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R P Forsyth

Publications and source records attributed to R P Forsyth.

At least 19 recordsLinked to original sources

Computer programs for the radioactive microsphere technique. Determination of regional blood flows and other haemodynamic variables in different experimental circumstances.

Computer programs in FORTRAN IV have been designed to calculate regional blood flow values from injections of gamma radiation-emitting radioactive microspheres. The first program PRSO constitutes a file containing the names of organs, organ groups and systemic haemodynamic variables and data about the isotopes in use. The second program PRSI transfers the data of the particular experiment concerning protocol, systemic haemodynamic variables, organ weights, number of vials belonging to each organ and the radioactivity from each vial into a data file that is subsequently analyzed by the third program PRSII. One of 5 data conditions which later directs calculations in PRSII is determined by PRSI. PRSII deducts background radioactivity, decomposes the spectrum from the mixture of up to 6 nuclides using the "stripping' method, and corrects for isotope decay during the counting period. Depending upon the data condition, PRSII calculates one or more of the following variables: (i) cardiac output (CO); (ii) the distribution of CO; (iii) regional blood flow values and tissue vascular resistances; (iv) the distribution of blood flow within an arterial bed; (v) arteriovenous anastomotic blood flow; (vi) some specified systemic haemodynamic variables; and (vii) blood flow ratios. The systemic and regional haemodynamic data belonging to experiments are saved for later statistical analyses (e.g., mean, standard error of the variables, changes from the base line, comparison between two groups of experiments) by other programs. PRSO, PRSI and PRSII can be operated by investigators with little or no special training in computer use.

Animals↗

Regional and systemic haemodynamic changes evoked by 5-hydroxytryptamine in awake and anaesthetized rabbits.

The radioactive microsphere method has been used to study the effects of the infusions of 5-hydroxytryptamine (5-HT) on cardiac output and its distribution in both pentobarbital-anaesthetized and conscious rabbits. Doses of 5 and 10 microgram kg-1 min-1 caused progressive decreases in diastolic pressure and total peripheral resistance in the anaesthetized rabbits but not in conscious ones. There was no significant effect on systolic pressure, cardiac output or heart rate. However, in spite of minimal systemic changes, in both groups 5-HT evoked increases in blood flow to the brain, heart and stomach at the expense of the kidneys, skin, liver (hepatic artery) and lungs (bronchial artery plus arteriovenous anastomotic flow). The 10 microgram kg-1 min-1 dose at 5-HT also increased blood flow and decreased resistance in the extracerebral tissues of the head. The significance of these findings in relation to the possible role of 5-HT in the migraine syndrome has been discussed.

Anesthesia↗

The influence of methysergide on 5-hydroxytryptamine-induced changes in regional distribution of blood flow.

Systemic and regional haemodynamic variables were measured at the baseline and after saline or 5-HT infusions (5 microgram kg-1 min-1, i.v.) or methysergide injections (0.5 mg kg-1, i.v.). Cardiac output and its complete distribution were measured by the radioactive microsphere (15 micrometer diam) technique. Although 5-HT did not change the systemic variables, methysergide caused a moderate increase in systolic and mean blood pressure and heart rate. 5-HT caused a substantial increase in gastric and a moderate increase in cerebral and myocardial blood flow at the expense of that to the lungs (arteriovenous shunt + bronchial flows), kidneys and skin. While methysergide was able to reduce the vascular responses to 5-HT in stomach, skin, kidneys, heart, lungs and brain, the drug itself, like 5-HT, decreased the number of microspheres reaching the lungs. Since a large number of 15 micron microspheres can escape through the arteriovenous anastomoses to lodge in the lungs it seems likely that both 5-HT and methysergide can reduce the 'non-nutrient' flow through these anastomoses.

Animals↗

Hemodynamic effects of systemic and central administration of alpha-methyldopa.

Systemic and regional hemodynamic changes were measured in five restained conscious rhesus monkeys before and after a 2-hour intravenous infusion of 50 mg/kg of alpha-methyldopa and, in another group of five monkeys, 5 to 10 mg injected into a lateral cerebral ventricle. Both routes of administration evoked similar degrees of hypotension, bradycardia and decreased cardiac output, although the cerebral intraventricular (i.c.v.) injections had more immediate and long-lasting effects. Both groups had a similar pattern of changes in the redistribution of cardiac output and blood flow that lasted at least 4 hours. Blood flow was maintained in the hepatic and renal arteries and decreased in skeletal muscle, heart, brain and skin. In contrast, i.c.v. injections of alpha-methyldopamine and alpha-methylnorepinephrine given at the same site evoked dose-related pressor responses that lasted up to 4 hours. The data suggest that alpha-methyldopa has important central action that inhibits sympathetic outflow, but that its hypotensive effect is either mediated only by endogenously formed metabolites or that its mechanism of action is not directly related to these metabolites at sites around the lateral and third cerebral ventricles in the monkey.

Animals↗

Hemodynimic effects of systemic and central administration of clonidine in the monkey.

Systemic and regional hemodynamic changes were measured in restrained, conscious rhesus monkeys with indwelling arterial and venous catheters before and after clonidine (5 and 15 mug/kg) was slowly infused intravenously or smaller doses (2 mug/kg) were injected into a lateral cerebral ventricle. Dye-dilution cardiac outputs and the complete distribution of cardiac output were obtained intermittently with the use of the radioactive microsphere method. After the higher intravenous dose and the intraventricular injection, systemic arterial pressure was significantly lowered for 30-45 min. Both of these groups had similar changes in the redistribution of cardiac output and blood flow that outlasted the hypotensive period. Blood flow was maintained or increased in the hepatic and renal arteries at the expense of skin; flow to skeletal muscle and brain also decreased during the first hour. These data support previous studies that indicate that the primary action of clonidine is in the central nervous system and, in addition, add new information about the regional blood flow changes evoked by clonidine.

Animals↗

Metabolic disposition and cardiovascular effects of methyldopate in unanesthetized rhesus monkeys.

Methyldopate, the ethyl ester hydrochloride salt of alpha-methyldopa (alpha-MD), is used extensively in the treatment of severe hypertension. We have developed a high-pressure liquid chromatographic assay to determine the plasma-time concentrations of alpha-MD after intravenous administration of methyldopate and alpha-MD in the monkey in an effort to evaluate the bioavailability of alpha-MD and the extent of in vivo hydrolysis of the amino ester to the amino acid. The results establish that in this experimental situation methyldopate is not metabolically equivalent to alpha-MD.

Animals↗

Regional blood-flow changes during 72-hour avoidance schedules in the monkey.

Systemic and regional blood-flow measurements were made in five restrained monkeys before and during 72 hours of continuous work on an avoidance schedule. Systemic arterial pressures were elevated throughout the stress, initially owing to an increase in cardiac output, and after 72 hours owing to an increase in total peripheral resistance. Changes in the resistance in skeletal muscle blood vessels were closely related to these changes in total peripheral resistance.

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