Reduced febrile responses to peripheral and central administration of pyrogen in aged squirrel monkeys.

There is long-standing controversy as to whether fever capacity is reduced in aged man. Although loss of this cardinal sign of disease would be an impediment to diagnosis and treatment, there has been no previous research on altered febrile responses using aged primate models. In the present experiments the febrile reaction to IV Salmonella typhosa endotoxin was reduced in monkeys over 14 years old and in one-third of those 10-14 years of age compared with that of younger animals. In response to injections of endotoxin into the lateral cerebral ventricle (ICV), animals over 10 years old showed small or no fevers. Injections of probenecid (ICV), an inhibitor of central inactivation of leukocytic pyrogen and prostaglandin, augmented fever caused by IV and ICV endotoxin and hyperthermia caused by ICV PGE2 in animals under 10 years of age. However, in older animals probenecid increased fever caused by ICV endotoxin only, although the increased response was still less than one quarter that of younger animals. The results indicate that old squirrel monkeys have decreased febrile responses that may be traced to alterations in central sensitivity to pyrogens.

Hypothermia produced by peripheral and central injections of chlorpromazine in aged rabbits.

Hypothermia produced by IV administration of chlorpromazine (CPZ, 0.5-2.0 mg/kg) in a thermoneutral environment was greater in rabbits 2-4.5 years old than in animals under 24 months of age. One microgram CPZ given intracerebroventricularly (ICV) produced greater hypothermia in the older animals in tests performed in a thermoneutral environment while 0.25 and 0.5 microgram doses did not. The hypothermogenic effect of all three ICV doses of CPZ was enhanced in older rabbits exposed to cold. The brain of the older rabbit appears to be more sensitive to the hypothermogenic effects of CPZ. The findings suggest that this widely used tranquilizer can contribute to accidental hypothermia of the aged.

Computer analysis of cardiovascular parameters.

A computer program is described for the analysis of several cardiovascular parameters frequently measured or derived in the chronically instrumented dog model. Data are stored on magnetic tape and are subsequently analyzed with the Apple IIe microcomputer equipped with the ADALAB (Interactive Microware, Inc.) analog-to-digital convertor. Not limited to the chronically instrumented animal model, the program is capable of analyzing left ventricular pressure, three channels of regional myocardial segment length, coronary flow velocity as measured by the Doppler ultrasonic flow technique, and two channels of systemic arterial pressure. Derived data include: left ventricular dP/dtmax, left ventricular pressure-heart rate product, left ventricular ejection time, tension time index; percent segment length shortening and velocity of shortening, dL/dt(s)max, regional stroke work and power, duration of systole and diastole; mean coronary flow velocity, peak diastolic and systolic flow velocity, and true mean systemic arterial pressure.

Microcomputer-based analysis of cardiovascular indices.

A microcomputer-based program has been developed which performs rapid and accurate acquisition of cardiovascular data from instrumented animals or isolated perfused hearts with concurrent analysis and display of the hemodynamic indices. The system allows real-time viewing of the data in four alternative graphic displays. These include: (1) a strip-charge type display of all channels; (2) a full screen display of any single channel; (3) display of pressure-segment length; and (4) trend graphs (cumulative change with time) of calculated hemodynamic indices such as heart rate, systolic and diastolic blood pressure, percent change in myocardial segment length, mean blood flow and percent change in arterial diameter. Precise analysis of both transient and steady-state events may be performed on any segment of data stored on the hard disk. The data at any point in the experiment may be accessed by cursoring through any trend graph of the derived indices, by recalling special event markers or by using the automatic time markers. The calculated results are printed and stored in ASCII files which can be transferred to spreadsheets, databases, graphics or statistical programs.