What is the clinical evidence from this study?

Study design: Other. Population: Myocardial infarction and heart failure. Intervention: Cariporide vs. Control diet. Primary outcome: Depression of left ventricular increase in pressure over time (LV +dP/dt) in large infarcts (p=<0.01).

February 1, 2001

Na+/H+ exchange inhibition reduces hypertrophy and heart failure after myocardial infarction in rats

Q: What are the key findings of this study?

Cariporide reduced the depression of LV +dP/dt (23.1% vs 34%, P<0.01) and the increase in LV end-diastolic pressure (447% vs 1225%) in rats with large infarcts after coronary artery ligation.

Key Result

Cariporide reduced the depression of LV +dP/dt (23.1% vs 34%, P<0.01) and the increase in LV end-diastolic pressure (447% vs 1225%) in rats with large infarcts after coronary artery ligation.

Structured PICO

Does cariporide reduce hypertrophy and heart failure progression in rats after myocardial infarction?

Population

Rats subjected to coronary artery ligation followed by 13-15 weeks of cariporide or control diet.

Intervention

Cariporide (NHE-1 inhibitor) administered via diet immediately after occlusion for 13-15 weeks

Comparator

Control diet

Outcome

Hypertrophy and heart failure parameters including LV +dP/dt, LV end-diastolic pressure, LV dilation, tissue weights, and cell sizesurrogate

NHE-1 inhibition with cariporide attenuates hypertrophy and heart failure progression after myocardial infarction in a rat model.

Main Result

Absolute Event Rate: 23.1% vs 34%

p-value: p=<0.01

Abstract

We investigated the effect of sodium/hydrogen exchange inhibition (NHE-1) on hypertrophy and heart failure after coronary artery ligation (CAL) in the rat. Animals were subjected to occlusion (or sham) of the left main coronary artery and immediately administered a control diet or one consisting of the NHE-1 inhibitor cariporide for 13-15 wk. Hearts were separated by small [30% of LV) infarcts. CAL depressed change in left ventricular increase in pressure over time (LV +dP/dt) in small and large infarct groups by 18.8% (P < 0.05) and 34% (P < 0.01), respectively, whereas comparative values for the cariporide groups were 8.7% (not significant) and 23.1% (P < 0.01), respectively. LV end-diastolic pressure was increased by 1,225% in the control large infarct group but was significantly reduced to 447% with cariporide. Cariporide also significantly reduced the degree of LV dilation in animals with large infarcts. Hypertrophy, defined by tissue weights and cell size, was reduced by cariporide, and shortening of surviving myocytes was preserved. Infarct sizes were unaffected by cariporide, and the drug had no influence on either blood pressure or the depressed inotropic response of infarcted hearts to dobutamine. These results suggest an important role for NHE-1 in the progression of heart failure after myocardial infarction.

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