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R G Dacey

Publications and source records attributed to R G Dacey.

At least 37 records · Page 2Linked to original sources

Local and conducted vasomotor responses in isolated rat cerebral arterioles.

We tested the hypothesis that conduction of vasomotor responses occurs in cannulated and isolated rat cerebral penetrating arterioles. Both at the site of stimulation (local) and 500-650 microns distant from it, we observed the diameter responses and time courses thereof to pressure-ejected vasoactive stimuli. ATP locally caused an initial constriction (response onset at 0.3 s, average diameter 85% of control at 450-ms pulse with a maximum at 1.6 s after stimulation) followed by a secondary dilation (111% at 7 s). Conducted vasodilation of 111% was observed over a distance of 520 microns. Prostaglandin F2 alpha (PGF2 alpha) constricted the vessels locally (80%) and caused conducted vasodilation (110%). For both ATP and PGF2 alpha the local constriction occurred simultaneously to the conducted vasodilation. Adenosine dilated the vessels (123%) but produced only inconsistent conducted vasodilation. Hydrogen ions initially constricted the vessels (88%) and then dilated them to 113%. Thus, although ATP and PGF2 alpha are strong promoters of conduction, adenosine and hydrogen ions are not. Paradoxically, ATP and PGF2 alpha caused conducted vasodilation even though the initial local response was a vasoconstriction, indicating that in cerebral arterioles conduction may be mediated through endothelial cell mechanisms rather than through smooth muscle cell communication.

Acids↗

Magnetic neurosurgery.

Because of the complex shape of many brain structures, the ideal brain probe would be highly flexible and give the neurosurgeon the ability to independently and precisely control movement of the probe tip. A magnetic surgery system has been developed that implements this concept. Flexible brain probes with small permanent magnetic tips are placed on the brain surface through a small burr hole and then magnetically manipulated within the brain. Drive forces are produced by an array of six superconducting magnets suspended within a cryostatic helmet. They produce a maximum force of 3 times the threshold needed to move the probe through the parenchymal tissues at its normal speed of 1 mm/s. Computer-controlled magnetic impulses precisely direct the probe movement in any direction desired with movement accuracy of 0.47 mm in phantom gels. Probe position is monitored 3 times per second with orthogonally oriented microchannel plate X-ray systems, X-ray dose from a 3-hour simulated procedure is comparable to that of a chest X-ray. In vivo and in vitro feasibility studies have been carried out in dog and pig brains. Preclinical trials are planned for clinical applications including implantation of flexible brachytherapy threads.

Equipment Design↗

Jugular bulb temperature: comparison with brain surface and core temperatures in neurosurgical patients during mild hypothermia.

Blood temperature at the jugular bulb was monitored in 10 patients undergoing neurovascular procedures that used induced mild hypothermia, and its correlation with surface brain, core, and peripheral temperatures was determined. The study was motivated by the difficulty encountered in directly measuring global brain temperature and the poor correlations between various core and peripheral sites temperatures and brain temperature, particularly during deep hypothermia. Although not statistically significant, previous studies have suggested a trend toward higher brain temperatures. Temperatures from the jugular bulb (collected using a No. 5 French Swan-Ganz catheter) as well as from subdural, pulmonary artery, esophagus, tympanic membrane, and bladder sites were analyzed during three surgical conditions: prior to incision, with the dura open, and after closure of the dura. No complications related to placement of the jugular bulb catheter, induced hypothermia, or temperature monitoring were seen. The authors found that jugular bulb temperature was similar to pulmonary artery and esophageal temperatures; although prior to incision it tended to be higher than that found at the pulmonary artery, most commonly by 0.2 degrees C. Surface brain temperature was cooler than all other temperatures (p < 0.05), except that of the tympanic membrane, and was particularly sensitive to environmental variations. Finally, as has been shown by others, bladder temperature lagged substantially behind core temperatures particularly during rapid cooling and rewarming of the patient. In summary, monitoring of jugular bulb temperature is a feasible technique, and temperatures measured in the jugular bulb are similar to core temperatures.

Adult↗

Hospital resource utilization in the treatment of cerebral aneurysms.

The authors reviewed clinical and financial data for all patients treated for nontraumatic subarachnoid hemorrhage (SAH) and unruptured cerebral aneurysms at their institution between June 1993 and December 1994. This study sought to identify specific areas of high resource utilization that may be amenable to reduction of expenditures without compromising quality of care. Detailed hospital financial data were correlated with clinical grade and course. Areas of high resource use were identified based on patient charges and category-specific loaded hospital cost. Patients were divided into four groups: Group 1, surgically treated unruptured aneurysms (28 patients); Group 2, acute SAH (42 patients); Group 3, SAH with vasospasm (32 patients); and Group 4, SAH with negative angiogram (10 patients). Total cost per patient (mean +/- standard deviation in thousands of U.S. dollars) was highest for Group 3 (38.4 +/- 21.3; vs. Group 1, 12.7 +/- 8.8; Group 2, 22.6 +/- 20.9; and Group 4, 25.0 +/- 33.5) and correlated with hospital length of stay, Hunt and Hess grade, and Fisher grade. Areas of highest hospital cost were not always reflected in patient charges. The three areas of highest cost accounted for 48.5% of the total cost and were: 1) intensive care unit (ICU) room (Group 1, 2.5 +/- 3.5; Group 2, 7.0 +/- 9.2; Group 3, 11.0 +/- 7.8; and Group 4, 7.9 +/- 14.1); 2) arteriography (Group 1, 1.7 +/- 1.2; Group 2, 2.1 +/- 1.5; Group 3, 4.1 +/- 2.1; and Group 4, 2.2 +/- 0.7); and 3) ICU medicosurgical supplies (Group 1, 1.7 +/- 0.8; Group 2, 2.0 +/- 1.5; Group 3, 3.7 +/- 1.7; and Group 4, 2.0 +/- 3.0). It is concluded that cost containment strategies should be based on cost rather than charge and novel approaches will be required to reduce the cost of treating patients with SAH. Such approaches might include preventing vasospasm, reducing ICU stay, selective use of arteriography, and reducing the cost of supplies.

Aged↗

Effects of oxyhemoglobin on local and propagated vasodilatory responses induced by adenosine, adenosine diphosphate, and adenosine triphosphate in rat cerebral arterioles.

After subarachnoid hemorrhage (SAH), cerebral arteries display impaired vasomotor control, resulting in decreased regional cerebral blood flow. Recently, propagation of vasomotor responses has been recognized as an important regulatory mechanism in microcirculation. In this study, the authors tested the hypothesis that oxyhemoglobin (OxyHb) inhibits the vasodilatory effect of chemical mediators such as adenosine and adenine nucleotides at a local and/or propagated site. Penetrating intracerebral arterioles were surgically isolated from the middle cerebral arteries of rat brains, cannulated, and observed videomicroscopically in an organ bath under an inverted microscope. The effects of 10(-5) M OxyHb on vasoactive responses to adenosine, adenosine diphosphate (ADP), and adenosine triphosphate (ATP) were examined. The drugs were extraluminally applied either to the bath (10(-10)-10(-3) M) or, using pressure microejection (pipette concentration 10(-2) M), locally. The ATP and ADP initially constricted and then significantly dilated the vessels after both extraluminal application and microapplication. Furthermore, local microstimulation by these drugs produced conducted vasodilation. Adenosine elicited significant vasodilation after both extraluminal and local stimulation. Again, conducted vasodilation was observed. The vasomotor responses that were induced by a maximum local stimulation corresponded in magnitude to those observed at bath concentrations of 10(-5) to 10(-4) M of the same drug. Pretreatment with OxyHb constricted arterioles to an average of 87% of control and blunted extraluminally induced dilation at low concentrations (10(-10)-10(-8)) of ATP and ADP, but did not affect vasodilation induced by 10(-4) M or greater concentrations of ATP, ADP, or adenosine. Although the local response to local microstimulation was unaltered, propagated vasodilation as a response to ATP, ADP, and adenosine was significantly attenuated by OxyHb. These findings indicate that vasodilatory propagation plays an important role in the regulation of brain microcirculation and that its impairment by OxyHb could, in part, explain the cerebral hypoperfusion that is observed after SAH.

Adenosine↗

Review of magnetic neurosurgery research.

Image guided surgical techniques are often used to provide useful localizing information during the course of otherwise "standard" surgical procedures. In this review, a magnetic surgery system (MSS) is described that couples image guidance methods with a novel magnetic treatment delivery system. The MSS was designed with the unique capacity to manipulate an implant remotely, to follow complex curvilinear paths, and to implement serial movements over time without reoperation. Magnetically tipped intracerebral implants are placed on the brain surface and then directed along a target trajectory by means of externally generated magnetic gradients. The location of the implant is calculated by comparing preoperative magnetic resonance imaging (MRI) imaging data with intraoperative biplanar fluoroscopic images. A command computer presents the surgeon with relevant MRI-derived images and implements movement commands by sending currents of various strength to the six superconducting magnets suspended about the subject's head. The results of multidisciplinary preclinical research and development work are reviewed.

Brain↗

Safety of hypertensive hypervolemic therapy with phenylephrine in the treatment of delayed ischemic deficits after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Hypertensive hypervolemic therapy has been shown to reverse delayed ischemic deficits after aneurysmal subarachnoid hemorrhage. Concern has been raised about systemic complications of therapy, including pulmonary edema and myocardial ischemia, especially when high doses of vasopressors are used. Patients in whom delayed ischemic deficits were treated with hypervolemia and phenylephrine were prospectively evaluated for signs of systemic toxicity. METHODS: Twenty-four consecutive patients treated with hypertensive hypervolemic therapy after aneurysmal subarachnoid hemorrhage were studied. Sixty-seven percent had underlying cardiac disease, vascular disease, or hypertension. No patient was excluded because of age or preexisting cardiac disease. Patients were closely monitored for signs of congestive heart failure (physical examination, chest x-ray films, arterial blood gases, cardiac index, pulmonary artery wedge pressure, and oxygen requirement). Indicators of cardiac ischemia and other extracerebral toxicity that were monitored included cardiac enzymes, electrocardiograms, serum creatinine, electrolyte and lactic acid levels, gastrointestinal motility, and urine output. RESULTS: Volume expansion and phenylephrine infusion produced an increase in several hemodynamic parameters including pulmonary artery wedge pressure, which rose 28% (13 +/- 3.6 to 16 +/- 1.9 mm Hg), mean arterial blood pressure, which rose 25% (99 +/- 12.5 to 123 +/- 11.4 mm Hg), and systemic vascular resistance, which rose 46% (1234 +/- 294 to 1739 +/- 315 dyne.s-1.cm-5); however, there was no change in cardiac index (3.9 +/- 0.9 to 4.0 +/- 0.6 L.min-1.m-2). There were no clinically significant episodes of pulmonary edema requiring a change in vasopressor therapy and no myocardial infarctions. Phenylephrine was stopped in only one patient (incidence, 4%; 95% confidence interval, 0% to 12%), who developed an exacerbation of his preexisting bradycardia. There was no evidence of noncardiac organ system toxicity. Eighty-eight percent of the patients exhibited neurological improvement. CONCLUSIONS: Hypertensive hypervolemic therapy with the use of high-dose phenylephrine can be administered with acceptable systemic toxicity, even in patients with previous cardiac disease, provided that close monitoring is performed. To minimize risk, aggressive treatment should probably be reserved for patients with signs of delayed ischemia rather than administered prophylactically.

Adult↗

Severe thrombocytopenia following intraarterial papaverine administration for treatment of vasospasm.

Selective intraarterial infusion of papaverine is used in the treatment of symptomatic cerebral vasospasm. The authors report two episodes of severe thrombocytopenia in a patient that were related to intraarterial administration of papaverine. A 70-year-old man with a right internal carotid artery aneurysm underwent craniotomy and aneurysm clipping. He became lethargic 8 days after the hemorrhage occurred. Cerebral angiography revealed moderate vasospasm. In addition to hypervolemic-hypertensive therapy, the patient was treated on two occasions with intraarterial administration of papaverine. Within 24 hours of both treatments he developed severe thrombocytopenia. On one occasion epistaxis requiring transfusion of blood products occurred. Laboratory data support the diagnosis of immune-mediated papaverine-induced thrombocytopenia. The authors conclude that intraarterial administration of papaverine for treatment of vasospasm can be associated with severe, rapidly reversible thrombocytopenia.

Aged↗

Intraoperative digital subtraction angiography: a review of 112 consecutive examinations.

PURPOSE: To examine the effect of intraoperative angiography on neurosurgery and angiographic technical success, safety, and accuracy. METHODS: Angiographic studies, surgical reports, and hospital records were reviewed retrospectively for 112 consecutive procedures in which intraoperative angiography was performed during neurosurgery. The results of conventional postoperative angiograms in 28 of the 112 procedures were also reviewed. A portable digital subtraction angiography unit was used for all patients. Decisions in the operating room were based on review of stored videotaped images. RESULTS: Eighteen studies were obtained in 14 patients after arteriovenous malformation resection. Unsuspected residual nidus was identified and resected in 3 patients. The intraoperative angiogram also altered therapy for 2 patients undergoing staged resections of arteriovenous malformations. Sixty-six studies were performed after aneurysm clipping, with clinically significant changes in surgical therapy made in 5 patients. Of 28 examinations after carotid endarterectomy, 3 led to revision. Two complications of angiography occurred. One led to a permanent neurologic deficit, yielding a complication rate of 1.5% for stroke. Two examinations could not be completed because of technical factors. Two false-negative examinations were identified on postoperative studies. One patient with a normal intraoperative study after carotid endarterectomy thrombosed the repaired internal carotid artery after surgery. CONCLUSIONS: Intraoperative angiography altered surgery in 13 of 112 procedures on 104 patients. This study supports the use of intraoperative angiography in arteriovenous malformation resection and in complex aneurysm surgery, but not for routine carotid endarterectomy.

Angiography, Digital Subtraction↗

N omega-nitro-L-arginine constricts cerebral arterioles without increasing intracellular calcium levels.

The coupling between intracellular Ca2+ concentration ([Ca2+]i) and smooth muscle cell (SMC) contractility is well known, but recent reports suggest that SMCs can contract without an increase in [Ca2+]i. Penetrating arterioles were isolated from rat cortex, cannulated, and loaded extraluminally with fura 2. We used ratio imaging of corresponding vessel wall areas to estimate and correlate [Ca2+]i to the vessel diameter during various extraluminal treatments. Control diameter was 45.6 +/- 3.9 (SE) microns with an estimated [Ca2+]i of 181 +/- 18 nM. Extraluminal papaverine or pH of 6.8 dilated the vessels to 61.0 +/- 6.6 and 57.8 +/- 5.8 microns and decreased [Ca2+]i to 108 +/- 33 and 155 +/- 8 nM, respectively. Alkaline pH of 7.65 or the Ca2+ ionophore ionomycin constricted the arterioles to 34.8 +/- 3.9 and 30.0 +/- 5.8 microns and increased [Ca2+]i to 273 +/- 47 and 853 +/- 155 nM, respectively. These results show an inverse relationship between vessel diameter and [Ca2+]i. Blocking the production of endothelium-derived nitric oxide (EDNO) with N omega-nitro-L-arginine constricted the vessels to 34.4 +/- 3.5 microns without raising but lowering [Ca2+]i to 157 +/- 44 nM. The dissociation of vessel tone and estimated [Ca2+]i after EDNO blocking has not been reported before in cerebral arterioles and may indicate that EDNO regulates vascular tone in a Ca(2+)-independent manner.

Animals↗

Nitric oxide regulates cerebral arteriolar tone in rats.

BACKGROUND AND PURPOSE: Although cerebral penetrating arterioles are main regulators of the brain microcirculation, little is known about the effect of endothelium-derived relaxation factor on these vessels. This study examined the effects of nitric oxide synthase inhibitors on the spontaneous tone of isolated rat cerebral arterioles. METHODS: Intraparenchymal penetrating arterioles (53 to 102 microns in passive diameter) isolated from Sprague-Dawley rats were cannulated with glass pipettes and subjected to 60 mm Hg of intraluminal pressure. The diameter response to intraluminal and extraluminal treatments was observed with an inverted microscope. RESULTS: Extraluminal application of Nw-nitro-L-arginine (10(-5) mol/L) contracted the arterioles to 63.9 +/- 2.8% (P < .05) of the control diameter. This contracting effect was stereospecific and easily reversed by L-arginine dose dependently (10(-3), 10(-2) mol/L) but not by D-arginine. Intraluminally applied Nw-nitro-L-arginine also induced a similar degree of contraction. Another nitric oxide synthase inhibitor, NG-monomethyl L-arginine (10(-5), 10(-4) mol/L), applied extraluminally induced a dose-dependent contraction to 77.5 +/- 6.6% and 68.6 +/- 5.4% of the control (P < .05), which was also reversed by L-arginine. L-Arginine alone did not significantly affect vessel diameter, however. Treatment with indomethacin, a cyclooxygenase inhibitor, dilated the vessel to 115.2 +/- 7% (P < .05) but did not change the constricting effect of Nw-nitro-L-arginine. CONCLUSIONS: Nw-Nitro-L-arginine and NG-monomethyl L-arginine produce substantial contraction in isolated brain arterioles, suggesting that nitric oxide of brain arterioles is continuously produced within the vessel wall. The dilatory effect of indomethacin appears to be independent of the vasoconstriction induced by nitric oxide synthase inhibitor. In these vessels, the effect of nitric oxide synthase inhibitors is not mediated by an indomethacin-sensitive mechanism. A balance probably exists between factors tending to constrict these arterioles and the elaboration of nitric oxide from endothelial cells, which tends to dilate them. The production of nitric oxide from isolated vessels indicates that parenchymal and vessel wall sources of nitric oxide are probably important in brain microcirculatory regulation.

Animals↗

Effects of extravascular acidification and extravascular alkalinization on constriction and depolarization in rat cerebral arterioles in vitro.

The relationship between cell membrane potential, vessel diameter, and pH in small cerebral arterioles is not completely understood. This study involved direct, simultaneous measurement of cell membrane potential and vessel diameter at various extracellular pH levels. Arterioles ranging from 44 to 91 microns in diameter were isolated, transferred to a temperature-controlled microscope chamber, which was used as an organ bath, and observed through an inverted videomicroscope. Two vessel cannulation procedures were used: a single-sided cannulation with the other side occluded, and a double-sided and perfused cannulation. After cannulation, the vessels were pressurized to 60 mm Hg intraluminally and the bath temperature was raised to 37 degrees C. Cell membrane potentials of vessel wall cells were obtained after the bath temperature reached 37 degrees C with the vessels partly constricted and again after spontaneous tone (constriction) of the healthy vessels had developed. The effect of extraluminal pH on cell membrane potentials was studied by changing the bath pH from 7.3 to either 7.65 or 6.8 in the single-sided cannulation. The average cell membrane potential for vessels at 37 degrees C, with 60 mm Hg of intraluminal pressure and pH 7.3, was -37.5 mV. The cell membrane potential depolarized to -30.9 mV at pH 7.65 and hyperpolarized to -58.4 mV at pH 6.8, with a slope of 25.8 mV/pH unit. The effect of depolarizing extracellular potassium ions on the cell membrane potential was examined by perfusing two vessels with modified Ringer's solution containing 70 mM KCl. This perfusion method decreased the vessel diameter by 48% and depolarized the observed cell membrane potential from -41.9 to -19.8 mV, with a slope of -0.42 mV per percentage diameter change. These data provide the first measurements of membrane potentials of isolated penetrating arteriole wall cells in vitro. The results indicate that the cell membrane potential relates linearly to the vessel diameter. This new technique opens the possibility for studying vessel response to stimuli under controlled conditions and regulatory mechanisms such as the propagation of vasomotor responses.

Animals↗

Measurement of hydraulic conductivity in isolated arterioles of rat brain cortex.

We have developed a new method for quantification of arteriolar hydraulic conductivity (Lp) from isolated rat brain vessels. The volume flux of water per unit surface area across the arteriole wall (Jv/S) was assessed from measurements of silicon oil drop movement within an occluded vessel at two to three pressures (between 20 and 70 mmHg); the Lp was derived from the slope of the relationship between Jv/S and applied pressure. Lp was measured in isolated cerebral arterioles 1) at room temperature (22 degrees C) without spontaneous vessel tone (control Lp; n = 11), 2) at room temperature with 10(-4) M adenosine (n = 5), and 3) at 37 degrees C with vessels dilated submaximally with 10(-4) M adenosine (n = 6). Lp at 22 degrees C without adenosine was 13.2 +/- 4.2 x 10(-9) (+/- SE) cm.s-1.cmH2O-1 for all vessels studied. Lp values ranged from 1.2 to 44.1 x 10(-9) cm.s-1.cmH2O-1 with a median value that was 5.9 x 10(-9) cm.s-1.cmH2O-1. Lp increased significantly (on average, 2.6-fold) with adenosine at 37 degrees C but not with adenosine at 22 degrees C. Control Lp bore no relationship to either the development of spontaneous tone or the diameter response to pH change, two recognized indicators of vessel viability.

Adenosine↗

An in vitro comparative study of conducting vessels and penetrating arterioles after experimental subarachnoid hemorrhage in the rabbit.

The reactivity of rabbit basilar artery and penetrating arteriolar microvessels was studied in vitro using an isometric-tension measurement technique and an isolated perfused arteriole preparation, respectively. Comparisons were made between reactivities of normal vessels and those obtained from animals subjected to experimental subarachnoid hemorrhage (SAH) 3 days prior to examination. Subarachnoid hemorrhage produced significant increases in basilar artery contraction in response to increasing concentrations of serotonin (5-hydroxytryptamine) (10(-9) to 10(-5) M) and prostaglandin F2 alpha (10(-9) to 10(-5) M) when compared to normal arteries. In addition, SAH attenuated the relaxing effect of acetylcholine following serotonin-induced contraction and of adenosine triphosphate after KCl-induced basilar artery contractions. In contrast to the changes observed in large arteries, cerebral microvessels did not demonstrate significant differences in spontaneous tone or in reactivity to a number of vasoactive stimuli including application of calcium, serotonin, and acetylcholine. On the other hand, small but significant changes in arteriolar responsiveness to changes in extraluminal pH and to application of KCl were noted. Findings from this study suggest that intracerebral resistance vessels of the cerebral microcirculation are not greatly affected by the presence of subarachnoid clot, in contrast to the large arteries in the basal subarachnoid space. The small changes that do occur are qualitatively different from those observed for large arteries. These findings are consistent with the observation of significant therapeutic benefit with the use of calcium channel blockers without changes in angiographically visible vasospasm in large vessels. It is likely, therefore, that calcium antagonists may act to decrease total cerebrovascular resistance at the level of the relatively unaffected microcirculation after SAH without changing large vessel diameter.

Acetylcholine↗