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Biomedical subjects

D A Stump

Publications and source records attributed to D A Stump.

At least 37 records · Page 2Linked to original sources

Dog model for cerebrovascular studies of the proximal-to-distal distribution of sequentially injected emboli.

This study was undertaken to determine whether microemboli injected in a predetermined sequence would maintain that sequence once they came to rest in brain microvessels. If so, the injection of different-colored microspheres at different times could be used to bracket-in-time emboli that are known to be released into the circulation during cardiopulmonary bypass. We injected different-colored microspheres into the arterial circulation of anesthetized dogs before and after the injection of fat emboli and before and after cardiopulmonary bypass. Coronal slices of the dog brains were embedded in celloidin, sectioned at 100 microns, and stained for alkaline phosphatase. The afferent cerebrovasculature stained dark brown against a light background, and the proximal/distal orientation of many of the arterioles could be determined by following their course within the thick sections. When different types of emboli were found in a single arteriole, they appeared in the order injected or the order of occurrence in the bypass protocol in 99.3% of the 867 such arterioles counted. Therefore, the microemboli maintained their ordered sequence with only a very small degree of mixing. Once they came to rest, there was not sufficient collateral blood flow in the brain microvessels to move them into disordered positions. This dog model should facilitate studies of the time of release of microemboli within narrower windows of time during cardiopulmonary bypass.

Animals↗

Brain microemboli associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study.

Emboli in brain tissue after cardiopulmonary bypass were reported in the literature 30 years ago, but there is little objective evidence confirming the presence of emboli in the brain after cardiopulmonary bypass with more modern equipment and techniques. Recently, with alkaline phosphatase vascular staining, we found an acellular fatty material in brain microvasculature from autopsy material of patients who died shortly after cardiopulmonary bypass. These fatty intravascular collections range in diameter from 10 to 70 microns, a size that lodges in the smallest vessels of the microvasculature. They have been found in numbers sufficient to cause detectable neurologic dysfunction and are believed, but not proved, to be emboli. By sequentially injecting colored microspheres, we can determine when emboli occur during experimental cardiopulmonary bypass. In ongoing related studies, magnetic resonance imaging was performed before cardiac valve replacement in 39 patients for whom preoperative and postoperative neurologic and neuropsychologic testing was available. Preliminary results suggest that magnetic resonance imaging evidence of prior stroke is not a significant risk factor for cognitive or motor decrement after cardiopulmonary bypass.

Animals↗

Selection and clinical significance of neuropsychologic tests.

There have been major advancements in cardiac surgery over the past two decades and a concomitant decrease in mortality and major morbidity. The improved safety in cardiac procedures permitted 330,000 operations involving cardiopulmonary bypass in 1992. However, several recent studies have demonstrated that cardiac surgery poses substantial risk of negative neurologic and neuropsychologic outcomes. Although very few patients die as a result of a cardiac operation, more than two thirds of patients demonstrate evidence of neuropsychologic dysfunction postoperatively. The mechanisms contributing to neuropsychologic deficits after cardiopulmonary by-pass are uncertain. To characterize the incidence and severity of such deficits after cardiac operations, a concise battery of neuropsychologic tests that provides reliable evidence of subtle brain trauma is essential. With an objective, valid measure of brain injury, the etiology of neuropsychologic deficits can be identified and either eliminated or the effects ameliorated. The proper selection and use of neurobehavioral tools provides a basis to evaluate the efficacy of surgical and pharmacologic interventions to further improve neurologic outcome after cardiopulmonary bypass.

Brain Diseases↗

Air embolus risk with glass versus plastic syringes: in vitro study and implications for neuroangiography.

PURPOSE: To assess syringe use among neuroangiographers and evaluate air emboli produced with glass and plastic syringes. MATERIALS AND METHODS: Questionnaires on syringes use were sent to 100 members of the American Society of Neuroradiology (ASNR). An in vitro system counted emboli during injections of contrast material and saline solution with either glass or plastic syringes. At Doppler sonography, an embolic signal was defined as the power of the reflected amplitude with auditory and visual confirmation. RESULTS: Of 62 respondents, 11.3% used glass syringes exclusively and 80.6% used plastic exclusively. Glass breakage was experienced by 72.5%, and 40% of them recalled an injury associated with such a breakage. No statistically significant difference was found between glass and plastic syringes for introduction of air emboli, though two outlying values represented larger numbers of emboli in the group with plastic syringes and contrast material. CONCLUSION: No reason for the continued use of glass syringes was found. No statistically greater risk of air emboli was shown with plastic syringes, and risk of breakage and injury is prevented. Caution is advised when injecting contrast material with plastic syringes because more air emboli may be introduced.

Cerebral Angiography↗

Effect of chronic theophylline therapy on brain blood flow and function in adult asthmatics.

The impact of theophylline therapy on neuropsychological (NP) function in adult asthmatics is unclear. Additionally, whether the previously demonstrated acute reduction in cerebral blood flow (CBF) persists with continued administration of theophylline, or whether accommodation develops, has not been previously reported. We examined the effects of chronic theophylline administration on CBF and NP function in adults with mild to moderate asthma. Sixty adult patients with mild to moderate asthma were entered into this double-blind, placebo-controlled, crossover, random sequence study. Subjects received theophylline or placebo for 6 wk interposed with a 2-wk washout period. At the conclusion of Week 1 and Week 6 of each drug phase, patients received NP testing, and CBF was determined using the 133Xenon washout method. Forty-three patients completed the study. Theophylline administration was associated with small (6%), but statistically significant, reductions in CBF after both 1 and 6 wk of treatment. No differences consequent to theophylline administration were observed in any of the tests of NP function after 1 or 6 wk of therapy. While CBF was decreased after theophylline, the changes were small compared with previously reported decrements in CBF immediately after theophylline administration.

Adult↗

Phenylephrine does not reduce cerebral perfusion during canine cardiopulmonary bypass.

Gaseous microemboli during cardiopulmonary bypass (CPB) could injure the blood-brain barrier so that cerebral vasoconstriction would result from infusing alpha-agonist drugs, such as phenylephrine. Cerebral blood flow (radioactive microspheres) and metabolism were measured in seven dogs after rewarming from 150 min hypothermic CPB with bubble oxygenators used to produce gaseous microemboli. Phenylephrine (40 micrograms/min) was infused directly into the brachiocephalic artery so that aortic pressure before (80 +/- 2 mm Hg) and during (79 +/- 3 mm Hg) the infusion did not change. Neither blood flow to the cerebral hemispheres (P = 0.960), cerebellum (P = 0.854), and brainstem (P = 0.694) nor the cerebral metabolic rate for oxygen (P = 0.862) differed when values obtained before and after 30 min of phenylephrine infusion were compared. Cerebral vascular resistance was also unchanged by phenylephrine, being 1.22 +/- 0.10 mm Hg.mL-1.min-1 x 100 g-1 before infusion and 1.25 +/- 0.17 mm Hg.mL-1.min-1 x 100 g-1 during infusion (P = 0.849). Phenylephrine does not cause cerebral vasoconstriction after rewarming from hypothermic CPB, a finding which suggests that the blood-brain barrier is preserved during bypass.

Animals↗

Significance of gaseous microemboli in the cerebral circulation during cardiopulmonary bypass in dogs.

BACKGROUND: Gaseous microemboli during cardiac surgery may damage the brain by reducing cerebral blood flow (CBF). We examined whether the incidence of gaseous microemboli during 150-minute hypothermic (28 degrees C) cardiopulmonary bypass (CPB) adversely affects CBF (radioactive microspheres). METHODS AND RESULTS: Thirty anesthetized dogs were placed on CPB using bubble oxygenators with 50% O2 (n = 10) or 100% O2 (n = 10) to produce a wide range in the number of gaseous microemboli or membrane oxygenators with 50% O2 (n = 10) to avoid microemboli. The number of carotid artery microemboli occurring in a 1-minute interval was counted using a 5-MHz Doppler probe every 15 minutes for the duration of CPB, which lasted 258 +/- 5 minutes. With bubbled 100% O2, the number of microemboli averaged 4.1 +/- 1.7 emboli per minute on normothermic bypass and increased with cooling to 18.3 +/- 4.9 emboli per minute (P < .001). With bubbled 50% O2, the microemboli number was greater on normothermic bypass (19.8 +/- 9.8 emboli per minute, P = .0653 compared with bubbled 100% O2) and increased with cooling (100.3 +/- 18.7 emboli per minute, P < .001) to a greater extent than with bubbled 100% O2 (P < .001). In contrast, with membrane 50% O2, the emboli number was small (0.6 +/- 0.1 emboli per minute) and did not change with CPB temperature. CBF values were not reduced after termination of CPB, even when compared with prebypass values, being 48.3 +/- 7.5 mL/min per 100 g (bubbled 50% O2), 49.6 +/- 4.1 mL/min per 100 g (bubble 100% O2), and 44.5 +/- 2.8 mL/min per 100 g (membrane 50% O2, P = .7581). Similarly, regional perfusion to the cerebellum, hippocampus, and caudal brainstem was not adversely affected by microemboli. After CPB, cortical biopsies demonstrated no difference among groups with respect to lactate (P = .1753), energy charge (P = .5179), and brain water content (P = .939). Retinal histopathology indicated no differences among groups. CONCLUSIONS: These results indicate that: (1) the incidence of gaseous microemboli during hypothermia increases when a bubble oxygenator is used, and (2) global CBF and regional brain perfusion are not adversely affected by numerous gaseous microemboli.

Animals↗

Vasopressin and fetal cerebrovascular regulation.

Vasopressin (AVP) may increase cerebral blood flow (CBF) during hypoxemia by selective dilatation of cerebral vessels via endothelium-derived relaxing factor (EDRF) release. To test whether this action is relevant in the fetus, we produced isocapnic hypoxemia in halothane-anesthetized pregnant ewes. Fetal infusion of a V1 AVP antagonist reduced by 55% the increase in CBF during fetal hypoxemia. To test the role of this response during development, we examined the response to AVP in intact and endothelium-denuded femoral and basilar arterial rings in vitro from fetal, newborn, and adult sheep. AVP constricted femoral rings in an endothelium-independent manner, with increased potency in newborn and fetal compared with adult rings. AVP relaxed basilar rings in an endothelium-dependent manner, which was unaffected by indomethacin treatment, with increased potency in newborn and adult compared with fetal rings. We conclude that fetal cerebral vascular endothelium is functional and responsive to AVP and that circulating AVP during fetal hypoxemia contributes to increased CBF via this effect.

Animals↗

Cerebrovascular and cerebral metabolic effects of alterations in perfusion flow rate during hypothermic cardiopulmonary bypass in man.

Recent experimental and clinical investigations provide conflicting evidence regarding the effects of changes in the systemic flow rate from the pump oxygenator on cerebral blood flow and the cerebral metabolic rate of oxygen consumption. However, the results of existing clinical studies are difficult to interpret because of the confounding effects of differences in management of arterial carbon dioxide tension and use of anesthetic and vasoactive agents during cardiopulmonary bypass. To clarify the relationship among perfusion flow rate, cerebral blood flow, and cerebral metabolic rate of oxygen consumption in man during hypothermic cardiopulmonary bypass, we varied perfusion flow rate in random order to either 1.75 or 2.25 L.min-1.m-2 and studied cerebral blood flow (measured by clearance of xenon 133) and cerebral metabolic rate of oxygen consumption (estimated as the product of cerebral blood flow and the cerebral arteriovenous oxygen content difference) in patients managed with both the alpha-stat (group 1) and the pH-stat (group 2) methods of pH and arterial carbon dioxide tension adjustment. We measured the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. In each patient other variables known to exert effects on cerebral blood flow and cerebral metabolic rate of oxygen consumption, including temperature, arterial carbon dioxide tension, arterial oxygen tension, mean arterial pressure, and hematocrit, were maintained constant between measurements. In both groups, mean arterial pressure at both pump flow rates was similar because of spontaneous reciprocal alterations in systemic vascular resistance, that is, as perfusion flow rate declined, systemic vascular resistance increased; as perfusion flow rate increased, systemic vascular resistance declined. Under these tightly controlled conditions, pump flow variation per se exerted no effect on cerebral blood flow or cerebral metabolic rate of oxygen consumption in either group.

Blood Flow Velocity↗

Cerebral perfusion during canine hypothermic cardiopulmonary bypass: effect of arterial carbon dioxide tension.

Cerebral blood flow (radioactive microspheres), intracranial pressure (subdural bolt), and retinal histopathology were examined in 20 dogs undergoing 150 minutes of hypothermic (28 degrees C) cardiopulmonary bypass to compare alpha-stat (arterial carbon dioxide tension, 40 +/- 1 mm Hg; n = 10) and pH-stat (arterial carbon dioxide tension, 61 +/- 1 mm Hg; n = 10) techniques of arterial carbon dioxide tension management. Pump flow (80 mL.kg-1.min-1), mean aortic pressure (78 +/- 2 mm Hg), and hemoglobin level (87 +/- 3 g/L [8.7 +/- 0.3 g/dL]) were maintained constant. During bypass, intracranial pressure progressively increased in the alpha-stat group from 6.0 +/- 1.0 to 13.9 +/- 1.8 mm Hg (p less than 0.05) and in the pH-stat group from 7.7 +/- 1.1 to 14.7 +/- 1.4 mm Hg (p less than 0.05), although there was no evidence of loss of intracranial compliance or intracranial edema formation as assessed by brain water content. With cooling, cerebral blood flow decreased by 56% to 62% in the alpha-stat group (p less than 0.05) and by 48% to 56% in the pH-stat group (p less than 0.05). However, 30 minutes after rewarming to 37 degrees C, cerebral blood flow in both groups failed to increase and remained significantly depressed compared with baseline values. Both groups showed similar amounts of ischemic retinal damage, with degeneration of bipolar cells found in the inner nuclear layer in 67% of animals. We conclude that, independent of the arterial carbon dioxide tension management technique, (1) cerebral perfusion decreased comparably during prolonged hypothermic bypass, (2) intracranial pressure increases progressively, (3) ischemic damage to retinal cells occurs despite maintenance of aortic pressure and flow, and (4) a significant reduction in cerebral perfusion persists after rewarming.

Animals↗

Sodium nitroprusside infusion does not dilate cerebral resistance vessels during hypothermic cardiopulmonary bypass.

This study determined whether sodium nitroprusside (SNP) changes cerebral vascular resistance during stable, hypothermic cardiopulmonary bypass (CPB). Cerebral blood flow (CBF) was measured using Xenon clearance in 39 patients anesthetized with fentanyl. In 25 patients (group 1), CBF was measured before and during infusion of SNP at a rate sufficient to reduce mean arterial pressure (MAP) approximately 20%. In 14 other patients (group 2), CBF was measured before and during simultaneous infusion of SNP and phenylephrine; SNP was continued at a rate that had reduced MAP approximately 20% while phenylephrine was added in a dose sufficient to restore MAP to preinfusion levels. Patients within each group were randomized to maintenance of PaCO2 approximately 40 mmHg (groups 1a and 2a), uncorrected for body temperature, or to maintenance of PaCO2 approximately 50 mmHg (groups 1b and 2b). The following variables were maintained within a narrow range: nasopharyngeal temperature (26-29 degrees C), pump oxygenator flow (1.7-2.5 l.min-1.m-2), PaO2 (150-300 mmHg), and Hct (22-28 vol%). In each patient, controlled variables varied no more than +/- 5% between measurements. In group 1a (PaCO2 approximately 40 mmHg), MAP was 86 +/- 9 mmHg (mean +/- SD) before and 65 +/- 8 mmHg during SNP infusion (P less than 0.0001). CBF was 12 +/- 3 ml.100g-1.min-1 before and 10 +/- 2 ml.100(-1).min-1 during SNP infusion (P less than 0.01). In group 1b (PaCO2 approximately 55 mmHg), MAP was 86 +/- 11 mmHg before and 66 +/- 13 mmHg during SNP infusion (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Validity and reliability of an ultrasound device for detecting carotid emboli.

Cardioembolic mechanisms cause 15 to 20% of all strokes and may account for the high incidence of neurological dysfunction associated with cardiopulmonary bypass. Accurate identification of high-risk subjects and/or surgical techniques would allow more effective testing and implementation of preventive or therapeutic measures to help reduce morbidity and mortality. This article reports on validity and reliability testing of a new emboli detection device that allows continuous monitoring of the common carotid artery. The instrument appears to be capable of detecting accurately particles of 193 mu or less in diameter and is highly reliable both within and between observers. In preliminary clinical use, the instrument also detected embolic signals in all patients monitored during cardiopulmonary bypass, while none were detected in healthy control subjects. These results establish the validity and reliability of a new emboli detection device and suggest its potential application to emboli detection monitoring during cardiopulmonary bypass.

Cardiopulmonary Bypass↗

Cerebral blood flow decreases with time whereas cerebral oxygen consumption remains stable during hypothermic cardiopulmonary bypass in humans.

Recent investigations demonstrate that cerebral blood flow (CBF) progressively declines during hypothermic, nonpulsatile cardiopulmonary bypass (CPB). If CBF declines because of brain cooling, the cerebral metabolic rate for oxygen (CMRO2) should decline in parallel with the reduction in CBF. Therefore we studied the response of CBF, the cerebral arteriovenous oxygen content difference (A-VDcereO2) and CMRO2 as a function of the duration of CPB in humans. To do this, we compared the cerebrovascular response to changes in the PaCO2. Because sequential CBF measurements using xenon 133 (133Xe) clearance must be separated by 15-25 min, we hypothesized that a time-dependent decline in CBF would accentuate the CBF reduction caused by a decrease in PaCO2, but would blunt the CBF increase associated with a rise in PaCO2. We measured CBF in 25 patients and calculated the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. Patients were randomly assigned to management within either a lower (32-48 mm Hg) or higher (50-71 mm Hg) range of PaCO2 uncorrected for temperature. Each patient underwent two randomly ordered sets of measurements, one at a lower PaCO2 and the other at a higher PaCO2 within the respective ranges. Cerebrovascular responsiveness to changes in PaCO2 was calculated as specific reactivity (SR), the change in CBF divided by the change in PaCO2, expressed in mL.100 g-1.min-1.mm Hg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Hypercarbia depresses cerebral oxygen consumption during cardiopulmonary bypass.

No human studies have systematically examined the relations among PaCO2, cerebral blood flow, and the cerebral metabolic rate for oxygen during hypothermic cardiopulmonary bypass. We varied PaCO2 during hypothermic (26-28 degrees C) cardiopulmonary bypass and estimated the cerebral metabolic rate for oxygen by multiplying cerebral blood flow (measured using xenon-133 clearance) by the cerebral arteriovenous difference in oxygen contents. Patients were randomly assigned to either of two methods of managing PaCO2 (uncorrected for body temperature). In group 1 (PACO2 32-48 mm Hg, n = 13) the mean +/- SD cerebral metabolic rate for oxygen was 0.40 +/- 0.11 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 36 +/- 2.0 mm Hg and 0.40 +/- 0.14 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 45 +/- 2 mm Hg. and 49-72 mm Hg, n = 12) the mean +/- SD cerebral metabolic rate for oxygen was 0.31 +/- 0.09 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 55 +/- 3 mm Hg and 0.21 +/- 0.07 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 68 +/- 2 mm Hg. Group 2 values differed significantly from those in Group 1 (p less than 0.05). In both groups, cerebral blood flow increased as PaCO2 increased. During cardiopulmonary bypass, increasing PaCO2 increases cerebral blood flow and decreases the cerebral metabolic rate for oxygen.

Arteries↗

Regional cerebrovascular reactivity to carbon dioxide during cardiopulmonary bypass in patients with cerebrovascular disease.

In patients with cerebrovascular disease, hypercarbia may cause redistribution of regional cerebral blood flow from marginally perfused to well-perfused regions (intracerebral steal), as evidenced by regional cerebral blood flow studies during carotid endarterectomy. During hypothermic cardiopulmonary bypass, the pH-stat method of acid-base management produces relative hypercarbia. To determine whether pH-stat management produces relative hypercarbia. To determine whether pH-stat management induces intracerebral steals, we investigated nine patients with cerebrovascular disease undergoing coronary artery bypass grafting. During hypothermic cardiopulmonary bypass, arterial carbon dioxide tension was varied in random order between 40 mm Hg and 60 mm Hg (uncorrected for body temperature). Regional cerebral blood flow was measured by clearance of 133 xenon injected into the arterial inflow cannula. Nasopharyngeal temperature (26.8 degrees-28.0 degrees +/- 2.2 degrees-3.0 degrees C), perfusion flow rate (2.14-2.18 +/- 0.70-0.73 L/min/m2), mean arterial pressure (67-68 +/- 6-9 mm Hg), arterial carbon dioxide tension (302-308 +/- 109-113 mm Hg), and hematocrit (23% +/- 4%) were maintained within narrow limits in each patient during arterial carbon dioxide tension manipulation. Global mean cerebral blood flow values were similar to previously reported values in patients free of cerebrovascular disease; patients in this study averaged 15.2 +/- 2.5 ml/100 gm/min at an arterial carbon dioxide tension of 46.1 +/- 8.4 mm Hg and 25.3 +/- 6.1 ml/100 gm/min at an arterial carbon dioxide tension of 71.1 +/- 11.8 mm Hg. Carbon dioxide reactivity, defined as mean global cerebral blood flow (in ml/100 gm/min) divided by arterial carbon dioxide tension (in mm Hg), was similar in the region having the lowest regional cerebral blood flow and in the brain as a whole. No patient developed evidence of an intracerebral steal at the higher arterial carbon dioxide tension. During hypothermic cardiopulmonary bypass, higher levels of arterial carbon dioxide tension, such as those associated with the pH-stat management technique, are apparently not associated with potentially harmful redistribution of cerebral blood flow in patients with cerebrovascular disease.

Adult↗