Inhibition of ischemia-induced brain catecholamine alterations by clonidine

Miyazaki, Michihiko; Nazarali, Adil J.; Boisvert, Donald; Bayens-Simmonds, J.; Baker, Glen B.

doi:10.1016/0361-9230(89)90045-2

Cited by 10 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…), centrally acting modulators, such as alpharadrenergic agonists [53][54][55], may mitigate injul)' by providing sympatholysis, thereby affecting the response to ischemia. Perhaps most exciting are two relatively new approaches currently under active investigation: alteration of cerebral glutamate pathway responses and early reperfusion using fibrinolytic therapy [56,57].…”

Section: Noncardiac Surgerymentioning

confidence: 98%

Perioperative Stroke, Encephalopathy, and Central Nervous System Dysfunction

Mangano

1997

J Intensive Care Med

View full text Add to dashboard Cite

The leading cause of mortality in adult populations throughout the world is atherosclerosis, which results in cardiovascular and cerebrovascular complications and consumes substantive health care resources. The impact of atherosclerosis on patients undergoing surgery is also considerable, given the multiple stresses occurring during, and especially following, the surgical procedures, thereby precipitating vascular morbidity. Perioperative cerebrovascular morbidity and mortality occur in approximately 10% of the 600,000 patients who undergo cardiac surgery annually, consuming approximately $13 billion, which is expended on in-hospital, intensive care unit (ICU), and long-term specialized care for these neurological complications of stroke, encephalopathy, and cognitive dysfunction. Furthermore, risk of these outcomes will continue to increase as the surgical population ages. Principal among the etiologies of focal stroke and encephalopathy appear to be perioperative hypotension and precipitation of macroemboli and microemboli. As a result, new detection techniques for these events have been instituted, including (1) continuous hemodynamic monitoring, for detection of hypotensive episodes; (2) transesophageal echocardiography, for detection of aortic atherosclerosis, a potential source for emboli; and (3) transcranial Doppler sonography, for detection of cerebral emboli, as well as determination of cerebral blood flow. Recent large-scale multicenter studies have identified risk factors and indices for perioperative central nervous system (CNS) morbidity. Regarding therapy, a number of pharmacological approaches are currently under consideration; principal among these approaches are agents that can modulate the excitotoxic response, including glutamate receptor antagonists (NMDA, AMPA, metabotrophic), calcium channel blockers, free radical scavengers, and agents that modify the inflammatory white cell response. Although a number of laboratory, animal, and smaller clinical trials have been conducted, only one large-scale multicenter program to date has been conducted to assess the efficacy of adenosine modulation. These data, collected in more than 4,000 patients undergoing cardiac surgery, suggest that in addition to mitigation of myocardial injury, stroke also may be modulated by enhancing adenosine concentration in the area of cerebral ischemia. However, these preliminary findings must be validated in appropriately powered clinical trials. Finally, postoperative stroke and encephalopathy consume substantive resources, resulting in prolonged length-of-stay (17 days in-hospital 10 days for patients suffering Q-wavc infarction, vs 7 days for patients having no adverse outcome) and prolonged length-of-stay in the ICU following surgery (5 vs 3 vs 2 days, respectively). Hospital costs increase by approximately 3- to 4-fold in patients who suffer CNS outcomes following surgery. In conclusion, perioperative CNS morbidity and mortality is a critical problem that affects a substantial portion of the surgical population and consumes considerable health care resources. Over the next several years, attention must be focused on this important problem, and clinical and research resources should be redirected toward the solution of perioperative CNS morbidity.

show abstract

Section: Noncardiac Surgerymentioning

confidence: 98%

Perioperative Stroke, Encephalopathy, and Central Nervous System Dysfunction

Mangano

1997

J Intensive Care Med

View full text Add to dashboard Cite

show abstract

“…Brain catecholamines have been measured in animals processed by decapitation (Calderini et al, 1978;Gaudet et al, 1978 ;Cvejic et al ., 1980;Miyazuki, 1988 ;Adachi et al, 1991) and by the in situ freezing technique (Harik et al, 1986;Miyauchi et al, 1989) . Because NE levels decrease during cerebral ischemia (Gaudet et al, 1978 ;Cvejic et al, 1980;Harik et al, 1986;Miyazuki et al, 1988;Adachi et al, 1991), it is possible that decapitation ischemia alters the NE levels in the cortex and hippocampus. Our results indicate clearly that, in contrast to the levels of lactate and high energy phosphates, the NE levels of the cortex and the hippocampus are similar in brains isolated by the in situ freezing and the decapitation procedures.…”

Section: Discussionmentioning

confidence: 99%

Regional Levels of Lactate and Norepinephrine After Experimental Brain Injury

Prasad

Ramaiah

McIntosh

et al. 1994

Journal of Neurochemistry

View full text Add to dashboard Cite

The recently developed controlled cortical impact model of brain injury in rats may be an excellent tool by which to attempt to understand the neurochemical mechanisms mediating the pathophysiology of traumatic brain injury. In this study, rats were subjected to lateral controlled cortical impact brain injury of low grade severity; their brains were frozen in situ at various times after injury to measure regional levels of lactate, high energy phosphates, and norepinephrine. Tissue lactate concentration in the injury site left cortex was increased in injured animals by sixfold at 30 min and twofold at 2.5 h and 24 h after injury (p < 0.05). At all postinjury times, lactate concentration was also increased in injured animals by about twofold in the cortex and hippocampus adjacent to the injury site (p < 0.05). No significant changes occurred in the levels of ATP and phosphocreatine in most of the brain regions of injured animals. However, in the primary site of injury (left cortex), phosphocreatine concentration was decreased by 40% in injured animals at 30 min after injury (p < 0.05). The norepinephrine concentration was decreased in the injury site left cortex of injured animals by 38% at 30 min, 29% at 2.5 h, and 30% at 24 h after injury (p < 0.05). The level of norepinephrine was also reduced by ∼20% in the cortex adjacent to the injury site in injured animals. The present results suggest that controlled cortical impact brain injury produces disorder in the neuronal oxidative and norepinephrine metabolism.

show abstract

“…Glycine has also been shown to decrease desensitization of NMDA channels (Lerma et al, 1990), which, in the ischemic brain, could potentially lead to prolonged stimulation of the NMDA receptor (Vyklicky et al, 1990). High levels of glycine also cause norepinephrine release in the hippocampus, via strychnine-sensitive sites (Mangano et al, 1990;Raiteri et al, 1990), and catecholamines have been implicated by some as mediating neuronal damage following transient ischemia Miyazaki et al, 1989), although others have found conflicting results (see Blomqvist et al, 1985;Miyauchi et al, 1989). Baker et al (199 1) found that moderate hypothermia in rabbits significantly decreased hippocampal glutamate, aspartate, and glycine levels after ischemia, and this correlated with hippocampal protection.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Cyclohexyladenosine on the Penischemic Increases of Hippocampal Glutamate and Glycine in the Rabbit

Cantor

Zornow

Miller³

et al. 1992

Journal of Neurochemistry

View full text Add to dashboard Cite

We investigated the ability of N6-cyclohexyladenosine (CHA), a potent and selective agonist of the adenosine A1 receptor, to attenuate elevations of levels of extracellular hippocampal glutamate and glycine that result from episodes of transient global cerebral ischemia (TGCI). A total of 30 New Zealand white rabbits were randomly assigned to receive 0 (n = 5), 0.1 (n = 8), 1.0 (n = 6), 10 (n = 6), or 100 (n = 5) microM CHA. The drug was dissolved in artificial CSF (vehicle) and administered via a microdialysis probe placed stereotactically into the dorsal hippocampus. A second microdialysis probe placed into the contralateral hippocampus of each animal was perfused with vehicle alone. Ten minutes of TGCI was induced by neck tourniquet inflation and deliberate hypotension from 0 to 10 min. Microdialysis samples were collected as follows: every 20 min preischemia (at -80, -60, -40, -20, and 0 min); every 5 min during ischemia and in the immediate reperfusion period (at 5, 10, 15, and 20 min); and every 20 min for the remainder of the reperfusion period (at 40, 60, and 80 min). Samples were then analyzed for their concentration of glutamate and glycine by HPLC. Following 10 min of ischemia, glutamate levels increased to a peak of 3.28 +/- 0.55 times baseline and returned to preischemic levels by 40 min, i.e., during reperfusion. Glycine concentrations increased to 5.41 +/- 0.91 times over baseline and remained elevated for the duration of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Inhibition of ischemia-induced brain catecholamine alterations by clonidine

Cited by 10 publications

References 33 publications

Perioperative Stroke, Encephalopathy, and Central Nervous System Dysfunction

Perioperative Stroke, Encephalopathy, and Central Nervous System Dysfunction

Regional Levels of Lactate and Norepinephrine After Experimental Brain Injury

The Effect of Cyclohexyladenosine on the Penischemic Increases of Hippocampal Glutamate and Glycine in the Rabbit

Contact Info

Product

Resources

About