Intravascular infusions of plasma into fetal sheep cause arterial and venous hypertension

Abstract

Fetal volume control is driven by an equilibrium between fetal and maternal hydrostatic and oncotic pressures in the placenta. Renal contributions to blood volume regulation are minor because the fetal kidneys cannot excrete fluid from the fetal compartment. We hypothesized that an increase in fetal plasma protein would lead to an increase in plasma oncotic pressure, resulting in an increase in fetal arterial and venous pressures and decreased angiotensin levels. Plasma or lactated Ringer solution was infused into each of five twin fetuses. After 7 days, fetal protein concentration was 71.2 +/- 4.2 g/l in the plasma-infused fetuses compared with 35.7 +/- 6.3 g/l in the lactated Ringer-solution-infused fetuses. Arterial pressure was 68.0 +/- 3.6 compared with 43.4 +/- 1.9 mmHg in the lactated Ringer solution-infused fetuses (P < 0.0003), whereas venous pressure was 4.8 +/- 0.3 mmHg in the plasma-infused fetuses compared with 3.3 +/- 0.4 mmHg in the lactated Ringer solution-infused fetuses (P < 0.036). Six fetuses were studied on days 0, 7, and 14 of plasma protein infusion. Fetal protein concentration increased from 31.1 +/- 1.5 to 84.8 +/- 3.8 g/l after 14 days (P < 0.01), and arterial pressure increased from 43.1 +/- 1.8 to 69.1 +/- 4.1 mmHg (P < 0.01). Venous pressure increased from 3.0 +/- 0.4 to 6.2 +/- 1.3 mmHg (P < 0.05). Fetal heart rate did not change. Angiotensin II concentration decreased, from 24.6 +/- 5.6 to 2.9 +/- 1.3 pg/l, after 14 days (P < 0.01). Fetal plasma infusions resulted in fetal arterial and venous hypertensions that could not be corrected by reductions in angiotensin II levels.

Sequential growth of fetal sheep cardiac myocytes in response to simultaneous arterial and venous hypertension

“…This model of plasma infusion was developed to increase both fetal preload and afterload. As is illustrated by daily measurements (13), there is a gradual increase in mean fetal arterial pressure and central venous pressure with plasma infusion when compared with twin fetuses receiving the same volume of lactated Ringer solution. This model offers the unique opportunity to study the effects of both increased diastolic and systolic pressure load on the growing fetal heart.…”

“…Consistent with our hypotheses, we found that the hearts of hypertensive fetuses were heavier than those of controls. This growth may be considered adaptive in that it permits fetuses to maintain biventricular stroke volume in the face of greatly increased arterial pressures (13). During the first 4 days of plasma infusion (early phase), there was a large increase in hemodynamic load and cardiac mass, such that the heart-tobody weight ratio increased by 30% compared with controls (Table 2).…”

“…All experiments were begun at an average of 130 Ϯ 2 days of gestation (term is 145 days). Adult sheep plasma protein was infused in the fetal circulation as previously described (13). In brief, after baseline pressure measurements and blood samples were taken, intravenous infusion of plasma was started using a Gilson Minipuls-3 roller pump (Gilson, Middleton, WI).…”

“…Sheep plasma for fetal infusion was obtained from ewes that were to be killed, as previously described (13). Fetuses were collected following euthanasia of the ewe with a commercial pentobarbital sodium solution (ϳ65 mg/kg) or anesthesia of the ewe (induced with an iv injection of 10 mg diazepam and 400 mg ketamine, then maintained at a deep level with additional doses of ketamine) for blood collection.…”

“…To test this hypothesis, we slowly infused sterile sheep plasma in the vascular space of fetal sheep for either 4 or 8 days. The advantage of this technique is that it gradually imposes a substantial and quantifiable hemodynamic load by elevating both arterial and venous pressures (13). We then measured fetal heart and body weights and isolated the cardiac myocytes to determine the incidence of myocyte cell cycle activity, myocyte size, and the fraction of myocyte binucleation (as an index of terminal differentiation).…”