Tracer norepinephrine kinetics in coronary circulation of patients with heart failure secondary to chronic pressure and volume overload.

Controversy exists over the nature of the abnormality in cardiac sympathetic nerves in heart failure. In the cardiomyopathy of the Syrian hamster, reduction in tissue stores and increased turnover of norepinephrine is clearly associated with excessive sympathetic stimulation but in animal models and humans with heart failure secondary to mechanical overload there is evidence for depression of neuronal uptake. Because norepinephrine is both released and taken up by sympathetic fibers it is impossible to assess norepinephrine kinetics in an intact heart without separating these two functions. A technique for doing so has recently been developed in normal dogs and we therefore acquired similar data in humans with heart failure secondary to chronic pressure and volume overload. The technique involves the combination of transient norepinephrine tracer coronary sinus outflow in relation to intravascular and interstitial references after simultaneous injection into the left coronary artery and the measurement of endogenous norepinephrine concentrations in artery and coronary sinus. We found a marked reduction in cardiac norepinephrine release and uptake in a group of patients with clinical left ventricular failure secondary to mechanical overload, relative to a group of patients with no failure. Norepinephrine balance and overflow across the heart were not significantly different. We conclude that there is hypofunction of the cardiac sympathetic nerves in heart failure secondary to mechanical overload and that traditional methods are inadequate in assessing cardiac norepinephrine kinetics when there are simultaneous changes in neuronal uptake and release.

Idiopathic ventricular tachycardia. A review.

Idiopathic or unexplained VT occurs in a small but important subset of patients without clinically evident heart disease. The majority of these patients appear to have a structurally normal heart. The cause of the arrhythmias in these individuals is unclear and may never be recognized. Other patients with this condition may have minor abnormalities not sufficient to impair overall cardiac function. The significance of these abnormalities to the genesis of the arrhythmia is uncertain. Whether patients with minor abnormalities are more likely to harbor covert heart disease such as myocarditis or a focal defect is not known, nor is it resolved whether such patients warrant a more aggressive search for a structural cause. The question that remains in any patient not subjected to surgical or pathological exploration is whether undetermined heart disease is responsible for the arrhythmia. Continued correlation between functional (electrophysiological) and structural (pathological) data will provide meaningful information concerning the pathophysiology (substrate) of these arrhythmias. Because of the preservation of normal cardiac function, these arrhythmias are generally well-tolerated. Although the condition is usually associated with a favorable prognosis, the occasional deaths reported in patients with apparently idiopathic ventricular arrhythmias may not permit calling this condition benign. It would be important to know the extent to which unrecognized abnormalities play a role in the genesis of these tachycardias, and whether such patients are more predisposed to fatal arrhythmias or have a different natural history. If cases involving undetermined or covert heart disease were excluded from consideration, then a relatively homogeneous disease-free group may be identified with a truly benign condition and a uniformly favorable prognosis. In these cases, a primary electrical abnormality may prove to be the basis for the arrhythmia. These issues remain to be elucidated in future studies.

Membranous lupus nephropathy: a clinicopathologic study.

Twenty-eight patients with SLE and distinct, well-defined renal morphologic lesions of membranous nephropathy were followed up for 4 years. These patients comprised approximately 8% of the patients evaluated for SLE during a 12-year period. The patients with membranous lupus nephropathy had typical systemic features of SLE, and most of them had positive LE cell tests and ANA, low serum complement concentrations, and mildly elevated serum antinative DNA levels. Proteniuria and microscopic hematuria were usually discovered years after systemic symptoms of SLE had developed, Only two patients had slowly progressive renal failure, and most patients continued to have proteinuria. Prednisone treatment did not influence either proteinuria or renal function. In only one patient, the renal character of the disease changed drastically, demonstrating membranoproliferative glomerulonephritis. Six patients died (21%); most of these died of cardiovascular illnesses. The relatively benign and stable renal course of membranous lupus nephropathy in patients with otherwise typical SLE suggests that the renal pathogenesis is different from that of proliferative lupus nephritis.

Prazosin and congestive heart failure: short- and long-term therapy.

Reviewed here are the data from 34 patients given prazosin for chronic intractable heart failure. In 13 patients in whom hemodynamics were measured after the fifth 3 mg dose of prazosin was given, no attenuation was found. The cardiac index increased from 1.77 +/- 0.13 to 2.5 +/- 0.13 liters/min/m2 (p less than 0.001), and the pulmonary capillary wedge pressure decreased from 31,46 +/- 1.56 to 23.54 +/- 1.11 mg Hg (p less than 0.001). During long-term follow-up (15.9 +/- 1.5 months) the administration of spironolactone proved to be very useful. Within three months of starting prazosin therapy, none of the 15 patients discharged on a regimen of spironolactone needed readmission for edema, but 11 of the 13 patients discharged without a spironolactone regimen did. The addition of spironolactone or an increase in furosemide to the therapeutic regimen was helpful but a change to hydralazine was not. We concluded that prazosin causes short-term hemodynamic and long-term clinical improvement in patients with intractable heart failure; that spironolactone helps to prevent clinical attenuation but that more detailed studies are required to better characterize the attenuation to vasodilators seen in patients with congestive heart failure.

Acute effects of captopril on the coronary circulation of patients with hypertension and angina.

Patients with hypertension have a high incidence of coronary artery disease. Captopril, the angiotensin-converting enzyme inhibitor, was given to eight patients with hypertension and coronary artery disease; it decreased mean arterial pressure from 121 to 103 mm Hg (p less than 0.01) but had no effect on heart rate. The rate-pressure product decreased from 12.5 to 11.4 X 10(3) (p less than 0.01). The change in coronary blood flow (90 to 80 ml per minute) and myocardial oxygen consumption (965 to 852 ml per minute) tended to parallel the decrease in the rate-pressure product. Captopril did not change global myocardial lactate (20 to 34 percent) or oxygen (9.6 to 10.0 volume percent) extraction. Hence, captopril decreases the rate-pressure product and tends to decrease myocardial oxygen consumption without causing global myocardial metabolic deterioration.

Selective right ventricular dysfunction after coronary artery bypass grafting.

Preoperative and postoperative right (RVEF) and left ventricular ejection fractions (LVEF) were studied by means of radionuclide techniques in 15 patients undergoing coronary bypass operations. Three of them, all with right coronary artery lesions, had postoperative depression of RVEF without concomitant decrease in LVEF. In contrast to those with left ventricular dysfunction, the patients with selective RVEF depression did not have significant elevation of myocardial injury index calculated from creatine kinase isoenzyme (CK-MB) curves.

Graft-vs-host reaction.

Observations surrounding the clinical manifestations and pathological studies of a neonate who died at 9 weeks of age, indicate that distinctive cutaneous, histopathologic, and ultrastructural findings occur when graft-vs-host reaction (GVHR) complicates combined immune deficiency syndrome (CIDS). The prominence and specificity of the epidermal lesions, particularly a necrotic cell that occurs in association with satellite lymphocytes ("satellite cell necrosis" (SCN)), lead us to recommend that a cutaneous biopsy be performed to facilitate an early definitive diagnosis. Dermatologists can recognize GVHR at the bedside and establish the diagnosis with the pathological findings obtained from the skin biopsy.

Complete heart block in an Inuit family.

An Inuit family from Cape Dorset, Northwest Territories is described; six had documented complete heart block, one high grade atrioventricular block, one bi- or trifascicular block and all suffered syncope. One other member received a pacemaker for unknown reasons. Two of three middle-aged relatives had minor conduction abnormalities. All younger family members who were examined had no conduction problems. This suggests a heritable form of adult onset complete heart block, the largest series reported in the English literature.

Association between immediate termination of supraventricular tachycardia by carotid sinus pressure and carotid sinus hypersensitivity.

An association between rapid reversion of supraventricular tachycardia by carotid sinus stimulation and carotid sinus reflex hypersensitivity during sinus rhythm is described in a 55-year-old patient. The findings indicate that a high level of vagal tone facilitates vagal maneuvers in terminating some supraventricular tachyarrhythmias. The briskness of the response during tachycardia may also be a marker for underlying carotid sinus hypersensitivity.

Papillomatosis of the gallbladder associated with metachromatic leukodystrophy.

A 9-year-old boy with metachromatic leukodystrophy (MLD) was found to have diffuse papillomatosis of the gallbladder that was virtually obliterating the lumen of the gallbladder. To our knowledge, two other examples of this lesion have been reported previously in MLD.

Arboviruses in water birds (Ciconiiformes, Pelecaniformes) from Florida.

Sera from 360 ciconiform and pelecaniform birds collected in Florida (USA) from 1974 to 1990 were tested for serum neutralizing (SN) antibodies to eastern equine encephalitis (EEE), St. Louis encephalitis (SLE), and Everglades (EVE) viruses. Serum neutralizing antibodies to EEE virus were detected in 2%, to SLE virus in 7%, and to EVE virus in none of the samples. Pelecaniform birds (16%) had a higher antibody prevalence (P < 0.02) for SLE virus than did ciconiform birds (5%). Virus could not be isolated from 67 samples. Nestling birds with SN antibodies to both EEE and SLE viruses were found in both fresh water and marine colonies. Antibodies were more prevalent in adult and fledged juvenile birds than in nestlings.

Detrimental arrhythmogenic and sustained beneficial hemodynamic effects of oral salbutamol in patients with chronic congestive heart failure.

The long-term efficacy and potential side effects of oral sympathomimetic amines in the treatment of advanced congestive heart failure remain controversial. We studied the acute and chronic hemodynamic and arrhythmogenic effects of the beta-2 agonist, salbutamol, 6 mg by mouth four times/day, in 20 patients with NYHA classes III to IV congestive heart failure. Acutely, salbutamol increased the cardiac index (1.9 to 2.3 L/min/m2, p less than 0.01) and heart rate (92 to 97 bpm, p less than 0.01) while it decreased pulmonary capillary wedge pressure (35 to 31 mm Hg, p less than 0.01). Salbutamol increased the number of patients having episodes of ventricular tachycardia from two to six and increased the number of episodes of ventricular tachycardia from 2 to 27. Once salbutamol was discontinued, no further episodes of ventricular tachycardia occurred in these six patients. Six patients did not have long-term hemodynamic studies because of serious arrhythmias and two died. In the 12 patients who had long-term studies, the initial beneficial hemodynamic effects of salbutamol were maintained. Thus, although salbutamol may have beneficial long-term hemodynamic effects, it may cause serious arrhythmias in patients predisposed to develop arrhythmias.

A reassessment of "chordoid sarcoma". Ultrastructural and immunohistochemical comparison with chordoma and skeletal myxoid chondrosarcoma.

The relationship of "chordoid sarcoma" (CS) to chordoma and myxoid chondrosarcoma has been debated for several years. In order to reassess this issue, we studied 5 CS, 5 chordomas, and 3 skeletal myxoid chondrosarcomas ultrastructurally and immunohistochemically. By electron microscopy, CS demonstrated smooth cellular outlines, macular intercellular junctions, and cytoplasmic inclusions of matrix-like material. Chordomas displayed a closely similar fine structural appearance, but in addition contained small, membrane-bound, glycogen-containing inclusions. Skeletal myxoid chondrosarcomas resembled CS, except that the former lesions had spiculated cell membranes and lacked intercellular junctions. Immunohistochemically, all CS cases expressed vimentin and lacked cytokeratin (CK). Leu 7 and S100 protein were seen in four cases each of CS, and three of these tumors demonstrated diffuse or focal reactivity for epithelial membrane antigen (EMA). Similar phenotypic features were seen in chordomas, except that all of them stained diffusely for CK, as well as EMA. Skeletal myxoid chondrosarcomas expressed vimentin, S100, and Leu 7 uniformly, but were devoid of epithelial markers. In aggregate, these data support the classification of "chordoid sarcoma" as a form of chondrosarcoma, but reveal that it may exhibit an "epithelial" antigen in some cases.

Reduced aortocoronary sinus extraction of epinephrine in patients with left ventricular failure secondary to long-term pressure or volume overload.

Heart failure is associated with a reduction in tissue norepinephrine concentration, catecholamine fluorescence, and tyrosine hydroxylase activity. We hypothesized that this attrition of sympathetic nerve function might also be associated with a reduction in the ability of the neuronal membrane to sequester catecholamines. Since the heart does not release epinephrine, the cardiac extraction of epinephrine should be an index of the membrane uptake system. In 12 patients with documented left ventricular failure (pulmonary edema) secondary to mechanical overload and in 10 patients with no history of heart failure, we measured simultaneous plasma catecholamine concentrations in the aorta, coronary sinus, and femoral vein. The aortocoronary sinus extraction of epinephrine was 43 +/- 17% in the group with no evidence of heart failure but 0 +/- 14% in the group with failure. Net norepinephrine outflow (release minus extraction) was significantly higher in the group with failure, possibly because of reduced extraction. There was neither a reduction in the ability of the lower limb to extract epinephrine nor an increased norepinephrine outflow from the limb. These findings suggest that the sympathetic neuronal membrane uptake system is also depressed in the failing heart and that if the mechanism of catecholamine sequestration in the heart is related to that in the lower limb, the ablation of sympathetic nerve function is specific to the heart and is not a result of a generalized depression of the peripheral sympathetic nervous system.

Peritoneal dialysis for the treatment of pericarditis in patients on chronic hemodialysis.

Three cases of pericarditis with effusion associated with infection and occurring in patients under good biochemical control on hemodialysis are reported. Continuation of hemodialysis, even with regional heparinization, allowed further accumulation of fluid. Peritoneal dialysis was instituted, with subsequent improvement in all three patients. This treatment is recommended in the belief that it hastens the resolution of the condition and may obviate the necessity of establishing permanent or semi-permanent artificial pericardial drainage.