Search

1. The aim of the present investigation was to contrast the Ca[SUP2+] dependence of cardiac energy metabolism in two species with differential reliance on extracellular Ca[SUP2+] for excitation-contraction coupling. 2. We measured energy expenditure as the rate of oxygen consumption (&Vdot;O[SUB2]) of isolated, Langendorff-perfused hearts of rats and guinea-pigs during KCl arrest. In parallel experiments, we indexed intracellular Ca[SUP2+] concentration ([Ca[SUP2+][SUBi]) of isolated right-ventricular trabeculae, using the Ca[SUP2+] fluoro-phore fura-2 and ratiometric spectrofluorometry. By varying extracellular Na[SUP+] concentration ([Na[SUP+][SUBo]), &Vdot;O[SUB2]-[Na[SUP+])[SUBo] and [Ca[SUP2+][SUBi]-[Na[SUP+])[SUBo] relationships were constructed for each species. 3. Reduction of [Na[SUP+])[SUBo] during K[SUP+] arrest caused pronounced species-dependent elevations of both &Vdot;O[SUB2] and [Ca[SUB2+])[SUBi]. Despite the species dependence of both &Vdot;O[SUB2] and [Ca[SUP2+])[SUBi] on [Na[SUP+])[SUBo], a single species-independent &Vdot;O[SUB2]-[Ca[SUB2+])[SUBi] relationship obtained. 4. We infer that elevation of the metabolic rate of the arrested heart above its basal value is determined primarily by [Ca[SUP2+])[SUBi] and is not species dependent. [ABSTRACT FROM AUTHOR]

Objectives: (i) to characterize the electrophysiological properties of the slowly activating delayed rectifier potassium current, iKs, defined as the 293b-sensitive current, during the action potential (AP) of rabbit sino-atrial node (SAN) pacemaker cells; (ii) to evaluate the contribution of iKs to the pacemaker AP under physiological conditions and during β-adrenergic stimulation. Methods: Rabbit SAN pacemaker cells were studied using the perforated patch clamp technique in voltage–, AP– and current–clamp modes. Results: Voltage–clamp findings. Block of iKs by 293b is dose-dependent, with an IC50 (half block) in rabbit SAN cells of 1.35 μM and an IC80 (sub-maximal block) of 5 μM. Sub-maximal concentrations of 293b have no significant effects on long-lasting and transient inward calcium currents, iCa,L and iCa,T, inward hyperpolarization activated current, if, and transient outward current, ito. AP–clamp experiments. The 293b-sensitive current activates near the peak of the SAN pacemaker action potential, reaches a mean maximal current density of 1.0±0.3 pA/pF (n=8, cell capacitances 27 to 62 pF, mean 35±4.0 pF) during late repolarization, and inactivates towards the end of repolarization. Additionally, in two smaller cells (cell capacitances 15 and 23 pF), no discernible 293b-sensitive current component was detected. Current–clamp data. In spontaneously beating SAN cells under control conditions, sub-maximal block of iKs by 5 μM 293b has negligible effects on action potential characteristics and does not change average cycle length (n=11). In contrast, after pre-treatment with 10 nM isoprenaline to mimic β-adrenergic stimulation, cells showed a 293b-induced depolarization of maximum diastolic potential by 2.2±1%, a decrease in diastolic depolarization rate by 9.9±4%, and a slowing of late action potential repolarization by 28.7±10.2%, resulting in a prolongation of spontaneous cycle length by 9.8±3.0% (P<0.05, n=10; for all parameters). Conclusion: Our findings suggest that in rabbit SAN: (i) iKs is activated during the normal pacemaker AP; (ii) the contribution of iKs to beating rate is small under control conditions; and (iii) iKs contributes significantly to spontaneous pacemaker rate during β-adrenergic stimulation. [ABSTRACT FROM PUBLISHER]

Moderate pre-cordial mechanical impact can cause sudden cardiac death, even in the absence of morphological damage to the heart. This is the most severe expression of a condition termed, in the 19th century, Commotio cordis. Experimental studies performed in the early 1930s showed that sudden cardiac death after chest impact is brought about by an intrinsic cardiac response to the mechanical stimulus. The precise (sub-)cellular mechanisms of this response are still poorly understood. This article summarises experimental findings on the condition and relates them to the more recently established concept of cardiac mechano—electric feedback. As a result, an explanation of the mechanisms that give rise to sudden cardiac death by Commotio cordis and targets for further research are suggested. [ABSTRACT FROM PUBLISHER]

Objective: The aim was to determine the metabolic consequence of increasing the osmolality of a crystalloid cardioplegic solution during periods of cardiac arrest. Methods: Isolated hearts of guinea pig and rat were Langdendorff perfused with Krebs-Henseleit solution at 37°C and arrested by an increase in KCl. The rate of oxygen consumption was measured under standard isosmotic conditions and with the osmolality of the perfusate increased by addition of sucrose. Results: Increased osmolality stimulated the rate of myocardial oxygen consumption in a dose dependent manner. At optimal dose (about twice normal osmolality), the oxygen consumption of the arrested heart approximated that of the beating, non-working heart measured prior to arrest. Potentiation of cardiac resting metabolism was greater in the rat than in the guinea pig, whether expressed in absolute terms or relative to the metabolism of the beating heart. Metabolic potentiation was accompanied by an increase of passive or diastolic left ventricular pressure in the rat but not in the guinea pig. The metabolic response was unaffected by coronary vasodilatation (adenosine) and by inhibition of Ca2+ channels (verapamil); it was moderately diminished by perfusion with Ca2+-free solution. Procaine inhibited the hyperosmotic potentiation of oxygen consumption in a dose dependent manner. Conclusions: From the absence of passive force development in the guinea pig heart, it appears that the hyperosmotic stimulation of cardiac resting metabolism primarily reflects increased activity of the sarcoplasmic reticular Ca2+-ATPase subsequent to release of Ca2+ through a procaine inhibitable channel. Blunting of both the metabolic and mechanical responses in the guinea pig vis-a-vis the rat heart is attributed to the greater capability of the former to buffer myoplasmic Ca2+via the energetically neutral Na+-Ca2+ exchange mechanism.Cardiovascular Research 1994;28:485-493 [ABSTRACT FROM PUBLISHER]