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The relation between left ventricular function and renal excretion of sodium (Na+) was studied in rats with myocardial infarction (MI) and varying degrees of left ventricular dysfunction. Three groups of rats were defined: 1) control sustained no infarct, 2) small to moderate infarcts involved 10-40% of the left ventricular circumference, and 3) large infarcts involved greater than 40%. In conscious rats, Na+ excretion was measured after administration of saline load by gavage. Four hours after the load, rats with large MI excreted less than one half the amount of Na+ excreted by control rats, whereas rats with small to moderate MI excreted an intermediate amount. In a second group of anesthetized rats, Na+ excretion, renal hemodynamics, and ventricular performance were determined before and after acute intravenous volume expansion with a balanced salt solution. Rats with small to moderate MI demonstrated minimal impairment in ventricular pumping ability but excreted less Na+ after volume expansion than did control rats. However, rats with large MI demonstrated marked impairment in left ventricular performance and exhibited the least natriuretic response to volume loading. Glomerular filtration rate and renal plasma flow failed to increase with volume expansion in both groups of rats with MI. Thus Na+ excretion in response to acute volume loading was diminished in rats with large MI and markedly impaired cardiac performance but was also reduced in rats with small to moderate MI and minimal changes in ventricular pumping capacity.

To determine whether chronic antihypertensive therapy reduces cardiac mass and improves performance in spontaneously hypertensive rats (SHR) with marked left ventricular hypertrophy and evidence of cardiac dysfunction, 12-mo-old male and female SHR and age- and sex-matched normotensive rats (NORM) were treated for 6 mo with either tap water or tap water containing hydralazine or guanethidine. Cardiac performance was assessed by the peak stroke volume and cardiac indices attained during volume loading and by the maximum left ventricular pressure developed during an aortic occlusion. Passive diastolic pressure-volume curves were obtained in the potassium-arrested heart. Treatment prevented the progression of left ventricular hypertrophy in SHR and the marked deterioration in peak pumping ability observed in untreated male SHR and the modest impairment observed in female SHR. The peak developed pressure of both the male and female treated SHR was reduced toward that of NORM and was associated with a reduction in the left ventricular mass-to-volume ratio toward that of NORM. Thus chronic therapy with either hydralazine or guanethidine reduced cardiac mass and prevented the deterioration in cardiac pumping performance observed in SHR with sustained hypertension and marked cardiac hypertrophy.

It has been established that glucocorticoids and several nonsteroidal antiinflammatory drugs, when administered early after coronary occlusion, interfere with myocardial scar formation. To determine whether this action is associated with expansion of myocardial infarct during the first week of coronary occlusion and whether expansion affects ventricular function, the effects of indomethacin on the left ventricle in the early phase of infarction were studied. In a blinded randomized study, experimental myocardial infarction was produced in 17 open-chest dogs by ligation of the proximal left anterior descending coronary artery; the treated group (n 8) received 10 mg/kg iv indomethacin at 15 min and 3 hr after occlusion, and the control group (n 9) received saline. After 7 days, regional function expressed as percent change of area (%zXA) of the left ventricular cavity was calculated from short-axis two-dimensional echocardiograms at the level of the infarct, the animals were killed, and their hearts were examined. The ratio of infarct thickness to noninfarcted wall thickness was 1.20 + 0.08 (mean SEM) in the control group, and the ratio was lower in the indomethacin group, 0.96 + 0.04 (p < .025). An expansion index of myocardial infarction was calculated as previously described and was 1.02 0.04 in the control group vs 1.29 + 0.06 in the indomethacin group (p < .005). In eight dogs (six control and two treated) without expansion (expansion index less than 1.09), regional function expressed as %AA was 46.8 + 2.6% (SEM), and in nine dogs (six treated and three control) with expansion, %AA was significantly lower, 28.7 ± 4.0% (p < .005). In conclusion, indomethacin prevents the normal thickening of an infarct early in the healing phase; this interference with healing is associated with infarct expansion that in turn is associated with impaired regional function. Circulation 69, No. 3, 611-617, 1984. RECENTLY, it has been observed in our laboratory that treatment with indomethacin early after coronary occlusion causes marked thinning of myocardial scars when these are examined 6 weeks after experimental coronary occlusion.' Similar effects were observed when methylprednisolone was administered, and similar, although less striking, changes were induced by ibuprofen administration.3 In all of these studies, the collagen content of the thinned scars determined 6 weeks after coronary occlusion was that these antiinflammatory drugs cause early postinfarction expansion (thinning and dilatation of the necrotic zone within the first week of infarction and before fibrosis), with eventual deposition of normal collagen into a thinned infarct. The present investigation was designed to determine whether indomethacin causes early infarct thinning, whether there is a relationship between thinning and expansion, and whether the latter alters left ventricular function. MethodsExperimental preparation. Mongrel dogs of either sex with a mean weight of 14 + 5 kg (SD) were sedated with acepromazine maleate (1.0 mg/kg sc), an...

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