Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria.

OBJECTIVES: To elucidate the structural basis for the electrophysiologic remodeling induced by chronic atrial fibrillation (AF), we investigated connexin40 and connexin43 (Cx40 and Cx43) expression and distribution in atria of patients with and without chronic AF and in an animal model of AF with additional electrophysiologic investigation of anisotropy (ratio of longitudinal and transverse velocities). BACKGROUND: Atrial fibrillation is a common arrhythmia that has a tendency to become persistent. Since gap junctions provide the syncytial properties of the atrium, changes in expression and distribution of intercellular connections may accompany the chronification of AF. METHODS: Atrial tissues isolated from 12 patients in normal sinus rhythm at the time of cardiac surgery and from 12 patients with chronic AF were processed for immunohistology and immunoblotting for the detection of the gap junction proteins. The functional study of the cardiac tissue anisotropy was performed in rat atria in which AF was induced by 24 h of rapid pacing (10 Hz). RESULTS: Immunoblotting revealed that AF did not induce any significant change in Cx43 content in human atria. In contrast, a 2.7-fold increase in expression of Cx40 was observed in AF. Immunohistologic analysis indicated that AF resulted in an increase in the immunostaining of both connexins at the lateral membrane of human atrial cells. A similar spatial redistribution of the Cx43 signal was seen in isolated rat atria with experimentally-induced AF. In addition, AF in rat atria resulted in decreased anisotropy with slightly enhanced transverse conduction velocity. CONCLUSIONS: This experimental study showed that AF is accompanied by spatial remodeling of gap junctions that might induce changes in the biophysical properties of the tissue.

Therapeutic in vivo and in vitro effects of argon dye laser and hematoporphyrin derivative in lung cancer.

In clinical and experimental study the therapeutic efficacy of argon dye laser irradiation with hematoporphyrin derivative (HpD) was evaluated in lung cancer. A total of 14 lung cancer cases including 12 squamous cell, 1 adeno- and 1 small cell carcinomas were irradiated superficially 48 hours or more after i.v. injection of 3 mg/kg of HpD (100-300 mW, 20-30 min.). Human adenocarcinoma cells implanted subcutaneously into nude mice were photoirradiated (200 mW, 20 min.) 48 h after i.p. injection of HpD. The in vitro effect of phototherapy was studied in the same cell line after incubation in medium containing HpD compared to untreated, only irradiated or only in HpD incubated cells. Among 3 early stage squamous cell carcinoma cases 2 complete and 1 partial remissions were obtained. Among 11 cases including 10 with advanced and 1 with recurrent disease 7 demonstrated partial remission. In vivo, two of 9 mice had a complete tumor remission. In the in vitro study, tumor cells incubated in 30 micrograms HpD/ml showed severe cytotoxic effects resulting in cell death 12 hours after photo irradiation, whereas cells incubated in 30 micrograms HpD/ml only regenerated after initial cytotoxic reaction. Laser irradiation only had no effects. HpD phototherapy demonstrated a considerable antitumor efficacy and must be considered as one of the promising endoscopic treatments in cases with early stage primary lung cancer.