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Biomedical subjects

A P Fishman

Publications and source records attributed to A P Fishman.

At least 73 records · Page 4Linked to original sources
PubMed1983

Transcapillary movement of cationized ferritin in the isolated perfused rat lung.

We have identified the ultrastructural localization of anionic sites on the luminal surface of the pulmonary microvascular endothelium by perfusing isolated rat lungs with polycationized ferritin (CF). The ligand decorated preferentially the luminal plasmalemma, coated pits, intercellular clefts, and about half of the plasmalemmal vesicles open to the lumen. Decoration of the plasmalemma was not uniform particularly in the nonvesiculated regions of the endothelium. Perfusion of the lung with high salt solution completely abolished binding of CF to the plasmalemma, coated pits, and intercellular clefts but did not significantly decrease binding of CF to the diaphragm of the luminal plasmalemmal vesicles. This indicates the presence of highly charged anionic sites on these regions of the endothelium. CF was taken up by vesicles and discharged on the capillary membrane. Perfusion of the lungs at 4 degrees C completely abolished transport of CF across the endothelium but did not modify the pattern of binding to the luminal endothelial surface. These findings are regarded as evidence for a functional subspecialization of plasmalemmal vesicles in the pulmonary microvascular endothelium.

Animals↗
PubMed1982

Hypercapnic ventilation during exercise: effects of exercise methods and inhalation techniques.

The effect of exercise on the ventilatory response to inhaled CO2 is uncertain because previous studies using different techniques have come to different conclusions. We undertook to resolve this problem by using multiple techniques and confining our study to a uniform level of mild exercise (VO2 = 10 ml/kg min). One group of subjects exercised on a treadmill and was tested with both rebreathing and steady-state CO2 methods. A second group exercised on a bicycle while using the rebreathing method. We found that the ventilatory response to CO2 was unchanged by mild exercise, regardless of the method used for CO2 inhalation or the technique used for exercise. These results indicate that under controlled conditions mild exercise does not produce any change in ventilatory sensitivity to CO2.

Adult↗
PubMed1982

Endothelium: a distributed organ of diverse capabilities.

A historical survey of the growth of ideas about the circulation of the blood and about the endothelium is provided as a background to the specialized papers that follow. Over the years, in the course of clarifying its structure and function, the status of the endothelium has gradually evolved from that of an inert semipermeable barrier that determines the exchange of substances between blood vessels and tissue spaces to that of a specialized organ that is unusual in its dispersion throughout the body as the lining of blood vessels. This unique arrangement has enabled it to play different roles in different parts of the vascular tree and in different organs and to manifest distinctive responses to injury according to its structure and location. As a corollary, because its responsiveness is strongly influenced by its ambience and neighboring tissues, it seems inevitable that extrapolations from function in vitro to function in vivo require considerable prudence.

Arteries↗
PubMed1982

Origin, distribution, and blood flow of bronchial circulation in anesthetized sheep.

This anatomical-physiological study was undertaken to determine the suitability of the sheep for studies of the bronchial circulation. We designated the terminal portion of the bronchoesophageal artery, which runs to the trachea at the carina, as the "carinal" artery. Postmortem injections of india ink (9 sheep) and Batson's solution (4 sheep) into the carinal artery showed that the carinal artery supplied the bronchi of all lobes except the right apical lobe; the mass of the lung containing bronchi perfused represented 88 +/- 1% of total lung mass. Communications were also found between branches of the carinal artery and branches of the systemic arteries supplying the visceral pleura. In three of six sheep, the carinal artery wedge pressure measured in vivo indicated that patent collaterals were present, but that their incidence is variable. In additional postmortem casts of the aorta made in four sheep after ligation of the carinal artery, the bronchial microcirculation was not entered by the perfusing medium. These data indicate that the collaterals do not contribute significantly to bronchial blood flow and that the carinal artery is the major source of bronchial blood flow in the sheep. In 19 sheep, carinal artery flow, measured electromagnetically, was 0.46 +2- 0.09 ml . min-1 . kg body wt-1. Bronchial blood flow normalized for the weight of the lobes in which bronchi perfused by the carinal artery were located was 3.97 +/- 0.48 ml . min-1 . 100 g lung-1 (n = 11); carinal artery blood flow was 0.39 +/- 0.03% of cardiac output (n = 5). During the 90 min of observation, at normal aortic blood pressure (103 +/- 3.4 Torr), carinal artery blood flow was stable. In conclusion, determination of carinal artery blood flow affords a reliable approach to the bronchial circulation in the sheep.

Anesthesia↗
PubMed1982

Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure.

Muscular work requires the integration of cardiopulmonary mechanisms for gas exchange and O2 delivery. In patients with chronic cardiac failure, the response of these mechanisms may be impaired, and the pattern of O2 utilization (VO2) and gas exchange during exercise would thus provide an objective assessment of the severity of heart failure. Accordingly, rates of air flow, O2 uptake, CO2 elimination and minute ventilation were determined during progressive treadmill exercise in 62 patients with stable heart failure. Exercise cardiac output, systemic O2 extraction and lactate production were measured directly in 40 patients with heart failure of varying severity. As the severity of heart failure increased from class A to D, there was a progressive decrease in exercise capacity (from 1157 +/- 154 to 373 +/- 157 seconds) and maximum VO2 (23 +/- 3.2 to 8.4 +/- 1.5 ml/min/kg). These decreases corresponded with the reduced maximum cardiac output and stroke volume during exercise. The appearance of anaerobic metabolism (580 +/- 17 to 157 +/- 7 seconds of exercise) and the corresponding anaerobic threshold (17 +/- 0.34 to 7.1 +/- 1.5 ml/min/kg), determined noninvasively, were reproducible and correlated with the rise in mixed venous lactate concentration. No apparent untoward effects were experienced during or after the progressive exercise test. We conclude that the measurement of respiratory gas exchange and air flow during exercise is an objective, reproducible and safe noninvasive method for characterizing cardiac reserve and functional status in patients with chronic cardiac failure.

Adult↗
PubMed1982

Reflex effects of aerosolized histamine on phrenic nerve activity.

Studies were conducted in anesthetized, paralyzed dogs on the effect of aerosolized histamine on phrenic nerve activity. The paralyzed dogs were ventilated in phase with their recorded phrenic nerve activity at a constant inspiratory flow-rate, using a cycle-triggered ventilator. Phrenic nerve activity was measured before and during administration of aerosolized histamine while the inspiratory flow-rate and arterial blood gases were kept constant. In addition, before and after histamine, phrenic nerve activity was recorded for single bursts during which the ventilator was switched off. The effects of histamine on respiratory resistance were prevented by prior administration of isoproterenol and atropine. Although no changes occurred in respiratory resistance, histamine increased the instantaneous magnitude of phrenic nerve activity. The effect was evident early in the inspiratory period and was found even when the lungs were not inflated. Inflation of the lungs excited phrenic nerve activity; this effect increased after histamine. All of these actions of histamine were abolished by vagotomy. We conclude that histamine increased phrenic nerve activity during inspiration by a vagal reflex.

Aerosols↗
PubMed1982

Muscle fiber orientation and connective tissue content in the hypertrophied human heart.

To elucidate the structural correlates of cardiac failure in myocardial tissue, muscle fiber alignment and connective tissue volume fraction were measured at multiple sites in the left ventricular free wall and in the interventricular septum of 14 human hearts. Group 1 (five hearts; 280 +/- 20 gm.) had no evidence of cardiac disease, group 2 (five hearts; 380 +/- 30 gm.) had a history of systemic hypertension without clinical heart failure, and group 3 (four hearts;; 590 +/- 40 gm.) had both left ventricular overload and congestive failure. Fiber orientations were determined by measuring fiber angle relative to the circumferential direction (helix angle). The fraction of the myocardial volume occupied by connective tissue was determined by point counting. Our results indicate a smooth transition of helix angle from epi- to endocardial surface in the normal left ventricular free wall with nearly 55 per cent of the wall occupied by circumferentially oriented fibers near the cardiac equator (latitude of largest ventricular diameter); morphologically, the interventricular septum was nearly identical with the free wall. Fiber alignment was maintained in all three groups as was the fraction of wall occupied by circumferential fibers. Connective tissue volume fraction was, however, significantly increased (p less than 0.02) in hypertrophied hearts (groups 2 and 3) as compared with normal hearts, and at two of six sites in clinically failed hearts as compared with hypertrophied but functionally compensated hearts. Thus, muscle fiber orientation is not altered in the hypertrophied pressure-overloaded left ventricle, whereas connective tissue content is increased with the increase being greatest in the failing heart.

Adult↗
PubMed1981

Vasodilator and inotropic agents in treatment of chronic cardiac failure: clinical experience and response in exercise performance.

The sensations of breathlessness and fatigue limit the capacity of patients with chronic congestive cardiac failure (CHF) to participate in physical activities. As a result, patients with CHF gauge quality of life in terms of symptom-free activities they can undertake. Physicians attempt to alleviate these limiting symptoms and increase the exercise capacity of patients with CHF by therapeutic interventions. In recent years a variety of systemic vasodilators and inotropic agents have been introduced to aid digitalis and diuretics in improving cardiac performance in patients with CHF. Although the pumping function of the heart is enhanced at rest, it remains to be determined whether exercise tolerance is also improved. In this paper we review our clinical experience with a number of systemic vasodilators and positive inotropic agents, focusing particular attention on their influence on exercise performance in patients with CHF. This experience includes (1) 28-week double-blind study of hydralazine vs placebo in 19 patients with CHF, (2) 52-week double-blind crossover study of trimazosin (alpha 1 blockade) vs placebo in 27 patients with CHF of varying severity, and (3) open study of amrinone (positive inotropic agent) in 12 patients with CHF.

Aerobiosis↗
PubMed1981

Contractile mechanics and interaction of the right and left ventricles.

The heart and lungs, together with hemoglobin, provide for the transport of oxygen from the atmosphere to the metabolizing tissue. The oxygenation of blood and the circulation of oxygenated blood are precisely synchronized so that the heart and lungs constitute an integrated cardiopulmonary unit. The functional integration of the heart and lungs is fostered by their anatomic arrangement and mechanical interaction. The cardiopulmonary unit consists of the right and left ventricles (two in-series pumps composed of cardiac muscle), which are mechanically coupled by the lungs. The factors that control cardiac muscle shortening (fiber length, afterload and myocardial contractile state) also regulate the pumping behavior of each ventricle. Because the ventricles are aligned in series a perturbation in the mechanical events of one ventricle will influence the behavior of the other ventricle. The interventricular septum and pericardium further promote the mechanical interplay between ventricles. Intrathoracic pressure (the pressure that surrounds the cardiopulmonary unit) creates an additional interaction between the ventricles as well as the heart and lungs.

Acute Disease↗
PubMed1981

Role of carotid chemoreflex in respiratory acclimatization to hypoxemia in goat and sheep.

The role of the carotid body chemoreflex in the ventilatory acclimatization to chronic hypoxia was studied in the unanesthetized goat and sheep. The time-cours of changes in ventilation, PCO2, pH and PO2 of arterial blood and cisternal fluid (CF) were measured before and following exposure to a simulated altitude of 3660-5000 m, with and without intact carotid sinus nerves. At sea level, after section of carotid sinus nerves most animals hypoventilated chronically, and developed mild arterial hypoxemia and hypercapnia. Upon exposure to acute hypoxia, all of the intact animals hyperventilated and CF pH increased from 7.310 to 7.380 whereas after chemodenervation, the increase in ventilation was small and delayed, and CF pH decreased from 7.285 to 7.143. During exposure of the intact animals to chronic hypoxia, hyperventilation accompanied by decreases in arterial and CF P CO2 reached its peak in two days; these changes partially subsided during the next few days. Partial compensation of respiratory alkalosis occurred during the first day. In contrast, several chemodenervated animals died during chronic hypoxia; the survivors showed either a small decrease or an increase in Pa CO2. Thus, an intact peripheral chemoreflex drive during hypoxia is necessary for ventilatory acclimatization which raises the arterial and presumably tissue PO2 in spite of alkalosis. The new proposal is that a central tissue metabolic acidosis resulting from a direct effect of acute hypoxia is partly compensated as hypoxia is prolonged. This central compensation decreases ventilatory drive and hence opposes the ventilatory acclimatization during chronic hypoxia initiated by the peripheral chemoreflexes.

Acclimatization↗
PubMed1981

Hail and farewell.

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Periodicals as Topic↗
PubMed1981

Augmentation of phrenic neural activity by increased rates of lung inflation.

Studies were conducted in anesthetized paralyzed dogs using a cycle-triggered constant-flow ventilator, which ventilated the animal in phase with the recorded phrenic neural activity. Intermittently tests were performed in which the animal was ventilated with a different airflow for a single breath. Increased airflows, within the range generated during spontaneous breathing, caused an increased rate of rise of the moving average phrenic neurogram and a shortening of the duration of the nerve burst. The magnitude of the increase in the rate of rise of the neurogram was related to the level of inspiratory airflow. Tests with brief pulses of airflow showed that an increase in the rate of rise of the phrenic neurogram could be produced without inflating the lung above the resting tidal volume of the animal. Similar results were obtained with negative-pressure ventilation and the effects were abolished by vagotomy. This vagally mediated augmentation of phrenic neural output may accelerate the inspiratory volume change in the lung during spontaneous breathing at hyperpneic levels.

Animals↗
PubMed1981

Hail and farewell.

Explore the source record for details and available documents.

Periodicals as Topic↗