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Pressure and flow changes in the pulmonary circulation in exercising sheep: evidence for elevated microvascular pressure.

The purpose of this study was to measure hemodynamic and transvascular filtration changes in the lung during strenuous exercise in sheep. The specific goals were (1) to determine the nature of the reduction in pulmonary arterial pressure (Ppa) after its initial peak rise with onset of exercise; (2) to use a pulmonary artery catheter distal wedge technique ("microwedge") to better assess longitudinal changes in resistance in the pulmonary circulation with exercise; and (3) to compare lung lymph flow and protein concentration changes at comparable estimated microvascular pressure (Pmv) (mean Ppa - mean left atrial pressure) (Pla) x 0.4 + mean Pla) during exercise versus passive left atrial hypertension to determine whether exercise causes a higher than expected lymph flow. We found that cardiac output rises quickly and thereafter remains constant with constant-rate exercise, and, thus, the secondary reduction in Ppa was due to vasodilation and/or recruitment. The microwedge pressure rose more than did Pla, suggesting that actual Pmv was probably higher than that estimated. With hypoxia, most of the change in pulmonary vascular resistance was in upstream vessels (arteries and capillaries), as was most of the exercise-induced vasodilation. Lymph flow rose more quickly and was much higher during brief exercise than during left atrial hypertension at a comparable calculated Pmv, and lymph protein content decreased more quickly. The data point to a Pmv with strenuous exercise that is higher than expected.

Animals↗

Effect of catecholamines on pulmonary circulation at elevated vascular tone.

The effect of catecholamine stimulation on the longitudinal resistance and compliance distribution in the canine pulmonary vasculature was evaluated under control vascular tone and after vascular tone was elevated using the thromboxane analogue U-46619. The arterial-, venous-, and double-occlusion techniques were used to measure the segmental resistances and compliances in isolated dog lung blood perfused at constant flow. The results of this study indicate that at control vascular tone the catecholamines norepinephrine and epinephrine increase pulmonary vascular resistance and decrease pulmonary vascular compliance through alpha 1- and alpha 2-receptor-mediated stimulation with precapillary alpha 1- and alpha 2-receptors and postcapillary alpha 2-receptors interacting with precapillary and postcapillary beta 2-receptors. In addition, epinephrine appears to have a greater effect on beta 2-receptors than norepinephrine. When vascular tone was elevated, the effect of norepinephrine and epinephrine on pulmonary vascular resistance was not present, which may be due to the appearance of a more pronounced vasodilatory beta 2-receptor system and an attenuation of the alpha-mediated vasoconstrictor responses. In addition, neither catecholamine had any significant effect on pulmonary vascular compliance when vascular tone was raised. These data suggest that the adrenergic-receptor systems modulating pulmonary vascular resistance and compliance in the canine pulmonary circulation are altered when vascular tone is elevated. As a result, these altered pulmonary vascular responses may affect pulmonary capillary pressure, a major determinant of lung fluid balance.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Lipids in the pulmonary circulation after fatal trauma. A postmortem study.

Lipids in the pulmonary circulation were determined biochemically and histologically in seven patients (group A) who died following multiple blunt trauma and in five patients (group B) who died of some other traumatic or nontraumatic cause. Autopsy was performed on average 4.5 hours after death. Blood samples were collected from the right ventricle (RV) and the left atrium (LA). The vasculature of the left lung was perfused in a retrograde direction. The inferior lobe of the right non-perfused lung was examined histologically. Intravascular pulmonary fat was observed in 4/6 cases in group A and in 1/5 cases in group B. No intravascular fat was observed in the tissue samples of brain, liver or kidney. The concentration of free fatty acids (FFA) in blood from RV was higher than in blood from LA both in group A (P is less than 0.01) and in group B (P is less than 0.05). The considerable difference in concentrations of FFA between RV and LA and the low concentration of FFA in the lung perfusate may be due to some kind of "fixation" of FFA in the lung tissue, possibly connected with the aetiological factors of the fat embolism syndrome (FES).

Adult↗

The pulmonary circulation in essential systemic hypertension.

Seventy-one men, ages 16 to 59 years, were referred for systemic hypertension, which was without detectable cause and with limited organ damage (World Health Organization stages I to II). They performed a graded exercise test on the bicycle ergometer in the sitting position. Mean brachial intraarterial pressure, mean pulmonary artery and wedge pressures and cardiac output (Fick method) were measured. At rest mean brachial artery pressure ranged from 72 to 168 mm Hg. Mean pulmonary wedge pressure was significantly (p less than 0.05) related to mean brachial artery pressure at rest, at submaximal work (50 watts) and at the end of exercise (161 +/- 42 [standard deviation] watts). In each subject pulmonary vascular resistance was calculated as the slope of the relation between the pressure gradient across the pulmonary circulation and cardiac output from data at rest, at 50 watts and at the end of exercise; mean critical closing pressure was calculated as the intercept of this relation. Pulmonary vascular resistance averaged 0.63 +/- 0.37 mm Hg/liter/min and was significantly related to age (r = 0.28, p less than 0.05) but not to rest brachial artery pressure (r = 0.14) or pulmonary wedge pressure (r = 0.09, difference not significant for both). The mean critical closing pressure averaged 6.1 +/- 4.0 mm Hg and was not related to brachial artery pressure (r = -0.08) or to age (r = -0.18, difference not significant for both). It is concluded that there is neither a primary nor a secondary effect of systemic hypertension on the pulmonary vasculature in patients with World Health Organization stages I to II essential hypertension.

Adolescent↗

Rapid shallow breathing evoked by capsaicin from isolated pulmonary circulation.

Recently Green et al. (J. Appl. Physiol. 57:562-567, 1984) reported that pulmonary C-fibers initiate the prompt apnea evoked by pulmonary arterial injections of capsaicin; however, their role in the subsequent rapid shallow breathing of the pulmonary chemoreflex is still in dispute. To determine whether this reflex tachypnea is triggered by pulmonary C-fibers rather than by afferents further downstream, we separately perfused the pulmonary and systemic circulations in dogs anesthetized with either halothane or alpha-chloralose as the lungs were ventilated with a servo-controlled ventilator driven by phrenic nerve activity. Injection of capsaicin (10 micrograms/kg) into the pulmonary artery of the isolated pulmonary circulation evoked an immediate apnea followed by rapid shallow breathing. Injection of the same dose of capsaicin into the left atrium of the isolated pulmonary circulation had no effect. By contrast, when capsaicin was administered at a slower rate into the pulmonary artery (10-20 micrograms X kg-1 X min-1) rapid shallow breathing occurred but without apnea. Our results are consistent with the hypothesis that in spontaneously breathing animals, stimulation of pulmonary C-fibers can evoke rapid shallow breathing.

Anesthesia↗

Extending the usable size range of homografts in the pulmonary circulation: outcome of bicuspid homografts.

BACKGROUND: Small-sized homografts are often not available, making the use of surgically reduced cryopreserved homograft conduits appealing. METHODS: From January 1993 to January 2000, 21 large homografts were size-reduced by excising one leaflet and were implanted in the pulmonary circulation. Valve function was compared with 21 children-matched for weight, homograft size, and year of operation-who received a standard homograft. RESULTS: Implanted homograft size and patient weight were equivalent in both the bicuspid and standard groups. Median (range) in-hospital peak instantaneous echocardiographic gradient across the valve was 0 mm Hg (0 to 19) in the bicuspid group versus 0 mm Hg (0 to 17) in the standard group (p = 0.65). Median (range) in-hospital pulmonary insufficiency (scale of 0 to 4) was 2 (0 to 3) in the bicuspid group versus 1.5 (0 to 3) in the standard group (n = 10, p = 0.34). At a follow-up of 54+/-29 months there was no significant difference in conduit reinterventions between the groups. CONCLUSIONS: Surgical creation of a bicuspid valve in the pulmonary circulation results in a functionally equivalent conduit compared with standard homograft as measured by early and midterm valve function.

Cardiac Surgical Procedures↗

Multiple muscarinic receptor subtypes in the canine pulmonary circulation.

The vascular response to the muscarinic receptor agonist acetylcholine (ACh) in the presence of selected antagonists was examined in the isolated blood-perfused canine left lower lung lobe under conditions of normal (resting) and elevated vascular tone. At normal vascular tone, ACh (1-5 mumol) produced a dose-dependent increase in pulmonary arterial pressure (Ppa), total pulmonary vascular resistance (PVR), and downstream resistance (Rds) without altering upstream resistance (Rus). Pirenzepine (50 and 100 nM), the prototype M1-selective antagonist, and gallamine, an M2-selective antagonist, as well as atropine (50 nM) and secoverine (100 nM), nonselective antagonists, attenuated (P less than 0.05) the ACh-induced increase in Ppa and Rds. With elevated vascular tone induced by serotonin infusion, ACh produced a dose-dependent increase in Ppa in 19 of 25 lobes, although Rus decreased while Rds increased in all lobes. At high vascular tone, pirenzepine or gallamine attenuated the ACh-induced increase in Rds, whereas Rus was not affected. Secoverine and atropine antagonized ACh-induced increases in both Rds and Rus. The pA2 values (i.e., the negative log antagonist concentration requiring a doubling of ACh dose for an equivalent increase in Rds) for gallamine, pirenzepine, secoverine, and atropine were 6.1 +/- 0.1, 7.4 +/- 0.1, 8.3 +/- 0.2, and 10.2 +/- 0.3, respectively. These results suggest that 1) ACh increases PVR in the dog by constricting the venous segments (downstream) of the pulmonary circulation via activation of pulmonary vascular muscarinic receptors under conditions of both normal and elevated vascular tone, 2) both M1- and non-M1-muscarinic receptor subtypes appear to participate in mediating the ACh-induced increase in Rds, and 3) ACh moderately relaxes the upstream (arterial) vessels, especially under conditions of elevated tone.

Acetylcholine↗

The backflow from the pulmonary circulation for identification of the aortic origin of the bronchial arteries in experimental left single lung transplantation.

The ideal solution to the bronchial healing problems in lung transplant would be the reconstruction of the bronchial arteries at time of transplantation. The problems with this approach are essentially technical being difficult to identify and preserve the bronchial arteries in humans. The purpose of this paper is to report our experience with an experimental model in dog to easily identify and preserve bronchial circulation in single lung transplantation. The technique is based on the preservation during harvesting of the aortic origin of the first five couples of arterial orifices. Identification of the orifice(s) connected with the bronchial circulation is carried out by the backflow which takes place from the pulmonary circulation after organ reperfusion is resumed. The identified orifice(s) is then anastomosed to the descending recipient aorta, tangentially clamped.

Animals↗

Neurohumoral regulation of the pulmonary circulation during circulatory hypotension in conscious dogs.

We investigated the effects of circulatory hypotension (HYPO) on the left pulmonary vascular pressure-flow relationship in chronically instrumented conscious dogs and the role of five neurohumoral mechanisms in either mediating or modulating the response to this stimulus. HYPO was induced by acute (approximately 15-min) inflation of a hydraulic occluder implanted around the thoracic inferior vena cava, which decreased systemic arterial pressure to approximately 55 mmHg. HYPO resulted in active pulmonary vasoconstriction (53-66%; P < 0.01) in intact conscious dogs. Sympathetic alpha 1-adrenoreceptor block reduced (P < 0.01) the magnitude of HYPO-induced pulmonary vasoconstriction by 91-99%. Neither sympathetic beta-adrenoreceptor block nor cholinergic muscarinic receptor block had any significant effect on the magnitude of HYPO-induced pulmonary vasoconstriction. Surprisingly, angiotensin II receptor block increased (P < 0.05) HYPO-induced pulmonary vasoconstriction by 69-91%. In contrast, arginine vasopressin V1-receptor block reduced (P < 0.05) HYPO-induced pulmonary vasoconstriction by 34-41%. These results indicate that the pulmonary circulation of intact conscious dogs is actively regulated by three distinct neurohumoral mechanisms during HYPO. Sympathetic alpha 1-adrenoreceptor activation is the primary mediator of HYPO-induced pulmonary vasoconstriction. Angiotensin II and arginine vasopressin exert opposing pulmonary vasodilator and vasoconstrictor effects during HYPO, whereas sympathetic beta-adrenoreceptor and cholinergic muscarinic receptor activation do not appear to modulate the pulmonary vascular response to HYPO.

Adrenergic alpha-1 Receptor Antagonists↗

Differential reactivity in the pulmonary circulation.

A new method for relating regional intravascular resistance to pulmonary arterial, capillary, and venous pressure and volume was used to evaluate local differences of reactivity in the pulmonary blood vessels in the isolated lung lobe of the dog. Intravascular infusion of isoproterenol caused active dilatation of pulmonary arteries and veins. Capillary conductance (1/resistance) and volume increased, possibly as a result of the opening of previously closed capillaries. Serotonin infusion caused active constriction of both the pulmonary arteries and veins. A low dose of serotonin (1.5 mug/min per kg) caused predominant constriction of whichever vessels were upstream (arteries during forward perfusion, veins during reverse perfusion). A high dose of serotonin (4.5-5.0 mug/min per kg) caused constriction of both upstream and downstream vessels. Metabolic inactivation of serotonin by the lung is suggested as an explanation for these observations. Histamine infusion caused predominant venous constriction whether veins were upstream or downstream. Capillary volume and conductance decreased during forward and reverse perfusion, perhaps as a result of pericapillary edema formation. Large arterial vessels constricted slightly, whereas small arterial vessels appeared to be passively dilated.

Animals↗

[Intravenous digital angiography of pulmonary circulation].

Intravenous digital angiography was performed in 92 patients with pulmonary diseases. The examination yielded satisfactory results in 82/92 cases (89%). The most promising fields of application of pulmonary digital angiography are: vascular malformations (3 cases: 3%), pulmonary emphysema (24 cases: 26%) and pulmonary embolism (38 cases: 41%). In tumoral masses (14 cases: 15%) digital angiography showed dislocation of the surrounding pulmonary vessels but failed to demonstrate the intrinsic vascularity of the mass, deriving from the bronchial arteries. In post-lobectomy controls (10 cases: 11%) the examination gave a good demonstration of the absence of vascular supply at the site of the previous surgery. Intravenous digital angiography shows many technical limitations, namely a reduced resolution power and a small field of view; in addition, it requires patient immobility, which results sometimes impossible in critically ill patients. In spite of these inconvenients, however, intravenous digital angiography appears to be an important diagnostic step for the evaluation of pulmonary embolism and vascular malformations: in these conditions, digital angiography can be the procedure of choice.

Angiography↗

Effects of oxygen radicals on cysteinyl leukotriene metabolism and pulmonary circulation in young pigs.

The effects of oxygen radicals, generated by the hypoxanthine-xanthine oxidase (XO) system, on pulmonary circulation and release of cysteinyl-containing leukotrienes (LTs) were studied in pigs after XO infusion into the right atrium. A 2.3-fold increase in pulmonary vascular resistance (PVR) (p < 0.05 vs. baseline) and a 2.1-fold increase in LT release (p < 0.05 vs. baseline) was observed. Pretreatment with indomethacin and allopurinol attenauted the vascular response (p < 0.01 and p < 0.05 vs. XO), and the LT release was inhibited by allopurinol and catalase (p < 0.01 and p < 0.02 vs. XO). We conclude that oxygen radicals stimulate lipoxygenase metabolism. This coincides with the observed increase in PVR, however, no causal relationship can be derived from the data presented.

Animals↗

[Possibility of pulmonary circulation study with nongaseous radioactive isotopes].

This paper deales with the applications of radionuclides to the study of human pulmonary circulation for better knowledge of some morphological and dinamic functional aspects. At this time the methods used are divided in three groups in respect to the purpose. - Methods for static investigations of pulmonary perfusion, by scintigraphy with radioalbum aggregates. - Methods for dynamic investigation, general radiocardiography and selective right radiocardiography with radioalbum macroaggregates. - Methods for morpho-functional investigation, especially Isotopoangiocardiopneumography using gamma-camera and Tc99mO4. Here are treated the fields of applications, the purpose and the limits of these methods, used in a large number of and acquired pulmonary vascular diseases.

Heart Function Tests↗