Hypertension and hyperparathyroidism: Inverse relation of serum phosphate level and blood pressure

In a retrospective study of 120 patients with surgically proved primary hyperparathyroidism, 71 patients who were normotensive and 49 patients (41 percent) who were either hypertensive at the time of parathyroidectomy or had a history of hypertension were compared. The mean serum calcium levels in the normotensive and hypertensive patients were very similar (11.6 ± 0.1 [SEM] mg/dl, and 11.8 ± 0.1), ruling against the hypothesis that hypercalcemia per se is the dominant cause of the hypertension of hyperparathyroidism. The mean serum creatinine levels in the two groups were also very similar (1.02 ± 0.05 and 1.09 ± 0.05 mg/dl), indicating that the hypertension of hyperparathyroidism is not the consequence of advanced renal parenchymal damage. The hypertensive patients did not have a significantly higher prevalence of urolithiasis. A review of the data in this and related studies leads to the conclusion that the hypertension of hyperparathyroidism is heterogeneous in origin. The mean serum phosphate level in the hypertensive patients was significantly lower than that in the normotensive patients (2.20 ±0.06 mg/dl versus 2.69 ± 0.09 mg/dl, p < 0.02), which may be due to a decrease in renal tubular phosphate reabsorption secondary to hypertension.     

Reduced drug elimination in congestive heart failure: Studies using aminopyrine as a model drug

Aminopyrine disposition was studied in 11 patients with congestive heart failure (CHF) and 15 control patients. The aminopyrine metabolic clearance rate was 29.7 ± 7.1 ml/min (mean ± SEM) in the patients with CHF and 125.1 ± 5.7 ml/min (mean ± SEM) in the control patients (p < 0.01). The aminopyrine breath test was 2.6 ± 0.4 per cent (mean ± SEM) in the patients with CHF and 5.6 ± 0.3 per cent (mean ± SEM) in the control subjects (p < 0.01). Probably due to fluid retention in CHF, the apparent volume of distribution of aminopyrine increased to 63.3 ± 4.9 liters (mean ± SEM) in patients with CHF from 43.1 ± 1.9 liters (mean ± SEM) in control patients, thereby further impairing aminopyrine elimination in patients with CHF (p < 0.01). The aminopyrine breath test was measured in a group of eight patients before treatment for an acute episode of CHF and seven to 10 days after initiation of therapy: in each patient clinical improvement was associated with an increased aminopyrine breath test, mean values of aminopyrine breath test increasing from 2.8 per cent before treatment to 5.2 per cent after initiation of treatment (p < 0.01). These results suggest that in patients with CHF hepatic drug-metabolizing activity is impaired, and the volume of distribution of drugs is increased, with consequent retardation in rates of drug elimination.     

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.     

Rotor's syndrome: A distinct inheritable pathophysiologic entity

Urinary total, isomer I and isomer III coproporphyrin excretion was determined in 11 patients with Rotor's syndrome, 23 phenotypically normal family members, 16 patients with the DubinJohnson syndrome and 20 normal control subjects. Control subjects excreted 24.8 ± 1.3 per cent (mean SEM) of urinary coproporphyrin as isomer I. Patients with the Dubin-Johnson syndrome excreted 88.9 ± 1.3 per cent as urinary coproporphyrin I, and patients with Rotor's syndrome excreted 64.8 ± 2.5 per cent as urinary coproporphyrin I, significantly different from the control subjects and the patients with the Dubin-Johnson syndrome (p < 0.001). Eight phenotypically normal parents and children of patients with Rotor's syndrome excreted 42.9 ± 5.4 per cent as urinary coproporphyrin I, intermediate between results in patients with Rotor's syndrome and control subjects (p < 0.001). Total urinary coproporphyrin excretion was markedly increased in patients with Rotor's syndrome (332 ± 86 μg/g creatinine) as compared to that in control subjects (p < 0.001) or obligate heterozygotes (p < 0.025).With respect to urinary coproporphyrin excretion, Rotor's syndrome and Dubin-Johnson syndrome are both inherited as autosomal recessive traits and are separate pathophysiologic entities. Study of rare but distinct inheritable disorders, such as these, provide insight into the functional dissociation of hepatic transport mechanisms.     

Pre- and postoperative hemodynamic and cineangiocardiographic assessment of left ventricular function in patients with aortic regurgitation.

Hemodynamic and angiocardiographic analysis was performed prior to and 14 months on the average following valve replacement in 11 patients with severe, isolated, pure, chronic aortic regurgitation.The aortic diastolic pressure, reduced prior to surgery, reverted to normal as did the cardiac index. Left ventricular filling pressure, elevated prior to surgery, returned to normal while aortic systolic pressure did not vary substantially. The markedly increased stroke volume returned to normal as did the net left ventricular stroke work. Left ventricular end-diastolic and end-systolic volumes, also markedly elevated, decreased but did not return to normal levels.The shape of the left ventricle, which was more spherical than normal during end-systole prior to surgery, as evidenced by the decrease in the systolic axis ratio, reverted to normal.The ejection fraction, severely reduced before surgery, increased moderately (46 ± 13 vs 51 ± 19 per cent) as did the extent of circumferential fiber shortening (δD) (21 ± 8 vs 27 ± 12 per cent). The mean velocity of fiber shortening ($\text{VCF}$) increased significantly (0.68 ± 0.2 vs 1.03 ± 0.47 circ./sec.), as did the mean left ventricular ejection rate (1.32 ± 0.48 vs 1.91 ± 0.76).Comparative analysis of the evolution of left ventricular function indices and of extramyocardial factors (end-diastolic fiber stretching and impedance to ejection) showed that whereas in some cases myocardial damage appeared to be irreversible, in others dramatic improvement sometimes occurred following surgery. It was not possible, however, to determine the threshold below which the damage was irreversible.It may therefore be concluded that in some patients with severe regurgitation attended by profound myocardial insufficiency, correction of the valvular defect could produce not only clinical and hemodynamic improvement, but also improvement in myocardial contractile status.     

Right and left ventricular dysfunction in patients with chronic obstructive lung disease: Assessment by first-pass radionuclide angiography

To evaluate the relationship between right and left ventricular function in patients with obstructive lung disease, we studied 10 normal subjects (group 1) and 37 patients with chronic obstructive pulmonary disease by first pass radionuclide angiography. These 37 patients were divided into three groups: nine with mild chronic obstructive pulmonary disease (group 2), 20 with severe chronic obstructive pulmonary disease (group 3) and eight with severe chronic obstructive pulmonary disease and primary left ventricular disease (group 4). In each subject right ventricular ejection fraction (RVEF), left ventricular ejection fraction (LVEF) and ejection fraction during first third of systole (first third LVEF) were calculated. LVEF RVEF First-Third LVEF Group 1 0.60 ± 0.05 0.52 ± 0.03 0.29 ± 0.04 Group 2 0.61 ± 0.08 0.52 ± 0.03 0.29 ± 0.02 Group 3 0.58 ± 0.09 0.46 ± 0.091 0.24 ± 0.061 Group 4 0.51 ± 0.061 0.44 ± 0.091 0.20 ± 0.031 1 p < 0.05 versus 1. All subjects in group 2 had normal left ventricular and right ventricular function. In group 3,11 of 10 (55 per cent) had a low RVEF and three of 20 (15 per cent) a low LVEF. However eight of 20 in this group (40 per cent) had a depressed first-third LVEF. The correlation between decline in RVEF and first-third LVEF was good r = 0.73. We conclude that (1) certain indices of early systolic left ventricular ejection are abnormal in many patients with chronic obstructive pulmonary disease and correlate with the decline in right ventricular function; (2) this is not seen in patients with mild chronic obstructive pulmonary disease and is worse in patients with underlying left-sided heart disease.     

Divalent cation metabolism: Familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism

Twenty-three members of three families with a syndrome of hypercalcemia without hypercalciuria (familial hypocalciuric hypercalcemia) were compared to a group of 64 subjects with hypercalcemia due to typical primary hyperparathyroidism. Patients with familial hypocalciuric hypercalcemia had higher creatinine clearance values than those with primary hyperparathyrodism (115 ± 27 versus 87 ± 27 ml/min/1.73 m² (mean ± 1 standard deviation [SD] p < 0.0001). Although renal function was well preserved, the group with familial hypocalciuric hypercalcemia showed a mean serum magnesium concentration of 2.05 ± 0.17 meq/liter, significantly higher than that in normal subjects (1.74 ± 0.12 meq/liter, p < 0.0001) or than in the group with primary hyperparathyroidism (1.71 ± 0.21 meq/liter, p < 0.0001). In familial hypocalciuric hypercalcemia the degree of hypermagnesemia was directly proportional to the degree of hypercalcemia (R = +0.54, p < 0.01), contrasting with an inverse relation of serum calcium and magnesium concentrations in primary hyperparathyroidism (R = ?0.32, p < 0.02). Urinary excretion of both calcium (calcium:creatinine clearance ratio 0.006 ± 0.004 versus 0.024 ± 0.01, p < 0.0001) and magnesium (magnesium:creatinine clearance ratio 0.031 ± 0.0008 versus 0.047 ± 0.03, p < 0.003) was significantly lower in familial hypocalciuric hypercalcemia than in primary hyperparathyroidism. There was no evidence that abnormal protein binding of cations in serum from those with familial hypocalciuric hypercalcemia accounted for the hypercalcemia and hypermagnesemia or for the disproportionately low urinary excretion of divalent cations by rendering them resistant to glomerular filtration. After fractionation by electrophoresis on cellulose acetate, the major plasma protein components were quantitatively similar in both groups. Furthermore, ionized and ultrafiltrable calcium and ultrafiltrable magnesium showed consistent relations to total calcium and total magnesium concentrations in plasma from both groups. Therefore, in familial hypocalciuric hypercalcemia there are increased serum concentrations of the physiologically active forms of both calcium and magnesium, and the renal handling of the filtered load of these divalent cations differs in familial hypocalciuric hypercalcemia and primary hyperparathyroidism.     

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.     

Plasma alpha-cell glucagon in primary hyperparathyroidism

Plasma glucose, insulin, and alpha-cell glucagon profiles were examined in ten adults with uncomplicated primary hyperparathyroidism before and 8–12 wk after surgical removal of a single parathyroid adenoma. Treatment restored abnormal serum calcium and phosphorus concentrations to a normal range and reduced serum parathyroid hormone levels from 47 ± 4 to 16 ± 4 μ 1 Eq/ml (normal = 0–40). Plasma glucose curves during 100-g oral glucose tolerance, 30 min intravenous glucose (1.5 g/min), or arginine infusions (1.0 g/min) did not differ before and after surgery. However, basal and peak insulin concentrations were higher before treatment during these tests (p < 0.05). Basal glucagon levels were unaffected by hyperparathyroidism (72 ± 7 versus 77 ± 7 pg/ml). Peak 30 min values after arginine provocation were also similar before and after treatment as was maximal suppression of basal glucagon during glucose infusions. Four patients also received 400 g lean beef meals. Glucose and glucagon responses over 240-min periods were nearly identical before and after surgery despite higher insulin levels before treatment.It is concluded that elevated serum parathyroid hormone and plasma insulin concentrations in primary hyperparathyroidism do not relate to abnormalities of plasma alpha-cell glucagon in the basal state or after glucose, arginine, or protein administration.     

Effects of vasodilators on pulmonary hemodynamics and gas exchange in left ventricular failure

Nitroprusside (NP) has been shown to improve left ventricular function in patients with congestive heart failure, but despite an increased cardiac output and decreased pulmonary capillary pressure, arterial oxygen tension (P_aO₂) may fall. In order to determine the mechanism of this hypoxemia, and to determine if similar effects occur with non-parenteral vasodilators, hemodynamic, respiratory, and blood gas responses to NP, hydralazine (H), and hydralazine combined with isiosorbide dinitrate (H+N) were studied in 10 patients with left ventricular failure. At the dosages used, all three drug regimens increased cardiac output equivalently, but pulmonary vascular responses differed. NP and H+N decreased mean pulmonary artery pressure, pulmonary wedge pressure, and pulmonary arteriolar resistance, while H did not. NP decreased P_aO₂ by 10.4 mm. Hg (p < .01) and H+N decreased it by 5.3 mm. Hg (p < .06) while H did not alter P_aO₂. Arteriolar-alveolar oxygen gradient increased with NP (150 ± 39 per cent, p < .01) and with H+N (73 ± 23 per cent, p < .01) but not H alone (51 ± 16 per cent). Similarly, per cent change in venous admixture increased on NP (28.7 ± 3.3 to 38.5 ± 3.1 per cent, p < .01) and H+N (28.1 ± 3.3 to 36.8 ± 3.5 per cent, p < .01) but not H alone (28.1 ± 3.3 to 31.5 ± 4.1 per cent). There was no increase in arterial carbon dioxide tension or change in pulmonary function studies with any of the drugs. Due to the increase in cardiac output, oxygen delivery index (cardiac output times arterial oxygen content) increased with each regimen despite the changes in P_aO₂. Changes in arteriolar-alveolar oxygen gradient correlate with the changes in pulmonary arteriolar resistance. Thus vasodilators which have prominent pulmonary vascular effects can decrease P_aO₂ in patients with congestive heart failure, and this effect is most likely due to increasing ventilation-perfusion inequities.     

Comparison of the effects of diuretic therapy and low sodium intake in isolated systolic hypertension

Of 103 patients with isolated systolic hypertension, 71 were treated with diuretics and another 32 with low-sodium diet. In the 71 who were treated with diuretics, body weight decreased from 69.48 ± 1.47 to 68.60 ± 1.45 kg (p < 0.0005) and systolic blood pressure from 178 ± 2 to 152 ± 2 mm Hg (p < 0.0005). Plasma renin activity increased from 1.78 ± 0.30 to 7.32 ± 1.78 ng/ml per hour (p < 0.005) and urinary aldosterone from 10 ± 1 to 23 ± 4 μg per 24 hours (p < 0.005). The greatest decrease in systolic blood pressure occurred in patients in the low-renin group (?32 ± 2 mm Hg), whereas it decreased by 24 ± 2 mm Hg (p < 0.04) in the normal-renin group; however, blood pressure did not change significantly in the high-renin group. In the 32 patients who were treated with low-sodium diet, the 24-hour urinary sodium excretion decreased from 143 ± 10 to 48 ± 5 meq (p < 0.005), body weight decreased from 71.18 ± 2.50 to 70.17 ± 2.47 kg (p < 0.005), systolic blood pressure decreased from 174 ± 2 to 156 ± 3 mm Hg (p < 0.0005), and diastolic blood pressure decreased from 90 ± 1 to 87 ± 1 mm Hg (p < 0.01). Plasma renin activity increased from 2.25 ± 0.33 to 4.27 ± 0.43 ng/ml per hour (p < 0.005) and urinary aldosterone from 9 ± 1 to 15 ± 2 μg per 24 hours (p < 0.005). The decrease in the systolic blood pressure was related to the pretreatment 24-hour urinary sodium excretion (r = 0.40, p < 0.05). The smallest decrease in systolic blood pressure occurred in the patients with high renin values (?1 ± 9 mm Hg, n = 5), whereas the decrease in systolic blood pressure in the low-renin (n = 12) and normal-renin groups (n = 15) was similar, ?22 ± 2 mm Hg and ?21 ± 3 mm Hg, respectively (p < 0.005 compared with the high-renin group). These results indicate that both diuretic therapy and low-sodium diet are effective antihypertensive means in most patients with isolated systolic hypertension and low or normal plasma renin activity.     

Echocardiographic LV function in thyrotoxicosis.

Serial echocardiographic studies were made in 11 patients with thyrotoxicosis. In the untreated thyrotoxic state heart rate was increased (96 ± 14 (SD) beats/minute) as were measurements of left ventricular (LV) contractility. LV shortening fraction was 40 ± 6 per cent (mean ± SD), mean velocity of circumferential fiber shortening was 1.60 ± 0.32 circumferences/sec., and velocity of posterior wall motion 71 ± 13 mm./sec. Stroke index and cardiac index were increased: 52 ± 18 (SD) ml./beat per M.² and 5.0 ± 1.8 (SD) liter/minute per M.², respectively. Cardiac chamber size was normal in all but one very ill patient and did not change during the study. Treatment with propranolol, 60 mg./day, produced a dramatic and immediate improvement in the clinical state of the patient. Heart rate decreased to 84 ± 11 beats/minute (p < 0.01), stroke index increased marginally (p > 0.05), and cardiac index was unaltered (p > 0.05). There was no change in parameters of LV contractility (p > 0.05). Treatment with a specific antithyroid drug (methimazole or propylthiouracil) brought about further improvement in the clinical state and a further decrease in heart rate (p < 0.01). LV contractility decreased and after two to three months, when the patients were euthyroid, these measurements were in the range of normal (per cent shortening of the LV diameter 37 ± 4, p < 0.01; mean velocity of circumferential fiber shortening 1.31 ± 0.23 circumferences/sec., p < 0.05; maximum velocity of posterior wall motion, 46 ± 14 mm./sec., p < 0.01). Systolic time interval measurements were in keeping with these data. They showed enhanced LV performance in the control state, no change with propranolol, and they returned toward the range of normal after definitive antithyroid treatment.     

Clinical,electrophysiologic and hemodynamic profile of patients resuscitated from prehospital cardiac arrest

Of 352 prehospital cardiac arrest patients studied during a three year period, the initial mechanism recorded by rescue personnel was ventricular fibrillation in 220 (62 per cent), ventricular tachycardia in 24 (7 per cent) and bradyarrhythmias or asystole in 108 (31 per cent). Early survival was best in the group with ventricular tachycardia (16 of 24 patients resuscitated and survived hospitalization—67 per cent); the prognosis was worst in the group with bradyarrhythmias asystole (nine of 108 admitted to the hospital alive—none survived hospitalization); and 51 of 220 patients with ventricular fibrillation (23 per cent) were resuscitated and survived subsequent hospitalization, a significantly better outcome than previously reported for ventricular fibrillation.Central nervous system damage accounted directly or indirectly for 28 of 48 in-hospital deaths (59 per cent), and hemodynamic abnormalities for 31 per cent. Only five in-hospital deaths (10 per cent) were primary arrhythmic. The majority of survivors had evidence of left ventricular hemodynamic abnormalities (mean left ventricular end-diastolic pressure = 17.80 ± 8.99 mm Hg; mean cardiac index = 2.62 ± 0.72 liters/min/m²; mean ejection fraction = 38.58 ± 17.55 per cent), but approximately one third of the surviving patients had normal left ventricular function. Early in-hospital electrophysiologic data demonstrated persistent, drug-resistant complex ventricular arrhythmias during the first 72 hours; but intracardiac electrophysiologic studies elicited specific patterns only in patients with ventricular tachycardia, whose arrhythmias were reproducible in five of six patients studied. The risk of recurrent ventricular fibrillation in the first 72 hours was predicted better by coexistent conducting system abnormalities, than by the persistent ventricular arrhythmia alone.We conclude that the electrical mechanism of prehospital cardiac arrest provides early prognostic information, that early survival rates are improving and that one third of the discharged survivors have normal indices of left ventricular function. The presence of conducting system abnormalities identifies a subgroup at high risk for in-hospital recurrent ventricular fibrillation.     

Abnormal interventricular septal motion following cardiac surgery: clinical, surgical, echocardiographic and radionuclide correlates.

Interventricular septal motion was studied prospectively by echocardiography in 45 patients examined before and after cardiac surgery. In addition, nine of the patients underwent pre- and postoperative gated cardiac blood pool scintigraphy. All had normal septal motion preoperatively. Of the 40 patients whose surgery included cardiopulmonary bypass, 31 had abnormal and 9 had normal postoperative septal motion. All five patients without cardiopulmonary bypass had normal postoperative septal motion (p < 0.001). Among those patients undergoing cardiopulmonary bypass, there was no difference between those with normal and those with abnormal postoperative septal motion in clinical diagnosis, operative procedure, or surgical techniques (bypass time, aortic cross-clamp time, pericardium closed, prosthesis used), except that potassium arrest had been used more frequently in those with abnormal motion (18 of 31 vs 1 of 9, p < .02). Preoperatively, there was no difference in echocardiographic right ventricular dimension (8 ± 1 vs 8 ± 1 mm., mean ± SEM). However, postoperatively, those with abnormal motion had a larger right ventricle than those with normal motion (12 ± 1 vs 8 ± 1 mm., p < .005). The postoperative percent systolic septal thickening decreased in those with abnormal motion (42 ± 4 per cent to 23 ± 4 per cent) (p < 0.001) and did not change in those with normal postoperative motion (47 ± 7 per cent to 48 ± 4 per cent). These findings were corroberated on gated cardiac blood pool scanning, and in addition demonstrated that when present, the motion abnormality was more marked at the upper than the lower septum. These findings confirm that postoperative abnormal systolic septal motion and thickening are common but not invariable following cardiopulmonary bypass and that they appear unrelated to preoperative clinical diagnosis, hemodynamics, or surgical technique.     

Frequency spectra of the first heart sound and of the aortic component of the second heart sound in patients with degenerated porcine bioprosthetic valves

To determine the usefulness of the frequency of heart sounds in the assessment of porcine bioprosthetic valve degeneration, frequency spectra of phonocardiograms of the first heart sound and the aortic component of the second sound were analyzed in 31 patients with degenerated porcine bioprosthetic valves. Comparisons were made with 35 control patients whose valves were inserted 1 month or less. Among 23 patients with degenerated porcine bioprosthetic valves in the mitral position, the dominant frequency of the first heart sound was 95 ± 11 Hz, which exceeded the first sound in 18 controls (51 ± 3 Hz) (p < 0.01). The degenerated mitral porcine bioprosthetic valves of 14 patients showed calcification or fibrosis and the first heart sound in these patients was 115 ± 16 Hz, which exceeded that of control subjects (p < 0.001). The degenerated mitral porcine bioprosthetic valves of 9 patients showed torn leaflets only, and the first heart sound in these patients was 64 ± 9 Hz, which did not differ from that of control subjects. In the aortic position, 8 valves were degenerated and the aortic component of the second sound was 109 ± 12 Hz, which was higher than that in 17 control subjects (63 ± 4 Hz) (p < 0.001). Only 2 of these degenerated valves showed tears unaccompanied by calcific deposits or fibrosis, and the frequencies were comparable to that of control subjects. These observations indicate that the frequency of heart sounds in patients with degenerated porcine bioprosthetic valves becomes abnormally elevated when degeneration is accompanied by calcification or fibrosis, which causes the cusps to stiffen.     

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.     

Outpatient treatment of juvenile-onset diabetes with a preprogrammed portable subcutaneous insulin infusion system

Seven patients with juvenile-onset, insulin-dependent diabetes (aged 13 to 32 years) were continuously treated for 12 to 32 weeks while out of the hospital in their usual environment with a portable, batterypowered infusion pump which delivers insulin subcutaneously in basal (between-meal) doses with pulse dose increments before meals. Mean blood glucose levels (237 ± 28 mg/dl during conventional insulin therapy) fell to 105 ± 5 mg/dl after four weeks of pump treatment (p < 0.01) and were maintained at 80 to 104 mg/dl as pump treatment was continued beyond eight weeks. Glycosylated hemoglobin levels (16.0 ± 1.5 per cent before pump therapy) also fell within two weeks (p < 0.01) reaching normal values (9.9 ± 0.3) after eight weeks of pump therapy. Mean plasma cholesterol and triglyceride levels were elevated during conventional therapy and fell to normal after pump treatment. After the first month of pump treatment, only minor adjustments in insulin dose (< 5 per cent of total daily dose) were made. No episode of mechanical pump failure occurred during the 1,110 patient-days of treatment. Overinsulinization and underinsulinization due to human error were relatively rare (four and six episodes, respectively) and failed to result in symptoms of hypo- or hyperglycemia. All patients performed their usual home, work or school activities during pump treatment. We conclude that normalization or near normalization of blood glucose levels can be achieved with a portable subcutaneous insulin infusion system when continuously used to treat patients with juvenile-onset, insulindependent diabetes outside the hospital for three to eight months.     

Influence of volume expansion on proximal tubular sodium reabsorption in congestive heart failure

Proximal tubular sodium reabsorption was studied in ten patients with severe decompensated congestive heart failure when marked extracellular fluid volume expansion was present and again after diuresis to dry weight. The technique used was pharmacologic blockade of distal nephron sites by diuretic agents. The percentage of the filtered load of sodium reabsorbed by the proximal tubule increased from 68 ± 5 per cent to 85 ± 2 per cent and of chloride from 61 ± 6 per cent to 78 ± 4 per cent following reduction of the expanded extracellular volume. This increase could not solely be accounted for by change in filtered sodium load or enhanced aldosterone activity. It is concluded that although the proximal tubule responds in an appropriate manner qualitatively to volume stimuli, an enhanced fractional proximal sodium reabsorption at any given level of extracellular fluid volume may characterize the patient with congestive heart failure. The exact mechanism of sodium retention in heart failure must remain speculative.     

Global and regional left ventricular response to bicycle exercise in coronary artery disease. Assessment by quantitative radionuclide angiocardiography.

The left ventricular response to bicycle exercise was evaluated in 60 patients with coronary artery disease and in 13 normal control subjects. Left ventricular ejection fraction, mean normalized ejection rate and regional wall motion were determined using first-pass radionuclide angiocardiograms obtained at rest and again during peak graded bicycle exercise. All normal subjects demonstrated improved left ventricular function with exercise. Left ventricular ejection fraction increased significantly from 67 ± 3 per cent (mean ± SE) at rest to 82 ± 4 per cent with exercise (p < 0.001). Similarly, the left ventricular ejection rate increased significantly from 3.47 ± 0.31 sec^?1 to 6.53 ± 0.42 sec^?1(p < 0.001). In contrast, in 44 of 60 patients with coronary artery disease, the ejection fraction or ejection rate either decreased or remained the same with exercise. New or exaggerated regional wall motion abnormalities were detected in 28 of 60 patients with coronary artery disease. Over-all, global or regional evidence of compromised left ventricular reserve was found in 48 of 60 patients with coronary artery disease.The major determinant of an abnormal left ventricular response to exercise was the presence or absence of electrocardiographic evidence of myocardial ischemia. Left ventricular ejection fraction decreased or remained the same with exercise in all patients with coronary artery disease and electrocardiographic ischemia. New regional wall motion abnormalities were detected in 20 of these patients. In this group, the left ventricular ejection fraction decreased from 66 ± 2 per cent at rest to 58 ± 2 per cent with exercise (p < 0.001), whereas the ejection rate was unchanged by exercise (rest 3.33 ± 0.21 sec^?1; exercise 3.34 ± 0.22 sec^?1, p > 0.05). Of the 30 patients with coronary artery disease who exercised to symptom-limiting fatigue without electrocardiographic ischemia, 18 demonstrated compromised left ventricular reserve with exercise. Twelve of the remaining patients with coronary artery disease had normal left ventricular reserve, in eight of whom ventricular function was completely normal both at rest and during exercise. In this group exercised to fatigue, the left ventricular ejection fraction increased from 53 ± 4 per cent at rest to 58 ± 2 per cent with exercise (p < 0.001). The ejection rate also increased from 2.48 ± 0.24 sec^?1 to 3.67 ± 0.39 sec^?1 (p < 0.001). The direction and magnitude of the left ventricular responses to exercise were not affected by long-term oral propranolol administration in 22 patients. Based upon either abnormal exercise left ventricular reserve or abnormal global and regional left ventricular function at rest, the over-all sensitivity of this radionuclide technic for the detection of coronary artery disease was 87 per cent (52 of 60 patients). These data demonstrate that exercise ventricular performance studies provide important physiologic insights into left ventricular functional reserve as well as a sensitive noninvasive approach for the detection of coronary artery disease.