Biomedical subjects

M B Maron

Publications and source records attributed to M B Maron.

At least 37 records · Page 2Linked to original sources

PubMed1993

Effect of peak inspiratory pressure on the filtration coefficient in the isolated perfused rat lung.

Positive inspiratory pressure- (PIP) ventilated, isolated rat lungs become edematous when perfused at rates approximately the normal cardiac output. The study was conducted to test the hypothesis that high peak inspiratory pressures contribute to the edema development. Five isolated lungs were perfused at a rate of 24.4 +/- 2.2 ml.min-1.100 g body wt-1 with 40% whole blood (diluted with saline containing 4.0 g/100 ml bovine serum albumin) and ventilated with peak pressures ranging from 0 to 20 mmHg. The lungs exhibited edema at PIP values > 9.3 mmHg. The stable pulmonary vascular pressure and resistance suggested that the edema may have resulted from a PIP-induced increase in microvascular permeability. In a second study, the stability of the preparation was evaluated during a 3-h test period. Seven lungs were ventilated at a peak inspiratory pressure of 8.0 mmHg and perfused at 26.8 +- 1.7 ml.min-1 x 100 g body wt-1. Microvascular integrity was maintained for approximately 2 h as indicated by filtration coefficient measurements of 0.175 +/- 0.068, 0.197 +/- 0.066, and 0.169 +/- 0.067 g.min-1 x mmHg-1 x 100 g-1 at 25, 70, and 115 min, respectively, after initiation of the study. The results suggest that isolated rat lungs perfused at rates that parallel normal rat cardiac output and ventilated at low peak inspiratory pressures provide a viable mechanism for evaluation of the pathophysiology of microvascular injury.

Animals↗

PubMed1992

Effect of extreme elevations in venous pressure on reflection coefficient in the lung.

We determined whether the solvent drag reflection coefficient (sigma f) for total proteins of a canine perfused left lower lung lobe (LLL) preparation decreases at elevated venous pressures (Pv). We found that sigma f (estimated using the hematocrit-protein technique) remained constant at all Pv's (30-95 mm Hg) evaluated. These results were unanticipated, since previous studies reported increases in protein permeability at Pv's within this range. We conducted two additional studies to better understand the basis for these observations. In the first, we evaluated the effect of high Pv (85 mm Hg) on sigma f of a canine perfused forelimb preparation and found sigma f to be reduced. This difference in response suggests that the normal sigma f's observed in the LLL were not due to high Pv per se, but rather that there is some intrinsic difference between the pulmonary and the systemic circulations that accounts for the difference. The second study was designed to determine whether the normal sigma f's observed in the LLL at high Pv's provide meaningful information about pulmonary vascular endothelial permeability. We damaged LLL's with alloxan, oleic acid, or HCl and obtained near normal estimates of sigma f at high Pv. These results indicated that it is not possible to easily distinguish between a normal and a damaged pulmonary vasculature when sigma f is measured at high Pv. We suggest that the normal estimates of sigma f obtained at high Pv in the LLL results from an increased fraction of the transvascular flow occurring through pathways that exclude macromolecules.

Animals↗

PubMed1992

Factors involved in left ventricular dysfunction after massive sympathetic activation.

We sought to determine whether catecholamines are responsible for the depressed left ventricular (LV) function that follows massive sympathetic nervous system (SNS) activation and whether the additional myocardial energy demands of SNS-induced hypertension contribute to this disorder. An intracisternal injection of veratrine was used to intensely activate the SNS of anesthetized rabbits, and 150 min later, LV function was evaluated in vitro using established techniques. To assess catecholamine involvement, rabbits were pretreated with phentolamine, propranolol, or saline prior to SNS activation. Control animals received veratrine intravenously. In separate experiments, angiotensin II (ANG II) was administered to rabbits to produce hemodynamic and plasma catecholamine profiles comparable to that produced by intense SNS activity. LV function of hearts after either massive SNS activation or ANG II administration was significantly diminished compared with control (P less than 0.01) and could be prevented by pretreatment with the catecholamine antagonists. LV function was also not diminished in another group of animals in which arterial pressure was maintained near baseline throughout the SNS discharge, thus suggesting that the increased myocardial energy demand associated with the development of arterial hypertension contributes to the LV dysfunction. We conclude that toxic concentrations of catecholamines are responsible for SNS-induced LV dysfunction and that hypertension, most likely because of its ability to increase myocardial energy demand, is one of the important events that leads to depressed cardiac function.

Animals↗

PubMed1992

Circulating neuropeptide Y does not produce pulmonary hypertension during massive sympathetic activation.

We tested the possibility that neuropeptide Y (NPY) may contribute to the pulmonary hypertension that occurs after massive sympathetic activation produced by intracisternal veratrine administration in the chloralose-anesthetized dog. In six dogs, veratrine caused arterial NPY-like immunoreactivity (NPY-LI) to rise from 873 +/- 150 (SE) pg/ml to peak values of 3,780 +/- 666 pg/ml by 60-120 min. (In 3 animals, adrenalectomy significantly reduced the increases in NPY-LI.) In five additional dogs, we infused porcine NPY for 30 min in doses that increased arterial NPY-LI to 8,354 +/- 1,514 pg/ml and observed only minor changes in pulmonary hemodynamics. In three isolated perfused canine left lower lung lobe (LLL) preparations, increasing doses of NPY were administered, producing levels of plasma NPY-LI, at the highest dose, that exceeded those observed after veratrine administration by three orders of magnitude. No changes in LLL arterial or double-occlusion capillary pressures were observed at any dose. Similarly, no changes in LLL hemodynamics were observed in three additional lobes when NPY was administered while norepinephrine was being infused. We conclude that it is unlikely that NPY plays a role as a circulating vasoactive agent in producing the pulmonary hypertension and edema that occur in this model.

Adrenal Glands↗

PubMed1992

Pulmonary vascular protein sieving capability after exposure to high vascular pressures.

We evaluated the ability of the canine in situ left lower lobe (LLL) vasculature to sieve endogenous plasma proteins of various molecular radii (34-124 A) after LLL arterial pressure had been transiently elevated to 23.8 +/- 0.9 (control group, n = 5) or 92.3 +/- 1.4 (SE) Torr (high-pressure group, n = 9) by restricting LLL venous outflow under conditions of constant flow. After LLL flow was returned to natural perfusion, left atrial pressure was elevated in step increments, and LLL lymph and blood samples were collected until filtration-independent lymph-to-plasma protein concentration ratios (CL/CP) were obtained. The osmotic reflection coefficients (sigma d) for total proteins and seven protein fractions (separated by gradient gel electrophoresis) were calculated. The average total protein sigma d of the high-pressure group [0.51 +/- 0.06 (SE)] was significantly lower than that of the control group (0.68 +/- 0.03). Several LLLs of the high-pressure group, however, exhibited normal sigma d's. Protein fraction CL/CP's decreased with increasing molecular radius in both groups, but the CL/CP-molecular radius relationship was displaced upward in the high-pressure group. Pore analysis suggested that the decreases in sigma d could be explained by increases in the fractional flow through a large-pore system.

Animals↗

PubMed1991

"Murder mystery" for student practice of pulmonary physiology calculations.

We have developed an exercise designed to give students practice calculating arterial O2 content, O2 delivery, physiological dead space, dead space and alveolar ventilation, and alveolar partial pressure of O2 and CO2. The exercise is in the form of a "murder mystery" in which students are required to make these calculations to identify the murderer.

Education, Medical↗

PubMed1991

Hemodynamic basis for cocaine-induced pulmonary edema in dogs.

We tested the hypothesis that cocaine-induced impairment of left ventricular function results in cardiogenic pulmonary edema. Mongrel dogs, anesthetized with alpha-chloralose, were injected with two doses of cocaine (5 mg/kg iv) 27 min apart. Cocaine produced transient decreases in aortic and left ventricular systolic pressures that were followed by increases exceeding control. As aortic pressure recovered, left ventricular end-diastolic, left atrial (Pla), pulmonary arterial (Ppa), and central venous pressures rose. Cardiac output and stroke volume were reduced when measured 4-5 min after cocaine administration. Peak Ppa and Pla were 31 +/- 5 (SE) mmHg (range 17-51 mmHg) and 26 +/- 5 mmHg (range 12-47 mmHg), respectively. Increases in extravascular lung water content (4.10 to 6.24 g H2O/g dry lung wt) developed in four animals in which Pla exceeded 30 mmHg. Analysis of left ventricular function curves revealed that cocaine depressed the inotropic state of the left ventricle. Cocaine-induced changes in hemodynamics spontaneously recovered and could be elicited again by the second dose of the drug. Our results show that cocaine-induced pulmonary hypertension, associated with decreased left ventricular function, produces pulmonary edema if pulmonary vascular pressures rise sufficiently.

Animals↗

PubMed1990

Pulmonary vasoconstriction in a canine model of neurogenic pulmonary edema.

The intracisternal administration of veratrine to the chloralose-anesthetized dog produces pulmonary hypertension (PH) and neurogenic pulmonary edema (NPE). To determine whether pulmonary vasoconstriction, mediated by a circulating agent, contributes to the PH, the left lower lung lobe (LLL) perfusion of seven splenectomized (to keep hematocrit and blood viscosity constant) dogs was isolated so the LLL could be perfused at constant flow and outflow pressure with blood pumped from the pulmonary artery. The LLL was denervated by removing it from the dog. Veratrine (40-160 micrograms/kg) increased LLL arterial pressure by 39.2% and produced large increases in plasma catecholamine concentrations. The double-occlusion technique indicated that 74% of the increase in the LLL arteriovenous pressure gradient was due to an increase in venous tone. This pattern of vasoconstriction was similar to that previously observed during the infusion of exogenous catecholamines and suggested that catecholamines mediated the LLL response. The more severe degree of PH observed in the intact animal in NPE, however, suggests that passive rather than active changes in pulmonary hemodynamics are predominantly responsible for the development of PH in this disorder.

Animals↗

PubMed1990

Role of hemodynamics and vagus nerves in development of fibrin-induced pulmonary edema.

The rapid development of pulmonary edema that may occur in the rabbit after the intracisternal injection of a mixture of fibrinogen and thrombin has classically been considered to result from a vagally mediated increase in vascular permeability (G. R. Cameron and S. N. De, J. Pathol. Bacteriol 61: 375, 1949) and to not be dependent on hemodynamic mechanisms. We tested this hypothesis by evaluating the relationship between the degree of pulmonary hypertension and postmortem extravascular lung water content (EVLW) in both nonvagotomized (n = 10) and vagotomized (n = 7) rabbits administered thrombin (0.1 ml, 500 U/ml) and fibrinogen (1 ml, 27 mg/ml) intracisternally. No increase in EVLW was observed in either group unless pulmonary arterial pressure (Ppa) exceeded 25 Torr, and large increases in EVLW were only observed at higher Ppa's. These results thus indicate that some degree of pulmonary hypertension is required for the development of this form of edema. Because the vascular pressure required to produce edema in this model approaches that required to increase pulmonary vascular permeability in the rabbit, a pressure-dependent increase in permeability may be a common characteristic of neurogenic pulmonary edema in this species. Vagotomy had no protective effect but instead appeared to increase the amount of edema development for a given degree of pulmonary hypertension.

Analysis of Variance↗

PubMed1990

Excessive sympathetic nervous system activity decreases myocardial contractility.

The objective of this study was to determine whether myocardial contractility is depressed by intense activation of the sympathetic nervous system. A massive sympathetic discharge was produced by injecting veratrine or sodium citrate into the cisterna magna of anesthetized rabbits (n = 10). Two and one-half hr later, the hearts were isolated and their left ventricular (LV) performance evaluated and compared with the LV performance of hearts isolated from control animals (n = 10). LV performance was evaluated from steady-state peak isovolumic systolic and end-diastolic pressures that were generated at various end-diastolic volumes (LV function curves). The relationship between peak LV systolic pressure (or the average peak developed LV wall stress) and LV end-diastolic volume was rotated downward (P less than 0.01) in the hearts removed from rabbits treated with veratrine or citrate. The LV end-diastolic pressure or LV end-diastolic wall stress of these hearts was not different from control at any end-diastolic volume. The diminished ability of the experimental hearts to develop systolic pressure or wall stress suggests that intense sympathetic activation depressed contractility. Severely damaged myofibers, located largely in the subendocardium, were found in these hearts. Furthermore, the depressed contractility was not related to pulmonary edema since only 2 of 10 rabbits developed edema.

Animals↗

PubMed1989

Oxygen consumption after massive sympathetic nervous system discharge.

We evaluated the possibility that massive, sympathetic nervous system (SNS) activation [as may precede the development of neurogenic pulmonary edema (NPE)] increases O2 demand. O2 consumption (VO2) and plasma concentrations of the calorigenic agents, epinephrine (EPI) and norepinephrine (NE) were measured in alpha-chloralose-anesthetized dogs under control conditions and for 3 h after the administration of either 1) intracisternal (ic) veratrine to activate the SNS, 2) intravenous (iv) veratrine, 3) ic saline, or 4) ic veratrine, after clamping the adrenal blood vessels. VO2 increased 31.7 +/- 3.6% (SE), and EPI and NE increased to, respectively, 30,853 +/- 8,347 and 8,176 +/- 2,104 pg/ml in the ic veratrine group. No increases in VO2 and EPI and attenuated increases in NE were observed in the ic veratrine animals with clamped adrenals. No significant increases in VO2 or catecholamine concentrations were observed after ic saline or iv veratrine administration. These data suggest that the elevated VO2 may have been mediated by adrenal catecholamines and that an increased metabolic rate may complicate the ability of patients with severe NPE to balance O2 supply with demand.

Adrenal Glands↗

PubMed1989

Effect of elevated vascular pressure transients on protein permeability in the lung.

Neurogenic pulmonary edema (NPE) may develop in individuals with head trauma or seizures and is generally thought to have a hydrostatic basis in the severe degree of pulmonary hypertension that occurs. Recently, it has been suggested that vascular pressures may rise to levels that damage the vessels, leaving the patient at risk for further edema development. The objective of this study was to determine if pulmonary vascular protein permeability is increased in a canine isolated perfused left lower lung lobe (LLL) preparation by pressure transients that may occur in NPE. Venous pressure (Pv) was transiently raised to values ranging from 8 to 102 Torr in 19 LLL. One Pv transient was studied per LLL. After Pv was returned to normal, the osmotic reflection coefficient (sigma d) for total proteins was determined by the hematocrit-protein double indicator technique. No reduction in sigma d was observed until microvascular pressure exceeded 70 Torr. The average sigma d for the 11 LLL in which the peak microvascular pressure was less than 70 Torr was 0.74 +/- 0.03 (SE). Above this level sigma d fell linearly with increasing Pv, with a value of 0.26 being observed after the highest Pv transient. These results suggest that protein permeability may increase in patients with NPE who develop very large increases in pulmonary vascular pressures but may not be a universal occurrence in this disorder.

Animals↗

PubMed1988

Role of prostaglandins in blood-induced vasoconstriction of canine cerebral arteries.

We tested the hypothesis that the vasoconstriction produced by the application of blood to the adventitial surfaces of the vessels of an isolated perfused canine circle of Willis preparation was mediated by products of prostaglandin metabolism. In this preparation (perfused at constant flow and outflow pressure), topical application of blood produced an average 16.6 +/- 1.8 (SE) mm Hg increase in inflow pressure. This response could be prevented with four structurally dissimilar cyclooxygenase inhibitors (aspirin, indomethacin, ibuprofen, and meclofenamate), suggesting that the blood-induced increase in vascular resistance was mediated by prostaglandins. Imidazole, an inhibitor of thromboxane synthetase, had no effect on the blood response. Further support for the involvement of prostaglandins in this response was provided by additional experiments in which either arachidonic acid, prostaglandin E2 (PGE2), or PGF2 alpha were administered. All three treatments produced vasoconstriction. These results suggest that the vessels of this preparation are capable of synthesizing vasoconstrictor prostaglandins and indicate that they are reactive to known vasoactive prostaglandins.

Animals↗

PubMed1988

Effect of pathological blood histamine levels on canine coronary vascular permeability.

We evaluated the effect of systemically administered histamine on coronary vascular permeability (CVP) of pentobarbital-anesthetized, open-chest dogs with and without beta-receptor blockade. We determined changes in CVP by comparing prenodal cardiac lymph flow and lymph-to-plasma protein concentration ratio before and after 30 min of histamine infusion. Histamine was infused into the left ventricle at 150 micrograms/min to produce pathological blood histamine concentrations of approximately 0.5 micrograms/ml. Histamine increased CVP in only one of seven dogs without beta-receptor blockade but increased CVP in four of seven beta-blocked animals. In a second series of experiments, the effect of histamine on CVP was assessed in an in situ isolated heart-lung preparation. In this preparation, similar blood histamine concentrations increased CVP in the same fraction of experiments (4 of 7) as was observed for beta-blocked dogs. Therefore, isolating the heart from the effects of all systemically derived histamine antagonistic substances did not appear to make the coronary vessels any more vulnerable to histamine than only blocking the actions of catecholamines. We conclude that 1) catecholamines provide protection for the coronary microvasculature against histamine-induced increases in the CVP; and 2) the probability that vascular permeability will increase in the heart when histamine exposure occurs through the general circulation is remote. Thus, if histamine-induced increases in CVP occur, then they probably result from the release of histamine from myocardial storage sites.

Animals↗

PubMed1988

Calculation of the reflection coefficient from measurements of endogenous vascular indicators.

The solvent drag reflection coefficient (sigma) for total proteins can be estimated by comparing the relative degrees of concentration of erythrocytes and plasma proteins that occur during fluid filtration in an isolated perfused organ. In this analysis, we evaluated the accuracy of equations proposed by Pilati and Maron [Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H1-H7, 1984] and Wolf et al. [Am. J. Physiol. 253 (Heart Circ. Physiol. 22): H194-H204, 1987] to calculate sigma from these concentration changes. We calculated sigma with each equation using data generated from a mathematical model of fluid and solute flux in membranes with known sigma's. We found that the equation of Wolf et al. provided the closest approximation to the true sigma over the entire range of filtration fractions tested (0.1-0.6), with the differences between the two equations increasing with filtration fraction. At low filtration fractions, the difference in sigma obtained using either approach was found to be inconsequential. At larger filtration fractions, a closer approximation of the true sigma can be obtained using the equation of Wolf et al.

Animals↗

PubMed1988

Effect of papaverine on pulmonary vascular permeability to proteins.

Previous studies have suggested that papaverine, a drug commonly used in studies of transvascular fluid and solute exchange to eliminate confounding effects of changes in vascular tone, may itself increase vascular permeability. In this study, we determined the ability of papaverine to alter pulmonary vascular protein permeability by measuring the osmotic reflection coefficient (sigma) for total proteins in a canine isolated perfused left lower lung lobe (LLL) preparation. The reflection coefficient, determined by the hematocrit-protein double-indicator technique, for control LLL's was 0.83 +/- 0.04 (SE) (n = 7). In separate groups of LLL's, blood papaverine HCl concentrations of 10(-5), 10(-4), and 10(-3) M resulted in sigma's of 0.84 +/- 0.02 (n = 6), 0.73 +/- 0.04 (n = 7), and 0.53 +/- 0.04 (n = 6), respectively. When two LLL's from the 10(-4) M group with sigma's of 0.56 and 0.57 were excluded from the analysis, the average sigma for this group was 0.79 +/- 0.02. We conclude that papaverine increases protein permeability at a concentration of 10(-3) M but does so in only some lobes at 10(-4) M. These results suggest that caution be taken when using high concentrations of papaverine in fluid balance studies.

Animals↗

PubMed1988

Maximal aerobic power after competitive marathon running.

We evaluated the ability of a group of male runners (n = 4) to do maximal and submaximal exercise before and after they ran a competitive marathon (42.2 km) race. VO2max was determined 3 to 6 times in each runner, on alternate days, 1-4 weeks prior to the race, and again an equal number of times, once the runners had recovered from muscle soreness (avg. 7 days) after the race. Each test consisted of a 10 min treadmill walk (8.6% slope, 94 m.min-1 [3.5 miles.h-1]) followed by a 5 min run (8.6% slope, 188 m.min-1 [7 miles.h-1]). After this time, the speed was increased 10 m.min-1 every minute until exhaustion. No differences in VO2 were observed during submaximal exercise, and no reduction in VO2max occurred. One runner, however, exhibited a substantial and consistent increase in VO2max after the marathon (73.6 +/- 1.5 (SE) to 79.9 +/- 0.7 mL.kg-1.min-1, p less than 0.05). Treadmill exercise-induced increases in hematocrit, blood hemoglobin, and plasma protein, cortisol, lactate and norepinephrine concentrations were unaltered after the marathon. We conclude that, following a period of sufficient recovery from muscle soreness, oxygen delivery and utilization mechanisms remain intact after marathon running.

Adult↗

PubMed1987

Analysis of airway fluid protein concentration in neurogenic pulmonary edema.

Intracisternal administration of veratrine (40 micrograms/kg) in the alpha-chloralose-anesthetized dog produces fulminant neurogenic pulmonary edema (NPE). To determine whether the edema resulted from increased microvascular pressure or from increased permeability, the airway fluid-to-plasma protein (A/P) concentration ratios were compared for both total proteins and endogenous protein fractions of known molecular radii (37-114 A) from dogs with edema produced by either veratrine, alloxan (permeability edema), or combined left atrial pressure and volume overload (hemodynamic edema). High A/P ratios (0.98 +/- 0.05) were observed after alloxan administration, whereas lower values (0.54 +/- 0.04) were observed in hemodynamic edema. A/P ratios were observed after veratrine administration that formed a continuum (0.48-0.84) between these extremes. Veratrine animals with high overall A/P ratios exhibited elevated A/P ratios for all protein fractions, whereas animals with lower overall A/P ratios exhibited A/P protein fraction ratios similar to those observed in the hemodynamic group. These data indicate that both hemodynamic and increased permeability mechanisms may play a role to varying degrees in the development of this form of NPE.

Animals↗