Biomedical subjects

J S Janicki

Publications and source records attributed to J S Janicki.

At least 55 records · Page 3Linked to original sources

PubMed1990

Myocardial energetics and efficiency in patients with idiopathic cardiomyopathy: response to dobutamine and amrinone.

Nine consecutive patients having severe idiopathic dilated cardiomyopathy were studied for their response in ventricular function, coronary sinus blood flow and myocardial oxygen consumption, lactate extraction and efficiency following incremental doses of dobutamine, followed by the combination of dobutamine and the phosphodiesterase inhibitor amrinone. Results, presented as baseline and the response to the peak dose (15 micrograms/kg/min) of dobutamine and to the combination of dobutamine and amrinone (each at 15 micrograms/kg/min) (differences compared with baseline) were: wedge pressure decreased from 28 +/- 7 to 26 +/- 8 mm Hg (p = NS) and to 20 +/- 6 mm Hg (p less than 0.01); cardiac index rose from 1.47 +/- 0.44 L/min/m2 to 2.89 +/- 1.1 L/min/m2 (p less than 0.01) and to 3.64 +/- 1.05 L/min/m2 (p less than 0.001); myocardial oxygen consumption remained invariant (18 +/- 8, 17 +/- 5, and 19 +/- 5 ml/min) despite progressive increments in minute work from 2.96 +/- 1.1 to 6.98 +/- 3.9 kg - m/min (p less than 0.01) and to 9.38 +/- 4.3 kg - m/min (p less than 0.001); myocardial lactate extraction rose from 21 +/- 10% to 30 +/- 15% (p = NS) and to 35 +/- 10% with the addition of amrinone (p less than 0.01). No patient had net lactate efflux into the coronary sinus, and myocardial efficiency improved from 9.5 +/- 5% to 21.7 +/- 13.0% (p less than 0.01) and to 28.0 +/- 18.0% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗

PubMed1990

Reactive and reparative fibrillar collagen remodelling in the hypertrophied rat left ventricle: two experimental models of myocardial fibrosis.

STUDY OBJECTIVE: The aim was to compare the temporal sequence and structural relationship between perivascular and interstitial fibrosis and microscopic scarring seen in the left ventricle in response to either a transient or sustained stimulus to fibrosis. DESIGN: In 72 male Wistar rats (250-350 g) the transient stimulus model was based on the administration of isoprenaline (500 micrograms.kg-1) while the sustained stimulus model was produced by abdominal aortic banding with right renal artery constriction. Serial sections of myocardium were examined and compared at 4 and 12 weeks in each model and to corresponding controls. EXPERIMENTAL MATERIAL: The collagen specific stain, Sirius Red F3BA, was used to determine collagen volume fraction and the fibrillar nature of the fibrous tissue response seen by light microscopy. MEASUREMENTS AND MAIN RESULTS: Following isoprenaline a stable reparative fibrosis of the endomyocardium and increase in collagen volume fraction was seen without an interstitial or perivascular fibrosis of the non-involved myocardium. In unilateral renal ischemia, on the other hand, a progressive perivascular fibrosis was evident throughout the myocardium and from which fibrillar collagen extended into the extracellular space between muscle bundles creating an interstitial fibrosis; microscopic scarring of the endomyocardium became evident at 12 weeks. CONCLUSIONS: The reactive perivascular fibrosis of intramyocardial coronary arteries seen in renovascular hypertension is a progressive process that leads to an interstitial fibrosis and eventual microscopic scarring. In contrast, the endomyocardial scarring that follows isoprenaline induced myocyte necrosis is stable and intramural vessels in remote regions are not involved.

Animals↗

PubMed1990

Fibrillar collagen and remodeling of dilated canine left ventricle.

To test the hypothesis that in the failing volume-overloaded ventricle, the extracellular matrix and fibrillar collagen in particular are major determinants of the architectural remodeling of the myocardium, this histopathological study of the dilated, postmortem canine left ventricle secondary to rapid ventricular pacing or aortocaval fistula was undertaken. Using the picrosirius-polarization technique to enhance collagen birefringence, we sought to examine the structural integrity of the collagen matrix and interstitium. In the dilated failing ventricle secondary to rapid pacing, we found 1) interstitial edema and a disruption or disappearance of collagen fibers that were apparent within 6 hours of pacing, persisted for weeks, and subsequently were associated with muscle fiber disorganization within the endomyocardium, 2) interstitial fibrosis that was present in the midwall and epimyocardium with chronic pacing, and 3) an early remodeling of intramyocardial coronary arteries that included medial swelling with smooth muscle degeneration followed by proliferative lesions involving fibroblasts and a subsequent perivascular and medial fibrosis. Many of these findings were still evident 48 hours after pacing had been discontinued. In contrast, the collagen matrix and interstitium seen with ventricular dilatation secondary to the circulatory overload that accompanies an aortocaval fistula were indistinguishable from that in sham-operated controls. Thus, we conclude that unlike the chamber enlargement and preserved ventricular function that accompany an aortocaval fistula, ventricular dilatation and failure caused by rapid pacing are based on an architectural remodeling of the myocardium. This structural dilatation involves the extracellular matrix and interstitium and appears to be related to altered permeability of intramyocardial coronary arteries. The mechanism or mechanisms involved in the pathogenesis of myocardial remodeling with rapid ventricular pacing require further investigation.

Animals↗

PubMed1990

Remodeling of the rat right and left ventricles in experimental hypertension.

Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles.

Aldosterone↗

PubMed1990

Long-term reproducibility of respiratory gas exchange measurements during exercise in patients with stable cardiac failure.

Present-day technology has greatly facilitated the monitoring of respiratory gas exchange in the clinical exercise laboratory. Despite the growing use of these techniques to assess the severity and progression of disease or therapeutic response in patients with heart failure, the long-term reproducibility of oxygen uptake (VO2), carbon dioxide production, minute ventilation, heart rate (HR), and blood pressure at rest and during incremental exercise in such patients, to our knowledge, has not been evaluated. Therefore, the purpose of this study was to quantify the reproducibility of these variables along with exercise duration, maximum VO2 (VO2max) and anaerobic threshold in a group of 16 patients (61 +/- 7 years, 14 male) with chronic, stable cardiac failure of varying severity and etiology who had five or more incremental treadmill exercise tests over a period of time that ranged from 3 to 22 months. For each variable, reproducibility was represented by the coefficient of variation (CVAR). Except for exercise duration, CVAR was not a function of the severity of heart failure and, for all variables, patient-to-patient variation in CVAR was approximately 9 percent. The maximum CVAR for HR, systolic blood pressure, VO2, and VO2max was generally below 10.5 percent and for exercise duration and anaerobic threshold it was less than 12.5 percent. Based on this retrospective analysis, it is concluded that reproducible respiratory gas exchange and HR exercise responses are obtainable over extended periods of time in patients with stable, chronic cardiac failure. Exercise duration, however, is less reproducible in patients with moderate to severe failure.

Aged↗

PubMed1990

Influence of the pericardium and ventricular interdependence on left ventricular diastolic and systolic function in patients with heart failure.

The pericardium, because of the nature of its pressure-volume relation, can influence left ventricular diastolic and systolic pump function. During an acute increase in heart size that results in the stretching of the pericardium, the elastic properties of the pericardium restrict further cardiac dilatation and curtail the ability of the ventricles to increase stroke volume. In addition, the pericardium enhances the degree to which increments in right ventricular volume would alter left ventricular diastolic distensibility. Ventricular interdependence is enhanced as a direct consequence of pericardial elastic properties. During the heightened venous return associated with marked muscular work, we found evidence of pericardial constraint in 31 of 61 patients with heart failure of varying severity and diverse etiology. The occurrence of pericardial constraint, which was characterized by stroke volume becoming invariant and an equivalent rise in right atrial and pulmonary capillary wedge pressures as work load was raised during incremental upright exercise, was independent of the degree to which maximum oxygen consumption was reduced or, equivalently, the severity of heart failure. In contrast, when pericardial constraint was not apparent during our exercise protocol, stroke volume did not become invariant, and the increments in pulmonary capillary wedge pressure were two- to threefold that of right atrial pressure. Thus, the pericardium can have a substantial role in determining the limits to left ventricular diastolic and systolic function.

Exercise↗

PubMed1989

Response in oxygen uptake and ventilation during stair climbing in patients with chronic heart failure.

To examine the level of muscular work and ventilatory response to stair climbing (mobile Stairmaster staircase, 1 step/2.5 s), respiratory gas exchange, ventilation, heart rate and arterial pressure were monitored in patients with chronic heart failure and their response compared with that of normal individuals. Aerobic capacity (maximal oxygen uptake) and anaerobic threshold during treadmill exercise were also determined and used to ascertain the metabolic cost of stair climbing. No differences were observed in the response of mean arterial blood pressure between the 12 patients and 10 normal subjects during exercise or recovery. However, the heart rate and oxygen consumption obtained during exercise were significantly lower in the patients with chronic heart failure than in the normal subjects (p less than 0.05). All patients with a maximal oxygen uptake less than 20 ml/min/kg during treadmill exercise had an oxygen uptake during stair climbing that exceeded their anaerobic threshold and, consequently, they attained a significantly (p less than 0.01) higher level of ventilation during exercise and recovery. This was not the case for those patients with greater aerobic capacity. Therefore, it is concluded that stair climbing for the 12 patients with heart failure and moderate to moderately severe impairment in aerobic capacity represents strenuous anaerobic exercise. The resultant excess ventilation may explain the limiting sensation of dyspnea that is frequently experienced by these patients during and after stair climbing.

Adult↗

PubMed1989

Myocardial energetics: experimental and clinical studies to address its determinants and aerobic limit.

The major determinants of myocardial oxygen consumption (MVO2) were examined in the isolated, servo-regulated, canine heart in which coronary perfusion pressure, heart rate, ventricular volume and pressure could be individually monitored and controlled. We found that the integral of systolic wall force and the time derivative of systolic force development were major determinants of MVO2, Net MVO2, seen in response to increments in contractility (dobutamine) and heart rate, were the result of the relative increments in each of these determinants. Additional studies were performed to assess the heart's metabolic reserve and aerobic limit (i.e., before the onset of lactate production). We found that with increments in left ventricular work, mediated by increments in filling volume, heart rate, and contractility (dobutamine), myocardial lactate production could be induced, but was dependent on the level of coronary perfusion pressure. When the aerobic limit of the myocardium was exceeded, its performance declined and pulsus alternans appeared. In patients with cardiomegaly and advanced heart failure given the phosphodiesterase inhibitors enoximone and piroximone we did not observe a rise in MVO2 or the appearance of lactate production in the majority of patients. When patients with documented idiopathic (dilated) cardiomyopathy and marked heart failure received hemodynamically significant doses of dobutamine alone or in combination with amrinone, there again was no evidence of lactate production or a rise in MVO2, while a marked improvement in ventricular function was noted. Thus, these agents served to improve the efficiency of the dilated failing heart. Hence we would conclude that in most cases, the dilated failing heart has an adequate metabolic reserve. It performance, and indeed its efficiency, can be improved with pharmacologic agents having positive inotropic properties without adversely altering myocardial energetics.

Aerobiosis↗

PubMed1989

Patterns of myocardial fibrosis.

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.

Animals↗

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

Angiotensin and the remodelling of the myocardium.

1. From a morphologic standpoint, the myocardium has three compartments: cardiac myocytes; intramyocardial coronary arteries with a microcirculation; and an interstitium composed largely of fibrillar collagen. As long as intercompartmental equilibrium exists, myocardial mechanics and energetics and myocyte viability will each be preserved. 2. The hypertrophic process seen with left ventricular pressure overload secondary to renovascular hypertension alters this equilibrium because of the adverse remodelling of intramural coronary arteries and fibrillar collagen. The pathogenetic mechanism(s) responsible for the observed myocardial fibrosis, having reactive and reparative components, remains to be elucidated. 3. Attractive circumstantial evidence, however, has been obtained to incriminate circulating angiotensin II in this process. Five lines of evidence favouring the role of angiotensin II in promoting the reactive perivascular and interstitial fibrosis and the reparative fibrosis are presented, including the potential cardioprotective effects of angiotensin converting enzyme inhibitors.

Adult↗

PubMed1989

Primary pulmonary hypertension. Vascular structure, morphometry, and responsiveness to vasodilator agents.

The use of pharmacologic agents in the treatment of pulmonary hypertension has not proved to be uniformly successful or predictable. One possible reason for the vagaries in response is that the pulmonary vascular lesions are not consistent. We examined the relation between the structure of the pulmonary resistance vessels in unexplained (primary) pulmonary hypertension and the response to pulmonary vasodilators. Our study involved 19 patients with clinically unexplained pulmonary hypertension (mean pressure, 59 +/- 14 mm Hg). After characterizing them clinically and performing control hemodynamic measurements, we determined the acute effects of a series of vasodilator agents that have different mechanisms of action. In 16 patients, lung biopsy material was related to the hemodynamic studies; in nine patients, including six who had undergone open lung biopsy, the hemodynamic studies were related to the pathologic changes found at autopsy. Histologic specimens from all 19 patients were evaluated qualitatively and sorted into three subsets of hypertensive pulmonary arteriopathy: medial hypertrophy (with minimal intimal proliferation), arteriopathy with plexiform lesions (associated predominantly with concentric laminar intimal proliferation and fibrosis), and arteriopathy with microthrombotic lesions (associated predominantly with eccentric intimal proliferation and fibrosis). The 16 lung biopsies were also quantitated by morphometric techniques. Using a decrease in calculated pulmonary vascular resistance of more than 30% accompanied by a decrease in mean pulmonary arterial pressure of at least 10% to define vasodilation, only four patients were responders. The patients varied considerably in their responses to different vasodilator agents. Patients with similar clinical and hemodynamic profiles differed considerably with respect to the nature of their pulmonary vascular obstructive lesions and their responses to vasodilator agents. Qualitative histologic examination of lung tissue did not provide a basis for predicting how individual patients would respond to vasodilator agents. However, quantitative morphologic analysis of the initial open lung biopsy specimens did prove helpful in predicting acute responsiveness to vasodilator agents and the subsequent clinical course of these patients with unexplained (primary) pulmonary hypertension. An intimal area of more than 18% of the vascular cross-sectional area had an 85% predictive value for identifying the patients who did poorly during the first 36 months of follow-up.

Adolescent↗

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

Pathogenesis of heart failure.

The myocardium consists of three compartments: cardiac muscle cells; a nutritive microcirculation; and an extracellular matrix composed largely of fibrillar collagen. The hypertrophic remodeling of the myocardium, which involves each of these compartments, can be adaptive or pathologic. This article reviews the remodeling process and the current state of our knowledge regarding the pathogenetic features of pathologic hypertrophy with heart failure.

Cardiomegaly↗

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↗