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Biomedical subjects

N Hugo

Publications and source records attributed to N Hugo.

At least 37 records · Page 2Linked to original sources

Comparative myocardial imaging in the baboon with 123I-labelled ortho and para isomers of 15-(iodophenyl)pentadecanoic acid (IPPA).

The use of various animal models for researching radioiodinated fatty acid cardiac metabolism has been proven to be risky. This fact is here confirmed in the higher primate. Six baboons were injected on different occasions with 123I-labelled para and ortho isomers of 15-(iodophenyl) pentadecanoic acid (123I-pPPA and 123I-oPPA, respectively) for dynamic scintigraphy, followed by a Na123I injection at 30 min for blood background correction. Times for maximum myocardial tracer uptake (Tmax), and half-times of clearance (two phases T1/2(1) and T1/2(2)) from biexponential fitting of the time-activity curves proved statistically not different for pPPA and oPPA (P > 0.05). A repeat study at a later stage on the same baboons included pretreatment (2 h pretracer) with a carnitine palmitoyl transferase I inhibitor (Extomoxir; 10 mg kg-1) to block myocardial beta-oxidation. Time-activity curves with Tmax, T1/2(1) and T1/2(2) followed as above and were compared to the initial uninhibited values. Blocking of the carnitine shuttle was demonstrated by significantly increased retention of 123I-pPPA and 123I-oPPA. Thus both the tracers are beta-oxidized in the baboon myocardium, which is different in rat and human studies. In rats both isomers wash out from the myocardium, but 123I-oPPA is not metabolized. In humans the 123I-pPPA is beta-oxidized as with rats, but the 123I-oPPA is retained in the lipid pool of the myocardium. Simultaneous multiple consecutive gated blood pool studies (six of 1 min each) provided encouraging perfusion-related, background corrected images, and corresponding uptake information.

Animals↗

Gated blood pool SPECT and phase analysis to assess simulated Wolff-Parkinson-White syndrome in the baboon.

This study assesses the diagnostic potential of a tomographic technique with phase analysis to detect premature electroventricular contraction patterns simulated by pacing in the baboon. The data of gated SPECT were analysed by backprojection of the Fourier coefficients, followed by angulation and integration to thick slices of the entire ventricular mass yielding separate ventricular contraction patterns in three perpendicular views. Electrodes were implanted in each baboon: at the sinoatrial node; posterior, left ventricular; anterior left ventricular; on the left and the right lateral ventricular walls. The atrium was stimulated throughout at a fixed rate. Subsequent ventricular stimuli followed during the QRS complex, such to invoke the appearance of pre-excitation QRS morphology. The first points of activation (FPA) from this algorithm were correctly detected for the RV, for the anterior and posterior sites, although the latter two manifested first points in the RV. LV pacing manifested also as a FPA in the RV, but was followed by a true subsequent point in the LV.

Algorithms↗

Drug effects on cerebral blood flow in the baboon model--acetazolamide and nimodipine.

The sensitivity of the baboon model under anaesthesia for single photon emission computed tomography (SPECT) of the brain with 99mTc-HMPAO, as recently developed by us to study cerebral blood flow patterns, was investigated using drugs that are known to increase cerebral blood flow, e.g. acetazolamide, the carbonic anhydrase inhibitor and nimodipine, the calcium channel blocker. Increases in cerebral blood flow for both acetazolamide and nimodipine were observed that correspond well with other studies. Statistically significant regional specificity was noted for acetazolamide and nimodipine. Interestingly a combination of these drugs did not enhance cerebral blood flow but rather decreased it in comparison with the individual drug responses. The results were correlated with arterial blood pressure, heart rate, pCO2 and pO2. A blood pressure decrease was noted for both drugs, while acetazolamide had a marked influence on pO2. The results indicate that the baboon model is sensitive for evaluation of drug effects on cerebral blood flow.

Acetazolamide↗

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↗