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Biomedical subjects

M Kleen

Publications and source records attributed to M Kleen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Normovolaemic haemodilution and hyperoxia have no effect on fractal dimension of regional myocardial perfusion in dogs.

Hypervolaemic haemodilution makes myocardial perfusion more homogenous as reflected by reduced fractal dimension of regional myocardial perfusion. The clinically more commonly performed acute normovolaemic haemodilution, however, has not yet been studied in this respect. Hyperoxic ventilation with 100% oxygen is used in conjunction with haemodilution to compensate for low oxygen content by increasing physically dissolved oxygen in plasma. Since hyperoxia is known to cause disturbance in microcirculatory regulation we studied the effects of acute normovolaemic haemodilution to haematocrit (hct) 20 +/- 1% and hyperoxia on regional myocardial perfusion heterogeneity in 22 anaesthetized dogs using fractal and correlation analysis. Regional myocardial perfusion was assessed with radioactive microspheres. The results of the study were that heart rate, blood volume and arterial pressure were unchanged during haemodilution. Cardiac index was 3.6 +/- 0.7 L min-1 m-2 before and 4.6 +/- 0.7 L min-1 m-2 after haemodilution (P < 0.05). Fractal dimension (D) of regional myocardial perfusion was 1.17 +/- 0.10 at baseline. Neither haemodilution (D = 1.19 +/- 0.10) nor hyperoxia (D = 1.17 +/- 0.10) altered fractal properties of regional myocardial perfusion. Spatial correlation of blood flow to adjacent tissue samples before haemodilution was 0.58 +/- 0.15. Haemodilution and hyperoxia did not significantly influence spatial correlation (0.57 +/- 0.12 vs. 0.60 +/- 0.09; ns). We conclude that neither acute normovolaemic haemodilution nor haemodilution in combination with hyperoxic ventilation alter physiological myocardial perfusion heterogeneity.

Animals↗
PubMed1998

Efficacy of inhaled prostanoids in experimental pulmonary hypertension.

OBJECTIVES: To evaluate the effects of inhaled prostacyclin (PGI2) and inhaled as well as intravenous prostaglandin E1 (PGE1) on thromboxane A2 mimetic-induced pulmonary vasoconstriction. Active pulmonary vasoconstriction was to be distinguished from passive resistance to blood flow. DESIGN: Prospective, randomized, crossover study. SETTING: Experimental animal laboratory. SUBJECTS: Eight anesthetized and paralyzed sheep. INTERVENTIONS: The stable thromboxane A2 mimetic, U46619, was infused in increasing dosage to obtain a stable pulmonary hypertension of approximately 30 mm Hg. Subsequently, PGE1 aerosol (0.6, 6, 58, 259 ng/kg/min), intravenous PGE, (0.5 microg/kg/min), or PGI2 aerosol (27 ng/kg/min) were administered in randomized order. MEASUREMENTS AND MAIN RESULTS: Active pulmonary vasoconstriction was assessed by determining the pulmonary pressure-flow relationship (PPFR). For measurement of pulmonary artery flow, an ultrasound flow probe was placed around the pulmonary artery after a sternotomy. Pulmonary arterial pressure was measured with a pulmonary artery flotation catheter. Flow was varied by partial occlusion of the inferior vena cava or incremental opening of an arterio-venous fistula between the large neck vessels. The primary end points were the slope of the resulting linear pressure-flow relationship, and pulmonary vascular resistance (PVR). Infusion of U46619 increased the slope of the PPFR (2.9+/-0.7 vs. 4.2+/-1.2 mm Hg/L/min [median+/-semi-interquartile range]; p < or = .05), and PVR (221+/-20 vs. 424+/-57 dyne x sec/cm5) (p < .05). Neither dose of PGE1 aerosol induced changes of the slope of PPFR or PVR. In contrast, intravenous administration of the same drug reduced the slope of the PPFR (4.0+/-1.0 vs. 3.1+/-0.4) (p < .05) but left PVR unchanged. Inhalation of PGI2 reduced both the slope of the PPFR, slightly but significantly, and PVR (424+/-98 vs. 323+/-26 dyne x sec/cm5) (p < .05). CONCLUSIONS: This study is the first to show reduction of active pulmonary vasoconstriction by PGI2 aerosol. Neither inhalation nor intravenous administration of PGE1 reduced PVR but the latter reduced the slope of PPFR. We conclude that PGE1 has potential for pulmonary vasodilation, but that it is ineffective as an aerosol, even in high doses, in sheep. PVR may fail to reflect drug-induced pulmonary vasodilation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Noninvasive measurement of regional cerebral blood flow by near-infrared spectroscopy and indocyanine green.

Clinicians lack a practical method for measuring CBF rapidly, repeatedly, and noninvasively at the bedside. A new noninvasive technique for estimation of cerebral hemodynamics by use of near-infrared spectroscopy (NIRS) and an intravenously infused tracer dye is proposed. Kinetics of the infrared tracer indocyanine green were monitored on the intact skull in pigs. According to an algorithm derived from fluorescein flowmetry, a relative blood flow index (BFI) was calculated. Data obtained were compared with cerebral and galeal blood flow values assessed by radioactive microspheres under baseline conditions and during hemorrhagic shock and resuscitation. Blood flow index correlated significantly (rs = 0.814, P < 0.001) with cortical blood flow but not with galeal blood flow (rs = 0.258). However, limits of agreement between BFI and CBF are rather wide (+/- 38.2 +/- 6.4 mL 100 g-1 min-1) and require further studies. Data presented demonstrate that detection of tracer kinetics in the cerebrovasculature by NIRS may serve as valuable tool for the noninvasive estimation of regional CBF. Indocyanine green dilution curves monitored noninvasively on the intact skull by NIRS reflect dye passage through the cerebral, not extracerebral, circulation.

Algorithms↗
PubMed1998

PEEP only partly restores disturbed distribution of regional pulmonary blood flow in lung injury.

The effects of lung injury, positive end-expiratory pressure (PEEP), and norepinephrine on heterogeneity of regional pulmonary blood flow (rPBF, radioactive microspheres) were investigated. We hypothesized that lung injury increases heterogeneity of rPBF and that PEEP ventilation reduces these effects. Heterogeneity of rPBF is scale dependent and was therefore assessed in detail. Local correlation (p), relative dispersion (RD), fractal dimension (D), perfusion gradients, and histograms of rPBF each measures a different aspect of heterogeneity. In eight anesthetized dogs, lung injury was induced with oleic acid and glass bead injection. Afterward, PEEP of 10-20 cmH2O was instituted. Norepinephrine was infused at 20 cmH2O PEEP. Heterogeneity increased upon lung injury (p, 0.44 +/- 0.09 vs. 0.24 +/- 0.09; RD, 0.36 +/- 0.06 vs. 0.64 +/- 0.12; both P < or = 0.05), but fractal dimension remained constant. PEEP did not change p, RD, or D. Perfusion gradients were reversed after lung injury (right, -27 +/- 18 vs. 196 +/- 115%; -24 +/- 18 vs. 282 +/- 184%; P < or = 0.05). PEEP (10 cmH2O) reduced gradients (116 +/- 73 and 143 +/- 62%, respectively; P < or = 0.05). Norepinephrine, in part, further reduced gradients (right, 50 +/- 58%; P < or = 0.05; left, 102 +/- 94%; P = NS). We conclude that oleic acid- and glass bead-induced lung injury produces abnormal distribution of rPBF. Of these changes, application of PEEP only reverses perfusion gradients.

Animals↗
PubMed1998

Hemodilution and hyperoxia locally change distribution of regional pulmonary perfusion in dogs.

In seven anesthetized dogs, the effects of acute normovolemic hemodilution (ANH) to a hematocrit of 20 and 8% and the effects of hyperoxic ventilation (100% oxygen) on distribution of regional pulmonary blood flow (rPBF; radioactive microspheres) were investigated. Normovolemia was monitored with blood volume measurements (indocyanine green dilution kinetics). Before ANH, fractal dimension (D) of rPBF in the whole lung was 1.19 +/- 0.09 (mean +/- SD). Spatial correlation (rho) of rPBF in the whole lung was 0.6 +/- 0.08. D is a resolution-independent measure for global rPBF distribution, and rho is the averaged flow relationship of directly neighboring lung samples. With regard to the entire lung, neither ANH nor hyperoxia changed D or rho. With regard to horizontal, isogravitational planes, ANH induced opposite changes of rPBF heterogeneity depending on the vertical location of the plane and the parameter used. In ventral planes, a change in relative dispersion (SD/mean) indicated decreased homogeneity. However, rho suggested more homogeneous perfusion. Hyperoxia restored baseline rPBF distribution. Our data suggest that ANH causes different alterations of heterogeneity of rPBF depending on location within the lung.

Animals↗
PubMed1997

Biochemical and cellular composition of alveolar epithelial lining fluid in anesthetized healthy lambs.

Pulmonary toxicity of inhaled materials is often evaluated by (repetitive) assessment of the composition of bronchoalveolar lavage (BAL) fluid or of epithelial lining fluid (ELF) in sheep and lambs. Knowledge of the typical constituents of these fluids obtained from healthy animals is essential for identification of pathologic changes. Few studies have dealt with normal constituents of BAL fluid or ELF in sheep and lamb. The comparability of these studies, however, is limited for reasons concerning the choice of model and BAL technique. The biochemical and cellular composition of alveolar ELF obtained by a standardized BAL procedure was examined in 15 pento-barbital anesthetized 4 months old Merino lambs unexposed to inhaled substances. ELF volume was calculated by using the urea dilution method. We found 20.3 x 10(5) leucocytes per ml ELF, 87.5% of which were alveolar macrophages. Basophils and neutrophils were practically absent while 5% of the counted cells were lymphocytes. 76% of recovered cells were viable. The ELF contained 7 mg/ml total protein; enzyme activities of LDH and AP were 1692 U/l and 145 U/l, respectively.

Anesthesia, Inhalation↗
PubMed1997

Effects of hemodilution on splanchnic perfusion and hepatorenal function. I. Splanchnic perfusion.

Perfusion of intestinal organs increases in response to acute normovolemic hemodilution (ANH). However, detailed studies on distribution of regional splanchnic organ perfusion during ANH are lacking. We therefore carried out this study to test the hypothesis that ANH does not cause disturbance of physiologic patterns of regional splanchnic organ blood flow. After governmental permission, 22 anesthetized dogs were instrumented to allow invasive hemodynamic measurements and intracardial injection of radioactive microspheres (diameter 15 micro m) for determination of regional organ perfusion. Measurements were made at baseline (hematocrit 37 +/- 3%) and after ANH with 6% hydroxyethyl starch (mol. wt. 200000 / 0.5) to hct 20 +/- 1%. After completion of the protocol, splanchnic organs were removed and dissected into small samples according to anatomical and functional principles. Regional perfusion was determined based on the microsphere content of each sample. Hepatic, intestinal, and pancreatic blood flow increased with ANH. Hepatic arterial blood flow rose by 86%, whereas portal venous perfusion increased by 28%. Small intestine mucosal perfusion was augmented by 68% while the non-mucosal tissue compartment of the gut wall received 32% more blood flow after ANH which is in proportion to the increase in cardiac index after ANH. This redistribution of intestinal flow might be the basis for the preservation of tissue oxygenation during moderate isovolemic anemia.

Animals↗
PubMed1997

Effects of hemodilution on splanchnic perfusion and hepatorenal function. II. Renal perfusion and hepatorenal function.

Hepatorenal perfusion and function were assxssed in 22 dogs undergoing acute normovolemic hemodilution (ANH) to a hematocrit (Hct) of 20% using 6% hydroxyethyl starch (200.000/0.5) as the diluent. Organ perfusion was determined with the radioactive microspheres method. Renal function was assessed by urinary output, creatinine clearance and fractional sodium excretion. Blood volume as well as hepatic function were derived from indocyanine green (ICG) dilution kinetics. Hepatocellular integrity was determined by serum enzymatic activity of glutamate-oxalacetate-transaminase (GOT) and glutamate-pyruvate- transaminase (GPT). ANH to Hct 20% did not change blood volume and mean aortic pressure, while heart rate was slightly elevated (p<0.05) by 5 beats per minute and cardiac output increased by 29% (p<0.05). In contrast to the liver, where arterial and portal venous blood flow increased (86% and 28%, respectively; p<0.05), total renal blood flow as well as intraorgan distribution of renal blood flow remained unchanged post-ANH. While creatinine clearance remained unchanged following ANH, urinary output and fractional urinary excretion increased (p<0.05). In response to enhanced hepatic blood flow after ANH, intravascular half-life of ICG was reduced (p<0.05) and ICG clearance increased (p<0.05). Serum enzymatic activity of GPT decreased upon ANH (p<0.05), while GOT activity remained unchanged. ANH to a Hct 20% does not impair hepatorenal function. Increased urinary output points out the necessity for proper adjustment of crystalloid infusion to maintain normal intravascular volume and avoid hypovolemia and the associated risk of tissue hypoxia.

Animals↗
PubMed1997

[Avoidance of homologous blood transfusion despite extreme blood loss].

We report the case of a 22-year-old woman who underwent two-step scoliosis surgery without allogeneic transfusion, although the intraoperative blood loss (3500 ml) during the first procedure was higher than the calculated blood volume (3250 ml). Preoperatively the patient had donated four units of autologous blood. Intraoperatively blood-saving methods were combined. During the first operation acute normovolemic hemodilution (target hemoglobin 9.0 g/dl) was applied and during the second operation controlled hypotension (systolic blood pressure 80 mmHg). Intraoperative auto-transfusion was used in both procedures. During the first operation severe normovolemic anemia (minimal hemoglobin 3.5 g/dl) was accepted while the patient was ventilated with FiO2 1.0. The hemoglobin concentration was 8.6 g/dl after the first procedure and had increased to 11.6 g/dl 4 weeks after the second procedure. No severe complications occurred during the postoperative phase. This case report shows that also in surgical procedures with extreme blood loss any allogenic transfusion can be avoided by the combination of blood-saving methods, acceptance of low intraoperative transfusion trigger and ventilation with 100% oxygen.

Adult↗
PubMed1997

A tool for balancing activity from isotopes used for the radioactive microsphere method.

The radioactive microsphere method for determination of regional organ blood flow is widely used in experimental studies. The measurement error of this method in part depends on balanced activities from the set of nuclides used. Achieving even distribution of half-life corrected activity is tedious due to the many calculations needed and is limited by minimal and maximal allowable amounts of microspheres per injection. In two experiments we showed that incorrect planning of microspheres numbers can lead to invalidation of results. Therefore, we developed a program that allows optimization of half-life corrected activities and tested it on an experimental series of 16 dogs. Despite large discrepancies of specific activities of nuclides, storage times and half-lives, balancing activities with the program succeeded: on the average, the accumulated gamma spectra consisted of 22.3 +/- 6.9 85Sr, 18.9 +/- 6.8 141Ce, 10.7 +/- 6.2 51Cr, 23.9 +/- 6.7 95Nb, 16.9 +/- 7.2 46Sc, and 7.3 +/- 2.7% 114mIn radiation, respectively.

Animals↗
PubMed1997

Effect of hypertonic saline/dextran on post-stenotic myocardial perfusion, metabolism, and function during resuscitation from hemorrhagic shock in anesthetized pigs.

Resuscitation using small volumes of hypertonic saline solutions normalizes cardiac output without fully restoring arterial pressure. This study compared the efficacy of either 7.2% saline/10% dextran 60 (HSDex) or the identical sodium load of normal saline (NS) to improve regional myocardial blood flow (MBF), contractile function, and oxygen metabolism in the presence of a critical coronary stenosis. Fourteen anesthetized, open-chest pigs (25 +/- 3.6 kg) were instrumented to assess left anterior descending coronary artery (LAD) flow, post-stenotic oxygen, and lactate metabolism, regional myocardial segment shortening (SS, sonomicrometry), and MBF (radioactive microspheres). After implementation of a critical LAD-stenosis, shock was induced by hemorrhage (mean arterial pressure (MAP) 45-50 mmHg for 75 min). Resuscitation was started by infusion (2 min) of either HSDex (n = 7,10% of blood loss) or NS (n = 7, 80% of blood loss); 30 min later 6% dextran 60 (10% of blood loss) was administered in both groups. The LAD-stenosis did not affect myocardial metabolism, SS, or MBF at rest. After hemorrhage, MBF remained unchanged from baseline in non-stenotic but decreased by 53% in post-stenotic myocardium (p < .05). The endo-epicardial flow ratio fell below 1.0 in both areas. SS decreased by 10-15% only in post-stenotic myocardium (p < .05). Resuscitation with both HSDex and NS restored cardiac index (CI) but not MAP. MBF increased above baseline values with either solution in non-stenotic while it remained at shock levels in post-stenotic myocardium, where ischemia persisted as evidenced by lactate production and depressed SS. Neither in non-stenotic nor in post-stenotic myocardium was the epi-endocardial flow ratio normalized upon resuscitation with HSDex or NS. We conclude that in the presence of a flow-limiting coronary stenosis, initial fluid resuscitation with both HSDex and the identical sodium load of NS failed to restore perfusion pressure, redistributed MBF in favor of normally perfused myocardium, and did not reverse ischemia in post-stenotic myocardium.

Animals↗
PubMed1997

Myocardial blood flow heterogeneity in shock and small-volume resuscitation in pigs with coronary stenosis.

Myocardial blood flow heterogeneity in shock and small-volume resuscitation in pigs with coronary stenosis. J. Appl. Physiol. 83(6): 1832-1841, 1997.-We analyzed the effects of shock and small-volume resuscitation in the presence of coronary stenosis on fractal dimension (D) and spatial correlation (SC) of regional myocardial perfusion. Hemorrhagic shock was induced and maintained for 1 h. Pigs were resuscitated with hypertonic saline-dextran 60 [HSDex, 10% of shed blood volume (SBV)] or normal saline (NS; 80% of SBV). Therapy was continued after 30 min with dextran (10% SBV). At baseline, D was 1.39 +/- 0.06 (mean +/- SE; HSDex group) and 1.34 +/- 0.04 (NS group). SC was 0.26 +/- 0.07 (HSDex) and 0.26 +/- 0.04 (NS). Left anterior descending coronary artery stenosis changed neither D nor SC. Shock significantly reduced D (i.e., homogenized perfusion): 1.26 +/- 0.06 (HSDex) and 1.23 +/- 0.05 (NS). SC was increased: 0.41 +/- 0.1 (HSDex) and 0.48 +/- 0.07 (NS). Fluid therapy with HSDex further decreased D to 1.22 +/- 0.05, whereas NS did not change D. SC was increased by both HSDex (0.56 +/- 0.1) and NS (0.53 +/- 0.06). At 1 h after resuscitation, SC was constant in both groups, and D was reduced only in the NS group (1.18 +/- 0.02). We conclude that hemorrhagic shock homogenized regional myocardial perfusion in coronary stenosis and that fluid therapy failed to restore this.

Acid-Base Equilibrium↗
PubMed1996

Aerosol production and aerosol droplet size distribution during mechanical ventilation (IPPV) with a new ultrasonic nebulizer.

Administration of drugs via the airway is increasingly practiced in ICU- and surgical patients. For this purpose, aerosols may be produced by either jet nebulization or ultrasonic droplet generation. In mechanically ventilated patients, aerosol delivery is often insufficient. The influence of the ventilatory pattern on nebulizer efficacy is poorly understood. In the present in vitro study we determined the efficacy of a new ultrasonic nebulizer in delivering aerosolized epoprostenol using defined ventilator settings. We determined aerosol delivery rates, the aerosol droplet size distribution and the impact of the connection tubing on drug delivery, applying adult and infant ventilation patterns. Aerosol production rates ranged from 0.28 to 0.57 ml per minute. Using an adult ventilator setting volume controlled ventilation (CMV) led to a higher aerosol production rate than pressure controlled ventilation (PCV) at identical tidal volumes and mean airway pressures (0.57 ml/min,CMV vs 0.39 ml/min, PCV). With an infant ventilator setting, nebulizer rates were lower than those found for the adult ventilator setting, but did not differ substantially between CMV and PCV mode (0.29 ml/min, CMV vs 0.28 ml/min, PCV). Aerosol delivery rates distal to the endotracheal tube changed according to aerosol production rates (adult mode: 0.18 ml/min, CMV vs 0.10 ml/min, PCV; infant mode: 0.03 ml/min, both CMV and PCV). In the infant ventilation mode, a higher percentage of the aerosol was trapped in the catheter mount as compared to the adult ventilation mode. Mass median droplet diameters for each of the four ventilator settings were almost identical (4.63 to 5.09 micron) and smaller than indicated in the product specifications (8 micron). Delivery rates and sizes of droplets delivered by the new ultrasonic nebulizer SUN 345(R) agree well with previously reported data from comparable settings using diverse nebulizer devices.

Adult↗
PubMed1996

Eight hours' inhalation of prostacyclin (PGI2) in healthy lambs: effects on tracheal, bronchial, and alveolar morphology.

OBJECTIVE: To study potential toxic effects of long-term (8 h) inhaled prostacyclin (PGI2) on respiratory tract tissues. DESIGN: In a prospective, randomized order, either PGI2 (n =7) or normal saline (n = 7) was aerosolized during a time period of 8 h in healthy lambs. SETTING: Institute for Surgical Research of the Ludwig-Maximilians University of Munich. ANIMALS: 14 health, anesthetized, ventilated lambs. INTERVENTIONS: All animals were endotracheally intubated followed by tracheotomy. PGI2 solution or normal saline was administered with a jet nebulizer (delivery rate 4-10 ml/h; mass median diameter of aerosol particles 3.1 microns). MEASUREMENTS AND RESULTS: Histomorphological changes after 8-h inhalation of PGI2 solution were compared to those after 8-h inhalation of normal saline. Tracheal and bronchoalveolar tissues were examined by light and electron microscopy in order to assess tissue damage induced by inhaled PGI2. Pathological changes were ranked by a blinded observer following a graduation system ranging from "absence of pathological changes" to "maximal pathological changes". Abnormalities were restricted to the trachea (focal flattening of the epithelium, loss of cilia, slight inflammatory cell infiltration) and alveolar tissue (focal alveolar septal thickening with slight inflammatory cell infiltration), but no statistically significant differences between the PGI2 and control groups were encountered. CONCLUSION: Our findings indicate the absence of PGI2 aerosol-related respiratory tissue damage after 8-h inhalation of PGI2.

Aerosols↗