Respiration-dependent ventricular pacing compared with fixed ventricular and atrial-ventricular synchronous pacing: aerobic and hemodynamic variables

A pacemaker that adapts heart rate in response to the patient's metabolic requirements has been developed. The pacemaker uses breathing frequency and tidal volume as the indicators of physiologic demand. Maximal physical work capacity, anaerobic threshold, oxygen uptake (16 patients) and hemodynamic variables (9 patients) were assessed with fixed rate (VVI), atrial synchronous (VDT/I) and respiration-dependent ventricular (VVI-RD) pacing. All subjects attained their anaerobic threshold in stress tests with VVI pacing. The maximal physical capacity (p less than 0.001), work time to attain the anaerobic threshold (p less than 0.01) and oxygen uptake (p less than 0.001) were significantly greater with VVI-RD than with VVI pacing. The transition from the supine to the standing position was characterized by a significant increase of cardiac index at rest with both VDT/I and VVI-RD pacing as compared with VVI pacing. Progressive increments in the cardiac index and average left ventricular stroke work index were significantly different at submaximal and maximal exercise when VVI and VVI-RD were compared. At maximal exercise, mean cardiac output was also significantly different: 10.21 +/- 2.5 (SD) liters/min with VVI, 11.2 +/- 0.8 liters/min with VDT/I (p less than 0.05) and 12.65 +/- 3.1 liters/min with VVI-RD (p less than 0.05) pacing. Maximal oxygen extraction values were greater with VVI and VVI-RD pacing than with VDT/I pacing. Pulmonary artery end-diastolic pressures at maximal exercise were within the normal range with the three different modes of pacing. In conclusion, there is a significant (25%) improvement in exercise performance with VVI-RD pacing as compared with VVI pacing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterogeneity of the erythrocyte Na-K pump status in human obesity

The number of Na-K pump units, the Na-K-ATPase activity, the K transport turnover rate per pump unit and the intracellular Na and K concentrations were measured in the erythrocytes of 56 obese patients and 20 normal subjects. No differences were found between the two groups. In obese patients, we failed to observe any influence of dietary habits, age of onset, or family history of obesity on the Na pump status. On the other hand, we found that the number of pump units was not a close reflection of the membrane cation transport and in some patients with an abnormally high number of pump units, an inappropriately low Na-K-ATPase activity was observed. We also identified two small groups of obese patients with, respectively, abnormally high or low K transport turnover rate per pump unit. Our study seems to support the hypothesis that abnormalities in the erythrocyte Na-K pump system are not usual in the obese population but are probably present only in a limited number of selected patients.     

Ventricular septal rupture after myocardial infarction: Diagnosis by two-dimensional and pulsed doppler echocardiography

Rupture of the ventricular septum in the acute phase of myocardial infarction (MI) requires prompt recognition for correct management. The 2-dimensional and pulsed Doppler echocardiographic findings are reported from 11 patients with ventricular septal (VS) rupture. VS rupture was confirmed by cardiac catheterization in 9 patients, surgery in 4 patients and necropsy examination in 3 patients. Two-dimensional echocardiography (echo) directly visualized the rupture in 7 patients and assessed the size and location of an associated aneurysm in 10. In all patients, M-mode pulsed Doppler echo allowed detection of the left-to-right shunting due to VS rupture, but failed to indicate the rupture site. M-mode pulsed Doppler echo was reliable for detecting VS rupture after MI. Conversely, 2-dimensional echo was less effective in the direct visualization of the rupture, but provided anatomic and functional information that was useful in medical and surgical management. Thus, the techniques are complementary and should be used in combination for the assessment of VS rupture in acute MI.     

Effect of acebutolol on left ventricular hemodynamics and anatomy in systemic hypertension

In 18 patients with mild or moderate essential hypertension who responded favorably to acebutolol antihypertensive therapy, echocardiography (echo) was performed in the basal condition and after 6 and 12 months of follow-up. Acebutolol induced a significant decrease in blood pressure (BP), from a basal value of 167 +/- 3/105 +/- 2 mm Hg to 138 +/- 5/90 +/- 2 mm Hg after 6 months (p less than 0.01) and to 134 +/- 3/91 +/- 3 mm Hg after 1 year (p less than 0.01), and in heart rate, from 75 +/- 3 to 63 +/- 2 beats/min after 6 months (p less than 0.01) and to 63 +/- 2 beats/min after 1 year (p less than 0.01). The decrease in BP was achieved through a decrease in cardiac output from 6.3 +/- 0.28 to 5.3 +/- 0.25 liters/min after 6 months (p less than 0.05) and to 5.32 +/- 0.2 liters/min after 1 year (p less than 0.05), which resulted from a reduction in heart rate; stroke volume did not show significant change during the treatment and left ventricular (LV) performance was improved. There was a parallel decrease in LV posterior wall and ventricular septal thicknesses and estimated LV mass. In patients with LV hypertrophy, the change in mass was significantly correlated with the change in heart rate both after 6 and 12 months of therapy (r = 0.6234, p less than 0.05 and r = 0.7121, p less than 0.05 after 6 and 12 months, respectively).     

Protective effects of simultaneous alpha and beta adrenergic receptor blockade on myocardial cell necrosis after coronary arterial occlusion in rats

Alpha and beta adrenergic receptor blocking agents have each been separately shown to reduce the extent of ischemic necrosis. This study was designed to assess whether the simultaneous blockade of both alpha and beta adrenergic receptors achieved by labetalol is also effective in reducing infarct size. Moreover, the effects of labetalol were compared with those of propranolol. Accordingly, 127 rats were randomly assigned to four groups: Three groups underwent coronary arterial occlusion (the first group [n = 40] did not receive any drug treatment; the second [n = 29] received labetalol, 25 mg/kg subcutaneously, 5 minutes and 24 hours after coronary occlusion; the third [n = 25] received propranolol 5 mg/kg subcutaneously at the same times). The fourth group of 33 rats was subjected to sham operation. After randomization, no difference in mortality was found among the four groups. All rats were killed 48 hours after coronary occlusion and the total creatine kinase activity of the left ventricle was measured. From this value, infarct size was calculated and found to average 66.5 ± 2.6 percent (mean ± standard error of the mean [SEM]) of the left ventricle in control rats and 44.6 ± 4.1 percent in labetalol-treated rats (p < 0.01). In contrast, in propranolol-treated rats infarct size was 56.6 ± 3.3 percent of the left ventricle, a value smaller than that in control rats (p < 0.05), but higher than that in labetalol-treated rats (p < 0.05).Another 16 rats underwent coronary arterial occlusion: 10 of these were treated with labetalol, whereas the remaining 6 served as a control group. These rats were killed 48 hours after occlusion; infarct size was measured by planimetry on histologic sections of serial slices of the left ventricle and was found to be 40.6 ± 2.7 percent of the left ventricle in control rats and 27.8 ± 3.7 percent in labetalol-treated rats (p < 0.005). Finally, in yet another 36 rats, divided into control and labetalol-treated groups of 15 and 21 rats, respectively, coronary occlusion was performed. These rats were killed 21 days after occlusion and infarct size was measured on histologic sections. Planimetry showed size of the infarct to be 30.5 ± 2.4 percent of the left ventricle in control animals and 15.2 ± 1.2 percent (p < 0.01) in labetalol-treated rats, showing that the extent of scarring after coronary arterial occlusion can be reduced by labetalol. Thus, myocardium acutely jeopardized by ischemia can be preserved permanently by combined alpha and beta receptor blockade.     

Tocainide for refractory symptomatic ventricular arrhythmias

Tocainide, an oral form of lidocaine, was employed in 120 patients with recurrent malignant ventricular arrhythmia refractory to conventional antiarrhythmic drugs. After discontinuation of all antiarrhythmic agents, patients underwent control studies including 48 hours of ambulatory electrocardiographc monitoring and maximal symptom-limited exercise testing. One hundred patients had frequent as well as repetitive ventricular premature beats whereas in 20 patients, because of infrequency of ectopic activity, invasive electrophysiologic studies were carried out to provoke a repetitive ventricular response.Tocainide therapy was begun at 1,200 mg daily and increased to 2,400 mg daily guided by drug efficacy and the occurrence of adverse effects. After 48 hours of treatment with a fixed dose, drug action was evaluated by repeat monitoring and exercise stress testing or electrophysiologic testing. Fifty-five patients (46 percent) responded to tocainide. The average daily dose of drug and peak blood levels were equivalent in responders and nonresponders. Adverse effects occurred in 42 patients (35 percent) and were primarily related to the central nervous system. Lidocaine predicted the response to tocainide in 78 percent of patients. Thirty-four patients were continued on long-term maintenance therapy. After an average follow-up period of 16 months (range 2 to 39), treatment with the drug was discontinued in nine patients. The remaining 25 patients have had no adverse effects and no recurrence of ventricular arrhythmia.     

Effects of unilateral cardiac sympathetic denervation on the ventricular fibrillation threshold

A train of gated stimuli scanning the entire vulnerable period was delivered to the right anterior or left posterior ventricular surface to study the ventricular fibrillation threshold in anesthetized and vagotomized dogs. Heart rate was held constant by atrial pacing. Measurements were obtained in control conditions and after surgical removal of one stellate ganglion. To avoid the shortcomings associated with an irreversible procedure like stellectomy, control fibrillation threshold measurements were also alternated with determinations during reversible blockade by cooling of one stellate ganglion. The results were similar with both techniques. In nine animals, ablation or cooling of the left stellate ganglion increased ventricular fibrillation threshold by 72 ± 35 (mean ± standard deviation) percent compared with control values (P < 0.001). By contrast, in 11 animals, ablation or cooling of the right stellate ganglion lowered the threshold by 48 ± 14 percent compared with control values (P < 0.001). Electrode location did not influence the results. The observed changes depended solely upon unilateral removal of cardiac sympathetic activity and were not demonstrable if such activity was low.

These results suggest that right and left cardiac sympathetic nerves may have different and specific effects on cardiac excitability. They also contribute to the understanding of the pathogenesis of the long Q-T syndrome (characterized by episodes of ventricular fibrillation associated with increased sympathetic activity) and increase the rationale for left stellectomy as the specific treatment for this illness. Left stellectomy, by raising the ventricular fibrillation threshold, may also represent an alternative measure in patients at high risk of sudden death from ventricular arrhythmias resistant to medical therapy.     

Two-dimensional echocardiographic recognition of complications of cardiac invasive procedures

Two-dimensional echocardiography allowed prompt recognition of a major complication of a cardiac invasive procedure in 6 patients. In 5 cases, a preinvasive echocardiographic study was available for comparison. In 1 patient with perforation of the ventricular septum by a temporary pacemaker, the catheter was visualized as it passed through the ventricular septum, with the tip located against the left ventricular posterolateral wall. In another patient, the intimal flap caused by aortic dissection after left-sided heart catheterization was clearly visualized. In 2 patients with hemopericardium secondary to cardiac perforation during right-sided cardiac catheterization, 2-dimensional echocardiography revealed pericardial effusion not noted in studies performed before the invasive procedure. Two patients in whom hemopericardium occurred from injury by the pericardiocentesis needle also were studied by 2-dimensional echocardiography. Postpericardiocentesis images revealed new intrapericardial abnormalities (a thrombus-like mass and fibrinous strands) not present in the echocardiographic studies performed before pericardiocentesis. Real-time 2-dimensional echocardiography appears to be a good tool in the recognition of the emergencies secondary to cardiac invasive procedures.     

Prevention of sudden death after repair of tetralogy of Fallot: treatment of ventricular arrhythmias

The majority of sudden deaths after repair of tetralogy of Fallot have been presumed to be due to ventricular arrhythmia; however, it remains to be demonstrated that antiarrhythmic medication reduces the incidence of sudden death. Since 1978, ventricular arrhythmias have been treated aggressively; these include any ventricular arrhythmia on routine electrocardiogram and more than 10 uniform premature ventricular complexes per hour on 24 hour electrocardiogram. A review was undertaken of 488 patients followed up for more than 1 month after repair of tetralogy of Fallot (mean follow-up time 6.1 years); 13.5% had ventricular arrhythmia on routine electrocardiogram. Ventricular arrhythmia appeared from 2 months to 21 years postoperatively (mean 7.3 years). Ventricular arrhythmias were significantly (p less than 0.01) related to: longer follow-up duration, older age at follow-up, older age at operation and higher postoperative right ventricular systolic and end-diastolic pressures. Ventricular arrhythmia on routine electrocardiogram occurred in 100% of those who later died suddenly compared with 12% of those who did not die (p less than 0.01). Treatment for ventricular arrhythmia was given to 46 patients and considered "successful" if there were fewer than 10 uniform premature ventricular complexes per hour on 24 hour electrocardiogram. A successful drug was found in 44 of the 46: 30 of 34 given phenytoin, 6 of 9 given propranolol, 1 of 7 given quinidine, 1 of 2 given disopyramide, 8 of 9 given mexiletine and 4 of 5 given amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute hypotensive and renin-stimulating actions of captopril before and during treatment with a beta-blocking drug

There is no general agreement on the relation between the hypotensive effect of captopril and the pretreatment plasma renin levels of hypertensive patients. To determine whether the hypotensive effect of captopril was directly related to plasma renin, the angiotensin-converting enzyme inhibitor was administered acutely to 10 essential hypertensive patients with normal or suppressed plasma renin activity before and after inhibition of renin secretion with propranolol. Captopril was equally effective in reducing blood pressure both when administered alone (25 mg: -29/-17; 50 mg: -37/-23 mm Hg) and after chronic treatment with propranolol (25 mg: -33/-20; 50 mg: -30/-20 mm Hg). The increase in renin induced by captopril was not decreased by propranolol therapy. The persistence of the hypotensive effect of captopril after renin suppression by propranolol suggests that this drug has some blood pressure decreasing properties independent of plasma renin.     

Hemodynamic response to exercise after propranolol in patients with mitral stenosis.

Hemodynamic response to exercise before and 10 minutes after propranolol (5 mg intravenously) was studied in 10 young patients with pure mitral stenosis who had normal sinus rhythm and no cardiac failure. After propranolol the mean heart rate and cardiac index at rest were lower than during the control state (respectively, 95 +/- 4 versus 82 +/- 3 beats/min, P less than 0.005; 3.4 +/- 0.2 versus 2.8 +/- 0.1 liters/min per m2, P less than 0.025). As a result, the mean pulmonary wedge pressure and mean mitral valve gradient at rest were lower (respectively, 22 +/- 2 versus 18 +/- 2 mm Hg, P less than 0.005; 24 +/- 2 versus 17 +/- 2 mm Hg, P less than 0.001). During exercise after propranolol the values of pulmonary wedge pressure and mitral valve gradient were lower than control values during exercise (respectively, 39 +/- 3 versus 30 +/- 2 mm Hg, P less than 0.005; 44 +/- 3 versus 32 +/- 3 mm Hg, P less than 0.005), again because of the lower heart rate and cardiac index (130 +/- 6 versus 104 +/- 6 beats/min, P less than 0.001; 4.6 +/- 3 versus 3.7 +/- 2 liters/min per m2, P less than 0.01). Left ventricular end-diastolic pressure and stroke index showed no significant changes. Thus, propranolol may benefit patients with pure mitral stenosis with sinus rhythm and no cardiac failure whose symptoms occur during those reversible conditions characterized by an increase in heart rate or cardiac output, or both.     

Short- and long-term experience with flecainide acetate in the management of refractory life-threatening ventricular arrhythmias

Thirty-eight patients with organic heart disease and history of sudden cardiac arrest or recurrent sustained ventricular tachycardia were treated with flecainide. Coronary artery disease was present in 33 patients. Previous antiarrhythmic therapy consisted of two to eight drugs (mean four). Fourteen patients were resuscitated from sudden cardiac death and 24 patients had chronic recurrent sustained ventricular tachycardia. Twenty-eight patients had electrophysiologic testing before and during flecainide treatment. Sustained ventricular tachycardia became noninducible in 5 patients, nonsustained in 5 patients and slowed in 13 patients (cycle length increased from 278 +/- 64 to 395 +/- 91 ms; p = 0.002). Three of the 14 patients with sudden cardiac death and 15 of the 24 patients with recurrent sustained ventricular tachycardia remained on long-term flecainide treatment. The mean left ventricular ejection fraction in 16 of these 18 patients was 37%. Nonlimiting side effects occurred in seven patients (18%). Proarrhythmic effects were seen in four patients (10%). At a mean follow-up time of 11 +/- 3 months, 15 patients (39%) had had no recurrence, including 5 who had inducible sustained ventricular tachycardia and 5 who did not on retesting during treatment. In the 18 patients who received long-term therapy, 3 late deaths occurred, 1 of which was of arrhythmic origin. These data suggest that flecainide is effective in about 40% of patients with severe refractory ventricular arrhythmias. Its value as a single drug in the treatment of sudden cardiac death remains to be defined.     

Control of late postoperative ventricular arrhythmias with phenytoin in young patients

Ventricular arrhythmias probably initiate the events leading to sudden death in patients who have recovered uneventfully from surgery for congenital heart disease. It is therefore recommended that antiarrhythmic therapy be given to all patients who have had surgery for congenital heart defects and who have ventricular arrhythmias found in a routine electrocardiogram taken after the immediate postoperative period. The response of ventricular arrhythmias to treatment was studied in six ambulatory patients aged 7 to 27 years (mean 16.5) who had had surgery a mean of 10.7 years before the arrhythmia was recognized. Four patients had unsatisfactory repair of the congenital defect; the two other patients had only a palliative operation. Each patient's electrocardiogram was monitored continually by tape recording. Each received phenytoin, 3.75 mg/kg body weight, every 6 hours for four doses, then 1.9 mg/kg every 6 hours until the serum concentration of phenytoin was 15 to 20 μg/ml. This serum concentration was maintained with the daily administration of 2.5 to 3 mg/kg every 12 hours. In the 24 hours before treatment, two patients had ventricular tachycardia, two had paired premature ventricular complexes and two had 10 or more single premature ventricular complexes/hour. After treatment, all patients had “effective control” (one or less premature ventricular complex/hour for 12 consecutive hours). This control was achieved with phenytoin in five patients, but one patient required the addition of disopyramide (2 mg/kg every 6 hours). All five patients undergoing a treadmill test before treatment had premature ventricular complexes during or after exercise; after treatment, only one had premature ventricular complexes after exercise. The patient who required two drugs was unable to perform a treadmill test. The mean effective serum phenytoin concentration, 15.7 μg/ml (range 8.5 to 20.0), was reached at a mean time of 61.2 hours (range 42 to 80) after the start of phenytoin therapy. Ataxia occurred in two patients with serum phenytoin concentrations of 16 and 20 μg, but not in the other four, three of whom had serum concentrations greater than 20 μg/ml. Echocardiographic, hematopoletic, hepatic and renal function indexes remained constant with treatment.It is concluded that (1) phenytoin suppressed ventricular arrhythmias in six children and young adults after surgery for congenital heart disease; (2) the effective serum concentration of phenytoin was approximately 15 μg/ml, but varied widely; and (3) this concentration was achieved within 48 to 72 hours when an oral loading dose was administered.     

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.     

Changes of the intralymphocytic sodium concentration after acute and chronic captopril administration

The effect of captopril on intralymphocytic sodium concentration in hypertensive subjects was studied. After acute and chronic treatment the intralymphocytic sodium content decreased. The possibility is discussed that a similar decrease might also occur in smooth muscle cells, thus enhancing the hypotensive effect of captopril.     

Long-term effectiveness of verapamil in stable and unstable angina pectoris. One-year follow-up of patients treated in placebo-controlled double-blind randomized clinical trials

The possibility that denervation supersensitivity might result from left stellectomy was investigated because of its potential clinical implications. The study was conducted in 12 conscious dogs by injecting norepinephrine as a bolus dose or as an infusion before and 2 to 4 weeks after left stellectomy. The variables analyzed were the first derivative of left ventricular pressure (dP/dt max) and the number of premature ventricular complexes. Under control conditions dP/dt max was unaffected by left stellectomy (3,572 +/- 280 versus 3,549 +/- 235 mm Hg/s). Bolus injections and infusions produced the same results and showed no difference in the increases in dP/dt max produced by norepinephrine observed before and after left stellectomy. For example, with the largest dose of norepinephrine, 1.25 microgram/kg, the changes from the control value were 4,533 +/- 269 and 5,032 +/- 668 mm Hg/s, respectively (difference not significant). The number of premature ventricular complexes resulting from the two largest doses of norepinephrine was significantly decreased after left stellectomy (85 +/- 12 versus 46 +/- 14, P less than 0.05), and ventricular tachycardia, which occurred in three dogs under control conditions, was never observed after left stellectomy. This study reveals another aspect of the antiarrhythmic effect of left stellectomy and demonstrates that it does not produce denervation supersensitivity.     

Left ventricular dynamics during long-term digoxin treatment in patients with stable coronary artery disease

Ten patients with stable coronary artery disease who did not have clinical congestive heart failure and had recovered (3 or more months) from coronary bypass graft surgery were given both intravenous and oral digoxin. Left ventricular performance was assessed weekly for 3 control weeks, during 4 weeks of long-term oral digoxin treatment and during 2 to 3 weeks of recovery. Serial noninvasive measurements of velocity of circumferential fiber shortening, ejection fraction, end-diastolic volume and cardiac output were obtained with computer-assisted fluoroscopic analysis of the motion of surgically implanted mid wall myocardial markers that outline the left ventricular cavity. During 4 weeks of oral digoxin therapy, mean serum digoxin levels were maintained between 1.2 ± 0.1 and 1.4 ± 0.1 ng/ml (mean ± standard error of the mean). Mean velocity of circumferential fiber shortening increased 15.6 percent from 0.65 ± 0.05 to 0.75 ± 0.05 circumferences/sec (P < 0.001) and ejection fraction increased 8.5 percent from 0.51 ± 0.03 to 0.55 ± 0.03 (P < 0.001). End-diastolic volume and cardiac output were not changed significantly. The inotropic response to oral digoxin was similar during the 4th week of treatment to that seen during the first week and the mean inotropic effect of chronic oral digoxin was not significantly less than that achieved by administration of 1 mg intravenously over 15 minutes. These data suggest that chronic oral digoxin treatment exerts a sustained inotropic effect on the nonfailing heart that persists for at least 4 weeks and is equivalent to that achieved with rapid intravenous digitalization.     

Positive feedback sympathetic reflexes and hypertension.

A pressor reflex that can be elicited from the thoracic aorta in conscious dogs is described. Distension of the aorta excites sympathetic afferent fibers and results in an increase in arterial blood pressure because of increased sympathetic outflow to the heart and blood vessels. The reflex center for this positive feedback mechanism is located in the spinal cord and, when the reflex is activated, it can modulate other negative feedback control systems.