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Biomedical subjects

D Garner

Publications and source records attributed to D Garner.

At least 55 records · Page 3Linked to original sources
PubMed1984

Chronic norepinephrine infusion and insulin and glucagon secretion in the dog.

The effect of epinephrine on glucose homeostasis has been studied extensively in many species, but there is little data on the effects of another catecholamine, norepinephrine. This study was designed to examine the alterations that occur in insulin and glucagon secretion during a chronic low-dose infusion of norepinephrine in free-roaming dogs. A total of four intravenous glucose tolerance tests and insulin-induced hypoglycemia tests were performed on each of five dogs infused with norepinephrine (1.4 g/min) for 3 mo and on each of eight control dogs. The infusion resulted in a threefold increase in plasma norepinephrine without a significant effect on blood pressure. Fasting serum glucose was elevated significantly in the norepinephrine-infused dogs [102.4 +/- 2.1 vs. 92.8 +/- 1.7 (SE) mg/100 ml]. Fasting plasma glucagon was elevated by the norepinephrine infusion (58.4 +/- 7.6 vs. 31.3 +/- 3.1 pg/ml), whereas fasting serum insulin was inhibited (12.3 +/- 1.3 vs 16.8 +/- 1.7 U/ml). Glucagon secretion in response to hypoglycemia was markedly enhanced in the infused dogs compared with controls. It has been reported that the infusion of norepinephrine in humans will inhibit insulin secretion and increase serum glucose concentrations but have no effect on serum glucagon concentrations. The stimulation of glucagon by norepinephrine has been demonstrated in the isolated, perfused canine pancreas but has not been reported previously in the free-roaming dog.

Adrenal Glands↗
PubMed1984

Norepinephrine increases beta-receptors and adenylate cyclase in canine myocardium.

Norepinephrine, a known inducer of myocardial hypertrophy, was found to have marked effects on the myocardial adrenergic system, which occurred prior to the development of a significant increase in heart weight. The chronic subhypertensive infusion (1.4 microgram/min) in free-roaming dogs produced a threefold increase in plasma norepinephrine (determined by radioimmunoassay). After 3 mo of infusion, right and left ventricular norepinephrine content (ng/mg protein) decreased significantly by twofold (right, 2.50 +/- 0.24; left, 2.08 +/- 0.36) compared with controls (right, 4.76 +/- 1.48; left, 4.65 +/- 1.49), and beta-receptor density (125I-pindolol) increased (right, 0.122 +/- 0.029; left, 0.153 +/- 0.021) over the controls (right, 0.082 +/- 0.015; left, 0.069 +/- 0.008 pmol/mg protein). Accompanying the beta-receptor changes, isoproterenol-stimulated adenylate cyclase activity also increased significantly [right, 29.2 +/- 2.1; left, 29.5 +/- 1.0 vs. controls, right, 13.8 +/- 1.1; left, 20.2 +/- 2.2 pmol adenosine 3',5'-cyclic monophosphate (cAMP) generated X min-1 X mg protein-1]. Because the above changes occurred in the absence of cardiac hypertrophy, it suggests that alterations in the myocardial adrenergic system are dependent on the stimulus (in this case norepinephrine) invoking the change and not the degree of hypertrophy. It also suggests that changes in the adrenergic system may not directly reflect the mechanism involved in the development of hypertrophy.

Adenylyl Cyclases↗
PubMed1983

Beta-adrenergic receptor and cyclic AMP alterations in the canine ventricular septum during long-term norepinephrine infusion: implications for hypertrophic cardiomyopathy.

Norepinephrine infusion in dogs has been shown to cause ventricular septal hypertrophy that mimics the syndrome of hypertrophic cardiomyopathy in humans. To characterize the mechanisms involved in septal hypertrophy, the adrenergic system of the right and left ventricles and the septum were analyzed before and after norepinephrine infusion. In the normal unperturbed state, the septum was found to be more sensitive to beta-adrenergic stimulation than either the right or left ventricles. That is, more cyclic AMP could be generated with a smaller dose of beta-agonist (isoproterenol) in septal tissue homogenate than in homogenates of the right or left ventricles. With infusions of norepinephrine (1.4 micrograms/min) to subhypertensive levels over 3 months, beta-receptor number increased twofold to threefold in the ventricles and septum. Adenylate cyclase activity also increased in the ventricles, but not in the septum. The sensitivity of adenylate cyclase to beta-agonist stimulation increased in the septum but remained unchanged in the right and left ventricles. We conclude that the alterations in the myocardial adrenergic system occur in response to the norepinephrine infusion and are not a consequence of hypertrophy. We formulated a hypothesis suggesting that depleted tissue stores of cyclic AMP and/or adenosine triphosphate may be one of the mechanisms involved in the development of hypertrophic cardiomyopathy.

Adenylyl Cyclases↗
PubMed1982

Ejection fraction derived using dye dilution and angiographic methods.

Ventriculographically derived ejection fraction (EF-V) is the most frequently used method to measure left ventricular (LV) function, However, significant error may result in the measurement of end-systolic volume (ESV), which is used to calculate EF-V. This error is ascribed to the variable, irregular, nonellipsoidal geometry of the end-systolic ventricular chamber. Since stroke volume (SV) is determined more accurately by dilution methods than by ventriculography, an improved measure of ESV can be calculated by subtracting green dye determined SV from the ventriculographic determined end-diastolic volume (EDV). The purpose of this study was to measure a correlated ejection fraction (EF-C) using EDV by ventriculography and SV derived using green dye. In eight anesthesized dogs cardiac outputs (COs) were calculated by green dye and left ventriculography. CO determined by ventriculography was greater than that measured by green dye (p less than 0.005). EF-V (55 +/- 15%) was always greater than EF-C (32 +/- 12%) (p less than 0.005). These studies (1) may partially explain the discrepancy in CO calculated from the use of dilution methods and ventriculography and (2) present a method to improve the calculation of LV ejection fraction.

Animals↗
PubMed1979

Increased ejection fraction produced by a long-term subhypertensive infusion of norepinephrine in the conscious dog.

Five mongrel dogs with chronically implanted catheters in the left atrium, mid-thoracic aorta, and right atrium were continuously infused with subhypertensive doses of norepinephrine for 3 months. Left ventricular cineangiography, determinations of aortic pressure, and cardiac output were performed in the conscious dog. After 3 months of continuous norepinephrine infusion, stroke volume increased from 38 +/- 3.0 to 67 +/- 8.0 ml. (p less than .01), the left ventricular end-diastolic volume increased from 72 +/- 6.4 to 89 +/- 12.9 ml. (p less than .05), and the ejection fraction increased from 52 +/- 3.6 to 76 +/- 3.6% (p less than .005). We postulate that norepinephrine results in an increased myocardial function by producing physiological myocardial hypertrophy.

Animals↗
PubMed1979

Comparison of ejection fraction and segmental circumferential fiber shortening velocity in the anesthetized and conscious canine.

A chronically and transseptally implanted left atrial catheter was utilized to perform repeated cineangiography in the conscious dog. The advantage of this preparation is that catheter placement does not require a thoracotomy. Left ventricular function was compared in the same pentobarbital-anesthetized and conscious dog. Anesthesia significantly depressed myocardial function as was demonstrated by a decrease in ejection fraction and segmental circumferential fiber shortening velocity (VCF) and an increase in end-diastolic volume. In addition, no difference in Vcf occurred between the base and the apex. Since anesthesia produced regional difference in the degree of depression of VCF, we conclude that anesthesia will produce patterns of ventricular contraction which are variable and unpredictable. Consequently, we recommend the use of the conscious dog and this preparation in order to evaluate myocardial function.

Anesthetics↗
PubMed1978

Human alpha-1-antichymotrypsin: purification and properties.

Human alpha-1-antichymotrypsin has been purified to homogeneity by the following sequential steps--(a) ammonium sulfate fractionation; (b) chromatography on Cibacron Blue Sepharose at pH 7.0; and (c) chromatography on SP-Sephadex C-50 at pH 5.5. The inhibitor has a molecular weight near 68,000 and contains approximately 26% carbohydrate alpha-1-Antichymotrypsin has an amino-terminal arginine and a carboxy-terminal glycine. It also has some homology with alpha-1-PI based on amino-terminal sequence analysis of both proteins. Complexes of alpha-1-antichymotrypsin with human chymotrypsin and human leukocyte cathepsin G are stable in sodium dodecyl sulfate and have molecular weights near 90,000 suggesting 1:1 complex formation on a molar basis between inhibitor and enzyme.

Amino Acid Sequence↗
PubMed1977

A new method for internal calibration of left ventricular cineangiography.

Previous methods of internal calibration for cineangiography have made use of reference objects such as catheters or wires of known length or diameter. Such devices have either insufficient X-ray resolution, or require a specific orientation within the ventricle which is difficult to confirm. External calibration methods, while eliminating these errors, can only estimate actual position of the left ventricle. The use of a Swan-Ganz balloon catheter as a calibration object diminishes these problems. When positioned within the left ventrical and filled with a radiopaque medium, the balloon is of sufficient size and density to avoid errors induced by previously employed objects. The inflated balloon geometry is simple and reproducible. The use of this internal calibration catheter markedly diminishes major sources of errors in the determination of ventriculograms for both dogs and humans.

Animals↗
PubMed1976

Technique for serial right and left ventricular endocardial biopsy in dogs.

A method is described for obtaining left and right ventricular endocardial biopsies repeatedly over a period of 3-6 mo in the dog. The left ventricular endocardial biopsy technique consists of the placement of a catheter via the venous route across the atrial septum and into the left ventricle. The biopsy catheter is in turn placed within this transseptal catheter. Tissues obtained by this method were satisfactory for both light and electron microscopic examination. At postmortem examination, only minimal and insignificant damage existed at the biopsy site. Consequently, we recommend this technique for the study of progressive pathologic changes in the endocardium that occur during the course of an experiment which can be identified and quantified in comparison to the control state.

Animals↗
PubMed1976

Technique for the performance of repeatable renal clearances in the conscious male dog.

A preparation for performance of renal clearances in the conscious dog is described. The important aspect of the technique is the use of a Pavlov sling and a specially designed restraining apparatus. Of most importance is the use of a 7 French Swan-Ganz balloon-tipped catheter for urinary bladder catheterization. The use of male dogs obviated the need for an episiotomy. No special training of the animals was required. The animals tolerated long-term and repeated catheterization without any evidence of infection or trauma.

Aminohippuric Acids↗
PubMed1975

Preparation for repeated study of left ventricular function in the conscious dog.

A method is presented for a relatively simple nontraumatic chronic left heart catheter preparation for the study of left ventricular hemodynamics in the conscious dog. In 30 dogs an 8 Fr Cordis catheter was modified and implanted into the left ventricle via the right atrial septum. Transseptal catheterization was performed without significant morbidity and mortality. Left ventricular cineangiograms and pressures and cardiac outputs have been repeatedly performed on fully conscious dogs with no apparent discomfort displayed by the dog.

Animals↗
PubMed1975

Acute pulmonary artery hypertension produced by distention of the main pulmonary artery in the conscious dog.

In order to delineate further the function of the main pulmonary artery as a receptor site, a specially designed Laks triple-lumen balloon catheter was inserted transvenously and positioned in the main pulmonary artery. In six conscious nonsedated dogs, inflation of a balloon in the main pulmonary artery produced acute reversible pulmonary arterial hypertension; the pressure beyond the balloon increased from a mean of 21/6 mm Hg to 43/14 mm Hg (P less than 0,001). This observed pulmonary hypertension occurred at an amount of balloon inflation which produced an increase in right ventricular systolic pressure (P less than 0.001), but no significant change occurred in cardiac output (P greater than 0.05) or right ventricular end-diastolic pressure (P greater than 0.1). Left atrial and pulmonary artery wedge pressures did not change or decreased slightly (P greater than 0.1 and P greater than 0.1, respectively). The calculated pulmonary vascular resistance increased (P less than 0.001), while the calculated systemic vascular resistance did not chang (P greater than 0.04). Therefore, we postulate that distention of the main pulmonary artery in the conscious dog reflexly produces constriction of pulmonary arterioles, and possibly venules, due to excitation of receptors probably located in the wall of the pulmonary artery or possibly the right side of the heart, or both.

Animals↗