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Biomedical subjects

J S Janicki

Publications and source records attributed to J S Janicki.

At least 73 records · Page 4Linked to original sources
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

Cardiopulmonary exercise testing in congestive heart failure.

Cardiopulmonary exercise testing includes the monitoring of respiratory gases and airflow to determine oxygen uptake, carbon dioxide (CO2) production, respiratory rate, tidal volume, and minute ventilation during a graded maximal exercise test. A plateau in oxygen uptake, which occurs despite an increase in work load, and which is termed maximal oxygen uptake (VO2 max), correlates with the maximal exercise cardiac output and can therefore be used to grade the severity of heart failure. The anaerobic threshold occurs at 60 to 70% of VO2 max and is another indicator of the severity of heart failure and, when attained, indicates that the patient is close to performing a maximal test. We have found VO2 max and anaerobic threshold to be objective measures of efficacy of both investigational and noninvestigational therapy in patients with heart failure. A pulmonary limitation to exercise can be identified by the failure to attain anaerobic threshold or VO2 max, as well as exhaustion of the ventilatory reserve, as estimated by maximal voluntary ventilation. Thus, cardiopulmonary exercise testing can be used to (1) grade the severity of heart failure, (2) objectively follow the response to therapy, and (3) differentiate a cardiac from a pulmonary limitation to exercise.

Carbon Dioxide↗
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

Physiologic correlates of the heart rate response to upright isotonic exercise: relevance to rate-responsive pacemakers.

Rate-responsive cardiac pacing requires a sensitive physiologic variable that is closely correlated with the heart rate-oxygen uptake relation, particularly in patients with heart failure whose cardiac output response to exercise is more dependent on heart rate. Accordingly, the heart rate response to upright exercise was measured in 81 patients with heart failure or hypertension, or both, and in 27 normal subjects. Oxygen uptake (VO2), minute ventilation (VE), cardiac output, right heart pressures and the mixed venous temperature, oxygen saturation (SvO2) and pH were analyzed throughout exercise. Linear regression analysis of these variables with heart rate revealed the following: 1) There was a highly linear heart rate-VO2 relation in each subject (the average slope of this relation was greater [p less than 0.05] in patients with more severe failure). 2) VE was highly correlated with exercise heart rate, and its slope was not different between normal subjects and patients. 3) Mixed venous temperature and pH were poor predictors of exercise heart rate, particularly at low or moderate levels of work; however, SvO2 was highly correlated with heart rate for all levels of work. Thus, in normal subjects and patients with heart failure or hypertension, or both, heart rate increases linearly with isotonic leg exercise. Minute ventilation and mixed venous oxygen saturation are highly correlated with this response and may serve as potential sensors for rate-responsive pacemakers.

Adult↗
PubMed1988

Hemodynamic, ventilatory and metabolic effects of light isometric exercise in patients with chronic heart failure.

Light isometric exercise, such as lifting or carrying loads that require 25% of a maximal voluntary contraction, is frequently reported to cause dyspnea in patients with heart failure. The pathophysiologic mechanisms responsible for the appearance of this symptom, however, are unknown. Accordingly, hemodynamic, metabolic and ventilatory responses to 6 min of light isometric forearm exercise were examined and compared in 20 patients with chronic heart failure and abnormal ejection fraction (24 +/- 9%) and 17 normal individuals. In contrast to findings in normal volunteers, exercise cardiac index did not increase whereas exercising forearm and mixed venous lactate concentrations increased (p less than 0.05) above levels at rest in patients with heart failure; at 90 s of recovery, blood lactate concentration remained elevated (p less than 0.05). The venous lactate concentration of the nonexercising arm, unlike that of the exercising forearm, was not altered. Oxygen uptake, carbon dioxide production and minute ventilation increased similarly in patients and normal subjects during exercise, but only in patients did each increase further (p less than 0.05) during recovery. Thus, in patients with heart failure, light isometric forearm exercise represents an anaerobic contraction with lactate production. The subsequent increase in carbon dioxide production leads to a disproportionate increase in minute ventilation and oxygen uptake during recovery that may be perceived as breathlessness.

Adult↗
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

Use of the cardiopulmonary exercise test to evaluate the patient with chronic heart failure.

Isotonic exercise testing imposes a physiological stress on the cardiopulmonary unit. Accordingly, monitoring of oxygen, carbon dioxide and air flow during an exercise test (i.e. a cardiopulmonary exercise test) can be used to assess heart function in patients with chronic heart failure. Specifically, an incremental treadmill cardiopulmonary exercise test represents a non-invasive means to determine aerobic capacity, or maximal oxygen uptake (VO2max ml min-1 kg-1), and anaerobic threshold (AT, ml min-1 kg-1). These objective measures of cardiopulmonary function are then used to grade the severity of failure and the functional capacity of the patient. In addition, they may be used to predict the cardiac reserve, or maximal cardiac index (CImax, l min-1 m-2) during exercise. That is, the severity is considered to be mild (class A) when AT greater than 14 or VO2max greater than 20, mild to moderate (class B) when AT falls between 11 and 14 or VO2max between 16 and 20, moderate to severe (class C) when AT ranges between 8 and 11 or VO2max between 10 and 16, and severe (class D) when AT less than 8 or VO2max less than 10. The predicted CImax for classes A, B, C and D are greater than 8, 6-8, 4-6 and less than 4, respectively. Finally, a major objective of medical therapy in patients with heart failure is to improve cardiac output and oxygen delivery to working skeletal muscle and thereby enhance effort tolerance. This therapeutic endpoint can be gauged by cardiopulmonary exercise testing from the response in AT and VO2max.

Anaerobic Threshold↗
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

Monitoring physical activity in ambulatory patients with chronic cardiac failure.

Static or dynamic work in patients with chronic cardiac failure elicits a variety of pathophysiologic responses that impair the ability of the cardiopulmonary unit to sustain O2 delivery at a rate that is commensurate with the O2 requirements of working skeletal muscle. Regional abnormalities in the circulation of skeletal muscle may further compromise nutritive blood flow to muscle. As a result, the patient experiences a sense of fatigue during physical activity. Dyspnea, or an abnormal awareness of breathing, may also accompany exercise in these patients. This sense of breathlessness may be due to an abnormally elevated work of breathing secondary to decreased pulmonary compliance, a heightened chemical drive to ventilation, and a possible imbalance in the O2 supply and demand of the respiratory muscles. The ambulatory monitoring of physical activity in patients with chronic cardiac failure has not been systematically examined. Potential monitoring techniques that may provide accurate and reproducible results regarding the exercise response in these patients include the thoracic impedance principle to measure minute ventilation and portable O2 uptake sensors.

Activities of Daily Living↗
PubMed1987

Pathophysiology of acute and chronic cardiac failure.

Cardiac (or myocardial) failure, a major health problem, can be defined using physiologic criteria that consider the adequacy of O2 delivery relative to the body's O2 requirements. In clinical terms, cardiac failure may be described in terms of its chronicity or the extent to which signs and symptoms of right- versus left-sided heart failure are dominant. Congestive heart failure is a clinical syndrome that consists of a constellation of signs and symptoms that arise from congested organs and hypoperfused tissues. Acute cardiac failure occurs because of a decrease in myocardial contractility that can be offset by the Frank-Starling mechanism. In chronic cardiac failure dilatation and myocardial hypertrophy serve to restore ventricular function. Other compensatory responses that are invoked include a salt avid kidney, which mediates an expansion of the intravascular space, and the activation of the adrenergic nervous and renin-angiotensin-aldosterone systems and an increase in circulating arginine vasopressin. The management of acute and chronic cardiac failure can be derived from an understanding of the pathophysiologic mechanisms responsible for their appearance and include improving cardiac performance, as well as the distribution of systemic blood flow to tissues based on physiologic priorities and moment to moment variations in O2 requirements.

Acute Disease↗
PubMed1987

Physiologic response to the inotropic and vasodilator properties of enoximone.

In patients with chronic cardiac failure, improvement in ventricular function is observed after the administration of enoximone, a phosphodiesterase inhibitor with inotropic and vasodilator properties. The relative contributions of positive inotropy and vasodilation to the improvement in pump performance, however, remain uncertain. Therefore, findings from a series of dog experiments designed to resolve this issue are reviewed. Also, our current understanding of the physiologic response to enoximone in patients with cardiac failure, including the responses of myocardial oxygen consumption and efficiency, are considered. It is concluded that, enoximone produces a substantial (66 +/- 2% in dogs) increase in contractility, a relatively minor increase in heart rate (0 to 12%) and a decrease in systemic vascular resistance (-28 to -49%). These are the ranges of average responses based on review of published findings. These physiologic responses lead to an improvement in the pumping function of the failing heart; cardiac output (23 to 83%) and stroke work index (17 to 88%) are increased, and pulmonary capillary wedge pressure (-19 to -59%) and right atrial pressure (-29 to -60%) are decreased. The influence of enoximone on myocardial oxygen consumption is less consistent (-18 to +33%). Nevertheless, enoximone improves the efficiency of the failing heart.

Animals↗
PubMed1987

Long-term oral enoximone therapy in chronic cardiac failure.

Sixty-nine patients with chronic heart failure of moderate to advanced severity were treated with oral enoximone (mean dose 1.8 +/- 0.5 mg/kg every 6 to 8 hours) for an average of 35 weeks (range 1 to 129). Before long-term therapy in 56 patients, oral enoximone was shown to augment cardiac output by more than 30%. In 13 outpatients enoximone was initiated without hemodynamic monitoring. Within 12 weeks of therapy the majority of surviving patients were improved by at least 1 New York Heart Association functional class. In a subset of 30 patients who were able to perform reproducible treadmill exercise before entry, average maximal O2 uptake increased from 14.9 ml/kg/min at baseline to 17.6 ml/kg/min (p less than 0.05) at 2 to 4 weeks and remained increased at 17.4 ml/kg/min (p less than 0.05) at 12 weeks. Adverse gastrointestinal effects occurred in 11 patients and were generally mild. The 12 month survival rate was 44%; etiology of death was cardiogenic shock in 17 patients and 10 patients died suddenly while at home. Thus, improvements in symptoms and maximal VO2 were observed in many patients with moderate to severe heart failure during long-term therapy with enoximone. Controlled trials will be needed to establish the safety and efficacy of this promising new drug.

Administration, Oral↗
PubMed1987

Measurement and interpretation of maximal oxygen uptake in patients with chronic cardiac or circulatory failure.

Rapidly responding gas analyzers have simplified the monitoring of oxygen uptake (VO2) in the clinical exercise laboratory. An incremental, exhaustive, upright exercise test can be safely used to determine the plateau in oxygen uptake during exercise, or maximal VO2 (VO2max), in patients with chronic cardiac or circulatory failure. We define VO2max in these patients as an increase in VO2 of less than 1 ml/min/kg despite an increment in work load. The value for VO2max indicates the patient's aerobic capacity; it also predicts the maximal cardiac output during exercise and therefore serves as an estimate of cardiac reserve and of the severity of cardiac or circulatory failure. Symptom-limited VO2 during exercise, termed maximum oxygen uptake but more appropriately peak VO2, bears no relationship to VO2max. The two terms should not be used interchangeably.

Cardiac Output↗
PubMed1987

Piroximone (MDL 19,205) in the treatment of unstable and stable chronic cardiac failure.

The hemodynamic and clinical response to oral and intravenous piroximone was examined in 25 patients with chronic cardiac failure secondary to ischemic or myopathic heart disease: 14 with severe failure, who were clinically unstable (group I), and 11 with stable failure of mild to moderate severity (group II) in whom maximal O2 uptake (VO2 max) to treadmill exercise could be monitored serially. Intravenous (0.5 to 1.0 mg/kg) and oral (0.7 to 4.9 mg/kg) piroximone significantly (p less than 0.05) improved right and left ventricular pump function in both groups while causing an insignificant rise in heart rate and reduction in arterial pressure. Myocardial O2 uptake was not altered acutely or subacutely after piroximone, and myocardial lactate production was not observed. The salutary hemodynamic response to oral piroximone was sustained for 5 hours and there was no evidence of tolerance to the third and fourth doses. In group II, VO2 max was increased (p less than 0.05) at 4, 8, 12, 24, and 48 weeks of oral piroximone therapy. Adverse gastrointestinal effects were observed in two patients and a supraventricular tachycardia in another. Thus, piroximone may prove useful in the long-term management of chronic cardiac failure. Controlled clinical trials should be undertaken to determine the ultimate efficacy and safety of piroximone in these patients.

Administration, Oral↗
PubMed1987

The effect of chronic pulmonary hypertension on left ventricular size, function, and interventricular septal motion.

The effect of right ventricular pressure overload secondary to chronic pulmonary arterial hypertension on left ventricular size and function and on interventricular septal motion was studied in 13 patients in whom coronary artery disease, hypertension, and hypoxemia were excluded. Regional and global left ventricular function were assessed by computer-assisted analysis of two-dimensional directed M-mode echocardiograms obtained within 24 hours of a hemodynamic study. Septal position and motion were further analyzed by delineating seven points along the right and left sides of the septum during a single cardiac cycle. All echocardiographic data were compared to those of 10 normal subjects. Mean values for right ventricular systolic, mean pulmonary artery and pulmonary capillary wedge pressures were: 71 +/- 26 mm Hg, 46 +/- 16 mm Hg, and 7 +/- 1 mm Hg, respectively. Septal motion was interpreted from the M-mode echocardiograms as normal in seven patients (group I) and abnormal in the remaining six patients (group II). The only hemodynamic parameter which distinguished these two patterns was delta P, the transseptal systolic pressure gradient across the interventricular septum, which was significantly different (p less than 0.02) in group I (delta P = 65 +/- 16 mm Hg) from that of group II (delta P = 21 +/- 24 mm Hg). As a result of abnormal septal position, the septal-free wall dimensions of the left ventricle were reduced, but there was no evidence of depressed left ventricular performance in these patients. We conclude that resting left ventricular function is well preserved in patients with pulmonary hypertension, despite significant alterations in septal position and left ventricular size.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Extracardiac pressure and ventricular haemodynamics.

To investigate the relative influence of pericardial and intrathoracic pressures on left and right ventricular diastolic and systolic pressures two experimental groups were studied: group 1-10 open chest dogs with a controlled pericardial effusion; and group 2 - five closed chest dogs with a controlled pneumothorax at constant transpulmonary pressure and lung volume. In both groups right and left ventricular diastolic pressures were linear functions of external pressure with respective slopes of 0.71 and 0.39 for group 1 and 0.80 and 0.78 for group 2. The left ventricular slope of 0.39 indicates that left ventricular volume decreased more with increments in pericardial pressure since a slope of approximately 1.00 would be expected if the filling volume was invariant. Accordingly, the fall in left ventricular systolic pressure that occurred in both groups was two to three times greater in group 1. Right ventricular systolic pressure fell in group 1 whereas it increased in group 2. It is concluded that there are no major differences between the influence of either type of external pressure on right ventricular filing. In contrast, the left ventricle, and in particular the filling pressure gradient between the pulmonary circulation and the left ventricle, is more sensitive to pericardial pressure.

Animals↗