Ischemic preconditioning does not acutely improve load-insensitive parameters of contractility in in vivo stunned porcine myocardium

AbstractObjective: Ischemic preconditioning has been shown to have no beneficial effect on segment shortening in in vivo regionally stunned myocardium. The purpose of this study was to determine whether ischemic preconditioning improves the recovery of postischemic ventricular function when contractility is assessed by load-insensitive measurements including end-systolic pressure length relations, preload recruitable stroke work, and preload recruitable stroke work area in in vivo regionally stunned porcine myocardium. Methods: Open chest, pentobarbital-anesthetized pigs were used. Regional ventricular function was monitored by measurements of segment shortening, stroke work, end systolic pressure length relations, preload recruitable stroke work, and preload recruitable stroke work area. The control group was submitted to 15 minutes of left anterior descending coronary artery occlusion and 3 hours of reperfusion. The preconditioned group underwent 2 cycles of 5-minute left anterior descending coronary artery occlusion and 10-minute reperfusion before 15 minutes of occlusion. Results: There was no infarct in either group. The preconditioning protocol significantly depressed preischemic segment shortening but not regional stroke work. Ischemic preconditioning had no significant beneficial effect on regional stroke work, end-systolic pressure length relations, preload recruitable stroke work, or preload recruitable stroke work area. Conclusions: These results confirm that ischemic preconditioning does not ameliorate in vivo porcine myocardial stunning and indicate that ischemic preconditioning may have a limited cardioprotective role during cardiac operation. (J Thorac Cardiovasc Surg 1999;117:810-7

Differential cardiovascular regulatory activities of the alpha1B- and alpha1D-adrenoceptor

ABSTRACT The regulation of cardiac and vascular function by th

What do contrast threshold equivalent noise studies actually measure? Noise vs. nonlinearity in different masking paradigms

The internal noise present in a linear system can be quantified by the equivalent noise method. By measuring the effect that applying external noise to the system’s input has on its output one can estimate the variance of this internal noise. By applying this simple “linear amplifier” model to the human visual system, one can entirely explain an observer’s detection performance by a combination of the internal noise variance and their efficiency relative to an ideal observer. Studies using this method rely on two crucial factors: firstly that the external noise in their stimuli behaves like the visual system’s internal noise in the dimension of interest, and secondly that the assumptions underlying their model are correct (e.g. linearity). Here we explore the effects of these two factors while applying the equivalent noise method to investigate the contrast sensitivity function (CSF). We compare the results at 0.5 and 6 c/deg from the equivalent noise method against those we would expect based on pedestal masking data collected from the same observers. We find that the loss of sensitivity with increasing spatial frequency results from changes in the saturation constant of the gain control nonlinearity, and that this only masquerades as a change in internal noise under the equivalent noise method. Part of the effect we find can be attributed to the optical transfer function of the eye. The remainder can be explained by either changes in effective input gain, divisive suppression, or a combination of the two. Given these effects the efficiency of our observers approaches the ideal level. We show the importance of considering these factors in equivalent noise studies

Adenosine Receptor-Mediated Cardioprotection—Current Limitations and Future Directions

Since the seminal reports of adenosine receptor-mediated cardioprotection in the early 1990s, there have been a multitude of such reports in various species and preparations. Original observations of the beneficial effects of A1 receptor agonists have been followed up with numerous reports also implicating A2A, A3, and most recently A2B, receptor agonists as cardioprotective agents. Although adenosine has been approved for clinical use in the United States for the treatment of supraventricular tachycardia and coronary artery imaging, and the selective A2A agonist, regadenoson, for the latter, clinical use of adenosine receptor agonists for protecting the ischemic heart has not advanced beyond early trials. An examination of the literature indicates that existing experimental studies have several limitations in terms of clinical relevance, as well as lacking incorporation of recent new insights into adenosine receptor signaling. Such deficiencies include the lack of experimental studies in models that most closely mimic human cardiovascular disease. In addition, there have been very few studies in chronic models of myocardial ischemia, where limiting myocardial remodeling and heart failure, not reduction of infarct size, are the primary endpoints. Despite an increasing number of reports of the beneficial effects of adenosine receptor antagonists, not agonists, in chronic diseases, this idea has not been well-studied in experimental myocardial ischemia. There have also been few studies examining adenosine receptor subtype interactions as well as receptor heterodimerization. The purpose of this Perspective article is to discuss these deficiencies to highlight future directions of research in the field of adenosine receptor-mediated protection of ischemic myocardium

Adenosine receptors and membrane microdomains

AbstractAdenosine receptors are a member of the large family of seven transmembrane spanning G protein coupled receptors. The four adenosine receptor subtypes—A1, A2a, A2b, A3—exert their effects via the activation of one or more heterotrimeric G proteins resulting in the modulation of intracellular signaling. Numerous studies over the past decade have documented the complexity of G protein coupled receptor signaling at the level of protein–protein interactions as well as through signaling cross talk. With respect to adenosine receptors, the activation of one receptor subtype can have profound direct effects in one cell type but little or no effect in other cells. There is significant evidence that the compartmentation of subcellular signaling plays a physiological role in the fidelity of G protein coupled receptor signaling. This compartmentation is evident at the level of the plasma membrane in the form of membrane microdomains such as caveolae and lipid rafts. This review will summarize and critically assess our current understanding of the role of membrane microdomains in regulating adenosine receptor signaling. This article is part of a Special Issue entitled: “Adenosine Receptors”