Left Ventricular Myocardial Edema: Lymph Flow, Interstitial Fibrosis, and Cardiac Function

We hypothesized that both acute and chronic accumulation of myocardial interstitial edema (extravascular fluid [EVF]) would compromise cardiac function. We also postulated that excess fluid within the myocardial interstitial space would potentiate interstitial fibrosis, thus further compromising function. Dogs were divided into three groups1) control, 2) chronic pulmonary hypertensive with right heart failure, and 3) chronic arterial hypertensive. The quantity of EVF, expressed as the unitless blood-free (wet weight-dry weight)/dry weight ratio, and interstitial fibrosis (collagen content) were determined and correlated with cardiac function at baseline and after acute elevation of coronary venous pressure and reduction of cardiac lymph flow. Control EVF was 2.90±0.20 (mean±SD), which increased to 3.45±0.16 after acute (3-hour) elevation of coronary sinus pressure. This EVF significantly compromised cardiac function. The EVF in chronically hypertensive dogs and in dogs with chronic right heart pressure elevations was 3.50±0.30 and 3.50±0.08, respectively. End-diastolic left ventricular interstitial fluid pressure increased from a control value of 14.9±3.1 (at EVF=2.9) to 24.8±3.7 (at EVF=3.5). An EVF of 3.5 produced ∼30% reduction of the heartʼs ability to maintain cardiac output at a left atrial pressure of 15 mm Hg. The compromised function in these chronic models is exacerbated after acute elevation of coronary venous pressure and reduction of cardiac lymph flow. Collagen levels were elevated by at least 20% in the chronic hypertensive dogs and in the nonhypertrophied left ventricles of dogs with chronic right heart pressure elevation. We conclude that acute myocardial edema compromises cardiac function and that chronic right heart pressure elevation and chronic arterial hypertension produce left ventricular myocardial edema, which also compromises function in these common pathological conditions. The presence of myocardial edema in these chronic models also potentiates interstitial fibrosis, leading to a further decrease in the heartʼs ability to function normally. (Circulation Research 1991;68:1713–1721)