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Biomedical subjects

J S Janicki

Publications and source records attributed to J S Janicki.

At least 91 records · Page 5Linked to original sources
PubMed1987

Cardiopulmonary exercise testing in clinical practice.

Cardiopulmonary exercise testing refers to the noninvasive measurement of respiratory gas exchange and air flow, together with heart rate, blood pressure, and the electrocardiogram. These data, obtained during an incremental exercise test, can be used to derive the aerobic capacity or VO2max, which is an objective measure of the severity of chronic cardiac and circulatory failure, as well as to predict the maximum cardiac output response to exercise. The additional monitoring of minute ventilation and arterial oxygen saturation can be used to distinguish ventilatory from cardiac or circulatory causes of exertional dyspnea. Finally, this information serves as an objective measure of functional capacity which can be monitored over time to assess the natural history of disease as well as its response to medical therapy.

Heart Function Tests↗
PubMed1987

Newer positive inotropic agents in the treatment of chronic cardiac failure. Current status and future directions.

Heart failure is a serious worldwide health problem of major proportions. For many physicians, digitalis (an inotropic agent of limited proportions) and diuretics have proven the standard of treatment for heart failure. Vasodilators have also gained acceptance in recent years. Nevertheless, many patients remain symptomatic and therefore attention has been given to the development of pharmacological agents with mechanisms of action targeted to cardiac and vascular smooth muscle. The newer generation of inotropic agents have clearly been shown to improve the pumping function of the failing heart in patients who remain symptomatic despite digitalis, diuretics and vasodilators, while myocardial oxygen consumption is not enhanced. Several uncontrolled trials with the phosphodiesterase inhibitors enoximone, milrinone and piroximone have concluded that these agents improve exercise capacity and thereby hold promise to enhance quality of life. Large scale controlled trials currently in progress will determine the ultimate efficacy, as well as safety, of these agents. Results to date with several orally active beta-adrenoceptor agonists suggest that their efficacy may be limited by the induction of ventricular arrhythmias.

Animals↗
PubMed1987

Physiologic versus pathologic hypertrophy and the pressure-overloaded myocardium.

The myocardium consists of myocytes and capillaries embedded in a connective tissue matrix. Myocardial mass, which is predominantly a function of myocyte size, is determined by systolic tension; when systolic pressure is gradually elevated above the normal range, mass will increase. The hypertrophic process is a continuum consisting of subtle transitions that take place within the muscular, collagenous, and vascular compartments; these transitions, however, need not be temporarily concordant. We would identify three phases to the hypertrophic process. First, there is an evolutionary phase, whereby the structural and biochemical remodeling of the various compartments of the myocardium is in transition, with each compartment having its own rate of adjustment. During this evolutionary phase, myocardial contractility, as reflected by stress-length and stress-velocity relations, may or may not be normal, but ventricular pump function and O2 delivery are preserved. Second, there is a physiologic phase during which the structural and biochemical remodeling of the compartments reaches a coordinated balance. The myocardial stress-length relation and ventricular function are each normal, but rate-dependent indices of contractility may be abnormal. During the physiologic phase of hypertrophy, the remodeled myocardium will revert to normal when the abnormal loading condition is removed. Finally, there is a pathologic phase. In this phase, compartment remodeling is no longer balanced (e.g., the ratio of structural versus maintenance proteins), and length and rate-dependent indices of myocardial contractility are depressed. Ventricular pump function is also abnormal in the pathologic phase; consequently. O2 delivery to the tissues is impaired. This imbalance in O2 demand and supply may be apparent at rest in more advanced expressions of disease or may appear during the physiologic stress of exercise in less severe disease. In the latter case, the patient's aerobic capacity is reduced to the extent that it can be used to grade the severity of heart failure and to predict the cardiac reserve. During the pathologic phase of hypertrophy, the structural and biochemical remodeling of the myocardium may be irreversible, although this may not be the case for each compartment. Finally, it is important to distinguish cardiac (or myocardial) failure from the clinical syndrome of congestive heart failure. The latter arises from congested organs and hypoperfused tissues; its clinical manifestations are dependent on the activation of the adrenergic nervous and renin-angiotensin-aldosterone systems and the presence of a salt-avid kidney. Congestive heart failure is a late clinical feature of chronic pressure overload and pathologic hypertrophy.

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

Myocardial hypertrophy in Macaca fascicularis. Structural remodeling of the collagen matrix.

The collagen skeleton in the myocardium of 37 non-human primates (Macaca fascicularis) was studied by scanning electron microscopy. Twenty-one hypertensive animals had "pressure-overload" myocardial hypertrophy of 4 to 80 weeks duration induced by unilateral perinephric cellophane insertion and 16 were normotensive controls. The purpose of the study was to examine possible remodeling of the collagen matrix of the hypertrophied pressure overloaded M. fascicularis myocardium. An extensive collagen matrix was demonstrated in nonoperated macaques, consisting of a weave which sequestered groups of myocytes and which was joined to the epimysium by long collagen tendons, and of numerous intermyocyte and myocyte to capillary struts. In addition, strands of collagen were seen crossing interfascicular planes. This collagen skeleton was studied at three periods of perinephritis-induced hypertension with hypertrophy: at 4 weeks (evolutionary); at 32 weeks with mild to moderate hypertension (early compensatory); and at 80 weeks with moderately severe hypertension (late compensatory). These sequential studies revealed that the matrix was remodeled. At 4 weeks there was slight thickening and increase in density of the weave. At 32 weeks, in addition to changes in the weave, the collagen strands became thick and pillar-like and the tendons increased in numbers and thickness, and at 80 weeks some myocytes became encased in collagen. The geometrical arrangement of the normal collagen matrix of the myocardium is similar to series and parallel elastic elements with respect to myocytes, and, accordingly, it may be responsible for the mechanical properties of the myocardium during diastole and systole. The structural alterations in the collagen skeleton which we observed in hypertrophy may play a significant role in deleteriously affecting ventricular function of the pressure-overloaded myocardium.

Animals↗
PubMed1987

Determination of aerobic capacity and the severity of chronic cardiac and circulatory failure.

The noninvasive determination of maximal oxygen uptake or VO2max, defined as a plateau in VO2 during incremental treadmill exercise, is an objective, reproducible, and negotiable measure of the severity of chronic cardiac or circulatory failure. Moreover, this noninvasive variable predicts the exercise cardiac output response and thereby the cardiac reserve. The lactate or anaerobic threshold has been validated in these patients from the response of mixed venous lactate to incremental exercise and has been shown to be another objective measure of the severity of chronic cardiac or circulatory failure. The anaerobic threshold can be reliably assessed from the response in breath-by-breath respiratory gas exchange by the use of multiple criteria, several of which can be monitored during the exercise test itself and the remainder of which can be measured during the recovery period. We find the breath-by-breath monitoring of respiratory gas exchange and air flow to provide the best means of assessing the anaerobic threshold and for identifying the plateau in VO2, or VO2max, in response to incremental treadmill exercise.

Aerobiosis↗
PubMed1986

Enoximone (MDL 17,043) for stable, chronic heart failure secondary to ischemic or idiopathic cardiomyopathy.

To examine the efficacy and safety of enoximone for treatment of patients with chronic, clinically stable cardiac failure secondary to ischemic or myopathic heart disease, 31 patients were enrolled into an early phase II trial. The hemodynamic response to intravenous and oral enoximone was assessed and compared with the response to dobutamine therapy (5 to 10 micrograms/kg/min). Maximal O2 uptake, an objective measure of effort tolerance, was serially monitored. Intravenous (1 to 2 mg/kg) and oral (1 to 2 mg/kg) enoximone improved (p less than 0.05) cardiac index while reducing right atrial and wedge pressures to a greater extent than dobutamine. The salutary hemodynamic response to oral enoximone was sustained for 6 to 8 hours and was not associated with subacute drug tolerance. Maximal O2 uptake was increased (p less than 0.05) at 2, 4, 8, 12, 24 and 52 weeks of oral enoximone therapy (1.4 +/- 0.5 mg/kg every 8 hours) while radionuclide ejection fraction at 65 weeks increased (p less than 0.05) from baseline (39 +/- 16% vs 30 +/- 9%). Nine patients, 8 of whom were in functional class III or IV on enrollment, died after a mean of 18 weeks: 4 from cardiac failure and 5 suddenly. Two patients had adverse gastrointestinal effects. Oral enoximone (1 to 2 mg/kg every 8 hours) appears to be useful in the short- and long-term management of clinically stable, chronic cardiac failure. Controlled phase III trials are warranted.

Administration, Oral↗
PubMed1986

Effects of new inotropic agents on exercise performance.

Symptoms of dyspnea and fatigue limit effort tolerance in patients with chronic cardiac failure. These symptoms may be consequent to an abnormal cardiocirculatory response to the increased O2 demand that accompanies exercise as manifested by: reduced ability to augment cardiac output in response to increased left ventricular filling pressure, inadequate vasodilatory response in exercising limbs, the onset of lactate production by muscle at relatively low levels of work, and increased work of breathing that accompanies pulmonary venous hypertension and abnormal compliance of the lung secondary to left ventricular dysfunction. The clinical experience with new positive inotropic agents in the long-term treatment of patients with chronic cardiac failure is accumulating rapidly. Attention has focused on the ability of these agents to improve exercise performance, particularly their ability to increase the aerobic capacity. The experience to date suggest that beta-adrenergic receptor agonists offer little advantage in this regard while causing ventricular arrhythmias. On the other hand, the phosphodiesterase inhibitors, MDL 17,043 and MDL 19,205, and the bipyridine derivatives, amrinone and milrinone, may improve exercise performance in many patients and exert a sustained effect during long-term therapy. Placebo-controlled, randomized trials will need to be performed, however, to determine the ultimate efficacy and safety of these agents. The most meaningful results for analysis will be obtained when objective parameters of exercise performance, such as aerobic capacity and anaerobic threshold, are monitored that are free of patient or physician bias.

Adrenergic beta-Agonists↗
PubMed1986

Cardio-pulmonary exercise testing in the evaluation of mitral and aortic valve incompetence.

Cardio-pulmonary exercise (CPX) testing can be used to discern the functional integrity of the right and left heart and pulmonary circulation in patients with chronic mitral or aortic valvular incompetence. The noninvasive determination of VO2 max and anaerobic threshold in these patients serves to assess the severity of chronic circulatory failure and to predict the maximum exercise cardiac output (or cardiac reserve). Invasive monitoring of right heart pressures and left ventricular filling (wedge) pressure identifies abnormalities in ventricular function and the pulmonary circulation that may not be otherwise apparent. Noninvasive and invasive CPX testing is therefore a valuable tool which can also be applied to the serial evaluation of these patients. CPX offers several advantages over traditional indices of ventricular function (e.g., resting cardiac output, filling pressure and ejection fraction) in that it objectively identifies the patients functional status, the heart's pumping reserve, and the integrity of the cardio-pulmonary unit. The utility of CPX, however, in assessing an early and subtle decline in left ventricular function and its ability to predict the appropriate timing for valve replacement in chronic mitral or aortic valvular incompetence remains to be elucidated.

Adult↗
PubMed1985

Pathophysiology of cardiac failure.

The pathophysiologic cycle of heart failure is initiated by myocardial failure that accompanies a reduction in myocardial contractility secondary to ischemic or myopathic heart disease. Reduction in cardiac output and oxygen delivery to the tissues is followed by vasoconstriction that raises systemic vascular resistance to preserve systemic arterial pressure while maintaining regional O2 availability. As a consequence, however, impedance to left ventricular ejection is increased, creating an additional hemodynamic burden for the failing heart. A vicious cycle ensues. Hemodynamic features of acute cardiac failure include decreases in cardiac output and mixed venous O2 saturation, together with increases in left ventricular filling pressure and systemic resistance. If hypotension is present with failure, there is a markedly decreased cardiac output or an inappropriate increase in systemic resistance. If acidosis is also present with hypotension and failure, cardiac output is severely decreased and lactic acid is increased. A major objective of medical therapy in acute heart failure is to enhance ventricular emptying, thereby increasing cardiac output and O2 delivery while decreasing left ventricular filling pressure, pulmonary venous pressure and vascular resistance. Potent intravenous drugs that have a positive inotropic effect on the myocardium, including amrinone and dobutamine, have been shown to increase ventricular emptying in patients with acute heart failure. Intravenous amrinone improves pump performance without adversely raising myocardial O2 consumption, thereby enhancing myocardial efficiency. These drugs also promote a degree of vasodilation through both direct and secondary effects on the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyridines↗
PubMed1985

Cardiopulmonary exercise testing for evaluation of chronic cardiac failure.

The heart, lungs and hemoglobin form the body's gas transport system, which links the atmosphere and its supply of O2 with tissue, while simultaneously providing for the elimination of the metabolic end-product, CO2, into the atmosphere. The transport of these respiratory gases must be in accordance with metabolic need. This is particularly evident during the physiologic stress of isotonic exercise, when the O2 requirements and CO2 production of skeletal muscle are increased. The monitoring of these respiratory gases during exercise, referred to as cardiopulmonary exercise testing (CAR-PET), can be used to assess heart and lung function in patients with cardiovascular or lung disease or both. Chronic cardiac failure (CCF) may be defined in physiologic terms as that circumstance in which the heart fails to provide tissue with O2 at a rate commensurate with aerobic requirements. In patients with CCF, CAR-PET represents a noninvasive means to determine aerobic capacity (that is, maximal O2 uptake) and anaerobic threshold during incremental treadmill exercise. It can also provide an objective measure of the severity of failure, the functional status of the patient and the heart's pump reserve. By using additional measurements of ventilation, arterial O2 saturation and, in selected cases, hemodynamic monitoring, the nature and severity of cardiovascular and pulmonary disease may be evaluated.

Anaerobiosis↗
PubMed1985

Milrinone in the treatment of chronic cardiac failure: a controlled trial.

This study examines the acute hemodynamic response to intravenous and oral milrinone in 12 patients with moderate to moderately severe heart failure. The patients received milrinone or placebo at random in an 8-week double-blind trial. Dosing level and schedule were determined by the hemodynamic results. Acute and chronic plasma samples for milrinone concentration were drawn from patients throughout the study. Milrinone was administered intravenously in successive doses of 25, 50, and 75 micrograms/kg. This resulted in a 16.5%, 12.5%, and 28.4% peak increase in cardiac index, with a concomitant 24%, 29%, and 38% decrease in pulmonary capillary wedge pressure. There were no significant relationships between any of the mean maximal hemodynamic values and milrinone plasma concentration. Six patients received milrinone and six patients received placebo; only five patients completed the blinded phase. There was no significant difference between the groups in exercise capacity, but the conditions of five of the six patients who received placebo deteriorated. In two of the patients who received milrinone the aerobic capacity improved greater than 2 cc/min/kg over baseline, and an additional two patients reported a marked subjective improvement. The results of this study indicate that oral milrinone in the management of patients with chronic cardiac failure would justify larger controlled studies.

Administration, Oral↗
PubMed1985

Lactate production during maximal and submaximal exercise in patients with chronic heart failure.

In patients with chronic heart failure whose cardiac output response to exercise is impaired, determination of anaerobic threshold may provide a useful and objective approach to grade the severity of heart failure. In such patients performing upright treadmill exercise to exhaustion, this study examined the reproducibility of the response of cardiac output and mixed venous lactate concentration when the exercise test was repeated the same or next day, the nature of this response after rest and exercise cardiac output levels were augmented by the cardiotonic agent amrinone and the response of lactate during symptom-limited submaximal exercise performed at either aerobic or anaerobic levels of work for each patient. Findings were: 1) the response of cardiac output and mixed venous lactate was reproducible (p less than 0.05) when assessed either the same or the next day; 2) when exercise cardiac output was increased (p less than 0.05) by oral amrinone therapy, the increase in lactate was delayed (p less than 0.05) to higher levels of muscular work and this was not true when cardiac output was unchanged; and 3) only submaximal anaerobic exercise was symptom limited and associated with an increase in lactate concentration. Thus, the lactate response and anaerobic threshold determination should prove useful to assess the severity of chronic stable heart failure and its response to pharmacologic intervention. The submaximal anaerobic exercise test may provide additional insights into the effort intolerance these patients experience.

Adolescent↗
PubMed1985

Evidence and quantitation of left ventricular systolic resistance.

Instantaneous left ventricular pressure is a function of both volume (elastic behavior) and flow (resistive behavior). However, a quantitative description of ventricular resistance and its effects on ventricular performance remains to be elucidated. Accordingly, ventricular resistive behavior was studied in six isolated canine hearts. Our experimental findings indicate 1) for a specified time (ts), volume (Vs), and contractile state (CS), the ventricular pressure-flow relation was linear (r = 0.96-0.99) within the range of flows examined (0-250 ml/s); 2) ventricular resistance increased with increments in ts, Vs, and CS, whereas the zero-pressure flow intercept was invariant; 3) resistance could be uniquely quantified as a linear function of isovolumetric pressure. In six experiments, the slope of this relationship ranged from 1.1 to 2.1 X 10(-3) s/ml while the intercept did not differ from zero; and 4) end-systolic elastance, estimated from end-systolic pressure-volume data, was in substantial error under the conditions of finite (greater than 35 ml/s) end-systolic flows. Finally, the results from a computer simulation of the coupled ventricular-arterial system indicated that ventricular resistance primarily affects the pulsatile nature of aortic flow. The unique isovolumetric pressure-resistance relation suggests that the rate-limiting properties of the contractile process may be causally related to the observed ventricular resistive behavior.

Animals↗
PubMed1985

The pressure-flow response of the pulmonary circulation in patients with heart failure and pulmonary vascular disease.

Although it is well known that the pulmonary circulation is altered in patients with pulmonary arterial or venous hypertension, the resultant hemodynamic behavior has not been systematically studied. We undertook to do so in a group of patients with pulmonary hypertension of diverse etiology. We measured pulmonary arterial (PAP) and occlusive wedge pressures and cardiac output at rest (i.e., standing) and during progressive upright treadmill exercise in 51 patients. Forty-two had chronic, stable, cardiac failure secondary to ischemic, myopathic or valvular heart disease and were grouped according to whether their mean PAP was less than (normotensive) or greater than (hypertensive) 19 mm Hg, and nine had pulmonary vascular disease of diverse etiology and were considered separately. In the majority of patients, we found that irrespective of whether the hypertension was arterial or venous in origin or etiology: the mean PAP-flow relationship was linear; pulmonary capillary wedge pressure was greater than or equal to the average closure pressure of the pulmonary vascular bed and could therefore be used as the downstream pressure in calculating pulmonary vascular resistance; and pulmonary vascular resistance declined with exercise. Notable exceptions to the third observation were patients with valvular heart disease or a resting pulmonary vascular resistance greater than 800 dyne-sec-cm-5.

Blood Pressure↗