To investigate whether serial incremental continuous positive airway pressure (CPAP) has any short-term or long-term advantages over face-mask oxygen therapy by way of intrapulmonary shunt reduction, 100 patients admitted to the coronary care unit for the treatment of acute cardiogenic pulmonary edema were studied. All patients received Swan-Cant catheterization, Hemodynamic and pulmonary function parameters were recorded over the next 6 h, and the patients were followed until hospital discharge. All survivors received regular follow-up at 1-month intervals in the outpatient clinic, During the first-stage investigation period (3 h) PaO2 in the CPAP group showed a significant increase, whereas the intrapulmonary shunt and alveolar-arterial oxygen tension gradient (P[A-a]On) was significantly reduced (p<0.005). The CPAP group had significantly lower rate-pressure product and higher stroke volume index compared with the control group, The therapeutic failure rate over 6 h was 24% in the CPAP group and 50%, in the control group (p<0.01). The CPAP group had a significantly lower incidence of tracheal intubation and ventilator therapy than the control group; however, there was no significant difference in short-term mortality and hospital stay between the two groups. In conclusion, although study size was not large enough to demonstrate a difference in mortality, CPAP therapy resulted in physiologic cardiovascular and pulmonary function improvement and significantly reduced the need for intubation; however, it did not decrease mortality in patients with acute cardiogenic pulmonary edema, and a much larger study is needed to investigate this possibility.

Objectives. This study attempted to evaluate the long-term efficacy of enalapril versus hydralazine therapy on left ventricular volume, mass and function as well as on the renin-angiotensin system in chronic asymptomatic aortic regurgitation.Background. We tested the hypothesis that early administration of a vasodilator drug might be able to reduce left ventricular dilation and mass expansion. Because the renin angiotensin system may be activated in chronic aortic regurgitation, early enalapril therapy might be beneficial.Methods. Between 1990 and 1993, 76 asymptomatic nonrheumatic patients with mild to severe chronic aortic regurgitation were enrolled in a randomized, double-blind trial comparing enalapril with hydralazine. All patients underwent serial noninvasive studies. Seventy patients completed the 12-month follow-up.Results. At 1 year, patients receiving enalapril had a significant reduction in left ventricular end-diastolic and end-systolic volume indexes (124 +/- 15 vs. 108 +/- 17 ml/m(2), p < 0.01; 50 +/- 12 vs. 40 +/- 14 ml/m(2), p < 0.01, respectively) and mass index (131 +/- 16 vs. 113 +/- 19 g/m(2), p < 0.01), whereas hydralazine therapy showed no significant changes. Both regimens not only had a significant reduction in left ventricular mean wall stress but also had a mild increase in exercise duration. Only enalapril therapy achieved a significant inhibition of the renin angiotensin system, in contrast to hydralazine therapy. Moreover, the multiple r(2) value from the analysis for end diastolic volume index using the two variables of age and treatment drugs was 72.1% (p < 0.01).Conclusions. Both regimens decrease left ventricular mean wall stress. Enalapril therapy achieves significant left ventricular mass regression, left ventricular end diastolic and end systolic volume index reduction and renin angiotensin system suppression. These findings suggest that early unloading enalapril therapy has the potential to favorably influence the natural history of chronic aortic regurgitation.

The aim of this study was to investigate the role of the renin-angiotensin-aldosterone system during anti-heart failure treatment with additional enalapril versus conventional vasodilator therapy (hydralazine + sorbitrate) and to assess whether or not enalapril can be suggested as the preferential vasodilator therapy in patients with chronic congestive heart failure. Over a 2.5-year period, 120 patients (New York Heart Association II-IV, creatinine less than or equal to 2.0 mg/dl) were enrolled in the study and randomly assigned to receive enalapril or hydralazine and sorbitrate therapy in addition to optimal digitalis and diuretics administration. At the end of a one-year followup, there was a tendency for mortality to be lower in the enalapril[correction of enlapril] group (4 cases) compared to the conventional group (9 cases), but the difference was not significant (p = 0.21). Both groups showed similar increases in plasma renin activity. The plasma aldosterone level decreased significantly in the enalapril group (p less than 0.005); whereas it rose significantly in the conventional group (p less than 0.005). The plasma norepinephrine level of the enalapril group fell significantly when compared with the conventional group. Thus, enalapril therapy achieved better reduction in the activating sympathetic system (p less than 0.0001). Reduction in the anti-diuretic hormone level was also found to be highly significant in the enalapril group, whereas no difference was seen in the conventional group. Furthermore, the serum creatinine level and blood urea nitrogen remained unchanged in the conventional group; whereas both were demonstrated to be reduced significantly in the enalapril group at a 1-year follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

The acute efficacy of rapid loading of oral long-acting enalapril in congestive heart failure remains to be established. We evaluated the efficacy of this treatment modality in 22 patients with chronic congestive heart failure N.Y.H.A. functional class ranging from II-IV with Creatinine level less than 2 mg/dl. Following hemodynamic evaluation, there was significant favorable change in the left ventricular functional curve. Moreover, acute hemodynamic assessment showed a significant reduction in pulmonary capillary wedge pressure from 19.2 +/- 4.8 to 17.2 +/- 4.7 mmHg (p less than 0.005) and an increases in stroke volume index from 28.3 +/- 9.2 to 33.1 +/- 7.5 ml/m (p less than 0.005). After rapid enalaprilization, blood pressure fell from 127 +/- 21/78 +/- 15 to 108 +/- 21/68 +/- 15 mmHg (p less than 0.005), systemic vascular resistance from 1725 +/- 602 to 1370 +/- 376 dyne.sec.cm-5 (p less than 0.05) and pulmonary vascular resistance from 262 +/- 19 to 218 +/- 65 dyne.sec.cm-5 (p less than 0.05). Cardiac index rose significantly from 2.43 +/- 0.62 to 2.60 +/- 0.50 l/min/m2 (p less than 0.05). In terms of neurohumoral assessments, there was a significant inhibition of the renin-angiotensin-aldosterone system. Aldosterone fell from 21.3 +/- 13.4 to 9.4 +/- 8.0 ng/dl and plasma renin activity rose from 3.3 +/- 4.6 to 11.3 +/- 11.0 ng/nl/hr (p less than 0.005). Plasma norepinephrine and epinephrine levels were found to have significant reduction in addition to antidiuretic hormone concentration. During short-term trial, left ventricular ejection fraction was significantly elevated from 27.5 +/- 6% to 32.8 +/- 10.8% (p less than 0.005). Thus, this limited study clearly demonstrates the rapid administration of enalapril not only achieves inhibition of renin-angiotensin-aldosterone system but also reduces preload and afterload significantly in the failing heart. We conclude that rapid enalaprilization is an effective methodology which still needs meticulous attention, providing significant hemodynamic and symptomatic benefits in patients with chronic congestive heart failure.

A group of consecutive 180 veteran patients with mild to moderate essential hypertension were chosen to participate in clinical antihypertensive trial for the purpose of defining the role of converting enzyme inhibitors and renin-angiotensin-aldosterone system in the management of mild to moderate hypertension patients. After a two-week placebo period, these patients were randomly assigned to regimens of converting enzyme inhibitors (enalapril or captopril with or without diuretics) or conventional therapy (diuretics with or without traditional vasodilators with or without beta-blockers). Each patient was regularly followed up every two weeks and doses were added until the diastolic blood pressure was equal to or lower than 90 mmHg. After 1 year of follow-up, only 162 patients completed the study. All high blood pressure was significantly reduced by these three regimens, but no significant difference of blood pressure control was noted. The mean left ventricular ejection fraction increased from 55.9 +/- 6.2 to 57.5 +/- 5.3% in captopril group (P less than 0.05, n = 59) and from 54.8 +/- 6.8 to 57.2 +/- 5.8% enalapril group (P less than 0.01, n = 53), in contrast to the insignificant change in control group (n = 50) (56.5 +/- 7.7 to 56.6 +/- 5.9%). The exercise duration also significantly increased only in converting enzyme inhibitors group (P less than 0.01). Furthermore, the plasma aldosterone level was significantly reduced by converting enzyme inhibitors therapy, whereas conventional therapy had no beneficial effect (P less than 0.01). Furthermore, the plasma aldosterone level was significantly reduced by converting enzyme inhibitors therapy, whereas conventional therapy had no beneficial effect (P less than 0.001). Concomitantly, antidiuretic hormone and plasma norepinephrine levels were also significantly reduced by converting enzyme inhibitors. In addition, converting enzyme inhibitors had a favorable trend to affect the metabolism of lipid in contrast to the conventional therapy. These results show that a first-step treatment of hypertension with converting enzyme inhibitors permits better left ventricular function and improves exercise tolerance by way of renin-angiotensin-aldosterone system inhibition. Thus, converting enzyme inhibitors might be suggested as the first step regimen in the treatment of hypertension.

Although continuous positive airway pressure (CPAP) therapy using a face mask is known to improve oxygenation, the intrapulmonary shunt reduction remains unsettled. Our study was designed to explore this issue. From 1985 to 1987 80 patients with acute cardiogenic pulmonary edema were randomly chosen to receive either serial CPAP therapy or high-flow face mask oxygen therapy without CPAP (control) for the purpose of evaluating the efficacy of CPAP therapy. After screening for exclusion, only 55 patients were included in the first 3-hour investigation period. PaO2 in the CPAP group showed a significant increase by the end of the initial study; whereas intrapulmonary shunt and alveolar-arterial oxygen tension gradient AaDO2 revealed simultaneously a significant reduction. Conversely, neither PaO2 nor intrapulmonary shunt (or AaDO2) in the control group demonstrated any significant beneficial changes. As for cardiovascular function, only the CPAP therapy achieved a significant reduction in rate pressure product in contrast to the control (face mask) therapy alone. In terms of therapeutic failure, 10 patients in the control group failed. However, in the CPAP group only 5 patients had failed at the end of the first 3-hour study period. Overall, the cumulative therapeutic failure rate was 28% in the CPAP group and 60% in the control group during a 6-hour observation study. However, there was no significant difference between the two groups in 24-hour hospital mortality.(ABSTRACT TRUNCATED AT 250 WORDS)