Constantinos J. Limas

Right ventricular infarction: Clinical and hemodynamic features

Abstract Six patients with acute myocardial infarction presented with hemodynamic evidence of predominant right ventricular failure, characterized by a mean right atrial pressure averaging 20.2 mm Hg and left ventricular filling pressure averaging 16.3 mm Hg. Autopsy in two cases revealed extensive involvement of the right as well as the left ventricle. Clinically the patients usually had evidence of diaphragmatic wall infarction, distended neck veins, hypotension and heart block. Pressure contours and mean pressure often showed no significant change as the catheter was advanced from the right atrium to the pulmonary artery. Shock in three patients was effectively treated with plasma volume expansion, to increase further right-sided pressure, or the administration of sodium nitroprusside, to reduce left-sided filling pressure. It is suggested that when right ventricular infarction accompanies left ventricular infarction, a unique clinical and hemodynamic syndrome occurs because the ability of the right ventricle to maintain adequate left ventricular filling is impaired. Recognition of this syndrome is vital if appropriate therapy is to be instituted.

Treatment of refractory heart failure with infusion of nitroprusside.

Abstract Sodium nitroprusside infused in 18 patients with intractable heart failure (nine with ischemic heart disease and nine with cardiomyopathy) produced a prompt reduction of left ventricular filling pressure (pulmonary wedge or left ventricular end-diastolic pressure) from an average of 32.2 to 17.2 mm Hg and a rise in cardiac output from an average of 2.98 to 5.2 liters per minute. Mean arterial pressure fell by 15 mm Hg, and heart rate was slightly but significantly slowed. Stroke volume and forward ejection fraction were nearly doubled. Responses were similar in ischemic heart disease and cardiomyopathy. A diuresis and natriuresis accompanied the infusion, and the clinical response was sustained in five patients in whom the drug was continued for 24 to 72 hours. These results suggest that intractable heart failure may be effectively treated by reduction in impedance to left ventricular ejection. (N Engl J Med 291:587–592, 1974)

Autoantibodies against beta-adrenoceptors in human idiopathic dilated cardiomyopathy.

Although it is recognized that the number of cardiac beta-adrenoceptors is reduced in human dilated cardiomyopathy, the mechanisms involved have not been defined. We examined the possible role of altered humoral immunity by comparing the effect of sera from patients with idiopathic dilated cardiomyopathy (n = 20), ischemic or valvular heart disease (n = 28), or controls with no known cardiac disease (n = 18) on the binding of radioligands to cardiac beta-receptors. The ability of sera from cardiomyopathic patients to inhibit the binding of [3H]dihydroalprenolol to rat cardiac membranes was significantly higher than that of the other two patient groups (40 +/- 5% at 50-fold serum dilution compared to 14 +/- 3% for the ischemic/valvular heart disease group, and 14 +/- 4% for the normal control group, p less than 0.001). A similar inhibition was exerted by IgG from cardiomyopathic patients. Only the number, not the affinity, of the beta-receptors was decreased by cardiomyopathic sera. This decrease could be prevented by preincubating the sera with anti-human IgG, indicating the presence of autoantibodies. Furthermore, the sera were ineffective against cardiac alpha 1-adrenoceptors and considerably less effective against lung beta 2-receptors. In addition to ligand binding inhibition, sera from cardiomyopathic patients could immunoprecipitate beta-adrenoceptors quantitatively from solubilized cardiac membranes. Positive sera inhibited significantly isoproterenol-stimulated adenylate cyclase with no effect on basal or NaF-stimulated activities. These results document the presence in sera from patients with idiopathic dilated cardiomyopathy of autoantibodies directed against the cardiac beta 1-adrenoceptor which may play an important role in the regulation of inotropic responsiveness to beta-agonists.

Reduced number of β-adrenergic receptors in the myocardium of spontaneously hypertensive rats

Abstract Inotropic response to β-adrenergic stimulation of the myocardium is decreased in hypertension. A biochemical basis for this decrease was provided by the observation that the number of β-adrenergic receptors — as reflected in specific [ 3 H]dihydroalprenolol binding — was diminished in the myocardium of spontaneously hypertensive rats without a change in the affinity of dihydroalprenolol for the binding sites or in the capacity of isoproterenol to displace dihydroalprenolol. The decline in β-adrenergic receptor numbers is not secondary to blood pressure elevation and may be related to increased sympathetic drive in spontaneously hypertensive rats.

Impaired left ventricular function in alcoholic cirrhosis with ascites. Ineffectiveness of ouabain.

Left ventricular function was assessed in 10 patients with alcoholic cirrhosis and ascites without clinical evidence of heart disease. In the resting state pulmonary wedge pressure (PWP) was normal (average 9.7 mm Hg), cardiac output (CO) was elevated (average 9.7 L/min) and systemic vascular resistance (SVR) was low (average 825 dynes-sec-cm−5). During infusion of angiotensin in a dose sufficient to raise diastolic arterial pressure 20 mm Hg, SVR increased to 1140 dynes-sec-cm-5 (P < 0.01) and PWP rose to 19.2 mm Hg (P < 0.001) with no change in CO. Resting hemodynamics were essentially unchanged in seven patients restudied 45-60 min after intravenous administration of 0.5 mg ouabain. Repeat infusion of angiotensin after ouabain again resulted in a rise in PWP to an average of 17.0 mm Hg (P < 0.001) with no significant change in CO. In seven additional cirrhotic patients with ascites, systolic time intervals were unchanged by 0.5 mg ouabain whereas in four normal volunteers the same dose resulted in significant shortening of total electromechanical systole, pre-ejection period and left ventricular ejection time. These data indicate that depression of the left ventricular response to an increase in afterload is a uniform finding in alcoholic patients with cirrhosis and ascites. The absence of clinical symptoms of heart disease, therefore, could be attributed to the low systemic vascular resistance characteristic of cirrhosis. Since acute administration of ouabain neither improved left ventricular function nor altered systolic time intervals, digitalis may have a limited place in the therapy of this form of cardiac impairment.

Soluble Interleukin-2 Receptor Levels in Patients With Dilated Cardiomyopathy Correlation With Disease Severity and Cardiac Autoantibodies

BACKGROUND There is evidence that autoimmunity plays an important role in the initiation and progression of myocardial injury in dilated cardiomyopathy. Abnormalities of both cellular and humoral immunity have been described in this disease. Soluble interleukin-2 receptor (sIL-2R) levels in the serum reflect activation of T lymphocytes in the periphery or in tissues. The present study explored the possibility that activation of cellular immunity is frequent in patients with idiopathic dilated cardiomyopathy and may have functional consequences. METHODS AND RESULTS Serum sIL-2R levels were determined with an enzyme-linked immunosorbent assay in 50 dilated cardiomyopathy patients, 30 patients with ischemic heart disease, and 22 normal control subjects. In addition, the presence of anti-beta-receptor and antimyosin antibodies was sought in the serum of cardiomyopathy patients. High sIL-2R levels (> 1400 pg/mL) were found in 38% of the dilated cardiomyopathy patients but only 6% of the ischemic heart disease patients. The group of sIL-2R-positive patients was characterized by higher average age, a higher percentage of women, and more severe disease (lower ejection fraction, higher left ventricular filling pressures, and lower cardiac output). Although the prevalence of cardiac autoantibodies did not correlate with the presence of high sIL-2R levels, higher titers of autoantibodies were found predominantly in the sIL-2R-positive group. CONCLUSIONS T-lymphocyte activation, as reflected in elevated sIL-2R levels, is frequent in patients with dilated cardiomyopathy and is associated with more severe disease. Cellular and humoral immune activation may correlate with progression of the disease process.

Predominant right ventricular dysfunction after right ventricular destruction in the dog

Abstract Right and left ventricular function was assessed by observing the response to rapid blood volume expansion before and after extensive cauterization of the right ventricle in open chest dogs. In the control period, left ventricular end-diastolic pressure surpassed right ventricular end-diastolic pressure by an average of 11.5 mm Hg after volume expansion whereas, after destruction of the right ventricle, pressure in this chamber surpassed pressure in the left ventricle by an average of 4 mm Hg. In contrast, after left ventricular damage, left ventricular end-diastolic pressure averaged 25 mm Hg more than right ventricular end-diastolic pressure. Despite extensive damage to the right ventricular free wall, the right ventricle continued to generate a near normal pressure and aortic flow could be increased above control levels by volume expansion. We conclude that, in contrast to previous evidence, damage to the right ventricle produces a syndrome of predominant right ventricular dysfunction. However, cauterization of the entire free wall of the right ventricle does not reproduce the more profound right ventricular dysfunction noted in infarction of the right ventricle in man.

Minoxidil in Severe Hypertension with Renal Failure Effect of its Addition to Conventional Antihypertensive Drugs

Abstract Minoxidil, a new vasodilator antihypertensive compound, was given to 9 uremic patients with severe hypertension uncontrollable with currently available drugs. Addition of minoxidil in doses of 5 to 10 mg twice daily to their prior therapy, resulted in satisfactory control of blood pressure in all patients. Supine blood pressure fell from a control value of 200 ± 6/124 ± 3 to 164 ± 5/91 ± 2 mm Hg (mean and standard error) after administration of minoxidil, and no patient experienced orthostatic hypotension. Tachyphylaxis has not been seen during a follow-up period averaging 26 weeks. Side effects resulting from minoxidil have been limited to mild hypertrichosis in 2 patients, nausea in another 2 and fluid retention, which was readily controlled by either hemodialysis or furosemide. Minoxidil appears, therefore, to provide a means for controlling blood pressure in patients with severe hypertension resistant to all other antihypertensive drugs.

Phosphorylation of cardiac sarcoplasmic reticulum by a calcium-activated, phospholipid-dependent protein kinase

Abstract Cardiac sarcoplasmic reticulum is phosphorylated by a cytosolic Ca 2+ -activated, phospholipid-dependent protein kinase. This phosphorylation is independent of cyclic nucleotides and enhanced by unsaturated diacylglycerols; saturated diacylglycerols, mono- and tri-glycerides are ineffective. Diacylglycerol stimulation is due to increased Ca 2+ sensitivity of the kinase reaction. Protein kinase catalyzed phosphorylation results in enhanced Ca 2+ -transport ATPase activity and may be an important determinant of cardiac sarcoplasmic reticulum function.

Anti-beta-receptor antibodies in human dilated cardiomyopathy and correlation with HLA-DR antigens

The mechanisms responsible for the decline in the density of beta-adrenoceptors in the failing myocardium have not been adequately defined. It is a possibility that the nature of the process leading to heart failure may determine, in large part, the pathogenesis of this decline. Sera of some patients with dilated cardiomyopathy contain antibodies directed against the beta-adrenoceptor, as judged by ligand binding inhibition, immunoprecipitation and immunoblotting assays. Because deranged immune function is thought to play a role in dilated cardiomyopathy, immunogenetic markers of the propensity to develop anti-beta-receptor antibodies were sought. The prevalence of HLA-DR4 was significantly higher in dilated cardiomyopathy patients (40 vs 24% in 511 normal subjects, pc less than 0.001). In contrast, no association was found between HLA phenotypes and alcoholic cardiomyopathy. Furthermore, 72% (13 of 18) of the HLA-DR4 dilated cardiomyopathy patients had anti-beta-receptor antibodies compared to 22% (7 of 33) HLA-DR4-negative patients; in the latter, presence of antibody was linked to the HLA-DR1 phenotype. Conversely, 67% (15 of 23) of the antibody-positive patients were typed as HLA-DR4 compared to only 10% of the antibody-negative patients. Interestingly, none of the 23 antibody-positive patients were typed as HLA-DR3 while 37% of the antibody-negative did. Only 25% of alcoholic cardiomyopathy patients had anti-beta-receptor antibodies and no preponderant HLA association could be demonstrated. These results suggest that the presence of anti-beta-receptor antibodies in patients with idiopathic dilated cardiomyopathy may be under the control of the major histocompatibility locus.