Detection of ischemic wall dysfunction: Comparison between M-mode echocardiography and sonomicrometry

The quantification of regional ventricular function by M-mode echocardiography was compared to that by sonomicrometry in 10 closed-chest, sedated swine during temporary occlusions of the left circumflex coronary artery. Wall thickening during systole (%WT) was calculated to quantitate regional myocardial function, and percentage of fractional shortening (%FS) was calculated from both sonomicrometer tracings and M-mode echocardiograms. Ventricular dimensions at end diastole and end systole were also compared before and after 2 minutes of coronary artery occlusion. Both techniques detected significant changes in wall thickness, %WT, and %FS after occlusion. Changes in %WT during coronary artery occlusion detected by M-mode echocardiography and sonomicrometry had a significant linear relationship (p < 0.05). Discrepancy between the two techniques in the measurement of wall thickness at end diastole was attributed to the difficulty in measuring relatively small distances with M-mode echocardiograms. However, we conclude that the clinical M-mode echocardiogram is capable of detecting acute regional wall dysfunction associated with ischemia.     

Comparison of hemodynamic responses to nifedipine and nitroprusside in severe chronic congestive heart failure

The hemodynamic effects of 20 to 40 mg of oral nifedipine were compared with those of intravenous nitroprusside in 11 patients with severe chronic congestive heart failure (CHF). In each patient, both drugs were administered to produce similar reduction of systemic vascular resistance (SVR) (29 ± 13% with nifedipine and 29 ± 12% with nitroprusside, difference not significant [NS]). At this comparable decrease in systemic vascular resistance, significant differences in hemodynamic responses to both drugs were noted: Nifedipine caused a smaller increase in cardiac index (20 ± 20% vs 40 ± 24%, p < 0.02) and a larger decrease in mean blood pressure than nitroprusside (16 ± 9% vs 8 ± 10%, p < 0.05). In addition, nifedipine produced a smaller decrease in mean pulmonary artery wedge pressure (13 ± 24% vs 36 ± 21%, p < 0.001) and pulmonary vascular resistance than nitroprusside (6 ± 42% vs 26 ± 46%, NS. Mean right atrial pressure decreased with nitroprusside, from 10 ± 7 to 5 ± 3 mm Hg (p < 0.05), but not with nifedipine (10 ± 7 mm Hg before and after nifedipine administration, NS). Left ventricular stroke work index increased with nitroprusside (20 ± 8 to 27 ± 9 g-m/m², p < 0.05), but did not change with nifedipine (21 ± 9 vs 21 ± 10 g-m/m², NS). These data show that nifedipine has an arteriolar dilatatory action in patients with CHF. However, compared with nitroprusside, nifedipine had a significantly larger hypotensive effect and had a lesser effect on right and left ventricular filling pressure, cardiac output and left ventricular function.     

Canine electrophysiology of encainide, a new antiarrhythmic drug

Encainide, a new benzanillide derivative with high potency and a good therapeutic/toxic ratio, was evaluated with the use of standard His bundle recording techniques to determine its effects on the cardiac conduction system in closed chest animals. Twenty mongrel dogs weighing 18 to 29 kg were anesthetized with 4 percent chloralose and classified into groups: group 1, a control group and groups 2,3, and 4, which were given 0.3, 0.9 and 2.7 mg/kg body weight, respectively, of encalnide In an intravenous infusion over a 15 minute period. Plasma concentration, blood pressure, surface electrocardiogram and atrlal and His bundle electrograms were recorded before, during and after drug infusion for a total of 120 minutes. Heart rate, A-H and H-V intervals, the QRS complex and Q-Tc interval were measured every 5 minutes during sinus rhythm and with constant atrial pacing. In addition, sinus nodal recovery time and atrial, atrioventrlcular (A-V) nodal and left ventricular refractory periods were measured before and immediately after infusion and every 30 minutes for 2 hours. Peak plasma concentration averaged 450 ng/ml in group 2,1,300 ng/ml in group 3 and 4,000 ng/ml in group 4. Blood pressure was not altered at any dose level throughout the study. The QRS complex and H-V interval were significantly prolonged (P < 0.005) at doses of 0.9 mg/kg and greater. These effects correlated well with plasma concentration. There was no significant change in heart rate, corrected sinus nodal recovery time, A-H interval, Q-Tc Interval atrial, A-V nodal or left ventricular refractory period. It is concluded that, unlike other antiarrhythmic agents, encainide prolongs His-Purkinje system conduction without significantly affecting conduction or refractoriness of other parts of the cardiac conduction system in animals.     

Spurious scintiphotographic recurrence of pulmonary emboli

Pulmonary perfusion scintiphotographs in patients with acute, extensive pulmonary embolism have disclosed instances in which Scintiphotographic changes thought to indicate embolic recurrence were not substantiated by clinical-angiographic observations. These spurious Scintiphotographic recurrences reflected changes in the regional distribution of pulmonary vascular resistance secondary to different rates of embolic resolution or distal migration of emboli. To document the influence of changes in vascular resistance upon perfusion scintiphotographs, studies were performed in animals subjected to various sequences of pulmonary arterial obstruction by balloon catheters. Scintiphotographic changes mimicking, but not representing, recurrence of embolism were produced. Observations in both animals and man indicate that the diagnosis of embolic recurrence based on Scintiphotographic changes alone should be made with caution, particularly in patients with multiple emboli and pulmonary hypertension.     

Serum and urinary lipoproteins in the human nephrotic syndrome: evidence for renal catabolism of lipoproteins

The urinary excretion of lipoproteins and the possibility of catabolic alterations on glomerular filtration were investigated in four nephrotic subjects differing in etiology, serum lipoprotein profile, and 24 hr urinary output of protein and lipids. The apolipoproteins and lipoproteins of urine were compared with those of serum with respect to distribution profile, physical properties, and composition. Lipoprotein particles resembling the serum very low, intermediate, low, and high density lipoproteins (VLDL, IDL, LDL, and HDL, respectively) in density, particle size, and morphology were isolated from the urine. As expected from molecular sieving effects during glomerular filtration, the urinary HDL were more abundant than the lower density lipoproteins even when the plasma LDL was elevated markedly. However, little sieving effect was seen within the urinary HDL, which comprised a broad spectrum of particle sizes including the larger HDL₂, whose average diameter was similar to that of the plasma HDL. A sieving effect was not seen in the urinary LDL, except for a greatly increased proportion, about 20% of total particles, of HDL-like species. Intact apolipoproteins were not found in the concentrated urinary fraction isolated by ultrafiltration between the limits of 10⁴ and 5 × 10⁴ daltons. On the basis of immunoreactivity, gel electrophoresis, and amino acid composition, apolipoproteins B and AI are the major and minor proteins, respectively, of urinary LDL, and apo B is the major protein of the urinary IDL and VLDL. Apolipoproteins AI, AII, CI, CIII, and possibly AIV were isolated from the urinary HDL. As much as 20% of the protein moiety of the urinary HDL appeared to be large apolipoprotein fragments with molecular weights and isoelectric points similar to those of apo CII and apo CIII. The fragments were derived in part from apo AI, the least acidic form of which was lost preferentially. The lower density classes of urinary lipoproteins also appeared to have lost apo E and apo C's and to have undergone partial proteolysis. Apparently, the surface-exposed, readily exchangeable apolipoproteins are subject to proteolytic degradation upon glomerular filtration.     

Pulsed Doppler echocardiography in the diagnosis and estimation of severity of aortic insufficiency

Detection and estimation of the degree of chronic aortic insufficiency with pulsed Doppler echocardiography was attempted in 27 patients documented to have aortic insufficiency on aortography. Twenty-five patients had associated aortic stenosis or mitral valve disease, or both. A disturbed diastolic flow within the left ventricular outflow tract was recorded in all but one patient (Doppler sensitivity 96 percent). Aortic insufficiency was clinically undetected In three patients (clinical sensitivity 89 percent). In a small number of patients Doppler echocardiography also appeared to be highly specific for this disorder. The Doppler technique estimated the degree of aortic Insufficiency by assessing the distribution of diastolic flow within the outflow tract and the body of the left ventricle. A significant correlation between the Doppler method and the angiographic estimation of aortic insufficiency was found (r = 0.88, p < 0.01).     

The comparative value of serum thyroglobulin measurements and iodine 131 total body scans in the follow-up study of patients with treated differentiated thyroid cancer

This study is an attempt to unify the evaluation of patients with well-differentiated thyroid cancer after ablative therapy. As such, serum thyroglobulin determinations on and off thyroid hormone (T₄) therapy and iodine 131 total body scans were examined in 53 patient studies. No metastases were found in patients whose thyroglobulin value was undetectable (< 1 ng/ml). Values during T₄ therapy that were detectable, even as low as 4.2 ng/ml, were occasionally associated with metastases. After T₄ withdrawal, thyroglobulin value and scan were obtained. Neither metastasis nor clinically detectable cancer was found in patients whose thyroglobulin value was less than 10 ng/ml while off T₄. Conversely, a value greater than 10 ng/ml was often associated with documented metastases even when the scan was negative. In summary, a thyroglobulin value less than 1 ng/ml during T₄ therapy or less than 10 ng/ml off T₄ therapy suggests successful therapy and a routine scan could be avoided unless clinically indicated. However, a value greater than 10 ng/ml suggests the presence of metastasis despite a negative scan. Thyroglobulin determination substantially improves the management of these patients.     

Tocainide therapy for treatment of ventricular arrhythmias: assessment with ambulatory electrocardiographic monitoring and treadmill exercise

Tocainide has shown promise in the acute suppression of ventricular arrhythmias and in the treatment of such arrhythmias considered refractory to other drugs. However, there is little experience with tocainide therapy using currently acceptable statistical end points in patients not receiving conventional antiarrhythmic drugs concurrently. Accordingly, a double-blind, crossover study design was used to compare the effects of 2 week periods of placebo therapy and small dose (400 mg every 8 hours) tocainide therapy in 10 patients with ventricular arrhythmias who were not receiving quinidlne, procainamide or disopyramide. Ventricular arrhythmias were assessed with 24 hour ambulatory electrocardiographic monitoring and treadmill exercise. Individual patients not responding to small dose tocainide with at least an 80 percent decrease in ventricular premature complexes on ambulatory monitoring were given doses of 600 mg and then 800 mg every 8 hours. Small dose tocainide therapy resulted in a decrease in ventricular premature complexes/hour from 364 ± 98 (standard error) to 127 ± 50 (p < 0.05) and 5 of 10 patients had at least an 80 percent decrease. At higher dose levels, two additional patients had at least an 80 percent decrease. The response of ventricular arrhythmias during treadmill exercise was comparable with that during ambulatory monitoring. Side effects were minor or nonexistent in the seven patients who responded to tocainide, and effective mean serum concentrations were 4.4 ± 1.9 μg/ml, a value significantly lower than that previously reported to suppress refractory ventricular arrhythmias. It is concluded that tocainide is an effective agent in patients not receiving concurrent therapy with conventional agents and that patients selected because of refractory ventricular arrhythmias may require higher serum concentrations of the drug than unselected patients.