Central dexmedetomidine attenuates cardiac dysfunction in a rodent model of intracranial hypertension.
OBJECTIVE
To determine if central sympathetic blockade by dexmedetomidine, a selective alpha(2) adrenergic receptor agonist, prevents cardiac dysfunction associated with intracranial hypertension (ICH) in a rat model.


METHODS
Following intracisternal administration of dexmedetomidine (1 microg.microL(-1), 10 microL volume) or the stereoisomer levomedetomidine (1 microg.microL(-l), 10 microL volume) in halothane-anesthetized rats, a subdural balloon catheter was inflated for 60 sec to produce ICH. Intracranial pressure, hemodynamic, left ventricular (LV) pressures and electrocardiographic (ECG) changes were recorded. Plasma and myocardial catecholamines and malondialdehyde (MDA) levels were measured.


RESULTS
After levomedetomidine administration, subdural balloon inflation precipitated an increase in mean arterial pressure (149 +/- 33% of baseline), heart rate (122 +/- 19% of baseline), LV systolic pressure (LVP), LV end-diastolic pressure (LVEDP), LV developed pressure (LVDP), LV dP/dtmax and rate pressure product (RPP) (132 +/- 19%, 260 +/- 142%, 119 +/- 15%, 126 +/- 24% and 146 +/- 33% of baseline value, respectively). ICH decelerated LVP fall (tau), as tau increased from 7.75 +/- 1.1 to 14.37 +/- 4.5 msec. Moreover, plasma norepinephrine levels were elevated (169 +/- 50% of baseline) and there was the appearance of cardiac dysrhythmias and other ECG abnormalities. This response was transient and cardiac function deteriorated in a temporal manner. Intracisternal dexmedetomidine prevented the rise in plasma norepinephrine, blocked the ECG abnormalities, and preserved cardiac function. Moreover, dexmedetomidine attenuated the rise in MDA levels.


CONCLUSIONS
The results demonstrate that dexmedetomidine attenuates cardiac dysfunction associated with ICH. Our results provide evidence for the role of central sympathetic hyperactivity in the development of cardiac dysfunction associated with ICH.
Hall
Sean R R
SR
Department of Anesthesiology, Queen's University, Kingston General Hospital, 76 Stuart Street, Kingston, Ontario K7L 3N6, Canada.
Wang
Louie
L
Milne
Brian
B
Hong
Murray
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D020927:Dexmedetomidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects; D006331:Heart Diseases / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D006334:Heart Function Tests / Q000187:drug effects / Q000379:methods; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D019586:Intracranial Hypertension / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D002395:Catecholamines; D008315:Malondialdehyde; D020927:Dexmedetomidine; D009638:Norepinephrine