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Biomedical subjects

U Herold

Publications and source records attributed to U Herold.

13 recordsLinked to original sources
PubMed1998

Interruption of bronchial circulation leads to a severe decrease in peribronchial oxygen tension in standard lung transplantation technique.

OBJECTIVE: In clinical practice lung transplantation is the only procedure where the transplanted organ is left without its own arterial perfusion. With the interruption of the bronchial arteries the nutritive support is dependent on collateral flow by the pulmonary artery and the oxygen tension of desaturated central venous blood, representing an abnormal physiology. METHODS: To analyze this problem systematically, we used a standard single left lung transplantation model in the pig (n = 12). In accordance with the clinical standard, lung preservation was performed with modified Euro-Collins solution with addition of prostacycline. The duration of ischemia was set to 4 h. Before and after single left lung transplantation tissue oxygen tension in the peribronchial tissue was measured with Licox tissue pO2 microprobes. For validation, the myocardial tissue oxygen tension was recorded simultaneously. The hemodynamic assessment included continuous flow measurement of the left and right pulmonary artery using Transsonic ultrasound flow probes. After transplantation the animals were observed for 4 h. For hypothetic augmentation of collateral blood flow to the peribronchial tissue we administered Nitric oxide (10 ppm) to the ventilation in six pigs (group B). Six pigs (group A) served as a control without the addition of nitric oxide (NO). All pigs were ventilated with a FiO2 of 0.5 resulting in paO2 values between 160 and 200 mmHg. RESULTS: In both groups single lung transplantation led to a significant decrease in peribronchial tissue oxygen tension throughout the observation period. Pre-Tx values of peribronchial tissue oxygen tension (38.31 +/- 6.56 mmHg) decreased to 9.72 +/- 2.55 mmHg in group A and 10.3 +/- 3.61 mmHg in group B after 4 h, which could not be altered by a FiO2 of 1.0 (P < 0.0001). The addition of NO in group B led to a significantly augmented flow in the left pulmonary artery (0.63 +/- 0.31 l/min in group B vs. 0.46 +/- 0.26 l/min group A, P < 0.001) representing 67 vs. 49% of the pre-Tx flow in groups B and A, respectively, but the peribronchial tissue oxygen tension was not influenced (P > 0.05). In both groups A and B, the central venous pO2 did not differ in the postoperative period (41.83 +/- 3.27 mmHg group A vs. 43.26 +/- 2.98 mmHg group B) and was kept in a comparable range to the pretransplantation values (45.23 +/- 3.41 mmHg pre-Tx). CONCLUSIONS: The persistence of a very low peribronchial tissue oxygen tension in the early phase after lung transplantation cannot be influenced by improved pulmonary artery flow and solely relates to the central venous pO2, which cannot be augmented by the addition of NO. This mechanism might be a trigger for anastomotic healing problems, infectious complications and later development of obliterative bronchiolitis (OB).

Animals↗
PubMed1997

Critical illness polyneuropathy: a new iatrogenically induced syndrome after cardiac surgery?

OBJECTIVE: Critical illness polyneuropathy (CIP) is a newly described severe complication after open heart surgery leading to tetraplegia for weeks to months. The purpose of the study was to gather further information on critical illness polyneuropathy developing in patients after cardiac surgery and to evaluate the hypothetical risk factors possibly related to the onset of this neurological disorder. METHODS: From July 1994 to October 1995, 7 out of 1511 patients undergoing open heart surgery developed critical illness polyneuropathy, which was diagnosed on the basis of electromyographic and nerve conduction features. The only common clinical finding was an intensive care unit (ICU) stay beyond seven days, therefore a similar group of 37 patients staying longer than seven days in the intensive care unit during the same period of time was evaluated and retrospectively compared to the 7 patients developing critical illness polyneuropathy. Univariate analysis of several traits was performed to evaluate possible risk factors. RESULTS: 4 Out of 7 patients in the CIP group died, all due to multiple organ failure, in contrast to 3/37 patients in the control group, again due to multiple organ failure. Patients developing CIP were staying significantly longer in the ICU (62+/-3 versus 14+/-8 days, P < 0.01) and had a significantly longer time on ventilator support (50+/-28 versus 7+/-13 days, P < 0.01) The incidence of sepsis was significantly higher in the CIP group than in the control group (85.7 versus 10.8%, P < 0.01). Compared to the control group the proportion of patients receiving corticosteroids (100 versus 10.8%, P < 0.01) and increased dosages of epinephrine and norepinephrine was higher in the CIP group (85.7 versus 35.1%, P < 0.05). Furthermore, the proportion of patients requiring chronic venovenous hemodiafiltration was significantly elevated in the CIP group (85.7 versus 5.4%, P < 0.01). CONCLUSIONS: CIP, despite it's benign nature due to it's spontaneous remission in patients who survive, is a disturbing complication following cardiac surgery which is associated with high mortality, a prolonged stay in the ICU, as well as an extended time on ventilator support. Interventions like chronic hemodiafiltration, the application of corticosteroids and the administration of high doses of catecholamines are more frequent in patients with CIP. Whether this indicates a causal relationship remains to be elucidated.

Adrenergic alpha-Agonists↗
PubMed1995

"Cardioplegia on the contractile apparatus level": evaluation of a new concept for myocardial preservation in perfused pig hearts.

UNLABELLED: The concept of a reversible desensitization of the myocardial contractile apparatus for calcium by 2,3 Butanedione Monoxime (BDM) as a method to improve the myocardium's tolerance to cold ischemia was evaluated in normal pig hearts (n = 14). The results were compared to those obtained after application of Bretschneider's HTK cardioplegic solution. METHODS: Series I) After BDM treatment (concentrations: 0-30 mmol/L) the isometric force output and the intracellular calcium transients (measured using the FURA-2 ratio method) of electrically driven (1 Hz) isolated left-ventricular muscle strips excised from beating pig hearts (n = 14) were recorded simultaneously in order to analyse the mode of action of BDM; Series II) The cardioprotective effects of BDM (30 mmol/L) and Bretschneider's cardioplegic solution (HTK) were compared in a large-animal model: after "in situ perfusion" of pig hearts with either 2000 ml ice-cold BDM solution (30 mmol/L) (n = 7) or 2000 ml HTK (n = 7) the hearts were explanted and stored at 4 degrees C in the same solutions for up to 42 h. The contractile properties of muscle fibres, excised after storage periods of 8, 24, and 42 h from these hearts were analyzed in terms of isometric force development and isotonic shortening. 280 muscle fibres from 14 pigs were used for measurements. RESULTS: Series I) In pig myocardium a dose-dependent reduction of isometric force development was found after BDM application. The shape and the amplitude of the intracellular calcium transient were also affected by BDM. At 30 mmol/L BDM no force development could be elicited despite the presence of an intracellular calcium transient (amplitude < 70% of the control). Series II) Shortening, calcium transient, and force of left-ventricular muscle strips of pig myocardium excised after storage periods for up to 42 h showed complete recovery when BDM was applied. In contrast HTK perfusion allowed complete recovery of these parameters when the storage period did not exceed 6 hours. CONCLUSION: Under the given experimental conditions reversible desensitization of the contractile apparatus for calcium results in a considerable prolongation of the tolerance to cold ischemia in explanted pig hearts. The present study shows that the protective effects of BDM are not only present when isolate muscle fibres were stored (and the extracellular space is large) but also after storage of complete hearts in a solution in a solution containing BDM. Thus BDM may become a useful agent to enlarge the storage period of donor hearts in heart transplatation considerably.

Animals↗
PubMed1993

Increased resistance against shortening in myocardium from recipient hearts of 7 patients transplanted for dilated cardiomyopathy.

UNLABELLED: The contractile behaviour of demembranized atrial and ventricular myocardium of 7 patients transplanted for end-stage heart failure (ESHF) was analyzed. Atrial muscle specimens of patients undergoing coronary artery bypass surgery (n = 9) and pig papillary muscle were used as reference preparations (n = 9). Extreme care was taken for dissection and mounting the muscle fibres (0.3 x 6 mm) in order to keep the passive series compliance small. Calcium sensitivity, cross-bridge cycling rate (estimated by the force-clamping technique and calculation of the shortening velocity at zero load [Vmax]) and isometric force development were measured. Analysis on light- and electronmicroscopic level was carried out. RESULTS: 1) Calcium sensitivity was not altered in ESHF patients; 2) the velocity of the force generating process (cross-bridge cycling rate) was normal in ventricular and reduced in atrial ESHF myocardium, 3) maximum isometric force development was reduced in ventricular, but not in atrial myocardium of ESHF patients, and 4) Vmax was significantly reduced in ventricular and atrial ESHF myocardium (p < 0.0001). Perimysial and endomysial fibrosis was present in ventricular, not in atrial myocardium of ESHF patients. CONCLUSION: A normal cross-bridge cycling rate in left-ventricular ESHF myocardium combined with a decreased capability of muscle shortening indicates the presence of a resistance against shortening localized either on the cross-bridge level or/and due to intra- and pericellular fibrosis. Left-ventricular contractile dysfunction in patients with end-stage heart failure may be related to a normal contractile apparatus contracting within an abnormal intracellular or interstitial environment.

Animals↗
PubMed1992

Contractile behaviour of skinned papillary muscle in mitral valve disease.

The contractile behaviour of Triton-X 100 skinned left ventricular papillary muscle from 19 patients undergoing cardiac surgery for mitral valve stenosis: n = 6, mitral valve incompetence: n = 7, or combined mitral valve disease: n = 6 was analyzed. At supramaximal activation the "vibration induced force clamping technique" was used for isometric analysis of time course and extent of isometric postvibration force recovery. Afterloaded contractions were applied for extrapolation of the maximum shortening velocity at zero load (Vmax). The Calcium sensitivity was analysed by variation of the free EGTA-buffered Calcium concentration at a passive resting force of 2 mN at 26 degrees C. In different types of mitral valve disease the characteristics of isometric force development were unaltered in terms of maximum force development, force per square mm, Calcium sensitivity and the time course of isometric contraction after force clamping. However the capability to shorten as expressed by Vmax was reduced in mitral valve incompetence (3.87 +/- 0.37 ML/s) as compared with mitral valve stenosis (5.29 +/- 0.35 ML/s) or combined mitral valve disease (4.83 +/- 0.51 ML/s). The ratio between the inverse value of Vmax and the time constant of isometric force development after force clamping was significantly different in mitral valve incompetence as compared with other types of mitral valve disease (p < 0.0001). These data argue for the presence of different resistances against shortening in various types of mitral valve disease, due to altered cross-bridge cycling characteristics or to morphological factors.

Adult↗
PubMed1991

Analyzing contractile responses in demembranized pig papillary muscle fibres: the influence of calcium, resting force, and temperature.

The influence of calcium, resting force and temperature on the contractile behaviour in isolated demembranized ("skinned") pig papillary muscle fibers (n = 36) was analysed. Demembranisation excludes the influence of any membrane related processes on the contractile response as the myofilaments are in direct contact with the bathing medium. Resting force (1 mN-9 mN), temperature (22 degrees C or 32 degrees C) and pCa 7.0-4.3 were varied and the contractile response was analyzed by studying the time constant and the extent of post vibration force recovery (PVFR) of the activated preparations (the vibration method). Additional constant-load experiments and detection of sarcomere-length were carried out. There was an inverse-linear relationship between time constants of post vibration force recovery and maximum shortening velocity as estimated by constant load experiments. Resting force affected the extent of force development but not the time constant of post vibration force recovery and modulated the pCa-force relationship without altering the calcium concentration required for half-maximal activation (calcium sensitivity). In contrast lowering the bath temperature from 32 degrees C to 22 degrees C caused a significant leftward shift of the pCa-force relationship potentially due to changes of the contractile filaments' calcium sensitivity. The effect of temperature on the myocardial contractile system is of special interest as hypothermia is frequently used in cardiac surgery. Analysis of alterations of the contractile proteins' calcium sensitivity during the rewarming period of the patient may provide further insight in the pathophysiology of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1991

[A preclinical study of the organ distribution and radiation dosage of radioiodinated iodolisuride].

The distribution in rats of 125I-iodo-lisuride was studied. Three rats each were sacrificed at fixed intervals between 5 min and 24 h p.i., and the radioactivity was measured in isolated organs and parts of the body. The organ distribution and biexponential blood disappearance were similar to values for unlabeled lisuride. The radiation dose was estimated for man assuming a 123I label. The resulting doses were comparable to those from other radiopharmaceuticals in clinical use.

Animals↗
PubMed1982

Allergoprints in horse allergic children.

In order to determine the allergenic activity of five purified horse allergens, 22 children allergic to horses according to history, skin test, and leukocyte histamine release were evaluated. Washed leukocytes from all patients were tested for allergen-induced histamine release utilizing four epidermal horse allergens (Ags 6, 9, 11, and 15) and horse serum albumin. Crossed radioimmunoelectrophoresis was carried out with a standard horse dander extract and serum from each patient. The results showed considerable variation in the individual allergoprints. Ag 11 had the highest mean allergenic activity. Sensitivity to horse serum albumin was demonstrated three times. Our data show that the amount of serum IgE antibodies bound by horse allergens correlates significantly with the capacity of the allergens to induce histamine release from washed leukocytes.

Adolescent↗