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J R Kirsch

Publications and source records attributed to J R Kirsch.

At least 91 records · Page 5Linked to original sources
PubMed1991

Polyethylene glycol-conjugated superoxide dismutase fails to augment brain superoxide dismutase activity in piglets.

We studied the effect of intravenously administered polyethylene glycol-conjugated superoxide dismutase (8,000 units/kg) on brain superoxide dismutase activity in 44 1-2-week-old piglets in the absence and presence of global cerebral ischemia and reperfusion. Four groups (n = 6 each) of piglets not exposed to ischemia were studied. Enzyme administration increased plasma superoxide dismutase activity from less than 5 to 142 +/- 8 units/ml (mean +/- SEM) without increasing brain activity (e.g., activities in the caudate were 7.9 +/- 0.5 and 8.1 +/- 0.4 units/mg protein) for up to 2 hours following administration. Four additional groups (n = 5 each) of piglets were given either enzyme or polyethylene glycol 5 minutes prior to 10 minutes of global cerebral ischemia induced by aortic cross-clamping followed by either 5 or 45 minutes of reperfusion. Enzyme administration increased plasma superoxide dismutase activity from less than 5 to 144 +/- 5 units/ml but failed to increase brain activity even after 45 minutes of reperfusion (e.g., activities in the caudate were 8.5 +/- 0.3 and 8.6 +/- 0.6 units/mg protein). We conclude that intravenous polyethylene glycol-conjugated superoxide dismutase does not increase superoxide dismutase activity in the brain despite global ischemia and reperfusion.

Animals↗
PubMed1991

Conjugated superoxide dismutase reduces extent of caudate injury after transient focal ischemia in cats.

We tested the efficacy of preischemic and postischemic systemic treatment with 30,000 units polyethylene glycol-conjugated superoxide dismutase in a reperfusion model of focal cerebral ischemia. Forty-one anesthetized cats underwent 2 hours' occlusion of the left middle cerebral artery and both common carotid arteries followed by 4 hours of reperfusion. Cats were blindly assigned to one of three groups: treatment with vehicle (10% polyethylene glycol in saline, n = 17), pretreatment with drug 3 hours before ischemia (n = 12), and posttreatment with drug at the time of reperfusion (n = 12). Size of the ischemic injury was calculated from 2,3,5-triphenyltetrazolium chloride staining. Injury in the caudate nucleus was significantly reduced with pretreatment (28 +/- 6% of ipsilateral caudate volume, mean +/- SEM) compared with the vehicle (56 +/- 8%). Posttreatment did not significantly ameliorate caudate injury (46 +/- 10%). Between the first and second hours of ischemia ipsilateral caudate blood flow determined using microspheres increased significantly from 11 +/- 4 to 16 +/- 5 ml/min/100 g with pretreatment, but blood flow remained constant throughout ischemia with vehicle (8 +/- 2 ml/min/100 g) and posttreatment (10 +/- 3 ml/min/100 g). The size of cortical injury (vehicle, 17 +/- 5%; pretreatment, 11 +/- 3%; posttreatment, 17 +/- 5% of hemispheric volume) did not differ significantly among groups. Somatosensory evoked potential recovery did not differ among groups. We conclude that pretreatment with conjugated superoxide dismutase can ameliorate the extent of injury in an end-artery region, such as the caudate nucleus, in a reperfusion model of focal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Age-related cerebrovascular response to global ischemia in pigs.

We tested the hypothesis that 1- to 2-wk-old pigs (piglet) have improved recovery of cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and somatosensory-evoked potentials (SEP) compared with 6- to 8-mo-old pigs (pig) after transient global cerebral ischemia. All animals were anesthetized with pentobarbital sodium. After tracheostomy ventilation was adjusted to maintain normoxia (arterial oxygen pressure, 100-150 mmHg) and normocarbia (arterial carbon dioxide pressure, 35-40 mmHg). Arterial blood gases, blood pressure, and hemoglobin concentration remained within physiological limits throughout the experiment. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta. During ischemia the electroencephalogram and SEP became isoelectric within 40 and 120 s, respectively. At 10 min of reperfusion hyperemia occurred in most brain regions (e.g., whole brain: piglet, 270 +/- 45%; pig, 316 +/- 48%). In pigs delayed hypoperfusion occurred in all regions except white matter. In contrast, piglets only had delayed hyperperfusion to the brain stem and caudate nucleus. Throughout reperfusion CMRO2 was decreased in pigs (3.3 +/- 0.4 to 1.9 +/- 0.2 ml.min-1.100 g-1) but was not different from control (2.7 +/- 0.3 ml.min-1.100 g-1) in piglets. By the end of reperfusion SEP amplitude was closer to control in piglets than pigs (55 +/- 9 vs. 32 +/- 4% of control). We conclude that 1- to 2-wk-old piglets have quicker return of CBF, CMRO2, and SEP to control values after global ischemia, which mechanistically may explain previous reports of improved neurological recovery in young animals after transient ischemia.

Aging↗
PubMed1990

Cerebrospinal fluid atrial natriuretic factor in intracranial disease.

We tested the hypothesis that the concentration of atrial natriuretic factor in the cerebrospinal fluid is an indicator of brain injury in patients with intracranial disease. Atrial natriuretic factor concentration was measured in 72 samples of cerebrospinal fluid from 28 patients with intraventricular drains and in nine samples from outpatient controls undergoing diagnostic lumbar puncture. Levels were correlated with diagnosis; systemic fluid administration; concentration of atrial natriuretic factor in the plasma; intracranial pressure; sodium, glucose, and protein concentrations, osmolality, and cell count in the cerebrospinal fluid; sodium concentration in the serum; and hemodynamics. Atrial natriuretic factor concentration was highest in cerebrospinal fluid from patients with intracerebral hematoma, followed by those with obstructive hydrocephalus and subarachnoid hemorrhage (19 +/- 2, 13 +/- 3, and 8 +/- 2 pg/ml, respectively); atrial natriuretic factor concentration was less than 4 pg/ml in the controls. Patients treated with fluid restriction had significantly higher atrial natriuretic factor levels than those receiving maintenance or high-volume fluids (16 +/- 3, 8 +/- 2, 10 +/- 1 pg/ml, respectively). The concentration of atrial natriuretic factor in the plasma was significantly elevated in patients with intracerebral hematoma and subarachnoid hemorrhage (155 +/- 38 and 92 +/- 20 pg/ml, respectively) and did not correlate with fluid administration or the concentration of atrial natriuretic factor in the cerebrospinal fluid. Neither cerebrospinal fluid nor plasma concentrations of atrial natriuretic factor correlated with intracranial pressure; cerebrospinal fluid sodium, glucose, or protein concentrations, osmolality, or cell count; serum sodium concentration; or hemodynamics. We conclude that the concentration of atrial natriuretic factor in the cerebrospinal fluid is a nonspecific indicator of brain injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1990

Anesthetic modulation of cerebral hemodynamic and evoked responses to transient middle cerebral artery occlusion in cats.

We measured cerebral blood flow and somatosensory evoked potentials during transient focal cerebral ischemia in cats to compare the effects of four commonly used anesthetic regimens: ketamine/fentanyl/N2O (fentanyl), pentobarbital, ketamine/alpha-chloralose (alpha-chloralose), and ketamine/halothane/N2O (halothane). Six cats in each group were subjected to 60 minutes of left middle cerebral artery occlusion followed by 120 minutes of reperfusion. Although the amplitude of the initial somatosensory evoked potential wave complex was highest in the alpha-chloralose group (58.6 +/- 16.5 microV) and smallest in the halothane group (27.5 +/- 5.7 microV), amplitude fell by 75% in all groups upon occlusion. Baseline cerebral blood flow varied substantially between groups (e.g., in the right intersylvian gyrus: fentanyl, 96 +/- 12; pentobarbital, 30 +/- 5; alpha-chloralose, 24 +/- 3; and halothane, 76 +/- 11 ml/min/100 g). Occlusion decreased cerebral blood flow to subcortical (e.g., left caudate) structures in all groups (fentanyl, 29 +/- 11%; pentobabital, 45 +/- 12%; alpha-chloralose, 27 +/- 13%; and halothane, 18 +/- 5% of baseline). Postischemic hyperemia occurred in the cortical regions of cats anesthetized with pentobarbital or alpha-chloralose that had reduced cerebral blood flows during occlusion but not in cats anesthetized with fentanyl (cerebral blood flow during occlusion not different from that of cats anesthetized with pentobarbital or alpha-chloralose) or halothane. After 120 minutes of reperfusion, cerebral blood flow had returned to baseline values in all groups. Recovery of cerebral blood flow and somatosensory evoked potential amplitude at that time did not differ among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1990

Failure of endotoxic shock to elicit superoxide anion production in pig brain.

Endotoxin shock in pigs alters cerebral blood flow regulation. This study sought 1) to evaluate global cerebral electrical function using somatosensory evoked potential and 2) to determine if superoxide anion free radical (O2-) is generated in brain following endotoxin infusion. Five female pigs received E. coli endotoxin (0.1 mg/kg i.v.) and supplemental fluid to maintain cardiac output at control levels. Somatosensory evoked potential was generated before and after endotoxin infusion, and nitroblue tetrazolium (NBT) precipitation in cranial windows was used to determine O2- production by brain. Following endotoxin infusion, mean arterial blood pressure, cerebral perfusion pressure, and systemic vascular resistance fell by 50% and cerebral oxygen extraction increased. The amplitude and the latency of somatosensory evoked potential performed 60 min after endotoxin were unchanged from that generated at control. No precipitation of NBT in cranial windows was observed, indicating that O2- was not generated. Since endotoxin shock did not alter cerebral electrical function and O2- was not generated by brain, we conclude that alterations in cerebral blood flow regulation observed in fluid-resuscitated endotoxic shock do not result from inadequate cerebral oxygen consumption, nor is the extracellular production of O2- involved in the pathogenesis of this disorder.

Animals↗
PubMed1989

Current concepts in brain resuscitation.

The area of cerebral resuscitation has become an exciting area of research in critical care medicine. It is a complicated field, however, which has seen attempts to protect the brain using a single therapy such as barbiturates ultimately disappoint investigators in the field. It is likely that much more work needs to be done in understanding the intracellular metabolic and biochemical effects of ischemia before therapies can be designed that are likely to be effective. This work might ultimately require knowledge of how ischemia or hypoxia interrupt cellular RNA and DNA machinery before these effective therapies can be developed. Before we are discouraged by the difficulty of the task, however, it is useful to review how much progress has been made in understanding the pathophysiology of ischemic brain injury in the past decade, so that we may be challenged to continue our efforts in this exciting area of critical care medicine.

Animals↗
PubMed1989

Sodium and water regulation in a patient with cerebral salt wasting.

Hyponatremia, in patients with central nervous system disease, can be attributable to impaired free water excretion (syndrome of inappropriate secretion of antidiuretic hormone) or to excessive sodium excretion (cerebral salt wasting). We present a patient with a parietal glioma and hyponatremia characterized by salt wasting and dehydration. Rehydration and sodium repletion corrected the sodium and volume deficits; withdrawal of supplemental sodium resulted in recurrence of dehydration and hyponatremia. We determined sodium and water balance and measured plasma atriopeptin, antidiuretic hormone, and aldosterone. Plasma atriopeptin ranged from 8 to 44 pg/mL (normal, less than 45 pg/mL); antidiuretic hormone was not elevated at 4 to 5 pg/mL, and aldosterone was slightly elevated at 1040.25 pmol/L. The concentrations of these hormones could not directly explain the natriuresis; interactions with neural or other humoral factors may be involved. In evaluating such patients, careful attention to sodium and water balance is important to guide appropriate therapy.

Adult↗
PubMed1989

Brain resuscitation. Medical management and innovations.

In this article, we have reviewed the pathophysiology and several therapeutic strategies for cerebral ischemia. It seems likely that there will never be simple therapeutic answers to the complex pathophysiology of cerebral ischemia as we now understand it. Ultimate therapies will probably involve combinations of interventions designed to block several ongoing pathophysiologic processes in neuronal death. Progress in this field will likely be slow and difficult.

Amino Acids↗
PubMed1988

Effect of centrally administered encephalinamides on regional cerebral blood flow in the dog.

(D-ala2)-met5-encephalinamide (AM encephalinamide) and (D-ala2)-leu5-encephalinamide (AL encephalinamide) were administered into the cisterna magna in anesthetized dogs to determine whether these opiates effected the neurohypophyseal circulation differently than the circulation of other brain areas. At the beginning of the experimental protocol, animals were given either mock cerebral spinal fluid (CSF) or 5 or 25 mg of AM encephalinamide or 5 mg of AL encephalinamide in equal volumes of mock CSF into the cisterna magna. By 60 min after intracisternal injection, radiolabeled AM encephalinamide distributed throughout the brain with the highest concentration being in the area of the brainstem. Sixty minutes after intracisternal injection, heart rate was decreased 29.0 +/- 5.1%, 41.3 +/- 4.4%, and 36.0 +/- 3.6%, and MABP was decreased 25.2 +/- 8.0%, 26.4 +/- 2.4%, and 32.3 +/- 2.6% in animals treated with AL encephalinamide (5 mg), AM encephalinamide (5 mg), and AM encephalinamide (25 mg), respectively. Neither AL encephalinamide or AM encephalinamide altered CBF or CMRO2 when compared with animals treated with mock CSF, whereas both AL encephalinamide and AM encephalinamide reduced neurohypophyseal blood flow by 30 min (43 +/- 11%, AL encephalinamide; 35 +/- 7%, AM encephalinamide, 5 mg; 46 +/- 8%, AM encephalinamide, 25 mg); the reduction was sustained throughout the 60-min protocol (34 +/- 10%, AL encephalinamide; 37 +/- 3%, AM encephalinamide, 5 mg; 38 +/- 4% AM encephalinamide, 25 mg). Plasma arginine vasopressin was transiently elevated 15 (326 +/- 75%, AL encephalinamide; 323 +/- 109%, AM encephalinamide, 25 mg) and 30 min (271 +/- 68%, AL encephalinamide; 368 +/- 136%, AM encephalinamide, 25 mg) in animals treated with AL encephalinamide or AM encephalinamide (25 mg). Intravenous naloxone administered at the end of the 60-min encephalinamide protocol was associated with a rise toward control values in heart rate and MABP in the AL encephalinamide group and in heart rate, MABP, and neurohypophyseal blood flow in both the AM encephalinamide 5 mg and 25 mg groups. These data suggest that encephalinamides may play a role in the regulation of neurohypophyseal blood flow through their actions on opiate receptors.

Animals↗
PubMed1986

Current concepts in brain resuscitation.

In spite of the tremendous amount of effort and money put forth to reduce morbidity and mortality associated with global cerebral ischemia, the outlook for patients suffering an ischemic insult remains dismal. The lack of a sufficient substrate supply during the period of ischemia as well as the production of toxic metabolites in response to ischemia have been incriminated as key factors causing brain damage. As discussed in this article, modes of therapy have included efforts to minimize the duration of ischemia (eg, effective cardiopulmonary resuscitation, hemodilution, heparinization, calcium antagonists) and decrease the production of toxic metabolites (eg, barbiturates, calcium antagonists). Although the barbiturates have also been proposed to decrease the metabolic needs during ischemia, they have no therapeutic value for global cerebral ischemia. The initial evaluation of the calcium antagonists has been more promising.

Animals↗
PubMed1985

Cerebral blood flow measurement techniques in infants and children.

The tremendous growth of interest in neurologic intensive care and in the pathophysiology of the cerebral circulation in the past few years has resulted in increasing numbers of studies that document alterations in cerebral flow during the course of various diseases or as a response to treatment of them. Before pediatricians come to conclusions based on these studies, it is important to have an understanding of the techniques involved. The techniques are complex and difficult but are based on understandable principles. They also have limitations and are subject to misinterpretations. Pediatricians should become knowledgeable about some of these techniques and their limitations because it is likely that they will be applied with increasing frequency in the next several years. We are on the threshold of exciting discoveries in abnormalities of cerebral blood flow and cerebral metabolism not only in critically ill children but also in children with congenital and learning disorders.

Adolescent↗
PubMedDate not supplied

Skin conductance and heart rate in women with premenstrual syndrome.

This study investigated the effects of the menstrual cycle phase on certain components of autonomic arousal and task performance. Premenstrual syndrome (PMS) women and matched controls (non-PMS) were tested both premenstrually and postmenstrually. The conditions selected were a) the presentation of 10 tones, b) a proofreading performance task, and c) a word-association learning task. Skin conductance and heart rate were continuously monitored. No significant effects were found on baseline physiological measures, or on proofreading or word-association performance. A significant point in cycle effect for skin conductance and HR orienting response to the tones was found showing smaller HR and skin conductance responses postmenstrually. Several significant PMS classifications by point in menstrual cycle interactions were found. These indicated that, paradoxically, the non-PMS subjects showed higher spontaneous skin conductance responding during the word association task and higher skin conductance responses to tones prior to menses. While in contrast, PMS subjects yielded higher responding on the same measures postmenstrually. On stress ratings, PMS subjects reported experiencing more stress postmenstrually. Results are discussed in terms of the possible role of expectancy factors and inaccurate self-monitoring.

Adult↗
PubMedDate not supplied

Butanediol induced ketosis increases tolerance to hypoxia in the mouse.

In previous studies from our laboratory a positive correlation between elevated blood ketone levels and the survival time (ST) during hypoxia (4-5% oxygen) was observed in fasted and alloxan diabetic mice. To test the hypothesis that ketosis was somehow increasing the tolerance of mice to hypoxia, we induced ketosis by either oral (PO), intraperitoneal (IP), or intravenous (IV) 1,3-butanediol (BD). Blood beta-hydroxbutyrate increased from 0.33 +/- 0.06 mM to 3.32 +/- 0.08 mM for PO, 1.2 +/- 0.2 mM for IV and 0.83 +/- 0.15 mM for IP. BD was associated with an increase in ST to 458% (n = 19) when given PO, 217% (n = 12) by IP route, and 560% (n = 13) by the IV route. The effect of ambient temperature (Ta) on this phenomenon was evaluated at 12, 22, 32, and 34 degrees C. At each Ta, IV BD at 1.4 mmole/mouse was associated with an increase in ST to 525, 559, 151, and 145% of control, respectively. The absolute ST of both control and treated mice was greater at Ta of 12 and 22 degrees C. Hypoxia, however, was associated with a decrease in body temperature in each group. It is concluded that the artificial induction of ketosis by BD is associated with an increase in ST of mice exposed to hypoxia.

Animals↗
PubMedDate not supplied

Hypoxic tolerance enhanced by beta-hydroxybutyrate-glucagon in the mouse.

A coorelation has been observed between increased blood ketones and the tolerance of mice to hypoxia (4-5% oxygen). In previous studies fasted mice, alloxan diabetic mice and mice given 1,3-butanediol were found to be ketotic and to have increased tolerance to hypoxia. We attempted to induce a similar increased hypoxic tolerance by direct elevation of blood ketones with IV and IP beta-hydroxybutyrate (BHB). No increase in hypoxic tolerance was observed with BHB alone. Inasmuch as fasting and alloxan diabetes are both associated with elevated blood glucagon (G), hypoxic tolerance tests were made 30 min after G alone or a combination of G plus BHB. The mice given G alone or BHB alone had hypoxic survival times not different from saline controls. The mice given G plus BHB had increased survival times that could not be explained on the basis of a G mediated alteration in blood BHB.

Animals↗
PubMedDate not supplied

Role of tissue lactate and substrate availability in 1,3-butanediol-enhanced hypoxic survival in the mouse.

Previously we found that 1,3-butanediol-treated mice live longer during hypoxia. We hypothesized that 1,3-butanediol could reduce the brain's accumulation of potentially cytotoxic lactate and/or elevate brain substrate availability (ketones or glucose) and thus maintain the brain's energy producing capability even during reduced oxygen availability. To test these hypotheses, whole brain metabolites from normoxic and hypoxic mice, pretreated with 1,3-butanediol or insulin, were compared to saline controls. During hypoxia both pretreated groups had lower brain lactate than controls. If lactate accumulation was the sole factor responsible for hypoxic tolerance, insulin should have increased brain lactate since insulin has been shown previously to reduce hypoxic tolerance. In normoxic mice the ratio of lactate to pyruvate and the level of malate and fumarate were not changed by 1,3-butanediol as is found with other agents known to protect the hypoxic animal. When substrate availability was directly elevated by beta-hydroxybutyrate and glucose administration hypoxic survival time increased thus implicating substrate availability as an important factor in hypoxic tolerance. We conclude that reduced brain lactate and augmented substrate availability both contribute to 1,3-butanediol-enhanced hypoxic tolerance in this animal model.

Animals↗