Computer simulation of coronary flow waveforms during caval occlusion.

OBJECTIVES: Mathematical modeling of the cardiovascular system is a powerful tool to extract physiologically relevant information from multi-parametric experiments. The purpose of the present work was to reproduce by means of a computer simulator, systemic and coronary measurements obtained by in vivo experiments in the pig. METHODS: We monitored in anesthetized open-chest pig the phasic blood flow of the left descending coronary artery, aortic pressure, left ventricular pressure and volume. Data were acquired before, during, and after caval occlusion. Inside the software simulator (CARDIOSIM) of the cardiovascular system, coronary circulation was modeled in three parallel branching sections. Both systemic and pulmonary circulations were simulated using a lumped parameter mathematical model. Variable elastance model reproduced Starling's law of the heart. RESULTS: Different left ventricular pressure-volume loops during experimental caval occlusion and simulated cardiac loops are presented. The sequence of coronary flow-aortic pressure loops obtained in vivo during caval occlusion together with the simulated loops reproduced by the software simulator are reported. Finally experimental and simulated instantaneous coronary blood flow waveforms are shown. CONCLUSIONS: The lumped parameter model of the coronary circulation, together with the cardiovascular system model, is capable of reproducing the changes during caval occlusion, with the profound shape deformation of the flow signal observed during the in vivo experiment. In perspectives, the results of the present model could offer new tool for studying the role of the different determinants of myocardial perfusion, by using the coronary loop shape as a "sensor" of ventricular mechanics in various physiological and pathophysiological conditions.

An animal model to detect the neuropsychological toxicity of anticancer agents.

The unexpected discovery that certain chemotherapeutic agents used in the treatment of childhood cancers have neurocognitive side effects has prompted a search for techniques that identify those medications that place children at risk. An animal model for the assessment of resultant neurocognitive toxicity is described which makes use of simple classical conditioning. We have shown that rats learn about environmental events more slowly following neonatal administration of methotrexate. The changes after methotrexate exposure are not related to stimulus characteristics or to perceptual abilities, but rather to damage to the neural systems involved in acquisition, retention, or recall. Similar problems with learning have been observed in children treated with methotrexate. An effective animal model such as the one described here may help detect and avoid antineoplastic agents that produce severe cognitive defects in childhood cancer patients.

An animal model to detect learning deficits following treatment of the immature brain. Studies using radiation and methotrexate.

Learning deficits have been noted in children with acute leukemia given methotrexate (MTX) with and without cranial irradiation (RT) for prophylaxis. A rat model has been developed to assess treatment effects on learning. The test used was altered performance of a simultaneous discrimination task in a standard operant conditioning box, employing the mean number of days needed to score 80% correct responses as the criterion. An illustrative experiment distributed suckling rats among four groups: (1) 36 controls; (2) 14 cranial RT (1,000 R); (3) 14 MTX (5 mg/kg i.p.); (4) 36 RT + MTX 24 h later, and (5) 12 undernourished controls (to match poor weight gain patterns of treated animals). Survivors were tested 10-12 weeks later: values for groups 1-5 in order were 3.9, 4.1, 4.7, 5.0 and 4.0 days. Only group 4 results were significantly different from group 1 (p = less than 0.05).

Syntheses and tissue distribution of 99m-Tc-sulfonylureas.

Four new tolbutamide analogs were prepared and evaluated as hypoglycemics. Hypoglycemic action was observed in two members of the class, and 99m-Tc-chelates were tested as potential radiopharmaceutical imaging agents.