In 55 Sprague-Dawley rats (mean wt, 277 +/- 6.2 g) exposed to hypobaric hypoxia (air at 380 mmHg), and 23 weight-matched controls kept in room air, pulmonary and systemic artery pressures were measured daily for 2 wk via indwelling catheters. After each day of exposure, 1 or 2 hypoxic rats, to a total of 20, and 5 control rats were killed during the experiment. In these rats, the pulmonary arterial tree was injected post mortem with barium-gelatin and inflated with formaldehyde solution, and three structural features were quantified microscopically: 1) abnormal extension of muscle into peripheral arteries where it is not normally present (EMPA); 2) increased wall thickness of the normally muscular arteries, expressed as a percentage of external diameter (%WT); and 3) reduction in artery number expressed as an increase in the ratio of alveoli to arteries (A/a). Mean pulmonary artery pressure (Ppa) rose significantly after day 3 of hypoxic exposure (P less than 0.05) and had doubled by day 14; the mean systemic artery pressure (Psa) of hypoxic rats and Ppa and Psa of control rats were unchanged. The level of Ppa correlated with the degree of structural changes; for EMPA, r = 0.84; for %WT, r = 0.64; and for A/a, r = 0.73 (P less than 0.001 in all.

In awake rats with indwelling catheters, the development of pulmonary hypertension after feeding Crotalaria spectabilis seeds is followed. Hypoxemia is excluded as a factor. Other hemodynamic changes are found before hypertension. After 7 days, pulmonary artery pressure (Ppa) is normal, 17.17 +/- 0.30 (SE) mmHg and from 14 days significantly increased (P < 0.01). Oxygen consumption (Vo2) is significantly increased by day 7 (control 22.72 +/- 2.13 ml . min-1 . kg-1; Crotalaria 42.47 +/- 2.95; P < 0.001). and cardiac index (CI) is significantly above normal after 7, 14, and 21 days (control 350 +/- 31 ml . min-1 . kg-1; 7 days Crotalaria 476 +/- 28; P < 0.02); pulmonary vascular resistance (PVR) increases to six times normal at day 33 (control 0.033 +/- 0.003 U/kg; 33 days Crotalaria 0.194 +/- 0.020; P < 0.001). The pulmonary arteries of these same rats were studied by quantitative morphometric techniques. The first change, muscle in smaller and more peripheral arteries than normal, is detected when Vo2 and CI are increased. Increased medial thickness of arteries < 200 micrometer diameter follows with Ppa rises. Even later, the larger arteries increase their media as the number of peripheral arteries falls and right ventricular hypertrophy becomes apparent, and hypertension and increased PVR are well established.

To study the influence of age and sex on the hemodynamic and structural response of the pulmonary vascular bed to chronic hypobaric hypoxia, "infant" Sprague-Dawley rats from 8 days old and "adult" rats from 9 wk old, each group including both sexes, were exposed to half atmospheric pressure for 1 mo and then allowed to recover in room air for up to 3 mo. During hypoxic exposure, pulmonary artery hypertension (Ppa) developed in all groups. The level of Ppa was similar in both male and female infant and in male adult rats but was significantly lower (P < 0.01) in the female adult rats. After recovery in room air, only partial regression of Ppa had occurred in all groups (P < 0.001). In male and female adult rats, recovery values were similar but infant rats had more residual Ppa than adults (P < 0.001). The structural changes that developed during hypoxia, especially the abnormal presence of muscle in small and peripheral intra-acinar arteries, were more severe in male adult rats compared with female adults (P < 0.01) and in infants of both sexes compared with male adults (P < 0.01). After recovery, residual structural changes were present in all rat groups but were most severe in the infants (P < 0.01).

SUMMARY. We banded the left pulmonary artery in rats to investigate, in the same animal, the effect of both increased and decreased flow on the lung vasculature and to determine how these hemodynamic states modify the structural changes produced by a 2-week exposure to hypobaric hypoxia. In unanesthetized rats, pressures were recorded from the main pulmonary artery and aorta via indwelling catheters, cardiac output was calculated by the Fick principle, and pulmonary and systemic vascular resistance estimated. Technetium-99m macroaggregated albumin was injected and radionuclide activity counted separately over the right and left lungs as a measure of flow. At postmortem, right and left ventricles of the heart were weighed and the lungs injected to permit analysis of arteriograms and morphometric assessment of structural changes in the pulmonary vascular bed. Flow in the left lung was reduced to one-fifth normal in rats with left pulmonary artery bands. In "room air" rats, pressure proximal to the left pulmonary artery band and in the right lung was slightly higher than in nonbanded controls, but not as high as in nonbanded or banded hypoxic rats. Changes in flow and pressure in both lungs of "room air" rats with left pulmonary artery bands were associated with a mild degree of extension of muscle into peripheral pulmonary arteries normally nonmuscular, medial hypertrophy of normally muscular arteries, and reduced arterial density. These three structural changes were present in both lungs of "hypoxic" rats but were much more severe. High flow in the right lungs of "hypoxic rats" with left pulmonary artery bands worsened only the degree of extension. Decreased flow and pressure in the left lungs of these animals prevented both the extension and the medial hypertrophy of hypoxia, but not the severe reduction in arterial density. It seems that the latter may occur as a direct response to low oxygen tension, whereas extension and medial hypertrophy are influenced by altered flow and pressure, respectively. (Circ Res 52: 432-441, 1983) IN previous studies, we observed that rats, during a 2-week exposure to chronic hypoxia, develop a progressive rise in pulmonary artery pressure associated with structural changes in the pulmonary vascular bed (Rabinovitch et al., 1979). The structural changes consist of extension of muscle into peripheral arteries normally nonmuscular, increased medial wall thickness of normally muscular arteries, and reduced arterial density relative to alveolar. In the present study, we banded the left pulmonary artery in the rat to determine for the first time in the same animal how increased flow (to the right pulmonary vascular bed) and decreased flow (to the left) might alter the structural remodeling of chronic hypoxia. Methods Animals StudiedTwenty-four adult male Sprague-Dawley rats (mean weight 336 ± 33 g) were used; 15 were selected randomly to be kept in room air (room air rats) and 11 to be exposed to chronic hypobaric hypoxia (air at 380 torr) for 2 weeks (hypoxia rats). Seven of the 15 ro...

Blood O2 saturations were measured by microscopic oximetry in the small coronary veins of wither open-chest or isolated and blood-perfused dog hearts. Subendocardial saturations (average 34%) were significantly lower than subepicardial (average 52%) in isolated hearts contracting isovolumically at systolic and coronary perfusion pressures of 100 mmHg. Saturations of botb regions fell and were not significantly different from each other (both averaged 16%) with partial coronary occlusion. When MVo2 was increased by calcium infusion, subendocardial saturations fell sharply to about 2% and were significantly, lower than subepicardial (average 10%). Conversely, when MVo2 was decreased by ventricular decompression, saturations rose equally in subendocardium (average 40%) and subepicardium (average 45%) (not significant). These data illustrate the efficacy of cascular autoregulation in isolated hearts. In open-chest dogs, as in isolated hearts with partial coronary occlusion, subendocardial (average 20%) saturations were not significantly diffenent from each other and ranged from 0 to 70%, suggesting the possibility of significant differences either in regional coronary flow or MVo2, or both, in closely adjacent areas throughout the myocardium.