Effects of a localized high-flow anastomosis between the aorta and left lower lobe pulmonary artery on great vessel flow and pulmonary arterial reactivity in the contralateral lung

Abstract

Objectives To assess effects of a localized anastomosis between the aorta and left lower lobe pulmonary artery (LLLPA) on flows through central vessels, and on vascular reactivity of small PAs distal or contralateral to the shunt. Methods Flow rates in major vessels and tensions from small PAs from left and right lower lobes were determined 48 hours after creation of an end-to-side anastomosis of the LLLPA to the aorta. Results Anastomoses increased flow through the LLLPA from 194 ± 6 to 452 ± 18 ml/min immediately after anastomosis and to 756 ± 19 ml/min by the time of harvest (n=88, p<0.05). Flow rates in main PAs from hosts with anastomoses were lower (557 ± 26 versus1033 ± 244 ml/min) while aortic root flows were not different from controls (1370 ± 53 compared to 1120 ± 111 ml/min; p = 0.07). Wet-to-dry weights of the both lungs and aortic flow rates were proportional to shunt flow rates. PA rings harvested from the right (unshunted) lobe of high flow hosts exhibited increased reactivity to the thromboxane agonist U46619 and phenylephrine relative to those of left PAs from the same animal or those of control hosts. Conclusions Our studies are the first to identify enhanced reactivity of PAs in a lung contralateral to a localized high output shunt between an aorta and pulmonary artery. These observations suggest that patients with localized systemic-to-pulmonary shunt could exhibit modified vascular tone in remote pulmonary arteries.

Mechanisms underlying increased reactivity of pulmonary arteries contralateral to a localized high-flow anastomosis

“…We chose the time frame of 48 hours because changes in protein expression potentially related to differences in vasoactivity should reasonably be expected by this time, and pilot experiments supported changes in vascular reactivity within 2 days. Our experiments demonstrated enhanced endothelial-dependent reactivity of PAs contralateral to the shunt (4) relative to that of control and ipsilateral PAs. We hypothesized that either decreased synthesis of a vasodilatory product or enhanced release of a constrictor from right (contralateral) PAs would account for this difference in reactivity to thromboxane agonists.…”

“…PAs from the unshunted right lower lobes of high flow pigs exhibited higher tension to U46619 than matched left PAs distal to the shunt 48 hours after anastomosis whereas the opposite relationship was true in PAs from low flow hosts (reference 4 and figure 1). We tested the contribution of NOS to differential reactivity by treatment 30 minutes before constriction with U46619 with the L-arg analog L-NMMA (10 −3 M) which stereospecifically inhibits NOS (8).…”

“…For details of this procedure, see companion paper (4) and our previous publication (5). All animals received care in compliance with the “Guide for the Care and Use of Laboratory Animals” published by the National Institutes of Health.…”

“…Tension measurements were obtained according to methods previously published by us (6; 4). Pulmonary artery rings, micro-dissected free of adherent lung tissue and 1–2 mm in diameter, were held in ice-cold physiological saline solution (PSS in mM: NaCl 130, CaCl 2 2.5; NaHCO 3 15; MgSO 4 1.2; NaH 2 PO 4 1.2; KCl 4.7; glucose 5.5, HEPES 10 and EDTA 0.026, pH 7.4) until use.…”