Angiotensin II fails to induce preconditioning in vivo--the protective role of myocardial stretch due to pressure overload.
BACKGROUND
Angiotensin II (Ang) has been successfully used as a preconditioning analogue in isolated rabbit hearts. It is also known that local concentrations of Ang accelerate ischemic injury in vivo, while activation of stretch receptors protects ischemic hearts.


OBJECTIVE
First, to investigate further whether Ang can mimic preconditioning in vivo. Second, to test the hypothesis that there is an activation of stretch receptors, and that the larger infarct from the left atrium Ang compared with that from the intravenous Ang may be associated with the ischemic injury caused by local administration.


METHODS
Male rabbits were divided into four groups - a control group, an ischemic preconditioning group with 5 min ischemia, a left atrial group and an intravenous group with 5 min Ang infusion. All animals were subjected to prolonged ischemia and reperfusion. A second series of experiments was also performed with five groups that had a 5 min mechanical obstruction of the aorta (Ao clamp), also used as a preconditioning analogue with or without the stretch receptor blocker gadolinium (Gd).


RESULTS
Contrary to what was expected from the ex vivo experiments, Ang failed to mimic preconditioning (infarct size 39.6 6.1%, 13.7 4.1%, 52.2% 6.9% and 31.2 4.8%, respectively for the above groups). Interestingly, however, when Ang was infused intravenously, it produced a significantly smaller infarct compared with that observed after the same dose was infused into the left atrium (P<0.05). The infarct size was 17.0 3.7% in the Ao clamp group, which was an effect completely prevented by Gd (45.8 4.2%, P<0.01). Although Gd did not alter infarct size in the control and ischemic preconditioning groups, it increased infarct size when added to the intravenous Ang group (Gd-intravenous Ang 48.6 3.3%, P<0.05 compared with intravenous Ang).


CONCLUSIONS
Ang fails to mimic preconditioning in vivo, but salvage of ischemic myocardium can be emanated from pressure overload.
Iliodromitis
Efstathios K
EK
Onassis Cardiac Surgery Center, Athens, Greece. elbee@ath.forthnet.gr
Vlahakos
Demetrios V
DV
Bofilis
Elias
E
Karavolias
George K
GK
Tasouli
Androniki
A
Kremastinos
Dimitrios T H
DT
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005682:Gadolinium / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000517:prevention & control*; D009204:Myocardial Revascularization; D011312:Pressure; D011817:Rabbits; D012016:Reference Values; D012680:Sensitivity and Specificity
D000804:Angiotensin II; D005682:Gadolinium