Basal nonselective cation permeability in rat cardiac microvascular endothelial cells

The presence of a basal nonselective cation permeability was mainly investigated in primary cultures of rat cardiac microvascular endothelial cells (CMEC) by applying both the patch-clamp technique and Fura-2 microfluorimetry. With low EGTA in the pipette solution, the resting membrane potential of CMEC was -21.2 +/- 1.1 mV, and a Ca2+-activated Cl- conductance was present. When the intracellular Ca2+ was buffered with high EGTA, the membrane potential decreased to 5.5 +/- 1.2 mV. In this condition, full or partial substitution of external Na+ by NMDG(+) proportionally reduced the inward component of the basal I-V relationship. This current was dependent on extracellular monovalent cations with a permeability sequence of K+ > Cs+ > Na+ > Li+ and was inhibited by Ca2+, La3+, Gd3+, and amiloride. The K+/Na+ permeability ratio, determined using the Goldman-Hodgkin-Katz equation, was 2.01. The outward component of the basal I-V relationship was reduced when intracellular K+ was replaced by NMDG(+), but was not sensitive to substitution by Cs+. Finally, microfluorimetric experiments indicated the existence of a basal Ca2+ entry pathway, inhibited by La3+ and Gd3+. The basal nonselective cation permeability in CMEC could be involved both in the control of myocardial ionic homeostasis, according to the model of the blood-heart barrier, and in the modulation of Ca2+ -dependent processes. (C) 2002 Elsevier Science (USA).

Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA-salt hypertensive rats

1 This study has administered pirfenidone (5-methyl-l-phenyl-2-[1H]-pyridone) or amiloride to attenuate the remodelling and associated functional changes, especially an increased cardiac stiffness, in DOCA-salt hypertensive rats. 2 In control rats, the elimination half-life of pirfenidone following a single intravenous dose of 200 mg kg(-1) was 37 min while oral bioavailability at this dose was 25.7%. Plasma pirfenidone concentrations in control rats averaged 1.9 +/- 0.1 mug ml(-1) over 24 It after 14 days' administration as a 0.4% mixture in food. 3 Pirfenidone (approximately 250-300 mg kg(-1) day(-1) as 0.4% in food) and amiloride (I mg kg-1 day(-1) sc) were administered for 2 weeks starting 2 weeks post-surgery. Pirfenidone but not amiloride attenuated ventricular hypertrophy (2.69 +/- 0.09, UNX 2.01 +/- 0.05. DOCA-salt 3.11 +/- 0.09 mg kg(-1) body wt) without lowering systolic blood pressure. 4 Collagen deposition was significantly increased in the interstitium after 2 weeks and further increased with scarring of the left ventricle after 4 weeks; pirfenidone and amiloride reversed the increases and prevented further increases. This accumulation of collagen was accompanied by an increase in diastolic stiffness constant; both amiloride and pirfenidone, reversed this increase. 5 Noradrenaline potency (positive chronotropy) was decreased in right atria (neg log EC50: control 6.92 +/- 0.06; DOCA-salt 6.64 +/- 0.08); pirfenidone but not amiloride reversed this change. Noradrenaline was a more potent vasoconstrictor in thoracic aortic rings (neg log EC50: control 6.91 +/- 0.10; DOCA-salt 7.90 +/- 0.07); pirfenidone treatment did not change noradrenaline potency. 6 Thus, pirfenidone and amiloride reverse and prevent cardiac remodelling and the increased cardiac stiffness without reversing the increased vascular responses to noradrenaline.

Surgical programme at Royal Alexandra Hospital, Sydney, for Papua New Guinea children with congenital heart disease, 1978-1994

Objective : To report the history of the Royal Alexandra Hospital for Children (RAHC) Papua New Guinea (PNG) cardiac surgical programme and describe the selection, preoperative clinical features and postoperative outcome of children with congenital heart disease managed by the programme. Methods : Details for each of the PNG cardiac patients admitted to RAHC following selection by visiting cardiologists between 1978 and 1994 were entered into a database, and analysed and interpreted. Results : A congenital heart defect was confirmed in 165 of the 170 children selected. The male to female ratio was 1:1 and the mean age on admission to RAHC was 5.5 years. Almost all of the children for whom data were available (98%) had a weight for age and 41% had a height for age less than the 3rd centile. One-sixth had delayed milestones. A large number were tachypnoeic, in heart failure, or had pulmonary hypertension on admission. Ventricular septal defect and tetralogy of Fallot were the commonest defects, and lesions such as aortic stenosis, coarctation of the aorta and transposition of the great arteries were absent or rare. Thirty-one (19%) of the children selected initially did not receive surgery because of pulmonary hypertension, or because the lesions did not fall within the programme guidelines for operation. One hundred and twenty-nine children had corrective and four had palliative procedures. Half of the operated children had postoperative complications. Eight children died, all following open-heart procedures, giving a case fatality rate of 6%. Preoperative tachypnoea, hepatomegaly, cardiac failure and pulmonary hypertension were strongly associated with poor outcome. Conclusions : The programme was an arduous exercise for all organizations concerned, but achieved comparatively good short-term outcomes. The experience gained should assist in planning for similar programmes.

Differential modes of alaryngeal communication and long-term voice outcomes following pharyngolaryngectomy and laryngectomy

Patterns of vocal rehabilitation for 37 pharyngolaryngectomy patients and 55 total laryngectomy patients over a 5-year period were compared. An electrolarynx (EL) was introduced as the initial communication mode immediately after surgery for 98% of patients, with 30% of pharyngolaryngectomy and 74% of laryngectomy patients subsequently developing tracheoesophageal speech (TES) as their primary mode of communication. Follow-up with 14 of 37 pharyngolaryngectomy patients and 36 of 55 laryngectomy patients was conducted 1-6 years following surgery and revealed that 90% of the pharyngolaryngectomy patients maintained the use of TES in the long term compared to 69% of the laryngectomy group. Long-term outcomes relating to communication disability and handicap did not differ significantly between the two surgical groups, however the laryngectomy patients had significantly higher levels of wellbeing. Across the whole group of patients, statistical comparison revealed that patients using TES had significantly lower levels of disability, handicap and distress than EL users. Considering that lower levels of disability, handicap and distress are associated with TES, and the data supports that suitably selected patients can maintain functional TES in the long term, increased application of this form of communication rehabilitation should be encouraged where viable for the pharyngolaryngectomy population. Copyright (C) 2003 S. Karger AG, Basel.

Use of a thermodilution catheter to measure core body temperature, central venous pressure and cardiac output during anaesthesia and surgery in the dog

The use of thermodilution and other methods of monitoring in dogs during surgery and critical care was evaluated. Six Greyhounds were anaesthetised and then instrumented by placing a thermodilution catheter into the pulmonary artery via the jugular vein. A catheter in the dorsal pedal artery also permitted direct measurement of arterial pressures. Core body temperature (degreesC) and central venous pressure (mmHg) were measured, while cardiac output (mL/min/kg) and mean arterial pressure (mmHg) were calculated. A mid-line surgical incision was performed and the physiological parameters were monitored for a total of two hours. All physiological parameters generally declined, although significant increases (P<0.05) were noted for cardiac output following surgical incision. Central venous pressure was maintained at approximately 0mmHg by controlling an infusion of sterile saline. Core body temperature decreased from 37.1+/-0.6degreesC (once instrumented) to 36.6+/-0.60degreesC (at the end of the study), despite warming using heating pads. Physiological parameters indicative of patient viability will generally decline during surgery without intervention. This study describes an approach that can be undertaken in veterinary hospitals to accurately monitor vital signs in surgical and critical care patients.

CPR training in households of patients with chest pain

The objectives of this study are to (1) quantify prior cardiopulmonary resuscitation (CPR) training in households of patients presenting to the Emergency Department (ED) with or without chest pain or ischaemic heart disease (IHD); (2) evaluate the willingness of household members to undertake CPR training; and (3) identify potential barriers to the learning and provision of bystander CPR. A cross-sectional study was conducted by surveying patients presenting to the ED of a metropolitan teaching hospital over a 6-month period. Two in five households of patients presenting with chest pain or IHD had prior training in CPR. This was no higher than for households of patients presenting without chest pain or IHD. Just under two in three households of patients presenting with chest pain or IHD were willing to participate in future CPR classes. Potential barriers to learning CPR included lack of information on CPR classes, perceived lack of intellectual and/or physical capability to learn CPR and concern about causing anxiety in the person at risk of cardiac arrest. Potential barriers to CPR provision included an unknown cardiac arrest victim and fear of infection. The ED provides an opportunity for increasing family and community capacity for bystander intervention through referral to appropriate training. (C) 2003 Published by Elsevier Science Ireland Ltd.

Control of familial and renal cardiac diseases in English bull terriers: How to repair a damaged breed?

Control recommendations are presented for four genetic or familial diseases that cause significant morbidity and mortality in affected English Bull Terriers. Bull Terrier polycystic kidney disease is an autosomal dominant disease diagnosed by detecting a minimum of three renal cysts, with cysts present in both kidneys, and similarly affected family members to confirm the inherited nature of the cysts. Bull Terrier hereditary nephritis is an autosomal dominant disease diagnosed in otherwise normal animals with urinary protein: creatinine ratios persistently >0.3 and no significant urinary sediment, a family history of the disease, and characteristic glomerular basement membrane lesions. Mitral valve myxomatous degeneration and left ventricular outflow tract obstruction in Bull Terriers are familial diseases diagnosed by auscultating characteristic murmurs in affected animals. Excluding animals with these clinical signs from the breeding pool will reduce the prevalence rates of these diseases, however maintenance of an effective population size is also important. Providing breeders with information on genetics, including the risks associated with inbreeding and the benefits of outcrossing, is likely to improve canine breeding practices, thus increasing fitness and fecundity of these purebred dogs.

Influence of magnetically-induced E-fields on cardiac electric activity during MRI: A modeling study

In modern magnetic resonance imaging (MRI), patients are exposed to strong, time-varying gradient magnetic fields that may be able to induce electric fields (E-fields)/currents in tissues approaching the level of physiological significance. In this work we present theoretical investigations into induced E-fields in the thorax, and evaluate their potential influence on cardiac electric activity under the assumption that the sites of maximum E-field correspond to the myocardial stimulation threshold (an abnormal circumstance). Whole-body cylindrical and planar gradient coils were included in the model. The calculations of the induced fields are based on an efficient, quasi-static, finite-difference scheme and an anatomically realistic, whole-body model. The potential for cardiac stimulation was evaluated using an electrical model of the heart. Twelve-lead electrocardiogram (ECG) signals were simulated and inspected for arrhythmias caused by the applied fields for both healthy and diseased hearts. The simulations show that the shape of the thorax and the conductive paths significantly influence induced E-fields. In healthy patients, these fields are not sufficient to elicit serious arrhythmias with the use of contemporary gradient sets. However, raising the strength and number of repeated switching episodes of gradients, as is certainly possible in local chest gradient sets, could expose patients to increased risk. For patients with cardiac disease, the risk factors are elevated. By the use of this model, the sensitivity of cardiac pathologies, such as abnormal conductive pathways, to the induced fields generated by an MRI sequence can be investigated. (C) 2003 Wiley-Liss, Inc.

Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients with end-stage heart failure before pacemaker implantation

We evaluated patients with end-stage heart failure who have a high likelihood of response to cardiac resynchronization therapy (biventricular pacing). It appears that 20% of patients do not respond to this expensive therapy despite the use of selection criteria (dilated cardiomyopathy, heart failure, New York Heart Association class II or IV, left ventricular election fraction 120 ms). The presence of left ventricular dys-synchrony is needed to result in improvement after cardiac resynchronization therapy. (C)2003 by Excerpta Medica, Inc.

Obesity is associated with worse peritoneal dialysis outcomes in the Australia and New Zealand patient populations

Although obesity is associated with increased risks of morbidity and death in the general population, a number of studies of patients undergoing hemodialysis have demonstrated that increasing body mass index (BMI) is correlated with decreased mortality risk. Whether this association holds true among patients treated with peritoneal dialysis (PD) has been less well studied. The aim of this investigation was to examine the association between BMI and outcomes among new PD patients in a large cohort, with long-term follow-up monitoring. Using data from the Australia and New Zealand Dialysis and Transplant Registry, an analysis of all new adult patients (n = 9679) who underwent an episode of PD treatment in Australia or New Zealand between April 1, 1991, and March 31, 2002, was performed. Patients were classified as obese (BMI of greater than or equal to30 kg/m(2)), overweight (BMI of 25.0 to 29.9 kg/m(2)), normal weight (BMI of 20 to 24.9 kg/m(2)), or underweight (BMI of