Key result
Administration of milrinone and ouabain increased contractility without increasing mitral regurgitation, while enalaprilat and milrinone decreased left atrial dimension in dogs.
Why the study?
Do cardiovascular drugs (enalaprilat, nitroglycerine, ouabain, milrinone) improve LV function without increasing MR in dogs with mitral regurgitation?
RCT (n=9)
Random order
Do cardiovascular drugs (enalaprilat, nitroglycerine, ouabain, milrinone) improve LV function without increasing MR in dogs with mitral regurgitation?
Positive inotropes (milrinone, ouabain) increased LV contractility without increasing mitral regurgitation in a canine model, challenging the hypothesis that strengthening LV contraction worsens MR.
May inform inotrope selection in canine MR; challenges hypothesis that increased contractility worsens regurgitation.
Background:There have been few trials in which dogs with mitral regurgitation (MR) have been treated with various cardioactive drugs to determine effects on left ventricular (LV) function. Hypothesis:Four classes of cardiovascular drugs may improve LV function in dogs with MR without increasing MR. Animals:Nine mature dogs were included in the study. Methods:MR was produced in 9 dogs. Five months later under butorphanol narcosis, parameters of LV function and left atrial dimension (LAD) were monitored by LV micromanometry and echocardiography/Doppler. Dogs were given (in random order) enalaprilat, nitroglycerine, ouabain, milrinone, and placebo. Results:Nitroglycerin produced no significant change; milrinone and ouabain increased contractility; ouabain decreased heart rate; and there was evidence that enalaprilat and milrinone decreased LAD. Milrinone and ouabain decreased isovolumetric contraction time and therefore the time available for MR. There was no evidence that a positive inotrope increased MR despite increasing LV contractility and stroke volume. Conclusion and Clinical Importance: This study contradicts the hypotheses that (1) strengthening the left ventricle may increase MR and (2) treatment of MR (even before symptoms of heart failure develop) may decrease LAD. It is reasonable that strengthening the force of LV contraction should increase the driving pressure for MR; however, this effect did not appear to increase MR. Although some investigators believe that treating dogs with MR with afterload reducers and decreasing hindrance to ejection of blood from the LV to aorta may lengthen life by decreasing MR, there did not appear to be a reduction in MR, at least in response to the angiotensin-converting enzyme (ACE) inhibitor.
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Nakayama et al. (2007) conducted an RCT in Mitral regurgitation (n=9). Enalaprilat, nitroglycerine, ouabain, and milrinone vs. Placebo was evaluated on Left ventricular function, left atrial dimension, and mitral regurgitation severity. Administration of milrinone and ouabain increased contractility without increasing mitral regurgitation, while enalaprilat and milrinone decreased left atrial dimension in dogs.
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