Antinociceptive and Hemodynamic Effects of a Novel α2-Adrenergic Agonist, MPV-2426, in Sheep 

1999 ◽  
Vol 91 (5) ◽  
pp. 1425-1425 ◽  
Author(s):  
James C. Eisenach ◽  
Patricia Lavand'homme ◽  
Chuanyao Tong ◽  
Jen-Kun Cheng ◽  
Hui-Lin Pan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cord Blood ◽  
Intrathecal Injection ◽  
Adrenergic Agonists ◽  
Hemodynamic Effects ◽  
Adrenergic Agonist ◽  
Spinal Cord Blood Flow ◽  
Arterial Blood

Background alpha2-Adrenergic agonists produce analgesia primarily by a spinal action and hypotension and bradycardia by actions at several sites. Clonidine is approved for epidural use in the treatment of neuropathic pain, but its wider application is limited by hemodynamic side effects. This study determined the antinociceptive and hemodynamic effects of a novel alpha2-adrenergic agonist, MPV-2426, in sheep. Methods Forty sheep of mixed Western breeds with indwelling catheters were studied. In separate studies, antinociception to a mechanical stimulus, hemodynamic effects, arterial blood gas tensions, cerebrospinal fluid pharmacokinetics, and spinal cord blood flow was determined after epidural, intrathecal, and intravenous injection of MPV-2426. Results MPV-2426 produced antinociception with greater potency intrathecally (ED50 = 49 microg) than epidurally (ED50 = 202 microg), whereas intravenous administration had no effect. Intrathecal injection, in doses up to three times the ED95, failed to decrease systemic or central arterial blood pressures or heart rate, whereas larger doses, regardless of route, increased systemic arterial pressure. Bioavailability in cerebrospinal fluid was 7% after epidural administration and 0.17% after intravenous administration. Intrathecal MPV-2426, in an ED95 dose and three times this dose, produced a dose-independent reduction in thoracic and lumbar spinal cord blood flow. Conclusions MPV-2426 shares many characteristics of other alpha2-adrenergic agonists examined in sheep, but differs from clonidine and dexmedetomidine by lack of antinociception and minimal reduction in oxygen partial pressure after large intravenous and epidural injections. No hemodynamic depression was observed after intrathecal injection at antinociceptive doses. These results suggest this compound may be an effective spinal analgesic in humans with less hypotension than clonidine, although its relative potency to cause sedation was not tested in this study.

Cardiorespiratory and Spinal Cord Blood Flow Effects of Intrathecal Neostigmine Methylsulfate, Clonidine, and Their Combination in Sheep 

1995 ◽  
Vol 82 (2) ◽  
pp. 428-435 ◽  
Author(s):  
David D. Hood ◽  
James C. Eisenach ◽  
Chuanyao Tong ◽  
Ellen Tommasi ◽  
Tony L. Yaksh
Keyword(s):  
Spinal Cord ◽  
Clinical Trials ◽  
Blood Flow ◽  
Cord Blood ◽  
Intrathecal Injection ◽  
Central Venous ◽  
Spinal Cord Blood Flow ◽  
Arterial Blood ◽  
Thoracic Spinal ◽  
Flow Effects

Background Intrathecal neostigmine may produce analgesia by itself and may enhance analgesia from spinal clonidine. Before clinical trials, the spinal cord blood flow effects of these drugs alone and in combination should be examined in animals. Methods Conscious, nonpregnant ewes with indwelling vascular and thoracic spinal catheters received intrathecal injection of 0.2 or 2 mg neostigmine, 0.2 mg clonidine, or 2 mg neostigmine plus 0.2 mg clonidine. Mean systemic and pulmonary arterial and central venous pressures, heart rate, and cardiac output were monitored, arterial blood was sampled for blood gas tensions and pH, and spinal cord blood flow was determined by colored microsphere injection before and at 15, 60, and 240 min after spinal study drug injection. Results Neostigmine alone did not affect cardiorespiratory variables or spinal cord blood flow. Intrathecal clonidine alone decreased systemic arterial and central venous pressures, whereas these effects were not observed with addition of neostigmine. Clonidine or neostigmine alone or the combination of clonidine and neostigmine did not affect spinal cord blood flow. Conclusions Intrathecal neostigmine alone or in combination with clonidine does not reduce spinal cord blood flow, an important preclinical toxicity issue. These results provide additional support for initial clinical trials of intrathecal neostigmine for analgesia.

A Physiologic Assessment of Intrathecal Amitriptyline in Sheep 

1997 ◽  
Vol 86 (5) ◽  
pp. 1094-1103 ◽  
Author(s):  
Sergio E. Cerda ◽  
Chuanyao Tong ◽  
Dwight D. Deal ◽  
James C. Eisenach
Keyword(s):  
Blood Pressure ◽  
Spinal Cord ◽  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cord Blood ◽  
Intrathecal Injection ◽  
Spinal Cord Tissue ◽  
Spinal Cord Blood Flow ◽  
Tissue Concentrations ◽  
Hemodynamic Variables

Background Intrathecal injection of amitriptyline enhances antinociception from intravenous morphine and reduces neuropathic pain behavior in animals. This study represents part of a preclinical assessment of intrathecal amitriptyline to determine its safety for use in humans. Methods Low thoracic intrathecal, femoral, and pulmonary arterial catheters were inserted in 18 adult ewes, followed 96 h later by intrathecal injection of saline or 5 mg amitriptyline and by determination of spinal cord blood flow, hemodynamic variables, behavioral changes, cerebrospinal fluid concentrations of catecholamines and amitriptyline, and spinal tissue concentrations of amitriptyline. In six other ewes, low thoracic intrathecal and femoral arterial catheters were inserted and blood pressure and heart rate were measured after intrathecal injection of saline or 0.25, 1, or 5 mg amitriptyline. Four other ewes received cervical intrathecal injection of 5 and 10 mg amitriptyline, and antinociception was determined. Results Thoracic intrathecal injection of amitriptyline produced dose-dependent sedation but did not significantly affect spinal cord blood flow or hemodynamic variables. Spinal cord tissue concentrations of amitriptyline were 100 times greater in tissue near the tip of the thoracic intrathecal catheter compared with cervical cord tissue. Cerebrospinal fluid concentrations of catecholamines did not significantly change after amitriptyline was administered. Cervical intrathecal injection of 5 mg amitriptyline produced mild antinociception, whereas 10 mg produced intense sedation and, in one sheep, seizures and death. Conclusions Although other preclinical toxicity studies are necessary before introducing intrathecal amitriptyline for use in humans, this study did not reveal dangerous changes in blood pressure or spinal cord blood flow from this agent.

Effect of altering cerebrospinal fluid pressure on spinal cord blood flow

1994 ◽  
Vol 58 (1) ◽  
pp. 112-115 ◽  
Author(s):  
Shigeru Kazama ◽  
Yoshihiko Masaki ◽  
Shigeyoshi Maruyama ◽  
Akira Ishihara
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cord Blood ◽  
Fluid Pressure ◽  
Cerebrospinal Fluid Pressure ◽  
Spinal Cord Blood Flow

scholarly journals Blood supply and vascular reactivity of the spinal cord under normal and pathological conditions

2011 ◽  
Vol 15 (3) ◽  
pp. 238-251 ◽  
Author(s):  
Nikolay L. Martirosyan ◽  
Jeanne S. Feuerstein ◽  
Nicholas Theodore ◽  
Daniel D. Cavalcanti ◽  
Robert F. Spetzler ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cord Blood ◽  
Blood Supply ◽  
Vascular Reactivity ◽  
Vascular System ◽  
Spinal Cord Blood Flow ◽  
Arterial Blood ◽  
Severity Of Injury ◽  
Cord Injury

The authors present a review of spinal cord blood supply, discussing the anatomy of the vascular system and physiological aspects of blood flow regulation in normal and injured spinal cords. Unique anatomical functional properties of vessels and blood supply determine the susceptibility of the spinal cord to damage, especially ischemia. Spinal cord injury (SCI), for example, complicating thoracoabdominal aortic aneurysm repair is associated with ischemic trauma. The rate of this devastating complication has been decreased significantly by instituting physiological methods of protection. Traumatic SCI causes complex changes in spinal cord blood flow, which are closely related to the severity of injury. Manipulating physiological parameters such as mean arterial blood pressure and intrathecal pressure may be beneficial for patients with an SCI. Studying the physiopathological processes of the spinal cord under vascular compromise remains challenging because of its central role in almost all of the body's hemodynamic and neurofunctional processes.

Lumbar Drain

2019 ◽  
pp. 907-911
Author(s):  
Jamie J. Van Gompel
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cord Blood ◽  
Low Risk ◽  
Communicating Hydrocephalus ◽  
Spinal Cord Blood Flow ◽  
Lumbar Drain ◽  
Csf Leaks

Lumbar drainage has a major role in neurosurgical and neurocritical care procedures. Lumbar drain insertion is a simple and, when done well, low-risk procedure. A lumbar drain is often necessary in the management of perioperative cerebrospinal fluid (CSF) leaks, the most common use, but it may be beneficial for patients with subarachnoid hemorrhage and communicating hydrocephalus and for patients undergoing surgery involving the aorta with possible damage to the spinal cord. CSF removal optimizes spinal cord blood flow. This chapter describes lumbar drain insertion and some of the associated perils and pitfalls.

scholarly journals Spinal Cord Blood Flow After Intrathecal Injection of Ropivacaine

1996 ◽  
Vol 82 (3) ◽  
pp. 636-640 ◽  
Author(s):  
Jens D. Kristensen ◽  
Rolf Karlsten ◽  
Torsten Gordh
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cord Blood ◽  
Intrathecal Injection ◽  
Spinal Cord Blood Flow
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