Biomedical subjects

John M Power

Publications and source records attributed to John M Power.

7 recordsLinked to original sources

PubMed2003

Ventricular constraint in severe heart failure halts decline in cardiovascular function associated with experimental dilated cardiomyopathy.

BACKGROUND: We have shown that passive ventricular constraint during moderate heart failure can halt progressive deterioration in cardiac function in an experimental model of ovine pacing induced heart failure (HF). We report on ventricular constraint in severe heart failure. METHODS: Eighteen adult merino sheep were used. Severe heart failure was induced in two stages, ie, high rate ventricular pacing for 21 days to produce moderate HF and then for 42 days to induce severe HF. A custom-made polyester mesh cardiac support device ([CSD] Acorn Cardiovascular, St Paul, MN) was implanted snugly around both ventricles through a lower partial sternotomy in 9 sheep (group 1). Rapid ventricular pacing was continued for a further 28 days in all animals to induce advanced HF. Cardiovascular functional indicators were determined using echocardiography and a submaximal treadmill exercise protocol at base line, moderate, severe, and advanced stages. The 9 sheep in group 2 were used as controls. RESULTS: Cardiovascular function was significantly depressed in all animals in advanced heart failure compared with base line, with left ventricular ejection fraction (LVEF) falling from 50% to 25% (p < 0.05) and LV +dp/dt((max)) declining from 1,777 to 1,243 (p < 0.05). However after CSD implantation cardiovascular function during exercise improved significantly despite ongoing rapid pacing, with LVEF increasing to 30% and LV +dp/dt to 1,499 (p < 0.05) in group 1. There were no significant changes in left ventricular long axis area (157 to 151 cm(2)) and short axis (6.8 to 6.1 cm) dimensions at the termination of pacing compared with those at time of CSD implant. Mitral regurgitation improved slightly from 2.5 to 2.19 after containment (p < 0.05) in group 1 but increased to 2.83 in group 2. CONCLUSIONS: Ventricular constraint in advanced heart failure with a custom-made polyester mesh device halted the decline in cardiac function seen in untreated animals with this pacing-induced animal model of heart failure. These results indicate potential clinical implications for ventricular containment in the treatment of end-stage heart failure.

Animals↗

PubMed2002

Age-related enhancement of the slow outward calcium-activated potassium current in hippocampal CA1 pyramidal neurons in vitro.

Aging is associated with learning deficits and a decrease in neuronal excitability, reflected by an enhanced post-burst afterhyperpolarization (AHP), in CA1 hippocampal pyramidal neurons. To identify the current(s) underlying the AHP altered in aging neurons, whole-cell voltage-clamp recording experiments were performed in hippocampal slices from young and aging rabbits. Similar to previous reports, aging neurons were found to rest at more hyperpolarized potentials and have larger AHPs than young neurons. Given that compounds that reduce the slow outward calcium-activated potassium current (sI(AHP)), a major constituent of the AHP, also facilitate learning in aging animals, the sI(AHP) was pharmacologically isolated and characterized. Aging neurons were found to have an enhanced sI(AHP,) the amplitude of which was significantly correlated to the amplitude of the AHP (r = 0.63; p < 0.001). Thus, an enhanced sI(AHP) contributes to the enhanced AHP in aging. No differences were found in the membrane resistance, capacitance, or kinetic and voltage-dependent properties of the sI(AHP). Because enhanced AHP in aging neurons has been hypothesized to be secondary to an enhanced Ca2+ influx via the voltage-gated L-type Ca2+ channels, we further examined the sI(AHP) in the presence of an L-type Ca2+ channel blocker, nimodipine (10 microm). Nimodipine caused quantitatively greater reductions in the sI(AHP) in aging neurons than in young neurons; however, the residual sI(AHP) was still significantly larger in aging neurons than in young neurons. Our data, in conjunction with previous studies showing a correlation between the AHP and learning, suggest that the enhancement of the sI(AHP) in aging is a mechanism that contributes to age-related learning deficits.

Action Potentials↗

PubMed2002

Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1 pyramidal neurons.

The cholinergic system is thought to play an important role in hippocampal-dependent learning and memory. However, the mechanism of action of the cholinergic system in these actions in not well understood. Here we examined the effect of muscarinic receptor stimulation in hippocampal CA1 pyramidal neurons using whole-cell recordings in acute brain slices coupled with high-speed imaging of intracellular calcium. Activation of muscarinic acetylcholine receptors by synaptic stimulation of cholinergic afferents or application of muscarinic agonist in CA1 pyramidal neurons evoked a focal rise in free calcium in the apical dendrite that propagated as a wave into the soma and invaded the nucleus. The calcium rise to a single action potential was reduced during muscarinic stimulation. Conversely, the calcium rise during trains of action potentials was enhanced during muscarinic stimulation. The enhancement of free intracellular calcium was most pronounced in the soma and nuclear regions. In many cases, the calcium rise was distinguished by a clear inflection in the rising phase of the calcium transient, indicative of a regenerative response. Both calcium waves and the amplification of action potential-induced calcium transients were blocked the emptying of intracellular calcium stores or by antagonism of inositol 1,4,5-trisphosphate receptors with heparin or caffeine. Ryanodine receptors were not essential for the calcium waves or enhancement of calcium responses. Because rises in nuclear calcium are known to initiate the transcription of novel genes, we suggest that these actions of cholinergic stimulation may underlie its effects on learning and memory.

Action Potentials↗

PubMed2002

Electrical remodeling of the atrium in an anatomic model of atrial flutter: relationship between substrate and triggers for conversion to atrial fibrillation.

BACKGROUND: Atrial flutter (AFL) and atrial fibrillation (AF) frequently coexist, yet the specific relationship between these arrhythmias, and particularly whether sustained AFL leads to AF, is unknown. METHODS AND RESULTS: We investigated the electrophysiological consequences of chronic AFL using an ovine anatomic right atrial Y-lesion model. AFL was induced in 7 animals, and 4 remained in sinus rhythm (controls). Sheep were monitored for spontaneous conversion of AFL to AF. Six of 7 sheep sustained AFL for 28 days. In 1 of 7 sheep, spontaneous conversion of AFL to AF occurred on day 5. AFL produced a highly significant fall in right and left atrial refractoriness (AERP, P<0.001), with 74+/-10% of the reduction occurring by day 3. Right atrial conduction velocity also fell significantly (baseline 89+/-9 cm/s versus day 28 64+/-14 cm/s, P<0.001) but over a slower time course. AERP and conduction velocity changes coincided with a characteristic biphasic decrease and increase in the AFL cycle length. The excitable gap (percent of AFL cycle length) increased from 13+/-3% at baseline to 46+/-8% by day 28 (P<0.001). Sustained AF (>30 seconds) was not inducible at baseline but after 28 days of AFL could be induced in 6 of 6 sheep by critically timed single or multiple extrastimuli delivered either in sinus rhythm or AFL. There was no significant change in any parameter in control sheep. CONCLUSIONS: In this model, AFL produced electrical remodeling and the substrate for sustained AF. However, spontaneous conversion to AF was uncommon, and the development of AF was dependent on specific triggers.

Animals↗

PubMed2002

Epicardial radiofrequency ablation of both atria in the treatment of atrial fibrillation: experience in patients.

BACKGROUND: Despite success with the Maze procedure and its modifications in treating atrial fibrillation, longer procedure times and increased morbidity have precluded widespread use. The operative treatment for atrial fibrillation associated with aortic valve disease and ischemic heart diseases have not been established. We report the early results of epicardial radiofrequency coagulation on both atria and discuss the availability of this procedure. METHODS: The Australasian database of radiofrequency ablation lists 130 patients with established or frequent intermittent atrial fibrillation that underwent various cardiac surgical procedures between March 2000 and March 2002. Forty patients without mitral valve disease underwent epicardial radiofrequency coagulation on both atria. Twenty-eight patients were in established chronic atrial fibrillation, 9 in paroxysmal atrial fibrillation, and 3 patients had atrial flutter. The primary surgical procedures were coronary artery bypass grafting in 19 patients, aortic valve replacement in 9, coronary artery bypass grafting plus aortic valve replacement in 8, and other procedures in 4 patients. RESULTS: The procedure increased the cross-clamp time by a mean of 10 minutes. Three patients required defibrillation postoperatively, within the first 3 months and have since stayed in sinus rhythm. One patient had late atrial flutter that was cardioverted to sinus rhythm. Sinus recovery rate was 93.7% (15 of 16 patients) at 6 months and 100% in 8 patients reviewed at 12 months. Atrial contractility was maintained. CONCLUSIONS: Epicardial radiofrequency coagulation may be a very effective way of converting patients with atrial fibrillation into sinus rhythm.

Aged↗

PubMed2002

An ovine model of tachycardia-induced degenerative dilated cardiomyopathy and heart failure with prolonged onset.

BACKGROUND: The aim of this study was to develop a model of long-term progressive heart failure (HF). METHODS AND RESULTS: A cardiac output flowprobe was implanted on the pulmonary artery of 9 adult sheep weighing 40 to 50 kg. Rapid ventricular pacing for 21 days at 160 to 190 bpm (rate A) resulted in moderate HF. Animals were then paced at 205 to 215 bpm (rate B) for 42 days (severe HF) and for 28 days at rate B (advanced HF). Data were collected at baseline and moderate, severe, and advanced HF during submaximal exercise testing and by transthoracic echocardiography in sinus rhythm. There were marked increases in left ventricular (LV) area, mitral valve regurgitation, and LV end-diastolic pressure and decreases in LV wall thickness, LV ejection fraction, positive and negative dP/dt(max), and positive (dP/dt(max))/P throughout the pacing protocol. CONCLUSIONS: This ovine HF model incorporates the progressive nature of human HF and allows examination of both structural changes and hemodynamic parameters of HF during and after exercise challenge.

Animals↗

PubMedDate not supplied

Passive ventricular constraint.

Heart failure (HF) is a progressive degenerative and malignant syndrome with a large number of aetiologies including coronary artery disease, chronic hypertension, exposure to toxins, bacteria and viruses and in a significant percentage of HF patients, the causal mechanism is unclear. The HF trail of morbidity and mortality is well documented and is characterised by step-like periods of relative symptomatic stability, compensation, separated by decompensatory episodes. The homeostatic response to the decline in cardiac function is diverse and involves most organs. There is an increase in resting rate, intra-cardiac hormone production (catecholamines, aldosterone, etc.) and in particular structural changes occur with increased mass and dilatation (dilated cardiomyopathy, DCM). DCM is associated with decreased cardiac output, contractility and energy efficiency and an increase in pro-arrhythmia and conduction defects. Kass et al. (Circulation 91(9) (1995) 2314) first demonstrated in patients who had undergone a dynamic cardio-myoplasty procedure, that, preventing further dilatation in DCM was beneficial and that the improved cardiovascular status was largely independent of muscle stimulation. We hypothesised that this outcome could be achieved by implanting a fabric cardiac support device around both ventricles to the AV junction. Subsequently, it was shown by us and others (Kass et al., 1995) (Cardiovasc. Res. 44(3) (1999) 549); (Ann. Thorac. Surg. 70(4) (2000) 1275) (in different animal models of DCM) that passive ventricular constraint prevented further dilatation, initiated left ventricular volume reduction and reversed the decline in ejection fraction, mitral valve integrity and left ventricular contractility, when compared with untreated controls. Subsequent European and North American clinical trials in patients with DCM of varying aetiologies have shown equal promise and an absence of device related complications (Circulation 104(12 Suppl. 1) (2001) I270); (Ann. Thorac. Cardiovasc. Surg. 7(5) (2001) 278). The mechanisms behind this improvement have yet to be fully clarified however the support generated by the device upon the right and ventricular freewall would lower wall tension. Not only is passive ventricular constraint a very promising treatment modality for heart failure and DCM it should provide a useful research tool for the study of the role of ventricular dilatation in the progression of heart failure.

Animals↗