Stability of heterogeneity of myocardial blood flow in normal awake baboons

Abstract

Regional myocardial blood flow has been thought to be relatively uniform, in accord with the singular function of myocardial cells. However, considerable spatial heterogeneity has been observed in the hearts of anesthetized animals and in isolated hearts. Studies were undertaken in a total of 13 baboons. Eleven were awake, healthy animals sitting in chairs at rest or feeding, some performed mild leg exercise (wheel turning), and others were subjected to whole body heating; two were anesthetized, methodological controls. Microspheres (15 +/- 3 micron diameter, 0.5 X 10(6)/kg body weight) were injected via a catheter into the apex of the left ventricle while arterial blood was sampled at a constant rate for calculating cardiac output. Microspheres with different labels were injected at six intervals of 20 minutes to several hours. On sacrifice, the hearts were sectioned into 204 locatable pieces (left ventricle, 168; right ventricle, 27; and atria, 9). Average resting myocardial flow was 2.1 +/- 0.2 ml/g per min (mean +/- SD, n = 11). Left and right ventricles and atria comprised 70 +/- 2% (n = 13), 20 +/- 2%, and 10 +/- 2% respectively of the total heart mass while receiving 80 +/- 3%, 16 +/- 2%, and 4 +/- 2% of the total myocardial flow. Thus, mean left ventricular flow was 114 +/- 5% of the average for the whole heart, right ventricular flow was 81 +/- 13%, and atrial flow was 41 +/- 13%. Myocardial flow heterogeneity was marked; in left ventricle, regional flows ranged from one-third to two times the mean, the relative dispersion (= standard deviation/mean) of regional flows, corrected for methodological scatter and temporal variation, was 0.33 +/- 0.06 (n = 67) in the whole heart, 0.26 +/- 0.07 in left ventricle, 0.32 +/- 0.11 in right ventricle, and 0.22 +/- 0.19 in the atria. The pattern of regional flows in each heart tended to remain stable with time. In each piece averaged over time, the relative dispersion due to temporal heterogeneity was 0.11 +/- 0.03 (n = 2040) in the whole heart, 0.09 +/- 0.03 in the left ventricle, 0.15 +/- 0.05 in the right ventricle, and 0.23 +/- 0.06 in the atria. The conclusion is that the degree of spatial heterogeneity of local myocardial flows in conscious primates is similar to that of anesthetized animals and isolated hearts, and is much greater than that due to temporal fluctuations.

FIGURE 1

Schema for dividing the heart into identifiable pieces allowing reconstruction.

FIGURE 2

Regional myocardial blood flow in baboon #3 during heat stress. Each column portrays data from one injection of microspheres. The histogram at the top of each column is the normalized density function of relative flows f_i for the left ventricle alone, i.e., f_i/f_Lv, at the time of deposition of the microspheres. The four rings from above to below give the f_i in rings 1–4, base to apex; darker shades arc higher flows, as indicated by the scale in the left lower corner. Injections were made in the control state and during increasing heat stress at the body core temperatures noted at 1,2.5, and 5 hours after the control state.

FIGURE 3

Probability density functions of relative regional flows in the left ventricular myocardium in two baboons each receiving six microsphere injections over a period of 6 hours. Animals were seated at rest in either warm or neutral chamber temperatures. The ordinate is w_i, the fraction of the mass (per unit average flow) having flow f_i, the abscissa is the relative microsphere deposition density or flow, f_i relative to the mean for the whole heart. Left panel: (animal no. 4) Injections were at‘O,3, and 5 hours on the first day and at 0, 2.5, and 4 hours on the following day. The relative dispersions were 0.314, 0.239, 0.259, 0.262, 0.250, and 0.213 for the six experiments. The average relative dispersion (RD) was 0.256 ± 0.033 (n = 6). Right panel: (animal no. 5) The injections, all made on the same day, were at 0, 2, 2:05, 2:34, 2:42, and 252 hours after the first. The relative dispersions of these curves were 0.397, 0.380, 0.347, 0.364, 0.374, and 0.389 for an average of 0.375 ± 0.018 (n = 6).

FIGURE 4

The distribution of relative flows in the hearts of 13 awake baboons, from 13,114 estimates at four to six times in 2,706 tissue pieces. The solid line represents the distribution for the whole heart, while the dotted lines are its left ventricular (LV), right ventricular (RV), and atrial (Atr) components. The standard deviation (sd) for the whole heart curve is shown by the shaded region. The area under each curve represents its fraction of the total heart weight, and the mean is its flow relative to the total heart flow. These are, by definition, unity for the total heart curve. For the regional curves the values are: LV 0.70 and 1.14, RV 0.20 and 0.81, and atria 0.10 and 0.41. the relative dispersion of each curve is a measure of the spatial heterogeneity of the flow. The values are: whole heart 0.38, LV 0.30, RV 0.31 and atria 0.17.