Low-dose dopexamine's effect on lung and gut function after CPB in a sheep model.
OBJECTIVE
The lung injury regularly associated with cardiopulmonary bypass (CPB) may be linked to gut mucosal dysfunction occurring as the result of mucosal ischemia associated with nonpulsatile CPB. To examine this possibility we postulated that the weak-beta 2 agonist dopexamine would improve gut mucosal blood flow, thereby decreasing gut and lung dysfunction seen after CPB in sheep.


METHODS
Anesthetized sheep had 2 h of hypothermic (24 degrees C), nonpulsatile CPB, and 60 min of cold, blood cardioplegic arrest. After warming they were separated from CPB for 2 h of reperfusion. Before and during CPB, dopexamine at 2 micrograms/kg/min (n = 7) or saline (n = 7) were infused in a blinded fashion. Hemodynamic parameters were measured. Biatrial thromboxane B2 levels were obtained. Mesenteric arterial flow (QSMA), mucosal flow (Qmuc), FD-4 clearance (ClFD-4), and tonometric pHi were measured at baseline and 30-min intervals on, and after, CPB.


RESULTS
After CPB, similar reductions in MAP were seen (P < 0.05 vs. baseline), but heart rate and the mean pulmonary vascular resistance were significantly increased in the dopexamine animals (P < 0.05 vs. placebo). Plasma thromboxane was similarly increased in both groups after CPB (P < 0.05 vs. baseline), returning to baseline 1 h after CPB. The Qsma was not altered, but a statistically significant decrease in Qmuc and pHi occurred in both groups (P < 0.05 vs. baseline). In both groups FD-4 clearance reached a peak 30 min after CPB (P < 0.05; dopexamine vs. baseline). After 2 h neither of these changes returned to control levels.


CONCLUSIONS
In this ovine model, gut mucosal ischemia and increased permeability occur with hypothermic CPB, but dopexamine administration during CPB, compared to placebo, neither ameliorates these intestinal derangements nor reduces post-CPB lung pathophysiology.
Stamler
A
A
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Wang
H
H
Weintraub
R M
RM
Hariawala
M D
MD
Fink
M P
MP
Johnson
R G
RG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000098:blood supply*; D008168:Lung / Q000098:blood supply*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood
D000318:Adrenergic beta-Agonists; C046318:dopexamine; D013929:Thromboxane B2; D010100:Oxygen; D004298:Dopamine