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David S Warner

Publications and source records attributed to David S Warner.

60 records · Page 4Linked to original sources
PubMed2002

Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Endothelial nitric oxide synthase (eNOS) activity is decreased after subarachnoid hemorrhage (SAH). Simvastatin increases eNOS activity. We hypothesized that simvastatin would increase eNOS protein and ameliorate SAH-induced cerebral vasospasm. METHODS: Mice were treated with subcutaneous simvastatin or vehicle for 14 days and then subjected to endovascular perforation of the right anterior cerebral artery or sham surgery. Three days later, neurological deficits were scored (5 to 27; 27=normal), and middle cerebral artery diameter and eNOS protein were measured. The study was repeated, but simvastatin treatment was started after SAH or sham surgery. RESULTS: In SAH mice, simvastatin pretreatment increased middle cerebral artery diameter (SAH-simvastatin=74+/-22 micro m, SAH-vehicle=52+/-18 micro m, P=0.03; sham-simvastatin=102+/-8 micro m, sham-vehicle=105+/-6 micro m). Pretreatment reduced neurological deficits (SAH-simvastatin=25+/-2, SAH-vehicle=20+/-2, P=0.005; sham-simvastatin and sham-vehicle=27+/-0). Simvastatin pretreatment also increased eNOS protein. Simvastatin posttreatment caused a modest increase in middle cerebral artery diameter in SAH mice (SAH-simvastatin=56+/-12 micro m, SAH-vehicle=45+/-4 micro m, P=0.03; sham-simvastatin=92+/-13 micro m, sham-vehicle=99+/-10 micro m) and reduced neurological deficits (SAH-simvastatin=21+/-1, SAH-vehicle=19+/-2, P=0.009). Simvastatin posttreatment did not significantly increase eNOS protein. CONCLUSIONS: Simvastatin treatment before or after SAH attenuated cerebral vasospasm and neurological deficits in mice. The mechanism may be attributable in part to eNOS upregulation.

Animals↗
PubMed2002

Mouse model of subarachnoid hemorrhage associated cerebral vasospasm: methodological analysis.

The transgenic mouse has been used to study subarachnoid hemorrhage (SAH) induced delayed cerebral vasospasm (DCV). Methodological parameters have not been analyzed to validate this model and associated neurological deficits have not been described. We introduce a technique to quantify DCV and associated neurological deficits. C57BL/6J mice were subjected to SAH or sham surgery. Seventy-two hours later, the vasculature was cast in situ with India ink/gelatin at perfusion pressures of 40-60, 60-80, or 100-120 mmHg. Mice were perfused with and without microfiltration. Additional mice underwent grading of SAH size, measurement of vascular diameters, and neurological examination (score range 5-27; 27= normal). When cast at 60-80 mmHg, SAH was associated with an intraluminal cross-sectional diameter reduction in 3 of 7 ipsilateral vascular segments. At 40-60 mmHg, the diameter of only one segment was reduced. No changes were observed at 100-120 mmHg. Emboli prevented adequate perfusion of vascular segments in the absence of microfiltration. Median (interquartile range) neurologic score was reduced after SAH (sham, 27(27); SAH 11(7-17)). Deficits correlated with middle cerebral artery (MCA) diameter and SAH grade. MCA diameter also correlated with SAH grade. Only when utilizing microfiltration, controlling for hemorrhage size, and casting at perfusion pressures of 60-80 mmHg does India ink/gelatin vascular casting demonstrate consistent DCV that correspnds to neurological deficits. This allows measurement of both anatomical and clinical DCV in the mouse.

Animals↗
PubMed2002

Brain oxygenation and energy metabolism: part I-biological function and pathophysiology.

CONTINUOUS OXYGEN DELIVERY and CO(2) clearance are paramount in the maintenance of normal brain function and tissue integrity. Under normal conditions, aerobic metabolism is the major source of energy in the brain, but this system may be compromised by the interruption of substrate delivery and disturbances in cerebral metabolism. These disruptions are major factors contributing to ischemic and hypoxic brain damage resulting from traumatic brain injury, stroke, and subarachnoid hemorrhage. There is evidence that mitochondrial function also is reduced after injury. Furthermore, early impairment of cerebral blood flow in patients with severe injury correlates with poor tissue oxygenation and may be an important parameter in secondary damage. Recent advances in brain tissue monitoring in the intensive care unit and operating room have made it possible to continuously measure tissue oxygen tension and temperature, as well as certain aspects of brain metabolism and neurochemistry. Therefore, it is important to understand the physiological process and the pathophysiology produced by these events. This is Part I of a two-part review that analyzes the physiology of cerebral oxygenation and metabolism as well as some of the pathological mechanisms involved in ischemic and traumatic brain injuries. Brain tissue monitoring techniques will be examined in the second article of this two-part series. To understand cerebral oxygenation, it is important to understand cerebral blood flow, energy production, ischemia, acidosis, generation of reactive oxygen species, and mitochondrial failure. These issues provide the basis of knowledge regarding brain bioenergetics and are important topics to understand when developing new approaches to patient care.

Acidosis↗
PubMedDate not supplied

Altered perceptions after upper and lower extremity blocks: an initial investigation.

BACKGROUND AND OBJECTIVES: Nerve blocks frequently produce unusual altered perceptions in the extremities. We examined perceptual changes experienced after peripheral blocks. METHODS: Fifty consecutive patients having an upper or lower extremity block for surgery participated in this prospective study. Patients were divided into 2 groups: upper extremity (n = 20) and lower extremity (n = 30). Each group was asked a list of questions about perceptions of limb sensation, length, weight, and location and given a detailed 2-point discrimination test over the V(1)-V(3) divisions of the trigeminal nerve prior to block and sedation. While the extremity was still blocked, the exam was repeated before postanesthesia care unit discharge. RESULTS: In both groups, 98% of patients described altered limb perception. The perceptions in the upper extremity were: heaviness, 60%; numbness, 50%; warmth, 40%; pain, 30%; full or fat, 20%; floating, 5%; shorter, 0%; or thinner, 10%. The perceptions in the lower extremity were: numbness, 75%; heaviness, 46%; warmth, 33%; pain, 32%; full or fat, 36%; floating, 25%; shorter, 18%, or thinner, 7%. Upper extremity block patients were more likely to describe the limb as lighter (P <.0001); the lower extremity group was more likely to describe the limb as numb (P =.01) or floating (P =.0002). There was no difference in the ability to correctly identify the location of the limb between the groups. There was no difference in 2-point discrimination between each assessment for either group. CONCLUSION: The results of this study confirm and quantify the perceptions experienced by patients undergoing upper and lower extremity blocks. These perceptions are prevalent. This knowledge is helpful in providing patients with accurate preoperative preparation. Further investigation is warranted to determine the neurologic etiology of these observations.

Adult↗
PubMedDate not supplied

Paravertebral somatic nerve block compared with peripheral nerve blocks for outpatient inguinal herniorrhaphy.

BACKGROUND: Inguinal herniorrhaphy (IH) is a common outpatient procedure, yet postoperative pain and anesthetic side effects remain a problem. Paravertebral somatic nerve blocks (PVB) have the potential to offer unilateral abdominal wall anesthesia and long-lasting pain relief with minimal side effects. We compared PVB with peripheral neural blocks for outpatient IH. METHODS: Forty-six patients scheduled for IH were entered into this prospective, single-blind study. All patients underwent a standardized general anesthetic. Patients were randomly assigned to receive a PVB (levels T10-L2) preoperatively (n = 24) or an intraoperative peripheral block (PB) by the surgeon (n = 22), using 0.5% ropivacaine (40 mL). Opioid use, verbal analog pain scores, and side effects were documented for 72 hours. RESULTS: The use of opioids during surgery was less for the PVB group 162 +/- 70 mg than the PB group, 210 +/- 60 (P =.02). Need for opioids in PACU was less for the PVB group (39%) than the PB group (61%) (P =.002). Time until first pain after discharge was not different between groups, 312 +/- 446 minutes (PB) and 425 +/- 384 minutes (PVB) (P =.12). Of the PVB patients, 29% used no opioids at all compared with 18% of PB patients (P =.12). Mean time until first oxycodone use was similar between groups, 303 +/- 469 minutes (PB) and 295 +/- 225 minutes (PVB) (P =.18). Oxycodone use was also similar; 35 +/- 34 mg (PVB) versus 49 +/- 42 mg (PB) (P =.30). More patients in the PB group (50%) required antiemetic treatment in the postanesthesia care unit than the PVB group (21%) (P <.001). Side effects were similar at all other measurements. CONCLUSIONS: This study shows that PVB provides analgesia equivalent to extensive peripheral nerve block for inguinal herniorrhaphy, offering an alternative method of postoperative pain management and perhaps fewer side effects.

Abdominal Wall↗