Increased plasma catecholamines in high renin hypertension

Plasma Catecholamines, indexes of sympathetic nervous tonicity, were measured simultaneously with renin both supine and after standing plus furosemide In patients with primary hypertension and normotensive volunteers. Seventy percent of hypertensive patients with high renin levels had increased Catecholamines compared with a 14 percent incidence in the combined group with low and normal renin (P < 0.001). Basal Catecholamines were related directly to renin in the hypertensive patients and to blood pressure in the normal (P < 0.05), but not in the high and low renin subgroups, and inversely to percent increase of catecholamines after standing plus furosemide in hypertensive and normotensive patients (P < 0.01). Sympathetic nervous hypertonicity may be responsible for the elevation of blood pressure and for the activation of the renin-angiotensin system in patients with high renin hypertension.     

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.     

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.     

Idiopathic paroxysmal ventricular tachycardia with a QRS pattern of right bundle branch block and left axis deviation: A unique clinical entity with specific properties

Eiectrophysiologic evaluation before and after the serial administration of verapamil, lidocaine, propranolol, and procainamide was undertaken in 4 young, asymptomatic patients with recurrent, sustained ventricular tachycardia (VT). No patient had obvious organic heart disease. The electrocardiogram during sinus rhythm showed S-T depression and T-wave inversion over the inferior and lateral precordial leads in 3 patients. QRS morphologic characteristics during episodes of VT showed a pattern of right bundle branch block and left axis deviation. In all 4 patients, VT could be both induced and terminated with electrical stimulation. Verapamil terminated VT and prevented the induction of sustained VT in 3 patients, and markedly slowed the rate of VT in 1 patient. Procainamide effectively prevented the induction of sustained VT in 2 patients, and although ineffective in preventing induction in 2 patients, it slowed the rate of tachycardia in both. Lidocaine and propranolol did not prevent the induction of VT in any patient. These findings suggest that slow-response tissues may be involved in the genesis of VT in these patients, and that VT in these patients may represent a unique clinical entity with distinct electrocardiographic, electrophysiologic, and electropharmacologic properties.     

Hypertension and propranolol therapy: Effect on blood pressure,plasma catecholamines and platelet aggregation

The effects of propranolol on blood pressure, plasma catecholamine concentration and platelet aggregation were examined in 16 patients with uncomplicated primary hypertension. The patients were studied at rest, during isometric handgrip stress and 48 hours after sudden discontinuation of propranolol therapy. Plasma catecholamine concentration and platelet aggregation studies were also carried out in 11 age-matched normotensive and healthy subjects at rest.Plasma catecholamine concentration and platelet aggregation were greater in the hypertensive than in the normotensive subjects, but the difference reached statistical significance for aggregation only. Exercise significantly increased catecholamines and platelet aggregability. The administration of propranolol (240 mg/day) produced a significant decrease in systolic and diastolic blood pressure and in aggregation (the percent of light transmission at 1 μM adenosine diphosphate, at rest) and a significant increase in catecholamine concentration. However, propranolol did not prevent the changes in all these variables with exercise.The abrupt discontinuation of propranolol was not associated with any subjective or objective untoward cardiovascular effect or abnormal changes in plasma catecholamines. However, in some patients the platelet aggregation studies demonstrated a hyperaggregable state, which may be due to a state of supersensitivity of platelets to circulating catecholamines.     

Acute hemodynamic effect of oral nifedipine in severe chronic congestive heart failure

The temporal hemodynamic effects of oral nifedipine after a single dose of 20 to 40 mg were evaluated in 11 patients with severe chronic congestive heart failure (left ventricular ejection fraction 0.22 +/- 0.7 [mean +/- standard deviation]). Nifedipine significantly reduced systemic vascular resistance, from 1,850 +/- 493 to 1,315 +/- 398 dynes s cm-5 at 1 hour (29%), to 1,410 +/- 246 at 3 hours and to 1,523 +/- 286 at 6 hours (p less than 0.05). Cardiac index increased 21%, from 2.07 +/- 0.46 to 2.51 +/- 0.83 liters/min/m2 at 1 hour, to 2.38 +/- 0.53 liters/min/m2 at 3 hours (p less than 0.05) and to 2.24 +/- 0.41 liters/min/m2 at 6 hours. The group response of stroke volume to nifedipine was smaller. A peak increase of 17% was seen 3 hours after initiation of therapy (22.6 +/- 7.2 versus 25.5 +/- 6.1 ml/m2). This difference did not reach statistical significance. Mean blood pressure declined significantly, from 94 +/- 20 to 80 +/- 13 mm Hg at 1 hour, to 83 +/- 15 mm Hg at 3 hours and to 86 +/- 17 mm Hg at 6 hours (p less than 0.05) and was associated with no significant change in heart rate. The marked decrease in blood pressure resulted in a decrease in rate-pressure product from 12,272 +/- 4,230 to 10,500 +/- 2,074 mm Hg/min at 1 hour, to 10,374 +/- 2,735 mm Hg/min at 3 hours and to 11,047 +/- 3,813 mm Hg/min at 6 hours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of the increased frequency of cardiovascular abnormalities associated with mitral valve prolapse by two-dimensional echocardiography

Two-dimensional echocardiography (2-D echo) was performed in 86 consecutive patients with mitral valve prolapse (MVP) and in 25 normal subjects. In normal subjects, mitral leaflet thickness was 3.5 +/- 0.8 mm (mean +/- standard deviation) and the mitral leaflet thickness to aortic wall thickness ratio was 1.0 +/- 0.2. Patients with MVP were separated into 2 groups: those with normal mitral thickness (less than or equal to mean + 2 SD observed in normal subjects, i.e., less than or equal to 5.1 mm) and normal mitral thickness to aortic wall thickness ratio (less than or equal to mean + 2 SD observed in normal subjects, i.e., less than or equal to 1.4) (group I) and others in whom these values were increased (group II). In group I, mitral thickness was 3.6 +/- 0.6 mm and mitral thickness to aortic wall thickness ratio was 1.1 +/- 0.1, and in group II, mitral thickness was 8.8 +/- 1.2 mm and mitral thickness to aortic wall thickness ratio was 2.2 +/- 0.5. The only significant cardiovascular abnormalities in group I were mitral regurgitation in 2 patients and tricuspid valve prolapse in 1 patient. In group II, 7 patients had clinically significant mitral regurgitation, 8 had aortic root abnormalities, 4 had tricuspid valve prolapse and 6 had Marfan's syndrome. Cardiovascular abnormalities were present in 60% (18 of 30) of patients in group II and in 6% (3 of 56) of patients in group I (p less than 0.001). Two-dimensional echo enabled the identification of a subset of patients with MVP who had thickened mitral leaflets. These patients had an increased incidence of cardiovascular abnormalities.     

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

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

Effects of oral diltiazem in paroxysmal supraventricular tachycardia

Electrophysiologic studies were performed before and 2 hours after the oral administration of 270 mg of diltiazem in 3 divided doses at 8-hour intervals in 36 patients with paroxysmal supraventricular tachycardia (SVT). Before diltiazem, all 36 patients had induction of sustained SVT: 24 with atrioventricular (AV) reentrance incorporating an accessory pathway (Group 1) and 12 with AV nodal reentrance (Group 2). After diltiazem, 20 patients in Group 1 lost the ability to induce or sustain SVT because of increased anterograde normal pathway refractoriness in 19 patients and increased retrograde accessory pathway refractoriness in 1. Eight patients in Group 2 could no longer induce or sustain SVT because of increased anterograde slow pathway refractoriness in 2 patients and increased retrograde fast pathway refractoriness in 6. Diltiazem concentration in the blood, measured in 29 patients, was 156 ± 75 ng/ml (mean ± standard deviation). Fifteen patients, 2 with and 13 without induction of sustained SVT after diltiazem, were discharged on the same dosage of diltiazem and followed up 5 ± 3 months. The former 2 patients had attacks of sustained SVT, whereas the latter 13 have been free of sustained SVT. In conclusion, oral diltiazem prevents induction and sustenance of paroxysmal SVT in most patients and may be used as an alternative agent for the prophylaxis of SVT.     

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

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

Application of 2-dimensional contrast studies during pericardiocentesis

Two-dimensional echocardiographic contrast studies were performed in 16 patients with pericardial effusion. A 4-chamber view was obtained by positioning the transducer at the apex. The exploratory needle was visualized in 9 patients. Five milliliters of saline solution were injected through the exploring needle and a cloud of echoes indicated its position. Microbubbles were seen in all 16 patients. This technique enabled the operator to identify that the needle was inadvertently in the left ventricle in 2 patients and in the right ventricle in 1. Furthermore, in 2 patients, when fluid could not be aspirated, the contrast study confirmed that the needle was in the pericardial sac; in both cases, pericardial fluid could be aspirated with slight manipulation of the needle. In a patient with a stab wound a negative contrast effect indicated the probable site of laceration. Thus, 2-dimensional contrast echocardiography was useful in locating needle position, which facilitated pericardiocentesis.     

Valvular heart disease: A perspective

Valve replacement has been one of the most important advances in the management of patients with valvular heart disease. The 10 and 15 year survival rate after isolated aortic and mitral valve replacement with the Starr-Edwards valve is 56 and 44%, respectively. At 5 and 7 years, survival with the Björk-Shiley, porcine bio-prosthesis and the Starr-Edwards valve is similar. Patients operated on during the last 5 to 10 years have a much better survival rate than those operated on in the 1960s; therefore, the 10 and 15 year survival of those operated on recently should improve.All patients with a mechanical prosthesis need long term anticoagulant therapy with drugs of the Coumadin type. Porcine bioprostheses have a low failure rate up to 5 years after valve replacement; after this, valve failure occurs at an increasing rate, but the incidence at 10 and 15 years is not known. Valve replacement usually produces a marked improvement in the symptomatic status of the patient because of improved hemodynamics; ventricular function is improved in selected subsets of patients. The role of long-term vasodilator therapy has not been fully determined. Antibiotic prophylaxis for secondary prevention of rheumatic carditis and for prevention of infective endocarditis is important.     

Neurogenic factors in low renin essential hypertension

The interrelationships between blood pressure, plasma catecholamines and plasma renin activity (PRA) were studied in 12 patients with low PRA, in 18 patients with essential hypertension and normal PRA and in 11 normal subjects, after being supine for 1 hour, standing 1 hour and after the oral administration of furosemide, 80 mg. Patients with low PRA were older and had higher (p < 0.05) mean blood pressure levels (113 ± 4.2 mg Hg) than patients with normal PRA (103 ± 1.9 mm Hg). Plasma norepinephrine levels were 145 ± 14 ng/liter in normal volunteer subjects, 202 ± 25 ng/liter in hypertensive subjects with normal PRA and 203 ± 26 ng/liter in hypertensive subjects with low PRA. The increase of plasma norepinephrine and epinephrine after standing 1 hour and after the administration of furosemide was similar in hypertensive subjects with low or normal PRA and in normal volunteer subjects. However, the increase in PRA after standing or after the administration of furosemide was significantly reduced in patients with low PRA. These data suggest that patients with low PRA have a normally responsive sympathetic nervous system and that the low PRA may be due to a defective renin response to the sympathetic nerve stimulation. Blood pressure was significantly correlated with plasma catecholamines in normal volunteer subjects (r = 0.71, p < 0.05) and in the hypertensive patients (r = 0.49, p < 0.05). An analysis of the regression lines for the two groups suggests that increased vascular reactivity to catecholamines may account for the increased blood pressure at each level of catecholamines in hypertensive subjects as compared to normal volunteer subjects. Basal plasma aldosterone levels were similar in patients with low and with normal PRA.Norepinephrine clearance was lower in hypertensive than in normotensive subjects.     

Humoral hypercalcemia of malignancy: A syndrome in search of a hormone

A woman with hypercalcemia and a hypernephroma confined to the left kidney underwent nephrectomy and subsequent resolution of hypercalcemia. Serum parathyroid hormone was undetectable in peripheral blood as well as in the left renal vein at surgery. Parathyroid hormone was also undetectable in the tumor extract using three different antisera to parathyroid hormone. Measurement of plasma prostaglandin E and 13,14-dihydro-15-keto-prostaglandin E₂ revealed levels within the normal range. The serum 1,25-dihydroxyvitamin D concentration was below normal and nephrogenous cyclic adenosine monophosphate was markedly elevated. The humoral agent responsible for hypercalcemia in this patient was not identified. This case emphasizes the need to search for new hypercalcemic factors in patients with hypercalcemia of malignancy.     

Determination of cardiac output by transcutaneous continuous-wave ultrasonic Doppler computer

To evaluate the accuracy of a new, portable, continuous-wave Doppler computer (Ultracom) in measuring cardiac output (CO), simultaneous thermodilution CO and Doppler CO were measured in triplicate in 39 selected patients. Technically adequate Doppler CO studies were obtained in 36 patients. Aortic root diameter was measured by echocardiography and the cross-sectional area was calculated. A continuous-wave Doppler transducer was placed in the suprasternal notch, directed toward the ascending aorta and angled until the maximal velocity signal was achieved. The systolic velocity integral was computed using fast Fourier transform technique. The Doppler CO was computed from the equation: CO = aortic cross-sectional area X systolic velocity integral X heart rate. Interobserver and intraobserver variability studies were also performed. CO measured by thermodilution ranged from 1.86 to 10.1 liters/min (mean 5.26 +/- 1.91 [+/- standard deviation]) and CO by the Doppler method ranged from 1.63 to 10.9 liters/min (mean 5.32 +/- 1.83). The correlation coefficient was 0.97 (p less than 0.001) and standard error of the estimate was 0.42. The regression equation showed that Doppler CO = 0.408 + 0.93 X thermodilution CO. The correlation in 29 volunteers for interobserver variability was 0.98 (p less than 0.001) and in 18 volunteers for intraobserver variability was 0.97 (p less than 0.001). Thus, CO can be determined accurately in many patients using this Doppler technique by trained and experienced persons; intra- and interobserver variability is small.