Cardiac electrophysiology: normal and ischemic ionic currents and the ECG.

Basic cardiac electrophysiology is foundational to understanding normal cardiac function in terms of rate and rhythm and initiation of cardiac muscle contraction. The primary clinical tool for assessing cardiac electrical events is the electrocardiogram (ECG), which provides global and regional information on rate, rhythm, and electrical conduction as well as changes in electrical activity associated with cardiac disease, particularly ischemic heart disease. This teaching review is written at a level appropriate for first- and second-year medical students. Specific concepts discussed include ion equilibrium potentials, electrochemical forces driving ion movements across membranes, the role of ion channels in determining membrane resting potentials and action potentials, and the conduction of action potentials within the heart. The electrophysiological basis for the ECG is then described, followed by discussion on how ischemia alters cellular electrophysiology and ECG recordings, with particular emphasis on changes in T waves and ST segments of the ECG.

Using thermal stress to model aspects of disease states.

Exposure to acute heat or cold stress elicits numerous physiological responses aimed at maintaining body temperatures. Interestingly, many of the physiological responses, mediated by the cardiovascular and autonomic nervous systems, resemble aspects of, or responses to, certain disease states. The purpose of this Perspective is to highlight some of these areas in order to explore how they may help us better understand the pathophysiology underlying aspects of certain disease states. The benefits of using this human thermal stress approach are that (1) no adjustments for inherent comparative differences in animals are needed, (2) non-medicated healthy humans with no underlying co-morbidities can be studied in place of complex patients, and (3) more mechanistic perturbations can be safely employed without endangering potentially vulnerable populations. Cold stress can be used to induce stable elevations in blood pressure. Cold stress may also be used to model conditions where increases in myocardial oxygen demand are not met by anticipated increases in coronary blood flow, as occurs in older adults. Lower-body negative pressure has the capacity to model aspects of shock, and the further addition of heat stress improves and expands this model because passive-heat exposure lowers systemic vascular resistance at a time when central blood volume and left-ventricular filling pressure are reduced. Heat stress can model aspects of heat syncope and orthostatic intolerance as heat stress decreases cerebral blood flow and alters the Frank-Starling mechanism resulting in larger decreases in stroke volume for a given change in left-ventricular filling pressure. Combined, thermal perturbations may provide in vivo paradigms that can be employed to gain insights into pathophysiological aspects of certain disease states.

Cardiovascular Physiology Concepts

Página criada pelo médico Richard E. Klabunde, especialista em fisiologia cardiovascular, e professor da Marian University College of Osteopathic Medicine. Tem como escopo apresentar conceitos de fisiologia cardiovascular

Oxygen modulation of superoxide radical injury in the krebs-perfused, isolated rabbit heart.

Myocardial malondialdehyde concentration (MDA) as an index of membrane lipoperoxidation was measured in previously ischemic isolated rabbit hearts reperfused with Krebs solution equilibrated with different oxygen concentrations. Hearts were subjected to a ischemic period of 30 min at 4 degrees C and then reperfused at 37 degrees C with a Krebs-Henseleit solution equilibrated with 95% oxygen (group 1), 65% oxygen (group 2), or 21% oxygen (group 3). MDA concentration in nanomoles per gram protein (mean +/- SEM) at the end of reperfusion in group 1 (n = 5) was 357 +/- 18; in group 2 (n = 5) 282 +/- 18; and in group 3 (n = 5) 246 +/- 16 (p =.0008, group 1 vs. group 3; p =.0109, group 1 vs. group 2). The results support that oxidative stress after ischemia and reperfusion is modulated by the oxygen concentration of the reperfusate in the crystalloid-perfused isolated rabbit heart such that higher oxygen concentrations are associated with greater oxidative stress.

Role of nitric oxide and reactive oxygen species in platelet-activating factor-induced microvascular leakage.

Platelet-activating factor (PAF), released during inflammatory responses, increases microvascular permeability to fluid and macromolecules. Previous studies in the hamster cheek pouch microcirculation have shown that PAF-induced increases in permeability can be diminished by pretreatment with a nitric oxide synthase inhibitor indicating that nitric oxide is required for PAF to cause leakage, although nitric oxide itself does not cause leakage. We evaluated the hypothesis that PAF stimulates the production of reactive oxygen species (ROS) that then react with nitric oxide to form a new species that signals the increase in vascular permeability. The hamster cheek pouch microcirculation was used to quantify the leakage of FITC-dextran following topical application of PAF. PAF-induced leakage was markedly inhibited (70%) by prior superfusion of the cheek pouch with superoxide dismutase and catalase. Superfusing the cheek pouch with ROS generated by xanthine oxidase and hypoxanthine produced leakage similar to that observed with PAF. Pretreating the cheek pouch with a nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine, L-NA) inhibited ROS-induced leakage by 59% and PAF-induced leakage by 64%. The effects of L-NA and superoxide dismutase plus catalase on PAF-induced leakage were not additive. Systemic administration of mercaptoethylguanidine, a peroxynitrite scavenger, inhibited PAF-induced leakage by 60%. These results suggest that PAF-induced leakage may be mediated by an interaction between ROS and NO, perhaps through the formation of peroxynitrite or one of its products.