Prediction of prognosis in the UM-X7.1 hamster model of congestive heart failure using the Tei index.

BACKGROUND: Cardiac function is difficult to evaluate in small animal models of heart disease. The Doppler Tei index is a simple and non-invasive measure that can express global cardiac function even in small animal models of congestive heart failure. However, its ability to predict prognosis has not been evaluated. METHODS AND RESULTS: We tested the hypothesis that cardiac functional indices, such as the Tei index, can predict the prognosis of hamsters with cardiac dysfunction. The Tei index, defined as the sum of the isovolume contraction and relaxation time divided by ejection time, and the percent fractional shortening of the left ventricle was measured in 48 anesthetized male hamsters (19.7+/-0.4 weeks old) with cardiac dysfunction (UM-X7.1), using Doppler and 2-dimensional echocardiography. The hamsters were separated into 2 groups based on the median Tei index (0.50) and % fractional shortening (FS) (21%). Kaplan-Meier analysis determined the survival rates of the groups. Both the Tei index and %FS enabled significant distinction of better and poorer survival (p < 0.01), and the survival curves were less overlapped when the animals were separated according to the Tei index. CONCLUSION: The Tei index can predict prognosis in a small animal model of heart failure.

Repeated sauna therapy increases arterial endothelial nitric oxide synthase expression and nitric oxide production in cardiomyopathic hamsters.

BACKGROUND: Vascular endothelial dysfunction is involved in the pathophysiology of chronic heart failure (CHF). It has been reported that sauna therapy, which allows thermal vasodilation, improves vascular endothelial dysfunction in patients with CHF. The present study investigates the mechanisms through which sauna therapy improves endothelial dysfunction induced by CHF. METHODS AND RESULTS: Normal control and male TO-2 cardiomyopathic hamsters were used. Thirty-week-old TO-2 hamsters were treated daily with an experimental far infrared-ray dry sauna system for 15 min at 39 degrees C followed by 20 min at 30 degrees C. This procedure raised the rectal temperatures by about 1 degrees C. Arterial endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein expressions were examined, and serum concentrations of nitrate were measured. The expression of eNOS mRNA in the aortas of normal controls did not change, whereas those of the TO-2 hamsters decreased with age. Four weeks of sauna therapy significantly increased eNOS mRNA expression in the aortas of TO-2 hamsters compared with those that did not undergo sauna therapy. Sauna therapy also upregulated aortic eNOS protein expression. Serum nitrate concentrations of the TO-2 hamsters were increased by 4 weeks of sauna therapy compared with those that did not undergo sauna. CONCLUSION: Repeated sauna therapy increases eNOS expression and NO production in cardiomyopathic hamsters with heart failure.

Dystrophin upregulation in pressure-overloaded cardiac hypertrophy in rats.

Dystrophin is a cytoskeletal protein localized to the sarcolemma of skeletal and cardiac muscle, and neurons. We have recently demonstrated that a significant cardiac damage including myocytes injury, inflammation, and fibrosis, was found in dystrophin-deficient myocardium during pressure overload [Kamogawa et al., 2001: Cardiovasc Res 50:509-515]. However, little is known about how the cardiac sarcolemmal cytoskeleton produces qualitative and quantitative changes in response to pressure overload. Accordingly, we investigated dystrophin gene expression and protein accumulation during cardiac hypertrophy. Cardiac hypertrophy was produced by banding of the abdominal aorta of rats. Total RNA from the left ventricle of the heart was used for a quantitative reverse transcription-polymerase chain reaction (RT-PCR). Dystrophin mRNA expression significantly increased by 33 +/- 18% at 1 day (P < 0.05) and 45 +/- 19% at 2 days (P < 0.01) after banding, while G3PDH mRNA showed no significant change. RT-PCR for dystrophin tissue-specific exon 1 revealed that only muscle type promoter, but not non-muscle type promoter (brain and Purkinje-cell type), was activated immediately after banding. Immunohistochemistry for dystrophin showed intense cellular membrane staining with an increase in the perimeter of the myocytes by 14% at 3 days (46.3 microm, P < 0.01) and 19% at 7 days (51.2 microm, P < 0.01) after banding. Western blotting also showed dystrophin protein increased by 14 +/- 6% at 2 days (P < 0.05) and by 32 +/- 10% at 3 days (P < 0.01) after aortic banding. In conclusion, upregulation of dystrophin mRNA expression and protein accumulation occurs in response to cardiac hypertrophy. These data and the vulnerability of dystrophin-deficient myocardium to pressure overload suggest that dystrophin could play an important role in maintaining the integrity of the sarcolemma.