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.     

Effects of oral hydralazine on gas exchange in patients with cor pulmonale

Vasodilators lower total pulmonary vascular resistance in some patients with pulmonary hypertension, but If vasodilators worsen arterial oxygenation in cor pulmonale, as they do in some patients with left ventricular failure, the benefits of a decrease in vascular resistance would be offset by a lack of change or a deterioration in systemic oxygen delivery. Measurement was made of arterial and mixed venous blood gases, minute ventilation, shunt fraction, alveolar-arterial oxygen difference, pulmonary arterial pressures, and cardiac output before and four hours after a single dose of hydralazine, 75 mg orally, in six patients (Group I) and before and after 48 hours of hydralazine, 50 to 75 mg orally, every six hours In 10 patients (Group II). Cardiac output increased 36 percent in Group I and 48 percent in Group II. In both groups total pulmonary vascular resistance decreased (8.0 ± 2.8 to 6.1 ± 2.6 units in Group I, p < 0.01; 9.7 ± 3.7 to 5.6 ± 2.1 units in Group II, p < 0.01). Arterial P_O2 increased significantly both in Group I (61 ± 8 to 67 ± 10 torr, p < 0.05) and Group II (50 ± 13 to 54 ± 13, p < 0.05); however shunt fraction and alveolar-arterial oxygen difference were unchanged. The ratio of dead space to tidal volume decreased slightly in both groups, and minute ventilation increased significantly. Systemic oxygen delivery was increased by 39 and 51 percent in Groups I and II, respectively. Thus, gas exchange may be preserved or improved when hydralazine is used in the treatment of cor pulmonale.     

Improved exercise ejection fraction with long-term prazosin therapy in patients with heart failure

To study the effect of prazosin therapy on left ventricular function in patients with chronic stable heart failure, first pass radionuclide angiography at rest and during exercise was performed in 15 patients before the administration of prazosin and after seven to 12 weeks of prazosin therapy. There was no significant change in resting ejection fraction before and during prazosin therapy (36 ± 14 per cent versus 37 ± 14 per cent) (mean ± standard deviation). However, exercise ejection fraction increased from 34 ± 14 per cent to 42 ± 17 per cent (p < 0.01). The difference in ejection fraction from rest to exercise (ejection fraction response) changed significantly from ?2 ± 6 per cent before prazosin therapy to +5 ± 7 per cent during prazosin therapy (p < 0.01). Exercise duration increased from 368 ± 82 seconds to 476 ± 82 seconds (p < 0.01). Total work capacity measured in kilojoules increased from 12.6 ± 8.3 to 18.6 ± 10.4 (p < 0.01). The improved ejection fraction response during prazosin therapy correlated with the improved work capacity (r = 0.69, p < 0.01) and exercise duration (p = 0.59, p < 0.05). This improvement occurred despite a significant weight gain with prazosin from 72.2 ± 20.8 kg to 73.5 ± 20.8 kg (p < 0.01).These data suggest that long-term prazosin therapy is effective in the treatment of heart failure. However, the beneficial effects of prazosin, an alpha₁ blocking agent, may be evident only during exercise.     

Circulatory improvement after hydralazine or isosorbide dinitrate administration in patients with heart failure: Effect on metabolic responses to submaximal exercise

Hydralazine and isosorbide dinitrate can increase the cardiac output during submaximal exercise in patients with heart failure but whether this increase improves oxygen delivery to underperfused exercising muscle is uncertain. To investigate this question, we measured three systemic markers of skeletal muscle oxygen availability—exercise V?O₂, mixed venous lactate concentration and oxygen debt—during submaximal exercise in 15 patients with heart failure both before and after hydralazine (nine patients) or isosorbide dinitrate (eight patients) administration. Hydralazine increased the cardiac output during exercise from 4.9 ± 1.2 liter/min to 6.5 ± 1.8 liter/min (p < 0.01) but had no effect on exercise V?O₂ (control, 531 ± 135 ml/min; hydralazine, 489 ± 102 ml/min), peak lactate concentration (control, 18.3 ± 4.2 mg/dl; hydralazine, 17.9 ± 3.6 mg/dl) or oxygen debt (control, 474 ± 213 ml; hydralazine, 465 ± 170 ml) (all p > 0.10). Isosorbide dinitrate increased the cardiac output during exercise from 4.6 ± 0.9 liter/min to 5.3 ± 0.8 liter/min (p < 0.01) but also did not change exercise V?O₂ (control, 488 ± 62 ml/min; isosorbide, 473 ± 44 ml/min), peak lactate concentration (control, 19.2 ± 6.0 mg/dl; isosorbide, 21.4 ± 8.2 mg/dl) or oxygen debt (control, 522 ± 154 ml; isosorbide, 445 ± 147 ml) (all p > 0.10). We conclude that short-term administration of hydralazine or nitrates to patients with heart failure can substantially improve circulatory function during exercise but that this improvement probably does not enhance skeletal muscle nutritional flow.     

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.     

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.     

Cardiovascular effects of octreotide in patients with hepatic cirrhosis

Octreotide is thought to reduce splanchnic and variceal blood flow with minimal effects on the systemic circulation in cirrhotic patients with portal hypertension. However, we noticed significant bradycardia in some patients immediately after administration of bolus doses of octreotide. Therefore, we investigated the effect of intravenous octreotide on systemic hemodynamics in 59 patients with cirrhosis. In two double-blind, placebo-controlled protocols, 32 patients received a 25-μg bolus and 20 patients received an infusion of 50-μg/hr of octreotide/placebo. Immediately after the bolus dose of octreotide was administered, there were significant reductions in pulse rate (77 ± 3 vs. 65 ± 3 beats per minute, P < .01) and cardiac output (9.2 ± 0.8 vs. 7.9 ± 0.8 L/min; P < .01) and significant increases in mean arterial pressure (81 ± 3 vs. 87 ± 3 mm Hg; P < .05), mean pulmonary artery pressure (9.1 ± 1.0 vs. 16.6 ± 1.5 mm Hg; P < .01), right atrial pressure (3.8 ± 0.8 vs. 6.6 ± 1.0 mm Hg; P < .01), right ventricular pressure (7.1 ± 0.6 vs. 12.5 ± 1.3 mm Hg; P < .01), pulmonary capillary wedge pressure (4.8 ± 0.8 vs. 11.2 ± 1.4 mm Hg; P < .01), systemic vascular resistance, and pulmonary vascular resistance. Thirty minutes after the start of the infusion, there were significant increases in mean right atrial pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure. This study suggests that intravenous octreotide has significant effects on the systemic circulation in patients with cirrhosis and that these effects appear to be more marked after administration of bolus doses.     

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).     

Mechanism of action of hyaluronidase in decreasing myocardial ischemia post coronary occlusion in the isolated perfused rabbit heart

The influence of hyaluronidase (H) on subacute experimental myocardial ischemia was studied in isolated perfused rabbit hearts. Changes in ischemic area were assessed by epicardial nicotinamide adenine dinucleotide (NADH) fluorescence photography, an intrinsic high-resolution display of myocardial ischemia. Computerized determination of ischemic area was made from standardized photographs. Hyaluronidase was begun 20 minutes after coronary artery occlusion at 4 units/ml perfusate. NADH fluorophotographs were taken at 10-minute intervals up to 60 minutes of ischemia. Coronary sinus oxygen tension (P_csO₂), myocardial oxygen consumption (MV?O₂), and coronary flow were determined. After 70 minutes, the hearts were perfused with rhodamine solution to identify areas of myocardial perfusion. In 13 H-treated hearts 54.3% ± 3.7% (mean ± SEM) of the nonperfused area (rhodamine stained) was ischemic (NADH fluorescent). In 14 untreated hearts 79.8% ± 3.2% of the nonperfused area was ischemic (p < 0.0001) and the ischemic areas were uniform. The distance between perfused and ischemic tissue was 952 ± 78 μm in the H hearts and 504 ± 35 μm in the untreated hearts (p < 0.0001). In the H treated hearts P_csO₂ increased to 155% of the post-ligation control while it decreased to 79% in the untreated hearts (p < 0.0001). MV?O₂ decreased in the H-treated hearts to 62%; the untreated hearts had no further change. In the H-treated hearts, coronary flow increased to 146% of the post-ligation control while it fell to 91% in the untreated group (p < 0.0001). We conclude that H increases coronary flow while decreasing MV?O₂ during subacute ischemia. In H-treated hearts, significant amounts of myocardium remain normoxic within the nonperfused areas, and may potentially be salvaged after prolonged myocardial ischemia.     

Antianginal and myocardial metabolic properties of verapamil in coronary artery disease

To determine the metabolic cost of administering an experimental calcium antagonist, verapamil, to patients with coronary artery disease, 12 such patients were studied at rest and during stress with atrial pacing before and after intravenous treatment with verapamil (bolus dose of 0.1 mg/kg body weight, followed by infusion at 0.005 mg/kg per min). The mean (±standard deviation) aortic pressure at rest (98 ± 22 mg Hg), coronary sinus blood flow (88 ± 17 ml/min) and myocardial oxygen consumption (10.7 ± 2.4 ml O₂/min) decreased to 88 ± 20 mm Hg (p < 0.0004), 77 ± 14 ml/min (p < 0.03) and 8.8 ± 2.5 ml O₂/min (p < 0.01), respectively, after administration of verapamil. With atrial pacing, these values were 105 ± 25 mm Hg, 151 ± 50 ml/min and 18.5 ± 6.4 ml O₂/min, respectively, before infusion of verapamil, and then decreased to 87 ± 14 mm Hg (p < 0.006), 107 ± 31 ml/min (p < 0.0002) and 13.3 ± 4.4 ml O₂/min (p < 0.001) during infusion. Angina occurred in all patients with atrial pacing before verapamil (threshold to pain: 93 ± 67 seconds). After verapamil, the threshold to pain in six patients increased to 191 ± 183 seconds; and no pain was experienced by the remaining six (p < 0.0005). Before administration of verapamil lactate extraction decreased from 24 ± 9 to 10 ± 11 percent (p < 0.0002) during atrial pacing, and 9 (75 percent) of the 12 patients exhibited electrocardiographic S-T segment depressions. After administration of verapamil lactate extraction normalized to 22 ± 9 percent during atrial pacing, and the electrocardiogram reverted to baseline in all but one patient. These findings indicate that verapamil decreases left ventricular myocardial metabolic demands, and concomitantly greatly increases the threshold to angina.     

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.     

External,noninvasive cardiac assistance and nitrate administration for patients with unstable angina pectoris or acute coronary insufficiency

The influence of external, noninvasive counterpulsation, alone and in combination with sublingual nitroglycerin or isosorbide dinitrate, on left ventricular volumes and ejection fractions was investigated. Patients with unstable angina pectoris or acute coronary insufficiency were selected for this evaluation. Left ventricular volumes and ejection fractions were estimated using a gated blood pool scintigraphic technique. Twenty minutes of external counterpulsation did not significantly alter left ventricular end-diastolic volumes, end-systolic volumes, or ejection fractions in 13 patients. When sublingual isosorbide dinitrate (10 mg.) was combined with 20 minutes of external counterpulsation in eight patients, left ventricular end-diastolic volumes decreased 16 ± 7 per cent (p = .05), but neither left ventricular end-systolic volumes (12 ± 7 per cent) nor ejection fractions were significantly changed. When sublingual nitroglycerin (0.4 mg.) was combined with 15 minutes of external counterpulsation in three patients, left ventricular end-diastolic volumes decreased 21 ± 3 per cent (p < .01), end-systolic volumes decreased 25 ± 4 per cent (p < .02), and ejection fractions were not significantly changed. When left ventricular volumes and ejection fractions were measured 30 and 65 minutes after isosorbide dinitrate administration, 10 and 45 minutes after cessation of external counterpulsation, respectively, left ventricular end-diastolic volumes and end-systolic volumes were significantly decreased by approximately 20 per cent while ejection fractions were unchanged. When left ventricular volumes and ejection fractions were measured 25 minutes after nitroglycerin administration, 10 minutes after cessation of external counterpulsation, end-systolic volumes decreased 23 ± 2 per cent (p < .005) and end-diastolic volumes decreased 27 ± 3 per cent (p < .005). No significant changes in left ventricular end-diastolic or end-systolic volumes were seen 60 minutes after nitroglycerin administration. As in the other studies, left ventricular ejection fractions were unchanged. The results suggest that relatively short periods of external, noninvasive cardiac assistance do not alter left ventricular volumes or ejection fractions in patients with unstable angina pectoris or acute coronary insufficiency. Although external counterpulsation combined with a vasodilator such as isosorbide dinitrate or nitroglycerin decreases left ventricular volumes, it offers no advantage over vasodilator treatment alone.     

Exercise Capacity Improves after Transcatheter Closure of the Fontan Fenestration in Children

Objectives. This study evaluated the aerobic capacity, exercise capacity, and arterial oxygen saturation (O₂Sat) in children before and after transcatheter Fontan fenestration closure. Design. Observational study comparing exercise parameters and hemodynamics before and after transcatheter fenestration closure in Fontan patients. Outcome Measures. Working capacity, exercise duration, oxygen consumption (VO₂), and arterial O₂Sat were evaluated during aerobic exercise. Results. Twenty patients (mean age 11.4 years) underwent standardized exercise testing before and after fenestration closure. Twelve patients underwent cycle ergometry testing (mean age 14.8 years) (group1), and eight younger patients (mean age 6.4 years) underwent Bruce treadmill testing (group 2). The same exercise protocol was used in each patient before and after fenestration closure (interval between tests: 118 ± 142 days). Immediately following fenestration closure at cardiac catheterization, cardiac index decreased (3.0 to 2.1 L/minute/m²) and Fontan pressure increased (11 ± 2 to 12 ± 2 mm Hg) with an increased arterial saturation (92 to 96%) (P < .001). The total group demonstrated no significant change in pre‐ and postclosure maximal heart rates (164 ± 21 and 169 ± 19 bpm). Rest and exercise O₂Sat increased (89 and 82 to 95 and 92%) (P < .0001). Exercise duration increased (7.7 ± 1.9 to 9.2 ± 2.4 minutes) (P < .0005). Maximal VO₂, indexed maximal VO₂, and total working capacity in kilopond‐meters (kpm) increased (1.2 ± 0.5, 27 ± 7 and 2466 ± 1012 to 1.3 ± 0.4 L/minute, 31 ± 9 mL/kg/minute and 2869 ± 1051 kpm, respectively) (P < .005). Conclusion. In children with a univentricular heart after Fontan palliation, transcatheter fenestration closure improves exercise arterial O₂Sat and aerobic capacity despite a restricted resting cardiac output documented by catheterization immediately after the closure procedure.     

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.     

Heart Failure Impairs Muscle Blood Flow and Endurance Exercise Tolerance in COPD

Heart failure, a prevalent and disabling co-morbidity of COPD, may impair cardiac output and muscle blood flow thereby contributing to exercise intolerance. To investigate the role of impaired central and peripheral hemodynamics in limiting exercise tolerance in COPD-heart failure overlap, cycle ergometer exercise tests at 20% and 80% peak work rate were performed by overlap (FEV₁ = 56.9 ± 15.9% predicted, ejection fraction = 32.5 ± 6.9%; N = 16), FEV₁-matched COPD (N = 16), ejection fraction-matched heart failure patients (N = 15) and controls (N = 12). Differences (Δ) in cardiac output (impedance cardiography) and vastus lateralis blood flow (indocyanine green) and deoxygenation (near-infrared spectroscopy) between work rates were expressed relative to concurrent changes in muscle metabolic demands (ΔO₂ uptake). Overlap patients had approximately 30% lower endurance exercise tolerance than COPD and heart failure (p < 0.05). ΔBlood flow was closely proportional to Δcardiac output in all groups (r = 0.89–0.98; p < 0.01). Overlap showed the largest impairments in Δcardiac output/ΔO₂ uptake and Δblood flow/ΔO₂ uptake (p < 0.05). Systemic arterial oxygenation, however, was preserved in overlap compared to COPD. Blunted limb perfusion was related to greater muscle deoxygenation and lactate concentration in overlap (r = 0.78 and r = 0.73, respectively; p < 0.05). ΔBlood flow/ΔO₂ uptake was related to time to exercise intolerance only in overlap and heart failure (p < 0.01). In conclusion, COPD and heart failure add to decrease exercising cardiac output and skeletal muscle perfusion to a greater extent than that expected by heart failure alone. Treatment strategies that increase muscle O₂ delivery and/or decrease O₂ demand may be particularly helpful to improve exercise tolerance in COPD patients presenting heart failure as co-morbidity.     

Abnormalities of pulmonary artery wedge pressures in sleep-induced apnea

Six patients with sleep apnea syndrome were studied with continuous hemodynamic monitoring during sleep. Sleep apnea had been previously documented with an average number of apneas per hour of sleep ranging from 23 to 93 (mean 63). There was a significant decrease in heart rate during sleep (82 ± 5 to 69 ± 6, P < 0.01). There was a significant rise in systemic blood pressure (103 ± 2 mm Hg to 116 ± 6 mm Hg, P < 0.05) and pulmonary artery pressure (20 ± 1 mm Hg to 32 ± 5 mm Hg) during sleep. In addition, pulmonary artery wedge pressure increased (12 ± 2 mm Hg to 20 ± 3 mm Hg, P < 0.05) during sleep and 5 of the 6 patients developed an abnormal pulmonary wedge pressure. There was a significant decrease in P_O2 during sleep (71 ± 3 mm Hg to 49 ± 2 mm Hg, P < 0.005). These findings suggest that increases in pulmonary wedge pressures may be contributing to increase in pulmonary artery pressures in these patients during sleep.     

Effects of the converting enzyme inhibitor (SQ 20881) on the pulmonary circulation in man.

The effects of the converting enzyme inhibitor (SQ 20881) on the pulmonary circulation were investigated in 13 patients in whom systemic hypertension developed following coronary artery bypass surgery. Pulmonary vascular resistance was decreased by the inhibitor, from 128 ± 19 to 92 ± 20 dynes sec cm^?5 (or by 30 ± 7 per cent; P < 0.005), and this resulted in a decrease in mean pulmonary artery pressure from 17 ± 1 to 13 ± 1 mm Hg (or by 23 ± 3 per cent, P < 0.005). Consequently, right ventricular work was decreased by the inhibitor by 30 per cent (P < 0.01), despite an increase in cardiac output (increase in stroke volume) by 16 ± 6 per cent (P < 01). This increase occurred despite a 13 ± 3 per cent decrease in right ventricular filling pressure. The changes in pulmonary vascular resistance correlated with the pretreatment plasma renin activity (r = 0.74, P < 0.01), as did the decrease in mean pulmonary artery pressure (R = 0.82, P < 0.001), but neither change was related to the decrease in left ventricular filling pressure nor to changes in cardiac output or mean arterial pressure.These results indicate that blockade of the formation of angiotensin II by the converting enzyme inhibitor results in reductions in pulmonary vascular resistance and pulmonary artery pressure which are unrelated to alterations in left ventricular function. Thus, angiotensin inhibition may have therapeutic value in various clinical states characterized by pulmonary hypertension—especially if renin levels are high.     

Vasodilatory effect of aerosol histamine during pulmonary vasoconstriction in unanesthetized sheep

The effects of aerosol histamine on pulmonary vascular resistance during pulmonary vasoconstriction were studied in 12 unanesthetized sheep. Sheep were chronically instrumented with Silastic catheters in the pulmonary artery and left atrium, thermodilution Swan-Ganz catheter in the main pulmonary artery for measurement of cardiac output, and tracheostomy for delivery of hypoxic gas and/or aerosol histamine. Seven minutes of isocapnic hypoxia (Fl_O2 = 0.12) caused pulmonary artery pressure (P_PA) to increase from 17.2 ± 0.4 to 27.0 ± 1.0 cm H₂O (X¯ ± SEM, P < 0.05) and pulmonary vascular resistance (PVR) to increase from 3.94 ± 0.33 to 4.71 ± 0.38 cm H₂O · L^?1. min (P < 0.05). When sheep breathed a combination of aerosol histamine (5 mg/ml) and 12% O₂, P_PA rose only to 21.3 ± 1.11 cm H₂O and PVR decreased to 3.51 ± 0.31 cm H₂O · L^?1. min. This was a significantly (P < 0.05) smaller response compared to hypoxia alone. Aerosol histamine alone had no significant effect on P_PA or PVR. Meclofenamate did not restore the histamine-induced loss of hypoxic vasoconstriction. Aerosol histamine significantly blunted the pulmonary vasoconstriction caused by intravenous serotonin (8 μg/kg/min) and intravenous prostaglandin H₂-analog (0.74 μg/kg/min). It was concluded that in the awake sheep aerosol histamine acted as a pulmonary vasodilator only in the presence of pulmonary vasoconstriction. Pediatr Pulmonol 1987; 3:94–100 .     

Amrinone and exercise performance in patients with chronic heart failure

Whether cardiotonic agents can improve the ability of patients with chronic heart failure to exercise remains unknown. Accordingly, the circulatory and respiratory response of 11 patients with severe heart failure refractory to digitalis, diuretic drugs and vasodilators was assessed during upright treadmill exercise before, within 24 hours and after 4 weeks of therapy with amrinone. The purpose of this study was to determine the ability of amrinone therapy to improve exercise hemodynamics, effort tolerance and aerobic capacity of these patients. Acute intravenous administration of amrinone (1.8 ± 0.1 mg/kg body weight) produced the following changes (mean values ± standard error of the mean) in hemodynamic variables during supine rest; increased cardiac index (from 2.04 ± 0.39 to 2.99 ± 0.38 liters/min per m²; p <0.01) and reduced pulmonary wedge pressure (from 24 ± 6 to 14 ± 6 mm Hg; p <0.01) without altering heart rate or mean arterial pressure. Within 24 hours after administration of amrinone, wedge pressure decreased at the onset of (from 25 ± 7 to 14 ± 7 mm Hg) and throughout exercise (p <0.01), whereas the exercise response of cardiac output, arteriovenous oxygen difference, heart rate, pulmonary and systemic vascular resistances, maximal oxygen uptake and the pattern of ventilation remained similar to control values. However, after 4 weeks of amrinone therapy, exercise and aerobic capacities were increased 44 and 48 percent (p <0.03), respectively, whereas the ventilatory response was unchanged. Thus, amrinone is a potent cardiotonic agent that acutely improves the function of the failing heart at rest and during exercise; the maximal aerobic capacity was increased after 4 weeks of therapy. Amrinone therefore appears to hold promise for the management of patients with chronic heart failure.     

Pulmonary transit time and diffusion limitation during heavy exercise in athletes

To investigate relationships between pulmonary transit times (PTT) and pulmonary diffusion limitation during exercise, 10 high aerobic capacity athletes (V̇_O2max = 5.15 ± 0.52 l · min⁻¹) who had multiple inert gas elimination analysis evidence suggestive of diffusion disequilibrium were studied at rest and maximal exercise. Diffusing capacity for oxygen (Dl_O2) was calculated from the inert gas data. First pass radionuclide angiography was performed using ^99mTechnecium labeled erythrocytes and whole lung PTT and pulmonary blood volume (PBV) were calculated. PTT decreased from 9.32 ± 1.41 sec at rest, to 2.91 ± 0.30 sec during exercise and was correlated with diffusion limitation suggested by the inert gases (r = -0.58, P < 0.05). PBV increased during exercise to over 25% of whole blood volume and correlated with Dl_O2 (r = 0.82, P < 0.01). These data suggest that diffusion limitation is related to shortened PTT in athletes and that maximal recruitment of PBV may defend against diffusion limitation.