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Biomedical subjects

M F Petrini

Publications and source records attributed to M F Petrini.

18 recordsLinked to original sources

Cromakalim effects of acetylcholine-induced changes in cytosolic calcium and tension in swine trachealis.

The effects of cromakalim, an ATP-sensitive K+ channel activator, on changes in cytosolic calcium concentration [( Ca++]i) and tension induced by acetylcholine (ACh; 0.1-10 microM) were examined in swine tracheal smooth muscle. Cromakalim (10 microM) hyperpolarized muscle cells by approximately 18 mV from -58 mV (resting membrane potential) to -76 mV. Cromakalim relaxed muscle contractions evoked by ACh at a concentration of 0.1 microM, but not at higher concentrations. Measurement of [Ca++]i using Fura-2 demonstrated that except at 0.1 microM ACh, cromakalim did not alter peak increases in [Ca++]i. At 0.1 microM ACh, the peak transient was decreased, but not eliminated. Cromakalim reduced steady-state increases in [Ca++]i at ACh less than or equal to 1 microM, but not 10 microM ACh. Tension was similarly affected. These data suggest that ACh-induced increases in steady-state [Ca++]i and tension are inhibited by cromakalim-induced hyperpolarization. The initial ACh-induced transient increase in [Ca++]i is not greatly altered. Cromakalim did not alter the transient peak tension and [Ca++]i relationship. The relationship between steady-state [Ca++]i/tension (EC50 = 321 nM) obtained for control, cromakalim inhibition and after glibenclamide reversal of cromakalim inhibition falls to the left of the peak transient [Ca++]i/tension relationship (EC50 = 587 nM). Thus, the Ca++ sensitivity of the contractile proteins during steady-state stimulation by ACh was increased from that at rest. We conclude that electromechanical coupling is important in ACh-induced contraction at concentrations less than 1 microM. Pharmacomechanical coupling with little or no sensitivity to changes in potential is important at higher ACh concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Concentration-dependence of acetylcholine-induced changes in calcium and tension in swine trachealis.

Acetylcholine (ACh)-induced increases in intracellular calcium concentration ([Ca++]i) and tension were measured simultaneously in swine tracheal smooth muscle strips loaded with the calcium-sensitive fluorescent dye Fura-2. ACh at concentrations greater than or equal to 3 x 10(-8) M induced concentration-dependent increases in tension which reached a maximum at 10(-4) M. Increases in [Ca++]i occurred at all [ACh] tested (10(-8) to 10(-4) M). After addition of ACh at concentrations greater than 3 x 10(-7) M, [Ca++]i increased rapidly to a concentration dependent-peak then declined to a concentration-independent steady state approximately 250 nM above the resting [Ca++]i of 257 +/- 12 nM. There was a steep relationship (slope factor greater than 3) between the peak tension and the peak [Ca++]i reached at each [ACh]. The rate of decline of [Ca++]i to the steady state at [ACh] greater than 73 x 10(-7) M was well correlated with the peak [Ca++]i reached. We conclude that the peak increase in calcium induced by ACh sets the level of tension to be attained and the rate of decline of the transient increase in [Ca++]i. The steady-state [Ca++]i is sufficient for maintenance of tension.

Acetylcholine

Mechanical ventilation in patients with acute severe asthma.

PURPOSE: Acute respiratory failure necessitating intubation and mechanical ventilation in patients with acute severe asthma is relatively uncommon, and there are few data available regarding positive pressure ventilation in critically ill patients with asthma. We therefore decided to evaluate our experience with the use of mechanical ventilation for acute asthma and to critically review previous reports on this subject. PATIENTS AND METHODS: A retrospective analysis of all medical records of patients who required mechanical ventilation for acute severe asthma was performed for the period of 1980 to 1988. Various clinical parameters were reviewed and examined via Fisher's exact test for association with survival. RESULTS: Twenty-seven patients who underwent ventilation for a total of 32 episodes of mechanical ventilation comprised our study group. The overall mortality was 22%. A total of 76 complications were documented, including six episodes of barotrauma. The mean duration of artificial ventilation was 114 hours for nonsurvivors and 77 hours for survivors (p less than 0.05). CONCLUSION: Although there appears to be a trend toward increased survival after mechanical ventilation for acute asthma, ventilation of critically ill asthmatic patients continues to be a potentially perilous venture associated with significant morbidity and mortality.

Acute Disease

Communication between the PC and laboratory instruments.

In this paper we describe communications between a personal computer and any instrument with a serial port for the purpose of collecting data or controlling equipment and a program for performing this task. From a user-defined file, the software reads the communication parameters: baud rate, data bits, stop bits and parity. The communication protocol is also read: echo, acknowledge and end-of-transmission characters. The software can be used to determine the protocol, to check the integrity of the communications, and can form the basis of a program for more specific applications.

Equipment and Supplies

Effects of drug-induced pulmonary phospholipidosis on lung mechanics in rats.

Chronic administration of amphiphilic drugs to rats induces pulmonary phospholipidosis (P), a disease characterized by accumulation of phospholipids and large foamy macrophages in alveolar spaces. We investigated whether P induced by chlorphentermine (CPH) causes changes in lung volumes and mechanics in this species. Groups of rats were fed CPH (50 mg.kg-1.day-1) for 1, 2, 3, 5, 9, and 14 wk. After each treatment period, lung volumes and mechanics were studied in the anesthetized, paralyzed, supine rat. Partial pressure-volume (PV) curves were developed at 3 and 6 ml above functional residual capacity (FRC; PV3, PV6), followed by maximal [up to total lung capacity (TLC)] PV curves. FRC was determined by saline displacement. Lungs were then fixed for histopathological examination. A subgroup of animals was allowed a recovery period of 6 wk, after the 9 wk of CPH administration. Pair-fed rats served as controls (CTR) at each time point. Lung weight increased in CPH-treated (CPH-T) rats from 1.5 +/- 0.2 (SD) g at week 1 to 5.8 +/- 1.4 g at week 14, reflecting the development of P. TLC, FRC, transpulmonary pressure at FRC, the shape of maximal PV curves, and static expiratory lung compliance computed from maximal PV data points did not change in CPH-T rats. However, partial PV curves of CPH-T lungs (particularly PV3) were shifted downward and to the right of those of CTR at 2, 3, 5, and 9 wk, indicating increased recoil pressure in phospholipidotic lungs at these time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Pulmonary tissue volume and blood flow as functions of body surface area and age.

We measured pulmonary tissue volume (Vt) and capillary blood flow (Qc) by rebreathing acetylene as the soluble gas in 94 male and 82 female patients with normal healthy lungs. We found that the standard deviation of Vt was a function of Vt and that the standard deviation of Qc was a function of Qc; logarithm transforms were used to prevent this. A significant correlation exists between log Vt and body surface area (BSA) and log Vt and vital capacity (VC). For both sets of regressions older subjects (greater than or equal to 40 years of age) exhibited greater variability about the regression line than younger subjects; therefore the 2 age groups of subjects were analyzed separately for tissue volume. We describe regression equations of log Vt vs. BSA or VC for younger male, younger female, older male, and older female patients. The normal limits by sex and age groups are also included. A significant correlation was found between log Qc, BSA, and age. Thus 2 equations, for male and female patients, are used to predict log Qc based on these 2 covariates.

Adolescent

Teaching medical decision analysis: the hepatitis B vaccine.

The process of formal decision analysis is illustrated by using the case of the hepatitis B vaccine in a computer program designed to teach both subjects to medical students. The software presents the medical facts, determines personal risks, allows input of personal values and calculates utilities for the various branches of the decision tree. There are three possible choices: vaccinate; screen first for antibodies against the hepatitis B virus and vaccinate only if negative; and wait (do not vaccinate). The decision with the utility of the highest numerical value is assumed to be the best under the given set of circumstances. Unlike commercial packages, this software contains the information internally and does not require that the user be familiar with either medical decision analysis or with the medical aspects of hepatitis. The program is available for PC's.

Decision Making, Computer-Assisted

A regression analysis program to fit nonseparable equations.

A program to perform a nonlinear best fit for separable and nonseparable equations is described. This software is written in Turbo-Pascal so that it can be run both on CP/M systems or PC-DOS systems; in the latter, graphics can be performed using the Turbo Graphix Toolbox. From initial estimates the regression coefficients as well as the statistics are calculated. Two examples are shown: one of a separable equation describing receptor binding; the second of a nonseparable equation, describing the displacement of labeled agonist by an inhibitor. The only difference in the fit between a separable and a nonseparable equation is that the latter requires iterations for an estimate of the dependent variable every time that new regression coefficients are calculated.

Microcomputers

Distribution of ventilation and perfusion: a teaching model.

Models can be used as teaching tools to study complex phenomena. This model uses simplifications of blood gas subroutines to provide fast execution of the effect of the distribution of ventilation and blood flow in the lung on arterial blood gases. Assumptions are made that introduce only small errors but that avoid the use of iterations which would slow down execution. The use of Turbo-Pascal as the programming language allows for not only speed in development and execution but also portability to a variety of computers including CP/M systems and IBM-PCs.

Carbon Dioxide

Pulmonary function testing: custom programs for manual equipment.

Pulmonary Function Laboratories with manual equipment can expedite calculations and make them more accurate by using a programmable calculator that will compute functions and predictive equations. However, a custom-made set of programs is better than calculator libraries available from the manufacturer. With custom-made programs, calculations remain as the staff is used to receiving them, programs can be stored in the memory and called independently and only those tests used routinely need to be available.

Computers

Effect of acute hypoxia on airway and vascular exchangeable lung water spaces in dogs.

To determine if alveolar hypoxia causes subclinical noncardiogenic pulmonary edema, we measured in 8 dogs the rebreathing pulmonary tissue volume (Vt) and the pulmonary extravascular water volume using the single-pass double-indicator dilution method. After baseline measurements, the dogs were ventilated with the lowest concentration of oxygen that would not cause left ventricular failure (9 to 13% O2). One to 6 h of hypoxia had no effect on Vt, but caused a reversible 38% fall in pulmonary extravascular lung water volume by the indicator method (p less than 0.01). The ratio of the extravascular to vascular volumes estimated from the relative peak heights of the 2 indicator dilution curves did not change with hypoxia, which implies that hypoxia caused a derecruitment of pulmonary blood vessels rather than a real decrease in extra-vascular lung water volume. This conclusion is supported by our rebreathing measurement of the airway exchangeable tissue volume, which is virtually independent of tissue perfusion, and which did not fall during hypoxia. To determine if this alteration in the pulmonary circulation can cause pulmonary edema when the cardiac output is increased, we opened a femoral artery to femoral vein shunt in 9 additional dogs during ventilation with 9 to 13% oxygen. Cardiac output increased over 50% but pulmonary edema developed in only 1 dog, the dog that also had the highest mean pulmonary artery pressure of the group (35 mmHg versus group mean of 26 mmHg during hypoxia). We conclude that 1 to 6 h of alveolar hypoxia in dogs consistently decreases the volume of perfused lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Interaction of series and parallel dead space in the lung.

The volume of ventilation delivered to unperfused zones of the respiratory system (respiratory dead space) can be divided into the volume occupied by the conducting airways (series dead space) and the volume of unperfused alveolar space (parallel dead space). The effect of the interaction between these two components of dead space on steady-state gas exchange was first evaluated with a mathematical model. The presence of both parallel and series dead space was predicted to underestimate the dead space measured by the inert gas elimination technique (VDIG). This error was largest when the volumes of parallel and series dead space were equal. The size of the parallel dead space in the model could be calculated from measurements of VDIG made before and after adding a series dead space of known volume. In 16 anesthetized dogs series and parallel dead space were quantitated using the multiple inert gas elimination technique with addition of known volumes of series dead space. In five normal dogs, the series and parallel dead space averaged 20% and 13% of the tidal volume, respectively. In eleven dogs with the left pulmonary artery occluded the parallel dead space averaged 26%. This method represents the first means of quantitating these two anatomically separate components of wasted ventilation.

Animals

A computerized timing algorithm for determination of pulmonary tissue volume.

We developed a computerized method to measure pulmonary tissue volume (Vt) and capillary blood flow (Qc) that requires only a single interface for measurement of a soluble and an insoluble gas. The method uses a timing algorithm that replaces either a marker gas (C18O) or a volume signal. Gas concentrations are stored in digitized form. The data analysis consists of three parts: 1) initial and end-tidal samples found by using minima and maxima; 2) a timing algorithm derived from the end-tidal dead space method (ETDS, J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 782-795, 1978); and 3) calculations of Vt and Qc, also by the ETDS method. Both the timing and Vt and Qc agree well with the hand-calculated values, but the coefficient of variation of Vt is slightly improved (6 vs. 7% manually). We conclude that our computerized method is equivalent to the manual ETDS method, but it is faster and more accurate; in addition, it has the advantage of requiring only one interface without the use of expensive gases.

Capillaries

Uneven gas mixing during rebreathing assessed by simultaneously measuring dead space.

To evaluate the rate of gas mixing in human lungs during rebreathing maneuvers used to measure pulmonary tissue volume (Vt) and pulmonary capillary blood flow (Qc), we devised a method to determine the dead space during rebreathing (VRD). Required measurements are initial concentration of a foreign inert insoluble gas in the rebreathing bag, first mixed expired concentration, equilibrated concentration, volume inspired, and volume of the first expired breath. In subjects breathing rapidly at 30 breaths/min with inspired volumes in excess of 2 liters, VRD had values three or more times greater than the predicted anatomical dead space (VD). Breath holding after the first inspiration progressively diminished VRD so that after 10-15 s, it approximately equaled predicted VD. VRD measured with helium was smaller than VRD measured with sulfur hexafluoride. The reported degree of uneven ventilation from gravitational forces in normal humans can account for only about one-third of the difference between VRD and VD. These findings support the concept that mixing by diffusion between peripheral parallel airways is incomplete at normal breathing rates in humans and can result in errors as high as 25% in Vt and Qc.

Humans

Pulmonary tissue volume in dogs during pulmonary edema.

Pulmonary tissue volume (Vt) and pulmonary capillary blood flow (Qc) were measured in anesthetized dogs by analyzing end-expiratory concentrations of dimethyl ether (DME), acetylene (C2H2), and sulfur hexafluoride during a 30-s rebreathing maneuver. Vt was compared to the postmortem lung weight of control dogs and dogs with hemodynamic and nonhemodynamic (alloxan) pulmonary edema. Qc was compared to the cardiac output measured by dye dilution. A 100-ml increase in alveolar volume (VA) in the range of 1-2 liters resulted in a 9 +/- 3 ml increase in Vt. Vt measured at a VA of 1.9 liters measures 114 +/- 18% of the postmortem lung weight in 20 control dogs and in 6 dogs with moderate edema (lung weight < 250% of predicted). Vt measured only 53 +/- 14% of the lung weight in 11 dogs with more severe edema. DME and C2H2 gave the smae mean values of Vt, but the reproducibility of a series of 3-7 measurements was greater with DME (coefficient of variation was 5% with DME and 8% C2H2). Qc measured 96 +/ 15% of the cardiac output during the rebreathing maneuver, but the maneuver caused a 4-40% fall in the cardiac output. These data show that Vt determined by rebreathing DME is between 86% and 135% of the lung weight in dogs with pulmonary edema until the lung weight is greater than 250% of the predicted value.

Animals

A Gaussian method to improve work-of-breathing calculations.

The work of breathing is a calculated index of pulmonary function in ventilated patients that may be useful in deciding when to wean and when to extubate. However, the accuracy of the calculated work of breathing of the patient (WOBp) can suffer from artifacts introduced by coughing, swallowing, and other non-breathing maneuvers. The WOBp in this case will include not only the usual work of inspiration, but also the work of performing these non-breathing maneuvers. The authors developed a method to objectively eliminate the calculated work of these movements from the work of breathing, based on fitting to a Gaussian curve the variable P, which is obtained from the difference between the esophageal pressure change and the airway pressure change during each breath. In spontaneously breathing adults the normal breaths fit the Gaussian curve, while breaths that contain non-breathing maneuvers do not. In this Gaussian breath-elimination method (GM), breaths that are two standard deviations from that mean obtained by the fit are eliminated. For normally breathing control adult subjects, GM had little effect on WOBp, reducing it from 0.49 to 0.47 J/L (n = 8), while there was a 40% reduction in the coefficient of variation. Non-breathing maneuvers were simulated by coughing, which increased WOBp to 0.88 (n = 6); with the GM correction, WOBp was 0.50 J/L, a value not significantly different from that of normal breathing. Occlusion also increased WOBp to 0.60 J/L, but GM-corrected WOBp was 0.51 J/L, a normal value. As predicted, doubling the respiratory rate did not change the WOBp before or after the GM correction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult