Production and properties of digoxin-specific antibodies.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D H Schmidt.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The lethal dose of digoxin was determined by administering 10 ml of a digoxin-saline solution to 26 nonimmunized rabbits through an ear vein over a 10 min period. Rabbits receiving less than 0.45 mg/kg digoxin showed no toxic effect, whereas all 15 rabbits that received 0.5 mg/kg developed an early arrhythmia and died within 1 hr. Moreover, eight rabbits which had been immunized with antigens unrelated to digoxin or injected with Freund's adjuvant mixture all died after receiving 0.6 mg/kg digoxin. Thus, it was concluded that 0.6 mg/kg digoxin was uniformly lethal in rabbits that had not been immunized or had received antigens unrelated to digoxin. By way of contrast, 17 rabbits immunized with a digoxin-albumin conjugate in complete Freund's adjuvant formed digoxin-specific antibodies and survived doses of digoxin varying between 0.6 and 0.9 mg/kg. In 10 rabbits immunized with digoxin-albumin conjugates, digoxin-specific antibody titers were determined following the administration of digoxin. There was a significant fall in antibody titer. This study indicates that rabbits protected by digoxin-specific antibodies suffer no acute adverse effects from an amount of digoxin which is uniformly lethal in nonimmunized rabbits and in rabbits immunized with other antigens.
To determine whether digoxin-specific antibodies can reverse established digoxin toxicity in the dog, digoxin intoxication was produced by the intramuscular administration of digoxin, 0.09 mg/kg, on each of 3 consecutive days. All animals developed toxic arrhythmias (atrioventricular block, ventricular premature contractions and/or ventricular tachycardia). In control animals not receiving antidigoxin antibodies, the arrhythmias persisted throughout a 6 hr study period. Seven of the nine control dogs were dead within 24 hr and one moribund animal was sacrificed at that time; the last animal died within 48 hr.In contrast, in six of eight dogs given digoxin-specific antibodies in canine plasma and/or rabbit serum, the arrhythmias reverted to a sinus mechanism within 30-90 min after the start of the infusion. At the end of a 6 hr period of study, these six dogs were in normal sinus rhythm and all eight were alive and in normal sinus rhythm at the end of 72 hr. This study provides evidence that digoxin-specific antibodies can reverse severe established digoxin toxicity in the dog.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
While community participation has become widely practised there has been little systematic assessment of the processes involved. A framework has been developed to measure participation on a number of dimensions and this article applies this framework to a project in Tanzania. The framework helps to systematically assess the nature and extent of community participation, but a number of problems were identified as well. Suggestions are made as how to improve upon the framework and make it a useful tool for managers.
BACKGROUND: Treadmill testing is usually preferred over cycle ergometry because of the greater sensitivity in diagnosing coronary artery disease. Treadmill testing has only recently been used with radionuclide angiography (RNA) because patient motion makes RNA imaging difficult. In this study we evaluate the comparability of treadmill and cycle exercise RNA with a dual isotope motion correction technique. METHODS AND RESULTS: Volunteer patients (n = 27) performed first-pass RNA during maximal exercise using both cycle ergometer and treadmill. Exercise capacity was greater during treadmill exercise (8.1 +/- 2.4 vs 7.5 +/- 2.2 METs). Twenty-three of 27 treadmill and all cycle ergometer exercise studies were technically adequate. Maximal heart rate was greater during treadmill exercise (150 +/- 24 vs 143 +/- 25 beats * min-l), however, systolic blood pressure was greater during cycle ergometry (174 +/- 23 vs 188 +/- 25 mmHg), resulting in no difference in heart rate times systolic blood pressure (25.7 +/- 7.2 vs 26.9 +/- 6.0). There were no differences between treadmill and cycle ergometer for peak exercise left ventricular ejection fraction (56% +/- 13% vs 57% +/- 14%) (r = 0.89). Calculated left ventricular end-diastolic volume was not different at rest (183 +/- 42 ml vs 176 +/- 44 ml) but differed significantly at peak exercise (282 +/- 75 ml vs 231 +/- 60 ml). The clinical impression, based on wall motion and left ventricular ejection fraction was very similar between treadmill and cycle ergometer. CONCLUSION: Treadmill exercise RNA is feasible, with about 85% of studies likely to be technically adequate. The overall clinical results are very similar to cycle exercise RNA, although the ordinarily expected advantages of treadmill exercise were largely absent.
A new, electrically powered, total artificial heart, the Milwaukee Heart, has been developed. This device is undergoing testing in vitro. The unidirectional motion of the brushless DC motor (BDCM) affords easier motor control and reduces energy demand. Motors with a unidirectional motion have a longer life than those with bidirectional motion. This device requires less power due to the highly efficient mechanical design. It consumes 6.5 W of power at an average flow of 5 L/min into 100 mmHg of mean aortic pressure and 20 mmHg of mean pulmonary pressure. Pumping at 8 L/min it requires 9.6 W of power. The maximum pump flow is 10 L/min and overall efficiency is 20%. A slotted optocoupler is used to determine the position of the pusher plate at the start of left systole. The number of revolutions that the BDCM makes is counted from this position. There are 50 revolutions of the BDCM per stroke (using a 50:1 gear reducer connected to the motor). The position of the pusher plate is determined from the number of BDCM revolutions. Based on where the pusher plate encounters resistance from the bladder, the force on the left pump is increased or decreased. Left to right balance has been achieved by reducing the size of the right pusher plate in conjunction with varying right stroke volume. In vitro tests show that this new, electrically powered artificial heart provides reliable performance and satisfactory hemodynamic results.
The authors investigated what contractile force (CF) could be obtained from unconditioned latissimus dorsi muscle immediately after mobilization and for the 2 week vascular period of recovery. Latissimus dorsi muscle mobilization was performed on seven adult (4 experimental and 3 control) sheep leaving only the pedicle and the peripheral muscle intact. Telectronics stimulators (Myostim 7220; Teletronics Pacing Systems, Inc, Englewood, CO) were implanted. Immediately after mobilization 11-35% of the initial CF was lost. A 30 min fatigue test was performed 1 hr after mobilization (20 g/kg preload, 10 V, 10 Hz, 15 BPM, 6 impulses per burst) using a 1 min work-1 min rest regimen. Two sheep lost 2-12% of initial CF; two increased CF by 14-24%. At the end of the fatigue test, CF consisted of 74-89% of immobilized CF. Electrical stimulation training of the muscle was then initiated with the following regimen in the experimental animals only: 15 BPM, single impulses, 5 V, 10 Hz. Every day the muscle was exercised using a work-rest regimen to mimic cardiac assist, starting with 20 min on day 2, and increasing by 2 min per day until a total of 50 min was reached on day 16. All animals were retested for CF using a 42 min fatigue test on days 6, 11, and 16. On day 6, there was no fatigue evident in the experimental group during the 42 min test. CF after testing was 59-81% (mean 67%) of initial data. In the control group (animals with no electrical stimulation training protocol), CF decreased by 11% (from 64 to 53%). On day 11, there was no fatigue evident in the experimental group; CF in all animals increased by 2-8%. On day 16, there was also no fatigue evident in the experimental group; CF increased by 0-9%. An additional 20 min of continuous contraction (15 BPM) fatigue testing was performed on the muscle without rest between the tests. No fatigue was evident at the end of testing. Light microscopic analysis of latissimus dorsi muscle biopsy specimens taken on the days of testing showed no evidence of necrotic damage. Our investigations suggest that it may be possible to start muscle transformation immediately after mobilization and use the untrained latissimus dorsi muscle for cardiac assist immediately after surgery for short periods.
The authors investigated the multi-step mechanism of healing after cardiomyoplasty, focusing on the process of angiogenesis. The authors contend that enhancement of angiogenesis and prevention of ischemia-reperfusion injuries immediately after muscle mobilization will be effective in improving cardiomyoplasty results. After cardiomyoplasty, autologous biologic glue (ABG) was administered between the latissimus dorsi muscle (LDM) and myocardium. By 2 months, a new pseudo interlayer was present that bridged the gap between the LDM and myocardium. Neovascularization was visible in the form of numerous small capillaries. Marked degeneration of the LDM was noted, possibly caused by muscle ischemia-reperfusion damage after mobilization. Pockets were created of ischemic and nonischemic LDM to test for angiogenesis. One was left free of ABG (control); one received ABG only; one received ABG and pyrrolostatin. Some of the capillaries were large and had erythrocytes inside. biopsy samples showed 9.4 +/- 1.9% of the sample was occupied by blood vessels (compared with 3.6 +/- 0.7% in control muscle). These preliminary studies prove the feasibility of the authors' concept and provide evidence that angiogenesis can accelerate the healing process and provide an organic bridge between the LDM and myocardium after cardiomyoplasty.
Six adult sheep and four newborn lambs (5 days old) were implanted with stimulator leads into the latissimus dorsi muscle and connected to a Myostim 7220 pacing system (Telectronics Pacing Systems, Inc., Englewood, CO). Electrical stimulation was started immediately after the operation. After 8 weeks of electrical stimulation, contractile force (CF) in adult sheep decreased to 76-81%, and to 78-82% in lambs. After 2 weeks' delay, CF in adults was 96-98%, and only 89-93% in lambs. After a 30 min intensive stress test, unconditioned control muscle lost 39% in lambs and 43% in adults. Muscle conditioned for 8 weeks lost 7-8% CF. However, after 2 weeks' delay, CF in adult muscle lost 33%, but only 12% in lambs. After cessation of electrical stimulation, the LDH-5 and LDH-1 + 2 fractions reverted to initial levels in adults, whereas in lambs, these levels continued to follow trends established during electrical stimulation. In both adults and lambs, the percent area occupied by the mitochondria increased during electrical stimulation by 6.9% in adults and 6.5% in lambs. After electrical stimulation cessation, the percent area in adults returned to baseline levels, whereas it continued to be elevated in lambs (3.3% vs 5.1%, respectively). The transformed muscle of the lamb did not revert to baseline levels after a delay period.
We investigated the possibility of preventing further aggravation of muscle ischemia and necrosis in newly mobilized, unconditioned latissimus dorsi muscle (LDM) by utilizing short increments of stimulation with intervening rest periods. Adult St. Croix sheep (N = 12) weighing 30 +/- 8 kg were used in this study. Fatigue tests (30 min) using different stimulation regimens before and after LDM mobilization were performed on all animals; the length of time to return to baseline levels was also measured. Our investigation yielded results that contradict the conventional wisdom that any electrical stimulation damages newly mobilized LDM and will cause a considerable decrease in contractile force (CF). Stimulation regimens using continuous contractions at 30 and 60 contractions per minute (CPM) for 30 minutes were damaging to the LDM. CF also dropped significantly and returned slowly to baseline values: at 60 CPM, CF dropped to 50 +/- 4% and did not return to baseline even after 90 minutes of rest; at 30 CPM, CF dropped to 61 +/- 4% and baseline was restored after 80 minutes of rest. Electrical stimulation using continuous contractions at a slower rate (15 CPM) was tolerable, although a 23% decrease in CF was noted (p < 0.05 when compared to 60 CPM). These results did not satisfy us that such a regimen would be useful for cardiac assistance immediately after cardiomyoplasty. The work-rest regimen at 30 CPM also gave poor results: CF decreased to 75 +/- 2% and baseline was restored after 80 minutes of rest. Promising results were seen when utilizing a work-rest regimen at 15 CPM. The newly mobilized LDM showed no visible signs of fatigue: CF decreased minimally to 92 +/- 3% (p < 0.05 when compared to 30 CPM), and light microscopic analysis of biopsies revealed no morphological damage exceeding that typically seen after subtotal mobilization. Such results open avenues for future investigations: beginning electrical stimulation immediately after cardiomyoplasty (using a single impulse and a slow rate of contraction); decreasing the length of time necessary to obtain full cardiac assistance; and beginning partial cardiac assistance immediately after cardiomyoplasty (if needed) for approximately 30 minutes several times a day.
To assist in the development of an artificial blood pump, The Milwaukee Heart (MH-1), a new nuclear scintigraphy camera was used to study the wash-in and wash-out patterns of the MH-1. These studies indicate the MH-1 has an ejection fraction of 59.3%, with a stroke volume of 72 +/- 3 ml, and an afterload of 130 mmHg. Flow through the device is highly uniform, with no areas of stagnation. Regional ejection fraction images demonstrate homogeneous ejection from apex to base. The ability to scan through the first pass images allows study of wash-in, mixing, and wash-out of the tracer. In conclusion, this technique may provide a new approach to evaluating artificial heart pumps.
Explore the source record for details and available documents.