Circulatory transport of iodoantipyrine and water in the isolated dog heart

Abstract

The exchanges of ¹²⁵I-labeled 4-iodoantipyrine (I-Ap), ¹⁴C-labeled antìpyrine (¹⁴C-Ap), and tritiated water (THO) were studied in isolated blood-perfused, beating, nonworking dog hearts. From a first set of experiments, analysis of externally monitored myocardial clearance curves of I-Ap after its injection into coronary artery blood showed its washout to be flow limited at flows ranging from 0.8 to 3.8 ml · g⁻¹ · min⁻¹. Therefore, these curves can be used for estimating coronary blood flow. In a second set of experiments, coronary sinus dilution curves of simultaneously injected I-Ap and THO were found to be indistinguishable in shape at high coronary flows. At low flows (<1.8 ml · g⁻¹ · min⁻¹), THO curves showed an earlier upslope and higher peak than antipyrine, indicating either a diffusional shunt for water or a larger volume of distribution for antipyrine. ¹⁴C-Ap had a slightly faster washout than I-Ap. The differences are partially attributable either to differences in solubility of I-Ap, ¹⁴C-Ap, and THO in erythrocytes or to differences in their volumes of distribution, and partially to diffusional shunting of water.

FIGURE 1

¹²⁵I-Ap washout curves after bolus injection at various flows. F/W is the flow per gram of myocardium. Top: Curves w were obtained with a detector sensitive to isotope emissions from entire isolated heart; curves cp were obtained with tighter collimation over region supplied by pump-perfused left anterior descending coronary artery in open-chest dog. Heart weights are shown in upper right corner. Recirculation of tracer in perfused coronary preparation results in higher tails on these curves. For H* (t) values of 0.9, 0.5, and 0.1, valves of F/W for each curve are listed (at arrows) in order of increasing values of F · t/W; for example, at H* (t) = 0.5, curve farthest to left was obtained at F/W = 0.5, and curve farthest to right was obtained at F/W = 3,1. Bottom: Curves from one experiment in which heart weight was obtained by continuous recording. Broken lines, F/W > 2.0; solid lines, 1 < F/W <2.0; dotted lines, F/W < 1.0.

FIGURE 2

Venous dilution curves for ¹²⁵I-Ap and THO from isolated dog heart. Ordinate is concentration-vs.-time curve normalized to unit area, $C(t)/\underset{u}{\overset{\infty }{\int }}C(t)\mathit{\text{dt}}$ and, because the injection durations were brief, can be considered to be the transport function, h(t), from injection site to sampling tubes.

FIGURE 3

Simultaneous venous dilution curves for ¹³¹I-Ap, ¹⁴C-Ap, and THO (tritiated water) in isolated dog heart.

FIGURE 4

Simultaneous venous dilution curves for ¹²⁵I-Ap and THO (tritiated water). Note that none of the curves in Figures 3 and 4 are monoexponential.

FIGURE 5

Effect of flow on ratios of peak heights of water curves (h_T (t_p)) to those of simultaneously recorded I-Ap curves (h_Ap(t_p)). Although scatter is great, there is tendency for water curves to have higher (and perhaps earlier peaks) at low flows. There is no apparent tendency for reverse to occur at high flows, which is what would occur if I-Ap became permeability limited to even a small extent.