Effect of alpha-adrenergic stimulation on regional contractile function and myocardial blood flow with and without ischemia.
BACKGROUND
The effect of alpha-adrenergic receptor activation on regional contractile function and transmural myocardial blood flow is controversial. Accordingly, the effects of selective alpha 1-(methoxamine) and alpha 2-(BHT 933) receptor stimulation on regional contractile function and transmural myocardial blood flow distribution were studied in 15 anesthetized open-chest dogs.


RESULTS
The alpha-adrenergic agonists were separately infused into the cannulated left circumflex coronary artery during control and ischemic conditions in the same animal. Mean coronary perfusion pressure was held constant by a servocontrolled pump in an extracorporeal circuit. Ischemia was created by reducing coronary perfusion pressure to the level at which percent systolic wall thickening (%WT) decreased by 54%. Contractile function during control conditions was unchanged, whereas under ischemic conditions a further significant decrease in %WT of 27% occurred with either alpha 1- or alpha 2-receptor stimulation without any change in the anterior (control) wall function. Both alpha 1- and alpha 2-receptor stimulations during control conditions resulted in a relatively uniform transmural decrease in blood flow with no change in the subendocardial-to-subepicardial blood flow ratio. With alpha 1-stimulation during ischemia (n = 13), there was a tendency toward decreased subepicardial blood flow with no change in subendocardial flow, resulting in an increased subendocardial-to-subepicardial blood flow ratio (0.61 +/- 0.23 to 0.82 +/- 0.40, p less than 0.05). alpha 2-Receptor stimulation during ischemia (n = 12) produced a significant decrease in subepicardial blood flow (0.45 +/- 0.20 to 0.35 +/- 0.12 ml/min/g, p less than 0.01) with no change in subendocardial blood flow, also resulting in an increased subendocardial-to-subepicardial blood flow ratio.


CONCLUSIONS
These results indicate the selective vasoconstriction in outer wall layers during ischemia mediated by either alpha 1- or alpha 2-receptors can cause a decrease in regional contractile function despite unchanged subendocardial blood flow and improved subendocardial-to-subepicardial flow ratio. This suggests an adverse effect of alpha-adrenergic vasoconstriction during ischemia in this coronary perfusion pressure-controlled canine model.
Seaweed Canyon Laboratory, Department of Medicine, University of California San Diego School of Medicine, La Jolla.
M I
MI
Miyamoto
H A
HA
Rockman
B D
BD
Guth
G
G
Heusch
J
J
Ross
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D008729:Methoxamine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; C015603:azepexole; D008729:Methoxamine