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Biomedical subjects

R I Cargill

Publications and source records attributed to R I Cargill.

29 records · Page 2Linked to original sources
PubMed1995

Abnormal myocardial repolarisation in response to hypoxaemia and fenoterol.

BACKGROUND: Prolongation of the QTc interval has been associated with cardiac dysrhythmias and sudden death. QTc dispersion (interlead variability in QTc interval) has recently been proposed as being a more sensitive marker of repolarisation abnormalities and shown to be a more specific index of arrhythmia risk. Although hypoxaemia and fenoterol have previously been shown to prolong the QTc interval, this does not reflect regional myocardial repolarisation abnormalities. METHODS: Electrophysiological effects were measured at baseline and after 30 minutes steady state hypoxaemia at an arterial oxygen saturation (SaO2) of 75-80% (study 1) and at baseline then 30 minutes after inhaled fenoterol 2.4 mg (study 2). From the ECG, lead II corrected QT interval (QTc) and overall corrected QT dispersion were measured using a computer linked digitising tablet according to standard criteria. RESULTS: QTc dispersion was increased during hypoxia compared with baseline values (mean (SE) 69 (6) ms v 50 (5) ms) and after fenoterol compared with baseline (79 (13) v 46 (4) ms), respectively. There was also an increase in QTc interval and heart rate after fenoterol (493 (23) v 420 (6) ms and 98 (3) v 71 (6) bpm, respectively). The heart rate was increased during hypoxaemia compared with baseline (78 (3) v 64 (2) bpm), but no change occurred in the QTc interval. CONCLUSIONS: Both hypoxaemia and fenoterol cause myocardial repolarisation abnormalities in man in terms of increased QTc dispersion, but only fenoterol increased the QTc interval. This may be relevant in the aetiology of arrhythmias in patients with acute severe asthma where beta agonist therapy and hypoxaemia coexist.

Adrenergic beta-Agonists↗
PubMed1995

Hypoxaemia and release of endothelin-1.

BACKGROUND: Secretion of the vasoconstrictor peptide endothelin-1 from vascular endothelium is increased by various stimuli. Whether hypoxaemia affects plasma levels of endothelin-1 in humans is unknown, but this may be important in the haemodynamic response to hypoxaemia. The plasma endothelin-1 concentrations in hypoxaemic humans has therefore been measured. METHODS: Plasma levels of endothelin-1 were measured by specific radioimmunoassay in 10 control subjects at rest and following 30 minutes of acute hypoxaemia (SaO2 75-80%) induced by breathing a nitrogen/oxygen mixture, and in 10 patients with hypoxaemic cor pulmonale. RESULTS: The plasma endothelin-1 concentration in control subjects was increased from a mean (SE) of 0.90 (0.11) pmol/l at baseline to 2.34 (0.34) pmol/l during hypoxaemia. In patients with cor pulmonale the plasma endothelin-1 concentration was 2.96 (0.34) pmol/l, raised in comparison with control subjects at rest but similar to levels in controls during hypoxaemia. CONCLUSIONS: Plasma levels of endothelin-1 were increased by hypoxaemia in humans. The raised levels observed in patients with cor pulmonale may largely be attributable to the effects of hypoxaemia, although the pathophysiological significance of these observations remains to be established.

Acute Disease↗
PubMed1995

Pulmonary vasorelaxant activity of atrial natriuretic peptide and brain natriuretic peptide in humans.

BACKGROUND: Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) exhibit in vitro pulmonary vasodilator activity, but little information is available regarding their effects in the human pulmonary vasculature. Their effects in the human pulmonary circulation and their ability to modulate the pulmonary pressor effects of angiotensin II have therefore been evaluated. METHODS: Eight healthy volunteers were studied on three separate occasions. Infusions of either ANP, BNP, or placebo were given for 60 minutes with a concomitant infusion of angiotensin II given for the final 30 minutes. Pulmonary haemodynamics were measured by pulsed wave Doppler echocardiography at baseline (T0), before commencing angiotensin II (T30), and at the end of the infusion period (T60). RESULTS: Mean pulmonary artery pressure (MPAP) showed a fall with ANP and BNP infusion at T30 compared with placebo. Although angiotensin II infusion had significant pulmonary pressor effects on all three study days, MPAP at T60 was lower when ANP (18.3 (2.0) mm Hg) and BNP (16.1 (1.5) mm Hg) were given concomitantly compared with placebo (21.8 (1.6) mm Hg). CONCLUSIONS: These findings indicate that both ANP and BNP exhibit pulmonary vasorelaxant activity in humans in terms of antagonism of the pulmonary pressor effects of angiotensin II. This would support the hypothesis that ANP and BNP act as circulating counter-regulatory hormones in states of pathological pulmonary vasoconstriction.

Adult↗
PubMed1995

Left ventricular systolic performance during acute hypoxemia.

STUDY OBJECTIVE: Although some of the cardiovascular responses to hypoxemia are well described, effects on myocardial contractility have not been defined. Such effects are readily assessed by noninvasive techniques and we have therefore evaluated Doppler-phonocardiographic parameters of systolic left ventricular contractility in normal humans rendered hypoxemic. DESIGN: Eight healthy male volunteers were studied. Parameters were measured after resting to achieve baseline haemodynamics, after 20 min moderate hypoxemia (SaO2 85 to 90%), and after a further 20 min of severe hypoxemia (SaO2 75 to 80%). Hypoxemia was induced by breathing a variable N2/O2 mixture. MEASUREMENTS: Pulsed-wave Doppler analysis of ascending aortic blood flow was combined with phonocardiography to measure indices of systolic left ventricular function at baseline and at the end of each period of hypoxemia. RESULTS: There was a significant, dose-related increase in cardiac output in response to hypoxemia, from 5.5 +/- 0.26 L/min at baseline to 6.1 +/- 0.08 L/min during moderate hypoxemia and to 7.0 +/- 0.23 L/min during severe hypoxemia. Likewise, heart rate increased significantly in dose-related fashion although stroke volume was not affected by either level of hypoxemia. Hypoxemia had no significant effects on systolic or diastolic blood pressures, but caused a significant reduction in systemic vascular resistance. Aortic peak and mean acceleration and acceleration time were not affected by moderate or severe hypoxemia. Although the systolic time intervals measured shortened significantly during severe hypoxemia, these were no longer significant when appropriate corrections were made for heart rate. CONCLUSIONS: Although cardiac output increases during hypoxemia, this is due to increases in heart rate but not to any effect on stroke volume. Parameters of left ventricular systolic function and myocardial inotropic state were also not affected by severe hypoxemia. Systolic left ventricular function and myocardial contractility are thus well preserved in normal humans during hypoxemia.

Acute Disease↗
PubMed1995

Human C-type natriuretic peptide: effects on the haemodynamic and endocrine responses to angiotensin II.

OBJECTIVE: The aim was to study the effects of high dose systemic human C-type natriuretic peptide (CNP) infusion in man on systemic and pulmonary haemodynamics and the renin-angiotensin system before and after infusion of angiotensin II. METHODS: Eight normal male volunteers were studied on two separate occasions when, after the subjects had been rested to reach a baseline haemodynamic state (T0), infusions of either human CNP (10 pmol.kg-1.min-1) or placebo (5% dextrose) were begun. After 30 min (T30) on each study day, a concomitant infusion of angiotensin II (6 ng.kg-1.min-1) was started, and both infusions ran together for a further 30 min (until T60). Measurements of systemic and pulmonary haemodynamic variables and the activity of the renin-angiotensin system were made at baseline (T0), after 30 min of CNP or placebo (T30), and after angiotensin II (T60). RESULTS: Infusion of CNP had no significant effects on systemic or pulmonary haemodynamics or on baseline renin-angiotensin system activity compared with placebo. Infusion of angiotensin II produced significant systemic and pulmonary pressor effects and also stimulated aldosterone secretion. There were, however, no significant differences between the changes induced by angiotensin II (expressed as the difference between T30 and T60) when CNP was infused compared with placebo: change in mean systemic arterial pressure with CNP 26.6(SEM 2.3) mm Hg v placebo 30.3(3.6) mm Hg; change in mean pulmonary artery pressure with CNP 11.7(2.5) mm Hg v placebo 10.9(1.0) mm Hg; change in aldosterone concentration with CNP 219(40) pmol.litre-1 v placebo 242(40) pmol.litre-1. CONCLUSIONS: At a dose of CNP which has previously been found to have marked haemodynamic effects in dogs, no effect on systemic or pulmonary haemodynamics was observed in man. Furthermore, CNP had no effect on the aldosterone or pressor responses to infused angiotensin II. The present study would suggest that CNP does not have a circulating endocrine role in cardiovascular homeostasis, although a paracrine role within vascular endothelium is perhaps more likely.

Adult↗
PubMed1995

Acute hypoxic pulmonary vasoconstriction in man is attenuated by type I angiotensin II receptor blockade.

OBJECTIVES: We examined the hypothesis that angiotensin II (ANG II) is a modulator of acute hypoxic pulmonary vasoconstriction (HPV) by looking at the effect of losartan, a selective type 1 ANG II receptor antagonist, on acute HPV in man. METHODS: Ten normal volunteers were studied on two separate days. They either received pre-treatment with losartan 25, 50, 100, 100 mg respectively on four consecutive days or matched placebo. They 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 (MPAP), cardiac output and hence pulmonary vascular resistance (PVR). RESULTS: Baseline MPAP and PVR (during normoxaemia) were unaffected by losartan pre-treatment compared with placebo. However, losartan significantly reduced MPAP at both levels of hypoxaemia compared with placebo: 14.7 +/- 0.7 vs 19.0 +/- 0.7 mmHg at an SaO2 85-90% (P < 0.01) and 20.0 +/- 0.7 vs 25.7 +/- 0.8 mmHg at an SaO2 75-80% (P < 0.05) respectively. Similarly losartan significantly reduced PVR compared to placebo: 191 +/- 9 vs 246 +/- 10 dyne.s.cm-5 at an SaO2 85-90% (P < 0.005) and 233 +/- 12 vs 293 +/- 18 dyne.s.cm-5 at an SaO2 75-80% (P < 0.05), respectively. Pre-treatment with losartan, however, had no significant effect on systemic vascular resistance although losartan compared to placebo resulted in a significant (P < 0.05) reduction in mean arterial pressure at an SaO2 75-80%: 78 +/- 2 vs 87 +/- 2 mmHg. CONCLUSIONS: Losartan had no effect on baseline pulmonary haemodynamics but significantly attenuated acute hypoxic pulmonary vasoconstriction, suggesting that angiotensin II plays a role in modulating this response in man via its effects on the type 1 angiotensin II receptor.

Adult↗
PubMed1994

Acute effects of hypoxaemia and angiotensin II in the human pulmonary vascular bed.

Hypoxaemia and angiotensin II both cause pulmonary vasoconstriction and co-exist as pathophysiological pulmonary pressor stimuli in patients with cor pulmonale. Evidence from animal studies, however, suggests that angiotensin II may modulate the hypoxic pulmonary vasoconstrictor response. We have therefore studied how hypoxaemia and angiotensin II interact in the human pulmonary vascular bed. Eight male volunteers were studied on two occasions. From baseline (T0) onwards, subjects breathed room air at one visit, and on the other, a nitrogen/oxygen mixture which rendered arterial oxygen saturation between 75% and 80%. After 30 min (T30), angiotensin II was infused for a further 30 min (until T60). Mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (PVR) were determined by pulsed-wave Doppler echocardiography at T0, T30 and T60. The change in MPAP (delta MPAP) due to hypoxaemia and angiotensin II together was 18.0 +/- 1.3 mmHg, significantly greater than the delta MPAP response to either hypoxaemia alone (13.4 +/- 1.1 mmHg) or angiotensin II alone (10.3 +/- 1.1 mmHg). In terms of change in PVR (delta PVR), the response to hypoxaemia and angiotensin II together (230 +/- 25 dyne.s/cm5) was no different from the response to ANG II alone (214 +/- 31 dyne.s/cm5), although both these were significantly greater than delta PVR with hypoxaemia alone (114 +/- 12 dyne.s/cm5). The delta MPAP and delta PVR responses to angiotensin II were significantly greater when normoxaemic than when hypoxaemic: delta MPAP mean difference 5.6 mmHg (95% confidence interval (CI) 3.0-8.2); delta PVR mean difference 98 dyne.s/cm5 (95% CI 16-181). Angiotensin II therefore produced significantly less pulmonary vasoconstriction when hypoxaemic compared with normoxaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The effects of angiotensin II on circulating levels of natriuretic peptides.

We have evaluated the differential release of A, B and C-type natriuretic peptides in response to incremental doses of angiotensin II (2, 4 and 6 ng kg-1 min-1). Baseline plasma concentrations of ANP (5.99 +/- 0.74 pmol 1-1) were significantly (P < 0.05) higher than BNP (1.53 +/- 0.48 pmol 1-1) or CNP (0.41 +/- 0.11 pmol 1-1). Angiotensin II infusion caused a significant (P < 0.05) increase in plasma ANP to 53.76 +/- 17.3 pmol 1-1 at 6 ng kg-1 min-1. Plasma concentrations of BNP and CNP were not significantly affected by angiotensin II. Arterial blood pressures and systemic vascular resistance increased (P < 0.001) in response to angiotensin II infusion. Thus, ANP, unlike BNP or CNP, is released acutely in response to the pressor stimulus of angiotensin II. This may represent a dissociation in release of the natriuretic peptides, in terms of short and long term responses to activation of the renin-angiotensin system.

Adult↗
PubMed1994

C-type natriuretic peptide levels in cor pulmonale and in congestive heart failure.

BACKGROUND: C-type natriuretic peptide (CNP) is a recent addition to the family of natriuretic peptides which includes atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Whilst the levels of ANP and BNP are increased in conditions such as congestive heart failure and cor pulmonale, abnormal levels of CNP in these conditions have not been reported. METHODS: Plasma levels of CNP were measured by specific radioimmunoassay in 12 young normal controls, 12 elderly normal controls, 12 patients with NYHA grade III-IV congestive heart failure, and in 16 patients with hypoxaemic cor pulmonale. RESULTS: Mean (SE) plasma levels of CNP were similar in young normal controls (0.46(0.03) pmol/l), elderly normal controls (0.43(0.05) pmol/l), and in patients with congestive heart failure (0.33(0.2) pmol/l). In patients with cor pulmonale, however, plasma levels of CNP were raised (1.39(0.27) pmol/l) 3.2-fold compared with age-matched controls. CONCLUSIONS: In cor pulmonale the increased plasma levels of CNP were not as great as the previously observed increases in levels of ANP (5.6-fold) or BNP (18.5-fold) in comparable patients. CNP may therefore be less important than ANP or BNP as a circulating counter-regulatory peptide in conditions of overactivity of the renin angiotensin system.

Adult↗