Severity of the cardiac impairment determines whether digitalis prolongs or reduces survival of rats with heart failure due to myocardial infarction.

BACKGROUND: The aim of the present study was to evaluate if the influence of digitalis on survival depends on the severity of cardiac dysfunction in heart failure (HF). METHODS AND RESULTS: Doppler echocardiogram (DE) parameters were analyzed in 84 Wistar control (C) and 80 Wistar rats treated with 0.1mg/100g/day of digitoxin (D) five days after coronary occlusion. The DE variables correlated with the survival of the animals were: myocardial infarction size, left chamber dimensions, fractional area change and E/A ratio. The animals were observed for up to 280 days. Mortality was worsened in rats in the D group with a myocardial infarction (MI)<37% and with better DE predictors of survival. Digitoxin was found to prolong survival in rats with an MI ≥ 37% and worse DE predictors. CONCLUSION: For the first time our study has shown experimentally that the action of digitalis glycosides can positively or negatively influence survival during treatment of HF. It prolongs survival of those in advanced state and compromises survival when there is less severity of the disease. In fact, the greater benefits occur when digitoxin was used in heightened ventricular dilatations and worse ventricular performance.

Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

BACKGROUND: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). METHODOLOGY/PRINCIPAL FINDINGS: 99mTc-labeled ASCs (1x10(6) cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. CONCLUSIONS: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

Digitoxin prolongs survival of female rats with heart failure due to large myocardial infarction.

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 >or=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/mm(2); P=.0286) and +dT/dt (CI: 24+/-3; D: 39+/-4 mg mm(2).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.

Left ventricle radio-frequency ablation in the rat: a new model of heart failure due to myocardial infarction homogeneous in size and low in mortality.

BACKGROUND: The purpose of the current study was to create a model of myocardial infarction (MI) that is homogeneous in size with a low immediate (24 hours) mortality. METHODS AND RESULTS: Male and female rats (n = 256) underwent left ventricle (LV) ablation (Ab) by a radiofrequency current (1000 kHz; 12 watts for 12 seconds) to promote a MI. A transmural MI occurred in all rats. Post-Ab complex arrhythmias were frequent (atrioventricular block, ventricular tachycardia, and fibrillation), which rapidly and spontaneously reverted to sinus rhythm. Among 66 male rats, immediate mortality occurred in 7.5%. Small MI size dispersion was characterized by smaller variability following Ab (x +/- SD: 45 +/- 8%) when compared with coronary occlusion (Oc; 40 +/- 19%). The histopathologic evaluations identified lesions similar to those which occurred following Oc, with scarring complete at 4 weeks. The hemodynamic and Doppler echocardiograms showed comparable increases in LV dimension, end-diastolic pressure, and pulmonary water content 1 and 4 weeks post-MI. Papillary muscle mechanics 6 weeks post-MI had matched inotropic and lusitropic dysfunction. CONCLUSIONS: LV Ab gave rise to a MI within a narrow size limit and with a low immediate mortality. LV Ab resulted in histopathologic evolution, ventricular dilation, and dysfunction, impairment in myocardial mechanics, and congestive outcome that reproduced a MI from Oc.