Maturation of coronary responsiveness to exogenous adenosine in the rabbit

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Abstract
Previous studies have indicated that some cardiac control systems, such as autonomic innervation, are incomplete in the newborn and undergo postnatal maturation. However, relatively little is known of maturational changes which will affect the ability of the coronary circulation to regulate blood flow during various interventions. We tested the hypothesis that the coronary circulation of the rabbit develops a progressive, age related increase in responsiveness to exogenous adenosine during the first 16 weeks of life. We examined the response of coronary circulation to exogenous adenosine in four age groups (6–10 days, 3–4 weeks, 7–8 weeks, 16 weeks) of rabbits by using an isolated heart preparation. Coronary flow was measured during an control period, during reactive hyperemia (following release of a 2 min coronary flow interruption), and during infusions of exogenous adenosine. All age groups had similar levels of control coronary blood flow, with a large increase in flow observed during reactive hyperemia. The volume of coronary flow was higher during reactive hyperemia (PP<0.01) flow response to exogenous adenosine than the other age groups. In addition, the 6–10-day-old animals required higher adenosine concentrations to produce an initial detectable coronary flow increase and to produce the maximal flow response. Additional studies demonstrated a significant reduction in percentage flow debt repayment after theophylline administration in adult rabbit hearts. However, neonatal rabbit hearts showed no change in flow debt repayment following theophylline. We conclude that the rabbit heart requires a period of maturation after birth before demonstrating an adult level of coronary responsiveness to exogenous adenosine.