Biomedical subjects

J R Kirsch

Publications and source records attributed to J R Kirsch.

At least 73 records · Page 4Linked to original sources

PubMed1993

Polyethylene glycol-conjugated superoxide dismutase improves recovery of postischemic hypercapnic cerebral blood flow in piglets.

We tested the hypothesis that administering polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) either before global cerebral ischemia or at the time of reperfusion would alter recovery of cerebral blood flow (CBF; microspheres) response to alteration in arterial PCO2 in pentobarbital-anesthetized, mechanically ventilated piglets (1 to 2-wk old). CBF was measured at an arterial PCO2 of approximately 3.3, 5.3, and 8.7 kPa before and 2 h after ischemia (10 min aortic cross clamp). To determine the effect of preischemic versus postischemic treatment with PEG-SOD, each piglet received two i.v. drug injections of either 30,000 U PEG-SOD or an equal volume of PEG diluent in a randomized, blinded fashion before ischemia and just before reperfusion. Cerebral oxygen consumption and somatosensory evoked potentials were measured during reperfusion as an assessment of brain function. During reperfusion, no group demonstrated delayed hypoperfusion. Hypercapnic CBF was less during reperfusion (48 +/- 6 mL/min/100 g) compared with preischemia (69 +/- 10 mL/min/100 g) in PEG/PEG-treated piglets. However, hypercapnic CBF during reperfusion was not different from preischemic values with either preischemic or postischemic PEG-SOD treatment. Improved return of hypercapnic CBF in PEG-SOD-treated piglets was not attributable to improved postischemic cerebral oxygen consumption. Somatosensory evoked potential amplitude was decreased similarly during reperfusion (approximately 25% of preischemic values) in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of intracarotid and intraventricular morphine on regional cerebral blood flow and metabolism in pentobarbital-anesthetized dogs.

Potent opiate analgesics, administered either epidurally, intrathecally, or intravenously, are a common adjunct to pain control in the perioperative period. Little is known, however, of the effects of opiate agonists on cerebral blood flow (CBF) and metabolism. Current studies are complicated by the hypotensive effects of these compounds and their route of administration. To circumvent these difficulties we studied the effects of intraventricular and intracarotid morphine sulfate, in doses that do not affect arterial blood pressure, on regional CBF and total cerebral oxygen consumption (CMRO2) in pentobarbital-anesthetized dogs. Five dogs received 0.04 mg/kg morphine via intracarotid injection. Five additional dogs received 0.2 mg/kg morphine via ventricular cisternal infusion over 5 min, and five control dogs received mock cerebrospinal fluid at the same infusion rate. CBF was measured using the radiolabeled microsphere technique. Intracarotid morphine decreased neurohypophyseal blood flow to 58% of control, but it did not alter blood flow to any other brain region, except caudate nucleus, or cause a change in CMRO2. Infusion of mock cerebrospinal fluid in the cerebral ventricles did not alter CBF or CMRO2. Ventricular-cisternal perfusion of morphine caused a transient increase in CBF (24 +/- 2 to 37 +/- 6 mL min-1 100 kg-1) but had no effect on spinal cord blood flow or CMRO2. Neurohypophyseal blood flow, however, decreased to 40% of control levels (480 +/- 76 to 176 +/- 42 mL min-1 100 kg-1) after 2 min and gradually returned to control levels at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

PubMed1993

N omega-nitro-L-arginine methyl ester prevents cerebral hyperemia by inhaled anesthetics in dogs.

The mechanism by which halothane, isoflurane, and nitrous oxide increase cerebral blood flow (CBF) is unknown. We assessed the cerebrovascular effects of nitrous oxide (70%; n = 6), isoflurane (1 minimum alveolar anesthetic concentration: 1.4%; n = 6) or halothane (1 minimum alveolar anesthetic concentration: 0.8%; n = 6) before and after blockade of nitric oxide (NO) synthase with 40 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) intravenously in dogs with baseline pentobarbital anesthesia. Baseline CBF (microspheres) was determined after 1 h of pentobarbital anesthesia. Cerebral perfusion pressure (CPP) was maintained during inhaled anesthetic or L-NAME by either hemorrhage or inflation of an intra-aortic balloon. Before L-NAME, halothane and isoflurane increased CBF (40 +/- 4 to 56 +/- 6 mL.min-1 x 100 g-1 and 43 +/- 6 to 78 +/- 12 mL.min-1 x 100 g-1, respectively) with no change in cerebral oxygen consumption (baseline: halothane, 2.6 +/- 0.2; isoflurane, 2.0 +/- 0.2 mL.min-1 x 100 g-1). On the contrary, nitrous oxide increased CBF similarly (40 +/- 6 to 57 +/- 8 mL.min-1 x 100 g-1), but increased cerebral oxygen consumption (2.2 +/- 0.3 to 3.0 +/- 0.3 mL.min-1 x 100 g-1). L-NAME decreased blood flow in the neurohypophysis by 80% with no change in blood flow in other brain regions. After L-NAME, reexposure to nitrous oxide, halothane, or isoflurane resulted in no change in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

PubMed1993

Altered cerebrovascular CO2 reactivity following subarachnoid hemorrhage in cats.

The authors tested the hypothesis that cerebral blood flow (CBF) reactivity to CO2 was blunted following subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was produced in five cats by performing four cisterna magna injections of blood in each (SAH Group). A second group of six cats was treated with an antifibrinolytic agent (AF) in addition to four cisterna magna blood injections (SAH+AF Group). Four cats received AF and four cisterna magna injections of saline (Control Group). The presence or absence of basilar artery vasospasm was determined by comparing baseline and follow-up selective angiograms. Cerebral blood flow reactivity was determined by randomly varying the concentration of inspired CO2 to alter PaCO2 from 20 to 75 mm Hg. Regional CBF was measured with radiolabeled microspheres. Basilar artery vasospasm was seen following subarachnoid injection of blood but not of saline. Normocapnic CBF was similar in all three groups in the brain stem (mean +/- standard error of the mean: SAH Group 46 +/- 6, SAH+AF Group 46 +/- 6, and Control Group 44 +/- 9 ml/min/100 gm) and in the supratentorial compartment (SAH Group 53 +/- 8, SAH+AF Group 61 +/- 9, and Control Group 51 +/- 13 ml/min/100 gm). At intermediate levels of hypercarbia (PaCO2 50 +/- 3 mm Hg), CBF increased similarly in all three groups (SAH Group 161% +/- 32%, SAH+AF Group 118% +/- 33%, and Control Group 174% +/- 19% compared to baseline); at higher levels of PaCO2 (60 +/- 3 mm Hg), CBF values were SAH Group 265% +/- 50%, SAH+AF Group 205% +/- 47%, and Control Group 159% +/- 30% of baseline. At the highest level of PaCO2 (75 +/- 6 mm Hg), supratentorial CBF did not increase as much in the SAH+AF Group as in the Control Group (179% +/- 59% vs. 463% +/- 58% of baseline, respectively). The authors conclude that, in this model of SAH, there is no change in normocapnic CBF; however, blood flow reactivity to hypercarbia is blunted. It is possible that this may result from a combination of narrowing of proximal large vessels and globally impaired reactivity of small vessels.

Angiography↗

PubMed1993

Histamine-2-receptor blockade does not affect hyperemia after cerebral ischemia in young swine.

OBJECTIVE: To determine whether histamine-2 (H2) receptor antagonists can blunt the increase in cerebral blood flow after cerebral ischemia. DESIGN: Prospective, randomized trial. SETTING: Animal laboratory. SUBJECTS: Piglets aged 1 to 2 wks. INTERVENTIONS: Three groups of piglets were anesthetized with pentobarbital, mechanically ventilated, and hemodynamically monitored. Each animal was randomized to receive one of three treatments 20 mins before ischemia: famotidine (0.6 mg/kg i.v.), cimetidine (5 mg/kg i.v.), or an equivalent volume of saline (3 mL). Ischemia was maintained for 15 mins by tightening ligatures around the brachiocephalic trunk and left subclavian arteries plus the induction of hemorrhagic hypotension (50 mm Hg). Reperfusion was initiated by the reinfusion of shed blood and removal of the ligatures. MEASUREMENTS AND MAIN RESULTS: The three groups were not different with regard to baseline arterial blood gases, cerebral perfusion pressure, microsphere-determined cerebral blood flow, or oxygen consumption (VO2). Ischemia (cerebral blood flow < 5 mL/min/100 g of tissue) was demonstrated in all brain regions for all groups during arterial ligation with hemorrhage-induced hypotension. Blood flow rates were increased compared with preischemic values in all regions at 7 mins of reperfusion. For example, mean forebrain blood flow rates increased from 36 +/- 3 to 95 +/- 14 (SEM) mL/min/100 g of tissue in the group receiving saline, from 36 +/- 3 to 102 +/- 9 mL/min/100 g of tissue in the group receiving famotidine, and from 31 +/- 4 to 119 +/- 26 mL/min/100 g in the group receiving cimetidine. Overall, the three groups did not differ in regard to blood flow rates and cerebral VO2 values during ischemia and at 30 mins of reperfusion. CONCLUSIONS: We demonstrated that famotidine or cimetidine as compared with saline did not affect the pattern or extent of hyperemia after ischemia. This finding does not support the hypothesis that a H2-receptor mechanism is necessary for postischemic hyperemia.

Animals↗

PubMed1992

Hypercapnic blood flow reactivity not increased by alpha-blockade or cordotomy in piglets.

We tested the hypothesis that differential sympathetic innervation explains the attenuated cerebral blood flow (CBF) response to hypercapnia (hyper) in fore-brain (fb) compared with brain stem in 1- to 2-wk-old piglets. In pentobarbital sodium-anesthetized piglets, CBF (microspheres) was measured during hypocapnia, normocapnia (normo), and hypercapnia [arterial CO2 partial pressure (PaCO2) of 25, 40, and 65 mmHg, respectively] in random sequence. After pretreatment values were obtained, piglets were randomized to undergo sham treatment (n = 5), high cervical spinal cord transection (n = 6), or pharmacological alpha-adrenergic blockade (prazosin 1 mg/kg + yohimbine 1 mg/kg, n = 6). After each experimental treatment, CO2 reactivity was again measured. Before experimental manipulation, hypercapnic reactivity [(CBFhyper - CBFnormo)/(PaCO2hyper - PaCO2normo)] in brain stem was approximately three times greater than in forebrain (e.g., sham; 3.6 +/- 0.8 vs. 1.2 +/- 0.3 ml.min-1.100 g-1.mmHg-1). Hypercapnic reactivity in forebrain was not increased by cord transection (1.4 +/- 0.3 vs. 1.1 +/- 0.2 ml.min-1.100 g-1.mmHg-1) or alpha-blockade (1.6 +/- 0.6 vs. 1.2 +/- 0.4 ml.min-1.100 g-1.mmHg-1). Likewise, hypercapnic cerebral vascular resistance (CVR) was unchanged by experimental treatment (e.g., CVRfb; cord transection 1.1 +/- 0.1 vs. 1.0 +/- 0.1; alpha-blockade 1.1 +/- 0.2 vs. 1.0 +/- 0.1 mmHg.ml-1.min-1.100 g-1). Hypocapnic vasoconstriction, however, was attenuated by both cord transection and alpha-blockade in forebrain and brain stem. We conclude that physiological stimulation of the noradrenergic component of the sympathetic nervous system does not explain regional differences in CBF reactivity during hypercapnia in 1- to 2-wk-old piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1992

Tirilazad mesylate does not improve early cerebral metabolic recovery following compression ischemia in dogs.

BACKGROUND AND PURPOSE: Tirilazad mesylate (U74006F) has been reported to improve recovery following cerebral ischemia. We conducted a randomized blinded study to determine if the drug would improve immediate metabolic recovery after complete cerebral compression ischemia. METHODS: Mongrel dogs were anesthetized with pentobarbital and fentanyl and treated with either vehicle (citrate buffer, n = 8) or tirilazad (1.5 mg/kg i.v. plus 0.18 mg/kg/hr, n = 8). Normothermic complete cerebral compression ischemia was produced for 12 minutes by lateral ventricular fluid infusion to raise intracranial pressure above systolic arterial pressure. Cerebral high-energy phosphate concentrations and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Cerebral blood flow was measured with radiolabeled microspheres, and oxygen consumption was calculated from sagittal sinus blood samples. Somatosensory evoked potentials were measured throughout the experiment. RESULTS: During ischemia, both groups demonstrated complete loss of high-energy phosphates and a fall in intracellular pH (vehicle, 5.76 +/- 0.23; tirilazad, 5.79 +/- 0.26; mean +/- SEM). At 180 minutes of reperfusion, there were no differences between groups in recovery of intracellular pH (vehicle, 6.89 +/- 0.07; tirilazad, 6.88 +/- 0.18), phosphocreatine concentration (vehicle, 89 +/- 16%; tirilazad, 94 +/- 24% of baseline value), oxygen consumption (vehicle, 2.6 +/- 0.2 ml/min/100 g; tirilazad, 1.8 +/- 0.5 ml/min/100 g), or somatosensory evoked potential amplitude (vehicle, 11 +/- 6%; tirilazad, 7 +/- 4% of baseline value). Forebrain blood flow fell below baseline levels at 180 minutes of reperfusion in the tirilazad-treated animals but not in the vehicle-treated dogs (vehicle, 28 +/- 4 ml/min/100 g; tirilazad, 18 +/- 5 ml/min/100 g). CONCLUSIONS: We conclude that tirilazad pretreatment does not improve immediate metabolic recovery 3 hours following 12 minutes of normothermic complete ischemia produced by cerebral compression.

Animals↗

PubMed1992

Monoclonal leukocyte antibody does not decrease the injury of transient focal cerebral ischemia in cats.

BACKGROUND AND PURPOSE: We tested the hypothesis that inhibition of leukocyte function by administration of monoclonal antibody 60.3 (MoAb 60.3) improves electrophysiological recovery and decreases injury volume following transient focal cerebral ischemia in cats. METHODS: Halothane-anesthetized cats underwent 90 minutes of left middle cerebral artery and bilateral common carotid artery occlusion followed by 180 minutes of reperfusion. Cats were assigned to receive either 2 mg/kg MoAb 60.3 (n = 8) directed at the CDw18 leukocyte antigen complex or an equal volume of diluent (sterile saline; n = 10) at 45 minutes of ischemia in a blinded fashion. RESULTS: Blood flow to the left temporoparietal cortex decreased to less than 5 ml/min/100 g with ischemia, but was minimally affected on the right side. Postischemic hyperemia occurred in the left caudate nucleus, whereas blood flow in other brain regions returned to control. No region demonstrated delayed hypoperfusion, and there were no differences between groups. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 10% of baseline amplitude at 180 minutes of reperfusion in both groups. Left hemispheric injury volume, as assessed by 2,3,5-triphenyltetrazolium chloride staining, was not affected by drug treatment (mean +/- SE values: MoAb 60.3, 37 +/- 5%; placebo, 38 +/- 7% of hemisphere). CONCLUSIONS: Inhibition of leukocyte function with MoAb 60.3 does not afford protection from severe focal ischemia and reperfusion in cats.

Animals↗

PubMed1992

Intra-arterial urokinase for treatment of retrograde thrombosis following resection of an arteriovenous malformation. Case report.

Retrograde thrombosis of feeding arteries is a potentially catastrophic complication occasionally reported following resection of arteriovenous malformations (AVM's). No successful therapy for this condition, which causes postoperative stroke, has previously been reported. A case of retrograde thrombosis of the left middle cerebral artery immediately following resection of a parietal AVM is reported in a patient with a retained intra-arterial catheter from preoperative embolization. The administration of urokinase within 4 hours of surgery resulted in dramatic clinical and angiographic improvement without hemorrhagic complications. While urokinase is considered highly experimental in this setting, this case demonstrates that thrombolytic agents should be viewed as therapeutic options worthy of further investigation.

Adult↗

PubMed1992

Evidence for free radical mechanisms of brain injury resulting from ischemia/reperfusion-induced events.

Free radicals have been implicated in the injury that occurs to brain tissue in response to ischemia and reperfusion insults. Confirmatory in vivo studies have been limited by the difficulty in measuring free radicals in brain tissue. This review discusses potential mechanisms for free radical production in brain tissue and the evidence supporting the therapeutic efficacy of free radical scavengers. Free radicals may be produced during ischemia/reperfusion as a result of multiple mechanisms involving normal regulatory systems of intra-/extracellular metabolism. For example, metabolism of free fatty acids by the cyclo-oxygenase pathway and adenine nucleotides by xanthine oxidase has been proposed to produce free radical adducts during reperfusion. Therapeutic strategies aimed at decreasing brain injury from free radical production include administration of free radical scavengers at the time of reperfusion. Pharmacologic interventions for protection from free radical injury in brain are hindered because of limited access to the site of free production.

Animals↗

PubMed1991

Preoperative lumbar epidural morphine improves postoperative analgesia and ventilatory function after transsternal thymectomy in patients with myasthenia gravis.

OBJECTIVE: To test the hypothesis that preoperative lumbar epidural morphine improves postoperative pain control and ventilatory function after transsternal thymectomy in patients with myasthenia gravis. DESIGN: The study design was randomized, placebo-controlled, and double-blind. SETTING: After surgery, all patients were admitted to the Neuroscience Critical Care Unit for evaluation and treatment. PATIENTS: All patients with myasthenia gravis who presented to the hospital for thymectomy were asked to participate in the study. Twenty patients were randomized to either the placebo or epidural morphine groups. INTERVENTIONS: Patients received either epidural morphine (7 mg in 14 mL of sterile saline) or saline (14 mL) before induction of anesthesia. Supplemental iv opioids were administered intraoperatively, with need determined by the anesthesiologist. MAIN OUTCOME MEASURES: The main outcome measures were indicators of postoperative pain (e.g., Visual Analog Pain Score, requirement for supplemental opioid administration, respiratory rate) and ventilatory function (e.g., forced vital capacity, negative inspiratory pressure). RESULTS: Immediately after surgery, the Visual Analog Pain Score in the placebo group was twice as high as the score in the epidural morphine group (placebo 7.0 +/- 1.3; epidural morphine 3.5 +/- 1.2, p less than or equal to .05). During the first eight postoperative hours, the placebo group required more opioids (0.22 +/- 0.03 vs. 0.12 +/- 0.04 mg/kg morphine equivalents, p less than or equal to .06) than the epidural morphine group. Later, both groups received similar amounts of opioids. Patients receiving epidural morphine had better initial recovery of forced vital capacity (at 8 hrs: 55 +/- 6% [epidural morphine] vs. 34 +/- 5% [placebo] of preoperative value, p less than or equal to .05). Respiratory rate was lower for the first 12 postoperative hours in the epidural morphine group, without a difference in PaCO2. There was no difference between groups for the duration of postoperative intubation or ventilation. CONCLUSIONS: Preoperative lumbar epidural morphine facilitates postoperative analgesia and improves initial postoperative ventilatory performance.

Adult↗

PubMed1991

Age-related cerebrovascular reactivity to CO2 after cerebral ischemia in swine.

We tested the hypothesis that cerebral blood flow (CBF) reactivity to CO2 after global ischemia takes longer to recover in 1- to 2-wk-old piglets than in 6- to 10-mo-old pigs. All animals were sedated with ketamine and anesthetized with pentobarbital sodium. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta for 10 min. The microsphere-determined CBF response to hypercapnia (arterial PCO2 approximately 65 mmHg) was depressed at 60 min of reperfusion (9 +/- 6% of preischemia; means +/- SE) and remained depressed at 120 min (33 +/- 23% of preischemia, means +/- SE) in young pigs. In older pigs, the response was also depressed at 60 min of reperfusion (21 +/- 9% of preischemia) but was not depressed at 120 min. The pattern for recovery of hypercapnic reactivity was present in most brain regions except cerebellum, where CO2 reactivity returned to control in young animals by 120 min of reperfusion. The response to hypocapnia (arterial PCO2 approximately 25 mmHg) was also better preserved in older pigs. In older pigs recovery of CO2 reactivity during reperfusion paralleled recovery of cerebral O2 consumption over time. We conclude that older pigs have quicker return of CBF CO2 reactivity following transient global ischemia, which may be due to age-related differences in mechanisms of vascular reactivity.

Aging↗

PubMed1991

Polyethylene glycol-conjugated superoxide dismutase fails to blunt postischemic reactive hyperemia.

We tested the hypothesis that superoxide dismutase (SOD) conjugated with polyethylene glycol (PEG-SOD) would alter hyperemia following complete global cerebral ischemia. Thirty minutes before ischemia pentobarbital-anesthetized piglets were assigned to receive 3 ml of either PEG-SOD (10,000 U/ml; n = 10), an equivalent concentration of PEG (n = 10), or saline (n = 10) in a randomized and blinded manner. Cerebral ischemia was sustained for 10 min by cross-clamping the ascending aorta. Measurements of cerebral blood flow (radiolabeled microspheres) and oxygen consumption were made before ischemia and at 2, 4, 8, 12, and 15 min of reperfusion. Plasma SOD activity was higher in PEG-SOD-treated piglets (134 +/- 8 U/ml) than in PEG or saline-treated piglets (less than 5 U/ml). All groups and all brain regions demonstrated postischemic hyperemia. There were no differences in blood flow between groups at any time point in any region. At 2 min of reperfusion, blood flow to cerebrum rose from 31 +/- 4 to 88 +/- 9 ml.min-1.100 g-1 (saline), 44 +/- 6 to 102 +/- 17 ml.min-1.100 g-1 (PEG), and 31 +/- 3 to 83 +/- 16 ml.min-1.100 g-1 (PEG-SOD). During reperfusion cerebral oxygen consumption was not different from preischemic values in any group. In conclusion, we demonstrated that exogenously administered PEG-SOD raises serum SOD activity but does not alter the patterns of early cerebral blood flow or metabolic recovery after 10 min of complete global cerebral ischemia in piglets.

Animals↗

PubMed1991

Hypothermic cerebral reperfusion and recovery from ischemia.

The effect of transient postischemic hypothermia (30 degrees C) on recovery of cerebral blood flow (CBF), oxygen consumption (CMRO2) and somatosensory-evoked potentials (SEPs) was determined in anesthetized dogs. Ischemia was produced for 20 min by intracranial pressure (ICP) elevation while core temperature was lowered by cooling externalized blood. Epidural temperature was controlled at 37.6 +/- 0.2 degrees C during ischemia, lowered to 30.0 +/- 0.1 degrees C during the first hour of reperfusion, and then rewarmed to 38.0 +/- 0.1 degrees C in experimental dogs (n = 8) and maintained at 38.0 +/- 0.1 degrees C in control dogs (n = 8). ICP was lower throughout reperfusion in experimental as compared with control animals. By 240 min of reperfusion, CBF was approximately 70% of control in both groups. CMRO2 was 60% of preischemic values in control animals and 74% in experimental animals (P = 0.077). A persistent uncoupling of CBF and CMRO2 was observed throughout reperfusion only in the control group. Recovery of SEP amplitude was significantly improved in the experimental group (26 vs. 11% of preischemic values). These data suggest that transient hypothermia reduces ICP and facilitates recovery of electrophysiological function after cerebral ischemia.

Animals↗

PubMed1991

Oxygen radical mechanisms of brain injury following ischemia and reperfusion.

This review addresses current understanding of oxygen radical mechanisms as they relate to the brain during ischemia and reperfusion. The mechanism for radical production remains speculative in large part because of the difficulty of measuring radical species in vivo. Breakdown of lipid membranes during ischemia leads to accumulation of free fatty acids. Decreased energy stores during ischemia result in the accumulation of adenine nucleotides. During reperfusion, metabolism of free fatty acids via the cyclooxygenase pathway and metabolism of adenine nucleotides via the xanthine oxidase pathway are the most likely sources of oxygen radicals. Although leukocytes have been found to accumulate in some models of ischemia and reperfusion, their mechanistic role remains in question. Therapeutic strategies aimed at decreasing brain injury have included administration of radical scavengers at the time of reperfusion. Efficacy of traditional oxygen radical scavengers such as superoxide dismutase and catalase may be limited by their inability to cross the blood-brain barrier. Lipid-soluble antioxidants appear more efficacious because of their ability to cross the blood-brain barrier and because of their presence in membrane structures where peroxidative reactions can be halted.

Animals↗

PubMed1991

Cerebrovascular CO2 reactivity during delayed vasospasm in a canine model of subarachnoid hemorrhage.

While the in vitro reactivity of cerebral conducting vessels following subarachnoid hemorrhage has been extensively studied, in vivo cerebrovascular CO2 reactivity has not been systematically investigated. We tested the hypothesis that, in the canine model of subarachnoid hemorrhage, the rise in cerebral blood flow normally seen with hypercapnia is blunted during delayed vasospasm. Four groups of animals were studied: one received two 4-ml subarachnoid injections of nonheparinized arterial blood into the cisterna magna (n = 8), one received three subarachnoid injections of 5 ml blood (n = 5), one received two subarachnoid injections of 4 ml saline (n = 5), and a control group (n = 5) had no subarachnoid injections or angiography. Basilar artery diameter was measured from baseline and follow-up angiography. We determined CO2 reactivity by randomly varying the concentration of inspired CO2 and measuring regional cerebral blood flow with radiolabeled microspheres. Basilar artery diameter was not affected by saline injection and was reduced by 26 +/- 2.9% in the two-hemorrhage group and 55 +/- 1.9% in the three-hemorrhage group. Baseline cerebral blood flow and CO2 reactivity were similar in all four groups. We conclude that, in this model of delayed vasospasm, regional cerebral vascular CO2 reactivity is intact and extrapolation of in vitro data regarding basilar artery diameter and reactivity to cerebral blood flow must be done cautiously.

Animals↗

PubMed1991

Suprasellar and intraventricular blood predict elevated plasma atrial natriuretic factor in subarachnoid hemorrhage.

Following subarachnoid hemorrhage, the plasma concentration of atrial natriuretic factor is elevated and appears to be independent of atrial stretch. While the hypothalamus and circumventricular organs contribute to sodium and intravascular volume regulation, their influence on atrial natriuretic factor is not known. We tested the hypothesis that, following subarachnoid hemorrhage, suprasellar cisternal blood, intraventricular blood, or ventricular enlargement would be associated with elevated plasma levels of atrial natriuretic factor. Computed tomograms of 26 patients performed less than or equal to 3 days after hemorrhage were analyzed to determine the presence of suprasellar or intraventricular blood and enlargement of the third or lateral ventricle. These results were correlated with the plasma atrial natriuretic factor and serum sodium concentrations. The initial atrial natriuretic factor concentration was elevated and was higher in patients with suprasellar or intraventricular blood than in those without (suprasellar: 131 +/- 20 and 54 +/- 10 pg/ml, respectively; intraventricular: 137 +/- 25 and 84 +/- 31 pg/ml, respectively). The atrial natriuretic factor concentration remained higher over the week following hemorrhage in patients with suprasellar blood than in those without (127 +/- 16 and 68 +/- 12 pg/ml, respectively). The atrial natriuretic factor concentration was not correlated with hyponatremia (125-134 meq/l) or age-corrected ventricular size. Hyponatremia did not correlate with the presence of intraventricular or suprasellar blood. Our data suggest that suprasellar and intraventricular blood disturb hypothalamic function, resulting in an elevated plasma atrial natriuretic factor concentration. The presence of a direct relation between atrial natriuretic factor and hyponatremia remains unclear.

Adult↗

PubMed1991

Age-related differences in recovery of blood flow and metabolism after cerebral ischemia in swine.

We tested two hypotheses: 1) that cerebral blood flow, oxygen consumption, and evoked potentials recover to preischemic values at 120 minutes of reperfusion more completely in 1-2-week-old piglets than in 6-10-month-old pigs after complete ischemia; and 2) that recovery of cerebral blood flow, oxygen consumption, and electrical function in piglets and pigs at 120 minutes of reperfusion is better after incomplete than after complete ischemia. During 30 minutes of ischemia produced by intracranial pressure elevation, cerebral blood flow determined by the microspheres technique was decreased to 0-1 ml/min/100 g with complete ischemia, to 1-10 ml/min/100 g with severe incomplete ischemia, or to 10-20 ml/min/100 g with moderate incomplete ischemia. During reperfusion after complete ischemia, both piglets and pigs demonstrated hyperemia but delayed hypoperfusion occurred in more brain regions in pigs, oxygen consumption returned to preischemic values in piglets but not in pigs (70 +/- 10% of preischemic values), and evoked potentials recovered better in piglets than in pigs (24 +/- 4% and 9 +/- 4% of preischemic values, respectively). Both piglets and pigs had fewer brain areas with hyperemia and hypoperfusion and improved oxygen consumption and electrical function during recovery from incomplete than from complete ischemia. We speculate that piglets tolerate complete ischemia better than pigs because of decreased reperfusion injury and that both groups recover better from incomplete than complete ischemia because of improved substrate supply during ischemia.

Aging↗