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.

Use of an accelerated chest pain assessment protocol in patients at intermediate risk of adverse cardiac events

Objective: To determine the feasibility, safety and effectiveness of a structured clinical pathway for stratification and management of patients presenting with chest pain and classified as having intermediate risk of adverse cardiac outcomes in the subsequent six months. Design: Prospective clinical audit. Participants and setting: 630 consecutive patients who presented to the emergency department of a metropolitan tertiary care hospital between January 2000 and June 2001 with chest pain and intermediate-risk features. Intervention: Use of the Accelerated Chest Pain Assessment Protocol (ACPAP), as advocated by the Management of unstable angina guidelines - 2000 from the National Heart Foundation and the Cardiac Society of Australia and New Zealand. Main outcome measure: Adverse cardiac events during six-month follow-up. Results: 409 patients (65%) were reclassified as low risk and discharged at a mean of 14 hours after assessment in the chest pain unit. None had missed myocardial infarctions, while three (1%) had cardiac events at six months (all elective revascularisation procedures, with no readmissions with acute coronary syndromes). Another 110 patients (17%) were reclassified as high risk, and 21 (19%) of these had cardiac events (mainly revascularisations) by six months. Patients who were unable to exercise or had non-diagnostic exercise stress test results (equivocal risk) had an intermediate cardiac event rate (8%). Conclusions: This study validates use of ACPAP. The protocol eliminated missed myocardial infarction; allowed early, safe discharge of low-risk patients; and led to early identification and management of high-risk patients.

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.

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.

Utilisation of outpatient cardiac rehabilitation in Queensland

Objectives: To determine patient participation rates in outpatient cardiac rehabilitation (OCR) programs; ascertain the barriers to participation; and evaluate the quality of OCR programs. Design and setting: Retrospective cohort study of patient separations from selected public and private Queensland hospitals; questionnaire survey of hospitals and all registered OCR programs. Participants: Patients discharged with cardiac diagnoses between 1 July 1999 and 30 June 2000 from 31 hospitals (24 public; 7 private). Main outcome measures: Rates of referral of hospitalised patients to OCR programs; rates of program attendance and completion; barriers to OCR referral and attendance. Results: 15186 patients were discharged with cardiac diagnoses from participating hospitals, of whom 4346 (29%) were referred to an OCR program after discharge, compared with an estimated 59% (8895/15 186) of patients who were eligible for such a program. Proportionately more patients were referred from secondary (38% [1720/4500]) and private (52% [2116/4031]; P < 0.001) hospitals than from tertiary (25% [2626/10 686]) and public (20% [2230/11 155]) hospitals. Patients undergoing coronary revascularisation procedures comprised 35% of discharges, but accounted for 56% of all program attendances. Fewer than a third of all referred patients completed OCR programs, and only 39% of available OCR program places were fully utilised. Catchment populations of programs with unused places had excess coronary mortality. Conclusion: There is significant underutilisation of facility-based OCR programs in Queensland. Procedures are required for identifying and referring eligible patients to existing programs and improving program compliance. Alternative OCR models are also required.