Cardiopulmonary effects of ketanserin infusion in human pulmonary embolism

The release of platelet-derived vasoactive substances, particularly serotonin (5-HT), have been implicated in the pulmonary vasoconstrictor response following acute pulmonary embolism. Therefore, we studied the effects of infusing ketanserin, a 5-HT blocking agent, upon pulmonary and systemic hemodynamics and gas exchange in 10 patients with severe acute pulmonary embolism. These patients evidenced 45 +/- 17% mean angiographic pulmonary vascular obstruction. Ketanserin significantly decreased the mean pulmonary arterial pressure from 26 +/- 6 to 23 +/- 5 mm Hg (p less than 0.001). The total pulmonary vascular resistance decreased from 9.1 +/- 3.2 to 8.3 +/- 2.5 mm Hg/L X min X m2 (p less than 0.001). However, the mean cardiac index was unchanged. The systemic arterial and right atrial pressures were significantly decreased after ketanserin. The PaO2 increased in all patients from 60.5 +/- 12.6 to 66.5 +/- 13.6 mm Hg (p less than 0.05), whereas the venous admixture was unchanged. This was attributed to an increased PVO2 (27 +/- 7 to 30 +/- 5 mmHg, p less than 0.01) secondary to a reduction of calculated peripheral oxygen consumption during ketanserin infusion. The results indicate ketanserin is a mild pulmonary vasodilator and can reduce the pulmonary hypertension and increase the PaO2 after pulmonary embolism.     

Hemodynamic effects of a combination of vasopressin and ketanserin in patients with hepatitis b-related cirrhosis.

We measured the hemodynamic effects of intravenous vasopressin, ketanserin (a 5-hydroxytryptamine-2 receptor blocker), and vasopressin plus ketanserin in 33 patients with hepatitis B-related cirrhosis. Thirteen patients received vasopressin alone (0.66 units/min), ten patients ketanserin alone (10 mg), and ten patients vasopressin followed by vasopressin plus ketanserin. Vasopressin alone reduced the hepatic venous pressure gradient (from 18 +/- 5, mean +/- S.D., to 9 +/- 3 mmHg, p less than 0.0001) and cardiac output (p less than 0.0001), but increased mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.0001), pulmonary capillary wedge pressure (p less than 0.0001), and systemic vascular resistance (p less than 0.001). There was no significant change in heart rate. Ketanserin alone produced a significant fall in the hepatic venous pressure gradient (from 16 +/- 4 to 13 +/- 3 mmHg, p less than 0.0001), mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.005), and pulmonary capillary wedge pressure (p less than 0.005). Heart rate, cardiac output, and systemic vascular resistance were not significantly changed. The addition of ketanserin to vasopressin corrected most of the systemic hemodynamic disturbances produced by vasopressin. This combination did not lead to a further reduction in the hepatic venous pressure gradient. We conclude that intravenous ketanserin reduces portal pressure in patients with hepatitis B-related cirrhosis. The addition of ketanserin to vasopressin improves the detrimental systemic hemodynamic effects of vasopressin without further reducing the portal pressure.     

Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure

Enalapril is a recently developed angiotensin-converting enzyme inhibitor that improves cardiac function at rest in patients with congestive heart failure. This study investigated the acute effects of enalapril on the cardiovascular response to exercise, and then evaluated the long-term effects of enalapril on exercise capacity and functional status during a 12 week placebo-controlled trial in patients with heart failure. Ten patients underwent hemodynamic monitoring while at rest and during incremental bicycle exercise before and after 5 to 10 mg of enalapril orally. At rest, enalapril decreased mean blood pressure 13% (p less than 0.01) and systemic vascular resistance 20% (p less than 0.05) and increased stroke volume index 21% (p less than 0.01). During maximal exercise, enalapril decreased systemic vascular resistance and increased both cardiac and stroke volume indexes. Enalapril acutely increased exercise duration (p less than 0.05) and maximal oxygen consumption (p less than 0.001). These 10 patients and an additional 13 patients were then randomized to either placebo or enalapril treatment and followed up for 12 weeks. Of the 11 patients assigned to active treatment, 73% considered themselves improved compared with 25% of the patients assigned to placebo treatment (p less than 0.02). During long-term treatment, exercise capacity increased in patients receiving enalapril (p less than 0.001) but was unchanged in patients receiving placebo (intergroup difference, p less than 0.05). During long-term treatment, no adverse effects of enalapril occurred. Thus, enalapril improves cardiac function at rest and during exercise. Compared with placebo, maintenance therapy with enalapril results in symptomatic improvement and increased exercise capacity.     

Efficacy of bucindolol in systemic hypertension

The hemodynamic effects of oral bucindolol, a non-selective beta-adrenergic blocking agent with intrinsic sympathomimetic activity and direct vasodilating properties, were studied at rest and during handgrip exercise with a flotation-directed pulmonary artery catheter in 12 patients with mild to moderate essential hypertension. After the initial dose of 150 mg of bucindolol, blood pressure (BP) was significantly reduced and cardiac output was increased (from 5.9 +/- 0.8 to 6.8 +/- 1.6 liters/min) in the supine position and during exercise (p less than 0.05). Systemic vascular resistance was reduced (from 1,555 +/- 339 to 1,311 +/- 467 dynes s cm-5, p less than 0.01) at rest and without significant changes during exercise. There were increases in heart rate (13 +/- 13%, p less than 0.01) and right atrial (69 +/- 77%, p less than 0.05), pulmonary arterial (38 +/- 24 %, p less than 0.001) and pulmonary artery wedge pressures (62 +/- 46%, p less than 0.001) during exercise. Bucindolol did not change these variables at rest or during exercise. Bucindolol increased plasma norepinephrine levels both at rest (from 330 +/- 151 to 588 +/- 320 ng/liter, p less than 0.01) and during exercise (from 468 +/- 220 to 685 +/- 390 ng/liter, p less than 0.05). After 4 weeks of bucindolol with doses of 50 to 200 mg 3 times daily, BP was reduced in both supine and standing positions (mean arterial BP of 11 +/- 7% [p less than 0.001] and 11 +/- 6% [p less than 0.001], respectively), without changes in cardiac output, systemic vascular resistance or plasma norepinephrine level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prospective evaluation of doxorubicin cardiotoxicity by rest and exercise radionuclide angiography

The role of rest and exercise radionuclide angiography (RNA) in predicting the cardiotoxic effects of doxorubicin was assessed prospectively in 48 patients who received a mean total doxorubicin dose of 522 mg/m2 (range 480 to 600). Thirty-three of these patients also received cyclophosphamide (mean 5,220 mg/m2). Left ventricular (LV) ejection fraction (EF) at rest progressively decreased from the baseline value of 55 +/- 9% to 52 +/- 8% after 338 mg/m2 to 47 +/- 8% after completion of doxorubicin therapy (p less than 0.001). In 42 patients (88%) EF at rest decreased after doxorubicin administration. Although no patient had known prior heart disease, the EF response to exercise was abnormal in 11 patients before doxorubicin. EF at rest after doxorubicin was significantly lower (41 +/- 6% vs 49 +/- 8%, p less than 0.02) in these 11 patients than in the 29 patients in whom the pretreatment EF response to exercise was normal, and in 4 of the 11 patients congestive heart failure developed. While age was an independent risk factor, cyclophosphamide did not appear to enhance the cardiotoxicity of doxorubicin. By multivariate analysis, age (p = 0.01) and EF at the midcourse of doxorubicin therapy (p less than 0.001) were the most significant predictors of final EF after completion of doxorubicin therapy; neither rest nor exercise EF before doxorubicin appreciably improved the predictive value of age and EF at midcourse of therapy. Thus, some depression of LV function occurs in most patients receiving doxorubicin, and patients with abnormal baseline function appear to be at greater risk of clinical congestive heart failure after doxorubicin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of lymphocyte beta-adrenergic receptors at rest and during exercise in ambulatory patients with chronic congestive heart failure

To investigate beta-adrenergic receptor dysfunction in congestive heart failure (CHF), the density of lymphocyte beta receptors and adenylate cyclase activity was measured at rest and at peak exercise in 30 patients with CHF and 7 age-matched control subjects. At rest, patients with CHF had reduced beta-receptor density (normals 33 +/- 2; CHF 21 +/- 2 fmol/mg protein; p less than 0.01) and isoproterenol-stimulated adenylate cyclase activity (normals 50 +/- 9; CHF 28 +/- 4 pmol/mg protein/min; p less than 0.05). Sodium fluoride-stimulated adenylate cyclase activity was also reduced (normals 98 +/- 17; CHF 48 +/- 12 pmol/mg protein/min; p less than 0.01). In the patients with CHF, there was no significant correlation between receptor density and peak exercise VO2, ejection fraction or resting plasma catecholamines. In the normal subjects, maximal exercise increased beta-receptor density by 100% (rest 33 +/- 2; exercise 67 +/- 7 fmol/mg protein) and isoproterenol-stimulated adenylate cyclase activity by 66% (rest 50 +/- 9; exercise 83 +/- 18 pmol/mg protein/min (both p less than 0.01]. In contrast, patients with CHF exhibited only a 58% increase in beta-receptor density (rest 20 +/- 3; exercise 32 +/- 6 fmol/mg protein; p less than 0.01) and no significant change in isoproterenol-stimulated adenylate cyclase activity (rest 27 +/- 5; exercise 24 +/- 5 pmol/mg protein/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Improvement in exercise capacity and associated changes in hemodynamics and left ventricular function after the addition of metoprolol to nifedipine in patients with stable exertional angina

In 10 men with stable exertional angina, the changes in exercise capacity, hemodynamics, and left ventricular (LV) function were measured after 20 mg sublingual nifedipine (N) and again after adding 100 mg oral metoprolol (M). Nifedipine alone did not significantly improve exercise workloads (+18%) and duration (+21%), but the addition of metoprolol increased both parameters by a further 37 and 32%, respectively (both p less than 0.005 vs. N). After nifedipine the onset of angina was slightly delayed (5.14 +/- 2.41 min placebo (P), 6.00 +/- 2.31 min N, p less than 0.1) and occurred at higher workloads (36 +/- 17 W P, 43 +/- 8 W N, p less than 0.1). After the addition of metoprolol, the onset of angina was delayed substantially more (9.57 +/- 2.22 min, p less than 0.001 vs. P and N) and occurred at much higher workloads (62 +/- 20 W, p less than 0.001 vs. P and N). At rest (R) and during exercise (E), nifedipine decreased systemic vascular resistance (-36% R, -27% E, both p less than 0.001) and mean arterial pressure (-18% R, -21% E, both p less than 0.001), and increased heart rate (+15% R, +11% E, both p less than 0.001), Pulmonary artery wedge pressure on exercise increased less (22 +/- 7 mmHg P, 13 +/- 5 mmHg N, p less than 0.001). After adding metoprolol, the major change was a reduced heart rate (-25% vs. N at R and E, both p less than 0.001), and arterial pressure was unaltered. Pulmonary artery wedge pressure on exercise increased to 18 +/- 5 mmHg (p less than 0.05 vs. N). Exercise LV ejection fraction and volume did not change significantly after adding metoprolol despite marked improvement in angina. In this acute exercise study in patients with stable exertional angina, metoprolol added to nifedipine markedly improved exercise capacity by preventing the increase in heart rate seen with nifedipine. In our patients with relatively normal LV function at rest, the combination was safe and produced no deleterious effects on LV function.     

Acute inotropic stimulation with dopamine in severe congestive heart failure: beneficial hemodynamic effect at rest but not during maximal exercise

Hemodynamic and metabolic effects of dopamine were studied at rest and during maximal exercise in 13 patients with severe chronic congestive heart failure (CHF). During exercise before the administration of dopamine, the stroke volume index increased from 17.1 +/- 5.2 ml/m2 at rest to 28.1 +/- 10.9 ml/m2 (p less than 0.001) at exhaustion, while pulmonary capillary wedge (PCW) pressure increased from 22.7 +/- 12.7 to 43.9 +/- 11.9 mm Hg (p less than 0.001). The arteriovenous oxygen difference increased from 8.9 +/- 2.3 ml/100 ml to 12.4 +/- 2.0 ml/100 ml (p less than 0.001) and oxygen uptake increased from 3.5 +/- 0.6 0.6 to 11.9 +/- 2.5 ml/kg/min (p less than 0.001). At rest, dopamine increased the stroke volume index to 23.3 +/- 8.1 ml/m2 (p less than 0.001) and reduced the PCW pressure to 20.5 +/- 1.1 mm Hg (p less than 0.05). However, during maximal exercise, the stroke volume index and PCW pressure were not changed by dopamine: 28.1 +/- 10.9 versus 28.6 +/- 10.2 ml/m2 (difference not significant [NS]) and 43.9 +/- 11.9 versus 42.5 +/- 11.2 mm Hg (NS), respectively. In contrast, the maximal heart rate achieved during exercise was significantly higher with dopamine, 140.3 +/- 29.3 versus 136.0 +/- 29.7 beats/min (p less than 0.05), which contributed to a slight augmentation in the maximal cardiac index, 3.82 +/- 1.13 versus 3.64 +/- 1.17 liters/min/m2 (p less than 0.05). Nonetheless, neither peak arteriovenous oxygen difference nor maximal oxygen uptake were significantly changed by dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Static exercise with congestive heart failure and the response to vasodilating drugs

The hemodynamic response to static exercise in 28 patients with congestive heart failure (CHF) was compared with that in 8 control subjects. Static handgrip exercise at 50% of the maximal voluntary contraction was performed to fatigue. In patients with CHF, pulmonary arterial wedge pressure increased from 20 +/- 18 to 31 +/- 10 mm Hg (p less than 0.001) (mean +/- standard deviation) and systemic vascular resistance increased from 1,730 +/- 454 to 2,151 +/- 724 dynes s cm-5 (p less than 0.001). Although cardiac index did not change significantly, stroke volume index and stroke work index decreased from 24 +/- 6 to 20 +/- 6 ml/m2 (p less than 0.001) and 28 +/- 11 to 25 +/- 12 g-m/s2 (p less than 0.05), respectively. In control subjects, pulmonary arterial wedge pressure did not change significantly; cardiac index increased from 3.6 +/- 0.3 to 4.0 +/- 0.4 liters/min/m2 (p less than 0.05) and systemic vascular resistance increased slightly, from 1,011 +/- 186 to 1,106 +/- 180 dynes s cm-5 (p less than 0.05). The effects of arterial dilation with hydralazine on the response to static exercise were assessed in 10 of the patients with CHF. Compared with predrug exercise, cardiac index increased 68% (p less than 0.01), stroke volume index increased 76% (p less than 0.01) and systemic vascular resistance decreased 47% (p less than 0.01) after administration of hydralazine. Thus, static exercise can have adverse effects on cardiac performance in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary vasodilatation and improved myocardial lactate metabolism after angiotensin converting enzyme inhibition with cilazapril in patients with congestive heart failure.

The effects of angiotensin converting enzyme inhibition on systemic and coronary hemodynamics and on myocardial lactate metabolism were investigated before and 2 and 6 hours after cilazapril at rest and during supine submaximal exercise in 10 patients with New York Heart Association class II or III chronic congestive heart failure. Angiotensin converting enzyme inhibition, indicated by a significant increase in plasma renin activity, resulted in significant reductions in blood pressure and systemic vascular resistance. Myocardial oxygen demand decreased (resting double product 10.9 +/- 3.7 vs 12.2 +/- 3.8 mm Hg beats/min 10(-3); p less than 0.05), but coronary sinus blood flow remained unchanged and calculated coronary resistance decreased (0.45 vs 0.5 units, rest 6 hours; p less than 0.05) suggesting coronary vasodilatation. Changes in coronary vascular resistance were directly related to changes in systemic vascular resistance (r = 0.75, p less than 0.5). Myocardial lactate extraction increased at rest (47 +/- 60 vs 134 +/- 132 mumol/min; p less than 0.5) and during exercise (27 +/- 54 vs 491 +/- 317 mumol/min; p less than 0.05) both in patients with coronary artery disease (n = 5) and idiopathic dilated cardiomyopathy (n = 5). Resting lactate production was converted to lactate extraction in two patients with coronary artery disease. Neither plasma catecholamine nor atrial natriuretic peptide concentrations changed significantly. The results suggest coronary vasodilation and improved aerobic myocardial metabolism by angiotensin converting enzyme inhibition in patients with congestive heart failure.     

The effects of urapidil therapy on hemodynamics and gas exchange in exercising patients with chronic obstructive pulmonary disease and pulmonary hypertension

To examine the hemodynamic changes induced by vasodilator therapy with urapidil during exercise in patients with chronic obstructive pulmonary disease (COPD) and their potential impact on symptom-limited maximal oxygen consumption, we studied 12 clinically stable patients using a randomized, crossover design. Placebo or urapidil (60 mg orally thrice a day) was given during 48 h preceding each incremental maximal exercise testing. Urapidil compared to placebo consistently lowered the pulmonary artery pressure either at rest from 29 +/- 2.5 to 24 +/- 1.5 mm Hg (p less than 0.001) or during exercise from 55 +/- 3 to 46 +/- 2 mm Hg (p less than 0.01). At rest, the systemic arterial pressure was reduced from 97.5 +/- 4 to 88.5 +/- 3 mm Hg (p less than 0.001) with no significant difference in heart rate or cardiac index. During exercise, systemic arterial pressure decreased from 135 +/- 4 to 119 +/- 3 mm Hg (p less than 0.001). As compared to placebo, urapidil tended to increase the cardiac index from 6.1 +/- 0.4 to 6.6 +/- 0.4 L/min.m2 (NS) and to decrease heart rate, from 122 to 116 beats/min (NS); the resulting stroke volume index increased with urapidil from 49 +/- 3 to 57 +/- 4 ml/m2 (p less than 0.01); at rest, urapidil did not induce alteration in gas exchange, while during exercise, C(a-v)O2 decreased from 8.6 +/- 0.5 to 7.7 +/- 0.4 vol% (p less than 0.01), SVO2 increased from 39.5 +/- 2 to 44.5 +/- 1.5% (p less than 0.01), and SaO2 from 82 +/- 2 to 85 +/- 2% (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Improvement in forward cardiac output without a change in ejection fraction during nitroglycerin therapy in patients with functional mitral regurgitation

Left ventricular volumes and forward aortic flow were measured using combined two-dimensional echocardiography and doppler cardiography in seven patients with decompensated congestive heart failure and functional mitral regurgitation prior to and during intravenous administration of nitroglycerin. Total stroke volume was calculated from the difference between end-diastolic and end-systolic volumes, and regurgitant mitral volume from the difference between total stroke volume and forward aortic flow. Regurgitant mitral volume fell from 19 +/- 9 to 3 +/- 3 mL/beat (p less than 0.001), while forward stroke volume increased from 35 +/- 8 to 45 +/- 9 mL/beat (p less than 0.001). The changes were well correlated (r = 0.8, p less than 0.001). Total stroke volume decreased from 54 +/- 12 to 48 +/- 6 mL/beat (p less than 0.05), and ventricular end-diastolic volume from 173 +/- 66 to 158 +/- 66 mL (p less than 0.05). Left ventricular ejection fraction did not change significantly: 33 +/- 9% vs 32 +/- 9% (NS). Thus, in patients with severe congestive heart failure and functional mitral regurgitation, intravenous nitroglycerin redistributes blood flow within the heart by decreasing mitral regurgitation and increasing forward aortic flow, without affecting left ventricular ejection fraction.     

Influence of upright exercise on pulmonary hemodynamics in left heart failure.

Studies in severe chronic stable heart failure (HF) indicate that pulmonary resistance might remain unchanged during exercise and could subsequently contribute to limitation in exercise capacity of these patients. We assessed the possible role of the exercise decreases in mixed venous oxygen tension on this phenomenon in fifteen patients with chronic congestive heart failure (N.Y.H.A. functional classes II to IV) who underwent a symptom-limited treadmill exercise test with hemodynamic monitoring as well as repeated arterial and mixed venous blood gas analysis. For all patients there was an increase in cardiac output (from 3.7 +/- 0.2 to 6.7 +/- 0.5 l/min, p less than 0.001) and pulmonary wedge pressure (from 16 +/- 2 to 31 +/- 3 mm Hg, p less than 0.001) along with exercise with highly significant decrease in total systemic resistance and no significant (from 25.6 +/- 1.5 to 15.8 +/- 1.0 U, p less than 0.001) changes in pulmonary vascular resistances. Arterial blood oxygen tension increased from 86 +/- 3 to 99 +/- 3 mm Hg (p less than 0.001) and mixed venous oxygen tension (PvO2) decreased from 33 +/- 1 to 22 +/- 1 mm Hg (p less than 0.001). Changes in pulmonary vascular resistance during exercise were inversely related to changes in PvO2 (r = -0.61; p less than 0.05). We conclude that the observed decrease in PvO2 might be a determinant of unchanged pulmonary vascular resistance during treadmill-exercise test in severe heart failure patients.     

Elevated plasma beta-endorphin levels in patients with congestive heart failure

Recent experimental studies show that the opioid system is important to the pathophysiology of cardiovascular impairment in congestive heart failure. Plasma beta-endorphin levels were measured in 37 patients with congestive heart failure and compared with those of 21 age- and gender-matched normal subjects. The relation of plasma beta-endorphin levels and cardiac function at rest and exercise capacity was assessed in 17 of the patients with dilated cardiomyopathy. Exercise capacity was determined by symptom-limited maximal treadmill exercise with expired gas analysis. Plasma beta-endorphin levels were elevated and correlated with the patients' New York Heart Association functional cardiac status (control: 14.0 +/- 4.4 pg/ml; class II: 17.9 +/- 3.6 pg/ml; class III: 28.3 +/- 8.8 pg/ml; class IV: 46.7 +/- 14.6 pg/ml, mean +/- SD). No relation was found between plasma beta-endorphin levels and left ventricular systolic performance as assessed by M-mode and Doppler echocardiography. Plasma beta-endorphin levels were negatively correlated with cardiac output determined by Doppler echocardiography and positively correlated with systemic vascular resistance (r = -0.733, r = 0.747, respectively, both p less than 0.001), but not correlated with calf blood flow as measured by a plethysmography. A good correlation was found between plasma beta-endorphin levels at rest and exercise capacity. The correlations with peak oxygen consumption, anaerobic threshold, and peak rate-pressure product were r = -0.721, -0.672, and -0.674, respectively (p less than 0.01). The data show that plasma beta-endorphin levels are elevated in patients with congestive heart failure and reflect, to some degree, the severity of the disease.     

Acute effects of dibutyryl cyclic AMP on renal circulation in congestive heart failure

Acute effects of dibutyryl cyclic AMP (DBcAMP) on hemodynamics, renal circulation and plasma catecholamine levels were examined in 8 patients with congestive heart failure, NYHA functional class II or III. Before and during intravenous infusion of dibutyryl cyclic AMP at 0.1 mg/kg/min for 30 min, hemodynamic variables, renal blood flow (RBF) and plasma catecholamine levels were investigated. 1) DBcAMP increased the cardiac index from 2.69 +/- 0.65 to 3.60 +/- 0.84 liter/min/m2 (+ 33.8%, p less than 0.001) and heart rate from 70.9 +/- 14.3 to 84.1 +/- 15.7 bpm (+ 18.6%, p less than 0.001) and decreased mean aortic pressure from 91.8 +/- 11.3 to 82.5 +/- 9.8 mmHg (-10.1%, p less than 0.001), and systemic vascular resistance from 1840 +/- 570 to 1260 +/- 370 dynes-sec-cm-5 (-31.6%, p less than 0.001). 2) RBF increased from 335 +/- 81 to 517 +/- 188 ml/min (+ 54.3%, p less than 0.05) and renal vascular resistance decreased from 2.33 +/- 0.61 to 1.52 +/- 0.68 x 10(4) dynes-sec-cm-5 (-34.5%, p less than 0.001). 3) Plasma norepinephrine levels increased significantly. The results indicate that DBcAMP is useful for the treatment of congestive heart failure because it improves cardiac hemodynamics by afterload reduction and has a strong vasodilating effect on renal vascular beds.     

Hemodynamic effects of moricizine at rest and during supine bicycle exercise: results in patients with ventricular tachycardia and left ventricular dysfunction

To evaluate the hemodynamic effects of moricizine, 20 patients with frequent nonsustained ventricular tachycardia (VT) with a mean left ventricular ejection fraction (EF) of 39 +/- 14% were enrolled in a prospective single-blind, placebo-controlled study. Hemodynamic measurements were performed at rest and during supine bicycle exercise on placebo and moricizine therapy (10 mg/kg/day). Although 16 of 19 patients experienced no rest or exercise deterioration in hemodynamic parameters during drug dosing, three patients had acute deterioration of pulmonary capillary wedge pressure and cardiac index (CI) on moricizine. During follow-up of 6 +/- 3 months, two subgroups were identified: 10 of 19 patients had effective long-term reduction in VT, whereas 9 of 19 patients had poor control of ventricular arrhythmia or congestive heart failure and were discontinued from the trial. Baseline EF and hemodynamic parameters at rest were similar in both patient subgroups. However, protocol dropouts had a hemodynamic response to exercise on moricizine that was significantly depressed as compared to patients with a favorable antiarrhythmic outcome (p less than 0.02). The following hemodynamic profile characterizes patients unlikely to have an antiarrhythmic response to moricizine: an increase in CI of less than 1.0 L/min/m2 and no increase in left ventricular stroke work index during supine exercise.     

Prolonged cardiac recovery from exercise in asymptomatic adults late after atrial correction of transposition of the great arteries: evaluation with magnetic resonance flow mapping.

After atrial correction of transposition of the great arteries (TGA), dysfunction of the systemic right ventricle at rest and during exercise has been reported. Information on changes in systemic right ventricular function during recovery from exercise is lacking. This study evaluates cardiac recovery from supine exercise using magnetic resonance (MR) imaging in patients with asymptomatic TGA after atrial correction. Flow in the ascending aorta, representing stroke volume of the systemic ventricle, was assessed with MR flow mapping in 10 asymptomatic patients with atrially corrected TGA and in 12 controls at rest during exercise and an 8-minute recovery period. In response to exercise, the patients had a smaller increase in heart rate, stroke volume, and cardiac output than did controls. After exercise, no significant difference in halftime of heart rate recovery was observed (patients, 48 +/- 7 seconds; controls, 39 +/- 4 seconds [p >0.05]). In the patients, the time course of stroke volume recovery was significantly different (p <0.001). Stroke volume in the patients, as a percent difference from rest, remained significantly elevated, from 2.5 minutes (+16 +/- 5% vs +7 +/- 6%; p <0.05) to 8 minutes (+4 +/- 7% vs -3 +/- 5%; p <0.05) after exercise. Subsequently, cardiac output remained significantly elevated, from 4.5 minutes (+27 +/- 13% vs +15 +/- 11%; p <0.05) to 7 minutes (+22 +/- 11% vs +12 +/- 12%; p <0.05) after exercise. We conclude that heart rate recovery is within normal limits in patients with atrially corrected TGA. Furthermore, cardiac recovery from exercise, assessed with MR flow mapping, is prolonged in patients with asymptomatic TGA after atrial correction. Abnormal recovery may reflect dysfunction of the systemic right ventricle and an altered metabolic response to exercise.     

Dynamic mitral regurgitation. An important determinant of the hemodynamic response to load alterations and inotropic therapy in severe heart failure

Cardiac performance and mitral regurgitation were measured by Doppler echocardiography and right heart catheterization in 12 patients with severe congestive heart failure who performed isometric exercise during control and intravenous administration of dobutamine and nitroglycerin. During control isometric exercise, mitral regurgitant volume increased from 18 +/- 13 to 31 +/- 17 ml (p less than 0.01), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially decreased. At rest, dobutamine decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 10 ml (p less than 0.05), while forward stroke volume increased from 46 +/- 13 to 55 +/- 15 ml (p less than 0.05). During isometric exercise, dobutamine tended to decrease mitral regurgitant volume (24 +/- 12 vs. 31 +/- 17 ml; NS) when compared with control exercise. At rest, nitroglycerin decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 11 ml (p less than 0.05), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially increased. Similarly, during isometric exercise, nitroglycerin decreased mitral regurgitant volume from 31 +/- 17 to 20 +/- 14 ml (p less than 0.05), while significantly increasing forward stroke volume. At control rest, the median mitral regurgitant fraction was 24% for the 12 patients. Neither dobutamine nor nitroglycerin changed significantly forward stroke and mitral regurgitant volumes at rest and during isometric exercise in the six patients with resting mitral regurgitant fraction below the median. In contrast, dobutamine and nitroglycerin significantly decreased mitral regurgitant volume and increased forward stroke volume both at rest and during isometric exercise in the six patients with mitral regurgitant fraction greater than the median.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left and right ventricular function at rest and during bicycle exercise in the supine and sitting positions in normal subjects and patients with coronary artery disease. Assessment by radionuclide ventriculography

To assess the hemodynamic influence of posture during radionuclide cardiac studies, rest and exercise electrocardiographically gated blood pool cardiac scintigraphy was performed in the supine and sitting positions in 22 normal subjects and in 20 patients with coronary artery disease (CAD). In normal subjects, left ventricular ejection fraction was higher in the sitting position both at rest (67 +/- 6% versus 64 +/- 5%, p less than 0.01) and during exercise (79 +/- 9% versus 76 +/- 6%, p less than 0.05). Left ventricular end-diastolic volume in the sitting position was smaller at rest (by 19 +/- 26%, p less than 0.001), but this variable was similar in both positions during exercise (p greater than 0.05). Left ventricular end-systolic volume was smaller in the sitting position both at rest, by 26 +/- 31 percent, and during exercise, by 14 +/- 20% (p less than 0.001). Left ventricular end-diastolic volume increased from rest to exercise, in the sitting position by 31 +/- 23% (p less than 0.001) and in the supine position by 6 +/- 22% (p greater than 0.05). In patients with CAD, similar left ventricular ejection fractions in both postures were found at rest and during exercise. Left ventricular end-diastolic volume in the sitting posture was smaller at rest by 16 +/- 22% (p less than 0.01) and during exercise by 8 +/- 18% (p less than 0.05). Sitting left ventricular end-systolic volume was smaller by 18 +/- 20% (p less than 0.001) at rest and by 14 +/- 21% (p less than 0.01) during exercise. Left ventricular end-diastolic volume increased from rest to exercise, in the sitting position by 45 +/- 36% (p less than 0.001) and in the supine position by 32 +/- 51% (p less than 0.01). Despite significant hemodynamic differences, the value of rest-exercise radionuclide cardiac studies to detect CAD was similar in the 2 positions.     

Effect of betaxolol on the hemodynamic, gas exchange, and cardiac output response to exercise in chronic atrial fibrillation

BACKGROUND: beta-blockade controls the ventricular response to exercise in chronic atrial fibrillation (AF), but the effects of beta-blockers on exercise capacity in AF have been debated. METHODS: Twelve men with AF (65+/-8 years) participated in a randomized, double-blind, placebo-controlled study of betaxolol (20 mg daily). Patients underwent maximal exercise testing with ventilatory gas exchange analysis, and a separate, submaximal test (50% of maximum) during which cardiac output was measured by a CO2 rebreathing technique. RESULTS: After betaxolol therapy, heart rate was reduced both at rest (92+/-27 vs 62+/-12 beats/min; p < 0.001) and at peak exercise (173+/-22 vs 116+/-24 beats/min; p < 0.001). Maximal oxygen uptake (VO2) was reduced by 19% after betaxolol (21.8+/-5.3 with placebo vs 17.6+/-5.1 mL/kg/min with betaxolol; p < 0.05), with similar reductions observed for maximal exercise time, minute ventilation, and CO2 production. VO2 was reduced by a similar extent (19%) at the ventilatory threshold. Submaximal cardiac output was reduced by 15% during betaxolol therapy (12.9+/-2.3 vs 10.9+/-1.3 L/min; p < 0.05), and stroke volume was higher (88.0+/-21 vs 105.6+/-19 mL/beat; p < 0.05). CONCLUSION: Betaxolol therapy in patients with AF effectively controlled the ventricular rate at rest and during exercise, but also caused considerable reductions in maximal VO2 and cardiac output during exercise. The observed increase in stroke volume could not adequately compensate for reduced heart rate to maintain VO2 during exercise.