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Biomedical subjects

R I Cargill

Publications and source records attributed to R I Cargill.

At least 19 recordsLinked to original sources
PubMed2001

Does the presence of hibernating myocardium in patients with impaired left ventricular contraction affect QT dispersion?

BACKGROUND: Hibernating myocardium is associated with increased cardiovascular events. Increased QT dispersion on the surface electrocardiogram is a marker for serious ventricular arrhythmias. In this study, we determine whether hibernating myocardium is associated with increased QT dispersion in patients with coronary artery disease and impaired left ventricular contraction. METHODS: Positron emission tomography with (13)N-ammonia and (18)F-fluorodeoxyglucose determined the presence of metabolic-perfusion mismatch defect. QT dispersion was measured by means of a digitizing tablet with validated software. QT intervals were measured on two separate occasions by two investigators blinded to the result of the positron emission tomography scans. RESULTS: Forty-two patients with impaired left ventricular contraction were studied. They were divided into two groups: group A was made up of patients with mismatch defects (n = 26) and group B was made up of patients with no mismatch defects (n = 16). The mean (SD) QT dispersion measurements were 61.7 +/- 29.8 ms and 70 +/- 24.6 ms for groups A and B, respectively (not significant). When the patients were divided according to the dominant viability status of the impaired myocardial segment, a similar result was found. The patients whose impaired myocardium was dominantly hibernating (n = 19) had a mean QT dispersion of 66.4 +/- 31.9 ms compared with 63.6 +/- 24.8 ms in the patients whose impaired myocardium was mainly scarred (not significant). CONCLUSIONS: QT dispersion is not affected by the presence of hibernating myocardium and is therefore not clinically useful in identifying patients with this phenomenon. This is in contrast with recent reports by other groups and calls for further investigation of this dichotomy.

Ammonia↗
PubMed1998

Left atrial thrombus as an early consequence of blunt chest trauma.

Thromboembolism is rarely considered in discussions of the complications of blunt chest trauma. The few cases of thromboembolism that have been reported in this setting have occurred in association with significant myocardial damage. A previously fit 23 year old woman was admitted to the intensive care unit following a road traffic accident. A day later, left atrial thrombus was demonstrated by transoesophageal echocardiography in the absence of any other evidence of important myocardial injury. Anticoagulation with heparin was cautiously introduced in spite of her extensive injuries, and there were no consequent bleeding complications. At hospital discharge on day 18 she was entirely well. Full anticoagulation with warfarin was continued for a further eight weeks at which time follow up transoesophageal echocardiography showed complete resolution of the thrombus.

Accidents, Traffic↗
PubMed1997

Haemodynamic and endocrine effects of type 1 angiotensin II receptor blockade in patients with hypoxaemic cor pulmonale.

OBJECTIVES: Angiotensin II (ANG II) is known to be a potent vasoconstrictor agent in the pulmonary circulation. Furthermore, type 1 ANG II receptor blockade with losartan attenuates acute hypoxic pulmonary vasoconstriction in normal subjects. The aim of this study was therefore to evaluate the haemodynamic and endocrine sequelae of type 1 ANG II receptor blockade in patients with hypoxaemic cor pulmonale. METHODS: Nine patients with chronic obstructive pulmonary disease (COPD) age 67 +/- 3 years with pulmonary hypertension and normal left ventricular systolic function were studied on two separate occasions in a double-blind, placebo-controlled, crossover study. They were randomised to receive either 50 mg of oral losartan or matched placebo. Pulsed wave Doppler echocardiography was used to measure cardiac output (CO), mean pulmonary artery pressure (MPAP) and hence systemic vascular resistance (SVR) and total pulmonary vascular resistance (TPR). Haemodynamic measurements and venous blood samples were taken at baseline and after 2 and 4 h. RESULTS: Maximal effects were observed at 4 h where losartan compared to placebo resulted in a significant reduction in both MPAP (28.6 +/- 2.0 vs 32.4 +/- 1.5 mmHg) and TPR (428 +/- 40 vs 510 +/- dyn.s.cm-5), respectively. Similarly losartan compared to placebo resulted in a significant reduction in MAP (87 +/- 4.5 vs 93 +/- 3.2 mmHg) and SVR (1293 +/- 94 vs 1462 +/- 112 dyn.s.cm-5), and significantly increased CO (5.58 +/- 0.43 vs 5.31 +/- 0.42 l/min). In addition, plasma aldosterone was significantly lower after treatment with losartan compared to placebo: 76 +/- 23 vs 164 +/- 43 pg/ml respectively. CONCLUSIONS: Thus, selective type 1 ANG II receptor blockade appears to have beneficial pulmonary and endocrine effects, suggesting a possible therapeutic role in the management of hypoxaemic cor pulmonale.

Aged↗
PubMed1997

Cardiopulmonary effects of endothelin-1 in man.

OBJECTIVES: Endothelin-1 levels are elevated in a number of conditions characterised by impaired cardiovascular performance and abnormal vasoconstriction such as congestive cardiac failure and primary and secondary pulmonary hypertension. The aim of the present study was to assess the effects of the vasoconstrictor peptide endothelin-1 on pulmonary and systemic haemodynamics and cardiovascular performance in normal man. METHODS: Ten healthy male volunteers were studied on two occasions in a randomised, double-blind, placebo-controlled, cross-over study and received systemic infusions of either endothelin-1 (0.75, 1.5 and 3 pmol.kg-1.min-1 for 30 min each) or saline placebo. Systemic and pulmonary haemodynamic parameters were monitored non-invasively by pulsed-wave Doppler, as were parameters of left and right ventricular diastolic filling and inotropic state. Effects on renin-angiotensin and natriuretic peptide system activity were also measured. RESULTS: Endothelin-1 infusion produced dose-related falls in heart rate, stroke volume and cardiac output. Systemic vascular resistance (SVR) increased from 1156 +/- 57 to 1738 +/- 115 dyn.s.cm-5, and total pulmonary vascular resistance (TPR) increased from 142 +/- 12 to 329 +/- 22 dyn.s.cm-5. Endothelin-1 caused significant impairment of left and right ventricular diastolic filling, even at a low dose which had no pulmonary or systemic pressor effects. Electromechanical and Doppler acceleration indices of inotropic state were also significantly impaired. Activity of the renin-angiotensin system was suppressed by endothelin-1 whilst plasma levels of atrial natriuretic peptide (ANP) were unchanged. CONCLUSIONS: Thus, in addition to systemic and pulmonary pressor effects our results suggest that endothelin-1 impairs overall cardiovascular performance by causing diastolic dysfunction and acting as a negatively inotropic agent. These effects were associated with compensatory changes in the renin-angiotensin system.

Adult↗
PubMed1997

Effects of frusemide and hypoxia on the pulmonary vascular bed in man.

AIMS: Diuretic therapy is conventionally used to treat oedema in patients with hypoxic cor pulmonale. This condition is associated with activation of the renin angiotensin system (RAS) with elevated levels of angiotensin II (ANG II), a potent pulmonary pressor agent. We explored the hypothesis that RAS activation by diuretic therapy might therefore worsen hypoxic pulmonary vasoconstriction via the effects of ANG II on the pulmonary vascular bed. METHODS: Eight normal volunteers were studied on 2 separate days. They either received 40 mg frusemide daily or placebo for 4 days and were then rendered hypoxaemic, by breathing an N2/O2 mixture for 20 min to achieve an SaO2 of 85-90% adjusted for a further 20 min to achieve an SaO2 of 75-80%. Pulsed wave doppler echocardiography was used to measure mean pulmonary artery pressure, cardiac output and hence pulmonary vascular resistance (PVR). RESULTS: Plasma renin activity (PRA) was significantly (P < 0.01) increased after prior treatment with frusemide compared with placebo at all time points. Prior treatment with frusemide significantly (P < 0.05) increased PVR compared with placebo at baseline: 185 +/- 17 vs 132 +/- 10 dyn s cm-5 at an SaO2 of 85-90%: 291 +/- 18 vs 229 +/- 16 dyn s cm-5 and at SaO2 of 75-80%: 356 +/- 12 vs 296 +/- 17 dyn s cm-5 respectively. However, the delta-PVR response to hypoxaemia was not significantly altered by frusemide compared with placebo. In contrast to its effect on the pulmonary vasculature prior treatment with frusemide did not significantly alter systemic haemodynamic parameters either at baseline or during hypoxia. CONCLUSIONS: Thus, prior treatment with frusemide increased baseline pulmonary vascular resistance and significantly augmented the hypoxaemic pulmonary vascular response in additive fashion. It is hypothesised that this effect of frusemide may be due to RAS activation with ANG II mediated pulmonary vasoconstriction.

Adult↗
PubMed1996

Acute neurohormonal responses to hypoxaemia in man.

We have studied the integrated neuroendocrine and haemodynamic effects of acute hypoxaemia in ten healthy volunteers studied on two separate occasions. After reaching a resting haemodynamic state, subjects breathed either room air or a nitrogen/oxygen mixture which rendered arterial oxygen saturation between 75% and 80%. Measurements of pulmonary and systemic haemodynamics were made and blood samples taken at baseline and after 30 min breathing air or the hypoxic gas. Blood was assayed for plasma sodium and potassium, renin-angiotensin-aldosterone system activity, natriuretic peptides, cortisol and catecholamines. Hypoxaemia significantly increased heart rate, cardiac output and mean pulmonary artery pressure (Ppa), but not mean arterial pressure compared with normoxaemia. Although plasma renin activity, angiotensin II and cortisol were unaffected by hypoxaemia, plasma aldosterone fell significantly in comparison with normoxaemia. This was associated with an increase in plasma atrial natriuretic peptide (ANP) but not b-type natriuretic peptide (BNP) during hypoxaemia whilst no changes were observed during normoxaemia. The increase in plasma ANP correlated positively with the increase in Ppa. During hypoxaemia there is therefore dissociation of the renin-angiotensin-aldosterone system where plasma aldosterone decreased, despite there being no effects on plasma renin activity and angiotensin II or on plasma cortisol. This dissociation may be due to increased levels of ANP but not BNP having specific inhibitory effects on aldosterone biosynthesis. ANP increased in proportion to the degree of pulmonary vasoconstriction induced by hypoxaemia which may indicate a counter-regulatory role.

Adrenal Cortex Hormones↗
PubMed1996

Comparative adrenal suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients.

BACKGROUND: A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis, each given by metered dose inhaler to asthmatic patients. METHODS: Twelve asthmatic patients of mean age 29.9 years, with a forced expiratory volume in one second (FEV1) 92.9% predicted and forced expiratory flow 25-75% (FEF25-75) 69.5% predicted, on less than or equal to 400 micrograms/day inhaled corticosteroid, were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400, 1000, 1600, 2000 micrograms and fluticasone propionate 500, 1000, 1500, 2000 micrograms. Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later. RESULTS: Serum cortisol levels compared with placebo (mean 325.2 nmol/l) were suppressed by fluticasone at doses of 1500 micrograms (211.6 nmol/l) and 2000 micrograms (112.3 nmol/l) and by budesonide at 2000 micrograms (243.4 nmol/l). Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms (95% CI for difference 42.9 to 219.2). The dose ratio (geometric mean) for the relative potency was 2.89 fold (95% CI 1.19 to 7.07). In terms of percentage suppression versus placebo, fluticasone propionate also produced greater effects (means and 95% CI for difference): budesonide 1600 micrograms (16.0) versus fluticasone propionate 1500 micrograms (40.9) (95% CI -0.6 to 50.6), budesonide 2000 micrograms (26.0) versus fluticasone 2000 micrograms (65.2) (95% CI 10.5 to 67.8). Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range (150 nmol/l) for fluticasone and five of 24 for budesonide. Fluticasone propionate also caused greater ACTH suppression than budesonide (as % versus placebo): budesonide 1600 micrograms (12.0) versus fluticasone propionate 1500 micrograms (31.9) (95% CI 7.6 to 32.1), budesonide 2000 micrograms (13.5) versus fluticasone propionate 2000 micrograms (44.4) (95% CI 13.2 to 48.7). For overnight 10 hour urinary cortisol (nmol/10 hours) there was a difference between the lowest doses of the two drugs: budesonide 400 micrograms (37.2) versus fluticasone propionate 500 micrograms (19.9) (95% CI 6.9 to 27.8). CONCLUSIONS: Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption. Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients.

Administration, Topical↗
PubMed1996

Effects of inhaled fluticasone propionate and oral prednisolone on lymphocyte beta 2-adrenoceptor function in asthmatic patients.

The aim of the study was to evaluate the facilitatory effects of inhaled corticosteroid on in vitro parameters of lymphocyte beta 2-adrenoceptor function in asthmatic patients. Serum cortisol level was also evaluated as a measure of systemic bioactivity. Ten (four female) asthmatic subjects were evaluated, mean (SEM) age was 28.6(2.0) years, and FEV1 was 79.9%(8.7) predicted. Single doses of inhaled placebo (PL), fluticasone propionate, 1,000 micrograms (F1000), fluticasone propionate, 2,000 micrograms(F2000), or oral prednisolone, 50 mg(PRED), were given at 10 PM the previous night and measurements were made 10 h later. Values for beta 2-receptor density (logBmax: fmol/10(6)cells) were significantly (p < 0.05) greater than PL with PRED but not with inhaled fluticasone (as means and 95% confidence interval [CI] for difference vs PL): PL, 0.27; F1000, 0.30; F2000, 0.32; and PRED, 0.48 (95% CI vs PL, 0.075 to 0.341). Maximal cyclic adenosine monophosphate (cAMP) responses to isoproterenol hydrochloride (isoprenaline (Emax; pmol/10(6)cells) mirrored those for Bmax: PL, 4.00; F1000, 4.68; F2000, 4.26; and PRED, 7.46 (95% CI vs PL, -0.01 to 6.91). Receptor affinity (Kd) was not significantly altered by any treatment. There was significant (p < 0.05) suppression of serum cortisol (nmol/L) with F2000 and PRED compared with PL: PL, 307.9; F1000, 323.2; F2000, 130.1 (95% CI vs PL, 69.76 to 285.8) and PRED, 51.8 (95% CI vs PL, 144.11 to 368.01). Thus, high-dose inhaled fluticasone propionate did not have any facilitatory effects on lymphocyte beta 2-adrenoceptor parameters as compared with oral prednisolone which upregulated beta 2-receptor density and increased cAMP response. In contrast, high-dose inhaled fluticasone (2,000 micrograms) significantly suppressed serum cortisol. In conclusion, there would appear to be a dissociation in systemic sensitivity between effects of inhaled corticosteroid on adrenal suppression and lymphocyte beta 2-adrenoceptor regulation.

Administration, Topical↗
PubMed1996

Lisinopril attenuates acute hypoxic pulmonary vasoconstriction in humans.

OBJECTIVE: We have studied the effects of angiotensin-converting enzyme (ACE) inhibition with lisinopril on acute hypoxic pulmonary vasoconstriction (HPV). DESIGN: Randomized, double-blind, placebo-controlled study in ten healthy volunteers. Subjects received four daily doses of lisinopril or matched placebo before attending the laboratory 5 h after taking the final dose. After reaching a resting hemodynamic state, subjects were made hypoxemic (SaO2, 75 to 80%) for 30 min. MEASUREMENTS: Pulmonary and systemic hemodynamic parameters were measured noninvasively at baseline and after 30 min of hypoxemia. RESULTS: Mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (TPR) were similar at baseline on both study days. The increase in MPAP induced by hypoxemia was significantly blunted by pretreatment with lisinopril (means and 95% confidence interval [CI] for difference) 13.4 mm Hg vs placebo 19.6 mm Hg (95% CI, 2.5, 9.9). Likewise, the TPR response to hypoxemia was significantly blunted by lisinopril: 124 dyne.s.cm-5 vs placebo 179 dyne.s.cm-5 (95% CI, 11, 99). Lisinopril had no confounding systemic effects on mean arterial pressure, cardiac output, or systemic vascular resistance at baseline or in response to hypoxemia. CONCLUSIONS: Lisinopril therefore significantly attenuated the pulmonary pressor response to hypoxemia without decreasing baseline MPAP or TPR. This suggests that angiotensin II might play a modulatory role during HPV in man and that ACE inhibition may be a useful adjunctive treatment in hypoxemic pulmonary hypertension.

Adult↗
PubMed1996

Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans.

STUDY OBJECTIVE: The inotropic, lusitropic, and electrophysiologic effects of acute hypercapnia in humans are not known. Although the effects of hypercapnia on the systemic circulation have been well documented, there is still some debate as to whether hypercapnia causes true pulmonary vasoconstriction in vivo. We have therefore evaluated the effects of acute hypercapnia on these cardiac indices and the interaction of hypercapnia with the systemic and pulmonary vascular beds in humans. PARTICIPANTS AND INTERVENTIONS: Eight healthy male volunteers were studied using Doppler echocardiography. After resting for at least 30 min to achieve baseline hemodynamic parameters (T(0)), they were rendered hypercapnic to achieve an end-tidal carbon dioxide (CO2) of 7 kPa for 30 min by breathing a variable mixture of CO2/air (T1). They were restudied after 30 min recovery breathing air (T2). Hemodynamic, diastolic, and systolic flow parameters, QT dispersion (maximum-minimum QT interval measured in a 12-lead ECG), and venous blood samples for plasma renin activity (PRA), angiotensin II (ANG II), and aldosterone (ALDO) were measured at each time point. RESULTS: Hypercapnia compared with placebo significantly increased mean pulmonary artery pressure 14 +/- 1 vs 9 +/- 1 mm Hg and pulmonary vascular resistance 171 +/- 17 vs 129 +/- 17 dyne.s.cm-5, respectively. Heart rate, stroke volume, cardiac output, and mean arterial BP were increased by hypercapnia. Indexes of systolic function, namely peak aortic velocity and aortic mean and peak acceleration, were unaffected by hypercapnia. Similarly, hypercapnia had no effect on lusitropic indexes reflected by its lack of effect on isovolumic relaxation time, mitral E-wave deceleration time, and mitral E/A wave ratio. Hypercapnia was found to significantly increase both QTc interval and QT dispersion: 428 +/- 8 vs 411 +/- 3 ms and 48 +/- 2 vs 33 +/- 4 ms, respectively. There was no significant effect of hypercapnia on PRA, ANG II, or ALDO. CONCLUSION: Thus, acute hypercapnia appears to have no adverse inotropic or lusitropic effects on cardiac function, although repolarization abnormalities, reflected by an increase in QT dispersion, and its effects on pulmonary vasoconstriction may have important sequelae in man.

Adult↗
PubMed1996

Angiotensin II receptor blockade and effects on pulmonary hemodynamics and hypoxic pulmonary vasoconstriction in humans.

STUDY OBJECTIVE: We examined the hypothesis that angiotensin II (ANG II) is a modulator of pulmonary vascular tone by examining the effects of ANG II blockade on pulmonary hemodynamics during normoxemia and hypoxemia in normal volunteers with an activated renin angiotensin system (RAS). PARTICIPANTS AND INTERVENTIONS: Eight normal volunteers, pretreated with furosemide, were studied on two separate occasions and received either an infusion of saralasin, 5 micrograms/kg/min, or placebo. After 20 min, they were rendered hypoxemic, by breathing N2/O2 mixture for 20 min to achieve arterial oxygen saturation (SaO2) of 85 to 90% adjusted for a further 20 min to achieve SaO2 of 75 to 80%. Doppler echocardiography was used to measure mean pulmonary artery pressure (MPAP), cardiac output, and hence total pulmonary vascular resistance (TPR). RESULTS: Saralasin compared with placebo resulted in a significant (p < 0.05) reduction in MPAP during normoxemia, 6.70 +/- 1.0 vs 11.7 +/- 1.3 mm Hg; at SaO2 of 85 to 90%, 14.7 +/- 1.4 vs 20.5 +/- 1.0 mm Hg; and at SaO2 of 75 to 80%, 18.1 +/- 1.9 vs 27.8 +/- 1.9 mm Hg, respectively. Likewise saralasin compared with placebo resulted in a significant reduction in TPR during normoxemia, 104 +/- 14 vs 180 +/- 20 dyne.s.cm-5; at SaO2 of 85 to 90%, 222 +/- 24 vs 295 +/- 21 dyne.s.cm-5; and at SaO2 of 75 to 80%, 238 +/- 21 vs 362 +/- 11 dyne.s.cm-5, respectively. The delta MPAP response to hypoxemia was likewise significantly (p < 0.01) attenuated by saralasin infusion compared with placebo: mean difference 5.0 mm Hg, 95% confidence interval (CI) 1.9 to 8.08, and there was a trend toward attenuation of the delta TPR response to hypoxemia (0.05 < p < 0.10): mean difference 47 dyne.s.cm-5, 95% CI, -10 to 105. CONCLUSION: In addition to causing pulmonary vasodilatation in the presence of an activated RAS, our results suggest that ANG II receptor blockade attenuates acute hypoxic pulmonary vasoconstriction and that ANG II may play a role in modulating this response in normal man.

Adult↗
PubMed1996

Atrial natriuretic peptide and brain natriuretic peptide in cor pulmonale. Hemodynamic and endocrine effects.

We have studied the hemodynamic and hormonal effects of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in eight patients with cor pulmonale. Subjects were studied twice and were given a 20-min placebo infusion followed by either ANP or BNP (3 pmol/kg/min then 10 pmol/kg/ min for 20 min each). Responses were measured after placebo infusion and following low-dose then high-dose ANP or BNP. Placebo infusion had no significant effects on either study day. Low-dose ANP and BNP significantly reduced mean pulmonary artery pressure (MPAP) from baseline by 3.7 mm Hg (95% confidence interval [CI], 1.4 to 6.1) and 3.0 mm Hg (95% CI, 0.6 to 5.4), respectively. High-dose ANP and BNP further reduced MPAP from baseline by 7.1 mm Hg (95% CI, 4.8 to 9.4) and 7.1 mm Hg (95% CI, 4.7 to 9.6), respectively. Effects on total pulmonary vascular resistance were similar. ANP and BNP had no confounding systemic hemodynamic effects. Plasma aldosterone was significantly suppressed from baseline by ANP: 156 pmol/L (95% CI, 93 to 220) after low dose, 275 pmol/L (95% CI, 207 to 343) after high dose; and by BNP: 92 pmol/L (95% CI, 30 to 153) after low dose, 159 pmol/L (95% CI, 98 to 220) after high dose. ANP and BNP produced dose-related pulmonary vasodilatation in patients with cor pulmonale, without worsening oxygen saturation or affecting systemic hemodynamics. ANP and BNP also exerted favorable neurohormonal effects by suppressing aldosterone.

Aldosterone↗
PubMed1995

Comparative effects of atrial natriuretic peptide and brain natriuretic peptide on the aldosterone and pressor responses to angiotensin II in man.

1. Atrial natriuretic peptide and brain natriuretic peptide have similar vasodilator and natriuretic properties, although little information is available regarding their relative effects as antagonists of the renin-angiotensin-aldosterone system. We have therefore compared how atrial natriuretic peptide and brain natriuretic peptide affect the systemic pressor and aldosterone responses to angiotensin II in eight male subjects. 2. Each subject was studied on three separate occasions, when they received a 60-min infusion of placebo, atrial natriuretic peptide (10 pmol min-1 kg-1) or brain natriuretic peptide (10 pmol min-1 kg-1), with a concomitant infusion of angiotensin II (6 ng min-1 kg-1) given for the final 30 min of the infusion period. The change in haemodynamic parameters and plasma aldosterone induced by angiotensin II was measured. Plasma concentrations of atrial natriuretic peptide (182 +/- 23 pmol/l) and brain natriuretic peptide (193 +/- 25 pmol/l) achieved at steady-state during the infusion on each study day were not significantly different. 3. Increases in mean arterial pressure in response to angiotensin II were significantly lowered by concomitant infusion of atrial natriuretic peptide (21.0 +/- 1.7 mmHg) and brain natriuretic peptide (20.1 +/- 1.9 mmHg) compared with placebo (29.0 +/- 4.1 mmHg). There were similar effects on systolic and diastolic blood pressure. Cardiac output was decreased on each study day to the same extent y angiotensin II infusion. Total systemic vascular resistance showed a non-significant trend towards an attenuated response to angiotensin II when atrial natriuretic peptide or brain natriuretic peptide was infused concomitantly in comparison with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Adverse effects of hypoxaemia on diastolic filling in humans.

1. Abnormalities of myocardial relaxation may occur as a consequence of myocyte hypoxia. We have therefore examined the effects of hypoxaemia on right and left ventricular diastolic function in 10 healthy male subjects. 2. After resting to reach baseline haemodynamics, subjects were rendered hypoxaemic by breathing a variable nitrogen/oxygen mixture. Oxygen saturation (SaO2) was maintained at 85-90% for 20 min and then at 75-80% for a further 20 min. Haemodynamic and diastolic filling parameters were measured noninvasively at baseline and at the end of each period of hypoxaemia. 3. Diastolic filling of both ventricles was significantly impaired by hypoxaemia. In comparison with baseline, left ventricular isovolumic relaxation time and transmitral E-wave deceleration time corrected for heart rate were significantly prolonged at SaO2 75-80%: mean difference in corrected relaxation time, 9.8 ms (95% confidence interval 1-19); mean difference in corrected deceleration time, 34 ms (95% confidence interval 11-56). Similarly, right ventricular isovolumic relaxation time and transtricuspid E-wave deceleration time were significantly prolonged at SaO2 values of 75-80% compared with baseline: mean difference in relaxation time, 20.3 ms (95% confidence interval 3-38); mean difference in deceleration time, 33 ms (95% confidence interval 11-55). 4. During hypoxaemia there were dose-related increases in heart rate, cardiac output and mean pulmonary artery pressure, but no effects on mean arterial pressure. 5. Hypoxaemia significantly impairs relaxation of left and right ventricles in normal humans. These changes may reflect impairment of intracellular calcium transport secondary to the effects of myocyte hypoxia.

Adult↗
PubMed1995

The role of the renin-angiotensin and natriuretic peptide systems in the pulmonary vasculature.

1. The role of vasoactive peptide systems in the pulmonary vasculature has been studied much less extensively than systemic vascular and endocrine effects. The current understanding of the role of the renin-angiotensin (RAS) and natriuretic peptide systems (NPS) in the pulmonary circulation is therefore reviewed. 2. Plasma concentrations of angiotensin II, the main vasoactive component of the RAS, are elevated in pulmonary hypertension and may interact with hypoxaemia to cause further pulmonary vasoconstriction. Pharmacological manipulation of angiotensin II can attenuate hypoxic pulmonary vasoconstriction but larger studies are needed to establish the efficacy of this therapeutic strategy in established pulmonary hypertension. 3. Although all the known natriuretic peptides, ANP, BNP and CNP are elevated in cor pulmonale, only ANP and BNP appear to have pulmonary vasorelaxant activity in humans. ANP and BNP can also attenuate hypoxic pulmonary vasoconstriction, suggesting a possible counter-regulatory role for these peptides. Inhibition of ANP/BNP metabolism by neutral endopeptidase has been shown to attenuate development of hypoxic pulmonary hypertension but this property has not been tested in humans. 4. It is also well established that there are potentially important endocrine and systemic circulatory interactions between the RAS and NPS. This also occurs in the pulmonary circulation and in humans, where at least BNP acts to attenuate angiotensin II induced pulmonary vasoconstriction. This interaction may be particularly relevant as a mechanism to counter-regulate overactivity of the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Cardiopulmonary interactions of salbutamol and hypoxaemia in healthy young volunteers.

1. Nebulised salbutamol is frequently used in the treatment of asthma and chronic obstructive pulmonary disease. Its effects on the cardiovascular system have been extensively investigated although as yet little is known concerning its effects on the pulmonary circulation, particularly during hypoxaemia. We have therefore examined the effects of nebulised salbutamol on pulmonary haemodynamics to see if it modifies hypoxic pulmonary vasoconstriction. 2. Eight healthy normal volunteers were studied on two separate occasions. After resting to achieve baseline haemodynamics patients were randomised to receive 5 mg salbutamol or placebo via a nebuliser. They were restudied after 30 min and then rendered hypoxaemic by breathing an N2/O2 mixture to achieve an SaO2 of 75-80%. Doppler echocardiography was used to measure mean pulmonary artery pressure (MPAP), cardiac output (CO) and hence pulmonary vascular resistance (PVR). 3. Treatment with salbutamol significantly increased MPAP during normoxaemia and hypoxaemia compared with placebo at 12.0 +/- 1.2 vs 8.0 +/- 0.7 mm Hg and 28.6 +/- 0.9 vs 25.2 +/- 1.0 mm Hg, respectively (P < 0.05). Salbutamol caused a significant increase in heart rate compared with placebo and effects were additive to those of hypoxia at 74 +/- 2 vs 67 +/- 3 beats min-1 during normoxaemia and 84 +/- 3 vs 77 +/- 4 beats min-1 during hypoxaemia, respectively (P < 0.05). Whilst systemic vascular resistance fell in response to salbutamol, PVR was unchanged by salbutamol during either normoxaemia or hypoxaemia. Cardiac output was increased by salbutamol and by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1995

Acute effects of ANP and BNP on hypoxic pulmonary vasoconstriction in humans.

1. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have pulmonary vasorelaxant activity with plasma concentrations being elevated in patients with hypoxaemic pulmonary hypertension. However, their effects on acute hypoxic pulmonary vasoconstriction (HPV), the initiating stimulus for pulmonary hypertension have not to date been investigated. We have therefore studied the effects of ANP and BNP on acute HPV in humans. 2. Eight healthy volunteers were studied on three separate occasions. After reaching a resting haemodynamic state (t0), an infusion of either ANP (10 pmol kg-1 min-1), BNP (10 pmol kg-1 min-1) or placebo (5% dextrose) was commenced. This was given alone for 30 min (t30) before subjects were rendered hypoxaemic (SaO2 75-80%) for a further 30 min (t60), with the initial infusion continuing to t60. Pulsed-wave Doppler analysis of pulmonary artery flow was used to measure mean pulmonary arterial pressure (MPAP) and hence total pulmonary vascular resistance (PVR) was calculated. 3. MPAP and PVR both tended to decrease in response to ANP and BNP infusion, although compared with placebo, the difference at t30 was only statistically significant for PVR. Hypoxaemia increased MPAP and PVR, although values at t60 were significantly lower following both ANP and BNP compared with placebo. 4. In terms of the actual change in PVR (delta PVR) induced by hypoxaemia (from t30 to t60), BNP (146(16) dyn s cm-5), but not ANP (183(21) dyn s cm-5) significantly attenuated delta PVR compared with placebo (194(26) dyns s cm-5): mean difference BNP versus placebo 48 dyn s cm-5, 95% Cl 3-93. An identical pattern was observed for delta MPAP where BNP (15.9(1.1) mmHg), but not ANP (18.0(1.2) mmHg) significantly attenuated delta MPAP compared with placebo (19.0(1.7) mmHg): mean difference BNP versus placebo 3.1 mmHg, 95% Cl 0.7-5.5. 5. Thus, although both ANP and BNP exhibit pulmonary vasorelaxant activity, only BNP significantly attenuated the MPAP and PVR responses to acute hypoxaemia. This suggests that the natriuretic peptides may have a role in attenuating pulmonary hypertension secondary to hypoxaemia.

Adult↗