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Biomedical subjects

P J Cowburn

Publications and source records attributed to P J Cowburn.

14 recordsLinked to original sources
PubMed2000

Cardiac compromise in a patient with Down's Syndrome: a lesson learnt.

A 49 year old burn victim with Down's Syndrome (Trisomy 21) was admitted with 15% body surface area (BSA) superficial burns. This was complicated by a large atrioseptal defect. Her course was stormy with difficulties encountered in managing her fluid status. Adequate fluid resuscitation was difficult to maintain with a fragile compromise between pulmonary insufficiency and renal impairment. She expired 12 days post-injury. Cardiac anomalies are not uncommon in the subgroup of patients with major burns who respond poorly to fluid resuscitation.

Acute Kidney Injury↗
PubMed1999

Impaired pulmonary diffusion during exercise in patients with chronic heart failure.

BACKGROUND: Pulmonary diffusion is impaired at rest in patients with chronic heart failure (CHF) and has been implicated in the generation of symptoms and exercise intolerance. The aim of this study was to determine whether pulmonary diffusion is impaired during exercise in CHF, to examine its relationship to pulmonary blood flow, and to consider its functional significance in relation to metabolic gas exchange. METHODS AND RESULTS: Carbon monoxide transfer factor (TLCO) and pulmonary blood flow (Q(C)) were measured by a rebreathe technique at rest and during steady-state cycling at 30 W in 24 CHF patients and 10 control subjects. Both patients and control subjects were able to raise TLCO and Q(C) during exercise. However, the patient group had a lower diffusion for a given blood flow (TLCO/Q(C)) both at rest (3.6+/-0.16 and 4.8+/-0.23 mL x L(-1) x mm Hg(-1); P<0.001) and during exercise (2.8+/-0.16 and 3.4+/-0.13 mL x L(-1) x mm Hg(-1) for CHF patients and control subjects, respectively; P<0.05). TLCO/Q(C) was related to the ventilatory equivalent for carbon dioxide (VEVCO(2)) production at 30 W (TLCO/Q(c) versus VEVCO(2), r = -0.58, P<0.01) and to peak exercise oxygen consumption measured during a progressive test (TLCO/Qc versus VO(2peak), r = 0.57, P<0.01) in these patients. CONCLUSIONS: Patients with CHF are able to recruit reserves of TLCO and Q(C) during exercise. However, the TLCO/Q(C) ratio is consistently impaired in these patients and relates to both exercise hyperpnea and peak exercise oxygen consumption. Whether this impairment in alveolar gas exchange is reversible in CHF and therefore is a potential target for therapy has yet to be determined.

Cardiac Output, Low↗
PubMed1999

Endothelin B receptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction.

OBJECTIVES: This study was designed to assess the functional importance of endothelin (ET)B receptors in patients with left ventricular systolic dysfunction (LVSD) by comparing the hemodynamic effects of ET-1, a nonselective ET(A) and ET(B) agonist, with ET-3, a selective ET(B) receptor agonist. BACKGROUND: Knowledge of the functional importance of ET(B) receptors in mediating vasoconstriction in chronic heart failure will help determine whether antagonists at both ET(A) and ET(B) receptors are required to fully prevent vasoconstriction to endogenously produced ET-1. METHODS: We infused ET-1 (5 and 15 pmol/min) and ET-3 (5 and 15 pmol/min) into two separate groups of eight patients with LVSD with similar baseline hemodynamic indices. Hemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. RESULTS: Endothelin-1 infusion led to systemic vasoconstriction, with a rise in mean arterial pressure (mean +/- SEM 100 +/- 3 to 105 +/- 3 mm Hg, p < 0.02) and systemic vascular resistance (1,727 +/- 142 to 2,055 +/- 164 dyn/s/cm(-5), p < 0.001) and a fall in cardiac index (2.44 +/- 0.21 to 2.22 +/- 0.20 liters/min/m , p < 0.01). Endothelin-3 infusion also led to systemic vasoconstriction, with a rise in mean arterial pressure (99 +/- 6 to 105 +/- 6 mm Hg, p < 0.01) and systemic vascular resistance (1,639 +/- 210 to 1,918 +/- 245 dyn/s/cm(-5), p < 0.01) and a fall in cardiac index (2.66 +/- 0.28 to 2.42 +/- 0.24 liters/min/m2, p < 0.05). Pulmonary hemodynamic measurements did not change significantly in either group. CONCLUSIONS: Both ET-1 and ET-3 infusions led to systemic vasoconstriction; the hemodynamic changes observed were of a similar magnitude at the same molar concentration. This suggests that ET(B) receptors are functionally important in mediating vasoconstriction, at least in the systemic circulation, in patients with LVSD.

Aged↗
PubMed1999

Structural and functional assessment of small arteries in patients with chronic heart failure.

The physiological response to a chronically failing heart is the implementation of compensatory mechanisms intended to support blood pressure. These mechanisms, which are not fully understood, increase peripheral vascular tone, thus increasing the strain on the weakened myocardium. This study investigated the structure and function of small arteries from heart failure patients and controls without heart failure in an attempt to identify abnormalities associated with heart failure which may be related to these mechanisms. Small arteries were dissected from gluteal biopsies and studied using wire myography. Arterial morphological parameters were measured and concentration-response curves constructed for a number of vasoconstrictor and vasodilator agonists. Plasma concentrations of neuroendocrine hormones were also measured. There were no morphological differences between small arteries from control subjects and those from patients with chronic heart failure. In heart failure patients, vasoconstrictor responses to endothelin-1 were significantly reduced, although plasma endothelin-1 levels were increased. Arteries from heart failure patients also showed evidence of an impaired neuronal uptake mechanism, since blockade by cocaine had no effect on noradrenaline-induced vasoconstriction in these vessels. These results suggest that small-artery structure is not altered in chronic heart failure and so cannot account for the heightened vascular resistance in this syndrome. However, abnormal neuronal uptake and impaired vasoconstriction in response to endothelin-1 may be associated with the complex compensatory phenomenon involved in heart failure.

Acetylcholine↗
PubMed1998

Endothelin-1 has haemodynamic effects at pathophysiological concentrations in patients with left ventricular dysfunction.

OBJECTIVES: Plasma levels of immunoreactive endothelin-1 (ET-1) are raised in chronic heart failure. Whether plasma ET-1 contributes to the haemodynamic derangement found in chronic heart failure is not known. We investigated the effects of exogenous ET-1 on the pulmonary and systemic vasculature in patients with left ventricular systolic dysfunction (LVD), with or without overt heart failure. METHODS: ET-1 was infused at 1, 5 and 15 pmol/min into a distal pulmonary artery of ten patients with LVD to achieve plasma concentrations of ET-1 similar to those found in patients with heart failure and pulmonary hypertension. Haemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four patients. RESULTS: Systemic haemodynamic changes occurred with ET-1 infusion: mean arterial pressure (100 +/- 3 [standard error of the mean]) to 107 +/- 3 mmHg; p < 0.01) and systemic vascular resistance (1699 +/- 118 to 2033 +/- 135 dynes s/cm5; p < 0.001) rose, while the cardiac index fell from 2.43 +/- 0.17 to 2.20 +/- 0.16 l/min/m2 (p < 0.002). Mean pulmonary artery pressure (21 +/- 2 mmHg) and pulmonary vascular resistance (151 +/- 14 to 147 +/- 14 dynes s/cm5) did not change however. CONCLUSIONS: Exogenous ET-1, when infused to achieve plasma concentrations similar to those in severe heart failure and pulmonary hypertension, causes systemic but not pulmonary vasoconstriction.

Aged↗
PubMed1998

Pulmonary and systemic responses to exogenous endothelin-1 in patients with left ventricular dysfunction.

Plasma levels of immunoreactive endothelin-1 (ET-1) are elevated in chronic heart failure (CHF) and have been reported to correlate closely with pulmonary hemodynamic measurements. We investigated the effects of exogenous ET-1 on the pulmonary vasculature in patients with left ventricular systolic dysfunction (LVD), with or without overt heart failure. ET-1 was infused at 1, 5, and 15 pmol/min into a distal pulmonary artery of 10 patients with LVD. Hemodynamics were measured by a thermodilution catheter and arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four patients. Systemic hemodynamic changes occurred with ET-1 infusion in a dose-dependent fashion. Mean arterial pressure (100 +/- 8-107 +/- 11 mm Hg; p < 0.01) and systemic vascular resistance (1,699 +/- 375-2,033 +/- 427 dynes/s/cm-5; p < 0.001) rose, whereas the cardiac index fell from 2.43 +/- 0.53 to 2.20 +/- 0.491/min/m2 (p < 0.002). However, mean pulmonary artery pressure (21 +/- 7 mm Hg) and pulmonary vascular resistance (151 +/- 43-147 +/- 43 dynes/s/cm-5) did not change. Exogenous ET-1, when infused into patients with LVD, causes systemic but not pulmonary vasoconstriction.

Aged↗
PubMed1998

Beta-blockers for chronic heart failure: from prejudice to enlightenment.

Experience accumulated from several large trials strongly suggest that beta-blockers should be used for the management of congestive heart failure (CHF). Beta-blockade should be added to conventional therapy such as diuretics, ACE inhibitors, and digoxin, as this was the approach used in the major trials. It is appropriate to treat patients with mild, moderate and, when stable, severe CHF. The benefits obtained include improvements in left ventricular function, reductions in symptoms and morbidity, improvement of quality of life, and delay of clinical progression, reflected by a reduced need for hospitalization and a reduction in mortality. Beta-blockers are much better tolerated, when used appropriately in selected patients, than was previously supposed.

Adrenergic beta-Antagonists↗
PubMed1996

Should all patients with atrial fibrillation receive warfarin? Evidence from randomized clinical trials.

Anticoagulants should be used more widely in patients with atrial fibrillation. Legitimate concerns exist about the risk/benefit ratio in younger patients with no risk factors and in patients over the age of 75 years. Use of lower doses of anticoagulation (potential target range INR of 1.5-2.5) than used heretofore is probably the solution to most of the problems associated with anticoagulation, but conclusive proof of the efficacy of this strategy is needed. Although aspirin may reduce the risk of stroke the effect may be no more than among patients with a similar level of cardiovascular risk factors and in sinus rhythm. As such, aspirin is a valid alternative for patients with atrial fibrillation at a low risk of stroke but should not be used as an excuse to withhold anticoagulants in patients at greater risk. Several larger studies investigating the effects of different intensities of anticoagulation and the use of aspirin-warfarin combinations are underway. Indeed SPAF-III, comparing a combination of low dose warfarin and aspirin with formal anticoagulation has been stopped and reported in March 1996. A summary of the results will appear in the July issue. Identification of the minimum effective dose of warfarin and effective monitoring systems remain a priority.

Aspirin↗
PubMed1994

Androgens and indoleamines interact to control sexual dimorphisms in the rat spinal cord.

Previous studies have shown that (i) androgen administration and (ii) depletion of serotonin can independently masculinise parts of the medial preoptic area and groups of motor neurons in the lumbosacral spinal cord when applied during the early postnatal period. We report here that these two control mechanisms interact in the neonatal female rat. Serotonin depletion by p-chlorophenyl alanine extends the 'critical period' during which androgens can act to stabilise neuron numbers within two sexually dimorphic motor neuron groups in segments L5-S1 (the spinal nucleus of bulbocavernosus and the dorsolateral nucleus), probably by slowing the rate of naturally occurring cell death. A non-dimorphic group of motor neurons (the ventromedial nucleus) was unaffected.

Androgens↗
PubMed1992

The effects of serotonin manipulation during the postnatal period on the development of sexually dimorphic and non-dimorphic lumbosacral motor neuron groups in the albino Swiss rat.

Serotonin (5-HT) may act during development as a neurotrophic agent. Evidence suggests that sexually dimorphic regions of the mammalian nervous system (which often possess sexually dimorphic patterns of 5-HT innervation) could provide a model for this aspect of 5-HT action. Albino Swiss rat pups were treated with p-chlorophenyl alanine (pCPA, 200 mg/kg) or 5-hydroxytryptophan (5-HTP, 75 mg/kg) for 14 days after birth. As adults, the number of motor neurons in the sexually dimorphic spinal nucleus of bulbocavernosus (SNB) and dorsolateral nucleus (DLN), together with the non-dimorphic ventromedial nucleus (VM) were analysed. Postnatal treatment with 5-HTP had a general effect of increasing motor neuron numbers in all three groups. However, pCPA treatment had a marked and specific effect on SNB neuron numbers, increasing these in both sexes (+250% in females and +60% in males) compared with control animals. The results suggest that the postnatal innervation of ventral horn motor neurons by 5-HT-containing terminals may affect cell death at this time.

Animals↗