Impact of the Birth Transition on Striated Muscle Function in Normal Development

Abstract

Considerable changes are expected in the regulation of myocardial and limb skeletal muscle perfusion from the pre‐ to post‐natal condition based on changes in gravitational force, work load, and arterial O2 content. Yet the impact of birth on the growth and function of microvasculature in striated muscle is poorly understood. Our objective was to assess resting and maximal microvascular flow in the cardiac left ventricle (LV; with high workload before and after birth), and biceps femoris (BF; hindlimb muscle with little workload before birth). We hypothesized that resting flow in the fetus exceeds that in the neonate because of low fetal arterial O2 content, but that flow reserve is greater in the neonate in order to support ambulation. We expected this increase in reserve to be greater in skeletal than myocardial muscle.Fetuses (N=8) were instrumented at 130 d gestational age (dGA, birth is at 146 d) and studied exteriorized from the uterus at 135 dGA. Lambs (N=8) were instrumented 2 d after birth and studied at 5 d. Instrumentation included arterial, venous, and left atrial catheters for systemic pressure monitoring, arterial blood sampling, and drug delivery; and an inflatable occluder around the descending thoracic aorta. Myocardial perfusion (Q) in mL/min/g of tissue was assessed by transthoracic contrast echocardiography at rest, during adenosine‐induced hyperemia, and during combined hyperemia and increased perfusion pressure produced by transient constriction of the postductal aorta. Work was determined by the product of heart rate and perfusion pressure. Hindlimb BF muscle Q was assessed at rest, and during contractile work produced by electrostimulation (2 Hz, 10 mA). Differences were assessed by the Mann‐Whitney U‐test. One fetus and one lamb were excluded from analysis because of abnormal blood gasses at the time of study.At rest, LV myocardial Q was 2‐fold higher in fetuses than neonates (Fig 1A), as was Q normalized to work; whereas, O2 delivery was similar between groups (Fig 1B). Maximal flow during hyperemia followed a similar pattern, with fetal Q, as well as Q per work, exceeding that in the neonate by a factor of 7, whereas maximal O2 delivery per work was similar between age groups. Skeletal muscle (BF) flow in the fetus was highly variable both at rest and during exercise. Median resting Q, resting O2 delivery, and exercised flow were all at least 5‐fold higher in the fetus than neonate, however the difference only reached statistical significance for resting flow (Fig 1A,B). Exercise O2 delivery was similar between ages. Flow reserve was similar between the fetus and neonate in both myocardium and skeletal muscle (Fig 1C).At rest, elevated flow in the fetal LV supported similar levels of O2 delivery per work as found in the newborn. Surprisingly, there was a tendency for increased O2 delivery in the fetal skeletal muscle compared to the newborn; we speculate that this reflects differences in regulation of non‐nutritive flow between the ages studied. Overall, the results of this study suggest that despite the dramatically different physiological circumstances between the fetus and newborn, microvascular growth is regulated to preserve similar levels of flow reserve in both.