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Biomedical subjects

R L Hamlin

Publications and source records attributed to R L Hamlin.

At least 19 recordsLinked to original sources

Cardiac ultrastructural and electrophysiological abnormalities in postweanling copper-restricted and copper-repleted rats in the absence of hypertrophy.

Cardiac ultrastructural and functional characteristics were determined in copper-depleted and copper-repleted rats. Male weanling rats were randomized into five groups that were fed either copper-adequate or copper-deficient diets. After 5 wk, one group fed each diet was studied to obtain baseline values. At this time, one copper-adequate postweanling group continued to receive the adequate diet as control, one deficient postweanling group was fed the adequate diet to evaluate the effect of copper repletion and one postweanling adequate group was fed the deficient diet to evaluate copper depletion in relatively older rats. These dietary treatments were continued for six additional weeks. Copper-depleted rats of both ages exhibited significant cardiac ultrastructural pathology and electrocardiogram abnormalities and the postweanling copper-depleted rats exhibited these abnormalities in the absence of hypertrophy and anemia. Increased mitochondrial volume density, disarranged cristae, and nonaligned myofibrils with disturbances at Z-bands were displayed. Additionally, all copper-depleted rats demonstrated fragmented basal laminae at capillary-myocyte interface. Increased QRS amplitude and notching and greater QT intervals were displayed. Copper-repleted rats exhibited some, but not total, reversal of these abnormalities. These results suggest that capillary-myocyte interface changes may play an important role in the developing pathology of copper depletion.

Animals

Effects of enalapril and clonidine on glomerular structure, function, and atrial natriuretic peptide receptors in SHHF/Mcc-cp rats.

Seven-month-old, lean male SHHF/Mcc-cp rats, a model of spontaneous hypertension, progressive renal dysfunction, and congestive heart failure (CHF), were treated with either clonidine (CL) or enalapril (EN) or received no treatment (CON) for 20 weeks. CL significantly decreased systolic blood pressure (SBP), kidney weights, and severity of renal lesions as compared with untreated CON. EN produced a decrease in SBP comparable to that in CL. Kidney weights and severity of renal histologic changes in the EN group were intermediate between those of the CL and CON groups. Despite similar plasma atrial natriuretic peptide (ANP) concentrations, CL treatment resulted in a significant increase in the density of guanylate cyclase-linked glomerular ANP receptors, whereas EN treatment resulted in a significant decrease in the total number of ANP receptors and in the number of nonguanylate cyclase-linked receptors and an increase in overall binding affinity. These findings demonstrate that antihypertensive agents will slow progression of renal injury in SHHF/Mcc-cp rats and that CL is more effective than EN in alleviating progressive kidney damage in this model. Furthermore, different classes of antihypertensive drugs may alter the density or ratio of biologically active and clearance ANP receptor sites in the glomerulus.

Animals

Electrocardiographic activity and cardiac function in copper-restricted rats.

The temporal sequence of events leading to cardiac dysfunction during copper restriction in the Long-Evans rat was studied over a 6-week period. Weanling rats were fed either copper-adequate (6 mg Cu/kg diet, n = 25) or copper-restricted (less than 1 mg Cu/kg diet, n = 25) diets for varying periods of time for up to 6 weeks. Beginning at 2 weeks after weaning and weekly thereafter, five rats from each diet were evaluated for cardiac function, and sacrificed, and indicators of copper deficiency were determined on several tissues. Electrocardiograms began showing indications of cardiac disease at Week 3 in the copper-restricted rats, at which time cardiac hypertrophy and other signs of copper deficiency were apparent. Greater QT intervals and QRS amplitudes were observed in copper-restricted rats at various weeks. Peak + and - dP/dt maxs did not differ by diet copper treatment for any of the time intervals studied, nor was any notable difference in developed left ventricular pressure apparent. Hematocrit and liver copper levels were decreased in copper-restricted rat hearts at all weeks. These results suggest that the onset of cardiac dysfunction in copper deficiency is rapid, with both dysfunction and hypertrophy apparent within 3 weeks after copper restriction and when liver copper levels have declined.

Animals

Measurements of left and right ventricular pressures and their derivatives by transcutaneous puncture in rats.

Eighteen rats were anesthetized with xylazine/ketamine and placed in right lateral recumbency, and a small incision was made in the skin of the left hemithorax. A 21-gauge, 1-inch, short-beveled hypodermic needle, attached directly to a pressure transducer filled with degassed saline solution, was advanced through the incision into the left ventricle and then advanced through the septum into the right ventricle. High-fidelity tracings of right and left ventricular pressures and their derivatives were obtained through this approach in 13 rats. In 5 rats, measurements of right ventricular pressures were obtained by additional right ventricular puncture through the incision in the left hemithorax. Right and left ventricular pressures were recorded on single occasions in 18 rats, twice at 2-week intervals in 6 rats, and 3 times at 2-week intervals in 3 rats. Minimal hemopericardium was observed, but most rats had evidence of hemorrhage on the visceral pericardium. Left and right ventricular pressures can be measured rapidly, safely, and repeatedly in anesthetized rats by this method.

Anesthesia

Viscosity and rheologic properties of blood from clinically normal horses.

Blood viscosity (BV) was measured in 32 healthy horses at 6 spindle speeds (60, 30, 12, 6, 3, and 1.5 rpm) and for PCV of 40%, using a digital rotational cone and plate microviscometer. Also, in 7 of 32 horses, BV was measured 3 times each, for 3 PCV values (20, 40, and 60%), and at each spindle speed to determine effect of PCV on BV and machine and among-horse variations. Total plasma protein and fibrinogen concentrations were measured in all horses, using a standard refractometer and heat precipitation, respectively. In 7 of 32 horses, quantitative fibrinogen concentration was measured, using a quantitative fibrinogen assay. Plasma protein and fibrinogen concentrations were measured to determine their effect on BV. Plasma total protein (6.0 to 7.5 g/dl) and fibrinogen (100 to 400 mg/dl) concentrations were within normal reference range for our laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Evidence for or against clinical efficacy of preload reducers.

A preload reducer is any compound or maneuver that decreases end-diastolic ventricular volume. The determinants of preload and elevated preload are described in this article. Methods to lower preload and the future of preload reduction are discussed.

Animals

Copper deficiency in a genetically hypertensive cardiomyopathic rat: electrocardiogram, functional and ultrastructural aspects.

The effect of copper deficiency on cardiac function and structure was studied in a strain of rats (SHHS/Mcc-cp) known to develop cardiac failure as adults. Restriction of dietary copper (less than or equal to 1 mg/kg vs. 6 mg/kg in adequate diets) at weaning in both sexes for a 6-wk period produced cardiac hypertrophy. Male rats developed more severe copper-deficiency symptoms than their female counterparts. In both sexes of copper-deficient rats, there was an increase in cardiac length, width, free ventricular wall thickness and septum thickness. Electrocardiographic tracings revealed greater QRS height among male copper-deficient rats. Heart rate also was substantially reduced in this group. The increased volume of myocardium occupied by mitochondria in the copper-deficient male rats might result in increased electrical resistance that would increase the QRS height; hypertrophy or anemia also could be contributory. Some male copper-deficient rats had prolongation of the QRS in a bundle branch block pattern. Maximal rates of rise and fall for left ventricular pressure were reduced in male copper-deficient rats. The gross histology indicated that this type of heart failure was more concentric than eccentric. The copper-deficient male rat may serve as a useful model for studying the concentric cardiac hypertrophy that occurs in humans.

Animals

Clinical toxicology of cardiovascular drugs.

Drugs used to treat cardiovascular diseases have low therapeutic indices, may produce the very pathophysiologic effects that it is hoped they will reverse, and are used commonly in aged animals with multisystemic diseases for which they are receiving other compounds. These factors predispose to undesirable drug reactions and interactions. It is difficult to determine, a priori, which animals will respond with profound toxic manifestations; therefore, resuscitative measures, including drugs and devices, must be available at all times, and the clinician must be schooled in their use. In particular, class IA antiarrhythmics, digitalis glycosides, and antineoplastic compounds, all used relatively frequently, have great potential for producing toxicosis. An important role of the clinician with regard to cardiovascular toxicology lies in providing consultation to both the pharmaceutical industry and governmental regulatory agencies. Because the worst aspects of cardiovascular toxicosis lie in electrical disturbances of the heart, and because electrocardiography is the best method for studying these electrical properties, the clinician and adviser to the pharmaceutical industry and the FDA must be well schooled in electrocardiography.

Animals

Exercise alters cardiac myosin isozyme distribution in obese Zucker and Wistar rats.

Recent evidence suggests that exercise training may significantly increase the expression of the cardiac myosin isozyme V1 in the diabetic heart, a change associated with improved cardiac functional capacity. To test this hypothesis, cardiac myofibrillar adenosinetriphosphatase (ATPase) activity and myosin isozyme profiles were determined in trained and sedentary male hyperinsulinemic obese Zucker (OZT, OZS) and obese Wistar (OWT, OWS) rats. Lean sedentary (LZS, LWS) animals served as age-matched controls. Myofibrillar ATPase activity and the relative quantity of the high-ATPase isozyme V1 was significantly lower in both strains of sedentary obese rats than in the respective lean sedentary controls (P less than 0.05). Both 5 (OZT) and 10 wk (OWT) of moderate treadmill training increased these markers of cardiac myosin biochemistry in the obese animals (P less than 0.05). Thus, endurance exercise training remodels the cardiac isomyosin profile of hyperinsulinemic rats and, in doing so, may enhance cardiac contractility and functional capacity. Such changes may reflect an improvement in glucose availability and utilization in these hearts.

Animals

Influence of phenytoin on isoproterenol-induced myocardial fibrosis in rats.

A study was designed to determine whether phenytoin (PHE) prevents the myocardial necrosis and subsequent fibrosis produced by isoproterenol (ISO). Seven groups of female rats of the Wistar strain were used. Rats in groups 1 and 5 served as controls. Rats in group 3 were injected SC with 85 mg of ISO/kg of body weight for 2 consecutive days. Rats in groups 2 and 6 received 100 mg of PHE/kg orally. Rats in groups 4 and 7 received both PHE and ISO. There were 6 to 9 rats/group. Effects of ISO and PHE were evaluated gravimetrically, histologically, and electrocardiographically. Heart weight/body weight ratios for each group receiving ISO, with or without PHE, were greater than for groups not receiving ISO (P less than 0.05). Light microscopic examination of heart sections of rats given ISO alone or ISO + PHE revealed multiple and diffuse areas of fibrosis. Fibrosis in hearts from rats receiving PHE + ISO was less severe than that in hearts from rats receiving ISO alone, but the difference was not statistically significant. Electrocardiographic changes of statistical significance were not observed in rats receiving any compound (alone or in combination), when compared with the control groups of equal age.

Animals

Selective vagal postganglionic innervation of the sinoatrial and atrioventricular nodes in the non-human primate.

The distribution of parasympathetic postganglionic nerves to the atrioventricular (AVN) and sinoatrial nodal (SAN) regions was investigated in the non-human primate heart. Eight male monkeys (Macaca fascicularis) weighing 5.5-7.0 kg. were anesthetized (alpha-chloralose, 50 mg/kg and urethane, 500 mg/kg) and instrumented to measure arterial pressure, electrocardiogram, atrial and ventricular electrograms. The cervical vagi were electrically stimulated (20 Hz, 4 V, 2 ms) before and after selective denervation (D) of the AVN and/or SAN. Vagal stimulation was repeated during atrial pacing to assess parasympathetic modulation of AVN conduction. Ablation of parasympathetic pathways to the AVN, accomplished by the disruption of the epicardial fat and surface muscle layer at the junction of the inferior vena cava and inferior left atrium eliminated (P less than 0.01) the dromotropic effects of vagal stimulation without affecting the heart rate response (right vagus, before D, paced: atrial rate 218.0 +/- 6.3, ventricular rate 67.1 +/- 23.7; after D: atrial rate 210.3 +/- 6.4, ventricular rate 210.3 +/- 6.4 beats/min, means +/- S.D.). In sharp contrast, surgical dissection of the fat pad overlying the right pulmonary vein-superior vena cava junction significantly (P greater than 0.01) attenuated negative chronotropic effects of vagal stimulation (left vagus, before D the R-R interval increased by 832.7 +/- 146.4 ms, 209.5% increase; after D 37.4 +/- 18.0 ms, 8.8% increase). These data demonstrate discrete vagal efferent pathways innervate both the SAN and AVN regions of the non-human primate heart.

Animals

The effect of UK14,304-18 (an alpha-2 adrenergic agonist) on myocardial blood flow during cardiopulmonary resuscitation.

Several recent studies have suggested that adrenergic drugs with peripheral postsynaptic alpha-2 agonist properties increase aortic diastolic pressure (ADP), and thus in the setting of CPR, may improve myocardial blood flow (MBF). This preliminary study investigated the effect of UK14,304-18, a postsynaptic alpha-2 adrenergic agonist on ADP, MBF, myocardial oxygen delivery/utilization (MDO2/MVO2), endocardial/epicardial blood flow ratio (EN/EP), coronary sinus oxygen content (CcsO2) and extraction ratio (ER) during CPR. Five swine were instrumented for MBF measurements using tracer microspheres. Catheters were also placed to measure arterial oxygen content (CaO2) and CcsO2. ADP, MBF, MDO2/MVO2, EN/EP, ER, CaO2 and CcsO2 were measured during normal sinus rhythm (NSR), and during CPR following a 10-min cardiorespiratory arrest. Following this, each animal received 2.0 mg/kg of UK14,304-18 through a right atrial line. ADP, MBF, MDO2/MVO2, EN/EP, ER, CaO2 and CcsO2 were again determined. Defibrillation was then attempted. To determine whether UK14,304-18 improved ADP, MBF and MDO2 over MVO2, compared to CPR alone, results were compared using a paired Student t-test. Statistical significance was considered at the P less than or equal to 0.05 level. No significant improvement in ADP, MBF, MDO2 or ER was noted following the administration of UK14,304-18. The lack of improvement in ADP and MBF may be secondary to a centrally acting postsynaptic alpha-2 agonist effect because of disruption of the blood brain barrier following a prolonged cardiac arrest or because of pharmacologically or structurally distinct populations of peripheral postsynaptic alpha-2 adrenoreceptors that develop in this setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists

The effect of norepinephrine versus epinephrine on regional cerebral blood flow during cardiopulmonary resuscitation.

alpha-Adrenergic drugs improve cerebral blood flow (CBF) during cardiopulmonary resuscitation (CPR), in part, by reversing carotid artery collapse and by shunting blood from extracerebral to intracerebral vascular structures. Adrenergic drugs with beta 2-agonist properties may cause peripheral vasodilation, and thus may be less beneficial in this setting. The purpose of this study was to compare epinephrine (E), an alpha 1,2, beta 1,2-agonist, with norepinephrine (NE), an alpha 1,2, beta 1-agonist, on CBF during CPR. Twenty swine each weighing greater than 15 kg were instrumented for regional CBF measurements using tracer microspheres. Regional CBF was measured during normal sinus rhythm (NSR). Animals were then placed into ventricular fibrillation (VF). After ten minutes of VF, the animals received closed-chest CPR using a mechanical thumper. Regional CBF was measured during CPR. After three minutes of CPR, the animals were allocated to receive either E, 0.20 mg/kg (N = 5); NE, 0.08 mg/kg (N = 5); NE, 0.12 mg/kg (N = 5); or NE, 0.16 mg/kg (N = 5). Regional blood flows were again measured following drug administration. CBFs following drug administration were compared using an analysis of covariance adjusting for baseline differences during CPR. A Newman-Keuls multiple comparison was used to follow-up significant (P less than or equal to .05) differences. Statistical significance was considered at P less than or equal to .05. There was a clinically significant improvement in cerebral cortical flow with NE, 0.12 mg/kg, and NE, 0.16 mg/kg, compared with NE, 0.08 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Nutrition and the heart.

Nutritional deficiencies (e.g., carnitine in dogs, taurine in cats) resulting in cardiomyopathy, and nutritional excesses (e.g., calories leading to obesity, sodium leading to hypertension) have emerged as important considerations in cardiology. These dietary factors may become particularly exaggerated in altered physiological and/or pathological states (e.g., pregnancy, old age, primary cardiovascular disease). Unfortunately, we do not have complete information on requirements for essential nutrients, nor do we know the precise role nutrition may play in the production of so-called old-age diseases or on the interactions among other organ systems (e.g., kidney, liver) and the heart.

Animals

Estimating the duration of ventricular fibrillation.

As the duration of time between the onset of ventricular fibrillation and the application of defibrillation (downtime) increases, the rate of successful resuscitation decreases. Results of recent animal studies suggest that the rate of successful resuscitation may be increased after a prolonged cardiorespiratory arrest when pharmacologic therapy is instituted before defibrillation. An accurate estimation of downtime could be critical in selecting the most appropriate therapeutic intervention. The purpose of our study was to determine whether changes in the frequency or amplitude of the ventricular fibrillation ECG signal during cardiac arrest could be used to estimate downtime. We characterized the dynamics of both total power and frequency distribution of the power in the ECG during ventricular fibrillation in 11 swine to determine whether enough information existed in either parameter to estimate downtime. The median frequency of the power spectrum was used to track power distribution. Both parameters followed a dynamic, repeatable pattern. However, median frequency showed less intersubject variability than did total power. A mathematical model of median frequency was developed and used with data obtained from ten additional swine to estimate downtime. The model estimated downtime to within 1.3 minutes of actual downtime between one and ten minutes of ventricular fibrillation. Our study has identified a new, potentially useful parameter for studying various management strategies in ventricular fibrillation as a function of downtime.

Animals

The effect of norepinephrine versus epinephrine on myocardial hemodynamics during CPR.

Alpha-adrenergic agonists improve myocardial blood flow during CPR by increasing aortic diastolic pressure. Adrenergic agonists with beta-2 properties may enhance peripheral vasodilation and may prove less beneficial during CPR. The purpose of this study was to compare epinephrine (E), an alpha-1,2; beta-1,2 agonist, versus norepinephrine, an alpha-1,2; beta-1 agonist, on myocardial hemodynamics during CPR. Twenty swine were instrumented for pressure, arterial and coronary sinus oxygen content (CAO2 and CCSO2, respectively), and myocardial blood flow measurements using tracer microspheres. CAO2, CCSO2, myocardial blood flow, myocardial oxygen delivery (MDO2) and myocardial oxygen consumption (MVO2), extraction ratio, and aortic diastolic pressure were determined during normal sinus rhythm and during CPR following a ten-minute arrest. After three minutes of CPR, the animals were allocated to receive either norepinephrine 0.08 mg/kg (n = 5), norepinephrine 0.12 mg/kg (n = 5), norepinephrine 0.16 mg/kg (n = 5), or epinephrine 0.20 mg/kg (n = 5). One minute after drug administration, all hemodynamic parameters were again determined. Three and one half minutes after drug administration defibrillation was attempted. A Newman-Keuls multiple comparison procedure was used to compare differences following drug administration. During CPR, aortic diastolic pressure averaged less than 13 mm Hg, and myocardial blood flow averaged less than 6 mL/min/100 g. All doses of norepinephrine and epinephrine improved all hemodynamic parameters over those seen during CPR. The two highest doses of norepinephrine significantly improved extraction ratio compared with norepinephrine 0.08 mg/kg (P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of direct mechanical ventricular assistance on myocardial hemodynamics during ventricular fibrillation.

Direct mechanical ventricular assistance (DMVA) is a method of biventricular circulatory support that employs a pneumatic device to apply both systolic and diastolic forces directly to the ventricular myocardium. This study investigated the effects of DMVA on myocardial hemodynamics when applied after a prolonged cardiopulmonary arrest. Seven swine weighting 28.3 +/- 2.5 kg were instrumented for regional myocardial blood flow (MBF) measurements using tracer microspheres. Ventricular fibrillation was then induced. After 10 min of ventricular fibrillation, CPR was initiated for 3 min. DMVA was then applied through median sternotomy. Defibrillation was attempted after 3.5 min of DMVA. If unsuccessful, DMVA was instituted for another 17.5 min and a subsequent defibrillation attempt was made. Arterial oxygen content (CaO2), coronary sinus oxygen content (CcSO2), myocardial oxygen delivery/consumption (mDO2/mVO2), extraction ratio (ER), and endocardial/epicardial blood flow ratio (EN/EP) were determined during CPR, during the initial application of DMVA (DMVA1), and after the subsequent 17.5 min of DMVA in those animals not initially defibrillated (DMVA2). Three of the seven animals were successfully defibrillated during DMVA1. After the additional 17.5 min of DMVA, only one other animal was defibrillated. There was a significant improvement in CaO2, CcSO2, MBF, mDO2, mVO2, ER, and EN/EP after DMVA1 compared to CPR. Only mVO2 and ER improved significantly after DMVA2. These findings support the concept that physical diastolic augmentation may improve myocardial hemodynamics when DMVA is applied during cardiac arrest.

Animals

Capillary basement membrane thickness and capillary density in sedentary and trained obese Zucker rats.

The purpose of this study was to determine whether the obese Zucker rat (OZR) develops diabeteslike peripheral vascular disease and evaluate the effects of exercise training (treadmill running, 15 m/min, 17% grade, 60 min/day, 5 days/wk, for 6 or 12 wk) on skeletal muscle vascular disease. Capillary density (CD) and capillary basement membrane (CBM) thickness were measured in the plantar muscle of sedentary and trained OZR and sedentary lean Zucker rats (LZRs). At 11 wk old, when profoundly obese, hyperinsulinemic, and insulin resistant, OZRs had lower CD and thicker CBM than LZRs. These characteristics are consistent with the expression of human diabetic microangiopathy and imply altered diffusion capacity due to increased diffusion distance and changes in the capillary wall. Between 11 and 18 wk of age, OZRs became hyperglycemic. No age-related changes in CD were observed in lean or obese animals, and OZRs had lower CDs than LZRs at 18 wk of age. CBM thickness decreased from 11 to 18 wk of age in both lean and obese animals, but the decline was proportionally greater in OZRs, and the CBM of obese animals was only slightly thicker than in lean 18-wk-old animals. Exercise training did not alter CD or CBM thickness in 11-wk-old animals. In contrast, training for 6 or 12 wk increased both CD and CBM thickness in 18-wk-old animals, normalizing CD but further increasing CBM thickness relative to LZRs. Correlational analysis revealed that CBM thickness is related to basal insulin concentration (r = .29, P less than .05) but not to basal glucose (r = .12, P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals