Increased coronary blood flow signals growth of coronary resistance vessels in near-term ovine fetuses.
We measured maximal coronary artery conductance in near-term fetal sheep before and after chronic infusion with adenosine to determine whether an increase in coronary flow without hypoxemia results in increased coronary vascular growth. Adenosine was infused into the circumflex coronary artery for 12 h each day for 4 days. Coronary flow was maintained at double the resting level by regulating the infusion of adenosine via a computerized servocontrol device signaled by a Doppler flow-velocity sensor. Total arterial hemoglobin, oxygen content, and hemodynamics were unchanged. Resting circumflex coronary blood flow increased from control of 250 +/- 111 to 530 +/- 216 ml x min(-1) x 100 g left ventricle(-1) with adenosine on day 1 and from 194 +/- 74 to 878 +/- 210 ml x min(-1) x 100 g left ventricle(-1) with adenosine on the last day (P < 0.01). Coronary conductance, determined during maximal vasodilation, increased from 14.0 +/- 5.0 to 26.9 +/- 3.9 ml x min(-1) x 100 g(-1) x mmHg(-1) over the 4 days (P < 0.001). Coronary flow reserve, the difference between resting and maximal myocardial blood flow interpolated at 40 mmHg, increased from 299 +/- 196 to 672 +/- 266 ml x min(-1) x 100 g(-1) (P < 0.001). Maximal coronary conductance was unchanged in control saline-infused fetuses (18.5 +/- 5.1 vs. 18.5 +/- 8.7 ml x min(-1) x 100 g(-1) x mmHg(-1)). We conclude that chronic intracoronary adenosine administration to the fetal myocardium modulates coronary vascular growth, even in the absence of tissue hypoxia.
Wothe
D
D
Department of Obstetrics, and Heart Research Center, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA.
Hohimer
A
A
Morton
M
M
Thornburg
K
K
Giraud
G
G
Davis
L
L
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006321:Heart / Q000196:embryology* / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011247:Pregnancy; D012756:Sheep; D014655:Vascular Resistance / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester