Ischemic cardiomyopathy and cerebral infarction in a young patient associated with khat chewing.

Khat is a stimulating agent used by many people in the Horn of Africa and the Arabian peninsula. Khat chewing is a known cardiovascular risk factor and is thought to cause vasoconstriction, systemic hypertension, and thrombogenicity. A 33-year-old Somalian man initially presented with loss of neurological function of the left arm, hazy vision, and headache. He smokes tobacco and chews two bundles of khat a week for more than 10 years. His ECG on admission showed a Q wave in V1 and V2 and 2 mm ST-elevations in V1, V2, and V3 and a terminal negative T wave in I, aVL, V2, V3, and V4, consistent with a recent, evolving anterior infarction. A noncontrast enhanced CT of the brain showed ischemia in the right middle cerebral artery vascular territory. An MRI showed recent ischemia in the vascular territory of the posterior division of the right middle cerebral artery. Coronary angiography showed a 70% stenosis with haziness of the proximal left anterior descending artery. Diagnostic tests and imaging are consistent with recent myocardial infarction in the LAD vascular territory because of coronary spasm and cerebral infarction in the middle cerebral artery vascular territory probably related to khat chewing.

Right-to-left atrial shunting with normal intracardiac pressures following cardiac surgery: pathophysiology and management.

We present a case of acute respiratory insufficiency with right-to-left atrial shunting under normal intracardiac pressures discovered several days after aortic surgery for aortic dissection. We discuss the possible mechanisms and management of right-to-left atrial shunting through an atrial septum defect with normal intracardiac pressures following cardiac surgery.

Cell transplantation for cardiac regeneration: where do we stand?

During the last decade transplantation of cells into the heart has emerged as a novel therapy for the prevention and treatment of heart failure. Although various cell types have been used, most experience has been obtained with the progenitor cells of skeletal muscle, also called myoblasts, and a wide array of bone marrow-derived cell types. The first preclinical studies demonstrated an improvement in global and regional heart function that was attributed mainly to a direct contractile effect of the transplanted cells. Furthermore, it was suggested that multiple cell types are able to form true cardiomyocytes and truly 'regenerate' the myocardium. More recent studies have questioned these early findings. Other mechanisms such as paracrine effects on the infarct and remote myocardium, a reduction in adverse remodelling and improvement of mechanical properties of the infarct tissue likely play a more important role. On the basis of encouraging preclinical studies, multiple early-phase clinical trials and several randomised controlled trials have been conducted that have demonstrated the feasibility, safety and potential efficacy of this novel therapy in humans. This review summarises the available evidence on cardiac cell transplantation and provides an outlook on future preclinical and clinical research that has to fill in the remaining gaps. (Neth Heart J 2008;16:88-95.).

Reduction in infarct size, but no functional improvement after bone marrow cell administration in a porcine model of reperfused myocardial infarction.

AIMS: Stem cell therapy after myocardial infarction (MI) has been studied in models of permanent coronary occlusion. We studied the effect of intracoronary administration of unselected bone marrow (BM) and mononuclear cells (MNC) in a porcine model of reperfused MI. METHODS AND RESULTS: In 34 swine, the left circumflex coronary artery was balloon-occluded for 2 h followed by reperfusion. Ten swine without MI served as controls. All swine underwent magnetic resonance imaging (MRI) 1 week post-MI. The next day, 10 of the 30 surviving MI swine received BM, 10 other MI swine received MNC, and the remaining MI swine received medium intracoronary. Four weeks later, all swine underwent a follow-up MRI. One week after MI, end-diastolic volume (92+/-16 mL) and left ventricular (LV) weight (78+/-12 g) were greater, whereas ejection fraction (40+/-8%) was lower than in controls (69+/-11 mL, 62+/-13 g, and 53+/-6%). Injection of BM or MNC had no effect on the MI-induced changes in global or regional LV-function. However, there was a significant reduction in infarct size 4 weeks after MNC injection (-6+/-3%) compared with the medium (-3+/-5%). CONCLUSION: Intracoronary injection of BM or MNC in swine does not improve regional or global LV-function 4 weeks after injection. However, a reduction in infarct-size was noted after MNC injection.

In vitro imaging of single living human umbilical vein endothelial cells with a clinical 3.0-T MRI scanner.

Iron oxide-labelled, single, living human umbilical vein endothelial cells (HUVECs) were imaged over time in vitro using a clinical 3.0-T magnetic resonance (MR) microscopy system. Labelling efficiency, toxicity, cell viability, proliferation and differentiation were assessed using flow cytometry, magnetic cell sorting and a phenanthroline assay. MR images were compared with normal light and fluorescence microscopy. Efficient uptake of iron oxide into HUVECs was shown, although with higher label uptake dose-dependent cytotoxic effects were observed, affecting cell viability. For MR imaging, a T2* weighted three-dimensional protocol was used with in-plane resolution of 39 x 48 microm2 and 100-microm slices with a scan time of 13 min. MRI could detect living cells in standard culture dishes at single-cell resolution, although label loss was observed that corresponded with the intracellular iron measurements. MR microscopy using iron oxide labels is a promising tool for studying HUVEC migration and cell biology in vitro and in vivo, but possible toxic effects of label uptake and loss of label over time should be taken into account.

High-resolution magnetic resonance imaging of iron-labeled myoblasts using a standard 1.5-T clinical scanner.

Myoblast transplantation is a promising means of restoring cardiac function in infarcted areas. For optimization of transplant protocols, tracking the location and fate of the injected cells is necessary. An attractive imaging modality for this is magnetic resonance imaging (MRI) as it is noninvasive and as iron-labeled myoblasts provide a signal attenuation in T2*-weighted protocols. The aim of this study was to develop an efficient iron-labeling protocol for myoblasts and to visualize single-labeled cells using a clinical 1.5-T scanner. Pig myoblasts were labeled with a superparamagnetic iron oxide (SPIO) agent using a liposome transfection agent. Labeling efficiency, toxicity, cell viability, and proliferative capacity were measured for 10 days. Magnetic resonance (MR) of myoblast cultures used a T2*-weighted three-dimensional protocol with a maximum in-plane resolution of 19.5 x 26.0 microm2 and 50 microm slices. Use of liposomes improved SPIO labeling efficiency. Labeling did not induce toxicity or affect cell viability or proliferation. The cell distribution as observed with light and fluorescence microscopy matched the signal voids observed in the MRI datasets. Liposomes promote fast, nontoxic and efficient SPIO labeling of myoblasts that can be tracked by MRI microscopy in clinical scanners using susceptibility-weighted protocols.

Cardiac transplantation of skeletal myoblasts for heart failure.

Heart failure has become the most prevalent cardiovascular syndrome, and its incidence continues to increase. Most cases of heart failure develop as a result of myocardial infarction. Although current treatment modalities have brought us the opportunity to reduce mortality and morbidity after myocardial infarction, our progress has plateaued due to our inability to treat the underlying problem, death of cardiomyocytes. Recently, a new option has emerged. Transplantation of undifferentiated cells into the damaged heart is a promising new treatment modality. These cells may have the capability of adapting to the cardiac environment, regenerating the damaged muscle, restoring cardiac function and preventing transition to heart failure. During the last few years many cell types have been proposed for cardiac repair and promising pre-clinical studies have moved some of these into the clinic. The most widely studied cell type is the progenitor cell of adult muscle, or the myoblast. When transplanted into the heart myoblasts are able to engraft and to a large degree regenerate the infarcted area. Although the feasibility of myoblast transplantation has been proven in animal models of infarction, many questions remain unanswered. In this review we will try to present an overview of where intracardiac myoblast transplantation stands and where it is heading. We also provide our insight into the future potential for myoblast transplantation clinically.

Dinitrophenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection.

BACKGROUND: Recent studies have postulated that mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel activation may modulate mitochondrial function with the resultant induction of a preconditioning phenotype in the heart. We hypothesized that the modulation of mitochondrial homeostasis might confer preconditioning-like cardioprotection. METHODS: We used a model of regional ischemia in Langendorff-perfused isolated rat hearts. Short-term administration of 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation and cyclosporin A (CSA), an inhibitor of mitochondrial respiration, was used in an attempt to elicit preconditioning-like cardioprotection. The anti-ischemic drug trimetazidine, known to attenuate CSA-induced disruption in mitochondrial function, and the mitoK(ATP) channel blocker 5-hydroxydecanoic acid (5-HD) were used to inhibit the effects of DNP and CSA. Finally, we studied the effect of trimetazidine on adenosine-induced and ischemic preconditioning. Risk zone and infarct size were measured and expressed as a percentage of the risk zone (I/R ratio). RESULTS: DNP, CSA and adenosine pretreatment reduced infarct size (I/R ratio: DNP 9.0+/-2.4%, CSA 12.5+/-1.4%, adenosine 11.9+/-3.6%, all P<0.001 vs. control, 30.2+/-1.3%) similarly to ischemic preconditioning (9.5+/-0.6%, P<0.001 vs. control). Trimetazidine limited the effect of ischemic preconditioning (22.2+/-2.0%, P<0.001 vs. ischemic preconditioning) and completely reversed the DNP, CSA, and the adenosine-mediated reduction in infarct size. 5-HD abolished the effect of ischemic preconditioning and CSA. CONCLUSION: DNP and CSA trigger preconditioning-like cardioprotection in the isolated rat heart. Trimetazidine, a known mitochondrial 'protector', attenuated both drug-induced and ischemic preconditioning. These data support the hypothesis that modulation of mitochondrial homeostasis may be a common downstream cellular event linking different triggers of preconditioning.