Search

Torsades de pointes (TdP) ventricular tachycardia typically occurs in the setting of early afterdepolarizations; it contributes to arrhythmias and sudden death in congenital and acquired heart disease. Window L-type Ca2+ current ( ICaL) has a central role in the arrhythmogenesis and may be particularly important under β-adrenergic stimulation. We studied the properties of ICaL in myocytes from the dog with chronic atrioventricular block (cAVB) that has cardiac hypertrophy and an increased susceptibility to TdP. Peak ICaL densities at baseline (K+- and Na+-free solutions, 10 mmol l−1[EGTA]pip) in cAVB were comparable to control, but inactivation was shifted to the right, resulting in a larger window current area in cAVB. Under β-adrenergic stimulation, the window current area was increased and shifted to the left, but less so in cAVB (maximum at −27 mV, versus−32 mV in control). ICaL during a step to −35 mV showed a transient reduction immediately after the peak. Test steps to 0 mV, simultaneous recording of [Ca2+]i and manipulation of sarcoplasmic reticulum (SR) Ca2+ release showed that this resulted from inhibition and fast recovery of ICaL with SR Ca2+ release. The extent of this dynamic modulation was larger in cAVB than in control (23 ± 2% of the initially available current, versus 13 ± 3%; P < 0.05). Early afterdepolarizations (EADs) in cAVB myocytes under β-adrenergic stimulation typically occurred in the window current voltage range and after decline of [Ca2+]i. In conclusion, in cAVB, the larger window current, its rightward shift and enhanced dynamic modulation by SR Ca2+ release may contribute to an increased incidence of EADs in cAVB under β-adrenergic stimulation. [ABSTRACT FROM AUTHOR]

The article introduces a report published within the issue, by G. Thomas, M. J. Killeen, A. A. Grace, and C. L.-H. Huang, on human long QT 3 syndrome.

Neuropeptide Y (NPY), a potent vasoconstrictor released from the sympathetic nerves, has been suggested to counterbalance sepsis-induced vasodilation. Thus, the changes in plasma and tissue NPY concentrations in relation to hemodynamic variables and inflammatory markers in a porcine model of moderate septic shock were investigated. Susceptibility of NPY to be removed by continuous hemofiltration in two settings has been also studied. Thirty-four domestic pigs were divided into five groups: (i) control group; (ii) control group with conventional hemofiltration; (iii) septic group; (iv) septic group with conventional hemofiltration; and (v) septic group with high-volume hemofiltration. Sepsis induced by fecal peritonitis continued for 22 h. Hemofiltration was applied for the last 10 h. Hemodynamic and inflammatory parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor-α, interleukin-6, and NPY) were measured before and at 12 and 22 h of peritonitis. NPY tissue levels were determined in the left ventricle and mesenteric and coronary arteries. Sepsis induced long-lasting increases in the systemic NPY levels without affecting its tissue concentrations. Continuous hemofiltration at any dose did not reduce sepsis-induced elevations in NPY plasma concentrations, nor did it affect the peptide tissue levels. The increases in NPY systemic levels were significantly correlated with changes in the systemic vascular resistance. The results support the hypothesis of NPY implication in the regulation of the vascular resistance under septic conditions and indicate that NPY clearance rate during hemofiltration does not exceed the capacity of perivascular nerves to release it., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)