Hemodynamic effects of supplemental oxygen administration in congestive heart failure

Objectives. This study sought to determine the hemodynamic effects of oxygen therapy in heart failure.Background. High dose oxygen has detrimental hemodynamic effects in normal subjects, yet oxygen is a common therapy for heart failure. Whether oxygen alters hemodynamic variables in heart failure is unknown.Methods. We studied 10 patients with New York Heart Association functional class III and IV congestive heart failure who inhaled room air and 100% oxygen for 20 min. Variables measured included cardiac output, stroke volume, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance, mean arterial pressure and heart rate. Graded oxygen concentrations were also studied (room air, 24%, 40% and 100% oxygen, respectively; n = 7). In five separate patients, muscle sympathetic nerve activity and ventilation were measured during 100% oxygen.Results. The 100% oxygen reduced cardiac output (from 3.7 ± 0.3 to 3.1 ± 0.4 liters/min [mean ± SE], p < 0.01) and stroke volume (from 46 ± 4 to 38 ± 5 ml/beat per min, p < 0.01) and increased pulmonary capillary wedge pressure (from 25 ± 2 to 29 ± 3 mm Hg, p < 0.05) and systemic vascular resistance (from 1,628 ± 154 to 2,203 ± 199 dynes's/cm⁵, p < 0.01). Graded oxygen led to a progressive decline in cardiac output (one-way analysis of variance, p < 0.0001) and stroke volume (p < 0.017) and an increase in systemic vascular resistance (p < 0.005). The 100% oxygen did not alter sympathetic activity or ventilation.Conclusions. In heart failure, oxygen has a detrimental effect on cardiac output, stroke volume, pulmonary capillary wedge pressure and systemic vascular resistance. These changes are independent of sympathetic activity and ventilation.     

Coronary hemodynamic effects of angiotensin inhibition by captopril and teprotide in patients with congestive heart failure

The coronary hemodynamic effects of vasodilator therapy with angiotensin-converting enzyme inhibitors (captopril arid teprotide) were studied in 11 patients with ischemic heart disease and severe congestive heart failure (CHF). Over 2 hours, systemic vascular resistance was reduced from 2,408 ± 240 to 1,715 ± 170 dynes·s·cm^?5 (p < 0.001), and cardiac output improved 18%, resulting in lower arterial pressure (101 ± 8 to 86 ± 5 mm Hg, p < 0.001) and left ventricular filling pressure (30 ± 2 to 21 ± 2 mm Hg, p < 0.001). Coronary sinus thermodilution blood flow parallelled perfusion pressure but did not significantly vary overall (160 ± 20 to 133 ± 12 ml/min, difference not significant [NS]). Coronary vascular resistance was unchanged. Although the left ventricular stroke work index rose slightly (37.7 ± 8.8 to 41.3 ± 7.9 g·m/m², p < 0.05), there was no change in the coronary arteriovenous oxygen content difference (10.8 ± 1.0 to 10.4 ± 1.0 ml/100 ml, NS) or calculated myocardial oxygen consumption (16.4 ±1.9 to 13.9 ± 1.6 ml/min, NS). The heart rate-systolic blood pressure product declined significantly during this period (8,824 ± 703 to 7,087 ± 514 beats·mm Hg, p < 0.02); this relief of cardiac effort was a function of the pretreatment plasma renin activity. A derived index of external myocardial efficiency improved 37% (19 ± 3 to 26 ± 6, p < 0.05), reflecting greater left ventricular work without increased oxygen demand.Enhancement of myocardial performance after converting enzyme inhibition appears dependent on reduction of angiotensin-mediated ventricular afterload and preload. The lack of coronary vasomotor effects in patients with advanced ischemic cardiomyopathy may reflect limited coronary vascular reserve. Improvement of heart failure in these patients developed without evidence of myocardial ischemia, since balance was maintained between oxygen supply and demand.     

Influence of severity of ventricular dysfunction on hemodynamic responses to intravenously administered verapamil in ischemic heart disease

The effects of verapamil, 0.145 mg/kg body weight, administered intravenously in a bolus injection followed by 0.005 mg/kg per min, on cardiovascular hemodynamics and on ventricular ejection fraction, determined with gated cardiac blood pool scanning, were studted in 25 patients, 8 with acute myocardial infarction and 17 with symptomatic coronary artery disease who were undergoing diagnostic cardiac catheterization. The mean (± standard deviation) plasma verapamil level, determined with a gas liquid chromatographic technique utilizing a nitrogen detector, was 161 ± 47 ng/ml (n = 8) during steady state conditions of drug infusion. In 15 patients with stable coronary artery disease having a normal or moderately reduced ejection fraction, verapamil reduced mean arterial pressure (?16 percent, probability [p] < 0.001), systemic vascular resistance (?23 percent, p < 0.001), stroke work index (?13 percent, p < 0.02), with no significant change in pulmonary vascular resistance, ejection fraction or heart rate; cardiac index was increased (+11 percent, p < 0.001) as was the stroke volume index (+7 percent, p < 0.01) and mean capillary wedge pressure (+10 percent, p < 0.01). In the seven patients with uncomplicated infarction, there was no effect on ejection fraction, heart rate or pulmonary vascular resistance. There was a decrease in systemic vascular resistance (?22 percent, p < 0.01) and mean arterial pressure (?16 percent, p < 0.01) with an increase in cardiac index (+27 percent, p < 0.05), stroke volume index (+4 percent, p < 0.05) and mean capillary wedge pressure (+17 percent, p < 0.02). In three patients, one wlth acute infarction and two with coronary artery disease, having a severely reduced ejection fraction and elevated mean capillary wedge pressure (20 mm Hg or greater), mean arterial pressure decreased markedly with a fall in stroke volume index and an abrupt increase in the mean pulmonary capillary wedge pressure. These findings were associated with clinical evidence of heart failure and dyspnea.It is concluded that (1) in patients with cardiac disease having a mild to moderate decrease in left ventricular ejection fraction accompanied by a normal or mildly elevated mean pulmonary capillary wedge pressure, the intrinsic depressant effect of verapamil is offset almost entirely by its potent vasodilator proporties, but (2) in patients with a severely reduced ejection fraction and a high pulmonary capillary wedge pressure, the depressant effects of the compound become clinically apparent with sudden further increases in pulmonary capillary wedge pressure and a decrease in stroke volume and mean arterial pressure.     

Determinants of circulatory response to intravenous hydralazine in congestive heart failure

To determine whether the circulatory response to hydralazine in heart failure is influenced by initial hemodynamic status or left ventricular (LV) chamber size, 28 patients with chronic LV dysfunction were studied. Hemodynamic measurements and echocardiographic LV end-diastolic dimension were correlated with the response to 20 mg of intravenous hydralazine and to a dose titrated in each patient to reduce systemic resistance by ≥ 20%. Hydralazine, 20 mg, decreased systemic resistance from 23 ± 8 to 18 ± 8 U(p < 0.01) and increased the cardiac index from 2.0 ± 0.5 to 2.5 ± 0.6 liters/min/m² (p < 0.01) and the stroke work index from 21 ± 11 to 24 ± 9 g · m/m² (p < 0.05). Titrating the dose to decrease systemic resistance by ≥ 20% increased the cardiac index further to 2.7 ± 0.6 liters/min/m² and the stroke work index to32 ± 9 g · m/m². The change in systemic resistance produced by 20 mg of hydralazine correlated only with initial systemic resistance (r = 0.53), suggesting that vascular response to hydralazine is a direct function of initial vascular resistance. The percentage change in stroke work index produced by 20 mg of hydralazine correlated directly with indexes of LV preloadend-diastolic wall stress (r = 0.69) and pulmonary wedge pressure (r = 0.43) and inversely with stroke work index (r = ?0.49), an index of ventricular work. Similar but less close correlations were observed when the dose of hydralazine was titrated. The hemodynamic response to hydralazine did not correlate with LV end-diastolic dimension or right atrial pressure. Thus, vascular response to moderate doses of hydralazine is related to initial systemic vascular resistance. LV pump response is related to the level of initial LV pump dysfunction but not to LV chamber size or right atrial pressure.     

Sustained beneficial effects of oral amrinone on cardiac and renal function in patients with severe congestive heart failure

Although effectiveness of oral amrinone has been demonstrated in animals, amrinone has been shown in human subjects to improve cardiac performance in the failing heart only after acute intravenous administration. Therefore, we studied the hemodynamic and renal effects of orally administered amrinone (50 to 300 mg) in 10 patients with advanced congestive heart failure. Cardiac index increased from 1.56 ± 0.41 (mean ± standard deviation) to 2.20 ± 0.43 liters/min per m² (p < 0.001); pulmonary wedge pressure decreased from 26.1 ± 5.7 to 17.0 ± 5.7 mm Hg (p < 0.001). Mean arterial pressure decreased from 86.0 ± 8.4 to 81.3 ± 7.7 mm Hg (p < 0.001) and systemic vascular resistance from 2,406 ± 603 to 1,693 ± 261 dynes sec cm^?5 (p < 0.001). Heart rate was unchanged. The onset of action ranged from 30 to 120 minutes and the duration of action from 4 to 7 hours after a single oral administration. After 24 hours of continuous therapy, no tachyphylaxis to amrinone was observed. A correlation (r = 0.62, p < 0.001) was found between the oral dose of amrinone and the percent increase in cardiac index. Left ventricular ejection fraction, determined in five patients, increased from 14 ± 8 to 21 ± 8 percent (p < 0.01). Effective renal plasma flow, measured in six patients, increased from 186.0 ± 72.0 to 231.1 ± 88.8 ml/min (p < 0.05) and the glomerular filtration rate from 82.2 ± 14.9 to 110.0 ± 20.6 ml/min (p < 0.05). Thus, this study demonstrates the cardiotonic efficacy of orally administered amrinone in human subjects and recommends its further investigation as a therapeutic agent for the continued treatment of congestive heart failure.     

Hemodynamic and coronary effects of intravenous labetalol in coronary artery disease

Labetalol, an alpha and beta receptor blocking agent, was evaluated in 11 patients with documented coronary artery disease and stable angina. The mean dose of labetalol was 1.5 (range 1 to 2) mg/kg. Cardiovascular effects began within 1 minute after injection and were maximal within 10 minutes. Mean arterial pressure decreased from 105 ± 13 to 81 ± 10 mm Hg (p < 0.0001), heart rate from 70 ± 10 to 66 ± 7 beats/min (p < 0.05) and the pressure-rate product from 10,322 ± 2,344 to 7,717 ± 1,650 (p < 0.001). Cardiac output and pulmonary wedge pressure did not change significantly. Mean pulmonary arterial pressure decreased from 20 ± 3 to 16 ± 2 mm Hg (p < 0.005). Systemic and pulmonary resistances also decreased significantly (p < 0.0001 andp < 0.01, respectively). Coronary sinus flow increased from 107 ± 26 to 118 ± 25 ml/min (p < 0.01) and coronary vascular resistance decreased from 1.0 ± 0.2 to 0.77 ± 0.1 mm Hg/ml per min (p < 0.001).Labetalol may be a useful adjunct in the treatment of angina not only because it diminishes myocardial oxygen requirements but also because it improves coronary hemodynamics. Thus, labetalol appears to have some advantage compared with the usual beta blocking agents with their potentially detrimental effects on coronary hemodynamics.     

Improvement in supine bicycle exercise performance in refractory congestive heart failure after isosorbide dinitrate: radionuclide and hemodynamic evaluation of acute effects

The acute effects of oral isosorbide dinitrate on exercise performance in congestive heart failure were evaluated in 11 patients. All patients underwent rest and supine bicycle exercise equilibrium radionuclide ventriculography and hemodynamic measurements before and after oral administration of isosorbide dinitrate, 40 mg four times a day for 24 hours. Ninety minutes after the last dose, isosorbide dinitrate increased the duration of exercise (+ 28 percent, probability [p] < 0.01) and the total work performed (+ 32 percent, p < 0.01); with this drug, significantly (p < 0.05) fewer patients terminated exercise because of dyspnea. At rest, the left ventricular ejection fraction increased after administration of isosorbide dinitrate (+ 14 percent of value before administration, p < 0.02); there were decreases in mean pulmonary arterial pressure (? 23 percent, p < 0.02), mean arterial pressure (? 8 percent, p < 0.05), systemic vascular resistance (? 18 percent, p < 0.005) and pulmonary vascular resistance (? 46 percent, p < 0.001). During comparable levels of exercise, isosorbide dinitrate decreased pulmonary capillary wedge pressure (? 19 percent, p < 0.001), mean pulmonary arterial pressure (? 23 percent, p < 0.001), mean arterial pressure (? 7 percent, p < 0.001), heart rate (? 5 percent, p < 0.01), systemic vascular resistance (? 20 percent, p < 0.01) and pulmonary vascular resistance (? 37 percent, p < 0.01), and increased cardiac index (+ 15 percent, p < 0.02), stroke volume index (+ 19 percent, p < 0.01) and stroke work index (+ 16 percent, p < 0.05). Ejection fraction did not change significantly (+ 7 percent, difference not significant [NS]). During maximal exercise, isosorbide dinitrate produced decreases in pulmonary capillary wedge pressure (? 15 percent, p = 0.05), mean pulmonary arterial pressure (? 15 percent, p < 0.01), systemic vascular resistance (? 23 percent, p < 0.05) and pulmonary vascular resistance (? 30 percent, p < 0.01) and increases in cardiac index (+ 30 percent, p < 0.001), stroke volume index (+ 31 percent, p < 0.001) and stroke work index (+ 40 percent, p < 0.001). Ejection fraction did not change significantly (+ 9 percent, p = NS). Ten minutes after exercise, isosorbide dinitrate produced decreases in pulmonary capillary wedge pressure (? 34 percent, p < 0.02), mean pulmonary arterial pressure (? 23 percent, p < 0.02), mean arterial pressure (? 10 percent, p < 0.01) and systemic vascular resistance (? 24 percent, p < 0.001) and increases in stroke volume index (+ 18 percent, p < 0.05) and ejection fraction (+ 12 percent, p < 0.05). It is concluded that oral isosorbide dinitrate, by causing reductions in preload and afterload, produces significant beneficial acute effects on left ventricular performance during exercise in patients with refractory chronic congestive heart failure.     

Prostacyclin therapy in patients with congestive heart failure

The acute hemodynamic effects of intravenous prostacyclin (PGI₂), in doses of 22 ± 11 ng/kg per min were studied in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean (±standard deviation) pulmonary capillary wedge pressure decreased from 21.0 ± 7.9 to 15.0 ± 6.6 mm Hg (p < 0.001), mean arterial pressure from 98.9 ± 12.8 to 76.2 ± 7.0 mm Hg (p < 0.001), systemic vascular resistance from 2,574 ± 384 to > 1,368 ± 283 dynes s cm^?5 (p < 0.001), pulmonary vascular resistance from 1,008 ± 451 to 443 ± 135 dynes s cm^?5 (p < 0.001) and pulmonary arteriolar resistance from 330 ± 111 to 189 ± 73 dynes s cm^?5 (p < 0.001). Heart rate increased from 78 ± 21 to 82 ± 24 beats/min (p = not significant [NS]), cardiac index from 2.0 ± 0.37 to 3.2 ± 0.59 liters/min per m² (p < 0.001) and stroke index from 27.6 ± 8.69 to 42.0 ± 0.62 cc/m² (p < 0.001). With prostacyclin, moreover, coldness of the limbs and face disappeared, and patients felt warmth and mild flushing of the face. After prostacyclin, plasma norepinephrine levels, renin activity and aldosterone concentrations rose from 824 ± 375 to 880 ± 468 pg/ml (NS), 0.68 ± 1.36 to 0.95 ± 1.21 ng/ml per h (NS), and 6.64 ± 2.50 to 6.38 ± 2.88 ng/dl (NS), respectively, while plasma epinephrine increased from 140 ± 80 to 250 ± 154 pg/ml (p < 0.025).     

Radionuclide ejection fraction and regional wall motion during atrial pacing in stable angina pectoris: Comparison with metabolic and hemodynamic parameters

To evaluate the effects of atrial pacing on radionuclide (RNA) ejection fraction (EF) and regional wall motion (RWM), transmyocardial lactate gradients and hemodynamics in stable coronary artery disease (CAD), 12 CAD patients underwent incremental atrial pacing during cardiac catheterization. EF declined from 0.60 ± 0.07 during control state to 0.51 ± 0.11 (p < 0.001) during submaximal pacing (Sub Max P) with 10 of 12 having decreased EF, six developing new RWM abnormalities, and five experiencing mild chest pain. During maximal pacing (Max P), EF declined further to 0.47 ± 0.10 (p < 0.001), with all patients having decreased EF and experiencing moderate to severe chest pain, and nine developing new RWM abnormalities. Percentage lactate extraction (Ex) decreased from +28.3 ± 9.4% to +17.4 ± 11.9% during Sub Max P (p < 0.01), with only one patient producing lactate. During Max P, percentage lactate Ex decreased to ?0.1 ± 15.3% (p < 0.001) with eight patients producing lactate. Significant increases in pulmonary capillary wedge pressure and systemic vascular resistance occurred during Max P, and in mean pulmonary artery pressure and mean systemic arterial pressure during both Sub Max and Max P. Significant decreases in stroke volume index and stroke work index occurred during both pacing levels and cardiac index did not change with pacing. This study demonstrates that RNA may be used to establish decreases in EF and RWM which occur in response to incremental atrial pacing in patients with stable CAD, and that these changes are more consistent and appear earlier than the metabolic consequences of myocardial ischemia induced by pacing stress.     

Favorable effects of hydralazine on the hemodynamic response to isometric exercise in chronic severe aortic regurgitation

The hemodynamic effects of isometric exercise and the response to hydralazine therapy were evaluated in 11 patients with chronic, severe aortic regurgitation (AR). Isometric exercise produced a significant increase in heart rate (from 78 ± 11 to 93 ± 19 beats/min [mean ± standard deviation], p < 0.05), mean blood pressure (from 83 ± 8 to 104 ± 20 mm Hg, p < 0.05), mean right atrial pressure (from 3 ± 2 to 7 ± 5 mm Hg, p < 0.05) and mean pulmonary artery wedge pressure (from 12 ± 7 to 18 ± 10 mm Hg, p < 0.05). Small and insignificant changes were seen in cardiac index (from 3.4 ± 0.8 to 3.9 ± 1.0 liters/min/m²), systemic vascular resistance (from 1,097 ± 257 to 1,171 ± 284 dynes s cm^?5), pulmonary vascular resistance (from 120 ± 76 to 130 ± 89 dynes s cm^?5) and stroke volume index (from 44 ± 10 to 43 ± 12 ml/m²). After oral hydralazine administration (100 to 300 mg), hemodynamic values during isometric exercise were: Heart rate increased further, to 105 ± 14 beats/min (p < 0.05), mean blood pressure was 102 ± 16 mm Hg (difference not significant [NS]) cardiac index increased markedly, to 5.2 ± 1.4 liters/min/m² (p < 0.05), stroke volume index increased to 49 ± 12 ml/m² (p < 0.05), right atrial pressure decreased slightly, to 5 ± 5 mm Hg (NS), pulmonary artery wedge pressure decreased to 14 ± 7 mm Hg (p < 0.05), systemic vascular resistance decreased to 903 ± 288 dynes s cm^?5 (p < 0.05), and pulmonary vascular resistance changed to 100 ± 66 dynes s crrr^?5 (NS). Thus, isometric exercise in patients with chronic severe AR is associated with only a slight and insignificant increase in systemic vascular resistance, but a marked increase in pulmonary artery wedge pressure. Direct arteriolar vasodilation with hydralazine results in a significant attenuation of pulmonary artery wedge pressure increase during isometric exercise and leads concomitantly to a significant augmentation of stroke volume and cardiac output. These findings substantiate the value of hydralazine therapy in patients with chronic, severe AR.     

Effect of diuresis on the performance of the failing left ventricle in man

To determine the effect of diuresis on the performance of the failing left ventricle, we measured cardiac output, pulmonary wedge pressure and M-mode echo left ventricular diastolic dimension before and after diuresis in 13 patients with heart failure. Diuresis increased stroke volume (43 ± 23 ml to 50 ± 18 ml (p < 0.05) and decreased pulmonary wedge pressure (28 ± 3 mm Hg to 19 ± 5 mm Hg (p < 0.01)), mean blood pressure (100 ± 14 mm Hg to 88 ± 10 mm Hg (p < 0.01)) and systemic vascular resistance (2,059 ± 622 dynes-sec-cm^?5 to 1,783 ± 556 dynes-sec-cm^?5 (p < 0.05)). Echo left ventricular diastolic dimension was not changed by diuresis (6.0 ± 0.8 cm to 6.0 ± 0.8 cm). Percent change in stroke volume correlated with systemic vascular resistance (r = 0.60, p < 0.05) and with left ventricular diastolic dimension (r = 0.62, p < 0.05) but not with pulmonary wedge pressure (r = 0.12) or right atrial pressure (r = 0.04). Thus, diuresis improved the performance of the failing ventricle and reduced afterload, but it did not alter left ventricular diastolic dimension, an index of preload. These data suggest that diuresis improves ventricular function by decreasing afterload.     

Afterload reduction with nifedipine in aortic insufficiency

The acute hemodynamic effects of nifedipine were assessed In 12 patients with severe isolated aortic Insufficiency during control conditions and 30 minutes after administration of nifedipine (20 mg sublingually). Left ventricular end-diastollc pressure decreased from 19 ± 8 (mean ± standard deviation) to 9 ± 5 mm Hg (probability [p] < 0.0001), mean aortic pressure from 98 ± 12 to 80 ± 9 mm Hg (p < 0.0001), systemic vascular resistance from 1,135 ± 280 to 794 ± 176 dynes·s·cm^?5 (p < 0.0002) and rate-pressure product from 11,732 ± 1,727 to 10,022 ± 1,103 mm Hg⁺ beats/min (p < 0.01). Forward cardiac index increased by 24 percent, from 3.8 ± 1.1 to 4.4 ± 0.8 liters/min per m² (p < 0.04). Left ventricular end-diastolic volume, ejection fraction and total stroke work index did not change significantly. Regurgitant fraction, measured in five patients, changed parallel with systemic vascular resistance. Left ventricular function was maintained while both preload and afterload were decreased. Regurgitant flow was moderated and myocardial oxygen demand decreased. This hemodynamically favorable condition, due to nifedlpine, is clinically important and suggests the need for further therapeutic trials.     

Haemodynamic effects of diltiazem at rest and during exercise in patients with previous myocardial infarction

A single blind study between placebo and diltiazem (25 mg i.v.single dose) was carried out on 20 male patients with previousmyocardial infarction and without exertional ischaemia. Patients, 50 ±6.1 (mean±SD) years of age, underwenta right heart catheterization with Seldinger's percutaneousapproach and brachial or radial artery percutaneous catheterization. Haemodynamic variables were recorded in the supine positionafter catheterization in baseline conditions at rest, aftera warming-up period of 6 min, before and after a first and secondexercise test with stepwise increments of 25 W per 3 min. Before the second exercise test, either placebo or diltiazem(25 mg) was injected intravenously in 3 min. In comparison with placebo, diltiazern significantly reducedresting blood pressure (P<0.001) and systemic vascular resistance(P<0001) and increased cardiac index (P<0.01); duringexercise it also reduced the mean pulmonary arterial pressure(P<005), pulmonary wedge pressure (P<0.05), total pulmonaryresistance (P<0.02), and increased the stroke volume (P<005). The present study demonstrated that intravenous diltiazem didnot induce a significant rise in cardiac index but reduced theafterload and slightly reduced the preload. Diltiazem also reducedmyocardial oxygen consumption and decreased blood pressure,mean right atrial pressure and slightly decreased the heartrate.     

The systemic and coronary haemodynamic effects of felodipine in patients with coronary heart disease

The cardiovascular effects of felodipine, a new arteriolar vasodilator,were studied in 22 patients with coronary heart disease. Therewere significant falls in blood pressure and systemic vascularresistance of 16 and 38% respectively (P = 0.001), thus affectingafter-load. Cardiac index and stroke index increased by 35 and12% respectively. There was reflex tachycardia-from 75 ±3to 85 ±3 b.p.m. (P =0.005). Coronary sinus blood /lowincreased from 134±9 to 191 ±17 ml/min (P<0.005)and myocardial arterio- venous oxygen difference narrowed from12.l±0.5 to 9.0±0.4 vols% (P<0.001) indicatingless oxygen usage. With the heart rate held constant by atrialpacing, cardiac index and stroke index increased by 30 and 26%(P<0.001), whilst systolic blood pressure and systemic vascularresistance fell by 20 and 29% (P<0.001). This would suggestthat the improved haemodynamics were largely secondary to after-loadreduction.     

Hemodynamic response to intravenous enalaprilat in patients with severe congestive heart failure and mitral regurgitation

The hemodynamic response 1 hour after 1.25 mg of intravenous (IV) enalaprilat was examined in 20 patients (mean age 75 years) with severe congestive heart failure (CHF) and mitral regurgitation (MR), secondary to ischemic heart disease (NYHA Class IV). Patients were classified into two groups based upon the magnitude of MR as derived from Doppler color flow imaging: Group I (n = 13) had severe MR and Group II (n = 7) had moderate MR. Acute therapy significantly reduced systemic vascular resistance index in both groups and provided effective afterload reduction. Although cardiac and stroke volume indices increased in both groups, an improved forward flow was significant only for Group I (cardiac index 2.2 ± 0.5 to 2.7 ± 0.51/min/m², p < 0.02). The magnitude of MR, acutely reduced in all patients, was similarly significant only for Group I (56 ± 10% to 31 ± 12%, p < 0.01). The reduction of both pulmonary capillary wedge pressure and mean arterial pressure was significant for both groups. This study supports the use of IV enalaprilat, a parenteral angiotensin-converting enzyme (ACE) inhibitor, as an effective and rapidly acting vasodilator in the management of selected patients with chronic heart failure and MR who require immediate hemodynamic improvement.     

Effects of removing oxygen from patients with chronic obstructive pulmonary disease

To determine the acute physiologic effects of removing oxygen from patients with chronic obstructive pulmonary disease (COPD) who are receiving long-term oxygen therapy, we made serial measurements in 20 patients during and after stopping low-flow oxygen therapy. Removing oxygen caused an increase in pulmonary vascular resistance, requiring 2 to 3 h to reach a new steady state. Removing oxygen therapy increased pulmonary vascular resistance index (PVRI) by 31% during rest (8.14 +/- 0.61 versus 6.23 +/- 0.51 units, p less than 0.001) and by 29% during exercise (8.11 +/- 0.9 versus 6.31 +/- 0.7, p less than 0.001). The increase in PVRI occurred because of an increase in pulmonary arterial pressure without a change in pulmonary capillary wedge pressure or cardiac index. At rest the increase in pulmonary arterial pressure caused by stopping oxygen correlated with the decrease in arterial oxygen saturation (r = 0.70, p less than 0.01). Removing oxygen decreased stroke volume index during rest and exercise. Although removing oxygen increased pulmonary vascular resistance, it did not affect systemic arterial pressure or vascular resistance. Stopping oxygen reduced arterial and mixed venous oxygen tension and oxygen delivery during rest and exercise. In patients who had a normal PaCO2 while breathing room air, removing oxygen therapy increased their oxygen consumption; conversely, in those patients who had an elevated PaCO2 while breathing room air, stopping oxygen therapy reduced oxygen delivery and oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in hemodynamic response to vasodilation due to calcium channel antagonism with nifedipine and direct-acting agonism with hydralazine in chronic refractory congestive heart failure

The hemodynamic response to a similar reduction of systemic vascular resistance after nifedipine and hydralazine administration was compared in a randomized crossover protocol in patients with severe chronic congestive heart failure (CHF). All 15 patients showed a 25% or greater reduction in vascular resistance with intravenous hydralazine (5 to 30 mg) and 11 patients showed a similar response with oral nifedipine (20 to 50 mg). In the latter 11 patients, despite similar reductions in systemic vascular resistance (35 ± 2% with nifedipine and 36 ± 4% with hydralazine, difference not significant), nifedipine resulted in a smaller increase in stroke volume index (from 23 ± 2 to 30 ± 2 ml/m² and from 24 ± 2 to 34 ± 2 ml/m² with hydralazine, p <0.05), cardiac index (from 2.0 ± 0.1 to 2.6 ± 0.2 liters/min/m² with nifedipine and from 2.0 ± 0.1 to 2.8 ± 0.2 liters/min/m² with hydralazine, p <0.05) and stroke work index (from 25 ± 3 to 27 ± 3 gm/m² with nifedipine and from 26 ± 2 to 32 ± 2 gm/m² with hydralazine, p <0.05). The decrease in blood pressure after nifedipine was slightly but not significantly larger than that with hydralazine (13 ± 3% vs 8 ± 2%). The changes in right atrial pressure, pulmonary artery wedge pressure and pulmonary vascular resistance were similar. The 4 patients who did not reduce their systemic vascular resistance by at least 25% with nifedipine had a worsening of their hemodynamic state as evidenced by 1 or more of the following findings: elevation of vascular resistance, decrease in cardiac index and increase in pulmonary artery wedge pressure. These results suggest that nifedipine exerts a clinically important negative inotropic effect in patients with severe chronic CHF that is only partially offset by its strong arteriolar dilatory effect. Hydralazine appears to be better than nifedipine when left ventricular afterload-reducing therapy is indicated in patients with severe CHF.     

Haemodynamic analysis of the effects of nicardipine and metoprolol alone and in combination in coronary artery disease

The circulatory consequences of concurrent slow-calcium channel(nicardipine) and cardioselective beta blockade (metoprolol)were evaluated in 20 patients with angiographically proven coronaryartery disease. The rest and exercise haemodynamic impact ofintravenous nicardipine (10mg) or metoprolol (10mg) alone wasdetermined by randomly allocating 10 patients to each drug;finally all patients were assessed on combination therapy. Theplasma levels of nicardipine (17 ±3 to 53 ±6 ngml-1) and metoprolol (36 ±5 to 97 ± 16 ng ml-1)achieved at the time of each study were in the established therapeuticrange.At rest nicardipine reduced systemic mean arterial pressureand systemic vascular resistance index; cardiac and stroke volumeindices increased without change in pulmonary artery occludedpressure. Metoprolol alone reduced systemic blood pressure,heart rate and cardiac index, and increased systemic vascularresistance index. Combination therapy reduced systemic arterialblood pressure and heart rate with relatively modest effectson cardiac index, systemic vascular resistance index and pulmonaryartery occluded pressure.During dynamic exercise nicardipinereduced systemic mean and diastolic arterial pressure and strokework index without change in other haemodynamic variables. Metoprololreduced exercise systemic arterial pressures, heart rate andcardiac index, and increased systemic vascular resistance indexand pulmonary artery occluded pressure. Combination therapyproduced changes similar to those at rest; at peak nicardipinepharmacodynamic activity, the cardiac depressant actions ofmetoprolol were largely offset by the induced reduction in leftventricular afterload.Thus these data suggest that nicardipineis safe to use concurrently with cardioselective beta-adrenoceptorblockade; moreover it may prove useful in offsetting some ofthe adverse haemodynamic effects of beta-blocking drugs in patientswith severe coronary artery disease.     

Comparison of hemodynamic responses to nifedipine and nitroprusside in severe chronic congestive heart failure

The hemodynamic effects of 20 to 40 mg of oral nifedipine were compared with those of intravenous nitroprusside in 11 patients with severe chronic congestive heart failure (CHF). In each patient, both drugs were administered to produce similar reduction of systemic vascular resistance (SVR) (29 ± 13% with nifedipine and 29 ± 12% with nitroprusside, difference not significant [NS]). At this comparable decrease in systemic vascular resistance, significant differences in hemodynamic responses to both drugs were noted: Nifedipine caused a smaller increase in cardiac index (20 ± 20% vs 40 ± 24%, p < 0.02) and a larger decrease in mean blood pressure than nitroprusside (16 ± 9% vs 8 ± 10%, p < 0.05). In addition, nifedipine produced a smaller decrease in mean pulmonary artery wedge pressure (13 ± 24% vs 36 ± 21%, p < 0.001) and pulmonary vascular resistance than nitroprusside (6 ± 42% vs 26 ± 46%, NS. Mean right atrial pressure decreased with nitroprusside, from 10 ± 7 to 5 ± 3 mm Hg (p < 0.05), but not with nifedipine (10 ± 7 mm Hg before and after nifedipine administration, NS). Left ventricular stroke work index increased with nitroprusside (20 ± 8 to 27 ± 9 g-m/m², p < 0.05), but did not change with nifedipine (21 ± 9 vs 21 ± 10 g-m/m², NS). These data show that nifedipine has an arteriolar dilatatory action in patients with CHF. However, compared with nitroprusside, nifedipine had a significantly larger hypotensive effect and had a lesser effect on right and left ventricular filling pressure, cardiac output and left ventricular function.     

Congenital heart disease and pulmonary artery hypertension. I. Pulmonary vasoreactivity to 15% oxygen before and after surgery

Pulmonary vasoreactivity at sea level was studied in 22 children before and in 15 children after corrective cardiac surgery for congenital heart disease and pulmonary artery hypertension; 8 children were studied both before and after cardiac surgery. During cardiac catheterization in 28 children, pulmonary and systemic hemodynamics were determined in room air and during breathing of 15% oxygen, which corresponds to a maximal hypoxic level commonly encountered during airplane travel. Before surgery, 19 of 22 children tolerated 15% oxygen (O2), which caused the following hemodynamic changes from room air status: the ratio of pulmonary to systemic arterial pressure increased from 0.70 to 0.78 (p less than 0.05), the ratio of pulmonary to systemic flow decreased from 2.2 to 2.0 (p greater than 0.05) and the ratio of pulmonary to systemic vascular resistance increased from 0.33 to 0.40 (p less than 0.02). In two children, severe pulmonary vasoconstriction developed within 5 minutes of 15% oxygen administration, requiring immediate discontinuation of hypoxia; neither patient had lasting deleterious effects. There was no evidence of increased pulmonary vasoreactivity in children with Down's syndrome compared with genetically normal children. After corrective surgery in 15 children (including both of the hyperreactors), no significant pulmonary vascular response to 15% oxygen was found. It is concluded that, in a small number of children with unrepaired congenital heart disease and pulmonary artery hypertension, pulmonary vascular hyperreactivity can be induced by breathing 15% oxygen; this reaction is life-threatening but reversible with the administration of 100% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)