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Biomedical subjects

N Hugo

Publications and source records attributed to N Hugo.

At least 19 recordsLinked to original sources

The baboon: an ideal model in biomedical research.

The baboon is a good animal model for research and investigations in physiology and pathophysiology, also using radiopharmaceutical techniques. It has several similarities to the human being, and all parameters in human physiology can be measured in the baboon model with the same or equal technical equipment. Fourier phase analysis in radionuclide ventriculography, hemodynamic reactions in a septic shock model, and investigations in conjunction with local anesthetics (eg, effects on cerebral blood flow) are typical types of research that have been or are currently being performed on the baboon. Institutes using the baboon model must be equipped with all instruments and operating facilities as would be needed for investigations in human beings. Ethical considerations must be regarded strictly and supervised by an ethics committee. Protocols must determine exactly why in vivo experimentation is preferred to in vitro tests. Anesthesia techniques in a baboon model allow study on the animal itself, eliminate pain (and stress) to the animal, and should not interfere with the aims of the investigation being performed.

Animals

In vivo assessment of regional microvascular albumin leakage during E. coli septic shock in the baboon model.

Changes in regional microvascular albumin flux during septic shock were studied noninvasively by scintigraphy in the baboon model. Use was made of an i.v. injection of 99mTc-labeled baboon serum albumin. Count ratios of lung to cardiac, liver to cardiac, and abdominal to cardiac regions were measured two-hourly for 6 hr in six control and six septic shock baboons (live E. coli) and compared. Increased ratios obtained during shock pointed to an increase in extravascular albumin. Linear regression lines fitted to these count ratios provided regional albumin leak indices. These indices demonstrated statistically significant increases (P less than 0.05) during septic shock for the abdominal region during the 6-hr study, and for all regions, but especially the abdomen, when data were calculated over 4 hr. Increasing ratios and leak indices correlated with postmortem data and with changes in neutrophil and platelet behaviour previously established during shock. Possible accompanying mediator releases could be responsible for the endothelial damage leading to the increased permeability.

Animals

The baboon model under anesthesia for in vivo cerebral blood flow studies using single photon emission computed tomographic (SPECT) techniques.

Single photon emission computed tomography of the brain can be useful in animal experimentation directed toward cerebral conditions. A well established and understood baboon model, necessarily under anesthesia, could be especially valuable in such investigations. Six normal baboons were studied under various anesthetic agents and their combinations: ketamine, thiopentone, pentobarbitone, and halothane. Cerebral blood flow (CBF) studies were performed with 99mTc-HMPAO. CBF effects from various anesthesia were detected, requiring careful choice of the anesthesia for cerebral investigations.

Anesthesia

Effect of Pseudomonas aeruginosa-derived pyocyanin and 1-hydroxyphenazine on pulmonary mucociliary clearance monitored scintigraphically in the baboon model.

The effect of products of the bacterium Pseudomonas aeruginosa on mucociliary lung clearance has been monitored in vivo in the baboon model by scintigraphy. Clearance was found to be inhibited by both 1-hydroxyphenazine and pyocyanin, and a dose-effect was illustrated by the former. This confirms previous in vitro results as well as results from work on guinea-pigs, and holds good prospects for the use of the baboon model under anesthesia in such investigations.

Aerosols

In vivo assessment of regional microvascular albumin leakage during E. coli septic shock in the baboon model.

Changes in regional microvascular albumin flux during septic shock were studied noninvasively by scintigraphy in the baboon model. Use was made of an i.v. injection of 99mTc-labelled baboon serum albumin. Count ratios of lung to cardiac, liver to cardiac, and abdominal to cardiac regions were measured every 2 hr for 6 hr in control and septic shock baboons, and compared. Increased ratios obtained during shock pointed to an increase in extravascular albumin. Linear regression lines fitted to these count ratios provided regional albumin leak indices. These indices demonstrated statistically significant increases (P less than 0.05) during septic shock for the abdominal region during the 6-hr study, and for all regions, but especially the abdomen, when data were calculated over 4 hr. Increasing ratios and leak indices correlated with postmortem data and changes in neutrophil and platelet behaviour previously established during shock.

Animals

A baboon model for in vivo assessment of mucociliary lung clearance.

A suitable baboon model (Papio ursinus) for assessing inhibitory effects on mucociliary lung clearance was required. Clearance of various dimensions of nebulized particles (99mTc-labelled) was monitored with the animals (n = 6) under either ketamine or pentobarbitone anaesthesia. The best prospect of substantial and reproducible clearance in spite of the inhibition by the anaesthesia were obtained with pentobarbitone, and using nebulized radiolabelled particles of diameter range between 10 and 45 microns, thus avoiding trapping in the non-ciliary alveoli.

Aerosols

The effect of fluid resuscitation on cardiac function changes monitored by radionuclide ventriculography in the septic shock baboon model.

Dramatic cardiac volume losses accompanied by a drop in arterial pressure and in pulmonary capillary wedge pressure (PCWP) were found to characterise the baboon model in bacterial septic shock. Loss of vascular tone and a probable vascular fluid leak were regarded as contributing factors. To prove this hypothesis an experiment was planned with the baboon model in septic shock, and an added protocol for fluid administration whereby the pulmonary wedge pressure was kept at 7 +/- 2 mm Hg. The six baboons served as their own controls. Raising PCWP by means of fluid loading resulted in an attenuation of the drop in left ventricular volumes, to a smaller decrease in stroke volume (SV) and smaller increases in left ventricular ejection fraction. The drop in arterial pressure remained and left ventricular stroke work therefore reflected the decrease in SV. Compliance as by EDV/PCWP remained unchanged. Fluid loading therefore, although not normalising the haemodynamic parameters, led to smaller changes and an improvement in some measures of cardiac function.

Animals

Left ventricular volume and function changes during beta-blockade and accompanying atrial pacing.

Radionuclide ventriculography was performed at rest and during transoesophageal pacing on nine anaesthetized baboons (Papio ursinus), alternatively with and without administration of a beta-blocker. Left ventricular volumes, cardiac output, and ejection fraction were determined at each heart rate. A gradual decrease in end-diastolic, end-systolic, and stroke volume followed with increasing heart rate, significantly more pronounced under beta-blockade. Cardiac output and ejection fraction showed no significant changes, although tendencies to increase were observed without beta-blockade. Comparisons of these parameter changes were drawn to those previously observed during the first 5 h of septic shock (E. coli). We conclude that the tachycardia present during this phase of shock is not the only contributory factor to cardiac function changes but that other depressant influences prevail as the added effect of the beta-blocker seems to suggest.

Adrenergic beta-Antagonists

Changes in phase analysis patterns of radionuclide ventriculograms obtained from baboons during atrial pacing, septic shock, and induced myocardial infarction.

Changes in intraventricular phase delays, phase angle histograms, amplitude images, and electrocardiograms (ECG) were investigated during oesophageal pacing with and without beta-blockade, after induced myocardial infarction, and during septic shock in the anaesthetized baboon model. Unavoidable triggering from the pacemaker spike and to a lesser extent increased heart rate were responsible for parameter changes during pacing. Myocardial infarction changed contraction patterns, which did not always correlate with conduction changes from the ECG's. Cardiac volume changes during septic shock could be responsible for the abnormal trends in phase angle spread and electrocardiographic data.

Animals

Fourier phase parameters with possible diagnostic importance as obtained from the radionuclide ventriculograms of normal baboons with and without cardiac catheterization and under prolonged anaesthesia.

The possible diagnostic importance of parameters defined from radionuclide ventriculograms and Fourier phase analysis was investigated for data from normal baboons (Papio ursinus) under prolonged anaesthesia (7 hours). Of the 14 animals, 7 were studied using indwelling cardiac catheters. Phase angle differences between the electromechanical activation of the septum and left lateral wall (LLW), and again between the activation of the septum and the apex indicated no significant differences (p greater than 0.05) for the consecutive hourly values for both catheterized and non-catheterized baboons. Consequently, average values and their ranges (mean +/- 1 S.D.) were obtained for these parameters in each group, and they did not differ significantly between the two groups. As could be expected, the activation delays between the septum and LLW, and the septum and apex differed with the latter being significantly longer. The phase angle histogram parameters of atrial peak width, left ventricular plus right ventricular peak width, (LV + RV), LV-to-RV peak separation and LV-to-atrial peak separation were similarly analysed and found not to change significantly between hourly measurements or because of catheterization. Therefore mean normal values and ranges were also obtained for these parameters, possibly to serve as baselines in the diagnosis of subtle conduction pathology.

Anesthesia, General

Evaluation of the clinical validity of the "integral spleen" method of renography analysis from parameter changes induced by pharmacological and surgical intervention.

A set of controlled experimental animal procedures involving pharmacological and surgical interventions was carried out to assess the clinical validity of the parameters calculated by the "integral spleen" method of renography analysis. There appeared to be a good correlation between the observed changes of these parameters and current pathophysiological information. In particular, the described method includes an original calculation of the filtration fraction without blood and urine sampling or a second tracer injection. This calculation was experimentally validated here.

Animals

Atrio-ventricular block in a baboon (Papio ursinus).

Atrio-ventricular (A-V) block occurring in an anesthetized chacma baboon (Papio ursinus) is analysed. Hemodynamic, 12-lead electrocardiographical (ECG), hematological and biochemical parameters were monitored and data before and after block are compared. Though biochemical and other abnormal values were encountered, no conclusive evidence of the cause of the block was found.

Anesthesia, General

Comparison of blood flow parameters measured by Doppler ultrasound and radionuclide techniques in the baboon (Papio ursinus).

Ascending aortic blood velocity was measured in the baboon (Papio ursinus) by using continuous wave Doppler ultrasound. The blood flow parameters thus obtained were compared to those by the standardized radionuclide technique. It appears that, due to the anatomical position of the ascending aorta and brachiocephalic trunks in relation to the ultrasound beam, Doppler ultrasound does not provide an accurate method of measuring aortic blood velocity in the baboon, which could be the reason for the poor correlation of the results from the two techniques.

Animals

Scintigraphic phase analysis of abnormal A-V conduction in a baboon.

During an interventional cardiac investigation on an anaesthetised baboon (Papio ursinus) the animal developed A-V block. Scintigraphic phase analysis leading to quantified intraventricular delays and histogram characteristics pointed to abnormalities which persisted even after A-V block was replaced by nodal tachycardia as was reflected by the electrocardiogram. This indicated towards an increased diagnostic sensitivity with the use of phase analytical methods.

Animals

A positive wave at the J-point of electrocardiograms of anaesthetized baboons (Papio ursinus).

Electrocardiograms were performed on 50 anaesthetized baboons (Papio ursinus). A positive deflection, referred to by us as the H-wave, consistently occurs at the junction between the QRS complex and the S-T segment. The significance of this deflection at the J-point, as the junction is known, is still to be established; however, characterization of the H-wave regarding amplitude and position with respect to the R-wave is done.

Animals