Atrial Myocardial Blood Flow during Acute Right Ventricular Pressure Load and Adenosine Infusion in Late Gestation Fetal Sheep

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.

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Myocardial blood flow and coronary reserve in chronically anemic fetal lambs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.277.1.r306 ◽

1999 ◽

Vol 277 (1) ◽

pp. R306-R313 ◽

Cited By ~ 8

Author(s):

Lowell E. Davis ◽

A. Roger Hohimer ◽

Mark J. Morton

Keyword(s):

Blood Flow ◽

Myocardial Blood Flow ◽

Coronary Blood Flow ◽

Coronary Flow ◽

Adenosine Infusion ◽

Fetal Sheep ◽

Coronary Reserve ◽

Flow Reserve ◽

Coronary Conductance ◽

The Difference

Chronic fetal anemia produces large compensatory increases in coronary blood flow in the near-term fetal lamb. To determine if increased coronary flow in anemic fetuses is associated with decreased coronary flow reserve or, alternatively, an increase in coronary conductance, we measured maximal coronary artery conductance during adenosine infusion before and during anemia. Isovolemic hemorrhage over 7 days reduced hematocrit from 30.6 ± 2.7 to 15.8 ± 2.4% ( P < 0.02) and the oxygen content from 7.3 ± 1.4 to 2.6 ± 0.4 ml/dl ( P < 0.001). Coronary blood flow increased from control (202 ± 60) to 664 ± 208 ml ⋅ min−1 ⋅ 100 g−1 with adenosine to 726 ± 169 ml ⋅ min−1 ⋅ 100 g−1 during anemia and to 1,162 ± 250 ml ⋅ min−1 ⋅ 100 g−1 (left ventricle) during anemia with adenosine infusion (all P< 0.001). Coronary conductance, determined during maximal vasodilation, was 18.2 ± 7.7 before and 32.8 ± 11.9 ml ⋅ min−1 ⋅ 100 g−1 ⋅ mmHg−1during anemia ( P < 0.001). Coronary reserve, the difference between resting and maximal myocardial blood flow interpolated at 40 mmHg, was unchanged in control and anemic fetuses (368 ± 142 and 372 ± 201 ml/min). Because hematocrit affects viscosity, anemic fetuses were transfused with blood to acutely increase the hematocrit back to control, and conductance was remeasured. Coronary blood flow decreased 57.3 ± 18.9% but was still 42.6 ± 18.9% greater than control. We conclude that in chronically anemic fetal sheep coronary conductance is increased and coronary reserve is maintained, and this is attributed in part to angiogenesis as well as changes in viscosity.

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Right ventricular pressure load accelerates myocyte maturation in fetal sheep

Journal of the Society for Gynecologic Investigation ◽

10.1016/1071-5576(95)94503-m ◽

1995 ◽

Vol 2 (2) ◽

pp. 338

Author(s):

G GIRAUD

Keyword(s):

Right Ventricular ◽

Ventricular Pressure ◽

Fetal Sheep ◽

Pressure Load

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Regional myocardial blood flow and myocardial function during acute right ventricular pressure overload in calves.

Circulation Research ◽

10.1161/01.res.44.4.531 ◽

1979 ◽

Vol 44 (4) ◽

pp. 531-539 ◽

Cited By ~ 17

Author(s):

M Manohar ◽

G E Bisgard ◽

V Bullard ◽

J A Will ◽

D Anderson ◽

...

Keyword(s):

Blood Flow ◽

Myocardial Blood Flow ◽

Right Ventricular ◽

Myocardial Function ◽

Pressure Overload ◽

Ventricular Pressure ◽

Regional Myocardial Blood Flow ◽

Regional Myocardial Blood

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Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00278.2005 ◽

2005 ◽

Vol 289 (6) ◽

pp. R1736-R1745 ◽

Cited By ~ 20

Author(s):

Christopher E. Mascio ◽

Aaron K. Olison ◽

J. Carter Ralphe ◽

Robert J. Tomanek ◽

Thomas D. Scholz ◽

...

Keyword(s):

Blood Flow ◽

Myocardial Blood Flow ◽

Right Ventricular ◽

Left Ventricular ◽

Glycolytic Enzymes ◽

Vegf Receptor ◽

Mrna Levels ◽

Fetal Anemia ◽

Fetal Sheep ◽

Metabolic Adaptations

Little is known about the vascular and metabolic adaptations that take place in the fetal heart to maintain cardiac function in response to increased load. Chronic fetal anemia has previously been shown to result in increased ventricular mass, increased myocardial vascularization, and increased myocardial expression of hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF). We therefore sought to determine whether chronic fetal anemia induces expression of HIF-1-regulated angiogenic factors and glycolytic enzymes in the fetal myocardium. Anemia was produced in chronically instrumented fetal sheep by daily isovolemic hemorrhage (80–100 ml) for either 3 ( n = 4) or 7 days ( n = 11) beginning at 134 days of gestation (term 145 days). Catheterized, nonbled twins served as controls. Isovolemic hemorrhage over 7 days resulted in decreased fetal hematocrit (37 ± 1 to 20 ± 1%) and arterial oxygen content (6.5 ± 0.4 to 2.8 ± 0.2 ml O2/dl). Myocardial blood flow and vascularization were significantly increased after 7 days of anemia. Myocardial HIF-1 protein expression and VEGF (left ventricular), VEGF receptor-1 (right ventricular), and VEGF receptor-2 (right ventricular, left ventricular) mRNA levels were elevated ( P < 0.05) in 7-day anemic compared with control animals. Myocardial expressions of the glycolytic enzymes aldolase, lactate dehydrogenase A, phosphofructokinase (liver), and phosphoglycerol kinase were also significantly elevated after 7 days of anemia. Despite the absence of a significant increase in myocardial HIF-1α protein in 3-day anemic fetuses, expressions of VEGF, VEGF receptor-1, and the glycolytic enzymes were greater in 3-day compared with 7-day anemic animals. These data suggest that HIF-1 likely participates in the fetal myocardial response to anemia by coordinating an increase in gene expressions that promote capillary growth and anaerobic metabolism. However, factors other than HIF-1 also appear important in the regulation of these genes. We speculate that the return of mRNA levels of angiogenic and glycolytic enzymes toward control levels in the 7-day anemic fetus is explained by a significantly increased resting myocardial blood flow, resulting from coronary vascular growth and increased coronary conductance, and a return to a state of adequate oxygen and nutrient delivery, obviating the need for enhanced transcription of genes encoding angiogenic and glycolytic enzymes.

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Maximal myocardial blood flow is enhanced by chronic hypoxemia in late gestation fetal sheep

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1992.263.4.h1327 ◽

1992 ◽

Vol 263 (4) ◽

pp. H1327-H1329 ◽

Cited By ~ 4

Author(s):

M. D. Reller ◽

M. J. Morton ◽

G. D. Giraud ◽

D. E. Wu ◽

K. L. Thornburg

Keyword(s):

Blood Flow ◽

Myocardial Blood Flow ◽

Left Ventricular ◽

Late Gestation ◽

Ventricular Free Wall ◽

Free Wall ◽

Fetal Sheep ◽

Arterial Pco2 ◽

Arterial Concentration ◽

Arterial Po2

The measurement of maximal myocardial blood flow gives information about the total cross-sectional area of the coronary resistance vessels. During a continuous left atrial infusion of adenosine (60 micrograms.kg-1.min-1), maximal myocardial blood flow was measured in 4 fetuses hypoxemic for a minimum of 5-8 days (pH = 7.33 +/- 0.01, arterial PCO2 = 49.8 +/- 4.2 Torr, arterial PO2 = 16.1 +/- 1.3 Torr, and arterial concentration of O2 = 5.3 +/- 1.2 ml/dl). These data were compared with an identically instrumented group of normoxemic fetuses (n = 7) following the same study protocol (pH = 7.38 +/- 0.02, arterial PCO2 = 43.1 +/- 3.8 Torr, arterial PO2 = 19.8 +/- 2.0 Torr, and arterial concentration of O2 = 7.9 +/- 1.0 ml/dl) (P < 0.05). At comparable arterial pressures, the maximal myocardial flow (ml.min-1.100 g tissue-1) for hypoxemic vs. normoxemic fetuses was 974 +/- 273 and 630 +/- 181 for the total myocardium, 986 +/- 367 and 602 +/- 192 for the left ventricular free wall, 1,025 +/- 346 and 614 +/- 178 for the septum, and 1,231 +/- 274 and 757 +/- 269 for the right ventricular free wall, respectively (P < 0.01). These data suggest that hypoxemia in the fetus can significantly alter the coronary vascular bed, which, if confirmed, would represent an important adaptation in the developing fetus.

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