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Biomedical subjects

R L Hamlin

Publications and source records attributed to R L Hamlin.

191 records · Page 11Linked to original sources
PubMedDate not supplied

Comparison of some pharmacokinetic parameters of 5 angiotensin-converting enzyme inhibitors in normal beagles.

This study was designed to determine the degree of inhibition of the angiotensin-converting enzyme (ACE) in 5 normal dogs given single doses of conventionally used ACE inhibitors (ACEis). In addition the time required for that inhibition to return to 50% of the difference between maximum and zero (control values) was measured as an estimate of duration of action. The 5 ACEis (with dosages given in parentheses) were benazapril (0.5 mg/kg), captopril (2.0 mg/kg), enalapril (0.5 mg/kg), lisinopril (0.5 mg/kg), and ramipril (0.25 mg/kg). Blood samples for ACE activities were obtained before dosing and at 1.5, 3.0, 6.0, 12.0, and 24.0 hours after dosing. All ACEis except captopril decreased ACE activities to approximately 25% of control by the 1.5- to 3.0-hour sample, and ACE activities returned to 50% of the difference by the 12-hour sample. The value of AVE activity returned to normal by 24 hours for benazapril, whereas values for ACE activity remained below normal for enalapril, lisinopril, and ramipril at 24 hours. For captopril, however, ACE levels decreased to approximately 80% of control by the 1.5-hour recording, and returned to levels not different from control by the 3-hour recording. Based upon this study performed on normal dogs given a single dose, no pharmacokinetic advantage or disadvantage is apparent for any ACEi except captopril, which, at the dosage used, decreased ACE levels to a much lesser degree and shorter time.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Hemodynamic and electrocardiographic effects of magnesium sulfate in healthy dogs.

We investigated the effects of graded dosages of magnesium given i.v. to anesthetized dogs on blood pressure, cardiac output, and electrophysiology. Magnesium was infused at 0.12 mEq/kg/minute until ventricular fibrillation occurred naturally or was provoked by programmed electrical stimulation or until arrest of the sinuatrial node in 8 dogs. Plasma total magnesium concentrations doubled in 1 minute of that infusion rate, and a hemodynamically safe plasma concentration of 12.2 mEq/L was achieved after 16 minutes of infusion. Heart rate, inotropy, lusitropy, and cardiac output increased up to a cumulative infusion dosage of magnesium of 1.0-2.0 mEq/kg, which produced plasma magnesium concentrations of 8.5-12.2 mEq/L (n = 5). Above the cumulative infusion dosage, inotropy decreased and lusitropy increased until death occurred between cumulative infusion dosages of 5.9 mEq/kg and 10.9 mEq/kg. Arterial pressure and vascular resistance decreased, and PQ interval and QRS complex increased, in a dose-dependent fashion. The relationship between ionized and total magnesium was y = 0.624x - 0.542 (r2 = .986), where y is ionized and x is total magnesium in mEq/L in 3 dogs. In conclusion, a cumulative infusion dosage of 0.1-0.2 mEq/kg of magnesium may be given without changing hemodynamic parameters, but with higher cumulative infusion doses heart rate accelerates. Hemodynamic parameters except those related to blood pressure continued to increase to a cumulative infusion dosage of 2.0 mEq/kg. At higher cumulative infusion dosages dogs became hypotensive and the PQ interval was prolonged. However, dangerous arrhythmias were not provoked until a total dosage of 3.9 mEq/kg.

Animals↗
PubMedDate not supplied

Effects of acute gastric distention and recovery on tendency for ventricular arrhythmia in dogs.

The gastric distention-volvulus (GDV) syndrome occurs commonly in large-breed dogs and may prove fatal in 15-68% of cases. Approximately 43% of cases with gastric distention (GD) or volvulus develop cardiac arrhythmias that can contribute to mortality. Most of these arrhythmias are ventricular in origin and ventricular fibrillation (VF) may be the cause of death. This study used an iatrogenic model of acute GD to investigate the prevalence of ventricular arrhythmias during acute GD and its recovery, if programmed electrical stimulation (PES) may uncover tendency to VF, if the Q-T interval corrected for heart rate (Q-Tc) of the electrocardiogram (ECG) predicts tendency to VF, and if hemodynamic changes predate VF. Eleven beagles, anesthetized with morphine and alpha-chloralose, and instrumented so that vascular pressures, cardiac output, and PES could be recorded, were used. Five were unperturbed, whereas acute GD to a pressure of 30 mm Hg for 1.5 hours was produced in 6 others. The results were as follows. No dogs with GD developed spontaneously occurring arrhythmias. VF was produced in no dogs by conventional PES, but occurred in all dogs (P < .05) with GD and none of the controls, using accelerated ventricular pacing. The Q-Tc interval of the ECG prolonged minimally in dogs with GD, and shortened (P < .05) in controls. Some hemodynamic changes did predate VF. In conclusion, dogs with acute GD have a tendency for VF, which may be uncovered by accelerated PES. The mechanism for the vulnerability to arrhythmia with GD is unknown.

Acute Disease↗
PubMedDate not supplied

Cardiovascular effects of intravenous diltiazem in dogs with iatrogenic atrial fibrillation.

Atrial fibrillation (AF) was induced in anesthetized Beagle hounds to determine the dose of diltiazem (D) that resulted in hemodynamic function similar to that observed during sinus rhythm (SR). Dogs were instrumented to record hemodynamic and electrophysiological parameters. Six dogs were given D, IV at cumulative doses of 0.063, 0.188, 0.438, 0.938, and 1.938 mg/kg, whereas 6 other dogs received vehicle in equivalent volumes. Plasma concentrations (PC) of D were measured. A cumulative dose of D between 0.438 and 0.938 mg/kg produced PC of 67.8 to 117.4 ng/mL and resulted in a heart rate (HR) closest to that observed during SR. At doses up to 0.938 mg/kg, no parameter of systolic function fell below that obtained during SR. At a dose of 0.938 mg/kg, the left ventricular end-diastolic and right atrial pressures exceeded those during SR. The rate-pressure product did not differ from that during SR at a dose of 0.938 mg/kg and fell below that during SR at the dose of 1.938 mg/kg. Left ventricular efficiency decreased from SR to AF, returned to values not different from those during SR at a dose of 0.938 mg/kg, and increased to values above those observed during SR at a dose of 1.938 mg/kg. In AF, slowing the HR with 0.438-0.938 mg/kg of D with resultant PC of 67.8-117.4 ng/mL results in cardiovascular function not different from that observed during SR.

Animals↗
PubMedDate not supplied

Correlation of cardiac enlargement as assessed by vertebral heart size and echocardiographic and electrocardiographic findings in dogs with evolving cardiomegaly due to rapid ventricular pacing.

Vertebral heart size (VHS) has been proposed as a method for quantifying cardiomegaly in dogs. This study was designed to determine how well echocardiographic and electrocardiographic findings correlated with VHS. Dogs were rapid-paced into varying degrees of cardiomegaly and were monitored by thoracic radiography, echocardiography, and electrocardiography during development of cardiomegaly. Echocardiographic and electrocardiographic parameters were compared with VHS. VHS increased with increased duration or rate of pacing or both, and left atrium-to-aorta ratio, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, P wave duration, and QRS duration correlated significantly with VHS. VHS (a score obtained from routine thoracic radiographs) seems to correlate well with both echocardiographic and electrocardiographic parameters. When 9 veterinarians, experienced in interpretation of cardiac silhouettes on radiographs, measured VHS from 1 normal dog and 1 dog with severe cardiomegaly, coefficients of variation (ratio of standard deviation to the mean) for their measurements were 2.7% and 2.8%, respectively. Thus, VHS could be established with great uniformity by experienced interpreters.

Animals↗
PubMedDate not supplied

Acute cardiovascular effects of diltiazem in anesthetized dogs with induced atrial fibrillation.

Atrial fibrillation (AF) is one of the most important arrhythmias of dogs. In a previous study, we determined the dosage of intravenously administered diltiazem necessary to reduce ventricular response (VR), cardiac output (CO), and mean systemic arterial pressure (P(Ao)) to values similar to those observed during sinus rhythm (SR) before induction of AF. The present study was conducted to establish an acute, effective dosage of diltiazem given PO. AF was produced by rapid atrial pacing in healthy, anesthetized Beagle Hounds. Dogs were instrumented to record hemodynamic and electrophysiological parameters. Four dogs were given 2.5 mg/kg diltiazem, and another 4 dogs were given 5 mg/kg diltiazem by stomach tube, whereas 4 other dogs received vehicle in equivalent volumes. Plasma concentrations of diltiazem were measured at various intervals after dosing. A dosage of 5 mg/kg diltiazem produced plasma concentrations of 32-100 ng/mL 3 hours after administration, concentrations within the published effective range for dogs with naturally occurring AF. Between 2 and 3 hours after this dosage, the rate pressure product (RPP) and an index of left ventricular efficiency returned to values similar to those observed during SR. Thus, we believe that diltiazem at anorally administered dosages of 5 mg/kg should be considered to produce therapeutic blood concentrations and favorable hemodynamic effects in dogs with naturally occurring AF. These data must be extrapolated with caution to dogs with long-standing AF produced by natural causes.

Administration, Oral↗
PubMedDate not supplied

Increased splenic capacity in response to transdermal application of nitroglycerine in the dog.

This study was conducted to determine if application of transdermal 2% nitroglycerine ointment (TDNG) to dogs anesthetized with alpha chloralose would produce splenic dilatation by relaxation of venous smooth muscle. Sonomicrometer crystals were applied to the spleen in each of 15 dogs, and a pressure-measuring catheter was inserted into a splenic vein. The sonomicrometer crystals permitted measurement of splenic dimension, which is known to correlate with splenic volume. Ten dogs were given 2.5 cm TDNG/10 kg, and 5 dogs (vehicle controls) were given only petrolatum, both applied to the inner surface of the auricular pinna. Splenic dimension in all dogs receiving TDNG increased significantly (P < .05) by 7.0 +/- 4.8%, whereas splenic dimension in dogs receiving petrolatum did not increase. Splenic venous pressures did not change significantly in either group. Spleens began to dilate 482 +/- 652 seconds after application of TDNG and achieved maximal dilatation at 861 +/- 632 seconds. Splenic dilatation occurred in the absence of elevation of splenic venous pressure, indicating that the dilatation probably resulted from relaxation of splenic smooth muscle. TDNG was absorbed transdermally and produced splenic dilatation in health dogs anesthetized with alpha chloralose. If the spleen is a sentinel for peripheral veins, then TDNG may increase venous capacity, retaining blood from the lungs and thereby functioning to reduce pulmonary congestion and edema in dogs with left-sided heart failure.

Administration, Cutaneous↗
PubMedDate not supplied

Myocardial infarction size and scar dimensions: the influence of activity.

OBJECTIVE: The purpose of this study was to determine myocardial infarct size and scar dimensions in experimentally infarcted rats that were randomly assigned to a moderate, mild, or no exercise condition after infarction. DESIGN: Pretest-posttest control group design (experimental). SUBJECTS: 57 male Harlan Sprague Dawley rats between 62 to 64 days of age and weighing 220 to 290 gm at the onset of the study. OUTCOME MEASURES: Infarction size, scar thickness, thinnest portion of scar. INTERVENTION: Mild exercise versus moderate exercise versus no exercise. RESULTS: No differences were found in infarct size, scar thickness, or thinnest portion of scar among the three groups. CONCLUSION: This study establishes that treadmill exercise, begun after an appropriate period of recovery, does not necessarily increase infarct size or scar thinning in the rat model. Further, animal and human studies are needed to fully explore the benefits and hazards of cardiac rehabilitation or exercise testing before or soon after discharge.

Animals↗
PubMedDate not supplied

Endotracheal suctioning-induced heart rate alterations.

The purpose of the experimental study was to identify mechanical and/or neural factors contributing to the heart rate alterations associated with endotracheal suctioning (ETS). Effects of catheter insertion alone and catheter insertion with the application of negative pressure on the partial pressure of arterial oxygen (PaO2) and heart rate prior to and following vagal blockade with atropine were examined. Eleven newborn swine less than 24 h of age were randomly exposed to (a) suction catheter insertion alone and (b) suction catheter insertion and the application of suction. Preoperatively, the subjects were anesthetized with ketamine and xylazine (.05 mL/kg). The ECG in lead II was recorded on a Gould 2600S recorder. Arterial blood (aB) O2 levels were withdrawn 1 min before and at 20 s, 1 min, 2 min, and 3 min following ETS and analyzed on a calibrated Corning 158 semi-automated aB gas machine. There was a significant decline in PaO2 from baseline at 20 s post ETS in both the no suction and suction protocols, p less than .05. The application of suction caused a greater decline in mean PaO2 (41 torr) compared to no suction (13 torr) at 20 s post ETS which was similar in pattern following vagal blockade (suction: 37 torr; no suction: 2 torr). Following the first pass of the catheter, mean heart rate (HR) declined 14 beats per min with suction and 9 beats per min with no suction. The difference was obliterated following the second pass of the catheter. There was no difference in the HR following vagal blockade.

Animals↗
PubMedDate not supplied

Mixed venous oxygen saturation and oxygen partial pressure as predictors of cardiac index after coronary artery bypass grafting.

OBJECTIVE: To determine the relationship between the mixed venous oxygen saturation (SvO2) and the cardiac index (CI) in individuals during the first 8 hours after coronary artery bypass grafting. DESIGN: Descriptive with a correlational design. SETTING: Cardiac intensive care unit at a university medical center in the midwestern United States. SUBJECTS: Twenty-one subjects (16 men and 5 women) undergoing coronary artery bypass grafting. OUTCOME MEASURES: SvO2, thermodilution cardiac output and CI measured every 2 hours during the first 8 hours after surgery. INTERVENTION: Elective coronary artery bypass grafting. RESULTS: Significant (p < 0.05) but moderate correlations between SvO2 and CI were found only at 6 and 8 hours after surgery (r = 0.66, p = 0.001; r = 0.44, p = 0.47). Secondary analysis determined that in subjects without lung disease, mixed venous oxygen tension (PvO2) had significant correlation with CI at all data collection times (r = 0.54 to 0.72; p = 0.003 to 0.02). CONCLUSIONS: The results of this study indicate that immediately after coronary artery bypass grafting, SvO2 cannot reliably predict CI. Although statistically significant results were found for the correlation between PvO2 and CI at all data collection times, the correlations were too low to support the use of the PvO2 as a reliable clinical predictor of CI without further study.

Adult↗