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Not all cardiac glycosides are equal: Could ouabain prove to be better than digoxin for heart failure?
Abstract
241 Microangiopathy masquerading as peripartum cardiomyopathy J. Fanning 1,2,∗ , D. Platts 1,2 , K. Shekar 1,2 , N. Raju 1 , J. Fraser 1,2 1 The
Prince Charles Hospital, Brisbane, Australia 2 The University of Queensland, Australia A 35-year-old, primigravida female required an urgent lower caesarean section at 39 weeks gestation for antepartum haemorrhage, secondary to placental infarction. Up to this point, the pregnancy had been uneventful, as was the immediate post-operative course for both the mother and baby. Over the subsequent fortnight, the mother had recurrent presentations in respiratory failure. CTPA revealed multiple right upper lobe sub-segmental pulmonary emboli and bilateral lung consolidation. Transbronchial biopsy was suggestive of organising pneumonia. Despite optimal medical management, she rapidly deteriorated into cardiogenic shock with severe biventricular failure, leading to a working diagnosis of peripartum cardiomyopathy. She was transferred to a quaternary cardiothoracic centre for consideration of VAECMO. Her ICU admission was complex with respiratory failure, multiple cardiac arrests, hypotension, fulminant hepatic failure, acute renal failure and transfusion dependence. Contrast TTE demonstrated multiple large thrombi in both ventricles and a perfusion defect suggesting distal left anterior descending occlusion. Multiple areas of intracranial haemorrhage/infarct and both splenic and pulmonary infarction were identified on CT. Her severe coagulopathic state precluded VA-ECMO and raised suspicion of an underlying microangiopathy. Empirical therapeutic plasma exchange was instituted with immediate improvement in her clinical condition. She was discharged from hospital two weeks later with minimal residual deficit. This case illustrates: 1) the diagnostic dilemma and management of microangiopathic conditions in critical illness; 2) the potential role of VA-ECMO as a bridge to recovery; 3) contrast echocardiography as a bedside modality in the assessment of myocardial perfusion, and; 4) special considerations in the peripartum patient with cardiogenic shock. http://dx.doi.org/10.1016/j.hlc.2015.06.242 242 Not all cardiac glycosides are equal: Could ouabain prove to be better than digoxin for heart failure? A. Garcia ∗ , C. Liu, W. Hannam, N. Fry, H. Rasmussen Kolling Institute of Medical Research, University of Sydney, Australia Pharmacological properties of cardiac steroids (CTSs) are widely assumed identical despite large differences in structure. However, a hydrophobic barrier in the access channel
S213
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to their binding site within the Na+ -K+ pump indicates the hydrophilic ouabain but not the hydrophobic digoxin must alter pump molecule structure to reach the site. Both drugs in high concentrations block the pump but effects at low concentrations might differ. To test this we voltage clamped cardiac myocytes and identified the electrogenic pump current (Ip, normalised to membrane capacitance) by current shift with elimination of extracellular K+ . Exposure to 10 nM ouabain for ∼1 - 2 min increased Ip relative to control (Figure). The increase persisted in Na+ -free extracellular solutions, ruling out Na+ influx and secondary pump activation and it persisted when solutions included L-NAME implying a direct effect on the pump molecule rather than NO synthase-dependent signalling. Digoxin and ouabain have similar binding affinities but digoxin had no effect. The traditional view that efficacy of CTS in heart failure is due to Na+ -K+ pump inhibition is incompatible with cytosolic Na+ levels in heart failure now known be raised and have harmful effects. The possibility that ouabain is a better drug than digoxin should be considered.
http://dx.doi.org/10.1016/j.hlc.2015.06.243 243 Obesity and activity in heart transplant: Is obesity post heart transplant related to patient activity levels? S. McKenzie 1,2 , R. Francis 2 , W. Chan 1,2,∗ , G. Javorsky 2 , N. Morris 3 , J. Walsh 2 1 School
of Medicine, The University of Queensland, Australia 2 The Prince Charles Hospital, Queensland Australia 3 School of Rehabilitation Sciences, Griffith University, Gold Coast, Australia Background and Aims: Weight gain and obesity is common after heart transplant (HTx) and associated with a worse prognosis. No studies have established whether there is any relationship between level of activity and HTx recipient obesity. We aimed to assess if there was a relationship between activity levels and obesity as determined by body mass index (BMI). Methods: Transplant recipients greater than 6 months post HTx were approached at time of routine review. Exclusions: rejection episode within 2 months, reduced left ventricular systolic function or a recent injury or illness that expected to reduce mobility. Subjects wore a Sensewear Pro 3 Armband for 7 days. This validated device provides information on energy expenditure, exercise intensity, sleeping duration and steps per day. Physical activity level (PAL) expressed was
241 Microangiopathy masquerading as peripartum cardiomyopathy J. Fanning 1,2,∗ , D. Platts 1,2 , K. Shekar 1,2 , N. Raju 1 , J. Fraser 1,2 1 The
Prince Charles Hospital, Brisbane, Australia 2 The University of Queensland, Australia A 35-year-old, primigravida female required an urgent lower caesarean section at 39 weeks gestation for antepartum haemorrhage, secondary to placental infarction. Up to this point, the pregnancy had been uneventful, as was the immediate post-operative course for both the mother and baby. Over the subsequent fortnight, the mother had recurrent presentations in respiratory failure. CTPA revealed multiple right upper lobe sub-segmental pulmonary emboli and bilateral lung consolidation. Transbronchial biopsy was suggestive of organising pneumonia. Despite optimal medical management, she rapidly deteriorated into cardiogenic shock with severe biventricular failure, leading to a working diagnosis of peripartum cardiomyopathy. She was transferred to a quaternary cardiothoracic centre for consideration of VAECMO. Her ICU admission was complex with respiratory failure, multiple cardiac arrests, hypotension, fulminant hepatic failure, acute renal failure and transfusion dependence. Contrast TTE demonstrated multiple large thrombi in both ventricles and a perfusion defect suggesting distal left anterior descending occlusion. Multiple areas of intracranial haemorrhage/infarct and both splenic and pulmonary infarction were identified on CT. Her severe coagulopathic state precluded VA-ECMO and raised suspicion of an underlying microangiopathy. Empirical therapeutic plasma exchange was instituted with immediate improvement in her clinical condition. She was discharged from hospital two weeks later with minimal residual deficit. This case illustrates: 1) the diagnostic dilemma and management of microangiopathic conditions in critical illness; 2) the potential role of VA-ECMO as a bridge to recovery; 3) contrast echocardiography as a bedside modality in the assessment of myocardial perfusion, and; 4) special considerations in the peripartum patient with cardiogenic shock. http://dx.doi.org/10.1016/j.hlc.2015.06.242 242 Not all cardiac glycosides are equal: Could ouabain prove to be better than digoxin for heart failure? A. Garcia ∗ , C. Liu, W. Hannam, N. Fry, H. Rasmussen Kolling Institute of Medical Research, University of Sydney, Australia Pharmacological properties of cardiac steroids (CTSs) are widely assumed identical despite large differences in structure. However, a hydrophobic barrier in the access channel
S213
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .
to their binding site within the Na+ -K+ pump indicates the hydrophilic ouabain but not the hydrophobic digoxin must alter pump molecule structure to reach the site. Both drugs in high concentrations block the pump but effects at low concentrations might differ. To test this we voltage clamped cardiac myocytes and identified the electrogenic pump current (Ip, normalised to membrane capacitance) by current shift with elimination of extracellular K+ . Exposure to 10 nM ouabain for ∼1 - 2 min increased Ip relative to control (Figure). The increase persisted in Na+ -free extracellular solutions, ruling out Na+ influx and secondary pump activation and it persisted when solutions included L-NAME implying a direct effect on the pump molecule rather than NO synthase-dependent signalling. Digoxin and ouabain have similar binding affinities but digoxin had no effect. The traditional view that efficacy of CTS in heart failure is due to Na+ -K+ pump inhibition is incompatible with cytosolic Na+ levels in heart failure now known be raised and have harmful effects. The possibility that ouabain is a better drug than digoxin should be considered.
http://dx.doi.org/10.1016/j.hlc.2015.06.243 243 Obesity and activity in heart transplant: Is obesity post heart transplant related to patient activity levels? S. McKenzie 1,2 , R. Francis 2 , W. Chan 1,2,∗ , G. Javorsky 2 , N. Morris 3 , J. Walsh 2 1 School
of Medicine, The University of Queensland, Australia 2 The Prince Charles Hospital, Queensland Australia 3 School of Rehabilitation Sciences, Griffith University, Gold Coast, Australia Background and Aims: Weight gain and obesity is common after heart transplant (HTx) and associated with a worse prognosis. No studies have established whether there is any relationship between level of activity and HTx recipient obesity. We aimed to assess if there was a relationship between activity levels and obesity as determined by body mass index (BMI). Methods: Transplant recipients greater than 6 months post HTx were approached at time of routine review. Exclusions: rejection episode within 2 months, reduced left ventricular systolic function or a recent injury or illness that expected to reduce mobility. Subjects wore a Sensewear Pro 3 Armband for 7 days. This validated device provides information on energy expenditure, exercise intensity, sleeping duration and steps per day. Physical activity level (PAL) expressed was