Summary

Introduction: Oxygen therapy is commonly used in emergency department and intensive care units without careful evaluation of its effects, especially on the haemodynamics and artery characteristics.



Materials and methods:  A prospective laboratory study evaluated brachial circulatory effects of normobaric hyperoxia using ultrasonography-Doppler. The study was set in a hospital research laboratory. The subjects were thirteen healthy volunteers. Investigations were performed under normal air ventilation and after 20 min of hyperoxic mixture ventilation using a high concentration mask. Two dimensional images and brachial blood flow velocities were recorded using ultrasonography and pulsed Doppler to study changes in cross sectional area, blood flow, resistance index, and cross-sectional compliance coefficient.



Results:  During hyperoxic exposure, mean PaO2 was 372 ± 21 mmHg. A significant decrease of heart rate was observed. Arterial pressures (systolic and diastolic arterial pressures) were not modified. A decrease of cross sectional areas at end diastole and end systole was observed. Pulsed Doppler study showed a decrease of brachial artery blood flow and an increase of the resistance index. Furthermore, a decrease of the cross-sectional compliance coefficient was observed during hyperoxic exposure in all subjects.



Conclusion:  This study using two-dimensional ultrasonography and pulsed Doppler could demonstrate an increase in brachial arterial tone and a decrease in brachial blood flow under normobaric hyperoxia.

Hyperoxia-induced arterial compliance decrease in healthy man

Because high partial pressures of oxygen (Of) can cause peroxidative cleavage of membrane lipids, it is plausible to hypothesize that hyperoxia alters the physical state and composition of lipids in the membranes of pulmonary endothelial cells and that manipulation of the lipid profile may modify endothelial cell tolerance to hyperoxic injury. To test this, porcine pulmonary artery endothelial cells were exposed to 95% O2 at 1 atmosphere absolute (ATA) in the presence or absence of as vacennic acid (CVA), a monounsaturated fatty acid (C18:1#11). Plasma membrane fluidity was assessed by fluorescence spectroscopy, plasma membrane lipid composition was quantitated using thin layer and gas chromatography, and cytotoxicity was monitored by measuring release of lactate dehydrogenase (LDH). Hyperoxia caused peroxidation of membrane lipids and decreased fluidity in three distinct lipid domains within the plasma membrane. Incubation with CVA was associated with a reduction in the degree of unsaturation of the cons...

Interaction between Oxygen and Cell Membranes: Modification of Membrane Lipids to Enhance Pulmonary Artery Endothelial Cell Tolerance to Hypoxia

The renin-angiotensin system is activated by congestive heart failure associated with a ventricular septal defect (VSD). To determine the effect of angiotensinconverting enzyme inhibition on the hemodynamics with VSD, the dose response curve of captopril was measured in lambs. Furthermore, the effect of captopril on the distribution of systemic output was determined by the radio-nuclide-labeled microsphere technique. A total of 12 lambs (less than 1 month old) with VSD were instrumented and a minimum of five animals was tested for each data point. Captopril (0.05–10 mg/kg) caused dose-dependent vascular changes. At a dose of 2 mg/kg, maximal hemodynamic effects were observed. The systemic resistance fell by 28 ± 9% (mean ± SD, p < 0.05, n = 9), whereas pulmonary arteriolar resistance rose by 113 ± 34% (p < 0.05). These vascular changes caused a reduction in the ratio of pulmonary to systemic flow from 3.31 ± 0.59 to 2.19 ± 0.29 (-34%, p < 0.05) and a reduction in left-to-right shunt volume by 30% (p < 0.05). The left atrial pressure fell from 17.3 ± 3.4 to 10.8 ± 2.8 mm Hg (-38%, p < 0.05). Mean aortic pressure was unchanged (71.2 ± 8.1 versus 67.4 ± 9.1). Forward flow from the left ventricle increased from 2.17 ± 0.46 to 2.86 ± 0.54 liter/min/M2 (p < 0.05). Microsphere-determined organ blood flow to the heart, kidney, liver, duodenum, and skeletal muscle was preserved after a 5 mg/kg dose of captopril and, in fact, tended to increase, but the changes were not significant. The myocardial endocardial to epicardial flow ratio increased from 1.17 ± 0.27 to 1.49 ± 0.14 (+27%, p < 0.05). The data indicate that captopril caused dose-dependent changes in the distribution of left ventricular output in lambs with VSD, reducing total pulmonary flow while preserving organ blood flow.

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Effects of captopril on the distribution of left ventricular output with ventricular septal defect.

We studied the response of the renin-angiotensin system (RAS) to a surgically created ventricular septal defect (VSD) in immature ovines and also the role of angiotensin II in the pathophysiology of VSD in the chronically instrumented ovine. Plasma renin activity (PRA) was increased from 2.39 +/- 1.1 to 3.78 +/- 1.4 ng/ml/hr (p less than 0.05, n = 17) after VSD but not after sham procedure. The change in PRA was positively correlated with the amount of left-to-right shunt through the VSD (r = 0.74, p less than 0.05). Inhibition of angiotensin II effect with saralasin (10 micrograms/kg/min) or angiotensin II production with captopril (2 mg/kg) lowered systemic resistance (Rs) by 14% and 34%, respectively (p less than 0.05), and raised pulmonary resistance (Rp) by 35% and 77%, respectively (p less than 0.05). Thirty minutes following captopril, the ratio of pulmonary to systemic flow (Qp/Qs) decreased from 3.31 +/- 0.18 to 2.15 +/- 0.18 (p less than 0.05) while total pulmonary flow fell from 7.15 +/- 0.38 to 5.92 +/- 0.34 l/min/M2 (p less than 0.05, n = 11). Systemic flow increased from 2.17 +/- 0.14 to 2.86 +/- 0.33 l/min/M2 (p less than 0.05) despite a reduction in left atrial pressure (17.3 +/- 1.0 vs. 13.0 +/- 1.7, p less than 0.01). Reinfusion of angiotensin II (0.02 micrograms/kg/min) into the central aorta after captopril returned the hemodynamics to baseline including a rise in Rs and fall in Rp. Exogenous angiotensin II alone (0.08 micrograms/kg/min) or a threefold stimulation in PRA with furosemide (2 mg/kg) caused little hemodynamic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Renin-angiotensin II response to the hemodynamic pathology of ovines with ventricular septal defect.

Hypoxia (10%-12% O2) preadaptation for 4-7 days effectively protects rats from oxygen toxicity. The present study was designed to investigate the hypothesis that the lung's microvascular endothelium shares in development of oxygen tolerance and therefore that endothelial metabolic function would be protected from oxygen toxicity by prior adaptation to hypoxia. Since pulmonary oxygen toxicity decreases lung capillary angiotensin converting enzyme (ACE) activity, we assayed converting enzyme active sites in an isolated perfused rat lung preparation as a marker for the development of oxygen toxicity and tolerance. Rats were exposed to air, hypoxia (10% O2 for 4 days), hyperoxia (greater than 95% O2 for 2 days) alone, or hypoxia followed immediately by hyperoxia. Lung vascular ACE content was quantitated by measuring the single pass binding of an iodinated-converting enzyme inhibitor, 125I-MK351A, a derivative of lisinopril. Hypoxia adaptation per se had no effect on ACE content reflected in normal 125I-MK351A binding, whereas hyperoxia exposure caused a significant decrease in lung vascular ACE. Hyperoxia-induced decreases in ACE content were prevented partially by hypoxia adaptation, indicating that ACE content on luminal endothelial surfaces was protected from oxygen toxicity. In isolated perfused lungs 125I-MK351A binding reflects development of oxygen tolerance after hypoxia preadaptation and suggests that lung endothelial metabolic function is protected from oxygen toxicity.

Hypoxia-Induced Oxygen Tolerance: Maintenance of Endothelial Metabolic Function

The effects of exposing rats to hyperoxia (100 percent O2) at normal atmospheric pressure for periods of 24-48 hours on components of the renin-angiotensin system and on blood pressure control were examined. Intrapulmonary conversion of angiotensin I (AI) to angiotensin (AII) was assessed using an isolated lung preparation perfused at constant flow. Exposure of rats to hyperoxia for 44-48 hours reduced single pass conversion of AI to AII in the pulmonary circulation from control levels of 82 ± 4 to 29 ± 5 percent (p < 0.001). AII levels in trunk blood of 44-48 hour O2 exposed animals were 5.2 ± 1.9 pg/ml, compared to 37.9 ± 10.0 pg/ml in controls (p < 0.001). Mean arterial pressure decreased significantly from 117 ± 4.3 to 103 ± 6.7 mmHg (p < 0.05) in the O2 exposed group despite a threefold increase in plasma renin activity. The pressor response to exogenous AI was significantly diminished by O2 exposure, while the pressor response to exogenous AII remained unchanged from control. Pulmonary angiotensin-c...

Winternitz

Papers

Hyperoxia-induced converting enzyme insufficiency in conscious rat: cardiovascular effects.