Effect of propionyl-L-carnitine on the mechanics of right and left papillary muscles from volume-overloaded rat hearts.
Propionyl-L-carnitine (PLC) was shown to improve global cardiac function in pressure overload hypertrophy by acting directly on muscle mechanics. We investigated whether PLC can effectively ameliorate papillary muscle mechanics in a volume overload (VO) model. We induced VO by constructing an aortocaval anastomosis in adult Wistar rats. Three experimental groups were studied: sham-operated controls and untreated and PLC-treated VO animals. Isometric function of right and left papillary muscle was studied 16-18 weeks later. PLC was administered in the drinking water at the dose of 180 mg/kg for the last 2 weeks before experiment. One-way analysis of variance (ANOVA) showed that in right papillary muscles from the untreated VO group the time course of the isometric contraction was significantly prolonged [time-to-peak tension (TPT, ms +/- SEM) from 126 +/- 4.9 to 156 +/- 7.1; time from peak tension to 30% relaxation (TRel) from 133 +/- 11.9 to 196 +/- 13.9; n = 11 and 8, respectively], and peak rates of contraction and relaxation normalized over developed tension were significantly decreased in comparison with sham [from (s-1 +/- SEM) 12.9 +/- 0.5 to 10.8 +/- 0.6, and from 7.2 +/- 0.6 to 5.2 +/- 0.4, respectively]. These parameters in the PLC VO group did not differ from sham (TPT, 140 +/- 5.7; TRel, 158 +/- 14.4; +dF/df/DT, 12.2 +/- 0.6; -dF/df/DT, 6.5 +/- 0.5; n = 8). Function of left papillary muscle was not modified by either VO or PLC treatment. Total carnitine levels in either ventricle free walls were unchanged by VO. PLC significantly increased total carnitine content of left ventricle free wall (from 5.4 +/- 0.28 to 7.0 +/- 0.50). The contraction changes observed in the right papillary muscle are likely to depend on the pressure overload occurring in the right chamber; moreover, they are unrelated to tissue carnitine depletion. PLC improved the altered right papillary muscle mechanics without exerting any apparent effect on the functionally normal left papillary muscle. PLC activity is independent of carnitine stores, but may presumably be ascribed to its anaplerotic properties.
Micheletti
R
R
Prassis Sigma-tau Research Institute, University of Milan, Italy.
Giacalone
G
G
Bianchi
G
G
D000714:Anastomosis, Surgical; D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014684:Venae Cavae / Q000601:surgery
D002316:Cardiotonic Agents; C003223:propionylcarnitine; D002331:Carnitine