Biography:

In the past James C. Eisenach has collaborated on articles with Weiya Ma and Ken-ichiro Hayashida. One of their most recent publications is Intravenous clonidine hydrochloride toxicity in pregnant ewes. Which was published in journal American Journal of Obstetrics and Gynecology.

More information about James C. Eisenach research including statistics on their citations can be found on their Copernicus Academic profile page.

James C. Eisenach's Articles: (14)

Intravenous clonidine hydrochloride toxicity in pregnant ewes

SummaryAdministration of intravenous clonidine hydrochloride has been advocated to rapidly control blood pressure in severe preeclampsia. To examine clonidine's acute maternal and fetal effects we intravenously injected 300 μg clonidine in eight chronically prepared normotensive near term ewes. Unlike intravenous saline solution injection, clonidine produced significant toxicity-intraamniotic pressure increased 97 ± 27% (p < 0.05), uterine blood flow decreased 55 ± 7% (p < 0.001), maternal and fetal serum glucose increased 158 ± 23% and 249 ± 91%, respectively (p < 0.001), and maternal and fetal PO2 decreased to 44 mm Hg ± 4 mm Hg and 13 mm Hg ± 1 mm Hg, respectively (p < 0.05). Maternal and fetal blood pressure and serum Cortisol were unaffected by clonidine, whereas heart rate decreased. No adverse maternal or fetal effects were noted with serum clonidine concentrations < 1.0 ng/ml. Direct fetal infusion of clonidine did not lower fetal arterial PO2 levels, although heart rates decreased and serum glucose levels increased. The multiple effects of clonidine infusion are best explained by actions on α2-adrenergic receptors. These results suggest that intravenous administration of clonidine may adversely affect the fetus by direct actions and by alterations in maternal physiology. (Am J Obstet Gynecol 1988;160:471-6.)

Intravenous clonidine hydrochloride toxicity in pregnant ewes

SummaryAdministration of intravenous clonidine hydrochloride has been advocated to rapidly control blood pressure in severe preeclampsia. To examine clonidine's acute maternal and fetal effects we intravenously injected 300 μg clonidine in eight chronically prepared normotensive near term ewes. Unlike intravenous saline solution injection, clonidine produced significant toxicity-intraamniotic pressure increased 97 ± 27% (p < 0.05), uterine blood flow decreased 55 ± 7% (p < 0.001), maternal and fetal serum glucose increased 158 ± 23% and 249 ± 91%, respectively (p < 0.001), and maternal and fetal PO2 decreased to 44 mm Hg ± 4 mm Hg and 13 mm Hg ± 1 mm Hg, respectively (p < 0.05). Maternal and fetal blood pressure and serum Cortisol were unaffected by clonidine, whereas heart rate decreased. No adverse maternal or fetal effects were noted with serum clonidine concentrations < 1.0 ng/ml. Direct fetal infusion of clonidine did not lower fetal arterial PO2 levels, although heart rates decreased and serum glucose levels increased. The multiple effects of clonidine infusion are best explained by actions on α2-adrenergic receptors. These results suggest that intravenous administration of clonidine may adversely affect the fetus by direct actions and by alterations in maternal physiology. (Am J Obstet Gynecol 1988;160:471-6.)

Intravenous clonidine hydrochloride toxicity in pregnant ewes

SummaryAdministration of intravenous clonidine hydrochloride has been advocated to rapidly control blood pressure in severe preeclampsia. To examine clonidine's acute maternal and fetal effects we intravenously injected 300 μg clonidine in eight chronically prepared normotensive near term ewes. Unlike intravenous saline solution injection, clonidine produced significant toxicity-intraamniotic pressure increased 97 ± 27% (p < 0.05), uterine blood flow decreased 55 ± 7% (p < 0.001), maternal and fetal serum glucose increased 158 ± 23% and 249 ± 91%, respectively (p < 0.001), and maternal and fetal PO2 decreased to 44 mm Hg ± 4 mm Hg and 13 mm Hg ± 1 mm Hg, respectively (p < 0.05). Maternal and fetal blood pressure and serum Cortisol were unaffected by clonidine, whereas heart rate decreased. No adverse maternal or fetal effects were noted with serum clonidine concentrations < 1.0 ng/ml. Direct fetal infusion of clonidine did not lower fetal arterial PO2 levels, although heart rates decreased and serum glucose levels increased. The multiple effects of clonidine infusion are best explained by actions on α2-adrenergic receptors. These results suggest that intravenous administration of clonidine may adversely affect the fetus by direct actions and by alterations in maternal physiology. (Am J Obstet Gynecol 1988;160:471-6.)

Intravenous clonidine hydrochloride toxicity in pregnant ewes

SummaryAdministration of intravenous clonidine hydrochloride has been advocated to rapidly control blood pressure in severe preeclampsia. To examine clonidine's acute maternal and fetal effects we intravenously injected 300 μg clonidine in eight chronically prepared normotensive near term ewes. Unlike intravenous saline solution injection, clonidine produced significant toxicity-intraamniotic pressure increased 97 ± 27% (p < 0.05), uterine blood flow decreased 55 ± 7% (p < 0.001), maternal and fetal serum glucose increased 158 ± 23% and 249 ± 91%, respectively (p < 0.001), and maternal and fetal PO2 decreased to 44 mm Hg ± 4 mm Hg and 13 mm Hg ± 1 mm Hg, respectively (p < 0.05). Maternal and fetal blood pressure and serum Cortisol were unaffected by clonidine, whereas heart rate decreased. No adverse maternal or fetal effects were noted with serum clonidine concentrations < 1.0 ng/ml. Direct fetal infusion of clonidine did not lower fetal arterial PO2 levels, although heart rates decreased and serum glucose levels increased. The multiple effects of clonidine infusion are best explained by actions on α2-adrenergic receptors. These results suggest that intravenous administration of clonidine may adversely affect the fetus by direct actions and by alterations in maternal physiology. (Am J Obstet Gynecol 1988;160:471-6.)

Intravenous clonidine hydrochloride toxicity in pregnant ewes

SummaryAdministration of intravenous clonidine hydrochloride has been advocated to rapidly control blood pressure in severe preeclampsia. To examine clonidine's acute maternal and fetal effects we intravenously injected 300 μg clonidine in eight chronically prepared normotensive near term ewes. Unlike intravenous saline solution injection, clonidine produced significant toxicity-intraamniotic pressure increased 97 ± 27% (p < 0.05), uterine blood flow decreased 55 ± 7% (p < 0.001), maternal and fetal serum glucose increased 158 ± 23% and 249 ± 91%, respectively (p < 0.001), and maternal and fetal PO2 decreased to 44 mm Hg ± 4 mm Hg and 13 mm Hg ± 1 mm Hg, respectively (p < 0.05). Maternal and fetal blood pressure and serum Cortisol were unaffected by clonidine, whereas heart rate decreased. No adverse maternal or fetal effects were noted with serum clonidine concentrations < 1.0 ng/ml. Direct fetal infusion of clonidine did not lower fetal arterial PO2 levels, although heart rates decreased and serum glucose levels increased. The multiple effects of clonidine infusion are best explained by actions on α2-adrenergic receptors. These results suggest that intravenous administration of clonidine may adversely affect the fetus by direct actions and by alterations in maternal physiology. (Am J Obstet Gynecol 1988;160:471-6.)

Chapter 23 - The Role of Medical Societies and Their Foundations in Supporting Entrepreneurs: A View From Anesthesiology

AbstractThere is a need for better education and better networking opportunities for innovative entrepreneurs in the specialty of anesthesiology as in all of medicine. Who best provides these depends on the structures and missions of national societies and foundations. In the case of the Foundation for Anesthesiology Education and Research, our mission to develop the next generation of physician-scientists in the specialty does not align with this, although we have sponsored some education and networking programs for entrepreneurs.

Research reportChronic constriction injury of sciatic nerve induces the up-regulation of descending inhibitory noradrenergic innervation to the lumbar dorsal horn of mice

AbstractPeripheral nerve injury in rodents results in hypersensitivity to mechanical and thermal stimuli accompanied by reduced antinociceptive efficacy of opioids and, in some models, sensitivity to sympathetic blockade. α2-Adrenergic receptor agonists increase in potency and efficacy after nerve injury in rodents and effectively relieve neuropathic pain in humans who do not get pain relief from opioids. However, the underlying mechanisms are unclear. It has been well known that the major noradrenergic innervation of the spinal dorsal horn originates from the locus coeruleus nucleus (LC) in the brainstem. Therefore, the aim of this study is to examine whether peripheral nerve injury that causes neuropathic pain modulates the noradrenergic innervation to the lumbar dorsal horn, in order to determine the possible anatomical substrates underlying increased potency and efficacy of noradrenergic receptor agonists in alleviating neuropathic pain. At 2 weeks after chronic constriction injury (CCI) of the sciatic nerve, a remarkable increase in tyrosine-hydroxylase (TH) and dopamine β-hydroxylase (DβH) immunoreactive (IR) axonal terminals was observed in the ipsilateral L4–L6 dorsal horn. Consistently, greater numbers of both TH- and DβH-IR neurons were detected in the ipsilateral LC. Interestingly, in the lower lumbar and upper sacral spinal dorsal horn, numerous TH-IR neurons were observed in the superficial dorsal horn (primarily lamina I). CCI of the sciatic nerve did not change the number of these TH-IR cells. These findings suggest that augmented descending inhibitory noradrenergic innervation to the dorsal horn could be one of the mechanisms underlying the increased effectiveness in the anti-allodynic effect elicited by α2-adrenergic receptor agonists.

Research reportIntrathecal injection of cAMP response element binding protein (CREB) antisense oligonucleotide attenuates tactile allodynia caused by partial sciatic nerve ligation

AbstractThe transcription factor cAMP responsive element binding protein (CREB) is important in regulating immediate-early genes and some late-effector genes involved in neuroplasticity in response to peripheral injury and stressful insults. Partial nerve injury elicited neuropathic pain is accompanied by increased phosphorylation of CREB in the ipsilateral spinal cord dorsal horn (Ma and Quirion, Pain 93 (2001) 295; Miletic et al., Pain 99 (2002) 493). The aim of this study is to determine whether increased phosphorylation of CREB in the dorsal horn contributes to the pathogenesis of neuropathic pain. Three weeks following partial sciatic nerve ligation (PSNL), daily intrathecal injection of antisense CREB oligodeoxynucleotide (ODN, 20 μg/day) for 5 days significantly attenuated tactile allodynia. The attenuation lasted for more than 4 days. Total CREB and phosphorylated CREB in both ipsilateral and contralateral dorsal horn neurons were dramatically reduced in antisense ODN injected PSNL rats 1 week after injection. The extent of reduction of total CREB and phosphorylated CREB containing cells in the dorsal horn ipsilateral to injury was greater than in the contralateral dorsal horn. These data suggest that phosphorylation of CREB is an important contributing event in the central plasticity of nerve injury and in the pathogenesis of neuropathic pain.

Research ReportActivation of glutamate transporters in the locus coeruleus paradoxically activates descending inhibition in rats

AbstractDescending noradrenergic inhibition is an important endogenous pain-relief mechanism which can be activated by local glutamate signaling. In the present study, we examined the effect of glutamate transporter activation by riluzole in the regulation of activity of locus coeruleus (LC) neurons, which provide the major inhibitory descending noradrenergic projection to the spinal cord. Local injection of riluzole into the LC dose-dependently reduced hypersensitivity in rats after L5-L6 spinal nerve ligation (SNL). This anti-hypersensitivity effect of LC-injected riluzole was blocked by intrathecal administration of the α2-adrenoceptor antagonist idazoxan and intra-LC co-injection of the AMPA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the gap-junction blockers, carbenoxolone (CBX) and meclofenamic acid (MEC). In brainstem slices from normal rats, riluzole increased phosphorylated cAMP response element binding protein (pCREB) expressing nuclei in dopamine-β-hydroxylase (DβH) containing cells in the LC. This riluzole-induced pCREB activation in LC neurons was also blocked by CNQX and CBX. In the primary astrocyte culture, riluzole enhanced glutamate-induced glutamate release. Contrary to expectations, these results suggest that activation of glutamate transporters in the LC results in increase of extracellular glutamate signaling, possibly via facilitation of glutamate release from astrocytes, and activation of LC neurons to induce descending inhibition, and that this paradoxical action of glutamate transporters in the LC requires gap-junction connections.

Knock down of the α5 nicotinic acetylcholine receptor in spinal nerve-ligated rats alleviates mechanical allodynia

AbstractNicotinic acetylcholine receptor (nAChR) agonists are known to alleviate neuropathic and inflammatory pain via activation of a heterogeneous population of receptors. However, the function of nAChRs in the maintenance of neuropathic pain is not known. Spinal nerve ligation (SNL) increases the spinal expression of the α5 nAChR subunit ipsilateral to injury. The α5 subunit is unique because it modifies numerous characteristics of existing functional nAChRs, but it does not form functional nAChRs when expressed alone or with β nicotinic subunits. Because there are no α5 subunit selective ligands, we used antisense oligonucleotides (ODNs) to assess the contribution of the α5 subunit to the maintenance of mechanical allodynia following SNL. Intrathecal antisense oligonucleotides were administered to SNL rats after the development of mechanical allodynia (10–12 days post-SNL). I.t. antisense specifically reduced α5 immunoreactivity (α5-IR) by 50–70% in the outer laminae of the dorsal horn and moderately alleviated mechanical allodynia. Furthermore, using the phosphorylation of cAMP response element-binding protein (pCREB) as a general marker of neuronal activation, a significant increase in pCREB immunoreactivity was observed in SNL rats. Treatment of SNL rats with α5-antisense significantly reduced pCREB immunoreactivity. These results suggest that the increased expression of the α5 nAChR subunit following SNL contributes to spinal CREB phosphorylation and the maintenance of mechanical allodynia.

Pupil responses and pain ratings to heat stimuli: Reliability and effects of expectations and a conditioning pain stimulus

Highlights•Acute changes in pupil diameter reflect changes in locus coeruleus activity.•Pupil dilation occurs in response to noxious stimulation, but the effect of heat stimuli on pupil response has not been tested.•In volunteers, pupil dilation correlates with heat temperature and with pain intensity.•The relationship between pupil dilation and pain intensity report is disrupted when cognitive load is increased.

Prior laparotomy or corticosterone potentiates lipopolysaccharide-induced fever and sickness behaviors

AbstractStimulating sensitized immune cells with a subsequent immune challenge results in potentiated pro-inflammatory responses translating into exacerbated sickness responses (i.e. fever, pain and lethargy). Both corticosterone (CORT) and laparotomy cause sensitization, leading to enhanced sickness-induced neuroinflammation or pain (respectively). However, it is unknown whether this sensitization affects all sickness behaviors and immune cell responses equally. We show that prior CORT and prior laparotomy potentiated LPS-induced fever but not lethargy. Prior CORT, like prior laparotomy, was able to potentiate sickness-induced pain. Release of nitric oxide (NO) from peritoneal macrophages stimulated ex vivo demonstrates that laparotomy, but not CORT sensitizes these cells.

Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression

AbstractCesarean delivery rates continue to increase, and surgery is associated with chronic pain, often co-existing with depression. Also, acute pain in the days after surgery is a strong predictor of chronic pain. Here we tested if mode of delivery or acute pain played a role in persistent pain and depression after childbirth. In this multicenter, prospective, longitudinal cohort study, 1288 women hospitalized for cesarean or vaginal delivery were enrolled. Data were obtained from patient interviews and medical record review within 36 h postpartum, then via telephone interviews 8 weeks later to assess persistent pain and postpartum depressive symptoms. The impact of delivery mode on acute postpartum pain, persistent pain and depressive symptoms and their interrelationships was assessed using regression analysis with propensity adjustment. The prevalence of severe acute pain within 36 h postpartum was 10.9%, while persistent pain and depression at 8 weeks postpartum were 9.8% and 11.2%, respectively. Severity of acute postpartum pain, but not mode of delivery, was independently related to the risk of persistent postpartum pain and depression. Women with severe acute postpartum pain had a 2.5-fold increased risk of persistent pain and a 3.0-fold increased risk of postpartum depression compared to those with mild postpartum pain. In summary, cesarean delivery does not increase the risk of persistent pain and postpartum depression. In contrast, the severity of the acute pain response to childbirth predicts persistent morbidity, suggesting the need to more carefully address pain treatment in the days following childbirth.

Original ReportPain Intensity and Duration Can Be Enhanced by Prior Challenge: Initial Evidence Suggestive of a Role of Microglial Priming

AbstractActivation of spinal microglia and consequent release of proinflammatory mediators facilitate pain. Under certain conditions, responses of activated microglia can become enhanced. Enhanced microglial production of proinflammatory products may result from priming (sensitization), similar to macrophage priming. We hypothesized that if spinal microglia were primed by an initial inflammatory challenge, subsequent challenges may create enhanced pain. Here, we used a “two-hit” paradigm using 2 successive challenges, which affect overlapping populations of spinal microglia, presented 2 weeks apart. Mechanical allodynia and/or activation of spinal glia were assessed. Initially, laparotomy preceded systemic lipopolysaccharide (LPS). Prior laparotomy caused prolonged microglial (not astrocyte) activation plus enhanced LPS-induced allodynia. In this “two-hit” paradigm, minocycline, a microglial activation inhibitor, significantly reduced later exaggerated pain induced by prior surgery when minocycline was administered intrathecally for 5 days starting either at the time of surgery or 5 days before LPS administration. To test generality of the priming effect, subcutaneous formalin preceded intrathecal HIV-1 gp120, which activates spinal microglia and causes robust allodynia. Prior formalin enhanced intrathecal gp120-induced allodynia, suggesting that microglial priming is not limited to laparotomy and again supporting a spinal site of action. Therefore, spinal microglial priming may increase vulnerability to pain enhancement.PerspectiveSpinal microglia may become “primed” (sensitized) following their activation by disparate forms of peripheral trauma/inflammation. As a result, such primed microglia may overrespond to subsequent challenges, thereby enhancing pain intensity and duration.

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