Left ventricular stroke volume in the fetal sheep is limited by extracardiac constraint and arterial pressure

Abstract

1. Extracardiac constraint and sensitivity to arterial pressure may be critical factors that limit the functional reserves of the developing fetal heart in utero. We hypothesise that extracardiac constraint is the predominant factor that limits fetal stroke volume (SV). To test this hypothesis we studied six chronically instrumented fetal sheep to determine the relative roles that extracardiac constraint and arterial pressure play in determining left ventricular (LV) function. 2. Pregnant ewes (128-131 days gestation, term = 147 days) were anaesthetised (5 mg kg(-1) Propofol I.V., then 1.5 % halothane, 50 % O(2), balance N(2)O by inhalation) and instrumented using sterile surgical techniques to record LV end-diastolic pressure (P(lved)), aortic pressure (P(ao)), pericardial pressure (P(per)), and LV SV. 3. After a minimum of 72 h recovery, LV function was assessed by altering fetal blood volume to vary P(lved). Ventricular function curves were generated using two measures of ventricular function, SV and stroke work index (SWI = SV x P(ao)), and two measures of ventricular filling, P(lved) and LV end-diastolic transmural pressure (P(lved,tm) = P(lved) - P(per)). 4. Although decreasing P(lved) from the resting level decreased SV, increasing P(lved) from the resting level did not increase SV because the ventricular function curve plateaued. This plateau was not explained solely by an increase in aortic pressure, as the plateau remained present in the SWI versus P(lved) curve. When extracardiac constraint was accounted for (SV against P(lved,tm)), the plateau was largely eliminated (approximately 80 %). The remaining portion of the plateau (approximately 20 %) was eliminated when both extracardiac constraint and arterial pressure were accounted for (SWI versus P(lved,tm)). 5. Thus, the major limitation upon LV function in the near-term fetus results from extracardiac constraint limiting ventricular filling while, at the same time, a much smaller limitation arises from increasing arterial pressure.

Figure 1. Ventricular function curve and breakpoint analysis in the near-term fetal sheep

Mean ventricular function curves (A and B) normalised as a percentage of the values of pressure and stroke volume (SV) or stroke work index (SWI) observed at the breakpoint. Decreasing left ventricular end-diastolic pressure (P_lved) from the breakpoint value decreased LV stroke volume and stroke work index (•). Increasing P_lved beyond the breakpoint value produced no further increase in stroke volume and a limited increase in stroke work index as plateaus developed in the LV function curves. The plateau was largely eliminated after accounting only for the limitations of ventricular preload that result from the constraining effects of the surrounding tissues (A, ○) and completely eliminated by accounting for both the limitations of ventricular preload and increasing arterial pressure (B, ○). Breakpoint analysis was used to determine the breakpoint values of P_lved (C and D) and LV end-diastolic transmural pressure (P_lved,tm; E and F). SS_tot, total sums of squares of the residuals from the two linear regressions. Symbols in A and B indicate means ± s.e.m., n = 6.

Figure 2. Pericardial and left ventricular end-diastolic transmural pressure in the near-term fetal sheep

Substantial increases in pericardial pressure accompanied increases in left ventricular end-diastolic pressure (P_lved, A), limiting the increase in left ventricular end-diastolic transmural pressure (P_lved,tm, B). Breakpoint analysis was used to determine the breakpoint values (C and D). SS_tot, total sums of squares of the residuals from the two linear regressions. Symbols in A and B represent mean values ± s.e.m., n = 6.

Figure 3. Heart rate, aortic pressure and +dP/dt_max in the near-term fetal sheep

Volume loading was accompanied by only minor changes in heart rate (HR) over the entire range of left ventricular end-diastolic pressure (P_lved, •) and transmural pressure (P_lved,tm, ○). Mean aortic pressure and +dP/dt_max both increased with volume loading. Symbols represent mean values ± s.e.m.n = 6 for HR and P_ao; n = 5 for +dP/dt_max.