Determinants of the initial effects of captopril on blood pressure, glomerular filtration rate, and natriuresis in mild-to-moderate chronic congestive heart failure secondary to coronary artery disease.

Whereas angiotensin-converting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r2 = 0.74): the decrease in serum angiotensin II (F ratio = 10.3, p < 0.01), the decrease in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, p = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r2 = 0.67): a decrease in renal plasma flow (F = 48.6, p < 0.01), low pretreatment glomerular filtration rate (F = 11.1, p < 0.01), and low absolute post-treatment serum angiotensin II (F = 5, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of two methods of determining renal perfusion with and without captopril pretreatment in groups of patients with left ventricular dysfunction.

Methods of effective renal plasma flow measurement by 125I-orthoiodohippurate elimination and para-aminohippurate clearance were compared with and without captopril pretreatment in 10 chronic heart failure patients and in 20 patients after transmural myocardial infarction. In the chronic heart failure group measurements of effective renal plasma flow by the two techniques were strongly correlated (r = 0.92, P < 0.00001), as was the captopril-mediated change in effective renal plasma flow by the two methods (r = 0.85, P = 0.002). However, in absolute terms para-aminohippurate clearance significantly exceeded 125I-orthoiodohippurate clearance by a mean (+/- SD) of 24.8 +/- 43.7 ml.min-1 (P < 0.05) so that only using the former technique was a significant increment in renal perfusion observed in response to converting enzyme inhibition. In the post-myocardial infarction group, correlations between the two methods were variable and much poorer than in the chronic heart failure group (r = 0.54, P = 0.01 and r = 0.74, P = 0.002 on consecutive days). Furthermore, captopril-mediated increments in effective renal plasma flow by the two techniques were unrelated (r = -0.19, P = 0.59). In this group 125I-orthoiodohippurate elimination significantly exceeded para-aminohippurate clearance (P < 0.05). This reversed association and the weaker relationships between methods in post-infarction as compared to chronic heart failure patients may be related to interference by thrombolytic or aspirin treatments.

Effectiveness of captopril in reversing renal vasoconstriction after Q-wave acute myocardial infarction.

The purpose of this investigation was to study whether favorable renal effects might contribute to the influence of captopril in offsetting ventricular dilatation after infarction. Effective renal plasma flow and glomerular filtration rate were estimated by isotope injection methods in 20 patients on days 2, 7, 8, 42 and 180 after a first transmural anterior myocardial infarction. After measurements on day 7, patients were randomized to receive either captopril 25 mg 3 times daily (n = 10) or placebo (n = 10) for the remainder of the study. At baseline (day 7) there were no differences between the 2 treatment groups in radionuclide left ventricular ejection fraction, effective renal plasma flow, glomerular filtration rate or neurohormones. Left ventricular ejection fractions (40 +/- 4% [mean +/- 2 SD] at baseline) were higher in the captopril- than the placebo-treated patients on days 42 (p < 0.05) and 180 (p < 0.01) after infarction. Effective renal plasma flow became significantly higher at all time points after randomization in the captopril-treated group than in the placebo group (p < 0.001). A similar but lesser trend was observed for glomerular filtration rate. Plasma atrial natriuretic factor and aldosterone were significantly higher in the placebo group (p < 0.05). Renal hemodynamic indexes were directly correlated with and neurohumoral indexes inversely correlated with ejection fractions. In a second group of 12 patients with higher baseline ejection fractions (48 +/- 4%) after an inferior infarction, none of these beneficial effects of captopril were demonstrable. It is proposed that in the setting of left ventricular dysfunction after infarction, a prompt and sustained improvement in renal hemodynamics, by reducing inappropriate fluid retention and thus ventricular preload, may be one contributory mechanism by which captopril prevents progression of left ventricular dilatation.

Comparison of three methods of glomerular filtration rate measurement with and without captopril pretreatment in groups of patients with left ventricular dysfunction.

Methods of glomerular filtration rate measurement by 51Cr EDTA elimination, inulin clearance and creatinine clearance were compared with and without captopril pretreatment in 10 chronic heart failure patients and in 20 patients after transmural myocardial infarction. Strong intermethod correlations were found in chronic heart failure patients (EDTA: inulin r = 0.87; EDTA: creatinine r = 0.84; inulin: creatinine r = 0.9; all P less than 0.00001). Despite this, substantial absolute differences were observed in results obtained by different techniques. In particular, creatinine clearance significantly overestimated both 51Cr EDTA (18.0 +/- 18.4 ml.min-1, mean difference +/- SD, P less than 0.001) and inulin clearance (26.8 +/- 17.0 ml.min-1, P less than 0.001). The slight reduction in 51Cr EDTA elimination on captopril versus placebo (-8.3 +/- 9.2 ml.min-1, P less than 0.05) was related to a similar treatment difference in inulin clearance (r = 0.67, p = 0.03), but changes observed by either method were unrelated to captopril-induced changes in creatinine clearance. Thus, creatinine clearance is an unsatisfactory means of assessing the effect of angiotensin converting enzyme inhibition on glomerular filtration rate in chronic heart failure. In the post-myocardial infarction group, correlations between methods were poorer (EDTA: inulin r = 0.79; EDTA: creatinine r = 0.76; inulin: creatinine r = 0.67). In this group no significant effect of captopril on glomerular filtration rate was detected by any technique. As compared to the chronic heart failure patients, the weaker relationship between techniques post-myocardial infarction may be related to interference by thrombolytic or aspirin treatment.

Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure.

BACKGROUND: Ten chronic heart failure patients were studied on three occasions in randomized double-blind fashion to compare the acute hemodynamic, neurohormonal, and renal sodium-handling responses to 1 mg captopril versus 25 mg captopril, both in the absence of loop diuretic therapy and during furosemide-stimulated natriuresis. METHODS AND RESULTS: Compared with placebo, 1 mg captopril caused nonsignificant decreases in mean arterial pressure and circulating angiotensin II level and had no effect on glomerular filtration rate as determined by 51Cr-EDTA elimination. Captopril (25 mg) produced marked suppression of serum angiotensin II with or without oral furosemide (both p less than 0.002), a marked decrease in mean arterial pressure (p less than 0.001) that was accentuated by furosemide (p less than 0.00001), and a decrease in glomerular filtration rate (p = 0.0007). No difference from placebo in renal sodium excretion was noted with either 1 or 25 mg captopril in the absence of furosemide. In contrast, while 25 mg captopril caused slight attenuation of the natriuretic response to furosemide, 1 mg captopril significantly enhanced furosemide-induced natriuresis (p less than 0.05). No correlation was found in our patients between the natriuretic effect of furosemide and either absolute mean arterial pressure or change in mean arterial pressure during the furosemide phase of each study session. This suggests that blood pressure is not the important factor mediating the divergent renal responses to furosemide of the two captopril dosage regimens. CONCLUSIONS: We propose that in the face of furosemide-induced postglomerular vasodilatation in chronic heart failure, captopril at a starting dose of 1 mg (but not 25 mg) preserves enough circulating angiotensin II to maintain efferent arteriolar tone and thus glomerular filtration, while offsetting the antinatriuretic renal tubular effects of angiotensin II.

Body composition in the cirrhotic patient with ascites: assessment of total exchangeable sodium and potassium with simultaneous serum electrolyte determination.

The precise mechanism of initiation and maintenance of the disturbed fluid and electrolyte balance in cirrhotic patients remains unclear. Measurement of total exchangeable potassium in 11 cirrhotic patients with ascites revealed marked depletion compared to 9 healthy volunteers. Total exchangeable potassium was 50.8 +/- 5.1 m moles/L TBW in the patient group compared to 75.2 +/- 3.4 m moles/L TBW in the control group (P less than 0.01, Mann-Whitney U Test). Total body exchangeable sodium measured 80.1 +/- 3.7 m mole/L TBW in the cirrhotic group, which is not significantly elevated compared to the value in healthy volunteers of 74.1 +/- 1.9 m mole/L TBW. Serum sodium was low in four of the cirrhotic patients (129-133 mEq/L); exchangeable sodium was low in only one of these four (53.4 m mole/L TBW). Serum potassium was low in two of the cirrhotics (2.6-2.9 mEq/L); total body potassium was depressed in both of these patients (43.5-50.1 m mole/L TBW). An additional three patients had a low total body potassium (29.6-48.9 m mole/L TBW) with normal serum levels (4.0-4.2 mEq/L). There was no correlation between serum and total exchangeable electrolyte levels (Pearson's regression, r = 0.16 and 0.23). This work confirms that serum levels are not reliable indicators of true body sodium and potassium stores. The decreased total exchangeable potassium appears to be related to loss of body cell mass rather than intracellular potassium depletion.(ABSTRACT TRUNCATED AT 250 WORDS)