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J B Caulfield

Publications and source records attributed to J B Caulfield.

At least 37 records · Page 2Linked to original sources
PubMed1991

Endothelium-dependent responses in long-term human coronary artery bypass grafts.

In the present study, responses of long-term human coronary artery bypass grafts (CABGs) to known endothelium-dependent vasodilators, acetylcholine, calcium ionophore A23187, thrombin, and histamine, as well as authentic nitric oxide, the putative endothelium-derived relaxing factor, were studied. Sixteen CAGBs were isolated within 1-2 hours from hearts of 14 patients receiving a cardiac transplant. A total of 109 ring segments were prepared from these CABGs and studied in vitro. The duration of the CABGs ranged from 7 months to 12 years. Addition of acetylcholine (0.01-10 microM), calcium ionophore A23187 (0.01-1.0 microM), thrombin (0.01-1.0 unit/ml), and histamine (0.01-1.0 microM) consistently produced a dose- and endothelium-dependent relaxation, reaching a maximum of -35.3 +/- 3.3%, -45.3 +/- 5.5%, -26.9 +/- 4.8%, and -17.8 +/- 2.5% (mean +/- SEM), respectively. No significant difference was observed among the CABGs with different duration of transplantation, whereas the relaxant responses of different segments along the entire length of a CABG were markedly different. These latter differences in the endothelium-dependent responses appear to correlate inversely with the development of intimal proliferative lesions in these CABGs. Addition of nitric oxide (0.01-10 microM) produced a potent dose- and endothelium-independent relaxation, which was also slightly depressed in CABGs with severe intimal proliferation. These results demonstrate that long-term transplanted human saphenous vein grafts retain their endothelium-dependent responses and that development of severe intimal proliferative lesions, rather than the duration of the grafts, result in marked alterations in the reactivity of these transplanted CABGs.

Coronary Artery Bypass↗
PubMed1990

Retention of endothelium-dependent vasodilatory responses in canine coronary arteries following cryopreservation.

In the present study, the cryoprotective effect of dimethyl sulfoxide (Me2SO) and fetal calf serum (FCS) on coronary endothelium and endothelium-dependent relaxation (EDR) responses was studied in isolated canine coronary arteries following cryostorage at -75 degrees C. Compared to the freshly isolated coronary arteries, the EDR responses to acetylcholine, thrombin, and calcium ionophore were not significantly altered following 1 day storage at -75 degrees C in the presence of 1.8 M Me2SO and 20% FCS. Prolonged cold storage to 7 days, however, resulted in a slight, but significant, rightward shift of the concentration-response curves of acetylcholine and thrombin, but not calcium ionophore. The maximum relaxant response after 7-day cryostorage was 80 to 85% of fresh controls. Omission of FCS from the cryostorage incubation medium further accentuated the loss of EDR responses to all three endothelium-dependent vasodilators tested. Scanning electron microscopic examinations of the intimal surface of the Me2SO and FCS cryostored canine coronary arteries confirmed the preservation of intimal endothelial cells following 1 or 7 days of storage at -75 degrees C, while significant patches of loss of endothelial cells were observed in the arteries cryostored only in the presence of Me2SO. No significant inhibitory effect of cryostorage was observed for the direct, endothelium-independent relaxation induced by isoproterenol, regardless of the presence or absence of FCS. These results demonstrate that slow freezing of canine coronary arteries to -75 degrees C in Krebs-Henseleit solution containing Me2SO and FCS provides good preservation of the vascular smooth muscle function and endothelium-dependent vasodilatory responses.

Animals↗
PubMed1990

Release of endothelium-derived relaxing factors from canine cardiac valves.

In the present study, the ability of intact cardiac valvular endothelial cells to release vasodilatory prostanoids and endothelium-derived relaxing factor was investigated. Endothelium-denuded canine coronary arteries were used for bioassay and contractile force recording. Insertion of small segments of cardiac valve (20-30 mm2) with intact endothelium into endothelium-denuded coronary arterial rings did not markedly alter the sensitivity nor magnitude of the coronary artery contractile response to KCl. In contrast, the prostaglandin F2 alpha (PGF2 alpha)-induced contraction was significantly depressed (70% decrease in magnitude and 216% increase in ED50), compared with contraction in the absence of valvular endothelium (5.52 +/- 0.49 g and ED50 of 1.18 +/- 0.02 microM, respectively). These alterations in PGF2 alpha-induced contractions were reduced to 38% decrease in magnitude and +66% in ED50 in the presence of 5 microM indomethacin. Addition of acetylcholine (0.1-30 microM) into these endothelium-denuded coronary artery/valve preparations resulted in a dose-dependent relaxation, reaching a maximum of -59.9 +/- 1.6% (mean +/- SEM of seven vessels). Preincubation of valvular endothelium with 5 microM indomethacin also reduced these acetylcholine-induced valvular endothelium-dependent relaxations to 40.4 +/- 5.5% (mean +/- SEM of 13 vessels). Addition of hemoglobin (3 microM) further attenuated relaxation to -16.0 +/- 7.7% (mean +/- SEM of 14 vessels), while superoxide dismutase (20 units/ml) potentiated the relaxant response to -81.3 +/- 9.4% (mean +/- SEM of 11 vessels) in the presence of indomethacin. These findings suggest that there is a continuous basal release of vasodilatory prostanoids and endothelium-derived relaxing factor from the valvular endothelium, which can be further stimulated with acetylcholine and superoxide dismutase, and inhibited by indomethacin and hemoglobin.

Acetylcholine↗
PubMed1990

Myocardial connective tissue alterations.

There is a complex network of collagen throughout the heart. It is composed of a hierarchy of fibrils and fibers ranging from 10 nm to 2-3 microns in diameter. This network can be broken down by ischemia, adriamycin administration, or disulfide administration in laboratory animals. Following loss due to coronary artery ligation, the ischemic area begins bulging within 3 h. General loss of portions of the collagen matrix is induced by intravenous oxidizing glutathione, and results in marked diffuse ventricular dilatation. Generalized collagen loss in the ventricles, as induced by disulfide administration or adriamycin infusion, persists for 6 months at which time evidence of some replacement is visible, and evidence of diffuse fibrosis is present. In humans, cardiac dilatation occurs in a variety of disease states without overstretch of sarcomeres. This presumes rearrangement of the muscle bundles, which can only occur with marked alterations of the collagen matrix. Ventricular dilatation, associated with viral myocarditis or puerperal cardiomyopathy, may persist for months, suggesting the collagen loss, as with the experimental animals, takes many months to repair. The cardiac dilatation may ameliorate, or, in some patients, deteriorate into heart failure. The animal experiments with loss of the collagen matrix, ventricular dilatation, and failure to replace the matrix for many months provide an explanation for persistent cardiac dilatation in various human diseases.

Animals↗
PubMed1988

Cardiac matrix alterations induced by adriamycin.

Adriamycin is toxic to humans and animals and causes cardiac lesions involving myocytes and the interstitial tissue. The present study used a single injection of adriamycin in rats. Focal loss of myocardial interstitial collagen occurred 2 weeks after a single injection of adriamycin. These foci become larger and more frequent through 6 weeks. Individual variation in response is evident after periods longer than 6 weeks. Concomitant with the focal loss is deposition of collagen in an abnormal distribution. Rather than the normal matrix being present, scars appear. The number and size of these scars is subject to variation from animal to animal. The collagen matrix loss is evident in some animals at 15 weeks after injection. These observations, coupled with the results of other studies on the myocardial collagen matrix, support the hypothesis that adriamycin cardiotoxicity is mediated in part by an affect on the collagen matrix.

Animals↗
PubMed1988

Inducible collagenolytic activity in isolated perfused rat hearts.

There is an extensive collagen network in the heart. The precise anatomy and function of this system has not been fully elucidated. The system does appear to contribute to diastolic compliance, and evidence indicates that the system may be important in directing the stress generated by sarcomeres to the ventricular cavity. Little is known about the mechanisms controlling collagen deposition and resorption in the heart. In this paper the authors demonstrate that disulfide reagents are capable of inducing a collagenolytic reaction in the isolated perfused heart that removes all components of the collagen matrix of the heart as visualized by scanning electron microscopy. The expression of collagenolytic activity requires perfusion of the heart for 1 hour with a disulfide reagent followed by 2 hours with Krebs-Hensleit alone. These results suggest that an inducible and active collagenolytic system exists in cardiac tissue and that this system may be expressed under conditions of oxidative stress.

Animals↗
PubMed1987

Arteritis in cardiac rejection after transplantation.

During a 4-year experience with cardiac transplantation, 33 hearts were obtained by autopsy or surgical resection for retransplantation. Arteritis was a feature common to all rejected hearts (14 of 14), but was absent in explanted hearts without rejection (0 of 19) (p = 0.001). Monitoring of acute cardiac rejection by endomyocardial biopsy (863 biopsies) was also reviewed, with special reference to the incidence of arteritis. Among the 16 patients with arteritis on 1 or more biopsies, 44% (7 patients, confidence limits 29 to 60%) suffered fatal rejection or underwent retransplantation because of irreversible rejection. Arteritis was seen in the small vessels obtained by endomyocardial biopsy in 4 of 5 persons who underwent biopsy within 3 days of death or retransplantation due to rejection and on none of the 6 persons who underwent biopsy within 3 days of death or retransplantation for causes other than rejection. Thus, arteritis is an important indicator for severe acute rejection, and although often reversible, may identify patients at higher risk for fatal rejection. Arteritis occurred in transplanted hearts subjected to varying combinations of cyclosporine, azathioprine and steroid therapy and could not be correlated with any drug regimen.

Arteritis↗
PubMed1985

Ventricular collagen matrix and alterations.

There is a complex extracellular structural matrix in the heart. This matrix appears to be composed of a variety of fibrils and fibers extending from the cell surface to the basal lamina and from the basal lamina to the matrix. The extensions into the extracellular region interconnect with a system of collagen bundles. The latter are so located that they would tether the myocytes to each other as well as tether the capillaries to the myocetes. There is an extensive weave of collagen analogous to the perimysium of skeletal muscle that separates groups of myocytes. The weave surrounding a group of myocytes is connected to adjacent weave patterns by long, tendonlike structures. The collagen matrix around cells disappears 2-3 hr after coronary-artery occlusion. In the periinfarct region of viable cells, the matrix is similarly lost and is replaced by scarlike collagen. Encephalomyocarditis virus causes a similar loss of the matrix in necrotic as well as some adjacent nonnecrotic regions. Replacement of the lost matrix is by scar tissue. The long-term appearance of the replacement fibrosis closely resembles the appearance of diffuse fibrosis as seen in a variety of conditions. These observations suggest that diffuse fibrosis can occur secondary to loss of the matrix both with and without myocyte necrosis. This may help explain the diffuse left ventricular fibrosis as seen in a variety of human disease.

Animals↗
PubMed1984

Early and late pathologic changes in the adrenal glands of mice after infection with herpes simplex virus type 1.

Intranasal infection of CH/HeN mice with herpes simplex virus Type 1 (HSV-1), VR3 strain, caused a high death rate in the 3-12 days following inoculation. Acute interstitial pneumonia and focal adrenal necrosis developed in almost all the animals. About 20% of the mice showed meningoencephalitis and myocarditis. Viral antigen was demonstrated by immunoperoxidase staining in the alveolar walls, around bronchi and blood vessels, and in focal areas of the adrenal cortex as early as 24-48 hours after infection. The virus disseminated probably hematogenously from the lungs and seemed to localize preferentially in the adrenals. In mice surviving the acute stage of infection a subcapsular cell reaction developed in the adrenal cortex. The extensive pneumonia and adrenal necrosis contributed to the high mortality rate of weanling mice infected with HSV-1. The route of viral inoculation and the age of the host animal seemed to influence the localization and outcome of the pathologic process.

Adrenal Cortex↗
PubMed1983

The effects of systole on left ventricular blood flow.

Coronary artery flow is complex. Flow in this system is divided into systolic and diastolic. However, systolic flow should be divided into two phases, isovolumetric and the ejection phase, since these two components are determined by completely different parameters. Flow through the myocardium is affected by the close mechanical coupling between myocytes and capillaries effected by the array of collagen struts and their disposition. This latter provides the anatomic arrangement that makes possible the integrated "massaging" effect postulated by Wiggers (26).

Animals↗
PubMed1981

The collagen matrix of the heart.

Scanning electron microscopy demonstrates an extensive and highly organized network of collagen in the left ventricle of all species examined. This system is arbitrarily divisible into three major components: a collagen weave network that surrounds groups of myocytes; an extensive array of collagen struts measuring 120 to 150 nm in diameter that extend from the basal lamina of a myocyte to the basal laminae of all contiguous myocytes; and an array of similar sized collagen struts that extend from the basal lamina of all capillaries to the basal laminae of all contiguous myocytes. The functions of the individual components of this complicated network are not well-defined. The weave network certainly contributes to the viscous and elastic properties of the heart. Myocyte-to-myocyte struts can prevent slippage of adjacent cells during the cardiac cycle and would ensure equal stretch of adjacent myocytes during diastole. Myocyte to capillary struts may be important in maintaining capillary patency during the early phases of systole. In rats. rabbits and hamsters this entire system is virtually absent at birth and develops rapidly to the adult form by 15 days.

Aging↗
PubMed1981

Mechanical and structural correlates of canine pericardium.

We have assessed viscoelastic properties of pericardium within the physiological range of stresses and related mechanical behavior to fiber direction as defined by scanning electron microscopy. Stiffness, stress relaxation, and creep were measured in samples taken from the anterior surface of 14 canine pericardia. Stress-strain relations generally were not exponential; stiffness at a stress of 1 g/mm2 ranged from 12.9 to 239 g/mm2 during stretch and varied both from pericardium to pericardium and with the orientation of the strip within the sample (anisotropy). The strips exhibited hysteretic behavior which was not promotional to rate of strain. Following a rapid increase in stress, creep averaged less than 1% and stress relaxation, 34% in a 30-minute test period. The orientation of the strip with the greatest stiffness was consistent from pericardium to pericardium, and correlated with a layer of collagen fibers oriented along the major axis of te strip.

Animals↗
PubMed1981

Structural basis of ventricular stiffness.

The morphologic component of ventricular stiffness has not been clearly delineated. This stiffness factor varies over wide ranges with the degree of distension, being very low at low volumes and very high at high volumes. It is constant in rats and hamsters from 30 days of age to 17 months, varying no more than 20%, with increases in mass of 4-fold. These parameters alone suggest a complex structure or structures. The ventricular stiffness factor of rats is about twice that of hamsters at all ages. This naturally occurring variation in stiffness of normal hearts from the two species provides an excellent model to examine for morphologic differences that might explain the variation in stiffness of the two ventricles. Hearts from each species from 1 to 7 months of age were examined by light microscopy and scanning and transmission electron microscopy. There is a major difference between the two species in the amount of collagen in the form of 120- to 150-nm. diameter bundles that form a weave around groups of myocytes. This system is far more extensive in rats than hamsters and is the only morphologic difference that can easily explain the divergence in stiffness between the two species.

Age Factors↗
PubMed1980

Morphology of connective tissue in skeletal muscle.

The arrangement and distribution of connective tissue in six different skeletal muscles and smooth muscle was examined by scanning electron microscopy. The endomysial arrangement of collagen was similar in all types of muscle and consisted of three components: (1) myocyte-myocyte connectives; (2) myocyte-capillary connectives; and (3) a weave network of collagen intimately associated with the basal laminae of the myocytes. The perimysium of the different muscles was qualitatively similar but quantitatively dissimilar. The perimysium consisted consisted of large tendon-like bundles of interwoven collagen which connected with the dense weave collagen that surrounded groups of muscles. The arrangement of the collagen in the perimysium and endomysium would explain differences in the mechanical properties of the different muscle. The contribution of the connective tissue to mechanical properties of muscle is discussed.

Animals↗
PubMed1979

Resistance of contracting myocardium to swelling with hypoxia and glycolytic blockade.

The interrelationship of myocardial metabolism, performance and tissue hydration was examined in isolated contracting rat, guinea pig and dog myocardium. Myocardial metabolism was altered by blocking aerobic, and both aerobic and anaerobic metabolism. Myocardial water content and distribution were measured in rat myocardium using 3H-inulin and 51Cr-EDTA as extracellular markers. Myocardial hydration was also evaluated by light and electron microscopy. The relative susceptibility of non-contracting slices of rat and guinea pig myocardium and kidney to swelling secondary to these interventions was also explored. Hypoxia resulted in a partially reversible reduction in mechanical function; hypoxia plus glycolytic blockade led to irreversible severe contracture and total loss of tension development. Neither hypoxia nor hypoxia plus glycolytic blockade resulted in increased total tissue or extracellular water in previously contracting preparations or in non-contracting slices of myocardium. On the other hand, there were significant increases in cellular water in similarly treated kidney slices after each intervention. Thus, despite severe, irreversible derangements of mechanical function, myocardium did not swell under conditions which produced swelling in renal cortex.

Animals↗