James A. Burbach

Naloxone stimulates oxygen consumption but not ventilation in hypothyroid hamsters.

Male golden Syrian hamsters made hypothyroid by 5 wk of propylthiouracil (PTU) treatment and control hamsters given tap water were studied. Both groups of nine animals demonstrated increased oxygen consumption after SC naloxone administration relative to saline treatment. Naloxone stimulated ventilation and ventilation in response to hypoxic (10% O2) and hyperoxic, hypercapnic (7% CO2 in oxygen) challenges in control hamsters. Relative to their responses to saline, PTU-treated hamsters exhibited no stimulation of ventilation nor of ventilation in response to the gas challenges after naloxone treatment. These results suggest that (a) the stimulation of oxygen consumption by naloxone does not directly increase ventilation; and (b) thyroid hormone status in the hamster affects opioid modulation of ventilation.

Effects of dystrophy and age on hamster tracheal smooth muscle function

Pharmacological and morphometric evaluations of airway smooth muscle were performed on tracheal segments from control and dystrophic hamsters at 50, 145 and 315 days of age. An age-related change in muscle volume index (a measure of the total smooth muscle per tracheal segment) was not observed in the control group but decreased with age in the dystrophic strain. In the control strain, correlations were not observed between age and maximum pharmacological response to the drugs tested, but a change in sensitivity to carbachol and KCl was noted at 145 days. In contrast, tracheal segments of dystrophic hamsters exhibited decreased maximum responses to carbachol, KCl, histamine, and isoproterenol at 315 days of age. When maximal contractile responses were normalized by muscle volume index, only the KCl maximum tension at 315 days was less than at 50 days of age. Changes in sensitivity to carbachol and KCl were also seen in tracheal smooth muscle of the dystrophic hamster at 145 days of age. At 315 days, histamine and isoproterenol-induced relaxation was less in dystrophic than in control tracheal smooth muscle. It is not possible to ascertain whether the decreased responses of the tracheal segments from the oldest dystrophic hamsters are due to dystrophy alone, or to a combination of dystrophy and aging.

Effects of thyroxine and naloxone administration on metabolism and ventilation in hamsters.

This study examined the interaction between hyperthyroidism and opioid receptor function on control of ventilation and metabolism in male Harlan hamsters 4 and 8 weeks after implanting thyroxine (T(4)) or placebo pellets. Metabolism, but not body temperature, increased in T(4)-treated hamsters relative to placebo-treated animals. After 4 weeks, body weights were greater in the T(4)-treated hamsters, but comparable to controls after 8 weeks. At that time, body length was greater in T(4)-treated hamsters than in controls. Thyroxine did not affect ventilation in air or in response to CO(2). Naloxone, an opioid receptor antagonist, decreased metabolism in T(4)-treated, but not in placebo-treated hamsters without affecting ventilation in air in either group. In the placebo group naloxone augmented the ventilatory response to hypercapnia by increasing frequency. These results negate our hypotheses that: (1) hyperthyroid hamsters exhibit greater ventilation in air and in response to hypercapnia than controls; and (2) that naloxone augments these effects.

Preferential localization of varying forms of photoactive 1,8-naphthalimide compounds within the atheromatous arterial wall

We are currently working with a novel class of photoactivated 4‐amino substituted 1,8‐naphthalimide compounds for tissue bonding. With promising results in other tissues, we are pursuing potential vascular applications. This study focused on determining the appropriate compound formulation(s), concentration, and exposure times to optimize penetration of the heterogeneous arterial wall.

Relationships among the R bodies of caedibacteria

Abstract Three distinct R body types are found in caedibacteria, type 51, type 7 and type Cc. The relationships among these R bodies were assessed by immunogold labeling, Western blotting and enzyme-linked immunosorbent assay techniques. Antisera raised against type 7 and type Cc R bodies cross-reacted with type 51 R bodies.

Lipidosis of Pulmonary Macrophages in the Dystrophic Hamster

Lavaged pulmonary macrophages of Bio 14.6 myopathic hamsters were compared with those from Bio F1B controls. Enlarged foamy macrophages were prevalent in the dystrophic strain. Lipidosis within this cell population was confirmed by morphologic and chemical analyses. The percentage of lipid-positive cells obtained from Bio 14.6 hamsters was three times greater than from control animals, but the total number of macrophages recovered from the lungs of dystrophic animals was approximately one-third lower compared to controls. Nearly two-thirds of the lipid-positive cells from the dystrophic strain were moderately to excessively engorged, whereas a similar percentage of the positive cells from control animals contained only sparse lipid inclusions. Qualitative ultrastructural differences were not observed between strains, but engorged macrophages of the dystrophic strain typically showed a predominance of lipid droplets with grey homogeneous material, crowded cytoplasmic organelles, and fewer primary lysosomes. Lipid analyses showed an 85% increase of total cellular lipids, a 486% increase of cholesteryl esters in neutral lipids, and increased 18:1 fatty acids in total lipids and the cholesteryl esters in cells from the Bio 14.6 strain. The etiology of the lipid excess has not been determined, but elevated chylomicrons and reduced alpha-lipoprotein values were observed in the serum of the dystrophic strain.

Structural abnormalities underlying alveolar hypoventilation and fluid imbalance in the dystrophic hamster lung.

Bio 14.6 dystrophic hamsters exhibit alveolar hypoventilation and increased lung hydration. This study evaluated whether age‐ and genotype‐related morphometric differences in lungs exist and correlate with the development of lung pathophysiology. Morphometry was used to characterize lungs of young (Y) and mature (M) control (C) and dystrophic (D) hamsters. With age, both C and D had increased barrier surface area [S(a‐b,p)] and morphometric diffusing capacity index [mdci], and decreased harmonic thickness. In C but not D, mean capillary diameter [dc] and parenchymal volume density [Vv(p,L)] increased with age, whereas barrier arithmetic thickness decreased. Chord length increased with age, whereas the ratio of parenchymal surface area to airspace volume [S/V] and the intersection density of the air‐blood interface [Iv(a‐b,s)] decreased in D but not C. At both ages, lung volume relative to body mass was greater in D than C. With that exception, no genotype differences were found in young hamsters. Mature D displayed lower Vv(p,L), S/V, dc, Iv(a‐b,s), S(a‐b,p), and mdci than mature C. Independent of age, chord length was greater but arithmetic thickness, airspace surface density, frequency of type II cells, and lamellar body area and volume density were lower in D than C. We conclude: 1) lung volume relative to body growth was greater in dystrophics than controls; 2) parenchymal remodeling was delayed or abnormal in dystrophics; 3) lower diffusing capacity in mature dystrophics may effect alveolar hypoventilation; 4) lower tissue volume, surface area, and the type II cell abnormalities in dystrophics could reduce sodium and water transport leading to greater lung hydration. Anat Rec 256:321–333, 1999.

Improved Preservation of Myocardial Ultrastructure in Perfusion-Fixed Human Heart Explants

Evaluation of fine structural changes due to human cardiac disease processes has been confounded by autolysis associated with autopsy specimens or tissue artifacts in biopsy samples. Based on animal experiments, it is recognized that perfusion fixation of the coronary vasculature of freshly excised tissue leads to optimum preservation of ultrastructure. Therefore, availability of fresh myocardial tissue from heart transplant programs should enable better assessment of pathologic changes in humans. Several freshly excised human expiants were perfusion fixed to determine if normal and pathologic assessment of fine structures was improved. Tissue samples from one control, three patients with heart failure, and one unsuitable donor with mitral regurgitation were examined by transmission (TEM) and scanning (SEM) electron microscopy. Light microscopy of 1 μrn tissue sections was used to select well-perfused areas with no tissue separation for subsequent electron microscopic evaluation. The control heart was indistinguishable from similar animal preparations. Details of nuclear pores, M lines, mitochondria, sarco-plasmic reticulurn, intercalated discs, intermediate filaments, and other fine structures were readily apparent by TEM. Endomysial struts and perimysial collagen fibers were apparent by SEM. Although the extracellular matrix compartment was clearly increased in failing hearts, alterations in collagen struts were not apparent. Scalloping of the nuclear and sarcolemmal mem-branes suggested that cytoskeletal tethering within myocytes was not altered in failure. There appeared to be a slight, but detectable, reduction in myo-fibrillar content in myocytes from patients with heart failure and the patient with mitral regurgitation. Mitochondria appeared to be smaller and more numerous in failing hearts. This preliminary examination suggests that improved preservation of myocardial ultrastructure should provide a better assessment of the underlying pathologic mechanisms in human heart diseases.

Structure and function of the respiratory system of the dystrophic hamster

The BIO 14.6 dystrophic hamster has been used extensively over the past 30 years as an animal model in which to study the mechanisms responsible for the development of cardiomyopathy and skeletal muscle dysfunction associated with muscular dystrophy. More recently, structural and functional aspects of the respiratory system of this animal model have been investigated. This review summarizes our current knowledge of ventilation, lung morphometry and mechanics, the structure and function of the diaphragm, tracheal and pulmonary vascular smooth muscle, and pulmonary macrophages in the BIO 14.6 dystrophic hamster. We conclude that many aspects of the structure and function of the respiratory system of this hamster warrant further investigation, including the development of alveolar hypoventilation, the causes of pulmonary vascular hyporeactivity, and the potential contribution of abnormal pulmonary macrophages to the pathogenesis of life-threatening respiratory disease in muscular dystrophy.