Muscular Compartments Research Articles

Estado nutricional de pacientes infectados por el virus de la inmunodeficiencia humana (VIH)

Objectives: Nutritional assessment in HIV infected patients must be a main objetive in the treatment of this disease. The main objetive of our work was to study the nutritional status with biochemical and anthropometrical parameters in a group of HIV infected patients. Material and methods: A total of 119 patients were evaluated. In all patients the next parameters were assessed: age, sex, treatment with anti-retroviral drugs, performed an anthropometric evaluation (weight, height, tricipital skinfold, arm circumference, arm muscular circumference and body mass index) and biochemical evaluation (albumin, prealbumin, transferrin, total proteins, triglycerides, cholesterol, lymphocites and count of CD4). Results: Patients had an average age 37.9±9.9 years, weight 64.5±13.2 kg and body mass index 22.5±3.5. The values of total proteins, albumin, prealbumin y transferrin were all normal, only patients with AIDS had low levels of transferrin (262.5±49.2 mg/dl vs 277.8±87.5; p<0.05). Percentil distribution of anthropometric parameters showed a deep depletion in muscular protein compartment, 53.1% of patients had skinfold under P 50, 91.8% had arm circunference under P 50, and 91.8% arm muscular circunference under P 50. High levels of triglycerides were detected in 30.5 %, these levels are related with the HIV phase and the number of antiretroviral drugs.. Conclusion: Nutritional status in HIV infected patients is good in our population, only a deep depletion in muscular proteic compartment was detected. Transferrin was decreased in AIDS patients. High levels of triglycerides were secondary to the number of antiretroviral drug taking by patients.

Valvular Density Alone Cannot Account for Sites of Chronic Venous Insufficiency and Ulceration in the Lower Extremity

ABSTRACTObjective: Class 6 chronic venous stasis is associated with abnormal venous hemodynamics and ulceration. Ulcers primarily occur over bones and tendon prominences but very rarely over muscular compartments. We hypothesized that the anatomical distribution of venous stasis ulcers in the lower extremity is related to a lower density of venous valves.Methods: The venous vasculature of six normal human legs was cast with resin, and their microvenous valvular anatomy was examined. Skin samples were obtained from the skin overlying the 1) Achilles' tendon, 2) anterior tibia, 3) medial malleolus, 4) lateral malleolus, 5) dorsal surface of the foot, 6) planta pedis, 7) dorsal aspect of the great toe; and from the skin regions overlying the 8) gastrocnemius, 9) tibialis anterior, and 10) peroneus muscles. The valvular and venous densities were determined in a scanning electron microscope, normalized to the size of specimens, and the valvular index was calculated. Analysis of variance with Bonferroni t‐test was used to compare the valvular index between the regions.Results: Venous valves were observed in all tissue regions. The diameter of veins with valves ranged from 18 µm to 803 µm. The valvular index for regions overlying bones/tendons (i.e., regions 1–7) was significantly higher versus those overlying muscular regions (i.e., regions 8–10) (p &lt; 0.05). The valvular index was not different (p = 0.51) when regions 1 and 2 (where ulcers almost never occur) were compared to regions 3, 4, 5, 6, and 7 (where ulcers frequently occur); nor were there differences between the vascular indexes of regions overlying muscle. The largest venous valves were observed in the plantar region, and the smallest‐sized ones were present in the peroneal region.Conclusions: This study shows that the density of venous valves is actually higher in regions of the human lower extremity overlying bones and tendons, where venous stasis ulcers are common, than those overlying muscular areas, where ulcers are rarely seen. Thus, valvular quantity alone cannot account for the higher clinical incidence of ulceration. It is likely that muscular pumping and/or valvular quality are important factors in preventing the development of venous stasis and ulceration in the lower extremity.

CONNECTIVE TISSUE AND THE HEART: Functional Significance and Regulatory Mechanisms

The heart has a three-dimensional extracellular fibrillar collagen scaffolding that normally serves a variety of functions important to tissue integrity and efficiency of muscular systolic pump and diastolic suction pump function (see article by Kovács). An adverse accumulation of extracellular matrix structural protein compromises tissue stiffness and adversely affects myocardial viscoelasticity, this leads to ventricular diastolic and systolic dysfunction. Hormonal factors, such as chronic, inappropriate (relative to dietary salt intake and intravascular volume) elevations in circulating angiotensin II and aldosterone, are accompanied by fibrosis of right and left sides of the heart. Hemodynamic factors regulate cardiac myocyte work and their adaptive hypertrophic growth. The relative contributions of hormonal and hemodynamic factors in regulating growth of muscular and nonmuscular compartments must form the basis for the selection of pharmacologic intervention that will optimize the management of symptomatic heart failure that accompanies hypertensive heart disease and ischemic cardiomyopathy. Cardioprotective strategies that prevent alteration of normal cardiac tissue structure by fibrosis and appearance of abnormal ventricular stiffness (viscoelasticity) are based on negating the generation of these hormones or interfering with their receptor-ligand binding. A regression of established cardiac fibrosis and improvement in abnormal ventricular stiffness is feasible. Experimental and clinical findings with lisinopril in hypertensive heart disease, where cardiac fibrosis and abnormal ventricular stiffness are present, indicate that such cardioreparation should be a targeted objective of pharmacologic intervention. Systematic analysis of this approach using a controlled clinical trial format is warranted. In recognizing the importance of viscoelastic elements in regulating the mechanical behavior of cardiac tissue, and in turn systolic and diastolic ventricular function, a broader tissue compartment based paradigm (ECM versus myocyte) for the management of heart failure emerges.

Fibrosis and hypertensive heart disease.

The normal myocardium is composed of a variety of cells: cardiac myocytes and noncardiomyocytes, which include endothelial and vascular smooth muscle cells and fibroblasts. Hypertensive heart disease involves a structural remodeling of muscular and nonmuscular compartments. It is not the quantity but rather the quality of myocardium that accounts for pathologic hypertrophy and predisposes to ventricular dysfunction and arrhythmias, which, in turn, confer increased risk of adverse cardiovascular events. Herein, factors regulating growth of these compartments are reviewed and in particular signals involved in promoting adverse remodeling of intramyocardial coronary arteries and arterioles by fibrous tissue.

Pulmonary and other examples of muscular malfunction, especially muro-sphincteric conflict in contractile chambers… commentaries

The mammalian body is composed of similar organs, the contractile chambers, which are therefore subject to similar inherent disorders. The basic unit is a muscular compartment which according to its function may or may not have sphincters. Muscles come in pairs, which normally cooperate. A universal form and cause of disease is failure of the essential reciprocity between mated muscles and allied groups. Clinicians encounter them as the inherent disorders of the hollow muscular organs/contractile chambers.

Hemorrhagic shock activates mast cells in the rat stomach wall.

The activation of mast cells (MC) and liberation of their mediators can play an essential role in initiating and controlling inflammatory processes in the wall of the gastrointestinal tract (GIT) due to ischemia. The role of MC in changes induced by hemorrhagic shock (HS) remains unknown. Heparin provided by MC seems to inhibit local inflammation and prevent DIC. The aim of this study was to evaluate the morphometric changes and biochemical activity of MC in the stomach wall after 75 minutes of hemorrhagic shock. The MC in mucosal, submucosal, muscular and serosal compartments of the various stomach wall regions were examined in shocked rats and in the control group. Additionally, the contents of glycosaminoglycans (GAG), measured as uronic acids concentration, as well as anticoagulative activity in the stomach wall were assessed. HS resulted in an evident increase in the number of mast cells detected in the stomach mucosa and serosa, in slight alterations in number of MC in the submucosal and muscular layers, a significant increase in size and changes of the shape of the MC. The elevation of the width, area, and circular shape of MC in all layers were noted. No clear and significant differences between various stomach regions in MC numbers and MC sizes could be shown. No reaction of other inflammatory cells at this stage of shock was observed. Highly significant increases in GAG concentration, and anticoagulative activity in the stomach wall due to shock were noted. The morphometric and biochemical data may indicate MC activation, especially in mucosa and serosa. The shock-induced migration of MC settled in the stomach wall seems to be possible. The results suggest an essential role of MC reaction in the stomach wall in the early phase of hemorrhagic shock.

The fat-free mass compartment influences serum leptin in men.

Recent experimental work in mice has demonstrated that leptin is synthesized by muscle cells. As this latter tissue is the main target for insulin-estimulated glucose disposal, we hypothesized that the muscular and fat-free mass (FFM) compartments might influence serum leptin levels in humans through increased insulin resistance. We evaluated body composition (through bioelectric impedance and anthropometrical parameters), insulin resistance (using the fasting insulin resistance index (FIRI) and insulin sensitivity (S(I)) from the minimal model analysis) and leptin levels in 140 men and 114 women. Serum insulin, FIRI and leptin levels were significantly increased in men in the highest quintile of FFM. Leptin levels positively correlated with FFM in men (r=0.24, P=0004) but not in women (r=0.02, P=not significant). With weight gain, however, approximately 25% of the additional weight is lean mass, so that obese people have higher fat-free mass than lean people. Hence, we performed a multiple linear regression analysis in a stepwise manner to predict leptin levels, in which fat mass (FM), FFM, and FIRI, but not age or waist-to-hip ratio (WHR) independently contributed to 32%, 6% and 3% of the variance in serum leptin levels in men. In women, FM (49%), FIRI (3.6%) and WHR (2.4%), but not FFM or age explained this variance. In a sample of 40 subjects, S(I) and leptin correlated with mid-arm muscle circumference (r=-0.51, P=0.03 and r=0.53, P=0.02) and mid-arm muscle area (r=-0.52, P=0.03 and r=0.53, P=0.02) in men (n=17) but not in women (n=23). The fat-free mass compartment contributes to the variability of serum leptin levels in men. Whether insulin resistance at this level mediates an increased production of leptin merits further research.

Workshop on Diagnosis and Treatment of Cardiac Maladaptive Remodeling

Heart failure is a major health problem. Accordingly, its pathophysiologic basis and pathogenic origins have received considerable research interest. To date much attention has focused on the importance of cardiac myocyte dysfunction and the adaptations of this muscular compartment as root causes of heart failure. Equally compelling to its origins, albeit less well recognized and understudied, is a role for the cardiac interstitium and its extracellular matrix. This dynamic compartment includes pluripotent fibroblasts with considerable phenotypic and functional diversity and a microenvironment composed of signaling molecules that regulate tissue homeostasis, including cell growth and behavior. Matrix remodeling provides a structural basis for ventricular diastolic and/or systolic dysfunction. This brief summary report overviews discussions held at an NHLBI-sponsored workshop focused on matrix remodeling in heart failure. Its purpose was to examine this remodeling process, not only for a better understanding of heart failure, but also to evaluate whether it would be a ripe target for preventive and therapeutic interventions.

Compartment syndrome. Exclusively the result of increased pressure in the muscular compartment?

The compartment syndrome (cs) is characterized by an increased tissue pressure in a limited space. Pathophysiologically, it is a multifactorial disease that is potentially induced by an initial trauma and develops according to the existence of cofactors. Cofactors are, for instance, the circulation of the patient and the initial treatment of the impending cs. In particular, the microcirculation is altered with endothelial destruction, development of a capillary leak, protein loss from intravasal space and the development of an interstitial and intracellular third space. An impaired drainage of the lymphatic and venous system causes a venous infarction. An arterial infarction results if the tissue pressure exceeds the arteriolar pressure. An accompanying ischemia reperfusion mechanism increases the trauma load. In disadvantageous cases, the patients are in danger of developing a multi-organ deficiency syndrome (MODS) by an uncontrolled inflammatory reaction, by intravasal volume loss and by a myonephropathic systemic reaction. Clinically, the patients suffer a disproportionate amount of pain, followed by neurological signs. Especially in noncompliant patients, tissue pressure measurement is useful. Resuscitation of the circulation as well as splitting of casts is important. In case of a manifest cs, dermatofasciotomy has to be performed as an emergency operation. Even if cs is diagnosed early and fasciotomy is carried out early, the development of sequellae cannot be avoided in every single case.

Hyperbaric Oxygen Therapy in the Management of Crush Injuries

Hyperbaric Oxygen (HBO) therapy is advocated for the treatment of severe trauma of the limbs in association with surgery because of its effects on peripheral oxygen transport, muscular ischemic necrosis, compartment syndrome, and infection prevention. However, no controlled human trial had been performed until now to specify the role of HBO in the management of crush injuries. Thirty-six patients with crush injuries were assigned in a blinded randomized fashion, within 24 hours after surgery, to treatment with HBO (session of 100% O2 at 2.5 atmosphere absolute (ata) for 90 minutes, twice daily, over 6 days) or placebo (session of 21% O2 at 1.1 ata for 90 minutes, twice daily, over 6 days). All the patients received the same standard therapies (anticoagulant, antibiotics, wound dressings). Transcutaneous oxygen pressure (PtCO2) measurements were done before (patient breathing normal air) and during treatment (HBO or placebo) at the first, fourth, eighth, and twelfth sessions. The two groups (HBO group, n = 18; placebo group, n = 18) were similar in terms of age; risk factors; number, type or location of vascular injuries, neurologic injuries, or fractures; and type, location, or timing of surgical procedures. Complete healing was obtained for 17 patients in the HBO group vs. 10 patients in the placebo group (p < 0.01). New surgical procedures (such as skin flaps and grafts, vascular surgery, or even amputation) were performed on one patient in the HBO group vs. six patients in the placebo group (p < 0.05). Analysis of groups of patients matched for age and severity of injury showed that in the subgroup of patients older than 40 with grade III soft-tissue injury, wound healing was obtained for seven patients (87.5%) in the HBO group vs. three patients (30%) in the placebo group (p < 0.05). No significant differences were found in the length of hospital stay and number of wound dressings between groups. For the patients with complete healing, the PtCO2 values of the traumatized limb, measured in normal air, rose significantly between the first and the twelfth sessions (p < 0.001). No significant change in PtCO2 value was found for the patients whose healing failed. The Bilateral Perfusion Index (BPI = PtCO2 of the injured limb/PtCO2 of the uninjured limb) at the first session increased significantly from 1 ata air to 2.5 ata O2 (p < 0.05). In patients with complete healing, the BPI was constantly greater than 0.9 to 2.5 ata O2 during the following sessions, whereas the BPI in air progressively rose between the first and the twelfth sessions (p < 0.05), reaching normal values at the end of the treatment. In conclusion, this study shows the effectiveness of HBO in improving wound healing and reducing repetitive surgery. We believe that HBO is a useful adjunct in the management of severe (grade III) crush injuries of the limbs in patients more than 40 years old.

The relation between thyroid function and nutritional status in HIV-infected patients.

The effects of human immunodeficiency virus (HIV) infection on thyroid function have been reported in only a few studies with discrepant results. The aim of this study was to assess the relation between nutritional status and thyroid function in HIV infected patients. Prospective, cross-sectional study. A 500-bed teaching and referral hospital serving a population of 450,000. Seventy-five consecutive HIV infected patients between 21 and 40 years of age (mean 31.8 +/- 0.9 years). Nutritional status was evaluated using the body mass index (BMI), triceps skinfold thickness (TSF), mid-arm muscle circumference (MAMC), and serum albumin concentration (SA). Hormone assays for serum T4, free thyroxine index (FTI), T3, reverse triiodothyronine (rT3), thyroxine-binding globulin (TBG), TSH and simultaneous CD4 lymphocyte counts were determined in all patients. Clinical stage was significantly related to nutritional status (P = 0.0001 for BMI, P = 0.0002 MAMC). The more poorly nourished groups had low mean serum T3 and rT3 levels, particularly for muscular (P = 0.0001 for T3 and P = 0.0076 for rT3) and visceral (P = 0.00001 for T3 and P = 0.0021 for rT3) protein compartments. Multivariate analysis showed that two factors, SA and MAMC, correlated significantly and independently with serum T3 and rT3. A close relation exists between serum thyroid hormone levels and nutritional status in HIV infected patients. These patients are probably euthyroid and the abnormal findings in the thyroid function tests are thus a reflection of the severity of illness.

Rostro-caudal distribution of reticulospinal projections from different brainstem nuclei in the lamprey

The reticulospinal (RS) system in the lamprey is responsible for the control of locomotion, postural corrections and steering. To perform these functions, the RS system has to affect different muscular compartments along the body axis selectively. In this study, the possibility that RS neurones in different nuclei may project to different parts of the spinal cord, was investigated. The rostro-caudal extent of single RS axons was defined by stimulating them antidromically while recording from their cell body. All recorded mesencephalic RS neurones projected to the caudal tip of the spinal cord. Of the rhombencephalic RS neurones, 26% of the recorded neurones did not reach the caudalmost fourth of the spinal cord and this proportion varied between the anterior (18%), middle (17%) and posterior (36%) rhombencephalic reticular nuclei. For these RS axons, the level of termination covered the whole rostro-caudal extent of the spinal cord. No correlation was found between the length of an axon and its conduction velocity or between the length of an axon and the rostro-caudal position of its cell body in the nuclei.

Functional Compartments of the Tensor Veli Palatini Muscle

To evaluate a dual role for the tensor veli palatini muscle in tubal and palatal function. The eustachian tube region of guinea pigs and macaques was fixed and processed for analysis by serial section histologic examination, micro-dissection, or both. The attachment, fiber direction, and regional relations of potentially discrete functional compartments in eustachian tube muscles were noted. The tensor veli palatini muscle in macaques has two anatomic sub-bellies. One appears to be a tubal dilator, the other to make the tube rigid along its longitudinal axis. No other muscle is directly associated with the eustachian tube in macaques. The tensor veli palatini muscle in guinea pigs has one gross belly that may affect palatal tensing and tubal dilation, rigidification, and stabilization. Other muscles of the eustachian tube in guinea pigs are a medial sub-belly of the medial pterygoid muscle, not previously described, and the levator veli palatini muscle. The muscular elements underlying tubal-palatal function in guinea pigs are more distinct and spatially separated than in macaques or humans. These differences may explain the confusion about the role of accessory muscles in tubal function. Muscular compartments of the eustachian tube complex in guinea pigs are easily accessible, which facilitates a more discrete and confident placement of electromyography electrodes. The guinea pig may be a useful model to better understand the interaction of multilevel compartmentalized physiologic sequences that underlie coordination of swallowing, breathing, and middle ear aeration.

Intramuscular Pressures Beneath Elastic and Inelastic Leggings

Leg compression devices have been used extensively by patients to combat chronic venous insufficiency and by astronauts to counteract orthostatic intolerance following spaceflight. However, the effects of elastic and inelastic leggings on the calf muscle pump have not been compared. The purpose of this study was to compare in normal subjects the effects of elastic and inelastic compression on leg intramuscular pressure (IMP), an objective index of calf muscle pump function. IMP in soleus and tibialis anterior muscles was measured with transducer-tipped catheters. Surface compression between each legging and the skin was recorded with an air bladder. Subjects were studied under three conditions: (1) control (no legging), (2) elastic legging, and (3) inelastic legging. Pressure data were recorded for each condition during recumbency, sitting, standing, walking, and running. Elastic leggings applied significantly greater surface compression during recumbency (20 +/- 1 mm Hg, mean +/- SE) than inelastic leggings (13 +/- 2 mm Hg). During recumbency, elastic leggings produced significantly higher soleus IMP of 25 +/- 1 mm Hg and tibialis anterior IMP of 28 +/- 1 mm Hg compared to 17 +/- 1 mm Hg and 20 +/- 2 mm Hg, respectively, generated by inelastic leggings and 8 +/- 1 mm Hg and 11 +/- 1 mm Hg, respectively, without leggings. During sitting, walking, and running, however, peak IMPs generated in the muscular compartments by elastic and inelastic leggings were similar. Our results suggest that elastic leg compression applied over a long period in the recumbent posture may impede microcirculation and jeopardize tissue viability.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of MRI in the investigation of leg oedema

Magnetic resonance imaging (MRI) was used in the diagnosis of various conditions giving rise to leg oedema, with special attention to the oedema after femoro-distal vascular reconstruction for obliterative atherosclerosis (n = 14). Patients with deep venous thrombosis (n = 6), chronic lymphoedema (n = 6) and closed muscular compartment syndrome (n = 2) were also investigated. Leg volume increase was measured according to the formula of a truncated cone. Interstitial fluid hydrostatic pressure (Pif) was recorded with the wick-in-needle technique. Spin echo series with 10 mm transverse slices were obtained with MRI. Following vascular reconstructions, leg volume increased 26% on the operated side. In the operated leg, no gradient in Pif was found between the posterior muscular compartment and the subcutaneous tissue. However, there was a significantly higher Pif in the subcutaneous tissue compared to the anterior muscular compartment (p less than 0.05). In the operated group, MRI revealed oedema around the entire circumference of the leg, mainly restricted to the subcutaneous tissue. In contrast, oedema of the leg muscles, particularly in the posterior compartments, was typical for patients having deep venous thrombosis. The group with chronic lymphoedema showed circumferential subcutaneous oedema alone or in combination with a fibrotic honeycomb pattern. Oedema of the affected muscular compartment was easily observed in patients who had a closed compartment syndrome. In conclusion, the use of MRI is promising in the investigation of conditions giving rise to leg oedema. It is likely that the formation of post-reconstructive oedema is taking place in the subcutaneous tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Postoperative radiotherapy in the treatment of extremity soft tissue sarcomas

From 1966 to 1983, 50 patients with extremity soft tissue sarcomas were treated with wide local excision and postoperative radiotherapy at the Mallinckrodt Institute of Radiology. The median follow-up was 70 months (range 28 to 168). Grade was the most significant factor affecting survival: all 11 patients with well differentiated tumor survived versus 6 8 patients with moderate and 17 31 patients with poorly differentiated tumors ( p < 0.01). In addition, lymph node involvement at diagnosis conferred a worse prognosis with only 2 5 patients alive after treatment ( p < 0.05). Eleven of 50 (22%) failed locally. Factors affecting local control included gross residual tumor after operation and limited treatment volume. Among the 35 patients who did not have gross residual tumor or limited treatment volume, two patients who received less than 5000 cGy failed locally versus 1 18 patients who received between 5000–6000 cGy and 2 15 patients who received more than 6000 cGy. Microscopically positive margins and a volume encompassing less than the total muscular compartment was not associated with an increase in the incidence of local failure. Eight patients developed local complication: five due to retreatment for local recurrence. Overall, 24 26 patients who are alive have had their limbs preserved with normal function.

Transcapillary forces in muscle compartments of lower limbs with deep venous thrombosis

Interstitial fluid pressure (Pif), plasma- and interstitial fluid colloid osmotic pressures (COPpl, COPif) were measured in muscle compartments of the calf in lower limbs of patients with deep venous thrombosis (DVT) and in contralateral limbs. Pif was measured with the 'wick-in-needle' technique in the anterior and deep posterior compartments in three periods of time following start of treatment for DVT. The first period was from 0-24 h, the second from 24-48 h and the third later than 48 h. We found a significant increase in both muscular compartments in legs with DVT compared to the contralateral in the three periods except for Pif in the anterior compartment in the third period. A significant reduction of Pif in both muscular compartments of limbs with DVT was found when comparing the first and second periods but not from the second to the third period. No difference was found in Pif in the muscular compartments of the contralateral limbs between the three periods. Interstitial fluid for COPif measurements was obtained by inserting intravenous cannulas in the deep posterior muscle compartment of the calf of limbs with DVT and contralateral limbs. In oedematous tissue it was possible to collect some fluid, but this was almost impossible in the non-oedematous tissues of the contralateral limbs. COPif was 4.2(2.4) mmHg (mean(SD)) in the deep posterior compartment of limbs with DVT, which is probably significantly reduced. Increased Pif and reduced COPif indicate increased transcapillary fluid filtration and reduced reabsorption as the main cause of oedema in muscular compartments in DVT of the lower limbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Compartment Syndromes in Athletes

Compartment syndromes occur frequently in the leg in association with athletics, but may occur in the forearm and many other muscular compartments as well. Similar inciting events may result in either acute or chronic forms with vastly different clinical presentations. With an understanding of the anatomy and pathophysiology, and the ability to directly measure compartment pressures, an accurate diagnosis can be readily made. Acute forms require immediate fascial release to minimize muscle and nerve injury. Surgical treatment of the chronic form is highly successful and usually allows an early return to athletics.

Patterns of myocardial fibrosis*1

The interstitium of the myocardium is composed of predominantly type I collagen; type III collagen is present to a lesser extent. The fibrillar collagens serve as tethers between muscle cells, muscle fibers, and blood vessels while also providing a scaffolding that supports the muscular and vascular compartments. In pressure overload hypertrophy, a continuous structural remodeling of the fibrillar collagen matrix is seen. What is initially an adaptive process that enhances tensile strength can eventuate in pathologic hypertrophy with muscle fiber entrapment, cell loss, and abnormal diastolic and systolic stiffness of the myocardium. Morphologically distinct patterns of myocardial collagen accumulation, or fibrosis, have been identified based on the alignment of thick and thin collagen fibers to one another and to cardiac muscle. Each pattern, representing either a reactive (without necrosis) or reparative process, can alter stiffness in a unique manner. The manner in which the interstitium regulates the nature and proportion of fibrillar collagen formation is unknown and deserving of further study. Such information may lead to the development of antifibrotic agents that counteract, prevent or modify disproportionate collagen remodeling in pressure overload hypertrophy. These agents may thereby ultimately represent corrective forms of therapy for the management of heart failure.

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.