scholarly journals Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep

2005 ◽  
Vol 289 (6) ◽  
pp. R1736-R1745 ◽  
Author(s):  
Christopher E. Mascio ◽  
Aaron K. Olison ◽  
J. Carter Ralphe ◽  
Robert J. Tomanek ◽  
Thomas D. Scholz ◽  
...  

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.

CHEST Journal ◽  
2003 ◽  
Vol 124 (1) ◽  
pp. 233-241 ◽  
Author(s):  
Emmanuel N. Simantirakis ◽  
George E. Kochiadakis ◽  
Konstantinos E. Vardakis ◽  
Nikolaos E. Igoumenidis ◽  
Stavros I. Chrysostomakis ◽  
...  

2002 ◽  
Vol 282 (4) ◽  
pp. H1359-H1369 ◽  
Author(s):  
Gregory B. Dalshaug ◽  
Thomas D. Scholz ◽  
Oliva M. Smith ◽  
Kurt A. Bedell ◽  
Christopher A. Caldarone ◽  
...  

To test the hypothesis that coronary flow and coronary flow reserve are developmentally regulated, we used fluorescent microspheres to investigate the effects of acute (6 h) pulmonary artery banding (PAB) on baseline and adenosine-enhanced right (RV) and left ventricular (LV) blood flow in two groups of twin ovine fetuses (100 and 128 days of gestation, term 145 days, n = 6 fetuses/group). Within each group, one fetus underwent PAB to constrict the main pulmonary artery diameter by 50%, and the other twin served as a nonbanded control. Physiological measurements were made 6 h after the surgery was completed; tissues were then harvested for analysis of selected genes that may be involved in the early phase of coronary vascular remodeling. Within each age group, arterial blood gas values, heart rate, and mean arterial blood pressure were similar between control and PAB fetuses. Baseline endocardial blood flow in both ventricles was greater in 100 than 128-day fetuses (RV: 341 ± 20 vs. 230 ± 17 ml · min−1 · 100 g−1; LV: 258 ± 18 vs. 172 ± 23 ml · min−1 · 100 g−1, both P < 0.05). In both age groups, RV and LV endocardial blood flows increased significantly in control animals during adenosine infusion and were greater in PAB compared with control fetuses. After PAB, adenosine further increased RV blood flow in 128-day fetuses (from 416 ± 30 to 598 ± 33 ml · min−1 · 100 g−1, P < 0.05) but did not enhance blood flow in 100-day animals (490 ± 59 to 545 ± 42 ml · min−1 · 100 g−1, P > 0.2). RV vascular endothelial growth factor and Flk-1 mRNA levels were increased relative to controls ( P < 0.05) in 128 but not 100-day PAB fetuses. We conclude that in the ovine fetus, developmentally related differences exist in 1) baseline myocardial blood flows, 2) the adaptive response of myocardial blood flow to acute systolic pressure load, and 3) the responses of selected genes involved in vasculogenesis to increased load in the fetal myocardium.


Circulation ◽  
1992 ◽  
Vol 86 (2) ◽  
pp. 581-588 ◽  
Author(s):  
M D Reller ◽  
M J Morton ◽  
G D Giraud ◽  
D E Wu ◽  
K L Thornburg

1982 ◽  
Vol 243 (5) ◽  
pp. H729-H731 ◽  
Author(s):  
D. J. Fisher ◽  
M. A. Heymann ◽  
A. M. Rudolph

We measured and calculated their product, regional myocardial oxygen delivery, in unanesthetized, previously instrumented fetal, newborn, and adult sheep. In the fetus, blood flow and oxygen delivery were greater to the right ventricular free wall than to the left ventricular free wall. In the left ventricular free wall oxygen delivery increased significantly after birth and later decreased to a level in the adult that was similar to that of the fetus. There was a progressive decrease in oxygen delivery to the right ventricular free wall during the developmental period that we studied. Although the inner-to-outer blood flow ratio was significantly lower for the left and right ventricular free walls of the fetuses as compared with the newborns and adults, the ratio was greater than one in all three groups for both of the ventricular free walls. These data demonstrate that the changes that occur in the circulation after birth are associated with significant alterations in right and left ventricular myocardial blood flow and oxygen delivery, which most likely reflect changes in regional myocardial metabolic demands. In addition, there are further significant changes in regional myocardial blood flow during the transition from the newborn to adult hemodynamics.


1984 ◽  
Vol 62 (5) ◽  
pp. 539-543 ◽  
Author(s):  
Gerald C. Taichman ◽  
Paul Byrne ◽  
George V. Forester ◽  
Wilbert J. Keon

The relative changes in myocardial blood flows within different parts of the heart were measured in anaesthetized thoracotomized dogs during and following effusive pericardial tamponade. Blood flows measured in a group of animals bled to the same arterial hypotensive levels served as experimental controls. The results demonstrate that regional myocardial blood flows to all areas were severely reduced during tamponade. Regional differences in the relative responses were evident; right and left atrial flows decreased more than left ventricular or septal flows which in turn decreased more than right ventricular flow. Significant changes in transmural flow distributions were seen as well; on a relative basis, left and right ventricular endocardial flows decreased more than epicardial and the flow within the left side of the septal wall decreased more than the right. Although decreases in aortic pressure and ventricular volumes can account for some of these changes in flow seen in tamponade, alterations in extravascular compression appear to further reduce the myocardial perfusion and may be responsible for the differences in regional responses. In further experiments when the pericardial cavity was drained following 2 h of tamponade, a hyperemic response was seen throughout the heart indicating that the myocardial flow during tamponade may-have been insufficient to meet the cardiac demands. In conclusion tamponade appears to result in a disproportionate decrease in myocardial blood flow to various parts of the heart which cannot be explained on the basis of a decrease in blood pressure or a reduction in ventricular volume.


1992 ◽  
Vol 263 (4) ◽  
pp. H1327-H1329 ◽  
Author(s):  
M. D. Reller ◽  
M. J. Morton ◽  
G. D. Giraud ◽  
D. E. Wu ◽  
K. L. Thornburg

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.


1996 ◽  
Vol 270 (2) ◽  
pp. H741-H749 ◽  
Author(s):  
J. J. Smolich ◽  
P. J. Berger ◽  
A. M. Walker

We studied the interrelation of changes in ventricular external work, myocardial blood flow, and O2 consumption at birth. Eleven fetal sheep were instrumented under general anesthesia at 133-134 days gestation with arterial, peripheral venous, and left atrial catheters, and in five fetuses, a catheter was also inserted into the coronary sinus. Fetal left ventricular (LV) and right ventricular (RV) outputs and myocardial blood flows (radioactive microspheres), hemodynamics, and LV O2 consumption were measured 1 wk later. Fetuses were delivered by cesarean section, and measurements were repeated 1 and 4 h after birth. RV minute work (mmHg.l.kg-1) was greater in fetuses (10.8 +/- 0.5 vs. 15.6 +/- 1.0 P < 0.001), but because of increased LV minute work (to 20.9 +/- 1.4, P < 0.005) and unchanged RV minute work, this pattern was reversed by 1 h after birth. RV myocardial blood flow (ml.min-1.100 g-1) was predominant in fetuses (234 +/- 25 vs. 306 +/- 27, P < 0.001), but this also reversed in lambs; this reversal was related to unchanged 1-h (248 +/- 16) and lower 4-h LV myocardial blood flow (199 +/- 9, P < 0.05) and a progressive fall in RV myocardial blood flow (1 h: 245 +/- 20, P < 0.05; 4 h: 174 +/- 12, P < 0.005). LV O2 consumption (ml.min-1.100 g-1) increased between fetal (8.1 +/- 0.6) and 1-h lambs (18.9 +/- 1.3, P < 0.005) because of a rise in the LV arteriovenous O2 content difference (3.6 +/- 0.4 vs. 7.5 +/- 0.6 ml/dl, P < 0.005). External work performed per unit myocardial blood flow (mmHg.l.ml-1) in the LV increased between fetal and 1-h lambs (1.92 +/- 0.14 to 3.33 +/- 0.15, P < 0.001) and, in the RV, between fetal and 4-h lambs (2.09 +/- 0.18 to 2.92 +/- 0.24, P < 0.01). The proportion of consumed O2 converted to external work was, however, similar in fetal (34.6 +/- 3.1%) and 1-h (31.3 +/- 2.9%) and 4-h lambs (34.5 +/- 3.6%). These findings indicate that 1) a switch from a fetal RV to a newborn LV dominance is due to increased LV pumping performance, 2) an associated switch in LV and RV myocardial blood flow patterns is mainly related to a fall in RV myocardial blood flow, 3) a postnatal rise in LV O2 consumption results from enhanced LV arteriovenous O2 extraction, not increased LV myocardial blood flow, 4) ventricular external work per unit myocardial blood flow increases postnatally, particularly in the LV, and 5) LV mechanical efficiency is not altered after birth.


2001 ◽  
Vol 40 (05) ◽  
pp. 164-171 ◽  
Author(s):  
B. Nowak ◽  
H.-J. Kaiser ◽  
S. Block ◽  
K.-C. Koch ◽  
J. vom Dahl ◽  
...  

Summary Aim: In the present study a new approach has been developed for comparative quantification of absolute myocardial blood flow (MBF), myocardial perfusion, and myocardial metabolism in short-axis slices. Methods: 42 patients with severe CAD, referred for myocardial viability diagnostics, were studied consecutively with 0-15-H2O PET (H2O-PET) (twice), Tc-99m-Tetrofosmin 5PECT (TT-SPECT) and F-18-FDG PET (FDG-PET). All dato sets were reconstructed using attenuation correction and reoriented into short axis slices. Each heart was divided into three representative slices (base, rnidventricular, apex) and 18 ROIs were defined on the FDG PET images and transferred to the corresponding H2O-PET and TT-SPECT slices. TT-SPECT and FDG-PET data were normalized to the ROI showing maximum perfusion. MBF was calculated for all left-ventricular ROIs using a single-compartment-model fitting the dynamic H2O-PET studies. Microsphere equivalent MBF (MBF_micr) was calculated by multiplying MBF and tissue-fraction, a parameter which was obtained by fitting the dynamic H2O-PET studies. To reduce influence of viability only well perfused areas (>70% TT-SPECT) were used for comparative quantification. Results: First and second mean global MBF values were 0.85 ml × min-1 × g-1 and 0.84 ml × min-1 × g1, respectively, with a repeatability coefficient of 0.30 ml ÷ min-1 × gl. After sectorization mean MBF_micr was between 0.58 ml × min1 ÷ ml"1 and 0.68 ml × min-1 × ml"1 in well perfused areas. Corresponding TT-SPECT values ranged from 83 % to 91 %, and FDG-PET values from 91 % to 103%. All procedures yielded higher values for the lateral than the septal regions. Conclusion: Comparative quantification of MBF, MBF_micr, TT-SPECT perfusion and FDG-PET metabolism can be done with the introduced method in short axis slices. The obtained values agree well with experimentally validated values of MBF and MBF_micr.


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