Current Cardiology Reviews - Volume 3, Issue 4, 2007

The metabolic syndrome (MSynd) refers to a clustering of cardiovascular risk factors characterized by obesity, impaired glucose tolerance/type 2 diabetes, atherogenic dyslipidemia, and hypertension. The tendency that multiple risk factors were often present in the same individual prompted researchers to search for the underlying pathophysiology of the MSynd. In an inventory of hypotheses on causative mechanisms for the MSynd, plausible mechanisms include insulin resistance, leptin resistance, visceral obesity, beta-cell dysfunction, endothelial dysfunction, neuroendocrine origin (sympathetic overactivity and vagal impairment, reduced serotonergic responsivity, endocannabinoid system overactivity), genetic predisposition and fetal origin. The etiology of the syndrome is complex and each hypothesis may explain part of the etiological cascade. More studies are needed to elucidate relevance of and relationship between diverse hypotheses.

Sustained or recurrent tachyarrhythmias are an important cause of fetal morbidity and mortality. The most common type of fetal tachycardia is supraventricular tachycardia, followed by atrial flutter. Other tachyarrhythmias such as atrial ectopic tachycardia, junctional reciprocating tachycardia and ventricular tachycardia are rare in fetal life. Appropriate management depends on accurate diagnosis. Ultrasound is essential for a precise knowledge of the electrophysiologic mechanism underlying the arrhythmia, and to examine the hemodynamic impact of the tachycardia both before and after the antiarrhythmic therapy. The information concerning the type of fetal tachyarrhythmia is usually inferred from the fetal heart rate, and the relationship between atrial and ventricular events as demonstrated by M-mode echocardiogram and Doppler flow signals. The decision to initiate pharmacological intervention depends on several factors and must be weighed against possible maternal and fetal adverse effects of the antiarrhythmic drugs. Several options are available when facing with a fetus with a tachycardia, ranging from close observation without therapy to direct administration of antiarrhythmic drugs into the fetal circulation. Although there are many series in the medical literature reporting that fetal tachycardias can be suppressed successfully using antiarrhythmic drugs given to the mother, currently there is no global consensus concerning the precise management of these fetuses. Certainly, the ultimate decision on the management of fetal tachycardias will vary from center to center. In this paper we will analyze our experience in the diagnosis and management of fetal tachyarrhythmias together with a review of modern literature in this topic.

Experimental models for the study of an ischemia reperfusion (IR) resistant myocardium include exercise, ischemia, and pharmacologic stimuli. While research utilizing all three of these models consistently demonstrates a cardioprotected phenotype, presently only exercise represents a viable intervention for humans. Nonetheless, knowledge gleaned from ischemic preconditioning research has contributed greatly to the progress in identifying mechanisms of exercise induced cardioprotection. Similarly, ongoing pharmacologic preconditioning investigations are a direct byproduct of ischemic preconditioning research. In this review we present a critical analysis of commonalities and differences between exercise, pharmacologic, and ischemic models of myocardial preconditioning. Specifically, we identify keys points that illustrate why exercise research may be valuable for translating ischemic preconditioning research into a viable intervention against IR injury. As part of this discussion, we first provide a brief introduction of the mechanisms responsible for IR mediated injury followed by a thorough discussion of exercise induced cardioprotection against IR injury.

Exercise performance declines in heart failure (HF). Reduced blood flow to active muscle has been thought to contribute to the abnormal responses in HF. Thus it is important to understand the mechanisms that regulate the autonomic responses during exercise in normal subjects and in patients with HF. Sympathetic nervous activity (SNA) is increased with exercise in normal subjects and is increased in HF subjects at rest and in response to exercise. Heightened peripheral SNA and the resultant increased neurovascular levels of norepinephrine (NE) evoke vasoconstriction. The NE response is accentuated in HF and this results in an increase in prominent vasoconstriction. Interstitial concentrations of NE ([NE]i) provide an outstanding index of NE concentrations at the neurovascular junction. Microdialysis methods allow us to collect interstitial NE samples from resting and active muscles of healthy control rats and rats with HF induced by myocardial infarctions. The completed experiments from this laboratory have shown that NEi rises in active muscle. Several muscle metabolites can alter the interstitial concentration of NE and in turn influence blood flow. For example, elevated interstitial ATP evoked by muscle stretch is linked to the rise in [NE]i. A purinergic P2X receptor is a family of cation-permeable ligand gated ion channels that open in response to extracellular ATP. The elevated NE induced by muscle stimulation is attenuated by a P2X receptor blocker, and is augmented by a nucleotidase inhibitor. This suggests a mechanism by which NEi is increased via P2X receptors on the sympathetic nerve terminals. K+ is also a stimulant of NE exocytosis from the sympathetic nerve. Interstitial K+ concentration increases with muscle contraction and K+ infused into the arterial blood supply of the hindlimb muscle increases [NE]i. In HF, an increase in the concentration of interstitial K+ is augmented. In addition, we have also examined NE response to sympathetic nerve stimulation and activity of NE uptake 1, a pathway by which NE is reabsorpted by presynaptic sympathetic nerves. Given level of sympathetic nerve stimulation leads to a greater NEi response in HF as compared with healthy control. This effect is due, in part, to reduced NE uptake 1 in HF. Our experimental results suggest that 1) ATP and P2X receptors; 2) muscle metabolite K+; and 3) the SNA and NE uptake 1 pathway play an important role in regulating neurovascular NE levels in HF.

The purpose of this review is to offer a concise discussion of existing data describing changes in the physical properties of the myocardium in response to ischemia. We argue that these measurable changes may be used as a basis for the development of newer diagnostic methods. Because of the challenges involved in the timely and accurate diagnosis of ischemia, newer methods-or those that will complement existing methods-are needed. Altered physical property surveillance encompasses concepts and theories that may be utilized for developing methods for detecting ischemia by sensing the resultant changes in the physical properties of the myocardium.

Stem cells have recently gained attention within Cardiology for their therapeutical application as a treatment in acute myocardial infarction and heart failure. Especially for larger infarct areas, direct myocardial application of bonemarrow derived progenitor cells or the subcutaneous treatment with colony-stimulating factors seems to lead to a small, but noticeable improvement of left ventricular performance. Given this current example of wider therapeutic use of stem cells and progenitor cells it seems warranted to take a closer look at the safety profile of this novel approach. Proarrhythmic properties of embryonic stem cells have already been reported several years ago, yet evidence is lacking that these experimental features are of relevance for daily clinical use of adult stem cells. This review will focus on the available data regarding the proarrhythmic potential of stem cell application based on the available experimental and clinical electrophysiologic data.

Angiotensin II is the main effector molecule of the renin-angiotensin system and has been implicated in regulating cell growth, inflammation and fibrosis, contributing to cardiac remodeling, growth and apoptosis. Cardiac remodeling is the determinant in the progression of heart failure. Thus, chronic activation of the renin-angiotensin system plays an important role in the structural and functional pathogeneses of heart failure. To date, most of the known physiological effects of Ang II in adult tissues are attributable to the AT1R although recent progress has shown some important actions of the involvement of AT2R. Clinical trials have documented consistent mortality and morbidity benefits of angiotensin receptor blockers in patients with chronic heart failure. Recent experimental studies link the beneficial effects of inhibiting Ang II to transforming growth factor-β1. Extracellular matrix accumulation in cardiovascular system is involved in vascular and cardiac hypertrophy and heart failure. Therefore, Ang II and TGF-β1 cross talk provides the pathophysiological insight in the development of cardiac fibrosis and heart failure. These molecular interactions might provide the beneficial effects of chronic AT1 receptor blockade, a known antifibrotic strategy, in patient with heart failure.