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.     

Hemodynamic effects of nifedipine versus hydralazine in primary pulmonary hypertension

The acute hemodynamic effects of both sublingual nifedipine (N) and intravenous hydralazine (Hy) were studied in 5 patients with primary pulmonary hypertension to ascertain whether the capacity for pulmonary vasodilatation was generalized or drug-specific, and to determine which of the 2 agents had preferential pulmonary vasodilatory effects. For the group as a whole, neither N nor Hy produced changes in heart rate, mean pulmonary capillary wedge or right atrial pressures. Both N and Hy reduced mean systemic arterial pressure (before N 90 ± 8 mm Hg, after N 76 ± 7 mm Hg, p < 0.01; before Hy 92 ± 11 mm Hg, after Hy 68 ± 8 mm Hg, p < 0.05), and decreased systemic vascular resistance (before N 1,558 ± 645 dynes s cm^?5, after N 1,192 ± 430 dynes s cm^?5, p < 0.05; before Hy 1,700 ± 415 dynes s cm^?5, after Hy 957 ± 285 dynes s cm^?5, p < 0.05). In addition, N administration resulted in an increased cardiac output (before N 4.5 ± 2.0 liters/min, after N 4.8 ± 2.0 liters/min, p < 0.01); Hy administration was associated with a more varied effect on cardiac output (before Hy 4.0 ± 1.0 liters/min, after Hy 5.3 ± 1.8 liters/min, p < 0.10, difference not significant [NS]). Although for the group neither agent decreased mean pulmonary artery pressure (PAP) (before N 51 ± 13 mm Hg, after N 44 ± 13 mm Hg, NS; before Hy 50 ± 15 mm Hg, after Hy 51 ± 15 mm Hg, NS) or pulmonary vascular resistance (before N 873 ± 458 dynes s cm^?5, after N 680 ± 450 dynes s cm^?5, NS; before Hy 945 ± 454 dynes s cm^?5, after Hy 715 ± 309 dynes s cm^?5, NS), 4 of 5 patients had a decrease in PAP after N and 1 had no change, and only 1 of 5 patients had a decreased PAP after Hy administration. Moreover, compared with the changes after Hy administration, PAP declined after N administration (δPAP after Hy 0.2 ± 9 mm Hg, after N ?7 ± 9 mm Hg, p < 0.05). The PA diastolic to mean PA wedge pressure gradient tended to decrease after N administration (after N ?5.0 ± 10 mm Hg, after Hy +4.7 ± 7 mm Hg, NS), suggesting more pulmonary vasodilatation after N administration. Moreover, the ratio of pulmonary to systemic vascular resistances was unchanged after N but increased after Hy administration (before N 0.55 ± 0.2, after N 0.53 ± 0.2, NS; before Hy 0.55 ± 0.2, after Hy 0.74 ± 0.3, p < 0.02), indicating the more balanced vasodilatory effect of N. Two patients were treated chronically with Hy but had intolerable adverse effects; 1 was subsequently treated successfully with N. A third patient had pulmonary edema (presumably neurogenic) 30 minutes after Hy administration; this patient later died. Another patient has symptomatically improved with chronic N therapy. Thus, N appears to be a more specific pulmonary arterial vasodilator than Hy in acute drug testing; in this small group of patients with primary pulmonary hypertension, N appears to be more efficacious when administered chronically.     

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.     

Prostacyclin in experimental myocardial ischemia: Effects on hemodynamics,regional myocardial blood flow,infarct size and mortality

To determine the actions of prostacyclin in acute myocardial ischemia, the left anterior descending coronary artery was ligated in 26 anesthetized dogs. At 15 and 45 minutes after coronary ligation, regional myocardial blood flow (ml/min per 100 g) and cardiac output (ml/min) were measured by the radiolabeled microsphere technique (strontium-85 or cerium-141 18 to 10μ]). The dogs were randomly allocated 17 minutes after coronary ligation to a control group (n = 17) or to treatment with prostacyclin infusion at 0.32 μg/kg per min for 6 hours (n = 9). Heart rate and cardiac output were unchanged (p > 0.05) by prostacyclin; mean systemic arterial pressure decreased from 121 ± 8 to 90 ± 3 mm Hg (mean ± standard error of the mean) (p < 0.01) and systemic vascular resistance from 2,690 ± 339 to 2,372 ± 398 dynes · s · cm^?5 (p < 0.05). Prostacyclin reduced blood flow in nonischemic myocardium from 116 ± 12 to 80 ± 3 ml/min (p < 0.01); flow in the ischemic zone was unchanged (p > 0.05) from 22 ± 5 to 20 ± 4 ml/min. Thus, the ratio of ischemic to nonischemic flow was increased by prostacyclin from 0.20 ± 0.03 to 0.25 ± 0.05 (p < 0.05); neither the ischemic nor the nonischemic endocardial/epicardial flow ratio was altered (p > 0.05). In the control dogs, all variables remained constant (p > 0.05) from 15 to 45 minutes. Mortality to 6 hours after coronary ligation was 0 of 9 in prostacyclin-treated versus 6 of 17 (35 percent) in control dogs (p < 0.06). Surviving dogs were killed 24 hours after ligation and infarct size, determined by planimetry and weight techniques, was 18 ± 2 percent of left ventricle in prostacyclin-treated dogs versus 22 ± 2 percent in control dogs (p > 0.05). Thus, prostacyclin in acute myocardial ischemia decreases myocardial oxygen demands, maintains ischemic myocardial blood flow while decreasing nonischemic flow, and greatly reduces early mortality.     

Comparison of hemodynamic actions of pirbuterol and dobutamine on cardiac function in severe congestive heart failure

There is considerable interest in the development of beneficial oral inotropic agents for sustained ambulatory management of patients with severe chronic congestive heart failure. Therefore, the hemodynamic actions of the oral beta adrenergic receptor agonist pirbuterol and of intravenous dobutamine were compared in nine patients with severe heart failure. Both agents produced similar effects on ventricular pump function: The cardiac index was markedly increased from 1.8 to 2.6 liters/min per m² (p < 0.005) by dobutamine and from 1.8 to 2.9 liters/min per m² (p < 0.001) by pirbuterol; stroke index was increased from 24 to 32 ml/beat per m² (p < 0.02) by dobutamine and from 23 to 35 ml/beat per m² (p < 0.001) by pirbuterol; the stroke work index was increased from 19 to 27 g-m/m² (p < 0.005) by dobutamine and from 20 to 28 g-m/m² (p < 0.005) by pirbuterol. However, although dobutamine did not change mean blood pressure or left ventricular filling pressure (p < 0.05), pirbuterol modestly decreased mean blood pressure from 83 to 75 mm Hg (p < 0.02) and moderately decreased left ventricular filling pressure from 23 to 18 mm Hg (p < 0.005). Dobutamine reduced total systemic vascular resistance 22 percent from 2,049 to 1,582 dynes s cm^?5 (p < 0.001), whereas pirbuterol reduced this index 42 percent (p < 0.05 versus dobutamine) from 2,068 to 1,150 dynes s cm^?5. Neither agent altered heart rate or the heart rate-systolic blood pressure product (p < 0.05).Thus, oral pirbuterol has dobutamine-like beneficial hemodynamic effects on left ventricular pump function but causes a greater decrease in total systemic vascular resistance consistent with the combined inotropic and peripheral vasodilator actions of this oral beta adrenergic receptor agonist. These salutary hemodynamic responses suggest that oral pirbuterol may be useful for the prolonged treatment of severe chronic congestive heart failure.     

Influence of verapamil therapy on left ventricular performance at rest and during exercise in hypertrophic cardiomyopathy

To determine the hemodynamic effect of verapamil at rest and during exercise, 18 patients with hypertrophic cardiomyopathy were studied before and after 7 weeks of treatment with oral verapamil (maximal dose, 720 mg/day). At rest and at peak exercise, verapamil produced a significant increase in left ventricular (LV) systolic performance in terms of stroke volume index (rest, from 43 ± 11 to 53 ± 11 ml/m², p < 0.001; exercise, from 46 ± 11 to 51 ± 10 ml/m², p < 0.01), whereas heart rate decreased (rest, from 81 ± 14 to 70 ± 11 min^?1, p < 0.001; exercise, from 150 ± 21 to 141 ± 18 min^?1, p < 0.01). Cardiac index at rest and during exercise remained unchanged. Systolic vascular resistance did not change at rest, but decreased significantly during exercise (974 ± 243 to 874 ± 174 dynes s cm^?5; p < 0.05). After verapamil administration, pulmonary artery pressures did not change at rest, but decreased significantly during exercise. This was probably due to a shift in the LV pressure-volume relation. The improvement in LV hemodynamics was associated with a significant increase in exercise capacity. The findings of this study indicate that in patients with hypertrophic cardiomyopathy, hemodynamic improvement at rest and during exercise can be achieved by chronic administration of verapamil.     

Effect of Transcatheter Aortic Valve Replacement on Right Ventricular–Pulmonary Artery Coupling

ObjectivesThe aim of this study was to test the hypothesis that the acute left ventricular (LV) unloading effect of transcatheter aortic valve replacement (TAVR) would improve right ventricular (RV) function and RV–pulmonary artery (PA) coupling in patients with severe aortic stenosis (AS).BackgroundRV dysfunction is an ominous prognostic marker in patients undergoing TAVR, suggesting that relief of obstruction might be less beneficial in this cohort. However, the left ventricle and right ventricle influence each other through ventricular interaction, which could lead to improved RV function through LV unloading.MethodsProspective invasive hemodynamic measurements with simultaneous echocardiography were performed in symptomatic patients with severe AS before and immediately after TAVR.ResultsForty-four patients (mean age 81 ± 8 years, 27% women) with severe AS underwent TAVR. At baseline, right atrial, PA mean (27 ± 7 mm Hg), and pulmonary capillary wedge (16 ± 4 mm Hg) pressures were mildly elevated, with a low normal cardiac index (2.3 l/min/m²). Pulmonary vascular resistance was mildly elevated (222 ± 133 dynes · s/cm⁵) and PA compliance mildly reduced (3.4 ± 01.4 ml/mm Hg). Following TAVR, aortic valve area increased (from 0.8 ± 0.3 to 2.7 ± 1.1 cm²; p < 0.001) with a reduction in mean aortic gradient (from 37 ± 11 to 7 ± 4 mm Hg; p < 0.001) and an increase in cardiac index (from 2.3 ± 0.5 to 2.5 ± 0.6 l/min/m²; p = 0.03). LV stroke work, end-systolic wall stress, and systolic ejection period decreased by 23% to 27% (p < 0.001 for all), indicating substantial LV unloading. RV stroke work (from 16 ± 7 to 18 ± 7 mm Hg · ml; p = 0.04) and tricuspid annular systolic velocities (from 9.5 ± 2.0 to 10.4 ± 3.5 cm/s; p = 0.01) increased, along with a decrease in PVR (194 ± 113 dynes · s/cm⁵; p = 0.03), indicating improvement in RV-PA coupling. Increased RV stroke work following TAVR directly correlated with the magnitude of increase in aortic valve area (r = 0.58; p < 0.001).ConclusionsAcute relief in obstruction to LV ejection with TAVR is associated with improvements in RV function and RV-PA coupling. These findings provide new insights into the potential benefits of LV unloading with TAVR on RV dysfunction in patients with severe AS.     

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.     

Augmentation of right ventricular performance in chronic obstructive pulmonary disease by terbutaline: A combined radionuclide and hemodynamic study

The acute hemodynamic and functional effects of the relatively selective beta₂ adrenoreceptor agonist, terbutaline, was evaluated in a well defined group of eight patients with chronic obstructive pulmonary disease, abnormal right ventricular performance and elevated pulmonary vascular resistance. Radionuclide and hemodynamic data were obtained simultaneously using first pass radionuclide angiocardiography and thermodilution pulmonary arterial catheterization. Terbutaline caused no change in right ventricular end-diastolic volume index but increased right ventricular stroke work index from 13 ±5 to 16 ± 6 g · m/m² (mean ± standard deviation; p < 0.025). Furthermore, pulmonary vascular resistance index decreased in all patients and for the group decreased from 623 ± 279 to 407 ± 204 dynes · s · cm^?5 · m² (p < 0.05). The extent of this decrease correlated linearly with the level of resting pulmonary vascular resistance (r = 0.76). Right ventricular ejection fraction increased significantly from 35 ± 10 to 46 ± 5 percent; terbutaline resulted in normalization (to greater than 45 percent) of the ejection fraction in five of the eight patients. The changes in right ventricular ejection fraction were greatest in patients with the highest level of pulmonary vascular resistance and the lowest baseline ejection fraction. Left ventricular ejection fraction also increased significantly from 62 ± 10 to 71 ± 10 percent; however, there was no correlation between the change in this variable and either systemic vascular resistance or baseline left ventricular ejection fraction. Systemic oxygen delivery increased from 45 ± 16 to 63 ± 19 ml/min per m² (p < 0.005) without any change in arterial oxygen tension. This study demonstrates that terbutaline results in substantial augmentation of right ventricular performance. This effect appears to be mediated predominantly through alterations in pulmonary vascular resistance. Terbutaline may provide significant cardiac benefits in addition to its salutory effects on the tracheobronchial tree.     

Hemodynamic effects of captopril in patients with severe chronic heart failure

The hemodynamic effects of captopril (SQ 14225), an oral inhibitor of angiotensin-converting enzyme, were measured in 10 patients with severe chronic heart failure poorly controlled by digitalis and diuretics. After administration of a 25 mg dose, the cardiac index increased from 1.82 ± 0.14 to 2.28 ± 0.30 liters/min/m² (p < 0.05) while pulmonary capillary wedge pressure decreased from 22.7 ± 2.0 to 14.7 ± 4.7 mm Hg (p < 0.05). Mean blood pressure and systemic vascular resistance decreased from 85.7 ± 6.7 to 71.2 ± 12.0 mm Hg (p < 0.001) and from 1,909 ± 246 to 1,362 ± 347 dynes-s-cm⁵ (p < 0.001), respectively. Heart rate did not change significantly. There was an inverse relation between maximal augmentation in cardiac index and maximal reduction in pulmonary capillary wedge pressure (r = ?0.82, p < 0.01). While most patients demonstrated a constant hemodynamic benefit after repeated administration of captopril, some exhibited a triphasic response with attenuation of effects after the second dose and restoration of effects after the third dose. These hemodynamic benefits were observed in patients with stable chronic heart failure whose plasma renin activity was within normal range (1.1 to 7.3 ng/ml/hour).     

Treatment of postoperative low output syndrome with intraaortic balloon pumping: Experience with 419 patients

Four hundred nineteen patients with postoperative low output syndrome were supported with intraaortic balloon pumping between September 1, 1972 and June 1, 1979. Overall, 226 patients (54 percent) were successfully weaned from pumping support and 188 (45 percent) were subsequently discharged from the hospital. Approximately 10 percent of the patients died after apparently successful weaning from the balloon pump. Patients who underwent aortocoronary bypass operations had significantly better survival rates than patients who underwent combined aortocoronary bypass and valve procedures (60 versus 28 percent, p < 0.01). Two hundred sixty-three of the 419 patients have been serially classified hemodynamically since 1975. During intraaortic balloon pumping, 134 of these 263 patients ultimately achieved and maintained class A hemodynamic status (cardiac index greater than 2.1 liters/min, with systemic vascular resistance less than 2, 100 dynes s cm^?5); all of these patients were successfully weaned from the balloon pump. Fortyone (16 percent) of the 263 patients achieved only class B status (cardiac index greater than 1.2 but less than 2.1 liters/min, systemic vascular resistance less than 2, 100 dynes s cm^?5); the mortality rate in this group was 46.3 percent. Eighty-eight of the 263 patients failed to progress beyond class C status (cardiac index less than 1.2 liters/min or systemic vascular resistance greater than 2, 100 dynes s cm^?5); the mortality rate was 96.6 percent during intraaortic balloon pumping. The differences in survival rates among patients in classes A, B and C were statistically significant (p < 0.001).The mean ages of survivors and nonsurvivors were not significantly different. Men had a 59 percent and women a 47.3 percent survival rate (p < 0.05). The duration of support was 60.2 ± 44.7 hours in survivors and 10.9 ± 21.1 hours in nonsurvivors, suggesting an early high attrition rate for unsuccessful postoperative support. Patients with balloons of 40 and 30 ml had significantly better survival rates (67 and 52 percent, respectively) than patients with 20 ml balloons (47 percent, p < 0.05).     

Acute and chronic hemodynamic effects of enalapril (MK-421) in congestive heart failure

Enalapril, a new long-acting angiotensin-converting enzyme inhibitor, was administered orally to 12 patients with stable congestive cardiac failure, NYHA function class III–IV. Acute and chronic hemodynamic effects were evaluated in addition to clinical response. The results of this open pilot study indicated marked reduction of pulmonary capillary wedge pressure from 21.8 ± 5.9 mm Hg (mean ± 1 SD) to 13.3 ± 4.5 mm Hg (P < 0.01) and peripheral resistance from 1837 ± 860 dynes · sec^?1 · cm^?5 to 1063 ± 584 dynes · sec^?1 · cm^?5 at 6 hr (P < 0.01). Well-tolerated hypotension with mean arterial pressure from 88.0 ± 11.6 mm Hg to 73.1 ± 11.7 mm Hg at 6 hr (P < 0.01) was recorded. No significant increase in cardiac output was observed. Angiotensin-converting enzyme activity was powerfully inhibited at the time of peak hemodynamic effect from 25.3 ± 9.8 U/ml to 4.9 ± 3.4 U/ml (P < 0.01) and sustained, but attenuated reduction at 24 hr (8.7 ± 4.7 U/ml) was observed. All patients reported subjective improvement and this clinical improvement has been sustained during follow-up from 19 to 21 months although baseline hemodynamic parameters at chronic re-catheterization did not demonstrate significant improvement. The pharmacodynamics and toxicity of enalapril as compared to captopril are discussed. The long half-life, low toxicity and gradual onset of action are seen as representing a clinical advantage with regard to patient therapy.     

Effects of acute and chronic minoxidil administration on rest and exercise hemodynamics and clinical status in patients with severe,chronic heart failure

The effects of acute and chronic oral administration of the vasodilator minoxidil on hemodynamics, oxygen consumption, exercise performance and clinical status were investigated in 10 patients with severe, chronic heart failure refractory to digitalis and diuretic therapy. The cardiac index was 1.99 ±0.38 liters/min/m² at rest and 2.88 ± 0.79 at symptom-limited maximal exercise on conventional therapy, compared with 2.64 ± 0.33 liters/min/m² at rest and 3.55 ± 0.84 at maximal exercise after short-term minoxidil administration (p < 0.02, control versus minoxidil at both rest and exercise). Stroke volume was increased after minoxidil treatment, without significant effect on heart rate. Systemic vascular resistance was decreased by minoxidil from 2,050 ± 722 to 1,325 ± 374 dynes-s/cm^?5 at rest and from 1,500 ± 830 to 1,206 ± 589 dynes· s/cm^?5 at maximal exercise (p = 0.01, control versus minoxidil). No significant effect was observed on left ventricular filling, right atrial, or mean pulmonary arterial pressure, but pulmonary vascular resistance decreased both at rest and on exercise (p < 0.05). Maximal exercise oxygen consumption increased from 8.9 ± 3.2 ml/kg/min on conventional therapy to 10.5 ± 2.4 on minoxidil therapy (p < 0.03), median maximal exercise work load increased from 25 to 50 W and median exercise duration increased from 6.0 to 9.0 minutes. On chronic minoxidil administration all 5 patients who completed a scheduled 6 week follow-up showed symptomatic improvement. However, worsening edema developed in all patients, requiring increased diuretic dosage and close supervision. Symptoms of ischemic heart disease worsened in 2 of 10 patients. We tentatively conclude that minoxidil may be a useful vasoactive agent in the pharmacologic therapy of severe chronic heart failure.     

The effect of isosorbide dinitrate on left ventricular size,wall stress and left ventricular function in chronic refractory heart failure: An echocardiographic study

To determine the effect of a long-acting vasodilator isosorbide dinitrate (ID) on ventricular performance, 16 patients with refractory congestive heart failure underwent echocardiographic studies during control and for a period of 2 hours after the administration of 10 mg of sublingual ID. The effects of ID were seen in 5 to 10 minutes, reached maximum at 30 ± 3 minutes lasted for 60 minutes and dissipated thereafter. At the maximal drug effect, a significant decline in mean blood pressure (74 ± 2 versus 81 ± 3 mm Hg, p < 0.001), left ventricular afterload (228 × 10³ ± 9 × 10³ dynes/cm² versus 273 × 10³ ± 12 × 10³ dynes/cm² p < 0.001), end-diastolic dimension (5.90 ± 0.13 versus 6.40 ± 0.15 cm, p < 0.005) and end-systolic dimension (4.8 ± 0.15 versus 5.50 ± 0.17 cm, p < 0.001) occurred. These changes were associated with a significant increase in per cent fractional shortening (19 ± 2 per cent versus 14.5 ± 1.3 per cent, p < 0.001), mean rate of circumferential fiber shortening (VCF) (0.78 ± 0.06 versus 0.61 ± 0.05 circumferences per second (circ/sec) p < 0.001) and normalized mean posterior wall velocity (VPW) (0.65 ± 0.05 versus 0.47 ± 0.03 sec^?1, p < 0.001) when heart rate was not significantly altered. All 16 patients were maintained on long-term ID therapy. Six of 16 patients (38 per cent) died within 17 to 270 days after the acute study. Nine of 16 patients have been followed for a period of three to 24 months and are clinically improved. These findings suggest that (1) ID reduces left ventricular size, preload and afterload, and improves ventricular performance; and (2) the use of ID might be of value as adjunctive therapy in acute/chronic management of refractory heart failure.     

Systemic and pulmonary hemodynamics in patients with non-cirrhotic portal fibrosis (NCPF) is similar to compensated cirrhosis

Background Non-cirrhotic portal fibrosis (NCPF) is an important cause of portal hypertension (PHT) and variceal bleeding, especially in the developing countries. While the hepatic parenchyma and liver functions are normal, the patho-anatomic defect in these patients is pre- and peri-sinusoidal in nature. Aim To study the systemic and pulmonary hemodynamic alterations in patients with NCPF and compare them with compensated cirrhotic patients. Patients and Methods Patients with NCPF (n = 20, mean age 29.3 ± 9.8 year) and matched Child’s A cirrhotic patients (n = 17, age 34.1 ± 9.8 year) who had bled in the past, underwent hemodynamic measurements using a balloon tipped catheter. Results In NCPF patients, the hepatic venous pressure gradient (HVPG) was significantly lower than in the cirrhotic patients (4.9 ± 1.5 mmHg vs. 15.7 ± 4.5 mmHg; P < 0.01). NCPF patients had hyperdynamic circulation and peripheral vasodilatation comparable to cirrhotic patients; cardiac output (8.0 ± 1.2 l/min vs. 8.4 ± 1.9 l/min; P = 0.4), cardiac index (5.4 ± 0.8 l/min/m² vs. 5.5 ± 1.9 l/min/m²; P = 0.86), mean arterial pressure (88.2 ± 14.1 mmHg vs. 89.9 ± 17.3 mmHg; P = 0.73), systemic vascular resistance (852.8 ± 204.3 dynes · s/cm⁵ vs. 854.1 ± 189.9 dynes · s/cm⁵; P = 0.98) and pulmonary vascular resistance (41.6 ± 18.1 dynes · s/cm⁵ vs. 41.3 ± 17.9 dynes · s/cm⁵; P = 0.95) were comparable in the two groups. Conclusions NCPF associated portal hypertension leads to a hyperdynamic state with high cardiac index and low systemic and pulmonary vascular resistance comparable to compensated cirrhosis. These novel observations suggest a primary role of portal hypertension in the development of hyperdynamic state.     

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.     

Sustained beneficial hemodynamic responses to large doses of transdermal nitroglycerin in congestive heart failure and comparison with intravenous nitroglycerin

The hemodynamic effects of a new transdermal preparation of nitroglycerin were evaluated in 9 patients with chronic congestive heart failure (CHF). A graded infusion of nitroglycerin was administered initially to establish the dose-response relation for nitroglycerin and estimate the dose of topical nitroglycerin to be applied. Significant hemodynamic improvement was observed 0.5 to 1.0 hour after the cutaneous application of the nitroglycerin-impregnated polymer. The peak effect occurred at 6 hours, with the left ventricular filling pressure decreasing from 24 ± 2 to 18 ± 1 mm Hg (mean ± standard error of the mean) (p < 0.01) and the cardiac index increasing from 2.0 ± 0.2 to 2.6 ± 0.2 liters/min/m² (p < 0.01). The systemic vascular resistance decreased from 1,860 ± 198 to 1,531 ± 162 dynes s cm^?5 (p < 0.01). Heart rate and mean arterial pressure were unchanged. Significant hemodynamic benefit was observed for 24 hours, and no rebound deterioration occurred upon withdrawal of the drug. The average dose of transdermal nitroglycerin applied was 51 ± 6 cm² (1.7 ± 0.2 mg/kg; 6 of the 9 patients received 64 cm²). Thus, topical application of a new nitroglycerin-impregnated polymer induces an improvement in cardiac performance that is sustained for 24 hours in patients with chronic CHF. However, substantial doses of the drug may be required to produce a satisfactory hemodynamic response in most patients with CHF.     

Hemodynamic effects of dibutyryl cyclic AMP in congestive heart failure

To evaluate the hemodynamic effects of dibutyryl cyclic AMP (DBcAMP) in congestive heart failure (CHF), right-sided cardiac catheterization was performed in 11 patients with CHF, and hemodynamic variables were investigated before and after infusion of various doses of DBcAMP at a rate of 0.025 to 0.2 mg/kg/min (mean 0.14 ± 0.077 [standard deviation]). DBcAMP reduced total systemic vascular resistance index from 3, 171 ± 1, 158 to 1,880 ± 554 dynes s cm^?5 · m² (mean ± standard deviation) and pulmonary arterial end-diastolic pressure from 23 ± 13 to 20 ± 11 mm Hg, and increased cardiac index from 2.24 ± 0.60 to 3.41 ± 1.02 liters/min/m². Mean arterial blood pressure decreased from 91 ± 14 to 84 ± 13 mm Hg, and heart rate increased from 91 ± 16 to 99 ± 13 beats/min. The increase in cardiac index was accompanied by a proportional decrease in total systemic vascular resistance index in all patients except 1. In 8 patients the decrease in pulmonary arterial end-diastolic pressure was accompanied by an increase or no change in the left ventricular stroke work index. In 6 patients, DBcAMP was given in incremental doses of 0.05, 0.1, and 0.2 mg/kg/min every 20 minutes, and 5 of 6 patients tolerated the full dose and showed dose-related hemodynamic changes for the incremental doses of DBcAMP. These data suggest that DBcAMP has powerful vasodilating effects on resistance vessels in patients with CHF; hence, it can be a useful vasodilating agent for treatment of CHF.     

Cardiovascular effects of breathing 95 percent oxygen in children with congenital heart disease

The hemodynamic effects of breathing 95% oxygen were evaluated in 26 children with congenital heart disease. Aortic, pulmonary arterial, right atrial, and pulmonary arterial wedge pressure, aortic and pulmonary artery oxygen saturation, and blood gas, cardiac index, and heart rate were measured in room air and after each patient had breathed 95 % oxygen for 10 (n = 26) and 20 (n = 5) minutes. Measurements were repeated with the patient again breathing room air for 10 (n = 11) and 20 (n = 6) minutes. After 10 minutes of 95% oxygen, arterial partial pressure of oxygen increased from 85 ± 13 to 420 ± 89 torr (p < 0.001). Aortic mean pressure increased from 80 ± 10 to 83 ± 10 mm Hg (p < 0.01), and systemic vascular resistance increased from 20 ± 7 to 26 ± 8 U (p < 0.001). The cardiac index decreased by 21 % from 3.96 ± 0.94 to 3.12 ± 0.74 liters/min/m² (p < 0.001) and the stroke index decreased by 11% (p < 0.001). A 23% decrease in oxygen consumption (p < 0.001) was observed, and oxygen transport decreased from 763 ± 179 to 600 ± 161 ml O₂/min/m² (p < 0.001). Cardiac index, stroke index, and systemic vascular resistance did not return to normal until 20 minutes after cessation of oxygen breathing. To determine whether reflex bradycardia is responsible for these oxygen-induced hemodynamic changes, heart rate was kept constant by atrial pacing in a second group of 5 patients. In these children, significant decreases in cardiac index, stroke index, and oxygen consumption, and increases in systemic vascular resistance also occurred with 95% oxygen. Thus, in children with acyanotic congenital heart disease, hyperoxia increases aortic pressure and systemic vascular resistance and decreases cardiac index, stroke index, oxygen consumption, and oxygen transport.     

Effect of prostacyclin and prazosin in the treatment of congestive heart failure; with special reference to the sympathetic nervous system

Therapy to decrease the load in congestive heart failure is now classified as acute and chronic vasodilator therapy. In this symposium, we presented prostacyclin (PG I2) as an acute and prazosin as a chronic vasodilator. Their hemodynamic and clinical effectiveness were evaluated and their effect on the sympathetic nervous system was also studied. We studied the effect of intravenous prostacyclin infusion in doses of 22 +/- 11 ng/kg/min in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean pulmonary capillary wedge pressure decreased from 21.0 +/- 7.9 to 15.0 +/- 6.6 mmHg (p less than 0.001), mean arterial pressure from 98.9 +/- 12.8 to 76.2 +/- 7.0 mmHg (p less than 0.001), systemic vascular resistance from 2,574 +/- 384 to 1,368 +/- 283 dynes X sec X cm-5 (p less than 0.001), pulmonary vascular resistance from 1,008 +/- 451 to 443 +/- 135 dynes X sec X cm-5 (p less than 0.001) and pulmonary arteriolar resistance from 330 +/- 111 to 189 +/- 73 dynes X sec X cm-5 (p less than 0.001). The cardiac index increased from 2.0 +/- 0.37 to 3.2 +/- 0.59 l/min/m2 (p less than 0.001), and the stroke index from 27.6 +/- 8.69 to 42.0 +/- 0.62 ml/m2 (p less than 0.001). Moreover, prostacyclin therapy counteracted the sensation of coldness of the limbs and face, and patients felt warmth and mild flushing of the face. The effect of prazosin on the exercise duration time until dyspnea was evaluated by the treadmill test.(ABSTRACT TRUNCATED AT 250 WORDS)