Increased right ventricular output and central pulmonary reservoir function support rise in pulmonary blood flow during adenosine infusion in the ovine fetus

2012 ◽  
Vol 302 (12) ◽  
pp. R1450-R1457 ◽  
Author(s):  
Joseph J. Smolich ◽  
Daniel J. Penny ◽  
Jonathan P. Mynard
Keyword(s):  
Blood Flow ◽  
Right Ventricular ◽  
Pulmonary Blood Flow ◽  
Ductus Arteriosus ◽  
Late Gestation ◽  
Adenosine Infusion ◽  
Flow Profile ◽  
Fetal Sheep ◽  
Time Flow ◽  
Flow Interactions

Although adenosine markedly increases fetal pulmonary blood flow, the specific changes in pulmonary trunk (PT), ductus arteriosus (DA), and conduit pulmonary artery (PA) flow interactions that support this increased flow are unknown. To address this issue, seven anesthetized late-gestation fetal sheep were instrumented with PT, DA, and left PA micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and after adenosine infusion to increase PA flow approximately fivefold. With adenosine infusion, DA mean and phasic flows were unchanged, but increases in mean PT (500 ± 256 ml/min, P = 0.002) and the combined left and right PA flow (479 ± 181 ml/min, P < 0.001) were similar ( P > 0.7) and related to a larger flow-increasing forward-running compression wave arising from right ventricular (RV) impulsive contraction. Moreover, while the increased PT flow was confined to systole, the rise in PA flow spanned systole (316 ml/min) and diastole (163 ml/min). This elevated PA diastolic flow was accompanied by a 170% greater discharge from a PT and main PA reservoir filled in systole ( P < 0.001), but loss of retrograde blood discharge from a conduit PA reservoir that was evident at baseline. These data suggest that 1) an increase in fetal pulmonary blood flow produced by adenosine infusion is primarily supported by a higher PT blood flow (i.e., RV output); 2) about two-thirds of this increased RV output passes into the pulmonary circulation during systole; and 3) the remainder is transiently stored in a central PT and main PA systolic reservoir, from where it discharges into the lungs in diastole.

Enhanced ventricular pump function and decreased reservoir backflow sustain rise in pulmonary blood flow after reduction of lung liquid volume in fetal lambs

2014 ◽  
Vol 306 (4) ◽  
pp. R273-R280 ◽  
Author(s):  
Joseph J. Smolich
Keyword(s):  
Blood Flow ◽  
Right Ventricular ◽  
Pulmonary Blood Flow ◽  
Ductus Arteriosus ◽  
Liquid Volume ◽  
Flow Profile ◽  
Fetal Sheep ◽  
Pump Function ◽  
Time Flow ◽  
Lung Liquid

Although a reduction in lung liquid volume increases fetal pulmonary blood flow, the changes in central flow patterns that sustain this increased pulmonary perfusion are unknown. To address this issue, eight anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), ductus arteriosus (DA), and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes, with blood flow profile and wave intensity analyses performed at baseline and after withdrawal of lung liquid via an endotracheal tube. Reducing lung liquid volume by 19 ± 6 ml/kg (mean ± SD) augmented right ventricular power by 34% ( P < 0.001), with distribution of an accompanying increase in mean PT blood flow (245 ± 63 ml/min, P < 0.001) to the lungs (169 ± 91 ml/min, P = 0.001) and across the DA (77 ± 92 ml/min, P = 0.04). However, although PT and DA flow increments were confined to systole and were related to an increased magnitude of flow-increasing, forward-running compression waves, the rise in PA flow spanned both systole (108 ± 66 ml/min) and diastole (61 ± 32 ml/min). Flow profile analysis showed that the step-up in PA diastolic flow was associated with diminished PA diastolic backflow and accompanied by a lesser degree of diastolic right-to-left DA shunting. These data suggest that an increased pulmonary blood flow after reduction of lung liquid volume is associated with substantial changes in PT-DA-PA interactions and underpinned by two main factors: 1) enhanced right ventricular pump function that increases PA systolic inflow and 2) decreased PA diastolic backflow that arises from a fundamental change in PA reservoir function, thereby resulting in greater passage of systolic inflow through the lungs.

Pulmonary trunk, ductus arteriosus, and pulmonary arterial phasic blood flow interactions during systole and diastole in the fetus

2011 ◽  
Vol 110 (5) ◽  
pp. 1362-1373 ◽  
Author(s):  
Joseph J. Smolich ◽  
Jonathan P. Mynard ◽  
Daniel J. Penny
Keyword(s):  
Blood Flow ◽  
Compression Wave ◽  
Ductus Arteriosus ◽  
Characteristic Impedance ◽  
Left Pulmonary Artery ◽  
Pulmonary Trunk ◽  
Late Gestation ◽  
Flow Profile ◽  
Fetal Sheep ◽  
Time Flow

Although the distribution of average fetal pulmonary trunk (PT) blood flow favors the ductus arteriosus (DA) over the lungs, the phasic aspects of this distribution during systole and diastole are not well understood. Accordingly, flow profile and wave intensity (WI) analyses were performed at baseline and during brief flow increases accompanying an extrasystole (ES) in 10 anesthetized late-gestation fetal sheep instrumented with PT, DA, and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes. At baseline, 83% of mean PT flow crossed the DA and 17% entered the lungs. However, early systolic flow associated with a forward-running compression wave (FCWis) was higher in the PA and predominant DA flow only emerged in midsystole when a large PA backward-running compression wave (BCWms), which reduced PA flow, was transmitted into the DA as a forward-running compression wave (FCWms) that increased flow. Subsequent protodiastolic forward DA flow occurring during pulmonary valve closure was associated with substantial retrograde PA flow, but insignificant PT flow. Conversely, forward DA flow in the remainder of diastole occurred with forward PT but near-zero PA flow. These flow and WI patterns, in conjunction with the results of mathematical modeling, suggest that 1) fetal PT flow preferentially passes into the PA during early systole due to a lower PA-than-DA characteristic impedance, while DA flow predominates in mid- and late systole due to flow effects arising from the PA BCWms, and 2) forward DA flow is mainly sustained by reversal of PA flow in protodiastole but discharge of a more central reservoir in diastole.

Enhanced central and conduit pulmonary arterial reservoir function offsets reduced ductal systolic outflow during constriction of the fetal ductus arteriosus

2012 ◽  
Vol 302 (1) ◽  
pp. R175-R183 ◽  
Author(s):  
Joseph J. Smolich ◽  
Daniel J. Penny ◽  
Jonathan P. Mynard
Keyword(s):  
Blood Flow ◽  
Ductus Arteriosus ◽  
Left Pulmonary Artery ◽  
Late Gestation ◽  
Compensatory Mechanism ◽  
Flow Profile ◽  
Fetal Sheep ◽  
Compression Waves ◽  
Reservoir Function ◽  
Time Flow

Constriction of the fetal ductus arteriosus (DA) has disparate effects on mean and phasic hemodynamics, as mean DA blood flow is preserved until constriction is severe, but DA systolic and diastolic blood velocities change with only mild constriction. To determine the basis of this disparity and its physiological significance, seven anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), DA, and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and during mild, moderate, and severe DA constriction (defined as pulmonary-aortic mean pressure differences of 4, 8, and 14 mmHg, respectively), produced with an adjustable snare. With DA constriction, mean DA flow was initially maintained but decreased with severe constriction ( P < 0.05) in conjunction with a reduction ( P < 0.05) in PT flow (i.e., right ventricular output). By contrast, DA systolic flow fell progressively during DA constriction ( P < 0.001), due to decreased transmission of both early and midsystolic proximal flow-enhancing forward-running compression waves into the DA. However, DA constriction was also accompanied by greater systolic storage of blood in the PT and main PA ( P < 0.025), and increased retrograde diastolic flow from compliant major branch PA ( P < 0.001). Transductal discharge of these central and conduit PA blood reservoirs in diastole offset systolic DA flow reductions. These data suggest that, during DA constriction in the fetus, enhanced central and conduit PA reservoir function constitutes an important compensatory mechanism that contributes to preservation of mean DA flow via a systolic-to-diastolic redistribution of phasic DA flow.

Altered endothelium-dependent responses in lambs with pulmonary hypertension and increased pulmonary blood flow

1996 ◽  
Vol 271 (2) ◽  
pp. H562-H570 ◽  
Author(s):  
V. M. Reddy ◽  
J. Wong ◽  
J. R. Liddicoat ◽  
M. Johengen ◽  
R. Chang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Endothelial Function ◽  
Pulmonary Blood Flow ◽  
Main Pulmonary Artery ◽  
Plasma Concentrations ◽  
Phosphodiesterase Inhibitor ◽  
No Synthase ◽  
Late Gestation ◽  
Fetal Sheep

To investigate early endothelial function associated with increased pulmonary blood flow, vascular shunts were placed between the ascending aorta and main pulmonary artery in 18 late-gestation fetal sheep. Four weeks after delivery, the lambs were instrumented to measure vascular pressures and blood flows, and blood was collected to measure plasma concentrations of guanosine 3',5'-cyclic monophosphate [cGMP, the second messenger to nitric oxide (NO)-mediated vasodilation] and L-arginine (the precursor for NO synthesis). The responses to the endothelium-dependent vasodilators acetylcholine (ACh, 1.0 microgram/kg) and ATP (0.1 mg.kg-1.min-1), the endothelium-independent vasodilators M & B-22948 (a cGMP-specific phosphodiesterase inhibitor, 2.5 mg/kg) and inhaled NO (40 ppm), and N omega-nitro-L-arginine (an inhibitor of NO synthase, 5 mg/kg) were then compared with responses in 12 age-matched controls. Vasodilator responses in control lambs were determined during pulmonary hypertension induced by U-46619 (a thromboxane A2 mimic). Shunted lambs displayed a selective impairment of endothelium-dependent pulmonary vasodilation, an augmented pulmonary vasoconstricting response to NO synthase inhibition, increased plasma cGMP concentrations, and decreased L-arginine concentrations. Taken together, these data suggest that lambs with pulmonary hypertension and increased pulmonary blood flow have early aberrations in endothelial function, as manifested by increased basal NO activity, that cannot be further increased by agonist-induced endothelium-dependent vasodilators.

scholarly journals Fasudil inhibits the myogenic response in the fetal pulmonary circulation

2008 ◽  
Vol 295 (4) ◽  
pp. H1505-H1513 ◽  
Author(s):  
Pierre Tourneux ◽  
Marc Chester ◽  
Theresa Grover ◽  
Steven H. Abman
Keyword(s):  
Blood Flow ◽  
Pulmonary Circulation ◽  
Ductus Arteriosus ◽  
Fetal Lung ◽  
Late Gestation ◽  
Time Dependent ◽  
Myogenic Response ◽  
Rock Inhibitor ◽  
Fetal Sheep ◽  
Rock Activity

In addition to high pulmonary vascular resistance (PVR) and low pulmonary blood flow, the fetal pulmonary circulation is characterized by mechanisms that oppose vasodilation. Past work suggests that high myogenic tone contributes to high PVR and may contribute to autoregulation of blood flow in the fetal lung. Rho-kinase (ROCK) can mediate the myogenic response in the adult systemic circulation, but whether high ROCK activity contributes to the myogenic response and modulates time-dependent vasodilation in the developing lung circulation are unknown. We studied the effects of fasudil, a ROCK inhibitor, on the hemodynamic response during acute compression of the ductus arteriosus (DA) in chronically prepared, late-gestation fetal sheep. Acute DA compression simultaneously induces two opposing responses: 1) blood flow-induced vasodilation through increased shear stress that is mediated by NO release and 2) stretch-induced vasoconstriction (i.e., the myogenic response). The myogenic response was assessed during acute DA compression after treatment with Nω-nitro-l-arginine, an inhibitor of nitric oxide synthase, to block flow-induced vasodilation and unmask the myogenic response. Intrapulmonary fasudil infusion (100 μg over 10 min) did not enhance flow-induced vasodilation during brief DA compression but reduced the myogenic response by 90% ( P < 0.05). During prolonged DA compression, fasudil prevented the time-dependent decline in left pulmonary artery blood flow at 2 h (183 ± 29 vs. 110 ± 11 ml/min with and without fasudil, respectively; P < 0.001). We conclude that high ROCK activity opposes pulmonary vasodilation in utero and that the myogenic response maintains high PVR in the normal fetal lung through ROCK activation.

Wave intensity analysis of right ventricular and pulmonary vascular contributions to higher pulmonary than aortic blood pressure in fetal lambs

2010 ◽  
Vol 299 (3) ◽  
pp. H890-H897 ◽  
Author(s):  
Joseph J. Smolich ◽  
Jonathan P. Mynard ◽  
Daniel J. Penny
Keyword(s):  
Blood Pressure ◽  
Right Ventricular ◽  
Pressure Difference ◽  
Compression Wave ◽  
Wave Intensity ◽  
Late Gestation ◽  
Pulmonary Vasculature ◽  
Fetal Sheep ◽  
Time Flow ◽  
Pressure Profiles

Although fetal pulmonary trunk (PT) blood pressure may exceed aortic trunk (AoT) pressure, the specific mechanism(s) underlying this pressure difference remain undefined. To evaluate the potential role of ventricular and vascular factors in the generation of a fetal PT-AoT pressure difference, nine anesthetized late-gestation fetal sheep were instrumented with PT and AoT micromanometer catheters to measure high-fidelity pressure and transit-time flow probes to obtain blood velocity. The PT-AoT instantaneous pressure difference (IPDPT-AoT) was calculated from PT and AoT pressure profiles. PT and AoT wave intensity (WI) was derived from the product of the appropriate pressure and velocity rates of change. While diastolic pressures were near identical, systolic PT pressure exceeded AoT pressure ( P < 0.001), with a maximal IPDPT-AoT of 6.5 ± 2.5 mmHg. The comparison of IPDPT-AoT with wave-related PT and AoT pressure changes indicated that 1) a greater pressure-generating effect of the PT forward-running compression wave arising from impulsive right ventricular contraction in early and midsystole accounted for 2.3 ± 2.3 mmHg (35%) of the maximal IPDPT-AoT and 2) a larger pressure-generating effect of a large midsystolic backward-running compression wave transmitted into the PT from the pulmonary vasculature contributed 4.0 ± 1.5 mmHg (∼60%) of the maximal IPDPT-AoT. These results indicate that the higher PT than AoT blood pressure observed in fetal lambs is a systolic phenomenon principally related to the combination of a relatively higher level of right ventricular pump function manifest in early and midsystole and a pressure-increasing energy wave arising from the fetal pulmonary vasculature in midsystole.

Ductus arteriosus wave intensity analysis in fetal lambs: midsystolic ductal flow augmentation is due to antegrade pulmonary arterial wave transmission

2009 ◽  
Vol 297 (4) ◽  
pp. R1171-R1179 ◽  
Author(s):  
Joseph J. Smolich ◽  
Jonathan P. Mynard ◽  
Daniel J. Penny
Keyword(s):  
Compression Wave ◽  
Ductus Arteriosus ◽  
Wave Transmission ◽  
Wave Intensity ◽  
Late Gestation ◽  
Intensity Analysis ◽  
Fetal Sheep ◽  
Blood Flows ◽  
Time Flow ◽  
Pulmonary Arterial

In midsystole, fetal pulmonary trunk (PT) and arterial (PA) blood flows characteristically fall, despite pulmonary blood pressure increasing, while ductus arteriosus (DA) flow continues to rise to a delayed peak. Wave intensity ( WI) analysis indicates that midsystolic fetal PT and PA flow reductions are related to a very large midsystolic PA backward-running compression wave (BCWms), which originates in the pulmonary microvasculature and is partially transmitted into the PT. This study tested the hypothesis that midsystolic augmentation of DA blood flow was related to transmission of the PA BCWms into the DA. DA, PT, and PA WI analysis was performed in eight anesthetized late-gestation fetal sheep instrumented with DA, PT, and left PA micromanometer catheters to measure pressure (P) and transit-time flow probes to obtain blood velocity ( U). In a subgroup ( n = 5), the main PA was briefly occluded to abolish wave transmission from the lungs. WI was calculated as the product of P and U rates of change. PA and PT WI profiles both contained a prominent BCWms, ∼5-fold larger in the PA ( P < 0.005), which increased P but decreased U. By contrast, the DA WI profile demonstrated a large midsystolic forward-running compression wave (FCWms), which increased DA P and U, and occurred 5 ms after PA BCWms. Furthermore, both DA FCWms and PT BCWms were abolished by main PA occlusion. These results suggest that the fetal PA BCWms undergoes retrograde transmission into the PT as a BCWms, but antegrade transmission into the DA as a FCWms that augments midsystolic DA flow.

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