Synchronization of Intracellular Ca Release in Multicellular Cardiac Preparations.

In myocardial tissue, Ca release from the sarcoplasmic reticulum (SR) that occurs via the ryanodine receptor (RyR2) channel complex. Ca release through RyR2 can be either stimulated by an action potential (AP) or spontaneous. The latter is often associated with triggered afterdepolarizations, which in turn may lead to sustained arrhythmias.

Etiology-dependent impairment of relaxation kinetics in right ventricular end-stage failing human myocardium.

Background: In patients with end-stage heart failure, the primary etiology often originates in the left ventricle, and eventually the contractile function of the right ventricle (RV) also becomes compromised. RV tissue-level deficits in contractile force and/or kinetics need quantification to understand involvement in ischemic and non-ischemic failing human myocardium.

Methods And Results: The human population suffering from heart failure is diverse, requiring many subjects to be studied in order to perform an adequately powered statistical analysis.

Myocardial Contractile Dysfunction Is Present without Histopathology in a Mouse Model of Limb-Girdle Muscular Dystrophy-2F and Is Prevented after Claudin-5 Virotherapy.

Mutations in several members of the dystrophin glycoprotein complex lead to skeletal and cardiomyopathies. Cardiac care for these muscular dystrophies consists of management of symptoms with standard heart medications after detection of reduced whole heart function. Recent evidence from both Duchenne muscular dystrophy patients and animal models suggests that myocardial dysfunction is present before myocardial damage or deficiencies in whole heart function, and that treatment prior to heart failure symptoms may be beneficial.

Effect of exercise training and myocardial infarction on force development and contractile kinetics in isolated canine myocardium.

It is well known that moderate exercise training elicits a small increase in ventricular mass (i.e., a physiological hypertrophy) that has many beneficial effects on overall cardiac health.

Dissociation of Calcium Transients and Force Development following a Change in Stimulation Frequency in Isolated Rabbit Myocardium.

As the heart transitions from one exercise intensity to another, changes in cardiac output occur, which are modulated by alterations in force development and calcium handling. Although the steady-state force-calcium relationship at various heart rates is well investigated, regulation of these processes during transitions in heart rate is poorly understood. In isolated right ventricular muscle preparations from the rabbit, we investigated the beat-to-beat alterations in force and calcium during the transition from one stimulation frequency to another, using contractile assessments and confocal microscopy.

Decreased RyR2 refractoriness determines myocardial synchronization of aberrant Ca2+ release in a genetic model of arrhythmia.

Dysregulated intracellular Ca(2+) signaling is implicated in a variety of cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia. Spontaneous diastolic Ca(2+) release (DCR) can induce arrhythmogenic plasma membrane depolarizations, although the mechanism responsible for DCR synchronization among adjacent myocytes required for ectopic activity remains unclear. We investigated the synchronization mechanism(s) of DCR underlying untimely action potentials and diastolic contractions (DCs) in a catecholaminergic polymorphic ventricular tachycardia mouse model with a mutation in cardiac calsequestrin.

Contractile parameters and occurrence of alternans in isolated rat myocardium at supra-physiological stimulation frequency.

The cardiac refractory period prevents the heart from tetanic activation that is typically used in noncardiac striated muscle tissue. To what extent the refractory period prevents successive action potentials to activate the excitation-contraction coupling process and contractile machinery at supra-physiological rates, such as those present during ventricular fibrillation, is unknown. Using multicellular trabeculae isolated from rat hearts, we studied amplitude and kinetics of contraction at rates well above the normal in vivo rat heart range.

Electrical characteristics of a split cathodal pacing configuration.

Several electrical configurations can be used for biventricular pacing to achieve cardiac resynchronization. Commercially approved biventricular pacing systems stimulate the RV with an endocardial lead and the LV with a unipolar lead positioned in the cardiac venous circulation using the tip electrodes of both leads linked as a common cathode. The distribution of current with this parallel circuit, split cathodal configuration is dependent on the separate impedances of the two leads.

Can the heart be chronically paced with electrodes on the pericardial surface?

During implantable defibrillator (ICD) operations, we measured acute and chronic transpericardial bipolar pacing thresholds through standard myocardial surface electrodes sewn on the pericardium for chronic ICD QRS rate-sensing use. We compared observations in 24 patients on day 0 with chronic measurements in seven patients at 27.4 +/- 12.

Pacing threshold spikes months and years after implant.

To determine patterns of variation in chronic pacing thresholds, we made 4,942 threshold measurements in 257 patients with 312 leads, at times from implant to 295 months (median 17 months) including 1,053 determinations in 46 children less than 12 years old. Motivation was late sudden death in two single-ventricle pacemaker-dependent children with multiple possible death causes. At stimulus duration 0.