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Biomedical subjects

C F Pilati

Publications and source records attributed to C F Pilati.

At least 19 recordsLinked to original sources
PubMed1995

Role of EDRF in the cardiopulmonary dysfunction produced by massive sympathetic activation.

This study was undertaken to determine whether endothelium-derived relaxing factor (EDRF) modulates the pulmonary and systemic hemodynamic responses to massive sympathetic nervous system (SNS) activation and, in so doing, also modulates the degree of SNS-induced left ventricular (LV) dysfunction and the likelihood for pulmonary edema formation. The SNS of 13 anesthetized untreated rabbits and 14 anesthetized rabbits pretreated with the EDRF inhibitor, N omega-nitro-L-arginine (L-NNA, 20 mg/kg), was massively activated with an intracisternal injection of veratrine. Pulmonary and systemic arterial pressures increased to the same extent in both groups, but LV end-diastolic pressure was significantly lower in untreated rabbits. During this time, cardiac output decreased by 37% in L-NNA pretreated rabbits compared with 8% in untreated animals. Peak systemic and pulmonary vascular resistances increased significantly in L-NNA rabbits, whereas only systemic vascular resistance increased significantly in untreated rabbits. However, this increase in systemic vascular resistance was threefold less than that observed for L-NNA-treated animals. Although the degree of LV dysfunction was greater in the L-NNA rabbits, pulmonary edema developed less frequently in this group. We suggest that when EDRF release is inhibited during massive SNS activity, pulmonary vascular resistance increases markedly, which causes the right ventricle to fail. We further suggest that the reduced right ventricular output maintains pulmonary microvascular pressure below levels required for edema development.

Animals↗
PubMed1994

Temporal changes in left ventricular function after massive sympathetic nervous system activation.

Intense activation of the sympathetic nervous system (SNS) decreases the contractile state of the rabbit left ventricle (LV). In this study, we determined the time course of LV dysfunction after massive central activation of the SNS in dogs. Veratrine (40-80 micrograms/kg) was injected intracisternally to activate the SNS in six chloralose-anesthetized dogs, and LV end-diastolic pressure (LVEDP), cardiac output, heart rate, and aortic pressure (Pa) were measured at 30-min intervals for 3 h. Pa increased from 147 +/- 8 (SE) to 272 +/- 7 mmHg (1 mmHg = 133.3 Pa) within 15 min, then declined to 148 +/- 16 mmHg by 1 h LV function curves (stroke work versus LVEDP or stroke work verus LV transmural pressure) showed a marked decrease in slope and a shift to the right within minutes after activating the SNS, which persisted for the duration of the experiment. These data indicate that LV contractility was diminished in these animals. No changes in LV function were observed in three dogs serving as time-matched controls. In three additional dogs, LV pressure was raised to a degree similar to that observed after SNS activation by constricting the ascending aorta for 1 h. These animals exhibited only modest shifts in the LV function curve during and after aortic constriction. Mean plasma catecholamine concentration increased by one to two orders of magnitude in animals after SNS activation, but only minor changes were observed in the other two groups. We conclude that myocardial contractility declines markedly soon after massive SNS activation and is not solely a function of the initial hypertensive period.

Acidosis↗
PubMed1994

Myocardial work load is a major determinant of norepinephrine-induced left ventricular dysfunction.

This study was conducted to determine whether increased myocardial energy demand plays a role in norepinephrine (NE)-induced left ventricular (LV) dysfunction. A range of arterial pressure-heart rate (P-R) products (myocardial energy demand) was produced in both conscious and pentobarbital sodium-anesthetized rabbits with the same dose of NE (10 micrograms priming bolus plus 2.5 micrograms.kg-1 x min-1 for 2.5 h). After NE treatment, LV function was evaluated in vitro and found to be markedly diminished in the rabbits that had an elevated P-R product. In contrast, LV function was not significantly affected when the P-R product was maintained near control levels during NE treatment. In separate experiments, rabbit hearts were isolated and exposed to NE (10,000 or 50,000 pg/ml) for 2.5 h under low P-R product conditions. These hearts exhibited a dose-dependent decrease in LV function that was modest compared with that observed in rabbits that had elevated P-R products during in vivo NE treatment. Our results suggest that high concentrations of NE may cause modest degrees of LV dysfunction independently of increases in myocardial energy demand, but the LV dysfunction is exacerbated when myocardial energy demand is elevated.

Anesthesia, General↗
PubMed1993

Persistent left ventricular dysfunction after cocaine treatment in rabbits.

The present study was undertaken to determine whether the diminished cardiac performance associated with cocaine administration persists after the drug has been eliminated from the body. Cocaine (5 or 10 mg/kg iv) was administered to conscious (n = 7) or pentobarbital-anesthetized (n = 7) rabbits, respectively. Seven conscious and seven anesthetized control rabbits received the saline vehicle. Two and one-half hours later, the hearts were removed from the animals and perfused under cocaine-free conditions. Left ventricular (LV) contractility was evaluated by plotting steady-state LV systolic and diastolic pressures as a function of LV end-diastolic volume (preload). LV systolic performance was diminished in a dose-related manner in hearts isolated from cocaine-treated rabbits, but was statistically different from control only at the higher cocaine dose (P < 0.05). In a second set of experiments, hearts (n = 6) were isolated, and their LV function was evaluated before, during, and after cocaine exposure. In these experiments, cocaine was added to the perfusate in increments to produce concentrations of 5, 10, and 15 mg/liter. After LV function was evaluated at the highest cocaine dose, cocaine-free perfusion conditions were restored, and LV function was reevaluated. In these experiments, cocaine produced a dose-dependent decrease in LV function that readily reversed when cocaine-free perfusion was reinstated. We conclude that cocaine diminishes LV contractility, and that the diminished cardiac performance may not readily reverse after in vivo exposure. Moreover, the rapid restoration of cardiac performance after exposure to cocaine in vitro suggests that the mechanism operating in vivo involves more than a simple direct action on the myocyte. Catecholamine cardiotoxicity does not appear to be a primary factor.

Anesthesia, General↗
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

Effect of intracoronary infusion of histamine or compound 48/80 on coronary vascular permeability and myocardial fluid balance.

This study was undertaken to determine if coronary vascular permeability (CVP) increases and if myocardial edema develops in the canine heart after local exposure to histamine. Histamine (50 or 15 micrograms/min) or compound 48/80 (0.1-0.2 mg/kg) was infused into the left anterior descending coronary artery (LAD) of open-chest dogs, and changes in CVP were determined by comparing prenodal cardiac lymph flow (Q1) and lymph-to-plasma protein concentration ratio (C1/Cp) before and during histamine or compound 48/80 treatment. CVP increased in most, but not all, experiments with both doses of histamine as indicated by simultaneous increases in both Q1 and C1/Cp. The injection of compound 48/80 into the LAD of four dogs caused unequivocal increases in CVP in only one experiment. Compared with the effect of histamine on the forelimb, the average increases in Q1 and C1/Cp were not large with either histamine or compound 48/80, which suggests that the increases in CVP were relatively small. Moreover, edema did not develop. These results indicate that the coronary microvasculature of the intact dog heart is relatively insensitive to increases in permeability produced by histamine. Furthermore, the release of histamine from myocardial mast cells would not be expected to play a major role in the myocardial edema that develops under various pathological conditions.

Animals↗
PubMed1990

Macromolecular transport in canine coronary microvasculature.

Coronary vascular osmotic reflection coefficients (sigma dS) for total protein, albumin (Alb), immunoglobulin (Ig)G, and IgM were determined in the anesthetized dog. Myocardial lymph was collected from the anterior interventricular lymphatic trunk, and the sigma dS estimated from filtration rate-independent lymph-to-plasma protein concentration ratios (CL/CPS). Lymph flows of at least 12 times base line were needed to produce filtration rate-independent CL/CPS, and these were achieved in 9 of 12 experiments. In these nine experiments, sigma dS for total protein, Alb, IgG, and IgM were, respectively, 0.67 +/- 0.02 (SE), 0.59 +/- 0.05, 0.70 +/- 0.03, and 0.87 +/- 0.01. The data were fitted to a model that showed that transvascular fluid and solute flux could be described by two populations of pores. A large pore system with an equivalent radius of 235 A was responsible for 39% of the transvascular volume flow. A small pore system less than 53 A accounted for the remaining flow. In a second group of experiments (n = 8), 60 min of ischemia decreased the sigma dS to 0.27 +/- 0.03, 0.07 +/- 0.05, 0.22 +/- 0.03, and 0.69 +/- 0.04 for total protein, Alb, IgG, and IgM, respectively. A single population of pores of 220 A could describe the entire transvascular volume flow. These results indicate that coronary vascular protein permeability is moderately high and can be increased significantly by ischemia.

Animals↗
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↗
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↗
PubMed1987

Effect of hemolysis on reflection coefficient determined by endogenous blood indicators.

The osmotic reflection coefficient (sigma) can be estimated from the increases in hematocrit and plasma protein concentration that result from fluid filtration occurring in an isolated perfused organ. We determined what effect perfusion pump-induced hemolysis has on the value of sigma determined by this technique in both the isolated canine left lower lung lobe (LLL) and forelimb by comparing estimates of sigma obtained before and after correction for hemolysis. Hemolysis was corrected by using the slopes of the relationships between hematocrit and plasma hemoglobin concentration and between the plasma protein and hemoglobin concentrations to correct hematocrit and protein concentration to a state of zero hemolysis. Uncorrected estimates of sigma in the LLL were 1.19 +/- 0.14 (SE) at a venous pressure (Pv) of 12 Torr (n = 7) and 0.90 +/- 0.02 at a Pv of 19 Torr (n = 6). Both sets of LLL's yielded sigma values of 0.77 +/- 0.03 after hemolysis correction. In the forelimb (n = 5), uncorrected and corrected estimates of sigma of 0.99 +/- 0.03 and 0.85 +/- 0.01, respectively, were obtained. The latter values were similar to sigma's (0.88 +/- 0.01) determined by lymph analysis in five additional forelimbs. We conclude that hemolysis results in overestimates of sigma. After hemolysis correction, this technique yields similar results to those obtained from lymph analysis for the forelimb and from published values for the LLL.

Animals↗
PubMed1985

Left ventricular function of the isolated, genetically obese rat's heart.

We sought to determine if left ventricular (LV) function of the heart from the adult, chronically obese animal is impaired. Hearts from 50 wk-old genetically obese female Zucker rats (624 +/- 13 g) and their lean littermate controls (275 +/- 5 g) were isolated during ether anesthesia, supported metabolically by retrograde aortic perfusion (6 ml/min, 35 degrees C) with physiological solution containing suspended canine erythrocytes (hematocrit, 20%), and the ventricles were paced at 180 beats/min. A distensible, fluid-filled balloon was placed in the LV, and pressure-volume (PV) relationships were obtained. The obese and lean end-diastolic PV curves were not different, and therefore the obese and lean LV chamber compliances were similar. Comparison of the systolic PV relationships demonstrated that the obese rat's heart had a greater pressure-generating capability, which probably was a reflection of its increased LV mass (0.96 +/- 0.03 vs. 0.72 +/- 0.02 g). The calculated average meridional (or circumferential) peak systolic wall stress in the LV of the obese rat's heart, however, was significantly reduced compared with control. This diminished ability to develop systolic stress from the same end-diastolic volumes suggests that the hypertrophied LV of the middle-aged obese rat's heart is dilated or that its contractility is depressed, or both.

Animals↗
PubMed1985

Pulmonary hemodynamics and lung water content during splanchnic ischemic shock.

Pulmonary hemodynamics and lung water content were evaluated in open-chest dogs during splanchnic arterial occlusion (SAO) shock. Mean pulmonary arterial pressure [Ppa = 13.0 +/- 0.6 (SE) mmHg] and pulmonary venous pressure (4.1 +/- 0.2 mmHg) were measured by direct cannulation and the capillary pressure (Ppc = 9.0 +/- 0.6 mmHg) estimated by the double-occlusion technique. SAO shock did not produce a significant change in Ppa or Ppc despite a 90% decrease in cardiac output. An 18-fold increase in pulmonary vascular resistance occurred, and most of this increase (70%) was on the venous side of the circulation. No differences in lung water content between shocked and sham-operated dogs were observed. The effect of SAO shock was further evaluated in the isolated canine left lower lobe (LLL) perfused at constant flow and outflow pressure. The addition of venous blood from shock dogs to the LLL perfusion circuit caused a transient (10-15 min) increase in LLL arterial pressure (51%) that could be reversed rapidly with papaverine. In this preparation, shock blood produced either a predominantly arterioconstriction or a predominantly venoconstriction. These results indicate that both arterial and venous vasoactive agents are released during SAO shock. The consistently observed venoconstriction in the intact shocked lung suggests that other factors, in addition to circulating vasoactive agents, contribute to the pulmonary hemodynamic response of the open-chest shocked dog.

Animals↗
PubMed1984

Effect of histamine on coronary microvascular permeability.

The effect of histamine on coronary vascular permeability was assessed under conditions of elevated venous pressure in the spontaneously beating, isolated canine heart perfused with autologous blood. The apparent volume of fluid filtered from the vasculature to the interstitium (VF) was calculated from the increase in plasma protein concentration and also from the increase in hematocrit. The ratio of the protein-filtered volume to the hematocrit-filtered volume (VF,Pr/VF,Hct) was used to evaluate changes in permeability. In the absence of histamine, the VF,Pr/VF,Hct was near unity (1.05 +/- 0.11), which indicated that the blood proteins and the red blood cells had concentrated equally. Thus the transudate was essentially protein free. On exposure to histamine (3.8 +/- 0.3 microgram base/ml blood), VF,Pr/VF,Hct decreased to 0.37 +/- 0.06 (P less than 0.001), which indicated that coronary vascular permeability had increased. This value remained constant throughout the 60 min of histamine exposure. Aortic perfusion pressure decreased significantly (P less than 0.05) from 111 +/- 11 to 84 +/- 5 mmHg during the 1st min of histamine exposure and rose slowly thereafter. In four of the seven hearts, concomitant increases in left ventricular isovolumic pressure development (13-31 mmHg) and heart rate (4-29 beats/min) were observed. In the remaining hearts, neither variable was affected by histamine. We conclude that histamine causes an increase in the permeability of the canine coronary microvasculature but fails to increase heart rate or left ventricular performance consistently.

Animals↗