Distinct regulations by calcium of cyclic GMP levels and catecholamine secretion in isolated bovine adrenal chromaffin cells

The effects of various calcium-dependent secretagogues on cyclic GMP levels and catecholamine (CA) secretion were measured in a preparation of bovine adrenal chromaffin cells. The secretory effect of acetylcholine (ACh; 8--10 fold stimulation) was mimicked by nicotine but not muscarine. Three--five fold stimulations of cyclic GMP levels were also obtained with ACh and muscarine but not nicotine. High concentration of K+, and the ionophore A23187, also elevated cyclic GMP levels. However, secretion produced by veratridine, ouabain, and the ionophore X537A was not accompanied by any rise in cyclic GMP levels. Removal of extracellular calcium significantly decreased both basal levels of CA secretion and of cyclic GMP and completely abolished their stimulation by ACh. The half-maximal effects of calcium on the cholinergic stimulations of cyclic GMP levels and of CA secretion were observed at 0.2 and 2.5 mM, respectively. Substitution of Ca2+ by Sr2+ was more effective in maintaining the cyclic GMP response than the secretory response. The calcium channel blockers Co2+, Mg2+ and Ni2+ inhibited the cholinergic stimulation of cyclic GMP more than that of CA release. On the other hand, the organic calcium channel blockers, verapamil and methoxyverapamil (D--600) were more effective antagonists of the secretory response. These data indicate that the cholinergic stimulations of CA secretion and of cyclic GMP levels in bovine adrenal chromaffin cells are regulated by calcium via two distinct mechanisms.     

Dynamic QT Interval Changes from Supine to Standing in Healthy Children

Background

QT-interval variations in response to exercise-induced increases in heart rate have been reported in children and adults in the diagnosis of long QT syndrome (LQTS). A quick standing challenge has been proposed as an alternative provocative test in adults, with no pediatric data yet available.

Left ventricular cavity obliteration: hemodynamic behavior of the postextrasystolic beat

Angiographic contrast media are known to induce alterations in cardiovascular dynamics which may result in acute pulmonary edema. The risk of pulmonary edema was previously shown to be negatively correlated to the level of colloid oncotic pressure (COP). It was also shown that the gradient between COP and left ventricular end-diastolic pressure (LVEDP) represents a better predictor of pulmonary edema than does LVEDP alone. The present report evaluates the effects of a bolus injection of contrast media on those pressures, as predisposing factors for pulmonary edema.Our data are based on 15 unselected patients admitted for coronary angiography. The plasma volume increased by 16.5% (2,903 to 3,384 ml.) at two minutes after injection of a 50 c.c. bolus of meglumine diatrizoate (Renographin 76%) and had returned towards normal at 30 minutes. In parallel the COP decreased from 23.4 ± 2.4 to 19.6 ± 2.3 mm. Hg (P < 0.001) to return the 22.7 ± 2.6. The COP-LVEDP gradient decreased by 8.7 mm. Hg (8.4 to ?0.3, P < 0.001). Such a gradient was well within the danger zone of pulmonary edema. These findings further clarify the mechanisms of pulmonary edema induced by contrast media.     

Rest and exercise ventricular function in adults with congenital ventricular septal defects

Rest and exercise right and left ventricular function were compared using equilibrium gated radionuclide angiography in 19 normal sedentary control subjects (mean age 28 years, range 22 to 34) and 34 patients with hemodynamically documented congenital ventricular septal defect (VSD) (mean age 27 years, range 20 to 40). The 34 patients with VSD were divided into 3 groups: those in Group 1 (17 patients) had pulmonary to systemic blood flow ratios of less than 2 to 1; those in Group 2 (12 patients) had prior surgical closure of VSD (mean interval from surgery 17 years, range 9 to 22), and those in Group 3 (5 patients) had Eisenmenger's complex. Gated radionuclide angiography was performed at rest and during each level of graded supine bicycle exercise to fatigue. Heart rate, blood pressure, maximal work load achieved, and right and left ventricular ejection fractions were assessed. The control subjects demonstrated an increase in both the left and right ventricular ejection fractions with exercise (0.70 +/- 0.07 to 0.79 +/- 0.05 and 0.46 +/- 0.06 to 0.57 +/- 0.04; p less than 0.001 for left and right ventricles, respectively). All study groups failed to demonstrate an increase in ejection fraction in either ventricle with exercise. Furthermore, resting left ventricular ejection fraction in Groups 2 and 3 was lower than that in the control subjects (0.59 +/- 0.09 and 0.54 +/- 0.06 versus 0.70 +/- 0.07; p less than 0.001) and resting right ventricular ejection fraction was lower in Group 3 versus control subjects (0.30 +/- 0.07 versus 0.46 +/- 0.06; p less than 0.001). Thus (1) left and right ventricular function on exercise were abnormal in patients with residual VSD as compared with control subjects; (2) rest and exercise left ventricular ejection fractions remained abnormal despite surgical closure of VSD in the remote past; (3) resting left and right ventricular function was abnormal in patients with Eisenmenger's complex; (4) lifelong volume overload may be detrimental to myocardial function.     

Nodular regenerative hyperplasia of the liver associated with macroglobulinemia: A clue to the pathogenesis

Nodular regenerative hyperplasia of the liver is an infrequent condition characterized by transformation of the hepatic parenchyma into nodules with only mild fibrosis. Little is known about the etiology except that there is usually an underlying chronic disease, such as Felly's syndrome, which antedates the development of clinical liver disease. It is poorly understood how the associated diseases contribute to the pathogenesis of nodular regenerative hyperplasia. Presented are four cases of nodular regenerative hyperplasia in which macroglobulinemia was also present. This new association suggests to us a hypothesis for the pathogenesis of nodular regenerative hyperplasia.

Histologic examination of the livers in these and other cases of nodular regenerative hyperplasia reveals widespread obliteration of the small portal veins. Postmortem angiography of one liver in the present series demonstrated that the nodules were well perfused and that the atrophic areas were poorly perfused with portal blood. This supports the view that atrophy of lobules results from a lack of portal blood supply and that nodules develop from lobules well supplied with portal blood. In each of the clinical conditions associated with nodular regenerative hyperplasia, including macroglobulinemia, inflammatory or thrombotic vascular lesions are found in many organs. Therefore, nodular regenerative hyperplasia may be the hepatic expression of a more widespread vascular disease.     

Ventricular arrhythmias during ergonovine-induced episodes of variant angina

Of 95 consecutive patients with active variant angina who underwent ergonovine testing in the coronary care unit while off treatment, 24 (25%) developed serious ventricular arrhythmias: ventricular tachycardia in eight, bigeminy in seven, pairs in five, and frequent ventricular extrasystoles in four. Ergonovine-induced arrhythmias were observed more often in patients with anterior than inferior ST segment elevation (p less than 0.05). ST segment elevation was significantly higher (10.3 +/- 8.1 vs 3.1 +/- 2.1 mm) in patients who developed arrhythmias. All ventricular arrhythmias began within 3 minutes after the onset of ST segment elevation. The intravenous administration of nitroglycerin eliminated arrhythmias in 22 of 24 cases; in only two patients did ventricular arrhythmias develop after the administration of nitroglycerin. Serious ventricular arrhythmias were found during spontaneous variant angina attacks in 14 of 24 patients with ergonovine-induced arrhythmias compared to 16 of 71 patients without ergonovine-induced arrhythmias (p less than 0.001). We conclude that arrhythmias during ergonovine testing are most often caused by ischemia and not reperfusion. Patients with arrhythmias during ergonovine-induced attacks are more likely to have arrhythmias during spontaneous attacks.     

Effect of pericardiocentesis on right and left ventricular function and volumes in pericardial effusion

To assess the effects of pericardial effusion on ventricular performance and volumes, electrocardiographically gated blood pool cardiac scintigraphy was performed immediately before and after 14 pericardiocenteses in 10 patients, 7 men and 3 women, aged 28 to 73 years (mean 50). Cardiac tamponade was present in 5 patients. After removal of 140 to 1,100 ml of pericardial fluid (527 ± 305 ml [mean ± standard deviation]), left ventricular (LV) ejection fraction increased from 63 ± 5 to 64 ± 4% (p > 0.05) and right ventricular (RV) ejection fraction decreased from 47 ± 4 to 46 ± 2% (p > 0.05). LV end-diastolic and end-systolic volumes increased (p < 0.01) by 28 and 33%, and RV volumes by 40 and 43%, respectively. There were 8 patients with normal LV function (ejection fraction > 60 %) and 6 patients with subnormal LV function. Changes in ejection fraction were nonsignificant in the 4 subgroups. LV end-diastolic volume changes were more marked (p < 0.01) in patients with cardiac tamponade (+ 56%) than in those without tamponade (+ 17%), and in those with normal LV function (+ 36%) than in those with subnormal LV function (+ 21%). RV end-diastolic volume increased more markedly (p < 0.05) in patients with tamponade (+ 72%) than in those without tamponade (+ 23%), but were similar in patients with normal (+ 38% ) and abnormal (+ 43% ) LV function. After pericardiocentesis, RV volume increased more markedly than did LV volume. Thus, hemodynamic and clinical improvement after pericardiocentesis may be related only to an increase in stroke volume. RV and LV ejection fraction, a measure of myocardial contractility, was not affected significantly by the presence of pericardial effusion, even in those patients who had cardiac tamponade.     

Superior vena cava syndrome: Case report: A complication of permanent transvenous endocardial cardiac pacing requiring surgical correction

Superior vena cava syndrome developed in a patient in whom an endocardial transvenous pacemaker had been inserted five years previously. Venography demonstrated an obstructing lesion at the junction of the superior vena cava and right atrium. Balloon catheter dilatation failed to afford any relief from her progressive symptoms. Exploration of the area revealed a benign fibrotic lesion encircling the pacemaker lead within the right atrium. Excision of the lesion, removal of the lead, and patching the right atrium with pericardium resulted in rapid cure.     

Propranolol in angina pectoris: duration of improved exercise tolerance and circulatory effects after acute oral administration.

The duration of the effects of single oral doses of 80 and 160 mg of propranolol was studied in 11 patients with stable, exercise-induced angina pectoris. After administration of both doses, plasma propranolol levels peaked at 2 hours in 8 of the 11 patients and thereafter declined exponentially with an average plasma half-life of 3.98 hours (range 1.4 to 4.3) after the 80 mg dose and 4.28 hours (range 1.9 to 5.4) after the 160 mg dose. There was wide interindividual variation in plasma propranolol concentration at any given time after each dose. Treadmill walking time to the onset of angina, the total duration of exercise and the total external work performed were significantly greater by 1 hour after each dose of propranolol than after placebo. This improvement in exercise tolerance persisted unchanged for 8 hours (P less than 0.001) and was still significant although less marked at 12 hours (P less than 0.05). Improvement in exercise tolerance after propranolol was associated with a significant reduction in S-T segment depression during exercise. Both at rest and during exercise, heart rate, systolic blood pressure and rate-pressure product decreased after propranolol, and these circulatory effects persisted for 12 hours. Changes in walking time, heart rate and systolic blood pressure were similar after 80 and 160 mg of propranolol. Despite the increase in exercise duration and in total work performed after propranolol, the rate-pressure product at the onset of angina was lower after propranolol. In view of the prolonged effects of single oral doses of 80 and 160 mg of propranolol, it is suggested that administration of propranolol twice daily should be adequate in treating patients with stable angina pectoris. These studies also demonstrate that routine measurement of plasma propranolol levels is of little practical value in the management of patients with angina pectoris.