Hope in primary pulmonary hypertension.
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Child↗
Biomedical subjects
J T Reeves
Publications and source records attributed to J T Reeves.
Distribution of mast cells and histamine in canine pulmonary arteries.
The distributions of mast cells and histamine along the canine pulmonary arterial tree were determined. Mast cell counts were made on toluidine blue stained histologic sections, and histamine concentration was measured in dissected arterial branches by an enzymatic-isotopic assay. Mast cell density and histamine concentration were greater in small muscular arteries compared to elastic arteries. In elastic arteries there was more histamine than would be expected by the number of mast cells found there, suggesting the presence of non-mast cell histamine in those vessels. In all arteries mast cells were located primarily in the adventitia. The finding of mast cells and histamine in greatest concentration in muscular pulmonary arteries suggests that these vessels are the major site of action of histamine and other mast cell contents within the pulmonary arterial tree.
Animals↗
Improved phonocardiogram system based on acoustic impedance matching.
We considered that phonocardiographic recording could be improved 1) by minimizing the acoustic impedance mismatch between the precordial tissue and transducer, 2) by optimizing the configuration of the impedance-matching medium and transducer design, and 3) by storing signals in digital form through analog-to-digital conversion of analog recordings made at the bedside. The use of an aqueous coupling medium to improve energy transmission increased signal voltage approximately 100-fold over presently used commercial devices. Further match to the crystal was achieved by a concentrating horn configuration for the aqueous medium. Measured frequency response of the device in the range 1 Hz to 1 kHz was better than two other commercially tested microphones. Inspection of comparative phonocardiograms showed more information from the new device than from the two other commercial devices. Unfiltered digitized signals, using our microphone in normal subjects, demonstrated good beat-to-beat repeatability, but analog filtering to obtain the conventional phonocardiogram showed significant loss of information. The new instrument appears to be superior to those commercial devices tested in recording heart sounds.
Acoustics↗
Pregnancy blunts pulmonary vascular reactivity in dogs.
Pregnancy decreases systemic vascular reactivity but comparatively little is known about the effects of pregnancy on the pulmonary circulation. Pulmonary vascular resistance (PVR) during acute hypoxia was lower (P < 0.01) in eight intact anesthetized pregnant dogs compared to the same animals postpartum. Mean pulmonary arterial pressure (Ppa) and PVR during infusion of prostaglandin (PG) F2 alpha were also reduced during pregnancy. Nonpregnant female dogs (n = 5) treated with estrogen (0.001 mg x kg-1 x da-1) for 2 wk had decreased Ppa (P < 0.01) during acute hypoxia compared to control measurements, but PVR was unchanged during hypoxia and PGF2 alpha infusion. Treatment with progesterone in four dogs had no effect on pulmonary vascular reactivity to hypoxia or PGF2 alpha. Inhibition of circulating PG with meclofenamate in four dogs during pregnancy did not appear to restore pulmonary vascular reactivity. Blunted pulmonary vascular reactivity is suggested by the limited data available for women, but is not seen in pregnant cows. We conclude that pregnancy decreases pulmonary as well as systemic vascular reactivity in the dog, but the mechanism is unclear.
Animals↗
Chronic propranolol treatment blunts right ventricular hypertrophy in rats at high altitude.
Chronic beta-receptor blockade has been reported to inhibit right ventricular hypertrophy in rats at high altitude. If so, we wanted to determine whether beta-receptor blockade or some other drug action were involved and whether the heart, the lung vessels, or blood alterations were affected. In rats, chronic treatment with DL-propranolol (2 mg/kg ip once daily) reduced right ventricular hypertrophy and polycythemia of chronic high altitude. D-Propranolol and metoprolol did not reduce hypoxia-induced right ventricular hypertrophy or polycythemia. In isolated lungs from low-altitude rats treated chronically with DL-propranolol or with D-propranolol the pressor response to acute hypoxia was blunted. Chronic DL-propranolol blunted the acute hypoxic pressor response and angiotensin II induced vasoconstriction in lungs from high-altitude rats. Two effects of DL-propranolol treatment were seen: 1) blockade of beta 2-adrenergic receptors, which reduced the right ventricular hypertrophy of high altitude through reduction of hematocrit; and 2) a non-beta-effect, which reduced vascular responsiveness to acute hypoxia in the isolated lung preparation.
Adaptation, Physiological↗
Moderation of hypoxic vasoconstriction by infused arachidonic acid: role of PGI2.
To determine the role of prostaglandins in modulating pulmonary circulatory responses, we examined the effect of the prostaglandin precursor, sodium arachidonate, on the pulmonary vascular resistance of mongrel dogs during alveolar hypoxia. When infused intravenously for 5 min during hypoxia, sodium arachidonate (1 mg/min) decreased pulmonary vascular resistance from 6.9 +/- 1.1 to 4.9 +/- 0.6 U (P less than 0.05). The vasodilation produced by sodium arachidonate was blocked by sodium meclofenamate, a cyclooxygenase inhibitor. By infusing radiolabeled sodium arachidonate and collecting aortic blood samples, we found from chromatographic and mass spectrometric analysis that a major prostaglandin produced was 6-keto-PGF1 alpha, the stable hydrolysis product of PGI2. Infusion of PGI2, but not PGE2, during hypoxia decreased pulmonary vascular resistance. We concluded that the prostaglandin precursor, sodium arachidonate, is a vasodilator of the pulmonary vasculature that has been constricted by alveolar hypoxia, probably because PGI2 is formed from the arachidonate. The pulmonary circulation may be similar to the systemic circulation where vasoconstriction results in the generation of vasodilatory prostaglandins that attenuate the constrictor effect.
Animals↗
Control of breathing in Sherpas at low and high altitude.
Sherpas are well known for their physical performance at extreme altitudes, yet they are reported to have blunted ventilatory responses to acute hypoxia and relative hypoventilation in chronic hypoxia. To examine this paradox, we studied ventilatory control in Sherpas in comparison to that in Westerners at both low and high altitude. At low altitude, 25 Sherpas had higher minute ventilation, higher respiratory frequency, and lower end-tidal carbon dioxide tension than 25 Westerners. The hypoxic ventilatory response of Sherpas was found to be similar to that in Westerners, even though long altitude exposure had blunted the responses of some Sherpas. At high altitude, Sherpas again had higher minute ventilation and a tendency toward higher arterial oxygen saturation than Westerners. Oxygen administration increased ventilation further in Sherpas but decreased ventilation in Westerners. We conclude that Sherpas differ from other high-altitude natives; their hypoxic ventilatory response is not blunted, and they exhibit relative hyperventilation.
Adaptation, Physiological↗
Calcium augments hypoxic vasoconstriction in lungs from high-altitude rats.
Isolated lungs from high-altitude rats compared with those from low-altitude rats have blunted hypoxic pressor responses. Because calcium is essential for the hypoxic pressor response and has been shown to be altered in the pulmonary arterial smooth muscle during high-altitude exposure, we wondered whether altered calcium metabolism might account for the blunted response. We attempted to unmask differences between high- and low-altitude rat lungs by altering extracellular calcium. The addition of calcium to the blood perfusate augmented the hypoxic pressure response of high-altitude lungs and depressed that of low-altitude lungs. Calcium addition did not affect pressor responses to angiotensin II, but slowed vasodilation after both angiotensin injection and removal of the hypoxic stimulus. The maximal KCl-induced contraction was blunted in rings of main pulmonary artery from high-altitude rats, but augmented in their aortic rings. Submaximally constricted (40 mM KCl) pulmonary arteries from low- but not high-altitude rats further constricted with calcium addition. Aortic rings exhibited an inverse behavior. Thus, calcium addition augmented the blunted vasopressor response in high-altitude rats lungs, possibly by an effect on lung arteries. The aorta and main pulmonary artery differ in calcium handling.
Adaptation, Physiological↗
Ventilatory acclimatization to high altitude is prevented by CO2 breathing.
The hypoxia of high altitude stimulates ventilation. If the resultant respiratory alkalosis inhibits the initial increase in ventilation, then with prevention of alkalosis, ventilation should rise immediately to a stable plateau. 4 subjects inspired CO2 (3.77%) from ambient air in a hypobaric chamber (PB = 440-455 Torr) during 100 h at high altitude. Ventilation (for given oxygen uptakes at rest and during exercise) increased promptly and remained stable. 4 control subjects exposed to high altitude without CO2 supplementation showed the expected progressive increases in ventilation with time. The hyperoxic CO2 ventilatory response curve shifted progressively to the left with time in the control subjects, but not in those given supplemental CO2. The latter group also failed to increase the ventilatory response to isocapnic hypoxia. Thus, CO2 supplementation at high altitude prevented the so-called "ventilatory acclimatization' from occurring. Prevention of respiratory alkalosis at high altitude probably permitted maintenance of [H+] at some central nervous system locus, thus allowing an uninhibited hypoxic stimulation of ventilation.
Acclimatization↗
Embryo transplanted calves: the pulmonary hypertensive trait is genetically transmitted.
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Altitude↗
Cardiac output is decreased and hypoxic vasoconstriction is intact in chronically hypoxic sheep.
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Adaptation, Physiological↗
Release of dilator prostaglandins from rat lung during angiotensin II-induced vasoconstriction.
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Angiotensin II↗
Ultrasonic pulsed Doppler transoesophageal measurement of aortic haemodynamics in humans.
Centreline blood velocity and exterior wall motion were measured in the descending aorta of humans using an oesophageal probe, a pulsed ultrasound Doppler velocity meter and an ultrasonic echo tracking system. The development of a method for easily measuring haemodynamics in the thoracic region using an oesophageal probe will provide an essentially non-invasive method for the assessment of cardiac function and the nature of blood vessels in that region. Detailed anatomical studies of the thorax were conducted by cross-sectioning of the thorax of a cadaver. Blood velocity waveforms were recorded from the descending aorta both during rest and exercise. In one volunteer, the peak centreline velocity increased from a resting value of approximately 30 cm s-1 to an exercise value of approximately 50 cm s-1. Vessel diameter waveforms similar to those for pressure were also recorded showing diameter changes of 1.8 mm. The accuracy and resolution of the technique would be improved by multicrystal probes and multigate ultrasonic flowmeters allowing for accurate calculation of the Doppler angle, imaging of vascular flow regions, and measurement of pulse wave velocity.
Adult↗
Postnatal changes in response of canine neonatal pulmonary arteries to histamine.
Postnatal development of histamine receptors in the canine pulmonary circulation was examined utilizing histamine cumulative dose-response curves of pulmonary arteries isolated from neonatal and adult dogs. The maximal contractile response to histamine was relatively low at birth (avg 0.069 g) and increased with postnatal age, reaching a maximum in the adult (avg 1.10 g). H2-receptor blockade with metiamide increased the contractile response to histamine during the first 2 wk of life (avg 0.38 g), suggesting H2-receptor dominance over H1-receptors in the newborn. Maximal developed tension, in response to KCl, gradually increased with postnatal age, suggesting progressive maturation of the smooth muscle response. In contrast to pulmonary arteries, isolated tracheal segments from puppies aged 1-5 days demonstrated large contractile responses (avg 5 g). Histamine (in microgram/g of wet wt of lung tissue) was absent in the lungs from 3rd trimester fetal dogs and rapidly increased over the first 2 wk of life, reaching a maximum in the adult. It is concluded that 1) the response of pulmonary arteries to histamine changes during the first 2 wk of life; 2) this change may reflect a decrease in H2-receptors and an increase in H1-receptors; 3) the contractile ability of pulmonary vascular smooth muscle increases with postnatal age; and 4) histamine is unavailable for physiological responses in the fetal dog pulmonary circulation.
Animals↗
Pregnancy-induced pulmonary hypertension in cows susceptible to high mountain disease.
Observations in several species suggest that pulmonary vascular reactivity may be reduced during pregnancy. We tested this hypothesis in two groups of unanesthetized cows, one "susceptible" and one "resistant" to high mountain or brisket disease. At the altitude of residence (1,524 m), mean pulmonary arterial pressure was elevated during pregnancy by 18% and total pulmonary vascular resistance by 32% in susceptible but not in resistant cows. During acute exposure to simulated altitudes of 2,120--4,550 m, pulmonary arterial pressure was increased by 16% and total pulmonary resistance by 28% during pregnancy in susceptible cows. The pulmonary pressor response to a 5 microgram/kg bolus of prostaglandin FIalpha was not different during pregnancy in either group. Resistant cows hyperventilated while pregnant, raising arterial partial pressure of oxygen (PaO2) by 6 Torr both at 1,524 m and, on the average, by 7 Torr at altitudes of 2,120--4,550 m. Susceptible cows increased their PaO2 less than did the resistant cows during pregnancy. The results indicated that pregnancy was associated with a greater rise in pulmonary arterial pressure and total pulmonary vascular resistance during acute hypoxia and failed to elicit as great a ventilatory response in susceptible than in resistant cows.
Altitude↗
Accentuated hypoxemia at high altitude in subjects susceptible to high-altitude pulmonary edema.
To investigate the hypotheses that activated coagulation, catecholamine release, or arginine vasopressin release are involved in the pathogenesis of high-altitude pulmonary edema (HAPE), we measured these variables in seven subjects susceptible to HAPE and in nine control subjects at an altitude of 1,600 m, and after 6 and 12 h at a simulated altitude of 4,150 m. Each subject was studied twice, once after 3 days of placebo medication and once after 3 days of premedication with aspirin and dipyridamole. At high altitude, HAPE-susceptible subjects showed significantly exaggerated hypoxemia and a slightly higher end-tidal carbon dioxide partial pressure that did not account fully for the hypoxemia. Fibrinolytic activity was significantly accelerated in both groups at high altitude, whereas other coagulation measurements, catecholamines and arginine vasopressin levels, and pulmonary function tests were not significantly changed. Similar findings were obtained after both placebo and platelet-inhibitor premedication. The results indicate that none of the three hypothesized mechanisms, i.e., activated coagulation, excessive catecholamine release, or antidiuresis, would account for HAPE susceptibility. Instead, HAPE-susceptible subjects exhibited exaggerated hypoxemia associated with relative hypoventilation and a widened alveolar-arterial gas pressure difference.
Adolescent↗
Vascular hypertrophy in cattle susceptible to hypoxic pulmonary hypertension.
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Animals↗
A closed lung system study of inert gas absorption.
The demonstration that the rate of rise of the alveolar fraction of nitrous oxide is enhanced when the inspired N2O concentration is high is termed the "concentration effect." A similar effect on a second gas has been termed the "second gas effect". These effects have been observed in open systems and attributed to differential changes between inspired and expired ventilation. The purpose of this investigation is to study these effects in a closed system. A breath-holding maneuver was utilized with a high and a low N2O concentration in argon and oxygen. The results indicate that breath holding with a high N2O concentration "concentrates" both the alveolar fraction of N2O and argon. These results are attributable to alveolar volume shrinkage as a consequence of the large absorption of N2O by the pulmonary blood. A mathematical model verifies this interpretation and suggests that volume shrinkage can be important in breath-holding maneuvers designed for noninvasive measurement of cardiac output and lung tissue volume.
Argon↗