Cyclosporine-insensitive mode of cell death after prolonged myocardial ischemia: Evidence for sarcolemmal permeabilization as the pivotal step.

A prominent theory of cell death in myocardial ischemia/reperfusion (I/R) posits that the primary and pivotal step of irreversible cell injury is the opening of the mitochondrial permeability transition (MPT) pore. However, the predominantly positive evidence of protection against infarct afforded by the MPT inhibitor, Cyclosporine A (CsA), in experimental studies is in stark contrast with the overall lack of benefit found in clinical trials of CsA. One reason for the discrepancy might be the fact that relatively short experimental ischemic episodes (<1 hour) do not represent clinically-realistic durations, usually exceeding one hour.

β-Adrenergic stimulation and rapid pacing mutually promote heterogeneous electrical failure and ventricular fibrillation in the globally ischemic heart.

Global ischemia, catecholamine surge, and rapid heart rhythm (RHR) due to ventricular tachycardia or ventricular fibrillation (VF) are the three major factors of sudden cardiac arrest (SCA). Loss of excitability culminating in global electrical failure (asystole) is the major adverse outcome of SCA with increasing prevalence worldwide. The roles of catecholamines and RHR in the electrical failure during SCA remain unclear.

Mitochondrial depolarization and asystole in the globally ischemic rabbit heart: coordinated response to interventions affecting energy balance.

Mitochondrial membrane potential (ΔΨm) depolarization has been implicated in the loss of excitability (asystole) during global ischemia, which is relevant for the success of defibrillation and resuscitation after cardiac arrest. However, the relationship between ΔΨm depolarization and asystole during no-flow ischemia remains unknown. We applied spatial Fourier analysis to confocally recorded fluorescence emitted by ΔΨm-sensitive dye tetramethylrhodamine methyl ester.

Does the combination of hyperkalemia and KATP activation determine excitation rate gradient and electrical failure in the globally ischemic fibrillating heart?

Ventricular fibrillation (VF) in the globally ischemic heart is characterized by a progressive electrical depression manifested as a decline in the VF excitation rate (VFR) and loss of excitability, which occur first in the subepicardium (Epi) and spread to the subendocardium (Endo). Early electrical failure is detrimental to successful defibrillation and resuscitation during cardiac arrest. Hyperkalemia and/or the activation of ATP-sensitive K(+) (KATP) channels have been implicated in electrical failure, but the role of these factors in ischemic VF is poorly understood.

Detection of mitochondrial depolarization/recovery during ischaemia--reperfusion using spectral properties of confocally recorded TMRM fluorescence.

Timing and pattern of mitochondrial potential (m) depolarization during no-flow ischaemia-reperfusion (I-R) remain controversial, at least in part due to difficulties in interpreting the changes in the fluorescence of m-sensitive dyes such as TMRM. The objective of this study was to develop a new approach for interpreting confocal TMRM signals during I-R based on spatial periodicity of mitochondrial packaging in ventricular cardiomyocytes. TMRM fluorescence (FTMRM) was recorded from Langendorff-perfused rabbit hearts immobilized with blebbistatin using either a confocal microscope or an optical mapping system.

Metabolic determinants of electrical failure in ex-vivo canine model of cardiac arrest: evidence for the protective role of inorganic pyrophosphate.

Rationale: Deterioration of ventricular fibrillation (VF) into asystole or severe bradycardia (electrical failure) heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown.

Objective: To determine metabolic factors of early electrical failure in an ex-vivo canine model of cardiac arrest (VF+global ischemia).

Role of KATP channel in electrical depression and asystole during long-duration ventricular fibrillation in ex vivo canine heart.

Long-duration ventricular fibrillation (LDVF) in the globally ischemic heart is characterized by transmurally heterogeneous decline in ventricular fibrillation rate (VFR), emergence of inexcitable regions, and eventual global asystole. Rapid loss of both local and global excitability is detrimental to successful defibrillation and resuscitation during cardiac arrest. We sought to assess the role of the ATP-sensitive potassium current (I(KATP)) in the timing and spatial pattern of electrical depression during LDVF in a structurally normal canine heart.

Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart.

Long-duration ventricular fibrillation (LDVF) in the globally ischemic heart is a common setting of cardiac arrest. Electrical heterogeneities during LDVF may affect outcomes of defibrillation and resuscitation. Previous studies in large mammalian hearts have investigated the role of Purkinje fibers and electrophysiological gradients between the endocardium (Endo) and epicardium (Epi).

High-precision recording of the action potential in isolated cardiomyocytes using the near-infrared fluorescent dye di-4-ANBDQBS.

The use of voltage-sensitive fluorescent dyes (VSD) for noninvasive measurement of the action potential (AP) in isolated cells has been hindered by low-photon yield of the preparation, dye toxicity, and photodynamic damage. Here we used a new red-shifted VSD, di-4-ANBDQBS, and a fast electron-multiplied charge-coupled device camera for optical AP (OAP) recording in guinea pig cardiac myocytes. Loading di-4-ANBDQBS did not alter APs recorded with micropipette.