Abstract:
AIMS:Adequate microcirculatory perfusion, and not just opening of occluded arteries, is critical to salvage heart tissue following myocardial infarction. However, the degree of microvascular perfusion taking place is not known, limited primarily by an inability to directly image coronary microcirculation in a beating heart in vivo. Haematopoietic stem/progenitor cells (HSPCs) offer a potential therapy but little is known about their homing dynamics at a cellular level and whether they protect coronary microvessels. This study used intravital microscopy to image the anaesthetized mouse beating heart microcirculation following stabilization. METHODS AND RESULTS:A 3D-printed stabilizer was attached to the ischaemia-reperfusion injured (IRI) beating heart. The kinetics of neutrophil, platelet and HSPC recruitment, as well as functional capillary density (FCD), was imaged post-reperfusion. Laser speckle contrast imaging (LSCI) was used for the first time to monitor ventricular blood flow in beating hearts. Sustained hyperaemic responses were measured throughout reperfusion, initially indicating adequate flow resumption. Intravital microscopy confirmed large vessel perfusion but demonstrated poor transmission of flow to downstream coronary microvessels. Significant neutrophil adhesion and microthrombus formation occurred within capillaries with the latter occluding them, resulting in patchy perfusion and reduced FCD. Interestingly, 'patrolling' neutrophils were also observed in capillaries. Haematopoietic stem/progenitor cells readily trafficked through the heart but local retention was poor. Despite this, remarkable anti-thromboinflammatory effects were observed, consequently improving microvascular perfusion. CONCLUSION:We present a novel approach for imaging multiple microcirculatory perturbations in the beating heart with LSCI assessment of blood flow. Despite deceptive hyperaemic responses, increased microcirculatory flow heterogeneity was seen, with non-perfused areas interspersed with perfused areas. Microthrombi, rather than neutrophils, appeared to be the major causative factor. We further applied this technique to demonstrate local stem cell presence is not a pre-requisite to confer vasculoprotection. This is the first detailed in vivo characterization of coronary microcirculatory responses post-reperfusion injury.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Kavanagh DPJ,Lokman AB,Neag G,Colley A,Kalia Ndoi
10.1093/cvr/cvz118subject
Has Abstractpub_date
2019-11-01 00:00:00pages
1918-1932issue
13eissn
0008-6363issn
1755-3245pii
5486400journal_volume
115pub_type
杂志文章abstract::We used the phase modulated rotating frame imaging technique to measure transmural distribution of phosphorus metabolites in 10 anaesthetised ventilated pigs using a double surface coil placed on the surface of the left ventricle. Anaesthesia was maintained in five animals with halothane, barbiturate and nitrous oxide...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.12.1015
更新日期:1989-12-01 00:00:00
abstract:OBJECTIVE:The aim was to validate echocardiographic assessment of acute changes of left ventricular stroke volume in normal rats. METHODS:By transthoracic use of a 7.5 MHz ultrasonic transducer, the left ventricular dimensions were determined before and during rapid atrial pacing and saline infusion in seven Wistar ra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.8.765
更新日期:1992-08-01 00:00:00
abstract:AIMS:Our previous studies demonstrated that inflammation contributes to atherosclerosis through disruption of the low density lipoprotein receptor (LDLr) pathway. However, this effect is overridden by rapamycin, which is an inhibitor of mammalian target of rapamycin (mTOR). This study investigated the role of the mTOR ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt203
更新日期:2013-12-01 00:00:00
abstract:AIMS:It is well established that leukotrienes (LTs), products of the 5-lipoxygenase (5-LO) pathway, participate in inflammatory tissue reactions and immune responses. In the present study, the impact of the 5-LO pathway on vasculogenesis of mouse embryonic stem (ES) cells was investigated. METHODS AND RESULTS:Immunohi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp385
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that prolonged physical exercise induces long-lasting effects on blood pressure and heart rate we studied 17 endurance runners before and after the 1995 Sandia Wilderness Crossing Research Run (46 km of rocky trails, average altitude 2500 m). METHODS:We evaluated the response of the ca...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00025-4
更新日期:1997-05-01 00:00:00
abstract:OBJECTIVE:At present little is known about the factors that regulate the expression of the endothelins and their receptors in cardiac tissue in vivo. The aim of this study was to investigate changes in expression of the endothelins (ET-1, ET-2, and ET-3) and their receptors (ETAR and ETBR) in the hypertrophied heart of...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract:AIMS:Diabetes impinges upon mechanisms of cardiovascular repair. However, the biochemical adaptation of cardiac stem cells to sustained hyperglycaemia remains largely unknown. Here, we investigate the molecular targets of high glucose-induced damage in cardiac progenitor cells (CPCs) from murine and human hearts and at...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs291
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:Calcitonin gene related peptide (CGRP) is a potent vasodilator found in sensory nerve endings in coronary arteries. The effect of intravenous CGRP on myocardial ischaemia, cardiovascular haemodynamics, and epicardial coronary artery stenoses was studied in patients with angina to investigate the possible role...
journal_title:Cardiovascular research
pub_type: 临床试验,杂志文章
doi:10.1093/cvr/27.8.1477
更新日期:1993-08-01 00:00:00
abstract:OBJECTIVE:The aim of this study is to investigate the idea that altered fibroblast contractile activity is involved in the pathogenesis of hypertensive heart disease (HHD). METHODS:Cell area and contraction are quantified using the traction force microscopy technique for cardiac fibroblasts isolated from both normoten...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.09.021
更新日期:2003-12-01 00:00:00
abstract::Currently, a high carbohydrate/low fat diet is recommended for patients with hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate plays in hypertension and the development of pathological left ventricular hypertrophy (LVH) has not been well characterized. Recent st...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.11.007
更新日期:2007-01-15 00:00:00
abstract:AIMS:The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw233
更新日期:2017-01-01 00:00:00
abstract::The influence of experimental diabetes on the endothelium mediated relaxation and contractile responses of canine isolated coronary arteries was studied in arteries removed from alloxan treated diabetic (280 mmol.kg-1) and control mongrel dogs. Strips with and without endothelium were suspended in Krebs bicarbonate so...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.8.537
更新日期:1988-08-01 00:00:00
abstract:UNLABELLED:Recent investigations have established the feasibility of using exogenously delivered angiogenic growth factors to increase collateral artery development in animal models of myocardial and hindlimb ischemia. OBJECTIVE:Our aim was to evaluate the ability of a stabilized form of acidic fibroblast growth facto...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00522-4
更新日期:2003-10-01 00:00:00
abstract:AIMS:Atrial fibrillation (AF) is the most common cardiac arrhythmia, and early-onset lone AF has been linked to mutations in genes encoding ion channels. Mutations in the pore forming subunit KV4.3 leading to an increase in the transient outward potassium current (Ito) have previously been associated with the Brugada S...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt028
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVE:Dexamethasone-eluting stents are currently under evaluation to prevent post-angioplasty restenosis. The efficacy and safety of dexamethasone as an anti-restenotic agent is still unclear. We assess the effect of perivascular delivery of dexamethasone on vascular pathology in a mouse model of restenosis. METHO...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.06.015
更新日期:2005-12-01 00:00:00
abstract::The cardioprotective effects of mioflazine, a recently developed cardiovascular drug, were investigated in 41 anaesthetised open chest Beagle dogs subjected to 1 h normothermic global myocardial ischaemia. The severity of the model is evidenced by the finding that only one out of 20 control dogs could be weaned from e...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.9.528
更新日期:1984-09-01 00:00:00
abstract:OBJECTIVE:Lower limb perfusion following arterial occlusion depends on the recruitment of collateral vessels. Blood flow through these collateral vessels may be jeopardized by hypersensitivity to vasoconstriction by serotonin (5-HT), as has been reported during hyperlipidemia and diabetes. Therefore the aim of this stu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00538-2
更新日期:2002-11-01 00:00:00
abstract::Diabetic cardiomyopathy is a term used to describe cardiac muscle damage-induced heart failure. Multiple structural and biochemical reasons have been suggested to induce this disorder. The most prominent feature of the diabetic myocardium is attenuated insulin signalling that reduces survival kinases (Akt), potentiall...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvs426
更新日期:2013-03-01 00:00:00
abstract:OBJECTIVE:The alpha adrenoceptor antagonist phentolamine prevents ischaemia related arrhythmias in rat, guinea pig, and cat heart. This effect has been related to the attenuation of ischaemia induced shortening of the action potential and has been ascribed to its alpha adrenoceptor antagonist properties. The aim of thi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.6.847
更新日期:1994-06-01 00:00:00
abstract::Conventional antithrombotic treatments with antiplatelet, anticoagulant or fibrinolytic drugs are not uniformly successful and are associated with hemorrhagic side effects. Thus, new approaches to the prevention and treatment of arterial thrombosis are desirable. The gene transfer approach is particularly attractive b...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00153-3
更新日期:1997-09-01 00:00:00
abstract::Atrial fibrillation is the most common cardiac arrhythmia with an overall prevalence of almost 1%. Increasing prevalence and associated risks such as stroke and mortality have increased the need for better and more reliable therapeutic treatment. This has stimulated research to elucidate the pathophysiological mechani...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00367-4
更新日期:2001-10-01 00:00:00
abstract::An isolated working rat heart preparation was used to characterise the temperature-dependency of the anti-ischaemic properties of nifedipine. In this study hearts were subjected to pre-ischaemic infusion with the St Thomas' cardioplegic solution with or without added nifedipine (0.075 mumol X litre-1). Hearts were the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.2.95
更新日期:1985-02-01 00:00:00
abstract:AIMS:Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that cont...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt057
更新日期:2013-07-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the effect on the coronary network of the interaction between high arterial blood oxygen tension (PaO2) and stimulation by the alpha adrenergic agonist phenylephrine or by serotonin in an isolated, blood perfused rabbit heart preparation. METHODS:Fresh pig erythrocytes in Krebs-Hen...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.9.1326
更新日期:1994-09-01 00:00:00
abstract:AIM:The aim of the study was to determine the potential for K(V)1 potassium channel blockers as inhibitors of human neoinitimal hyperplasia. METHODS AND RESULTS:Blood vessels were obtained from patients or mice and studied in culture. Reverse transcriptase-polymerase chain reaction and immunocytochemistry were used to...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq305
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the influence of coronary occlusion on myocardial interstitial noradrenaline levels in the ischaemic and non-ischaemic regions, using the dialysis technique. METHODS:In nine anaesthetised cats, regional ischaemia was produced by occlusion of the left anterior descending coronary ar...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.5.817
更新日期:1993-05-01 00:00:00
abstract:OBJECTIVES:M cells have been described in many mammalian species. They are thought to be relevant for the genesis of long QT intervals, afterdepolarizations and for dispersion in action potential duration and in repolarization time. Their role in the human heart is subject to debate. METHODS:We simulated action potent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.02.016
更新日期:2004-05-01 00:00:00
abstract::The hypothesis that cardiac surgery to interrupt accessory pathways also interrupts autonomic nerves to the canine ventricle and to the atrioventricular node was tested in four groups of dogs. Group 1 (n = 6) underwent dissection of the atrioventricular fat tissue and cryolesion created by application of a cryoprobe a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.3.163
更新日期:1988-03-01 00:00:00
abstract:OBJECTIVE:Myocardial adaptation has been reported to result from mild but chronic ischaemia in the hearts of patients with coronary artery disease. The aim of this study was to test the hypothesis that the responses of the chronically hypoxic myocardium to an episode of severe ischaemia, or the effects of acute ischaem...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.3.312
更新日期:1994-03-01 00:00:00
abstract:Aims:RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvx104
更新日期:2017-08-01 00:00:00