fibrillation. Advanced cardiac life support was begun after 4 min of nonintervention and 1 min of basic life support. Upon ROSC, the animals randomly received 125 mL of either normal saline (placebo, n = 8) or 7.2% NaCl and 10% hydroxyethyl starch 200,000/0.5 (HHS, n = 7). Myocardial and cerebral damage were assessed by serum concentrations of cardiac troponin I and astroglial protein S-100, respectively, up to 240 min after ROSC. In all animals, the levels of cardiac troponin I and S-100 increased after ROSC (P < 0.01). This increase was significantly blunted in animals that received HHS instead of placebo. The use of HHS in the setting of CPR may provide a new option in reducing cell damage in postischemic myocardial and cerebral tissues. IMPLICATIONS Infusion of hypertonic-hyperoncotic solutions (HHS) after successful cardiopulmonary resuscitation in pigs significantly reduced the release of cardiac troponin I and cerebral protein S-100, which are sensitive and specific markers of cell damage. Treatment with HHS may provide a new option to improve the outcome of cardiopulmonary resuscitation.

Hypertonic-hyperoncotic solutions decrease cardiac troponin I concentrations in peripheral blood in a porcine ischemia-reperfusion model

In this study we addressed the question of whether the measurement of cardiac Troponin I (cTnI) is able to reflect beneficial effects of hypertonic-hyperoncotic solutions after transient cardiac arrest. Ten pigs were anaesthetized and cardiac arrest was induced by electric fibrillation. After 5 minutes of global ischemia, cardiac arrest was reversed by electric defibrillation. Upon return of spontaneous circulation 5 animals received hypertonic-hyperoncotic solutions (10% Hydroxyethylstarch 200/0.5 and 7.2% NaCl). The other animals received equivalent volumes of physiological saline. We observed that cTnI serum levels of animals treated with hypertonic-hyperoncotic solutions were significantly lower than those treated with saline. We conclude that hypertonic-hyperoncotic solutions may have cardioprotective effects.

Cardiac troponin I and cardiac troponin T increases in pigs during ischemia-reperfusion damage.

In this study we addressed the question of whether the measurement of cardiac Troponin T (cTnT) and cardiac Troponin I (cTnI) is able to detect myocardial cell damage in an ischemia-reperfusion model in pigs. To answer the question 3 pigs were anaesthesized and a cardiac arrest was induced by electric fibrillation. After 5 minutes of global ischemia the cardiac arrest was reversed by electric defibrillation until normal perfusion was restored. We could clearly demonstrate an increase of cTnT and cTnI 30 minutes after reperfusion indicating myocardial injury during ischemia and subsequent reperfusion. The cTnT as well as the cTnI serum levels increased till 180 minutes after reperfusion. This ischemia-reperfusion injury is likely induced by oxygen radicals generated during hypoxia and subsequent reperfusion We conclude from our first results that troponin measurements with commercial available test kits may also reflect myocardial cell damage in pigs as it was recently demonstrated in rats. Further studies are needed for correlation of troponin serum levels and histopathological damage in this model especially if it is used to test beneficial or toxicological effects of radical neutralizing drugs.

Effect of cyclooxygenase inhibition in a canine model of unilateral pulmonary occlusion and reperfusion

Objectiveto assess the effects of the cyclooxygenase inhibitor diclofenac in a canine model of pulmonary occlusion and reperfusion of the left lower lobe (LLL).DesignTwelve adult beagle dogs (13–17 kg) were randomly assigned to a control group (n=6) and a diclofenac-treated group (n=6). Animals in the treatment group received 20 mg diclofenac sodium/kg as a single dose both before the experiment and at the end of surgical preparation; six animals served as controls.InterventionsIn the anesthetized animals, the left upper and middle lobes were resected. Circulation and ventilation of the LLL were selectively blocked by clamping. Complete occlusion of the LLL (30 min) was followed by periods of selective reperfusion (10 min, RP) and combined reperfusion and reventilation (120 min, RP/RV).Measurements and resultsReperfusion of the LLL resulted in a significant increase in pulmonary arteriial pressure (Ppa) in the early RP/RV period as compared to baseline values (25.3±4.7 vs 15.8±1.9 mmHg,p<0.05, pairedt-test). This increase was significantly inhibited in the diclofenac-treated animals (17.0±2.0 mmHg,p<0.01 vs controls, ANOVA).Gravimetrically determined extravascular lung water (EVLW) showed no significant difference in the continuously ventilated lobes of the right lung between diclofenactreated animals (3.8 ml/g dry weight) and controls (3.9±0.9 ml/g dry weight) at the end of the experiment. EVLW, however, increased significantly in the LLL of control animals after 2 h of combined reperfusion and reventilation, whereas this increase was significantly inhibited in the diclofenactreated animals (4.5±0.7 ml/g dry weight in the diclofenac group vs 6.5±1.3 ml/g dry weight in the control group,p<0.05).ConclusionsDiclofenac inhibits the increase in both pulmonary arterial pressure and EVLW during reperfusion and reventilation of LLL. Thus, these changes appear to be mediated by cyclooxygenase metabolites.

LACK OF DEPENDENCE OF CEREBRAL BLOOD FLOW ON BLOOD VISCOSITY

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)