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Biomedical subjects

T F Doyle

Publications and source records attributed to T F Doyle.

36 records · Page 2Linked to original sources
PubMed1976

Role of histamine in posttraumatic spinal cord hyperemia and the luxury perfusion syndrome.

The authors studied the effect of pretreatment of monkeys with antihistamines on hyperemia observed in the lateral funiculus of the spinal cord after severe experimental spinal cord trauma. After administration of Chlorpheniramine and Metiamide, the spinal cords were traumatized with a 600 gm-cm injury. Blood flow in the lateral funiculus at the injury site was then determined hourly for 6 hours. The blood flow at this site remained in the normal range at all times in all animals. Neither a hyperemia nor an ischemia could be demonstrated. This finding reaffirms the authors' previous observation that ischemia does not exist in the lateral funiculus after severe experimental spinal cord trauma, and explains the previous observation of hyperemia as a histamine-related phenomenon, easily blocked by the administration of Chlorpheniramine and Metiamide, potent antihistamines which together block both the H1 and H2 receptor sites.

Animals↗
PubMed1976

Effect of intracisternal phentolamine on cerebral blood flow after subarachnoid injection of blood.

The hydrogen clearance method was used to measure total and focal cerebral blood flow (CBF) in the monkey before and for 5 hours after a simulated subarachnoid hemorrhage (SAH). Some monkeys also received 0.2 to 1.0 mg/kg phentolamine intracisternally 3 hours after SAH. Results show that SAH did not change cerebrovascular resistance, but as cerebral perfusion pressure decreased, CBF fell transiently. Phentolamine injected intracisternally 3 hours after SAH produced a significant fall in arterial blood pressure; cerebrovascular resistance did not change but CBF decreased significantly. These data indicate that intracisternal phentolamine cannot be considered potentially useful to treat ischemic encephalopathy after SAH.

Animals↗
PubMed1976

Preserved autoregulation in the rhesus spinal cord after high cervical cord section.

The authors studied the effect of high cervical cord section on the phenomenon of autoregulation in the rhesus monkey with the hydrogen clearance method to measure focal spinal cord blood flow (SCBF). Laminectomies were performed at T7-11 and C1-2. The spinal cord was completely severed at C1-2. Under normocapnic conditions, SCBF was then measured in the thoracic spinal cord over a wide range of blood pressures (MAP). The MAP was either lowered by bleeding or raised by the intravenous infusion of angiotensin. Autoregulation was found to be intact between 50 and 125 mm Hg, following a pattern similar to the one observed in the intact animal.

Animals↗
PubMed1976

The effect of antihistamines on experimental posttraumatic edema of the spinal cord.

The present experiments were designed to test the effect of antihistamines on the formation of post-traumatic edema of the spinal cord. Ten rhesus monkeys received 600 gm cm injuries to the T10 level of the spinal cord. Five animals received antihistamine treatment and five animals acted as untreated controls. Posttraumatic edema was estimated using radio-active tagged serum albumin. A significant increase in radioactivity of the injured segment was demonstrated in both groups when compared to noninjured issue, but no difference was demonstrated in the radioactivity of the injured segment in the treated versus the nontreated group.

Animals↗
PubMed1976

Further studies on histamine in spinal cord injury and post traumatic hyperemia.

Using the hydrogen clearance method, focal spinal cord blood flow was measured in the lateral funiculus of Rhesus monkeys traumatized with a 600 gm cm injury to T10, pretreated with either chlorpheniramine or metiamide. The blood flow in the chlropheniramine treated animals either rose slightly or remained in the normal range. That in the metiamide treated animals remained in the normal range at all times in all animals. On the basis of these results we can further define the previously observed post traumatic lateral white matter hyperemia as mainly an H2 histamine related phenomenon.

Animals↗
PubMed1975

Autoregulation of spinal cord blood flow.

The response of SCBF to changes in pACO2 was tested in Rhesus monkeys under normotensive conditions. A sigmoid shaped response was demonstrated. At a pACO2 of 10 to 50 mm. Hg, SCBF remained constant and in the normal range. As the pACO2 was raised from 50 to 90 mm. Hg, SCBF increased. Further increases in the pACO2 above 90 mm. Hg failed to effect further changes in SCBF. We conclude from these data that SCBF is somewhat less responsive than CBF to changes in pACO2. Next, the effect of changes in MAP on SCBF was studied under normocapnic conditions. SCBF remained constant and in the normal range with an MAP of 50 to 135 mm. Hg. Above 135 mm. Hg, SCBF rose with further increases in MAP. With decreases in MAP below 50 mm. Hg, SCBF fell passively. It is our conclusion that autoregulation exists in the lateral white matter of the spinal cord and follows a pattern similar to that suggested for the cerebrum.

Animals↗
PubMed1975

Local spinal cord blood flow in experimental traumatic myelopathy.

Focal blood flow was measured in the lateral funiculus and center of the spinal cord in the rhesus monkey both before and after a 600 gm-cm injury at T-10. Measurements made by the hydrogen clearance technique showed that blood flow in the lateral funiculus more than doubled within 4 hours after injury, returned to normal by 8 hours, and remained in the normal range for 24 hours. At no time was a hypoperfusion in the lateral funiculus present. Blood flow in the center of the spinal cord, at the level of the lesion, began to fall within 1 hour following injury and continued to fall for 4 hours. These data challenge the notion that spreading ischemia of the white matter is an important factor in the pathophysiology of experimental spinal cord injury.

Animals↗
PubMedDate not supplied

Response of cerebral circulation to topical histamine.

To study the effect of histamine (HA) on brain blood flow and capillary permeability, bilateral parietal craniectomies were made in cats anesthetized with nitrous oxide and ketamine. The dura was removed and solutions of HA in mock cerebrospinal fluid (CSF) in varying concentrations ranging from 10(-5) M to 10(-1) M were irrigated continuously onto the exposed brain while local cerebral blood flow was determined polarographically by hydrogen clearance. Capillary permeability was assessed by determining HA's effect on the 125I-albumin space of the brain. Electrical activity was monitored by electrocorticography. HA consistently dilated pial blood vessels and produced within 15 min a dose-related local hyperemia that subsided 30--60 min after HA was removed. Hyperemia was blocked by cimetidine. HA had no appreciable effect on either the blood-brain barrier to albumin or the electrical activity of the cortex. HA is pharmacologically capable of participating directly in the acute hyperemic response of the brain's microcirculation to physiologic and pathologic stimuli but has little effect on cerebrovascular permeability to protein.

Animals↗
PubMedDate not supplied

Estimating total cerebral blood flow from the initial slope of hydrogen washout curves.

An initial slope index of total cerebral blood flow, measured by the hydrogen clearance technique, shows a high correlation with flows calculated by bicompartmental analysis. In 247 flow measurements done on 41 rhesus monkeys, a linear regression analysis between these two methods of calculating flow shows a correlation coefficient of 0.928 with a standard error about y values of plus or minus 7.63. The initial slope index is not only faster but does not require that a steady state be maintained for ten minutes.

Animals↗
PubMedDate not supplied

The effect of a simulated subarachnoid hemorrhage on cerebral blood flow in the monkey.

The hydrogen clearance method was used to measure local and total cerebral blood flow (CBF) in the rhesus monkey before and for five hours after a simulated subarachnoid hemorrhage (SAH). CBF remained stable after SAH unless SAH was associated with a fall in cerebral perfusion pressure. In addition, cerebrovascular resistance did not increase after SAH. These results suggest that vasoactive agents in fresh whole blood, and the arterial spasm they produce when added to cerebrospinal fluid (CSF), play only a limited role in the pathogenesis of ischemic encephalopathy that follows an SAH.

Animals↗
PubMedDate not supplied

Effect of topically applied serotonin on local cerebral blood flow.

It has been hypothesized that acute lesions of the brain enlarge through an autodestructive process. Serotonin (5HT), a potent cerebral vasoconstrictor, is believed by some to mediate the process by reducing cerebral blood flow (CBF) in tissue surrounding the lesion. The hypothesis was tested in cynomologus monkeys anesthetized with ketamine and nitrous oxide. Craniectomies, 7 mm in diameter, were performed in each parietal area. The dura was opened and polarographical electrodes of thin platinum wire were inserted into the parietal lobe cortex of each hemisphere. Mock cerebrospinal fluid (CSF) was irrigated continously onto the brain surrounding the electrodes, from which local CBF was determined repeatedly by the hydrogen-clearance technique. After baseline CBF was established, solutions of 5HT in mock CSF (in concentrations of 5 X 10(-7) M, 5 X 10(-5) M, and 5 X 10(-3) M) were irrigated onto one hemisphere while the opposite hemisphere served as control. 5HT failed to change CBF. Although 5HT is a potent vasoconstrictor, under physiologic conditions it apparently is unable to effect hemodynamically significant constriction of the peripheral cerebral vasculature of the anesthetized monkey brain.

Administration, Topical↗
PubMedDate not supplied

Cerebral blood flow in the monkey after focal cryogenic injury.

A focal cryogenic lesion was made in the left superior frontal gyrus of the anesthetized macaque brain. Cerebral blood flow (CBF) was determined by the hydrogen clearance technique before and during the 4 hours following trauma. Local CBF in tissue adjacent to the lesion increased in the first half hour after the lesion was made and then decreased during the ensuing 3 1/2 hours. Local CBF in the contralateral superior frontal gyrus, as well as total CBF and oxygen consumption, were unchanged by cryogenic trauma. The spread of vasogenic edema into uninjured tissue probably accounts for the observed decrease in local CBF. This experimental model may assist in discovering therapy to alter favorably the spatial and temporal profile of pathologic CBF changes in tissue surrounding an acute lesion of the brain.

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