Basis for use of digoxin in small birds.
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Animals↗
Biomedical subjects
R L Hamlin
Publications and source records attributed to R L Hamlin.
The effects of graded doses of epinephrine on regional myocardial blood flow during cardiopulmonary resuscitation in swine.
Although epinephrine has been shown to improve myocardial blood flow during cardiopulmonary resuscitation (CPR), the effects of standard as well as larger doses of epinephrine on regional myocardial blood flow have not been examined. In this study we compared the effects of various doses of epinephrine on regional myocardial blood flow after a 10 min arrest in a swine preparation. Fifteen swine weighing greater than 15 kg each were instrumented for regional myocardial blood flow measurements with tracer microspheres. Regional blood flow was measured during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun and regional myocardial blood flow was determined. Animals were then randomly assigned to receive 0.02, 0.2, or 2.0 mg/kg epinephrine by peripheral injection. One minute after drug administration, regional myocardial blood flow measurements were repeated. The adjusted regional myocardial blood flows (ml/min/100 g) for animals given 0.02, 0.2, and 2.0 mg/kg epinephrine, respectively, were as follows: left atrium, 0.9, 67.4, and 58.8; right atrium, 0.3, 46.2, and 38.5; right ventricle, 0.7, 82.3, and 66.9; right interventricular septum, 1.7, 125.5, and 99.1; left interventricular septum, 2.8, 182.8, 109.5; mesointerventricular septum, 16.8, 142.2, and 79.2; left ventricular epicardium, 19.2, 98.5 and 108.7; left ventricular mesocardium, 22.8, 135.0, and 115.8; and left ventricular endocardium, 2.5, 176.1, and 132.9). All comparisons between the groups receiving 0.02 and 0.2 mg/kg epinephrine were statistically significant (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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Carbon dioxide storage capacity of endurance and sprint-trained athletes in exercise.
The purpose of this study was to compare CO2 storage capacity of endurance and sprint-trained athletes during steady state exercise. Ten subjects, five sprinters and five distance runners, performed a submaximal treadmill exercise at two different work rates, 45% and 65% of VO2max. CO2 storage capacity was determined by measuring the excess CO2 washout associated with hyperventilation, normalized for body weight and expressed per unit change in mixed venous PCO2 (ml kg-1 Torr-1). Mixed venous PCO2 (PvCO2) was measured by rebreathing equilibration. It was found that CO2 storage capacities of the runners were significantly (P less than 0.05) greater than the sprinters at the two work rates. The sprinters CO2 storage capacities were 2.69 and 2.14 ml kg-1 Torr-1 at low and high work rates, respectively. The corresponding mean values for the runners were 4.56 and 3.92 ml kg-1 Torr-1, respectively. These results may be explained by the metabolic differences between the sprinters and runners. The sprinters' musculature depends more heavily on the glycolytic metabolic pathway, which is associated with an increased lactate production and hence a reduction in the combining power of the blood for CO2 during exercise. At the low work rate, the body's storage capacity for CO2 was significantly (P less than 0.05) greater than the higher work rate for both groups. Obviously, at the higher work level more blood would be presented to the lungs per unit time allowing an increase in CO2 clearance from the body stores.
Adolescent↗
Unipolar thoracic electrocardiograms in which P waves of relative uniformity occur in male horses.
Bipolar and unipolar limb leads and unipolar thoracic lead ECG were obtained from 100 male crossbred horses. P-wave morphologic features were classified according to positivity negativity and monopolarity dipolarity, and the percentage of horses that had P waves of a given morphologic class in each lead was calculated. P-Wave morphologic features of 4 precordial leads were most uniform, with greater than 80% of the horses having a single configuration.
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Unipolar thoracic electrocardiography that induces QRS complexes of relative uniformity from male horses.
Electrocardiograms were obtained from 100 male crossbred horses. In addition to standard limb leads, leads were taken from 12 points on the thorax. The QRS complexes were categorized into 1 of 8 forms on the basis of configuration and amplitudes of component deflections. Relative uniformity of QRS was determined for each lead, using the percentage of horses that possess a particular configuration. All unipolar thoracic leads, except those coplanar with the frontal plane, and lead aVR had great uniformity, with greater than 80% of the horses with a QRS of similar contour.
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Evaluation of flow-volume curves generated by forced-expiratory spirometry in anesthetized dogs.
Positive-pressure plethysmography was used to generate partial and maximal flow-volume data in 10 anesthetized dogs. Acetylcholine (ACh) administered IV induced significant (P less than 0.05) changes in tidal breathing, as evidenced by decreased tidal volume, increased respiratory rate and dynamic resistance, and decreased dynamic compliance. Partial forced-expiratory spirometry-determined from end inspiratory capacity and functional residual capacity, revealed changes in flow and volume as a result of ACh treatment. These changes were not seen in maximal curves (determined from total lung capacity). Peak expiratory flows were limited by the presence of an endotracheal tube. Use of instantaneous time-constant variables to evaluate the concavity or convexity of the downslope of a flow-volume curve did not reveal differences after IV ACh administration. Seemingly, partial forced-expiratory spirometry was useful in detecting bronchoconstriction in anesthetized dogs. Accepted techniques of flow-volume curve analysis for the evaluation of small airway function were not sensitive enough to detect bronchoconstriction in the dog.
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The comparative effects of epinephrine versus phenylephrine on regional cerebral blood flow during cardiopulmonary resuscitation.
Epinephrine in larger doses than currently recommended during cardiopulmonary resuscitation (CPR) has been shown to improve cerebral blood flow (CBF) following a 10-min arrest in a swine model. The purpose of this pilot study was to measure CBF during CPR, comparing high-dose epinephrine to a pure alpha-1 agonist, phenylephrine. Ten swine each weighing greater than 15 kg, were instrumented for regional CBF measurements using tracer microspheres. CBF was measured during normal sinus rhythm (NSR). Following 10 min of ventricular fibrillation, CPR was begun and regional CBF was again measured. Following 3 min of CPR, the swine were randomized to receive either epinephrine (0.2 mg/kg), or phenylephrine (0.1 mg/kg), through a peripheral intravenous line. Regional CBF was again measured 1 min after drug administration. Regional CBF following drug administration was compared using an analysis of covariance. Adjusted CBFs are expressed in ml/min per 100 g for epinephrine and phenylephrine, respectively: left cerebral cortex (12.5 vs. 2.3, P = 0.002); right cerebral cortex (13.0 vs. 2.8, P = 0.003); cerebellum (32.9 vs. 4.1, P = 0.004); midbrain (35.7 vs. 2.6, P = 0.0004), pons (30.3 vs. 2.9, P = O.006); medulla (49.5 vs. 13.6, P = 0.02) and cervical spinal cord (49.6 vs. 14.1, P = 0.003).
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Changes in QRS complex in dogs with normal and exaggerated tidal volumes.
The influence of normal and exaggerated ventilation on the QRS was studied in 10 dogs. Peak-to-peak amplitudes of QRS in 4 circumferential unipolar and 2 limb lead ECG were obtained during eupnea and during hyperinflation produced by intermittent positive pressure ventilation or negative extrathoracic pressure. Marked changes were not observed in any lead during eupnea. During hyperinflation to a transpulmonary pressure of 10 mm of Hg (whether by intermittent positive pressure ventilation or negative extrathoracic pressure), voltages decreased in leads I, V10, rV3, and aVF and were variable in leads V3 and V5. Radiography revealed that during the hyperinflation the heart was displaced to the nondependent side of the thorax further from the dependent electrodes and that the heart became generally smaller. Changes in voltage could be attributed to alterations in relationships between the heart and electrodes on the torso surface or to changes in volume conductor properties of the heart and torso.
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Use of the chicken heart in a Langendorff preparation.
Hearts isolated from healthy chickens were perfused with oxygenated Krebs-Henseleit buffer. Balloons were inserted into the left ventricle, filled with saline and attached to a pressure transducer for measuring left ventricular pressures. A bipolar electrogram was obtained between the atria and ventricles. Hearts so perfused manifested mechanical alternans for approximately 15 minutes, after which they sustained a regular sinus rhythm without mechanical alternans for at least 60 minutes. By infusing 0.1 ml increments of saline into the balloon located within the ventricle, Frank-Starling curves could be generated. This preparation has potential for use in pharmacologic evaluations.
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Human and canine ventricular vasoactive intestinal polypeptide: decrease with heart failure.
Vasoactive intestinal polypeptide (VIP) is a systemic and coronary vasodilator that may have positive inotropic properties. Myocardial levels of VIP were assayed before and after the development of heart failure in two canine models. In the first, cobalt cardiomyopathy was induced in eight dogs; VIP (by radioimmunoassay) decreased from 35 +/- 11 pg/mg protein (mean +/- SD) to 5 +/- 4 pg/mg protein (P less than 0.05). In six dogs with doxorubicin-induced heart failure, VIP decreased from 31 +/- 7 to 11 +/- 4 pg/mg protein (P less than 0.05). In addition, VIP content of left ventricular muscle of resected failing hearts in 10 patients receiving a heart transplant was compared with the papillary muscles in 14 patients (five with rheumatic disease, nine with myxomatous degeneration) receiving mitral valve prostheses. The lowest myocardial VIP concentration was found in the hearts of patients with coronary disease (one patient receiving a transplant and three receiving mitral prostheses) (6.3 +/- 1.9 pg/mg protein). The other patients undergoing transplantation had an average ejection fraction of 17% +/- 6% and a VIP level of 8.8 +/- 3.9 pg/mg protein. The hearts without coronary artery disease (average ejection fraction of this group 62% +/- 10%) had a VIP concentration of 14.1 +/- 7.9 pg/mg protein, and this was greater than in hearts of the patients with coronary disease and the hearts of patients receiving a transplant (P less than 0.05). Myocardial catecholamines were also determined in 14 subjects; a weak correlation (r = 0.57, P less than 0.05) between the tissue concentrations of VIP and norepinephrine was noted.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Electrocardiographic evaluation of the healthy raccoon (Procyon lotor).
Leads I, aVF, V3, and V10 ECG were obtained from 12 healthy raccoons anesthetized with xylazine and ketamine. Intervals and amplitudes of component deflections were remarkably uniform among the individuals. Vector orientation of QRS mimicked that for the dog; but the relatively low voltages to QRS mimicked those of cats. The QT interval varied inversely with heart rate, whereas the PQ interval varied directly with body weight. Relationship between heart rate and body weight was not significant (P greater than 0.05).
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Usefulness of a free radical scavenger in preventing doxorubicin-induced heart failure in dogs.
This study was designed to investigate whether either of 2 dosage schedules of N-acetylcysteine (NAC) was effective in preventing chronic doxorubicin-induced heart failure in dogs. Thirty-eight dogs were randomly assigned to 1 of 4 groups: controls, 10 dogs; doxorubicin only, 12 dogs; doxorubicin + low dose NAC, 8 dogs; and doxorubicin + high dose NAC, 8 dogs. All dogs except the controls received 1 mg/kg of doxorubicin weekly for 8 weeks and then every other week for 8 weeks. The doxorubicin + low-dose NAC group received 140 mg/kg of NAC 30 minutes before each dose of doxorubicin. The doxorubicin + high-dose NAC group received NAC before and then twice a day for 5 days. Systolic time intervals and echocardiograms were obtained weekly; cardiac catheterization was performed at the conclusion of the study. Of the 38 dogs in the study, 9 died; all deaths were in the doxorubicin treatment groups. The incidence of death was not different between the doxorubicin-only, the doxorubicin + low-dose and the doxorubicin + high-dose NAC groups. The noninvasive and the invasive and the catheterization data generally revealed poorer cardiac function of the doxorubicin treatment groups than in controls. However, no significant differences existed between the doxorubicin-only and doxorubicin + low-dose and doxorubicin + high-dose NAC groups. In conclusion, NAC in a low- or high-dose regimen did not significantly ameliorate doxorubicin cardiac toxicity. Because NAC is a free radical scavenger, perhaps doxorubicin cardiac toxicity is not a result of free radical generation.
Acetylcysteine↗
Hypoxia results in an increase in total systemic shunt flow in dogs.
There is considerable evidence to indicate that blood flow to many organs changes in response to hypoxia. However, since blood may traverse nutrient capillaries or be shunted through precapillary arteriovenous channels, measurements of total organ blood flow alone may not accurately reflect microcirculatory adaptations to hypoxia. To test this hypothesis, we determined the effect of controlled normoxic ventilation (PO2 = 86.4 +/- 2.8 Torr; N = 10) and controlled hypoxic ventilation (PO2 = 45.9 +/- 1.0 Torr; N = 5) on cardiac output, nutrient blood flow and total systemic shunt flow in dogs using radiolabelled 15 micrometers microspheres. The microspheres were injected from left heart catheters in each animal and total systemic shunt flow was estimated from the radioactivity present in pulmonary artery reference samples. Cardiac output, as well as nutrient blood flow to the heart and brain, was similar in both hypoxic animals and normoxic controls. Although we could detect no significant changes in nutrient blood flow to the remaining organs in response to hypoxia, total systemic shunt flow increased from a baseline value of 4.4% of cardiac output to a maximum value of 7.9% of cardiac output in hypoxic animals compared to 2.3% of cardiac output in normoxic animals at a similar time point (P less than 0.01). This hypoxia-induced increase in total systemic shunt flow may contribute to the overall decline in organ function often observed in this setting.
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Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin.
The purpose of this study was to correlate the exercise-induced changes of oxidant stress enzymes with possible modification of the response to the putative oxidant stressor doxorubicin. Enzymatic and histological changes were studied in mice placed on a 21-wk swim training program (1 h/day, 5 days/wk) with and without anthracycline administration. Doxorubicin (4 mg/kg) was administered intravenously through a tail vein on 10 separate days over a 7-wk period (twice weekly during weeks 10, 11, 14, 15, and 16). Blood, liver, and heart levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GP) were measured following the 9th and 21st wk. Myocardial histomorphological observations were made by light microscopy after 21 wk. Following 9 wk of training swim-trained animals had significantly elevated levels of CAT, SOD, and GP in blood, as well as elevated GP in liver. After 21 wk, trained animals, regardless of drug status, had elevated blood CAT and SOD activity and increased liver CAT and GP. Training also produced increases in blood GP, liver SOD, and heart CAT; however, in conjunction with doxorubicin these changes were not seen. The degree of cardiotoxicity was significantly greater in the sedentary drug-treated animals than in the swim-trained drug-treated animals. The results suggest a correlation between antioxidant enzyme levels in blood and liver and the degree of damage caused by an anthracycline drug. It was concluded that exercise ameliorates severe toxic damage caused by doxorubicin administration, possibly by increasing enzymes that combat free radical damage.
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Effects of graded pleural effusion on QRS in the dog.
Six anesthetized healthy dogs were placed in right lateral recumbency. Electrocardiographic leads I, aVF, V10, rV3, V3, and V5 were obtained during a control period and after introduction of pleural effusions ranging between 0.66 and 55 ml of isotonic saline solution/kg of body weight. Peak-to-peak amplitudes of QRS were measured, and the effusion required to decrease this amplitude by more than 1 SD from the mean of healthy dogs was determined for each lead tested. Sensitivity of detecting pleural effusion was greatest in lead I in which an effusion of 2.75 ml/kg could be detected. The QRS amplitudes in leads V10 and aVF were decreased to a significant level only at large effusions. Leads V3 and V5 were "blind," even to the greatest pleural effusions. Radiographs taken with the graded pleural effusion documented that the heart "floated" away from rV3 and toward V3 and V5, thus explaining the sensitivity of rV3 and insensitivities of V3 and V5. It seems that pleural effusion can be detected by using these leads in dogs in right lateral recumbency, that detection is best if serial recordings are taken, and that relatively high sensitivities are achieved using lead I.
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Effect of vasoactive intestinal polypeptide on the canine cardiovascular system.
Our purpose was to determine the effect of vasoactive intestinal polypeptide (VIP) on the cardiovascular system with special emphasis on coronary vascular effects. In section I, VIP was infused into six healthy and six cobalt-cardiomyopathic dogs at two infusion rates (0.02 and 0.05 micrograms/kg/min). Left ventricular end diastolic pressure and mean systemic pressure fell significantly in both groups. Heart rate rose in both, and maximum systolic dP/dt increased in the myopathic group. Cardiac output and regional blood flows were determined by serial left atrial injections of radioactive 15 +/- 3 mum (mean +/- SD) microspheres. In both groups, blood flow increased significantly to the esophagus, pancreas, atria, and ventricles and to the endocardial and epicardial regions of the left ventricular free wall. Blood flow to the brain decreased. In section II, VIP was infused intravenously at 0.1 micrograms/kg/min into six anesthetized dogs with coronary sinus flow, pulmonary artery, and systemic artery catheters inserted. Cardiac index rose from baseline (3.1 +/- 0.5 to 4.8 +/- 1.3 L/min/m2, P less than 0.005), as did coronary blood flow (90 +/- 25 to 159 +/- 54 ml/min, P less than 0.005) during the VIP infusion. Myocardial oxygen consumption rose from 14.1 +/- 3.9 to 19.8 +/- 5.4 ml/min (P less than 0.001), but the aorta-to-coronary sinus O2 difference decreased from 157 +/- 19 ml/L to 132 +/- 42 ml/L (P less than 0.05), and the percent O2 extracted from coronary blood also decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Digoxin in dogs: once a day or twice a day?
Healthy mature dogs were given digoxin orally at the same dose once a day (SID) or divided (BID) at 12-hour intervals. Blood concentrations of digoxin were determined by radioimmunoassay. When the drug was given SID, peak blood concentrations were higher than, but lowest blood concentrations were not different than, those obtained when the drug was given BID. Thus, average blood concentration throughout 24 hours was significantly (P less than 0.05) greater when digoxin was given SID than when given BID. This suggested a reduced rate of clearance and an increased risk for toxicosis for digoxin when given SID versus BID. Peaks of digoxin blood concentrations were lower when the drug was given BID rather than SID; however, we do not know whether the smaller fluctuations can be translated into greater efficacy and/or less toxicity. Unless those questions are answered, we recommend that digoxin be administered BID to mature dogs.
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Effects of disopyramide on the electrocardiogram and ventricular function in the unanesthetized dog.
The antiarrhythmic compound disopyramide has been shown to possess negative inotropic effects. The present study was conducted to establish the effects of graded doses of disopyramide on ventricular function and electrocardiograms from healthy, awake dogs. Electrocardiograms and echocardiograms were obtained during a control period, and during an experimental period in which the six dogs on test received 7.5, 15 or 30 mg disopyramide per kg body weight orally three times per day. Six other dogs served as vehicle controls. No changes of statistical significance occurred in heart rate. The PQ interval was prolonged at all doses, the QRS complex was prolonged only at the highest dose, and the QT interval was prolonged at the intermediate and high doses. Left ventricular pre-ejection period (PEP) was prolonged in a dose-dependent relationship, and the left ventricular ejection time (ET) was shortened only at the highest dose. The percent shortening fraction of the left ventricle (% delta D) decreased significantly at intermediate and high doses, while the ratio of pre-ejection period to ejection time increased in a dose-dependent relationship. Conclusions are that even in therapeutic levels disopyramide produces significant reduction in left ventricular function, and that ratio of PEP/ET correlates better with the dose of disopyramide than did % delta D. This study demonstrates the feasibility of evaluating cardiac effects of compounds by non-invasive means.
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