Electrophysiological effects of ketamine on human atrial myocytes at therapeutically relevant concentrations.

1. Ketamine is widely used for the induction of anaesthesia in high-risk patients with cardiovascular instability or severe hypovolaemia. However, the ionic mechanisms involved in the effects of ketamine at therapeutically relevant concentrations in human cardiac myocytes are unclear. The present study was designed to investigate the effects of ketamine on L-type Ca2+ (I(Ca)), transient outward K+ (I(to)), ultra-rapid delayed rectifier K+ (I(Kur)) and inward rectifier potassium (I(K1)) currents, as well as on action potentials, in human isolated atrial myocytes. 2. Atrial myocytes were isolated enzymatically from specimens of human atrial appendage obtained from patients undergoing coronary artery bypass grafting. The action potential and membrane currents were recorded in both current- and voltage-clamp modes using the patch-clamp technique. 3. Ketamine inhibited I(Ca) with an IC(50) of 1.8 micromol/L. In addition, 10 micromol/L ketamine decreased the I(Ca) peak current at +10 mV from 5.1 +/- 0.3 to 2.1 +/- 0.4 pA/pF (P < 0.01), but did not change the threshold potential, peak current potential and reverse potential. 4. Ketamine had no effect on I(to), I(Kur) or I(K1), but it reversibly shortened the duration of the action potential in human atrial myocytes. 5. In conclusion, ketamine, at a clinically relevant concentration, shortens the action potential duration of the human atrial myocytes, probably by inhibiting I(Ca).

[Effects of C-type natriuretic peptide gene transduction on neointimal hyperplasia and endothelial function after angioplasty].

OBJECTIVE: To investigate the effects of C-type natriuretic peptide (CNP) gene transduction on neointimal hyperplasia and endothelial function after angioplasty. METHODS: Eighty-four rabbits were divided into 3 equal groups, namely normal control group, alkaline phosphatase gene transduction group and CNP gene transduction group. The rabbits in the latter two groups were given high-cholesterol diet 7 d before the experiment, followed by establishment of restenosis models by injuring the iliac artery and the specified gene transfer via retroviral vectors. Those in the normal control group were fed with normal diet. Before high-cholesterol diet and killing respectively, 2 ml venous blood samples were taken for testing blood lipid and serum CNP concentration. In the two groups with gene transduction, the injured rabbit iliac arteries were harvested for ex vivo vascular ring tension test, histological and pathological examinations, as well as immunohistochemistry analysis of CNP. The lumen area, neointimal thickness, neointimal area, ratio of intimal to medial area were measured by image analysis system. RESULTS: There were no significant differences in blood lipid and serum CNP concentration between the two gene transduction groups at the same time points both before and after operation. In CNP gene transduction group, endothelium-dependent relaxation of the vascular rings was significantly improved in comparison with the other two groups (P<0.01), irrespective of L-Arg pretreatment, whereas endothelium-independent relaxation function varied little between the 3 groups (P>0.05). Poor relaxation function to Ach of the vascular rings was resulted after pretreatment with LMMA. CNP gene expression at the site of gene transfer was detected in the CNP gene transduction group and in 2 weeks after balloon injury, the neointimal thickness, neointimal area and ratio of the neointimal to tunica media area were markedly increased in the two gene transduction groups, but the measurements were significantly lower in CNP group (P<0.01). CONCLUSION: CNP gene can be successfully transferred and effectively expressed at the injured site in the blood vessels to decrease the hyperplasia and significantly improve endothelial function after angioplasty.

Ionic mechanisms of a novel neurotoxin from the sea anemone Anthopleura sp. in rat ventricular myocytes.

OBJECTIVE: To determine the ionic mechanisms of a novel neurotoxin rhk2a obtained from the sea anemone Anthopleura sp. in rat ventricular myocytes. METHODS: Whole-cell patch-clamp recording technique was used to record the sodium, calcium, and sodium-calcium exchange currents (I(Na), I(Ca, L), and I(Na-Ca), respectively) in the isolated single rat ventricular myocytes with or without rhk2a treatment. RESULTS: The current-voltage (I-V) relationship for whole-cell I(Na) in the non-treated and rhk2a-treated (at the dose of 1 micromol/L) myocytes showed no significant difference (P>0.05), but the time constants for inactivation (tau(h)) were significantly greater (P<0.05) for the treated cells over the entire course of the experiment, while the time constants for activation (tau(m)) exhibited no significant difference between the two cells. The inactivation curve of I(Na) of rhk2a-treated cells was similar to that of the non-treated cells, as with the I-V relationship for whole-cell L-type calcium current (I(Ca, L) and I(Na-Ca)). CONCLUSIONS: Delayed inactivation of Na(+) channel plays an important role in the positive inotropic effect of rhk2a, possibly resulting from the alteration in Na(+) channel kinetics induced by rhk2a. rhk2a does not directly affect I(Ca, L), or I(Na-Ca).