Yoshihiro Moue

Distribution of pulmonary blood flow in conscious resting rats

The pattern of pulmonary blood flow (PBF) distribution was determined in the rat, in which lung gravitational forces are minimal. Microspheres were infused into the inferior vena cava of 15 conscious, and 5 anesthetized rats. Relative scatter of specific PBF [(sample activity/sample weight)/(total activity/total weight)] in 28 lung samples was calculated. In 5 of the conscious rats, consecutive determinations were made 30 min apart. In 5 anesthetized rats, PBF was determined in prone and supine positions. Relative scatter of specific PBF varied from 0.84 to 1.12, with PBF being distributed preferentially to the hilar, central regions. There was a high correlation between consecutive measurements: y = 0.88 x +0.11 (n = 140, r = 0.92). By changing from prone to supine position, PBF to the topmost regions increased, and that to the lowermost regions decreased, by only 3 percent. The results indicate that in the conscious resting rat, PBF has a small but significant preferential distribution to the hilar, central regions, with lower blood flow to the peripheral regions of the lung.

Role of β-adrenergic and cholinergic systems in acclimatization to hypoxia in the rat

To role of beta-adrenergic and muscarinic cholinergic systems on maximal treadmill exercise performance and systemic O2 transport during hypoxic exercise (PIO2 approximately 70 Torr) was studied in rats acclimatized to hypobaric hypoxia (PIO2 approximately 70 Torr for 3 weeks, A rats) and in non-acclimatized littermates (NA rats). Untreated A rats had lower resting (fH) and maximal heart rate (fHmax) and cardiac output (Q), and higher maximal O2 uptake (VO2max) than NA. The only effect of cholinergic receptor blockade with atropine (Atp) was an increase in pre-exercise fH to comparable levels in A and in NA. beta 1-adrenergic receptor blockade with atenolol (Aten) lowered pre-exercise fH and (fHmax) to comparable values in A and in NA rats. However, since both pre-exercise fH and fHmax were lower in untreated A, the effect of Aten was relatively smaller in A. Aten reduced maximal exercise cardiac output (Qmax) in NA; however, tissue O2 extraction increased such that VO2max was not affected. Aten did not influence Qmax or any other parameter of systemic O2 transport in A. In conclusion the increased cholinergic tone may be responsible for the lower resting fH but not the lower fHmax of A; the integrity of the beta-adrenergic system is not necessary to attain VO2max in hypoxia either in A or in NA; the decreased response to beta-adrenergic stimulation in A limits the efficacy of this system on the mechanisms of systemic O2 transport and reduces the effect of its blockade on these mechanisms.

Cardiac Output and Regional Blood Flow Measurement with Nonradioactive Microspheres by X-Ray Fluorescence Spectrometry in Rats

Since its introduction (Rudolph and Heymann, 1967) a number of studies have employed the radioactive microsphere method to evaluate changes in cardiac output, regional blood flow, and distribution of pulmonary blood flow under various experimental conditions. Unfortunately, the storage, handling, processing and disposing of radioactive materials requires many precautions and restrictions. Recently, an X-ray fluorescence system and the technique of labeling microspheres with stable heavy elements were developed and used to assess the coronary, hepatic and renal blood flow of large animals (Morita et al., 1990; Mori et al., 1992; Sakamoto et al., 1992). However, this method has not been applied to the measurement of blood flow in small animals such as rats. Rats are one of the most commonly used experimental animals, since entire organs can be easily analyzed because of their relatively small size.

α2-Adrenergic-receptor response in reversible increase in hemoglobin concentration in intermittent hypoxia

We have previously shown that intermittent hypoxia (IHx, 10% O(2), 60 min/day) leads to an increase in the splenic alpha2-adrenoceptor response and results in a splenic contraction-induced reversible increase in hemoglobin concentration ([Hb]). In the present study, we determined whether IHx of shorter duration (15 min/day (15-min) and 30 min/day (30-min)), produced this phenomenon in rats. A significant increase in [Hb] during hypoxia was observed in both the groups, but its magnitude was larger in the 30-min IHx rats. Even when the cumulative exposure time (time/dayxdays) was shorter, the [Hb] increase was larger in the rats with longer daily hypoxic exposure. The alpha2-adrenoceptor antagonist yohimbine abolished the [Hb] increase of 15- and 30-min IHx. The increase in [Hb] following administration of the alpha2-adrenoceptor agonist oxymetazoline was also higher in 30-min IHx; indicating that the higher [Hb] produced by longer daily hypoxic exposure times is the result of increases in alpha2-adrenergic-receptor response of greater magnitude. In conclusion, IHx for periods as short as 15 and 30 min/day increases the splenic alpha2-adrenoceptor response and its magnitude reaches the maximum value depending on the daily hypoxic exposure time. A reversible increase in [Hb] constitutes a useful mechanism that protects organ oxygen supply during hypoxic episodes of variable duration and intensity.

Chronic hypoxia decreases heterogeneity of pulmonary blood flow distribution in rats

Pulmonary blood flow (PBF) distribution was studied in 15 chronically hypoxic rats (3 weeks, 10% O2 in N2) breathing 10% O2 (chronic hypoxia, CHx) and after 30 min of breathing air (acute normoxia, ANx). Controls were 15 normoxic littermates (normoxia, Nx) breathing air. Nonradioactive microspheres were infused into the inferior vena cava in the conscious resting state. The lungs were cut into 28 samples, and relative scatter of specific PBF was calculated as (sample activity/sample dry weight)/(total activity/total lung dry weight). In Nx, PBF had a small but significant preferential distribution to the hilar, central regions, with lower blood flow to the peripheral regions (central-to-peripheral pattern). In CHx, however, there was no significant difference between blood flows to the central, middle and peripheral regions of the lung. ANx resulted in no change in PBF distribution. The results indicate that CHx attenuates the central-to-peripheral gradient of PBF distribution, probably due to vascular structural remodeling developed in CHx.

Pulmonary blood flow distribution during acute hypoxia in conscious resting rats

The effect of hypoxia on pulmonary blood flow (PBF) distribution were studied in 11 conscious resting rats. Microspheres were infused into the inferior vena cava during normoxia (Nx), acute normobaric hypoxia (AHx, 10% O2, 30 min), and 30 min after removal of hypoxia (post-hypoxia, PHx). The lungs were cut into 28 samples, and relative scatter of specific PBF was calculated as (sample activity/sample dry weight)/(total activity/total lung dry weight). Changes in pulmonary arterial pressure (PAP) during AHx were determined in five additional rats. During Nx, PBF was distributed preferentially to the hilar, central regions, rather than to the periphery. AHx resulted in a decrease in PaO2 from 85.1 +/- 0.9 to 37.8 +/- 1.2 Torr (mean +/- SE). Mean PAP increased significantly from 14.9 +/- 0.6 in Nx to 21.2 +/- 1.0 Torr in AHx (mean +/- SE). However, PBF distribution remained unchanged. PHx restored arterial blood gases and PAP to control levels without changing PBF distribution. The results indicate that conscious resting rats do not demonstrate changes in PBF distribution during AHx.