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Volume 15, Issue 9, Pages 798-804 (November 2009)


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Digitoxin Prolongs Survival of Female Rats With Heart Failure Due to Large Myocardial Infarction

Izo Helber, MD, PhD1, Alexandra A. Dos Santos, MD, PhD1, Ednei L. Antonio, MSc1, Ronald L.G. Flumignan, MD1, Danilo S. Bocalini, MSc1, Camila Piccolo1, Mihai Gheorghiade, MD, FACC2, Paulo J.F. Tucci, MD, PhD1Corresponding Author Informationemail address

Received 1 October 2008; received in revised form 23 April 2009; accepted 4 May 2009. published online 26 June 2009.

Abstract 

Background

We analyzed whether digitoxin affects the survival of rats with congestive heart failure.

Methods and Results

The influence of digitoxin (0.1 mg·100 g·day, orally) on the survival of infarcted female rats (n=170) randomized as Control Infarcted (CI, n=85) or Digitoxin (D, n=85) was evaluated for 280 days. Mean survival was 235±7 days for CI and 255±5 days for D (log-rank test: P=.0602). Digitoxin did not affect survival in rats with congestive heart failure from myocardial infarction <40% of the left ventricle, but did prolong survival in rats with infarction ≥40%. The log-rank test defined higher mortality (P=.0161) in CI >40% (56%) than in D >40% (34%), with a hazard ratio of 2.03. Pulmonary water content and papillary muscle mechanics were analyzed in CI (n=7) and D (n=14) survivors. Significant differences were observed regarding pulmonary water content (CI: 82±0.3; D: 80±0.3%; P=.0014), developed tension (CI: 2.7±0.3; D: 3.8±0.3g/mm2; P=.0286) and +dT/dt (CI: 24±3; D: 39±4mgmm2·s; P=.0109).

Conclusion

In conclusion, long-term digitoxin administration reduced cardiac impairment after myocardium infarction, attenuated myocardial dysfunction, reduced pulmonary congestion, and provided the first evidence regarding the efficiency of digitoxin in prolonging survival in experimental cardiac failure.

Key WordsPsychological, survival

1 Cardiac Physiology and Physiopathology Laboratory, Federal University of São Paulo (UNIFESP), São Paulo, Brazil

2 Northwestern University, Chicago, IL

Corresponding Author InformationReprint requests: Dr. Paulo JF Tucci, Rua Estado de Israel, 181/94, CEP: 04022-000, São Paulo, Brazil. Tel: (5511) 5572-1452.

PII: S1071-9164(09)00142-0

doi:10.1016/j.cardfail.2009.05.002


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