Anesthetic preconditioning decreases arrhythmias and improves regional conduction in isolated hearts.

Objective: Anesthetic preconditioning (APC) is known to protect the heart against necrosis and contractile dysfunction, but protection against arrhythmias has not been well characterized. The authors hypothesized that APC alters the dispersion of electrophysiologic parameters to reduce arrhythmias after global (G) or regional (R) ischemia.

Design: Prospective vehicle-controlled study.

Role of S-nitrosothiol transport in the cardioprotective effects of S-nitrosocysteine in rat hearts.

The objective of this study was to determine if prior exposure of rat hearts to S-nitrosocysteine (CysNO) was able to provide protection against reperfusion injury. We probed NO release using the extracellular NO scavenger oxyhemoglobin (oxyHb), and we examined the involvement of the amino acid transport system L (L-AT), a known transporter of CysNO, using the L-AT competitor, L-leucine (L-Leu). Isolated (9- to 12-week-old Wistar male) rat hearts (six to eight per group) were perfused with CysNO (10 microM) for 30 min with or without the L-AT competitor L-Leu (1 mM) before 30 min of ischemia.

Reactive oxygen species as mediators of cardiac injury and protection: the relevance to anesthesia practice.

Reactive oxygen species (ROS) are central to cardiac ischemic and reperfusion injury. They contribute to myocardial stunning, infarction and apoptosis, and possibly to the genesis of arrhythmias. Multiple laboratory studies and clinical trials have evaluated the use of scavengers of ROS to protect the heart from the effects of ischemia and reperfusion.

Hypothermia augments reactive oxygen species detected in the guinea pig isolated perfused heart.

Hypothermic perfusion of the heart decreases oxidative phosphorylation and increases NADH. Because O(2) and substrates remain available and respiration (electron transport system, ETS) may become impaired, we examined whether reactive oxygen species (ROS) exist in excess during hypothermic perfusion. A fiberoptic probe was placed on the left ventricular free wall of isolated guinea pig hearts to record intracellular ROS, principally superoxide (O(2)(-).

Ischemic preconditioning: triggering role of nitric oxide-derived oxidants in isolated hearts.

There is evidence that oxidants generated during ischemic preconditioning (IPC) trigger or mediate cardioprotection. We examined whether a causal relationship exists between oxidant formation during ischemic preconditioning and cardioprotection. We monitored formation of dityrosine in crystalloid-perfused guinea pig isolated hearts after a preconditioning protocol and after prolonged ischemia.

Cardiotonic drugs differentially alter cytosolic [Ca2+] to left ventricular relationships before and after ischemia in isolated guinea pig hearts.

Objective: Cardiotonic agents may differentially alter indices of the cytosolic [Ca2+]/left ventricular pressure (LVP) relationship when given before and after ischemia. We measured and calculated systolic-diastolic [Ca2+], systolic-diastolic LVP, velocity ratios (VRs) d[Ca2+]/dtmax to dLVP/dtmax (VRmax), d[Ca2+]/dtmin to dLVP/dtmin (VRmin), and area ratio (AR, area Ca2+]/area LVP per beat) before and after 30 min global ischemia in guinea pig hearts.

Methods: Hearts were perfused with levosimendan, dobutamine, dopamine, or digoxin.

Reactive oxygen species precede the epsilon isoform of protein kinase C in the anesthetic preconditioning signaling cascade.

Background: Protein kinase C (PKC) and reactive oxygen species (ROS) are known to have a role in anesthetic preconditioning (APC). Cardiac preconditioning by triggers other than volatile anesthetics, such as opioids or brief ischemia, is known to be isoform selective, but the isoform required for APC is not known. The authors aimed to identify the PKC isoform that is involved in APC and to elucidate the relative positions of PKC activation and ROS formation in the APC signaling cascade.

Anesthetic preconditioning: effects on latency to ischemic injury in isolated hearts.

Background: Anesthetic preconditioning (APC) is protective for several aspects of cardiac function and structure, including left ventricular pressure, coronary flow, and infarction. APC may be protective, however, only if the duration of ischemia is within a certain, as yet undefined range. Brief ischemia causes minimal injury, and APC would be expected to provide little benefit.

Anesthetic preconditioning improves adenosine triphosphate synthesis and reduces reactive oxygen species formation in mitochondria after ischemia by a redox dependent mechanism.

Background: Mitochondrial changes that characterize the heart after anesthetic preconditioning (APC) or the mechanisms by which mitochondrial triggering factors lead to protection are unknown. This study hypothesized that generation of reactive oxygen species (ROS) during APC is required to initiate the mitochondrial protective effects, and that APC leads to improved mitochondrial electron transport chain function and cardiac function during reperfusion.

Methods: Isolated guinea pig hearts were subject to 30 min ischemia and 120 min reperfusion.

Na+/H+ exchange inhibition with cardioplegia reduces cytosolic [Ca2+] and myocardial damage after cold ischemia.

Cold cardioplegia protects against reperfusion damage. Blocking Na+/H+ exchange may be as protective as cardioplegia by improving the left ventricular pressure (LVP)-[Ca2+] relationship after cold ischemia. In guinea pig isolated hearts subjected to cold ischemia (4 h, 17 degrees C) and reperfusion, the cardioprotective effects of a Krebs-Ringer (KR) solution, a cardioplegia solution, a KR solution containing the Na+/H+ exchange inhibitor eniporide (1 microM), and a cardioplegia solution containing eniporide were compared.

Sevoflurane exposure generates superoxide but leads to decreased superoxide during ischemia and reperfusion in isolated hearts.

Unlabelled: Reactive oxygen species (ROS) are largely responsible for cardiac injury consequent to ischemia and reperfusion, but, paradoxically, there is evidence suggesting that anesthetics induce preconditioning (APC) by generating ROS. We hypothesized that sevoflurane generates the ROS superoxide (O(2)(.-)), that APC attenuates O(2)(.

Preconditioning with sevoflurane reduces changes in nicotinamide adenine dinucleotide during ischemia-reperfusion in isolated hearts: reversal by 5-hydroxydecanoic acid.

Background: Ischemia causes an imbalance in mitochondrial metabolism and accumulation of nicotinamide adenine dinucleotide (NADH). We showed that anesthetic preconditioning (APC), like ischemic preconditioning, improved mitochondrial NADH energy balance during ischemia and improved function and reduced infarct size on reperfusion. Opening adenosine triphosphate-sensitive potassium (K(atp)) channels may be involved in triggering APC.

Anesthetic preconditioning attenuates mitochondrial Ca2+ overload during ischemia in Guinea pig intact hearts: reversal by 5-hydroxydecanoic acid.

Unlabelled: Cardiac ischemia/reperfusion (IR) injury is associated with mitochondrial (m)Ca(2+) overload. Anesthetic preconditioning (APC) attenuates IR injury. We hypothesized that mCa(2+) overload is decreased by APC in association with mitochondrial adenosine triphosphate-sensitive K(+) (mK(ATP)) channel opening.

Ischemic preconditioning alters real-time measure of O2 radicals in intact hearts with ischemia and reperfusion.

Reactive oxygen species (ROS) are believed to be involved in triggering cardiac ischemic preconditioning (IPC). Decreased formation of ROS on reperfusion after prolonged ischemia may in part underlie protection by IPC. In heart models, these contentions have been based either on the effect of ROS scavengers to abrogate IPC-induced preservation or on a measurement of oxidation products on reperfusion.

Sevoflurane preconditioning before moderate hypothermic ischemia protects against cytosolic [Ca(2+)] loading and myocardial damage in part via mitochondrial K(ATP) channels.

Background: Brief sevoflurane exposure and washout (sevoflurane preconditioning [SPC]) before 30-min global ischemia at 37 degrees C is known to improve cardiac function, decrease cytosolic [Ca(2+)] loading, and reduce infarct size on reperfusion. It is not known if anesthetic preconditioning (APC) applies as well to hypothermic ischemia and reperfusion and if K(ATP) channels are involved. The authors examined in guinea pig isolated hearts the effect of sevoflurane exposure before 4-h global ischemia at 17 degrees C on cardiac function, cytosolic [Ca(2+)] loading, and infarct size.

Altered NADH and improved function by anesthetic and ischemic preconditioning in guinea pig intact hearts.

NADH increases during ischemia because O(2) shortage limits NADH oxidation at the electron transport chain. Ischemic (IPC) and anesthetic preconditioning (APC) attenuate cardiac reperfusion injury. We examined whether IPC and APC similarly alter NADH, i.

Anesthetic preconditioning: triggering role of reactive oxygen and nitrogen species in isolated hearts.

We postulated that anesthetic preconditioning (APC) is triggered by reactive oxygen/nitrogen species (ROS/RNS). We used the isolated guinea pig heart perfused with L-tyrosine, which reacts with ROS and RNS to form strong oxidants, principally peroxynitrite (ONOO(-)), and then forms fluorescent dityrosine. ROS scavengers superoxide dismutase, catalase, and glutathione (SCG) and NO.

Cardiac preconditioning with 4-h, 17 degrees C ischemia reduces [Ca(2+)](i) load and damage in part via K(ATP) channel opening.

Brief ischemia before normothermic ischemia protects hearts against reperfusion injury (ischemic preconditioning, IPC), but it is unclear whether it protects against long-term moderate hypothermic ischemia. We explored in isolated guinea pig hearts 1) the influence of two 2-min periods of normothermic ischemia before 4 h, 17 degrees C hypothermic ischemia on cardiac cytosolic [Ca(2+)], mechanical and metabolic function, and infarct size, and 2) the potential role of K(ATP) channels in eliciting cardioprotection. We found that IPC before 4 h moderate hypothermia improved myocardial perfusion, contractility, and relaxation during normothermic reperfusion.

Inhibition of Na(+)/H(+) isoform-1 exchange protects hearts perfused after 6-hour cardioplegic cold storage.

Objectives: Cardiac ischemia-reperfusion activates Na(+)/H(+) exchange; excess Na(+) and the resulting Ca(2+) overload, through reverse Na(+)/Ca(2+) exchange, cause cellular injury and cardiac dysfunction. We postulated that inhibiting the Na(+)/H(+) isoform-1 exchanger would add to the protection of hearts after long-term cold storage in acidic cardioplegic solution.

Methods: Guinea pig hearts were isolated and perfused at 37 degrees C with Krebs-Ringer's solution (KRS) and then switched to an acidic St.

Sevoflurane before or after ischemia improves contractile and metabolic function while reducing myoplasmic Ca(2+) loading in intact hearts.

Background: Ca(2+) loading occurs during myocardial reperfusion injury. Volatile anesthetics can reduce reperfusion injury. The authors tested whether sevoflurane administered before index ischemia in isolated hearts reduces myoplasmic diastolic and systolic [Ca(2+)] and improves function more so than when sevoflurane is administered on reperfusion.