Heart failure 63 years after traumatic arteriovenous fistula

Congestive heart failure developed in a patient 63 years after an initial bullet wound, sustained at age 12, and a subsequently acquired arterlovenous fistula of the left thigh. This is the longest reported interval between formation of an acquired arterlovenous fistula and development of cardiac decompensation. Clinical improvement after surgical closure of the fistula was dramatic. Objective evidence of improvement was documented with serial echocardiograms.     

Characterization of the ischemic process by regional metabolism.

The myocardial cell requires energy for contractile activity and for the work of internal maintenance. With the onset of ischemia mechanical performance is compromised. If the ischemia is severe and persistent, the energy necessary to maintain the internal millieu proves inadequate and cell death ensues. Ischemic heart disease is a regional phenomenon with normal and abnormal cell metabolism occurring side by side. The ischemic cell demonstrates hemodynamic, electrical and biochemical instability; its passage from a state of reversible to irreversible injury may persist for as long as 7 days and offers an opportunity to introduce interventions that may protect it and reduce ultimate infarct size. There is as yet no adequate objective means for predicting the mass of infarcted tissue. However, studies of regional metabolism, if properly conducted, may help define the adequacy of coronary vascular reserve and characterize the ischemic process. Current techniques utilize a myocardial pacing stress to induce an ischemic response. Although virtually every metabolic pathway is disrupted by severe ischemia, the assay of selected metabolities in arterial and coronary venous blood samples has provided information of diagnostic significance.     

Cardiac involvement in the Kugelbert-Welander syndrome.

Two cases of the Kugelberg-Welander syndrome (juvenile form of progressive spinal muscular atrophy) associated with cardiomyopathy and cardiomegaly are presented. The first patient, a 24 year old man, had atrial flutter with complete atrioventricular (A-V) block due to A-H block. Echocardiography revealed an increase in the left atrial and right ventricular dimensions. The second patient was a 26 year old man whose electrocardiogram revealed an A-V junctional rhythm, deep Q wave in leads I, aVL and V5 to V6 and an RS pattern in lead V1. Histologic examination of the myocardium in Case 2 showed slight interstitial fibrosis. Review of previously reported cases shows that (1) the atrium, the ventricular myocardium and A-V conducting tissue may be involved, and (2) atrial arrhythmias, A-V conduction disturbances and congestive heart failure may occur in the Kugelberg-Welander syndrome.     

Reciprocal rhythm in patients with normal electrocardiogram: Evidence for dual conduction pathways.

The present study refers to six patients in whom an A-V reciprocal rhythm could be documented; in four cases it took the form of sustained tachycardia. None of the patients showed any ECG feature of ventricular pre-excitation (PR interval of more than 0.12 sec. and normal QRS configuration). The extrastimulus method showed, at first, that the A-V conduction time of the premature beat varied only slightly with the decrease of the coupling interval. From a critical A1A2 interval there was a sudden lengthening of A2H2 preceding the occurrence of re-entrant beats. The curve of H1H2 responses reflected these changes, showing two distinct parts. The second part following the slowing of the impulse included the initiation zone of atrial echoes and of reciprocating tachycardia. These results suggest the existence of two A-V pathways, one fast and the other slow. The point at which the break between the two parts of the curve occurred might be related to the effective refractory period of the fast pathway. In the same way, when atrial pacing reached a critical rate, it induced an abrupt increase of AH in five cases. In the sixth patient, A-V conduction time remained unchanged up to 170 per minute. Ventriculoatrial conduction was always observed, the delay of which did not lengthen with the rate. In one case tachycardia could be induced by a premature ventricular beat without lengthening of the V-A time. It is concluded that in spite of a normal PR interval, the presence of dual A-V pathways may be implied in the genesis of reciprocal rhythm.     

Nomograms relating aldosterone excretion to urinary sodium and potassium in the pediatric population: Their application to the study of childhood hypertension

The lability and diurnal variation of blood pressure in normal and hypertensive children were examined and found to be less than that described in adults. Nomograms were prepared relating urinary sodium and potassium to urinary aldosterone in children ranging in age from infancy to 22 years. These nomograms reveal that the relation of aldosterone excretion to sodium excretion is described by a hyperbolic function. Most values for normal children, children with mild essential hypertension and children with severe essential hypertension fell between two hyperbolic curves representing the 5th and 95th percentile, respectively. Hypertensive children with low and high plasma renin activity were found to have an inappropriately high level of urinary aldosterone excretion in relation to urinary sodium excretion. No relation was found between potassium and aldosterone excretion. By means of these nomograms the normal standards for aldosterone excretion in children were refined, permitting classification of hypertensive children into distinct groups. This classification may have prognostic significance.     

Comparison of antihypertensive and hormonal effects of captopril and propranolol at rest and during exercise

Captopril and propranolol were given alone and in combination to 13 hypertensive men and the effects studied at rest (seated, supine and standing) and during exercise. The two drugs were equipotent at rest, and individual patients showed similar blood pressure responses to the two drugs. Both produced slight reduction of urinary aldosterone; when given in combination, both blood pressure and aldosterone were further reduced. During exercise the increase in blood pressure was unaffected by captopril but reduced by propranolol, and there was no correlation between individual responses to the two drugs. It is concluded that the similar effects of the two drugs on resting blood pressure are consistent with their effects on the renin-angiotensin system.     

Contrasting effects of acute beta blockade with propranolol on plasma catecholamines and renin in essential hypertension: a possible basis for the delayed antihypertensive response.

Blood pressure, heart rate, plasma renin activity, plasma norepinephrine and plasma epinephrine were determined in 11 patients with essential hypertension at rest before and 15, 30, 45, and 60 minutes after an intravenous infusion of 0.12 mg./Kg. propranolol given over five minutes. After propranolol mean blood pressure was unchanged; heart rate decreased by 14 per cent within 15 minutes and showed no further changes. Plasma renin activity decreased progressively by 48 per cent 60 minutes after propranolol, whereas plasma norepinephrine and epinephrine were always higher after propranolol than control values. Increases in norepinephrine were statistically significant at 30, 45, and 60 minutes (respectively 49, 39, and 45 per cent, P less than 0.005 at least) and those of epinephrine even at 15 minutes (respectively 60, 82, 62, and 94 per cent P less than 0.01 for all). These results indicate that acute beta blockade with propranolol incudes increases in circulating plasma norepinephrine and epinephrine which might be consequent to rapidly induced hemodynamic changes. This augmented sympathetic activity might explain why propranolol, when acutely infused, does not decrease blood pressure despite effective cardiac and renin blockade.     

Inefficacy of “therapeutic” serum levels of digoxin in controlling the ventricular rate in atrial fibrillation

Although therapeutic and toxic serum concentrations of digoxin have been established, there is sparse information permitting correlation of drug level with clinical effect. This study was undertaken to assess the radioimmunoassay serum digoxin levels in 30 patients with acute atrial fibrillation (38 determinations) and 30 patients with chronic atrial fibrillation (54 determinations). Those with chronic fibrillation were subdivided into those in clinically stable condition (14 patients), and those seriously ill and in clinically unstable condition (16 patients). Slowing of ventricular rate in patients with stable, chronic atrial fibrillation was accomplished in 10 of 16 instances by “therapeutic” and “subtherapeutic” levels of digoxin (less than 2 ng/ml). Ventricular rate was “controlled” (65 to 95 beats/min) with therapeutic levels of serum digoxin in only five instances of acute atrial fibrillation and seven of unstable chronic atrial fibrillation. In 43 studies (23 of acute atrial fibrillation, 20 of chronic atrial fibrillation), a rapid ventricular rate (95 to 140 beats/min) persisted in the presence of “therapeutic” or high levels of digoxin. Thirty-nine of these were in patients who were seriously ill with conditions such as infection, hypoxia or recent thoracotomy. Slowing of the ventricular rate required “toxic” concentrations of digoxin (2.5 to 6 ng/ml) in 15 instances. We conclude that sufficient amounts of digoxin to achieve “therapeutic” serum concentrations may fail to lower the ventricular rate in atrial fibrillation to less than 100 beats/min, especially when a serious, complicating illness coexists.     

Comparison of heart rate and blood pressure response to amyl nitrite, isoproterenol, and standing before and during acute beta-adrenergic blockade with intravenous propranolol

Heart rate responses to three different procedures (amyl nitrite inhalation, standing up, and isoproterenol infusion), were studied before and during acute adrenergic beta blockade with intravenous propranolol in three normal and six hypertensive subjects. Propranolol decreased, but did not completely abolish, the heart rate increase produced by amyl nitrite and standing, probably because of vagal participation (withdrawal) in heart rate increase produced by baroreceptor hypotension (amyl nitrite) and on assuming the upright posture. Heart rate responses to amyl nitrite varied greatly from patient to patient (from 27 to 97%), but the drug proved to be the most potent stimulus for heart rate increase as a result of its marked hypotensive effect. However, this vasodilator-induced acute hypotension was well tolerated, and without deleterious hemodynamic consequences, despite the presence of beta blockade. Different degrees of correlation in heart rate increase were observed with the three procedures, reflecting probably the varying sympathetic-parasympathetic participation in reflex heart rate control. It is concluded that from the clinical stand point, neither amyl nitrite administration nor standing up can be used as a test to assess acurately the degree of beta blockade, because both procedures activate vagal withdrawal which increases heart rate regardless of the degree of beta blockade.     

Hemodynamic characteristics of hypertension after coronary bypass surgery and effects of the converting enzyme inhibitor.

In 13 patients with hypertension after coronary bypass surgery, the underlying hemodynamic mechanism was an increased systemic vascular resistance. To elucidate the role of the renin-angiotensin system in left ventricular function, plasma renin activity and hemodynamic measurements were performed during the peak of the hypertensive episode and 15 to 30 minutes after the administration of the converting enzyme inhibitor SQ20881 (1 mg/kg body weight). Eight of the 13 patients responded to the inhibitor; in these patients control plasma renin activity was 8.78 ± 2.3 ng/ml per hour, and mean arterial pressure decreased markedly from 123 ± 6 to 101 ± 5 mm Hg (P < 0.005), due to a decrease in systemic vascular resistance from 22 ± 2 to 14 ± 1 units (P < 0.005). The decrease in systemic vascular resistance induced by the inhibitor correlated with the control plasma renin activity (r = 0.825, P < 0.05). In the responders, administration of the inhibitor also increased cardiac output from 5.26 ± 0.36 to 7.39 ± 0.61 liters/min (P < 0.005) because of an increase in stroke volume from 61 ± 3 to 78 ± 5 ml/beat (P < 0.005), although left ventricular filling pressure decreased from 8.5 ± 1 to 6.0 ± 1 mm Hg (P < 0.005). In the remaining five patients (nonresponders to the inhibitor), control plasma renin activity was 1.8 ± 0.3 ng/ml per hour (P < 0.05 compared with the responders), but the control hemodynamic data did not differ from those of the responders. In the nonresponders the small decrease in mean arterial pressure (from 128 ± 5 to 123 ± 4 mm Hg, P < 0.025) was due to a decrease in stroke volume and cardiac output, but systemic vascular resistance did not change. As in the responders, administration of the inhibitor decreased left ventricular filling pressure in this group from 8 ± 1 to 6 ± 0.8 mm Hg (P < 0.025).These results indicate that the renin-angiotensin system is often involved in postcoronary artery bypass hypertension. In patients with increased renin, blockade of angiotensin II improved left ventricular function by reducing afterload rather than preload, thus indicating that angiotensin II acts on the heart and veins.     

Functional importance of coronary collateral vessels

Angiographically demonstrable coronary collateral vessels are believed to preserve myocardial function at rest, but disagreement exists regarding the importance of collaterals in mitigating exercise-induced ischemic dysfunction. Therefore, we used radionuclide cineangiography during exercise to assess the left ventricular (LV) functional effects of collateral vessels in 125 patients with at least 1 major coronary artery that had greater than or equal to 90% diameter stenosis but without prior myocardial infarction. Regional LV function, graded on a 4-point scale, worsened during exercise by at least 1 grade in 14 of 43 regions (33%) with good collaterals, and in 70 of 98 without good collaterals (p less than 0.001). Of the 43 good collaterals, 14 were supplied by arteries with greater than or equal to 75% stenoses; 10 of 14 regions (71%) thus supplied worsened by at least 1 grade (p less than 0.01). The ischemia-mitigating effect of coronary collateral vessels also affected the magnitude of exercise-induced global dysfunction. Of 43 patients with only one greater than or equal to 90% stenotic artery, 18 had good collaterals; in these patients, average LV ejection fraction (EF) at rest was 51 +/- 8%; LVEF during exercise was 46 +/- 7%. In the 25 patients without good collaterals, LVEF at rest was 52 +/- 7%, and LVEF during exercise was 41 +/- 9% (p less than 0.005 vs good collaterals).(ABSTRACT TRUNCATED AT 250 WORDS)     

Chorea complicating oral contraceptive therapy: Case report and review of the literature

Oral contraceptive-induced chorea occurs infrequently; therefore, this serious complication of birth control pills may be generally unrecognized as a potential side effect. A patient with oral contraceptive-induced chorea is described and a review of the literature presented. A previous episode of chorea predisposes towards estrogen-progesterone-induced chorea; therefore, other methods of contraception should be considered in patients with a past medical history of Sydenham's chorea or chorea gravidarum. Vascular, immunologie and neurotransmitter abnormalities are discussed as possible etiologies for gestational steroid-induced chorea.     

Exercise versus cold temperature stimulation during radionuclide cineangiography: Diagnostic accuracy in coronary artery disease

To assess the relative efficacy of cold temperature stimulation and bicycle exercise in inducing ischemia detectable by radionuclide Cineangiography, we used both stresses to study 20 normal subjects and 54 patients with coronary artery disease (CAD), 42 of whom had not had myocardial infarction. Cold stimulation caused increases in heart rate and arterial pressure which were significantly less marked than those caused by exercise. Regional left ventricular dysfunction was induced by cold in 24 of 41 patients without previous infarction (57%) and by exercise in 34 of 42 patients (81%) (p < 0.05), but was absent in all normal subjects during either stress. Left ventricular ejection fraction increased during exercise in all normal subjects (average increase 18%) but decreased during cold stimulation in 12 of 20 subjects. Because of the disparate response of normal subjects to the 2 stresses, the sensitivity and specificity of radionuclide Cinean-giography were assessed over a wide range of ejection fraction changes independently for each stress. During exercise, at ejection fraction changes in which specificity was high, sensitivity also was high, but during cold stress, specificity was relatively poor at ejection fraction changes in which sensitivity was high, and sensitivity was relatively poor when specificity was high. During exercise, patients with anatomically severe (3-vessel, left main, proximal left anterior descending) disease manifested significantly greater reduction in ejection fraction than did patients with less severe stenoses (?10% versus ?3%, p < 0.001); cold stimulation did not lead to similar separation (?2% versus ?3%, difference was not significant). Therefore, when radionuclide Cineangiography is performed, exercise is more effective than cold stress in separating normal subjects from patients with fixed obstructive CAD and in identifying patients with anatomically severe CAD.     

Long-term efficacy of captopril in renovascular and essential hypertension

Captopril was used in primary and long-term treatment of 40 treatment-resistant hypertensive patients. Of these, 21 had renovascular hypertension, seven unilateral and fourteen bilateral, and 19 had essential hypertension, 10 with high-renin and 9 with normal-renin profiles. All patients were off treatment when started on captopril therapy and were treated for at least 12 months, on the average for more than 2 years. The strategy of systematic drug withdrawal used to find the lowest effective dose of captopril led to average doses of 150 to 300 mg/day. A diuretic agent was added in 17 of the 40 patients when diastolic pressure remained greater than 105 mm Hg and a beta-adrenergic blocking agent was added for tachycardia or additional pressure control in 16 patients. Captopril alone was effective in 14 of the 40 patients. In all groups, mean supine and standing blood pressure levels were maintained at less than 140/90 mm Hg without evidence of decreased effectiveness over time. Control and treatment systolic pressures were higher in patients older than 50 years. For patients of all ages, systolic but not diastolic pressure during captopril treatment was higher in the supine position than standing. Plasma renin activity remained significantly elevated over time and aldosterone excretion usually decreased despite concurrent diuretic therapy. Captopril alone or in combination with a diuretic or beta-adrenergic blocking agent is effective in long-term treatment of drug-resistant renovascular and essential hypertension.     

Effects of diuretic therapy in low-, normal- and high-renin isolated systolic systemic hypertension

In 30 patients with isolated systolic systemic hypertension, diuretic therapy decreased body weight from 71.33 +/- 2.67 to 70.37 +/- 2.65 kg (p less than 0.0005) and the systolic blood pressure from 174 +/- 3 to 156 +/- 3 mm Hg (p less than 0.0005). Diastolic blood pressure and heart rate did not change significantly. Plasma renin activity increased from 2.25 +/- 0.33 to 4.27 +/- 0.43 ng/ml/hour (p less than 0.0005) and urinary aldosterone from 9 +/- 1 to 16 +/- 2 micrograms/24 hours (p less than 0.005). The antihypertensive effect of diuretics was significantly related only to the pretreatment plasma renin activity (r = -0.50, n = 30, p less than 0.05), and therefore the greatest decrease in systolic blood pressure occurred in the low-renin group, whereas the smallest occurred in the high-renin group (-22 +/- 2 vs -3 +/- 9 mm Hg, p less than 0.005). The diastolic blood pressure was significantly decreased only in the low-renin group (-7 +/- 2 mm Hg, p less than 0.005). There were no significant changes in blood pressure in 11 untreated control patients. These results indicate that diuretics are effective antihypertensive agents in most patients with low- and normal-renin isolated systolic systemic hypertension.     

Renin and aldosterone suppression in the antihypertensive action of clonidine

In 18 hypertensive patients receiving a constant (100 mEq/day) sodium diet, treatment with clonidine (0.3 mg/day for 5 days) decreased blood pressure in 11 patients with high and normal renin levels and 7 with low renin levels. The high and normal renin group had early and rapid reductions in blood pressure and plasma renin activity. In contrast, the low renin group had a more gradual hypotensive response and only a small absolute decrease in plasma renin. For all patients, pretreatment renin levels were related to the initial decrease in blood pressure but not to the reductions measured after 5 days. Thus, two mechanisms of action of clonidine are possible, one related to acute inhibition of the renin-angiotensin system in patients with high and normal renin levels and another that is independent of renin mechanisms and occurs in all hypertensive patients. In six additional patients with high renin levels induced by prior sodium depletion (10 mEq/day sodium diet), clonidine did not reduce blood pressure or renin, thus indicating that the suppressive action of this agent on renin presser mechanisms occurs only in patients whose elevated renin levels are intrinsic to hypertension and unrelated to sodium depletion.Of the 18 patients receiving a normal sodium diet, 13 were classified as responding to treatment (decrease in both systolic and diastolic pressures of at least 10 percent). The five nonresponders had a greater weight gain and higher values for aldosterone excretion. For all patients, there was a significant correlation between decrements in blood pressure and in aldosterone, suggesting that the countervailing effects of fluid accumulation on blood pressure in nonresponding patients resulted from a failure of aldosterone to be suppressed. Changes in aldosterone, in turn, correlated significantly with changes in renin. Thus, the antirenin effect of clonidine enhances its antihypertensive action not only by acutely ablating renin-angiotensin pressor mechanisms, but also by inhibiting aldosterone production and thereby minimizing longer-term reactive volume retention during treatment.     

Role of the sympathetic nervous system in mediating the renin response to head-up tilt. Their possible synergism in defending blood pressure against postural changes during sodium deprivation.

To investigate the role of the sympathetic nervous system in controlling the response of renin to upright posture and the physiologic significance of this activation in cardiovascular homeostasis, the effects of 30 minutes of 65 ° head-up tilt were assessed before and during acute beta blockade with propranolol in patients with essential hypertension studied under conditions of low, normal and high sodium intakes. Before beta blockade mean blood pressure was always unchanged during tilt, whereas the absolute increases in renin were inversely related to the state of sodium balance. During beta blockade, the renin responses to tilt were always abolished and mean blood pressure was unchanged in sodium-loaded patients, whereas blood pressure decreased progressively during the last 15 minutes of tilt on normal and low sodium intakes. The hypotension was much greater in sodium-deprived patients, all of whom fainted.These results indicate that the increase in renin during upright tilt is mediated by beta adrenergic receptors independently of the state of sodium balance, and they suggest that the postural renin response can be an effector pathway of the sympathetic nervous system for supporting blood pressure during prolonged tilt. This pathway has minimal significance when sodium is present in excess, but it becomes more important when sodium is restricted.