Effects of late, repetitive remote ischaemic conditioning on myocardial strain in patients with acute myocardial infarction.

Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain.

Functional cardiac orexin receptors: role of orexin-B/orexin 2 receptor in myocardial protection.

Orexins/hypocretins exert cardiovascular effects which are centrally mediated. In the present study, we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative reverse transcription-PCR (RT-PCR), immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors (OXR).

Daily remote ischaemic conditioning following acute myocardial infarction: a randomised controlled trial.

Background: Remote ischaemic conditioning (rIC) is a cardioprotective tool which has shown promise in preclinical and clinical trials in the context of acute ischaemia. Repeated rIC post myocardial infarction may provide additional benefits which have not previously been tested clinically.

Methods: The trial assessed the role of daily rIC in enhancing left ventricular ejection fraction (LVEF) recovery in patients with impaired LVEF (<45%) after ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (P-PCI).

Regulation of vascular function and blood pressure by circadian variation in redox signalling.

There is accumulating evidence that makes the link between the circadian variation in blood pressure and circadian variations in vascular contraction. The importance of vascular endothelium-derived redox-active and redox-derived species in the signalling pathways involved in controlling vascular smooth muscle contraction are well known, and when linked to the circadian variations in the processes involved in generating these species, suggests a cellular mechanism for the circadian variations in blood pressure that links directly to the peripheral circadian clock. Relaxation of vascular smooth muscle cells involves endothelial-derived relaxing factor (EDRF) which is nitric oxide (NO) produced by endothelial NO synthase (eNOS), and endothelial-derived hyperpolarising factor (EDHF) which includes hydrogen peroxide (HO) produced by NADPH oxidase (Nox).

Remote ischemic preconditioning of cardiomyocytes inhibits the mitochondrial permeability transition pore independently of reduced calcium-loading or sarcKATP channel activation.

Ischemic preconditioning (IPC) inhibits Ca(2+)-loading during ischemia which contributes to cardioprotection by inhibiting mechanical injury due to hypercontracture and biochemical injury through mitochondrial permeability transition (MPT) pores during reperfusion. However, whether remote-IPC reduced Ca(2+)-loading during ischemia and its subsequent involvement in inhibiting MPT pore formation during reperfusion has not been directly shown. We have developed a cellular model of remote IPC to look at the impact of remote conditioning on Ca(2+)-regulation and MPT pore opening during simulated ischemia and reperfusion, using fluorescence microscopy.

The time-of-day variation in vascular smooth muscle contractility depends on a nitric oxide signalling pathway.

The dip in blood pressure during the resting-period is paradoxically associated with an increase in total peripheral resistance and occurs at a time when the vascular response to vasoconstrictor compounds is heightened, and to vasodilators reduced. However, the cellular mechanisms responsible for this time-of-day variation are not well defined. We have investigated the role of nitric oxide synthase (NOS) signalling in the control of contraction in mesenteric resistance arteries using wire myography, combined with quantitative PCR analysis of gene transcription and western blot analysis of protein.

Diurnal variation in excitation-contraction coupling is lost in the adult spontaneously hypertensive rat heart.

Background: Excitation-contraction coupling of the normotensive rat heart exhibits a time-of-day variation in its response to isoproterenol (ISO), with a decrease during the animal's active period. Pressure-induced hypertrophy is known to adversely affect the circadian clock in the heart and this study sets out to determine whether this alters the time-of-day variation in E-C coupling.

Method And Results: Hearts from juvenile (6-8 week) and adult (24-28 week) spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were isolated during the animals active and resting periods.

Phenylephrine preconditioning involves modulation of cardiac sarcolemmal K(ATP) current by PKC delta, AMPK and p38 MAPK.

Preconditioning of hearts with the α(1)-adrenoceptor agonist phenylephrine decreases infarct size and increases the functional recovery of the heart following ischaemia-reperfusion. However, the cellular mechanisms responsible for this protection are not known. We investigated the role of protein kinase C ε and δ (PKCε and PKCδ), AMP-activated protein kinase (AMPK), p38 MAPK (p38) and sarcolemmal ATP-sensitive potassium (sarcK(ATP)) channels in phenylephrine preconditioning using isolated rat ventricular myocytes.

Inotropic response of cardiac ventricular myocytes to beta-adrenergic stimulation with isoproterenol exhibits diurnal variation: involvement of nitric oxide.

Rationale: Although >10% of cardiac gene expression displays diurnal variations, little is known of their impact on excitation-contraction coupling.

Objective: To determine whether the time of day affects excitation-contraction coupling in rat ventricles.

Methods And Results: Left ventricular myocytes were isolated from rat hearts at 2 opposing time points, corresponding to the animals resting or active periods.

Ischemic preconditioning of the whole heart confers protection on subsequently isolated ventricular myocytes.

Current cellular models of ischemic preconditioning (IPC) rely on inducing preconditioning in vitro and may not accurately represent complex pathways triggered by IPC in the intact heart. Here, we show that it is possible to precondition the intact heart and to subsequently isolate individual ventricular myocytes that retain the protection triggered by IPC. Myocytes isolated from Langendorff-perfused hearts preconditioned with three cycles of ischemia-reperfusion were exposed to metabolic inhibition and reenergization.

Role of mitochondrial re-energization and Ca2+ influx in reperfusion injury of metabolically inhibited cardiac myocytes.

Objective: We used isolated myocytes to investigate the role of mitochondrial re-energization and Ca2+ influx during reperfusion on hypercontracture, loss of Ca2+ homeostasis and contractile function.

Methods: Isolated adult rat ventricular myocytes were exposed to metabolic inhibition (NaCN and iodoacetate) and reperfusion injury was assessed from hypercontracture, loss of Ca2+ homeostasis ([Ca2+]i measured with fura-2) and failure of contraction in response to electrical stimulation. Mitochondrial membrane potential was followed using the potentiometric dye tetramethylrhodamine ethyl ester.

Diazoxide causes early activation of cardiac sarcolemmal KATP channels during metabolic inhibition by an indirect mechanism.

Objective: We have used isolated myocytes to investigate the effects of diazoxide on sarcolemmal KATP channel (sarcoKATP) activity and action potential failure during metabolic inhibition, and the role of these channels in protection of functional recovery on reperfusion.

Materials And Methods: Isolated adult rat ventricular myocytes were exposed to metabolic inhibition (NaCN and iodoacetate) and reperfusion. Functional recovery was assessed from the ability of cells to contract on electrical stimulation and to recover calcium homeostasis, measured with fura-2.