Search PubMed⌕ Search

Biomedical subjects

R G Pearl

Publications and source records attributed to R G Pearl.

At least 55 records · Page 3Linked to original sources
PubMed1994

Adenosine produces pulmonary vasodilation in the perfused rabbit lung via an adenosine A2 receptor.

Adenosine is a potent pulmonary vasodilator that has been used in therapy for clinical and experimental pulmonary hypertension. To determine the receptor responsible for adenosine-induced pulmonary vasodilation, we studied the relative potency of four adenosine agonists in the isolated buffer-perfused rabbit lung during pulmonary hypertension due to infusion of the thromboxane A2 mimetic U46619. The ED50 values for pulmonary vasodilation were 1.9 x 10(-8) mol/L for 5'-N-ethylcarboxamidoadenosine (NECA), 4.5 x 10(-8) mol/L for 2-phenylaminoadenosine (CV-1808), 2.6 x 10(-6) mol/L for R(-)-N6-(2-phenylisopropyl) adenosine (R-PIA), and 6.5 x 10(-6) mol/L for cyclopentyladenosine, results consistent with an adenosine A2 receptor. Pretreatment with the adenosine A1 receptor antagonist cyclopentyltheophylline did not affect the dose-response curve to NECA, and pretreatment with the adenosine A2 receptor antagonist CGS 15943A increased the ED50 of NECA to 2.7 x 10(-7) mol/L. These results suggest that adenosine produces pulmonary vasodilation via activation of an adenosine A2 receptor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Inotropic therapy in the critically ill patient.

Inotropic support is an important therapeutic modality in the intensive care unit. There are three classes of agents available to the clinician: catecholamines, bipyridines, and cardiac glycosides. Each class increases inotropy by a different mechanism and each agent has distinct physiological and pharmacological actions. It is important to understand the underlying pathophysiology involved so the appropriate inotrope can be chosen on a rational basis. Prior to and during therapy invasive hemodynamic monitoring is required to ensure proper titration of the chosen agent. If an undesirable effect ensues, therapy can then be modified.

Amrinone↗
PubMed1993

Pulmonary capillary pressure measurement during global hypoxia in sheep.

Analysis of the pressure decay following pulmonary artery occlusion can be used to determine pulmonary capillary pressure and to calculate the magnitudes of the arterial and venous components of pulmonary vascular resistance. The separation of pulmonary vascular resistance into components has been termed "the longitudinal distribution of pulmonary vascular resistance" to emphasize the fact that different pressures occur at a number of sites in the pulmonary circulation. The longitudinal distribution of pulmonary vascular resistance is closely related to pulmonary capillary pressure. Several methods of data analysis have been proposed to determine pulmonary capillary pressure from the pressure decay following pulmonary artery occlusion. In this study, three methods of data analysis were applied to the model of hypoxic pulmonary vasoconstriction to evaluate the validity of the methodology in a well known model. Pulmonary artery occlusion pressure decay curves were obtained from eight halothane-anesthetized sheep during control conditions (FIO2 = 0.99) and during hypoxic ventilation (FIO2 = 0.14). Analysis of the pulmonary artery occlusion pressure decay curves indicated the following results: 1) Hypoxia increased mean pulmonary artery pressure by 105% and increased pulmonary vascular resistance by 149%; 2) the increase in the calculated arterial component of pulmonary vascular resistance accounted for 88% of the increase in pulmonary vascular resistance with hypoxia; and 3) hypoxia produced only a 1.0 mm Hg increase in pulmonary capillary pressure. These results are consistent with other evidence showing that hypoxia primarily produces precapillary pulmonary vasoconstriction and has little effect on pulmonary capillary pressure. Pulmonary artery occlusion pressure decay curve analysis appears to be a valid technique for the measurement of pulmonary capillary pressure during hypoxia in intact anesthetized animals.

Animals↗
PubMed1992

Biguanide-associated lactic acidosis. Case report and review of the literature.

PURPOSE: The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis. PATIENT: We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia. RESULTS: Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital. CONCLUSIONS: Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications.

Acidosis, Lactic↗
PubMed1992

Effects of prostaglandin E1 and hydralazine on the longitudinal distribution of pulmonary vascular resistance during vasoconstrictor pulmonary hypertension in sheep.

Pulmonary capillary pressure (Ppc) is dependent upon left atrial pressure, pulmonary venous resistance, and cardiac output. The effects of pulmonary vasodilators on Ppc will therefore depend upon any alterations in the longitudinal distribution of pulmonary vascular resistance (precapillary [arterial] and postcapillary [venous] components). We therefore studied the effects of two pulmonary vasodilators (prostaglandin E1 and hydralazine) on Ppc and the longitudinal distribution of pulmonary vascular resistance. Pulmonary hypertension was produced in sheep by the continuous administration of the thromboxane A2-mimetic U46619. Ppc was measured by analysis of pulmonary artery occlusion pressure decay curves. U46619 increased Ppc by 9 mmHg and increased both the arterial and venous components of pulmonary vascular resistance. Subsequent administration of prostaglandin E1 decreased Ppc by 5 mmHg and decreased both the arterial and venous components of pulmonary vascular resistance (by 50 and 69% respectively). Hydralazine produced smaller decreases in the arterial and venous components of pulmonary vascular resistance (by 35 and 49% respectively) and did not significantly reduce Ppc. We conclude that prostaglandin E1 but not hydralazine is effective in decreasing Ppc in this experimental model of pulmonary hypertension.

Alprostadil↗
PubMed1992

Longitudinal distribution of pulmonary vascular resistance after endotoxin administration in sheep.

BACKGROUND AND METHODS: Pulmonary hypertension may increase pulmonary capillary pressure and exacerbate pulmonary edema in acute respiratory failure. The effects of pulmonary hypertension on pulmonary capillary pressure depend on the longitudinal distribution of pulmonary vascular resistance. Since pulmonary hypertension occurs during acute respiratory failure, we hypothesized that acute respiratory failure may produce time-dependent changes in the longitudinal distribution of pulmonary vascular resistance. Therefore, we measured pulmonary capillary pressure and the longitudinal distribution of pulmonary vascular resistance in an animal model of acute respiratory failure. Escherichia coli endotoxin (2.5 to 5.0 micrograms/kg) was administered over a 1-hr period in eight anesthetized sheep. Pulmonary and systemic hemodynamics, including pulmonary artery occlusion pressure (PAOP), pulmonary capillary pressure, and the longitudinal distribution of pulmonary vascular resistance, were measured over the next 5 hrs. Pulmonary capillary pressure was estimated by analysis of the pressure decay following pulmonary artery balloon inflation. RESULTS: Endotoxin administration resulted in sustained pulmonary hypertension for the subsequent 5 hrs of the study. Pulmonary capillary pressure was increased 7 mm Hg above baseline at 0.5 and 0.75 hrs during the infusion of endotoxin but returned to baseline values at 1.5 hrs. Despite sustained pulmonary hypertension, pulmonary capillary pressure remained at baseline values for the duration of the study. Similar to pulmonary capillary pressure, pulmonary venous (or postcapillary) resistance was increased approximately four-fold over baseline at 0.5 and 0.75 hrs after initiating endotoxin administration, but returned to baseline values by the end of endotoxin administration and remained at baseline values throughout the remainder of the study. In contrast, pulmonary arterial (or precapillary) resistance remained at values approximately three times baseline during the infusion and throughout the duration of the study. CONCLUSIONS: In this experimental model of acute respiratory failure, the effects of endotoxin on the longitudinal distribution of pulmonary vascular resistance are time-dependent. If these data from animals can be extrapolated to humans, we speculate that the importance of pulmonary venoconstriction in exacerbating pulmonary edema may vary over time in patients with acute respiratory failure.

Animals↗
PubMed1992

Pulmonary artery catheterization: the right heart should not be left out--a case report.

Tricuspid valve stenosis in the setting of endocarditis is associated with a high morbidity. Diagnostic approaches incorporate a high clinical index of suspicion, echocardiographic evidence, and inferences about hemodynamic data derived from pulmonary artery catheterization. As demonstrated by the case presented herein, inadequate initial evaluation of right-sided pressures delayed the diagnosis and treatment of prosthetic tricuspid valve stenosis.

Adult↗
PubMed1991

Thermodilution cardiac output measurement with a large left-to-right shunt.

Cardiac output was measured by the thermodilution method in a patient with a left-to-right shunt undergoing cardiac catheterization. It appeared that the thermodilution method measured systemic rather than pulmonary blood flow. This occurred because of the slow injection of injectate in the presence of a large left-to-right shunt. Theoretical thermodilution cardiac output curves are provided to illustrate the interaction of these two factors when three different durations of injection and four different shunt sizes are used.

Adult↗
PubMed1991

A thromboxane analog increases pulmonary capillary pressure but not permeability in the perfused rabbit lung.

Thromboxane has been implicated as a mediator of pulmonary hypertension and pulmonary edema in acute respiratory failure. Pulmonary edema may result from increased pulmonary capillary hydrostatic pressure or from increased pulmonary vascular permeability. We therefore studied the effects of a stable thromboxane analog, U46619, on these two parameters in the perfused rabbit lung. Pulmonary capillary pressure was measured by the double vascular occlusion method, and pulmonary vascular permeability was estimated by measurement of the pulmonary fluid filtration coefficient (Kf). U46619 infusion produced pulmonary hypertension and lung weight gain; increased both the arterial (precapillary) and venous (postcapillary) components of pulmonary vascular resistance; and increased pulmonary capillary pressure from 4.7 +/- 0.5 to 9.0 +/- 0.7 mmHg (P less than 0.01). The isogravimetric pressure (equivalent to the capillary pressure corresponding to no lung weight gain) was 4.0 +/- 0.4 mmHg before U46619 and 4.6 +/- 0.4 mmHg during U46619. Therefore, U46619 significantly increased capillary pressure above isogravimetric pressure and resulted in the development of pulmonary edema. U46619 did not affect vascular permeability as measured by Kf. We conclude that pulmonary venoconstriction resulting in increased pulmonary capillary hydrostatic pressure is the major mechanism by which thromboxane produces pulmonary edema in isolated lungs.

Analysis of Variance↗
PubMed1991

Hemodynamic profiles of prostaglandin E1, isoproterenol, prostacyclin, and nifedipine in experimental porcine pulmonary hypertension.

BACKGROUND AND METHODS: We compared the hemodynamic effects of four vasodilators in experimental embolic pulmonary hypertension in a randomized controlled trial, using nine pigs weighing 16 to 23 kg. After anesthesia induction and cannulation with arterial, central venous, and thermodilution output pulmonary artery catheters, animals were repetitively embolized with glass beads (60 to 160 mu) in order to establish pulmonary hypertension (pulmonary artery pressure [PAP] doubled from baseline). Prostaglandin E1 (PGE1), isoproterenol, prostacyclin (PGI2), and nifedipine were compared at doses producing equivalent reduction in systemic BP. RESULTS: Only PGE1 and PGI2 decreased both PAP and pulmonary vascular resistance (PVR). PGE1 decreased PAP from 39 +/- 1 to 33 +/- 1 mm Hg; prostacyclin decreased PAP from 38 +/- 1 to 31 +/- 1 mm Hg and produced the largest increase in cardiac output (Qt). Isoproterenol did not change PAP, markedly increased heart rate (162 +/- 8 to 216 +/- 11 beats/min), and resulted in significant arrhythmias. Nifedipine increased PVR from 1044 +/- 113 to 1125 +/- 100 dyne.sec.cm-5 and decreased Qt. CONCLUSIONS: Vasodilators demonstrate unique hemodynamic drug profiles. Isoproterenol infusion is characterized by tachycardia and arrhythmias. Both PGE1 and PGI2 effectively decrease PAP and PVR. Nifedipine depressed Qt significantly in this glass-bead embolization model of acute pulmonary hypertension.

Alprostadil↗
PubMed1991

Isoproterenol prevents oxidant-induced injury in isolated rabbit lungs.

Increased vascular permeability in the adult respiratory distress syndrome is due in part to toxic oxygen metabolites. In the present study, we produced lung injury in the isolated rabbit lung with hydrogen peroxide (H2O2) and examined its prevention with isoproterenol. Pulmonary arterial pressure (Ppa) and the fluid filtration coefficient (Kf) were measured as indices of lung injury. Rabbits were divided into two groups, and 7 mmol/l H2O2 was administered in both groups. In one group, isoproterenol (2 micrograms/ml) was administered 10 min before H2O2 injury. Ppa increased transiently after H2O2 administration in the control group but was unchanged in the isoproterenol group. Kf was significantly increased by H2O2 administration in the control group but not in the isoproterenol group. We conclude that H2O2 increases pulmonary vascular permeability and that isoproterenol may protect against H2O2-induced pulmonary injury.

Animals↗
PubMed1991

Leukotriene synthesis inhibition and receptor blockade do not inhibit hypoxic pulmonary vasoconstriction in sheep.

Several lines of evidence suggest that leukotrienes may be mediators of hypoxic pulmonary vasoconstriction (HPV). However, the effect of leukotriene inhibition on HPV remains controversial. The present study investigated the effect of leukotriene synthesis inhibition and receptor blockade on HPV in the halothane-anesthetized sheep. After initial baseline measurements, the pulmonary pressor response to 15 min of global hypoxia (FIO2 = 0.13) was measured. A second set of baseline measurements was obtained and the sheep then received the combined cyclooxygenase/lipoxygenase inhibitor BW755C, the selective lipoxygenase inhibitor U60257, or the leukotriene receptor antagonist LY171883. Hemodynamic measurements were obtained after drug administration and during a subsequent hypoxic challenge (FIO2 = 0.13). Initial hypoxic challenge increased pulmonary artery pressure 68% and increased pulmonary vascular resistance 104%. Pulmonary hemodynamics after recovery from hypoxia were similar to initial baseline values. Drug administration had no significant hemodynamic effect. Hypoxic challenge after drug administration resulted in a pulmonary pressor response identical to the initial hypoxic challenge. Because leukotriene synthesis inhibition and receptor blockade did not alter the response to hypoxia, we conclude that leukotrienes are not obligatory mediators of HPV. A critical review of the literature supports a modulatory rather than an obligatory role for leukotrienes in HPV.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1990

Pressure measurement artifact with analog-to-digital conversion.

Pressure was transduced with the use of a fluid-filled catheter and standard medical monitoring equipment. When the signal was sampled at 200 Hz with an analog-to-digital converter, an artifact was observed. The 3.5-Hz artifact had an amplitude of 0.3 to 0.9 mm Hg and was caused by aliasing of a noise contaminant from the 2,403.5-Hz electrical excitation signal of the transducer. The artifact was completely eliminated with a 100-Hz low-pass filter. Electrical filtering is necessary for accurate acquisition of pressure measurements with analog-to-digital conversion, even when the sampling rate satisfies the Nyquist criterion for the frequency response of the mechanical system. Although the impact of the artifact is small in the clinical area, it is important under some research circumstances.

Amplifiers, Electronic↗