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Biomedical subjects

R Pick

Publications and source records attributed to R Pick.

At least 37 records · Page 2Linked to original sources
PubMed1989

Myocardial collagen remodeling in pressure overload hypertrophy. A case for interstitial heart disease.

The accumulation of collagen within the myocardium is termed fibrosis. In left ventricular pressure overload a reactive interstitial fibrosis, having distinctive biochemical and structural features, is seen. This reactive fibrosis occurs in the absence of myocyte necrosis, is progressive in nature, and initially is an adaptive response that preserves the force generating capacity, or active (systolic) stiffness, of the hypertrophied myocardium. Later in hypertrophy a reparative (or replacement) fibrosis occurs in response to cell loss, the pathogenesis of which is not clear. Nevertheless, independently of cell loss, interstitial fibrosis can have a detrimental influence on the diastolic and systolic stiffness of the myocardium and can result in pathologic hypertrophy with heart failure. In established hypertrophy with disproportionate collagen matrix remodeling (ie, interstitial heart disease), it would be desirable to retard the continued formation of collagen and, if necessary, degrade collagen fibers that are responsible for impeding the stretching and shortening of muscle fibers. Prevention of interstitial fibrosis in pressure overload hypertrophy with pharmacologic agents with both antihypertensive and antifibrotic properties must also be considered. Future research should address these issues with a view toward developing corrective and preventative forms of therapy. Such advances will require a better understanding of cardiac fibroblast growth, collagen synthesis and the regulation of collagen gene expression in the heart.

Animals↗
PubMed1989

Myocardial collagen and mechanics after preventing hypertrophy in hypertensive rats.

To determine if a remodeling of the collagen matrix would occur in the absence of hypertrophy and cell necrosis and if such a remodeling could alter active and passive stiffness of the intact myocardium, five rats with genetic hypertension (SHR) were treated (SHRT) with hydralazine for 32 weeks, beginning at four weeks of age, and compared to six age- and sex-matched SHR and seven Wistar-Kyoto genetic control rats (WKY). Left ventricular (LV) weight of SHRT was 17% lower (P less than .001) than that of SHR and 19% higher (P less than .01) than that of WKY. Collagen volume fraction of SHR (13.7 +/- 3.2%) and SHRT (9.9 +/- 1.8%) were greater (P less than .01) than WKY (5.0 +/- 1.9%). Diastolic and systolic stress-strain relations were determined in the isolated heart. A comparison of these relations revealed: 1) a 24% increase in passive stiffness for SHR and SHRT; and 2) a reduced zero-strain intercept (41% to 54%) and slope (36% to 48%) of the developed stress-strain relation for the SHRT. Thus, in SHR, collagen remodeling occurred in the absence of hypertrophy which suggests that the muscular and collagenous compartments of the myocardium are under separate controls. The excess accumulation of collagen in SHR and SHRT leads to abnormal passive stiffness, and the prevention of hypertrophy with hydralazine reduces active stiffness.

Animals↗
PubMed1989

Myocardial stiffness and reparative fibrosis following coronary embolisation in the rat.

The structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardium, was undertaken to address these issues. Collagen volume fraction (trichrome), fibrillar collagens (picrosirius-polarisation technique), and the stress-strain relations of the intact myocardium (isolated hearts) were determined 30 d after the infusion of microspheres into the left ventricle. Significant differences from controls included: (a) the presence of hypertension secondary to renovascular embolisation; (b) a greater volume fraction of collagen that included not only a meshwork of short, taut appearing, thick and thin collagen fibres, interposed between muscle in areas of cell loss, but also a perivascular fibrosis involving intramyocardial coronary arteries; (c) elevated active stiffness, and (d) a more exponential diastolic stress-strain relation with increased stiffness at strains of 5% or more. These findings suggest that the replacement fibrosis accompanying myocyte necrosis has distinguishing morphological features involving fibrillar collagen and which because of its structure, alignment, and location relative to muscle leads to enhanced myocardial stiffness, including a more exponential rise in the diastolic stress-strain relation. The perivascular accumulation of collagen suggests that additional factors other than microsphere induced necrosis were responsible for this reactive fibrosis.

Animals↗
PubMed1989

Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat left ventricle.

This study tested the hypothesis that with hypertrophy, the proportion, distribution, and structural alignment of fibrillar collagen are important determinants of myocardial stiffness. Toward this end, the collagen volume fraction (morphometry), the transmural or subendocardial distribution of collagen, and the structural arrangement of fibrillar collagens (picrosirius red) were examined in the hypertrophied ventricle secondary to pressure overload (abdominal aorta banding or perinephritis), isoproterenol, and pressure overload plus isoproterenol. In the same hearts, the slopes of the systolic and diastolic stress-strain relations of the left ventricle, representing its active and passive stiffness, respectively, were obtained. In comparison with controls, we found 1) for a moderate rise in transmural collagen, active and passive stiffness increased with pressure-overload hypertrophy; 2) following isoproterenol alone there was a marked increase in subendocardial collagen, and active and passive stiffness increased; 3) in pressure-overload hypertrophy plus isoproterenol, active stiffness declined. Passive stiffness was increased except when fibrosis and thinning of the interventricular septum occurred, in which case it decreased; and 4) fibrillar collagens involved in remodeling included the formation of either collagen strands and fibers in a greater number of previously collagen-free intermuscular spaces in pressure-overload hypertrophy, or a dense crisscrossing latticework of fibers that encircled muscle fibers after isoproterenol. Thus, an increase in fibrillar collagen in pressure-overload hypertrophy is partially adaptive in that it enhances the tensile strength and three-dimensional delivery of force by the myocardium, but at the expense of reducing distensibility. The appearance of a dense collagen meshwork within the subendocardium after isoproterenol can be considered pathological in that it entraps muscle fibers causing active stiffness to fall while impairing distensibility. Finally, fibrosis may paradoxically reduce passive stiffness if it leads to a thinning of the interventricular septum.

Animals↗
PubMed1989

Fibrosis-induced reduction of endomyocardium in the rat after isoproterenol treatment.

Isoproterenol treatment leads to endomyocardial fibrosis with muscle fibers encircled by fibrillar collagen. This study was undertaken in the rat to determine if muscle encased in collagen would subsequently become either necrotic or atrophic. For this purpose, we monitored the fibrillar nature of myocardial collagen, its alignment with muscle, and the morphology of the endomyocardium, together with the response in diastolic and systolic myocardial stiffness, immediately on completion (10 days) and 30 days after a course of subcutaneous isoproterenol (500 micrograms/kg/day). We found 1) left ventricular hypertrophy at 10 and 30 days with an increase in collagen volume fraction (p less than 0.01) that consisted of a meshwork of thick and thin collagen fibers that encircled endomyocardial muscle, 2) a variable reduction in endocardial muscle fiber diameter at 30 days with the greatest thinning seen in muscle encircled by fibrous tissue, and 3) an elevation (p less than 0.01) in the slope of the diastolic stress-strain relation at 10 and 30 days. The developed systolic stress-strain relation, which was elevated at 10 days (p less than 0.01), declined (p less than 0.05) with the reduction in endomyocardial muscle mass. Thus, endomyocardial muscle, encircled by fibrillar collagen, will atrophy over time, and this leads to a reduction in active stiffness. These findings may, in part, explain why progressive ventricular dysfunction accompanies chronic myocardial disease with endomyocardial fibrosis.

Animals↗
PubMed1989

Myocardial fibrosis in nonhuman primate with pressure overload hypertrophy.

Characteristics of pressure overload hypertrophy are known to include an accumulation of collagen (or fibrosis) and a biochemical remodeling of fibrillar type I and III collagens. The corresponding structural nature of myocardial fibrosis is less clear. This light morphologic study was undertaken to address this issue in the hypertrophied left ventricle of the nonhuman primate with experimental hypertension. For this purpose, the picrosirius red technique and polarization microscopy were used to examine the myocardium during the evolutionary, early, and late phases of established hypertrophy corresponding to 4, 35, and 88 weeks of experimental hypertension. Evidence of increased thin perimysial fiber formation, together with collagen fiber disruption and edema at 4 weeks of hypertrophy, was found when the chamber volume to left ventricular mass ratio was reduced. After 35 weeks, when this ratio was again normal, a greater number of intermuscular spaces contained both thick and thin perimysial fibers. In addition to this interstitial fibrosis, a reactive fibrosis consisting of a meshwork of thick and thin perimysial fibers was seen extending over muscle fibers. Finally, at 88 weeks, this fibrous meshwork had encircled muscle and there now was evidence of cell necrosis. The accompanying replacement fibrosis consisted of yet another distinctive orthogonal grid of thick and thin collagen fibers. Thus, a continuum of fibrillar collagen remodeling was seen in pressure overload hypertrophy in the nonhuman primate myocardium. Structurally distinct patterns of myocardial fibrosis were recognized based on the alignment of perimysial fibers with muscle that may explain the cellular remodeling and altered mechanical behavior of the concentrically hypertrophied myocardium.

Animals↗
PubMed1989

End-to-side and end-to-end vascular anastomoses with a carbon dioxide laser.

This study was designed to compare anastomoses performed with a carbon dioxide laser and conventional anastomoses performed with 7-0 polypropylene suture. In each of 80 rabbits, the divided left carotid artery was anastomosed by a continuous suture technique and the right carotid was anastomosed with a carbon dioxide laser. In each of 40 additional rabbits, both end-to-end and end-to-side laser anastomoses were performed on the same carotid artery. The laser technique involved the placement of three stay sutures (end-to-end technique) or four stay sutures (end-to-side technique) of 7-0 polypropylene and an everting laser seal at a power level of 65 mW. The 1-year overall patency rate was 98% (78/80) in laser anastomoses, 79% (63/80) in suture anastomoses, and 95% (38/40) in combined end-to-end and end-to-side laser anastomoses. Microscopic findings in laser anastomoses demonstrated degeneration of collagen and protein in the adventitia and media, but much less intimal injury than in suture anastomoses, with reendothelialization beginning earlier (within 7 days after anastomosis as compared with 2 to 4 weeks). The tissue tensile strength at 1 hour was less in laser anastomoses than in suture anastomoses, but the laser anastomoses still withstood an intraluminal pressure load of 380 mm Hg. Laser anastomosis improved the microscopic and histologic appearance of the intimal layer, allowing for rapid early reendothelialization and resulting in excellent patency rates.

Anastomosis, Surgical↗
PubMed1989

The fibrillar nature and structure of isoproterenol-induced myocardial fibrosis in the rat.

A study of isoproterenol-induced (1 mg/kg) myocardial fibrosis in the rat was undertaken, taking advantage of the differential colorization provided by thick and thin collagen fibers to picrosirius red and polarization microscopy. The objective was to monitor the sequence (day 1, 2, 3, 4, and 8), fibrillar composition, and nature of isoproterenol-induced collagen remodeling, which was found previously to adversely influence myocardial stiffness. The following were found: 1) a distortion and widening of intermuscular spaces on day 1 that was accompanied by the disruption of collagen fibers; 2) by day 2, these spaces were closing and a new fibrillar collagen network had appeared consisting primarily of thinner collagen fibers that crossed over muscle fibers; 3) the new fibrillar network took on a clear crisscrossing pattern on day 3 and 4 as an ever-increasing number of thicker fibers became entwined perpendicular to the thinner fibers; and 4) by day 8, a dense mesh of thick and thin collagen fibers had formed to encircle muscle while a greater number of intermuscular spaces, previously devoid of collagen, were now filled with thicker and thinner collagen fibers. Thus, isoproterenol-induced myocardial fibrosis is initiated by the appearance of interstitial edema and fibrillar collagen disruption and is followed soon thereafter by the formation of thinner collagen fibers that extend across muscle fibers and into which thicker collagen fibers become entwined in a crisscrossing pattern. Once formed, this mesh of collagen fibers encircles cardiac muscle. This pattern of fibrous tissue formation may entrap and isolate myocytes so that the mechanical behavior of muscle and the intact myocardium becomes abnormal.

Animals↗
PubMed1988

Structural vs. contractile protein remodeling and myocardial stiffness in hypertrophied rat left ventricle.

Left ventricular pressure overload will result in the hypertrophic growth of the myocardium and in the rat may include a remodeling of both the structural and contractile proteins. As a result, an adaptive rise in active stiffness, or the force generating capacity of the myocardium, may occur. The relative importance of structural vs. contractile protein remodeling to the hypertrophic response and active stiffness is unclear. Accordingly, we monitored the ratio of V1/V3 isomyosin and the fibrillar nature and volume fraction of myocardial collagen, together with the developed systolic stress-strain relation of the intact myocardium in the adult male Wistar rat after 8 weeks of abdominal aorta banding. In comparison to controls and for the 20% increase in left ventricular mass obtained with banding we found: (a) collagen volume fraction had increased significantly (6.2 +/- 2.0 vs. 3.6 +/- 1.0%) while the V1/V3 ratio did not change; (b) interstitial compartment remodeling included a perivascular accumulation of collagen around small intramyocardial coronary arteries and the appearance of more extensive fibrillar collagens; and (c) active stiffness increased significantly. Thus, the increase in active stiffness of the hypertrophied adult rat myocardium, seen with abdominal aorta banding, appears to be related to interstitial fibrosis and not a conversion of myosin isoforms.

Animals↗
PubMed1988

Collagen network remodelling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophy.

This study had two objectives: (a) to determine the accumulation of collagen and its structural remodelling in the hypertrophied rat left ventricle after 4 and 8 weeks of abdominal aorta banding; and (b) to correlate these findings with the diastolic stress-strain relation of the intact myocardium. In comparison to age and sex matched controls, the collagen volume fraction of the hypertrophied myocardium after 4 and 8 weeks of aortic banding increased significantly from 3.5(SD1.0)% to 7.8(4.2)% and 6.2(2.0)% respectively. This accumulation of collagen, or fibrosis, occurred in the absence of myocyte necrosis. Scanning electron microscopy showed increased density and thickness of the collagen weave and tendons. At 4 weeks, light microscopy showed interstitial oedema and disrupted collagen fibrils. Left ventricular diastolic stress-strain relations of both pressure overload groups were significantly steeper than that of the control group. Thus the response of the interstitium to the hypertrophic process that accompanies abdominal aorta banding is a complex process that includes a structural remodelling of the fibrillar collagen matrix and the early appearance of interstitial oedema, each of which may contribute to a rise in the passive stiffness of the intact myocardium.

Animals↗
PubMed1988

Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium.

Cardiac muscle is tethered within a fibrillar collagen matrix that serves to maximize force generation. In the human pressure-overloaded, hypertrophied left ventricle, collagen concentration is known to be increased; however, the structural and biochemical remodeling of collagen and its relation to cell necrosis and myocardial mechanics is less clear. Accordingly, this study was undertaken in a nonhuman primate model of left ventricular hypertrophy caused by gradual onset experimental hypertension. The amount of collagen, its light microscopic features, and proportions of collagen types I, III, and V were determined together with diastolic and systolic mechanics of the intact ventricle during the evolutionary, early, and late phases of established left ventricular hypertrophy (4, 35, and 88 weeks, respectively). In comparison to controls, we found 1) increased collagen at 4 weeks, as well as a greater proportion of type III, in the absence of myocyte necrosis; 2) collagen septae were thick and dense at 35 weeks, while the proportion of types I and III had converted to control; 3) necrosis was evident at 88 weeks, and the structural remodeling and proportion of collagen types I and III reflected the extent of scar formation; and 4) unlike diastolic myocardial stiffness, which was unchanged at 4, 35, or 88 weeks, the systolic stress-strain relation of the myocardium was altered in either a beneficial or detrimental manner in accordance with structural remodeling of collagen and scar formation. Thus, early in left ventricular hypertrophy, reactive fibrosis and collagen remodeling occur in the absence of necrosis while, later on, reparative fibrosis is present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The lymphatic drainage of the pericardial space in the dog.

The purpose of this study was to characterize definitively the lymphatic drainage system of the pericardial space in the dog. The reports on this subject, based on dissection experiments and acute dye injections, remain controversial, and our own previous studies have been incomplete. Seventeen dogs were studied using a radiographic technique. Micropulverized barium sulfate instilled into the pericardial sac was followed with serial chest x-rays in seven dogs with intact cardiac lymphatics, in seven dogs after section of the cardiac lymphatic drainage node (the cardiac lymph node) in the right upper mediastinum, and in three dogs after resection of cardiac drainage lymphatic nodes in the left upper mediastinum. These studies revealed that the lymphatic drainage of the pericardial space is via (a) the principal coronary lymphatic which drains from the left ventricular muscle and passes to the right upper mediastinum via the cardiac lymph node, (b) the lesser coronary lymphatic which drains the right ventricular muscle and passes to the left upper mediastinum, and (c) bilateral internal mammary (parasternal) lymphatic chains. These observations are important in planning experimental approaches to the effects of impairment of lymph drainage from the pericardial space. An understanding of the lymph drainage from the pericardial space may prove significant to understanding fibrotic reactions within it and the pathologic mechanisms of such entities as constrictive pericarditis.

Animals↗
PubMed1987

Collagen in the hypertrophied, pressure-overloaded myocardium.

The extracellular structural protein, collagen, is responsible for the functional integrity of the myocardium permitting reversible interdigitation and transmission of force between contracting myocytes. In the pressure-overloaded, hypertrophied myocardium, clinical and experimental evidence indicates that the proportion of collagen relative to muscle is increased. Factors that appear to influence collagen growth during the hypertrophic process include age, species, the rapidity with which the overload occurs, the nature of the lesion leading to the pressure-overload, and the severity and duration of the overload. Morphologically, the heart's collagen matrix consists of a complex weave with tendinous insertions that surrounds myocytes grouping them into myofibers, strands of collagen that connect adjoining myofibers, and collagenous struts that join myocytes to other myocytes and capillaries. In a primate preparation of perinephritis with systemic hypertension, it was observed that the tendinous elements of the weave and the strands of collagen lying between myofibers were increased in number and physical dimension. The functional consequences of a remodeling of the collagen matrix that accompanied myocardial hypertrophy remain to be elucidated. A better understanding of the dynamic behavior of the collagen matrix may offer new insights into the pathogenesis of ventricular dysfunction that accompanies the chronic pressure-overloaded state.

Animals↗
PubMed1987

Systolic time intervals in burn injury.

Systolic time intervals were studied in 28 young, previously healthy burn patients (TBS 10-90%) on 145 occasions. A NEK 116 type 3 channel recorder of 100 mm/sec paper speed was used. Synchronous ECG recordings in lead II, PCG in the m "1" frequency band, and external carotid pulse tracings were recorded. RR, QS2, S1S2, LVET, PEP, PEP/LVET and QT, QTc, QS2-QT intervals were measured in 5-10 cardiac cycles in each of the examinations. Calculation of the additional parameters ICT, LVET/ICT, DT, EVR, PRP, EF and SV values were correlated to the extent of, and the time elapsed since, burn injury. The derivated parameters and statistical analysis were performed on a Commodore 64 type computer based on a software program. Elongation of QTc (greater than 440 msec) and frequent electrodynamic failure (QT-QS2 greater than 40 msec) especially during the first postinjury week were found characteristic in severe injury. In 53% the PEP/LVET ratio was less than 0.31, mean 0.32 +/- 0.093. In 21 cases of severe hypovolaemia the increase of PEP raised this value beyond 0.41. With the exception of 3 examinations, QS2I was normal or shortened. Calculated EF were normal or increased, SV reduced being interdependent with burn extent and shortening of DT. In patients with severe burns, oxygenization was inadequate (EVR less than 0.8); it showed an inverse correlation to HR. The simultaneously high LVET/ICT ratio and shortened ICT values pointed to an increase in contractility.

Adult↗
PubMed1985

Factitious desquamative gingivitis simulating a possible immunologic disease.

A case of a unique factitious disorder resulted from self-inducement of oral lacerations, erosions, and abrasions. Previous medical investigations included evaluations by two general dentists, one oral surgeon, two periodontists, one internist, one otolaryngologist, and one infectious-disease physician. The patient had two gingival biopsies and one hospitalization. The lesions were unresponsive to several therapeutic regimens including temporary discontinuation of tooth brushing, antibiotics, and gingival dressings. The differential diagnosis included infectious, nutritional, immunologic, and factitious disorders. An apparent initial response to corticosteroids suggested the possibility of an immunologic inflammatory disease; however, no organic cause could be found. The enigma was resolved by discussion with the patient who reported that the lesions were self-induced and the manner in which this was done.

Adult↗
PubMed1984

Use of fibrin sealant for reinforcing arterial anastomoses.

Despite improvements in needles, sutures, and technique, hemorrhage remains a problem in cardiovascular surgery. In this study conventional vascular suture lines and suture lines reinforced with fibrin sealant are compared for blood loss and burst strength. Bilateral femoral arteries in 20 dogs were divided at 50% of their circumference and repaired with six 6-0 polypropylene sutures. Ten animals were systemically heparinized (3 mg/kg), and 10 were not on anticoagulants. The right femoral artery anastomosis was treated with fibrin sealant in all animals, and the left suture line served as the control. Three minutes after initiation of the sealing procedure, blood flow was reinstituted in both femoral arteries. After 3 minutes a significant difference in blood loss between the conventional suture technique and fibrin-reinforced anastomoses was noted in both heparinized (12.1 +/- 2.79 vs. 0.13 +/- 0.06 ml/min; p less than 0.01) and nonheparinized dogs (8.45 +/- 1.37 vs. 0.20 +/- 0.08 ml/min; p less than 0.001). After 30 minutes volume inflow and pressure catheters were inserted into snared compartments encompassing the femoral artery anastomosis. Continuous pressure recordings during volume loading with normal saline solution demonstrated increased bursting pressures of the fibrin-sealed suture lines in both the heparinized (317.5 +/- 13.18 vs. 135 +/- 23.17 mm Hg; p less than 0.001) and nonheparinized animals (474.5 +/- 26.82 vs. 311 +/- 29.31 mm Hg; p less than 0.001). Histologic examination revealed no fibrosis or foreign body reaction and complete resorption of the fibrin sealant within 3 weeks. Fibrin sealant, a powerful hemostatic agent produced from human donors not suffering from hepatitis, decreases blood loss and strengthens suture lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Evaluation of fibrin sealing for cardiovascular surgery.

Hemorrhage remains a problem in patients undergoing cardiovascular surgery. To evaluate fibrin sealant, a completely biodegradable hemostatic agent, three series of experiments were performed in mongrel dogs. In series I, 18 dogs had a 7 cm interposition of knitted Dacron (water porosity 1500 ml/min/cm2) in the descending aorta. In group A, all prostheses were treated with fibrin sealant and in group B by blood preclotting. Measurements of blood loss demonstrated 1.29 +/- 0.26 ml/min in group A as compared with 30.16 +/- 2.85 ml/min in group B (p less than .001). In series II, six dogs of each group were compared for thrombogenicity and platelet survival by using indium-111-labeled autologous platelets. According to Goldman et al., the thrombogenicity index was calculated. The mean thrombogenicity index for group A was 0.23 +/- 0.02 in contrast to 0.33 +/- 0.05 for group B (p greater than .05). Mean platelet survival was 5.59 +/- 0.23 days in group A in contrast to 5.34 +/- 0.05 days in group B (p greater than .05). In series III, the gluing potential was investigated by creating four types of injuries: four dogs had an aortic stab wound 3 to 5 mm, six dogs received a 10 to 15 mm stab wound to the left ventricle, seven dogs had a 3 cm laceration of the left atrial appendage, and four dogs had bilateral division of their carotid arteries. Wounds of the aorta and left atrial appendage were treated by partial clamping and the sole use of fibrin sealant, the carotid arteries were repaired by four simple sutures and fibrin sealant, and the left ventricular stab wounds were treated by the combined use of heterologous collagen and fibrin sealant without suture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗