[Cardiovascular effects of a calcium channel blocker in hypoxia caused by altitude].
OBJECTIVE
High altitude pulmonary oedema can be successfully treated and prevented by calcium channel blockers. Moreover, calcium entering in the cells could explain the congestive phenomena of acute mountain sickness (AMS). These findings led us to study the action of a calcium channel blocker, isradipine, in the prevention of non-complicated AMS.


METHODS
In a double blind randomized study, 20 healthy volunteers received 5 mg of isradipine (n = 6) or placebo (n = 6) for 8 days. After 5 days of treatment in normoxia, the subjects were rapidly transported to an altitude of 4350 m. The efficiency of the treatment was then estimated by the AMS symptom score, haemodynamic parameters and renal function.


RESULTS
The administration of isradipine did not significantly modify AMS symptom score nor most of other parameters measured in high altitude hypoxia. Heart rate was an average of 15 b/min lower in the isradipine group, probably because of a direct action of isradipine on the sinus node. Otherwise, the effects of hypoxia were similar in both groups and were in accordance with the literature. There was no clear explanation for the increase in cardiac output and stroke volume when the subjects moved from supine to standing position. Renal blood flow, measured by Doppler or para-aminohippuric acid clearance was not modified by hypoxia. Cerebral blood flow was elevated, due to the direct vasodilator effect of hypoxia. However this increase did not seem to be the main mechanism responsible for the congestive phenomena. On the other hand, the increase in capillary permeability (demonstrated by the increased transcapillary escape rate of albumin, and albuminuria) appeared to play a major role in the pathogenesis of AMS and high altitude cerebral oedema. Isradipine had no protective effect on these phenomena and its use should be restricted to the treatment of high altitude pulmonary oedema.
Dugas
L
L
Association pour la Recherche en Physiologie de l'Environnement (ARPE), UFR Médecine, Bobigny.
Dubray
C
C
Herry
J P
JP
Olsen
N V
NV
Court-Payen
M
M
Hansen
J M
JM
Robach
P
P
Ter-Minassian
A
A
Richalet
J P
JP
D000328:Adult; D000532:Altitude Sickness / Q000150:complications / Q000517:prevention & control*; D002199:Capillary Permeability / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D003118:Color Perception / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000517:prevention & control*; D017275:Isradipine / Q000494:pharmacology / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010919:Placebos
D010919:Placebos; D017275:Isradipine
Effets cardiovasculaires d'un bloqueur calcique en hypoxie d'altitude.