Hemorrhage during isoflurane-nitrous oxide anesthesia: effects of endothelin-A or angiotensin II receptor blockade or both.
BACKGROUND
The objective of this study was to determine whether endothelin-A receptor blockade (ETAB) impairs hemodynamic and hormonal regulation compared with controls and angiotensin II receptor blockade (AT1B) during hypotensive hemorrhage in dogs under isoflurane-nitrous oxide anesthesia.


METHODS
Six dogs were studied in four protocols: (1) control experiments (controls); (2) ETA blockade using ABT-627 (ETAB); (3) AT1 blockade using losartan (AT1B); and (4) combined AT1B and ETAB (AT1B + ETAB). After a 30-min awake period, isoflurane-nitrous oxide anesthesia was established (1.3 minimum anesthetic concentration). After 60 min of anesthesia, 20 ml blood/kg body weight was withdrawn within 5 min, and the dogs were observed for another hour. Thereafter, the blood was retransfused, and the dogs were observed for a final hour.


RESULTS
Anesthesia: Cardiac output decreased in all protocols, whereas mean arterial pressure decreased more in AT1B and AT1B + ETAB than in controls and ETAB. Hemorrhage: After 60 min, cardiac output had decreased less in controls than in all other protocols. Mean arterial pressure decreased more during ETAB than in controls, but most severely during AT1B and AT1B + ETAB. Angiotensin II increased further only in controls and ETAB, whereas vasopressin and catecholamines increased similarly in all protocols. Retransfusion: Mean arterial pressure remained below controls in all protocols but was lowest when the AT1 receptor was blocked. Cardiac output fully recovered in all but the ETAB protocol.


CONCLUSIONS
ETAB impairs long-term hemodynamic regulation after hemorrhage and retransfusion during anesthesia despite an activation of vasoconstrictive hormones. This suggests that endothelins have a role in long-term cardiovascular regulation. AT1B impairs both short- and long-term blood pressure regulation during anesthesia and after hemorrhage.
Höhne
Claudia
C
Clinic of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum, Charité, Humboldt-University of Berlin, Germany. claudia.hoehne@charite.de
Vogler
Pia
P
Frerking
Ilka
I
Francis
Roland C E
RC
Swenson
Erik R
ER
Kaczmarczyk
Gabriele
G
Boemke
Willehad
W
D000758:Anesthesia; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate; D006339:Heart Rate; D006470:Hemorrhage / Q000503:physiopathology*; D007530:Isoflurane / Q000494:pharmacology*; D009609:Nitrous Oxide / Q000494:pharmacology*; D044022:Receptor, Endothelin A / Q000502:physiology*; D011945:Receptors, Angiotensin / Q000502:physiology*; D012083:Renin / Q000097:blood; D014554:Urination
D002395:Catecholamines; D044022:Receptor, Endothelin A; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D007530:Isoflurane; D012083:Renin; D009609:Nitrous Oxide