Biomedical subjects

M Leeman

Publications and source records attributed to M Leeman.

At least 55 records · Page 3Linked to original sources

PubMed1993

Bisoprolol and atenolol in essential hypertension: effects on systemic and renal hemodynamics and on ambulatory blood pressure.

The acute and short-term responses to bisoprolol and to atenolol on systemic and renal hemodynamics and on ambulatory blood pressure (BP) were compared in a randomized double-blind cross-over study including 14 patients with mild to moderate essential hypertension. After a 4-week placebo period, the patients received either bisoprolol (10 mg once daily, o.d.) or atenolol (100 mg o.d.) for 4 weeks and were switched to the other drug after a new 4-week placebo period. Cardiac output (CO) was measured by Doppler echography, and renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by constant infusion techniques using [123I]iodohippurate and [51Cr]EDTA, respectively. Bisoprolol and atenolol decreased diurnal and nocturnal blood pressure (BP). Both drugs decreased heart rate (HR) and BP both acutely and after 4 weeks. During short-term treatment, CO was maintained with bisoprolol but reduced by atenolol (by 17%). RBF decreased after the first drug intake (by 9 and 12%, respectively) but returned to its baseline value after 4 weeks, so that calculated renal vascular resistance (RVR) was reduced (by 12 and 15%, respectively). Overall, GFR was not affected by treatment. Bisoprolol and atenolol are effective antihypertensive agents that preserve renal hemodynamics during short-term treatment.

Adult↗

PubMed1993

Is nitric oxide released in oleic acid lung injury?

Inhibitors of endothelium-derived nitric oxide synthesis or activity have been reported to enhance hypoxic vasoconstriction in isolated lung preparations. We hypothesized that methylene blue, a guanylate cyclase inhibitor, and N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, would increase pulmonary vascular tone and improve gas exchange in anesthetized and ventilated (inspired O2 fraction 0.4) dogs with oleic acid (OA) lung injury. Mean pulmonary arterial pressure-(Ppa) flow (Q) relationships (generated by a manipulation of venous return, which was increased by opening a femoral arteriovenous bypass or decreased by inflating an inferior vena cava balloon) and gas exchange (evaluated by arterial blood gases and SF6 intrapulmonary shunt determinations) were investigated before and after OA (0.06 ml/kg i.v.) and again after solvent (n = 8), methylene blue (8 mg/kg i.v., n = 10), or N omega-nitro-L-arginine (40 mg/kg i.v., n = 8) in a randomized order. OA administration induced pulmonary hypertension, decreased arterial PO2, and increased intrapulmonary shunt. After OA, solvent had no effect on pulmonary hemodynamics and gas exchange. Both methylene blue and N omega-nitro-L-arginine further increased Ppa at all levels of Q. Only methylene blue, however, improved gas exchange after OA (arterial PO2 from 71 +/- 6 to 89 +/- 12 Torr and intrapulmonary shunt from 44 +/- 6 to 34 +/- 6%, both P < 0.02). These results suggest that nitric oxide is released during OA lung injury and modulates pulmonary hypertension. Whether nitric oxide impairs the regulation of gas exchange in OA lung injury remains uncertain, however.

Amino Acid Oxidoreductases↗

PubMed1993

[Treatment of arterial hypertension after surgery of the abdominal aorta: comparison of captopril and nifedipine administrated sublingually].

Treatment of high blood pressure after abdominal aortic surgery requires, because of adynamic ileus, the use of intravenously or sublingually (SL) administered drugs. The hemodynamic responses to captopril 25 mg SL (n = 10) and to nifedipine 10 mg SL (n = 10) were studied for 2 hours in patients (mean age 66 years) with arterial hypertension (mean blood pressure, Pa > or = 115 mmHg) the day after abdominal aortic surgery. Patients with bilateral renal artery stenoses, identified with the preoperative angiogram, were excluded. Systemic arterial pressure and pulmonary vascular pressures were measured using a femoral catheter and a pulmonary artery catheter respectively. Cardiac output (Q) was determined by thermodilution. [table: see text] Captopril and nifedipine significantly decreased pulmonary artery pressure, pulmonary artery occlusion pressure and right atrial pressure. No deterioration of renal function was observed. In conclusion, captopril and nifedipine SL are effective and well tolerated for the treatment of high blood pressure after abdominal aortic surgery.

Administration, Sublingual↗

PubMed1992

Long-term acceptability of perindopril: European multicenter trial on 856 patients.

The acceptability of perindopril in the long-term treatment of patients with mild to severe essential hypertension was assessed in a large European multicenter trial including 856 patients. Diastolic blood pressure (DBP) at inclusion was 95-125 mm Hg after 1 month of placebo. Normalization of blood pressure was defined as a DBP less than or equal to 90 mm Hg. Treatment was started with perindopril 4 mg once daily and increased when necessary to 8 mg daily. If DBP was not controlled, a second drug (hydrochlorothiazide) and finally a third drug were added. After 1 year of treatment in all 690 evaluable patients, supine systolic and diastolic blood pressure decreased by 29 mm Hg (from 172 +/- 1 to 143 +/- 1 mm Hg, p less than 0.001) and 19 mm Hg (from 105 +/- 1 to 86 +/- 1 mm Hg, p less than 0.001), respectively. Perindopril monotherapy normalized blood pressure in 55% of patients and total percentage of normalization was 78%. The overall incidence of withdrawals for side effects was 6.8%, the most common side effect being cough (2.2%). The most frequent complaints reported were cough (7.0%), headache (5.6%), asthenia (5.1%), mood and/or sleep disturbance (5.1%), and dizziness (3.2%). The small changes observed in hematologic and biochemical parameters were not clinically relevant.

Adolescent↗

PubMed1992

Reappearance of a normal circadian rhythm of blood pressure after cardiac transplantation.

Twenty-four-hour blood pressure (BP) and heart rate profiles were recorded in 19 patients 1 and 7 months after cardiac transplantation using noninvasive ambulatory monitors and were analyzed using the periodogram method. These recordings were compared with those of control subjects matched for age, sex and daytime ambulatory BP. One month after transplantation, the nighttime decrease in systolic and diastolic BPs were attenuated in the patients as compared to the control subjects (p less than 0.001). The daily oral dose of prednisolone was inversely correlated with the magnitude of the nighttime decreases in systolic and diastolic BPs (r = -0.47 and -0.53, p less than 0.05). In contrast, 7 months after transplantation, the nighttime decrease in systolic and diastolic BPs reappeared in the patients and was of similar magnitude as that in the control subjects. When the immunosuppressive regimens during the 2 periods of recordings were compared, the reduction in the daily oral dose of prednisolone administered to the patients 7 months after transplantation was correlated with the observed increase in the day-night systolic and diastolic BP difference (r = 0.61, p less than 0.01 and r = 0.51, p less than 0.05). Thus, data show the reappearance of normal circadian BP profiles in patients with long-term heart transplants, and suggest that glucocorticoid administration may contribute to the abnormal nocturnal BP profiles observed 1 month after transplantation.

Blood Pressure↗

PubMed1992

Acute and chronic effects of lisinopril on renal and systemic hemodynamics in hypertension.

Acute and chronic effects of the converting enzyme inhibitor lisinopril on renal and systemic hemodynamics were studied in 12 patients with mild to moderate essential hypertension. After a washout period, cardiac output (measured by Doppler echography), renal plasma flow, and glomerular filtration rate (measured by isotopic techniques) were determined before and after oral administration of 20 mg lisinopril (visit 1). The same protocol was repeated after 3 months of lisinopril therapy 20 mg once daily (visit 2). Acute administration of lisinopril, both in untreated hypertensive patients (visit 1) and during long-term treatment (visit 2), decreased blood pressure (p < 0.05) and increased renal plasma flow (p < 0.05), while cardiac output and glomerular filtration rate were unchanged. Comparison of baseline parameters between visits 1 and 2 showed that chronic treatment with lisinopril decreased blood pressure and renal vascular resistance and that these effects were still significant 24-hours postdosage. We conclude that lisinopril is an effective antihypertensive agent with favorable renal hemodynamic effects.

Adult↗

PubMed1992

Blunted hypoxic vasoconstriction in oleic acid lung injury: effect of cyclooxygenase inhibitors.

Cyclooxygenase inhibitors have been reported to accentuate pulmonary hypertension and to improve gas exchange in oleic acid (OA) lung injury (Leeman et al. J. Appl. Physiol. 65: 662-668, 1988), suggesting inhibition of hypoxic pulmonary vasoconstriction by a vasodilating prostaglandin. To test this hypothesis, the hypoxic pulmonary vasoreactivity was examined at constant flow (Q; with an arteriovenous femoral bypass or a balloon catheter placed in the inferior vena cava) before and after OA in three groups of anesthetized and ventilated [inspired O2 fraction (FIO2) 0.4] dogs. Intrapulmonary shunt was measured using a SF6 infusion. A time control group (n = 7) had two consecutive hypoxic challenges after OA and received no drug. A treatment group (n = 6) received indomethacin (2 mg/kg iv) before the second hypoxic challenge after OA. A pretreatment group received indomethacin (2 mg/kg iv, n = 7) or aspirin (30 mg/kg iv, n = 6) before OA. In control and treated dogs, the hypoxic pulmonary vasopressor response was attenuated after OA. It was restored after indomethacin but also during the second hypoxic stimulus in the control dogs. After OA, gas exchange at FIO2 0.4 improved with indomethacin but not in controls. In pretreated dogs the hypoxic vasopressor response to hypoxia was preserved after OA, and gas exchange at FIO2 0.4 was less deteriorated compared with nonpretreated dogs (arterial O2 pressure 139 +/- 7 vs. 76 +/- 6 Torr, P less than 0.01, and intrapulmonary shunt 14 +/- 2 vs. 41 +/- 5%, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Cyclooxygenase inhibition aggravates pulmonary hypertension and deteriorates gas exchange in canine pulmonary embolism.

We examined the effects of cyclooxygenase inhibitors on pulmonary hemodynamics and gas exchange after experimental acute pulmonary embolism in 12 intact anesthetized dogs. Pulmonary hemodynamics were evaluated by pulmonary arterial pressure (Ppa)/cardiac output (Q) plots before and 60 min after autologous blood clot embolization and again 30 min after cyclooxygenase inhibition, either by acetylsalicylic acid (ASA, n = 6) or by indomethacin (INDO, n = 6). Gas exchange was assessed using the multiple inert gas elimination technique, at a constant intermediate Q, under each of these experimental conditions. Embolization increased Ppa at all levels of Q studied (p less than 0.001), increased true shunt (p less than 0.05), and shifted perfusion (Q) and ventilation (VA) distributions to lower and higher VA/Q (p less than 0.05), respectively. ASA and INDO further shifted Ppa/Q plots toward higher pressures (p less than 0.05). Concomitantly, the physiologic dead space increased after INDO (p less than 0.001), and the proportion of lung units with a high VA/Q increased and the inert gas dead space decreased after both ASA (p less than 0.05) and INDO (p less than 0.05). We conclude that, in experimental pulmonary embolism, structurally different cyclooxygenase inhibitors aggravate pulmonary hypertension and deteriorate gas exchange by an altered distribution of VA/Q essentially to lung units with a higher than normal VA/Q. These findings may be explained by changes in the distributions of both VA and of Q as a consequence of cyclooxygenase inhibition-associated increases in both bronchial and vascular tone in embolized lung regions.

Animals↗

PubMed1992

Almitrine and doxapram in experimental lung injury.

Almitrine and doxapram, two structurally unrelated peripheral chemoreceptor agonists, have been shown to enhance hypoxic pulmonary vasoconstriction in anesthetized dogs. We hypothesized that these drugs would increase pulmonary vascular tone and improve gas exchange in canine lung injury caused by oleic acid (OA). Pulmonary hemodynamics and gas exchange were investigated in pentobarbital-anesthetized dogs before and after intravenously administered OA 0.09 ml/kg and again after placebo (n = 6), almitrine 2 micrograms/kg/min (n = 6), or doxapram 20 micrograms/kg/min (n = 6) in a randomized order. Cardiac output (Q) was manipulated using a femoral arteriovenous bypass and an inferior vena cava balloon catheter to construct mean pulmonary artery pressure (Ppa)-Q plots in order to discriminate active from passive changes in Ppa. Gas exchange was assessed by measuring arterial PO2 and intrapulmonary shunt, determined using a sulfur hexafluoride infusion. OA increased Ppa over the range of Q studied, and it deteriorated gas exchange by an increase in intrapulmonary shunt. After OA, placebo had no effect on Ppa, arterial PO2, or intrapulmonary shunt. Both almitrine and doxapram further increased Ppa at all levels of Q studied, but they did not affect indices of gas exchange after OA. We conclude that in this experimental model of acute lung injury, almitrine and doxapram induce pulmonary vasoconstriction without, however, diverting blood flow toward better oxygenated lung regions.

Almitrine↗

PubMed1991

The pulmonary circulation in acute lung injury: a review of some recent advances.

1. According to the Starling resistor model of the pulmonary circulation, the pulmonary hypertension of oleic acid lung injury, an experimental model close to the early stage of clinical ARDS, primarily results from an increased vascular closing pressure which exceeds Pla and becomes the effective outflow pressure of the pulmonary circulation. Therefore, calculated pulmonary vascular resistance should be interpreted cautiously during haemodynamic investigations in patients with ARDS. 2. Part of this increased vascular closing pressure is functional. During acute lung injury pulmonary vasomotor tone can be reduced by vasodilators, or increased by cyclooxygenase inhibitors and almitrine. 3. Pulmonary vasodilation due to infused vasodilators usually impairs gas exchange in ARDS. 4. There is evidence that HPV is altered during ARDS. Drugs capable of enhancing the efficacy of HPV could improve gas exchange. If proven safe in the future, cyclooxygenase inhibitors and almitrine are interesting compounds to be tested in ARDS.

Acute Disease↗

PubMed1991

Acid-base status affects gas exchange in canine oleic acid pulmonary edema.

The effects of acidosis and alkalosis on pulmonary gas exchange were studied in 32 pentobarbital sodium-anesthetized intact dogs after induction of oleic acid (0.06 ml/kg) pulmonary edema. Gas exchange was assessed at constant ventilation and constant cardiac output, by venous admixture calculations and by intrapulmonary shunt measurements using the sulfur hexafluoride (SF6) method. Metabolic acidosis (pH 7.20) and alkalosis (pH 7.60) were induced with HCl and Carbicarb (isosmolar Na2CO3 and NaHCO3), respectively. Hypercapnia was induced by adding inspiratory CO2, whereas pH was allowed to change (respiratory acidosis, pH 7.20) or maintained constant (isolated hypercapnia). Mean intrapulmonary shunt and pulmonary arterial minus wedge pressure difference, respectively, changed from 44 to 33% (P less than 0.05) and from 9 to 10 mmHg (P greater than 0.05) in metabolic acidosis, from 44 to 62% (P less than 0.001) and from 12 to 8 mmHg (P less than 0.01) in metabolic alkalosis, from 40 to 42% (P greater than 0.05) and from 13 to 16 mmHg (P less than 0.05) in respiratory acidosis, from 42 to 52% (P less than 0.05) and from 8 to 12 mmHg (P less than 0.01) in isolated hypercapnia. These results indicate that acidosis, alkalosis, and hypercapnia markedly influence pulmonary gas exchange and/or pulmonary hemodynamics in dogs with oleic acid pulmonary edema.

Acidosis↗

PubMed1991

PEEP inhibits hypoxic pulmonary vasoconstriction in dogs.

The effects of an increase in alveolar pressure on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We therefore studied the effects of positive end-expiratory pressure (PEEP) on pulmonary hemodynamics in 13 pentobarbital-anesthetized dogs ventilated alternately in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). In this intact animal model, HPV was defined as the gradient between hypoxic and hyperoxic transmural (tm) mean pulmonary arterial pressure [Ppa(tm)] at any level of cardiac index (Q). Ppa(tm)/Q plots were constructed with mean transmural left atrial pressure [Pla(tm)] kept constant at approximately 6 mmHg (n = 5 dogs), and Ppa(tm)/PEEP plots were constructed with Q kept constant approximately 2.8 l.min-1.m-2 and Pla(tm) kept constant approximately 8 mmHg (n = 8 dogs). Q was manipulated using a femoral arteriovenous bypass and a balloon catheter in the inferior vena cava. Pla(tm) was held constant by a balloon catheter placed by left thoracotomy in the left atrium. Increasing PEEP, from 0 to 12 Torr by 2-Torr increments, at constant Q and Pla(tm), increased Ppa(tm) from 14 +/- 1 (SE) to 19 +/- 1 mmHg in hyperoxia but did not affect Ppa(tm) (from 22 +/- 2 to 23 +/- 1 mmHg) in hypoxia. Both hypoxia and PEEP, at constant Pla(tm), increased Ppa(tm) over the whole range of Q studied, from 1 to 5 l/min, but more at the highest than at the lowest Q and without change in extrapolated pressure intercepts. Adding PEEP to hypoxia did not affect Ppa(tm) at all levels of Q.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effects of vasodilators on gas exchange in acute canine embolic pulmonary hypertension.

Pulmonary vascular tone was investigated by the construction of pulmonary arterial pressure (PAP)/cardiac output (Q) plots, and gas exchange, by the multiple inert gas elimination technique, in 24 anesthetized dogs before and after pulmonary embolization of autologous clots. Three PAP/Q plots were obtained by a manipulation of venous return at baseline and 60 min and 110 min after embolization. Before the third PAP/Q plot, the dogs were randomly allocated to one of the following iv treatments: 1) placebo (n = 6); 2) prostaglandin E1 (PGE1) 0.4 microgram.kg-1.min-1 (n = 6); 3) hydralazine 2 mg/kg (n = 6); and 4) nitroprusside 10 microgram.kg-1.min-1 (n = 6). These vasodilators decreased systemic arterial pressure by a mean of 44%. Ventilation-perfusion (VA/Q) distributions were determined at the same Q (2.4 +/- 0.1 l.min-1.m-2, mean +/- SE) of each PAP/Q plot. Embolization increased the intercept and the slope of the PAP/Q plots (P less than 0.001). Distributions of VA/Q were only moderately impaired, with an increased dispersion of both VA and Q and a shift of VA distributions to higher VA/Q. PaO2 changed from 208 +/- 5 to 172 +/- 8 mmHg (P less than 0.01) (fraction of inspired O2 was 0.4). None of the treatments had any effect on VA/Q distributions. Placebo and PGE1 had no effect on PAP/Q plots. Hydralazine and nitroprusside reduced the slope of the PAP/Q plots. Thus, in this canine model of acute pulmonary embolism: 1) VA/Q distributions were moderately impaired accounting for only slight hypoxemia, and 2) pulmonary hypertension was partially reversible by hydralazine and by nitroprusside without associated non-flow-dependent change in VA/Q distributions and arterial oxygenation.

Acute Disease↗

PubMed1990

Enhancement of hypoxic pulmonary vasoconstriction by metabolic acidosis in dogs.

The effects of HCl infusion on multipoint mean pulmonary arterial pressure (PAP)/cardiac index (CI) plots in pentobarbital-anesthetized dogs whose lungs were ventilated alternately in hyperoxia (fraction of inspired O2 [FIO2], 0.4) and hypoxia (FIO2, 0.1) were investigated. Over the range of CI studied (1 to 5 l.min-1.m-2), hypoxia increased PAP in 22 dogs (responders) and did not affect PAP in 16 other dogs (nonresponders). In eight nonresponders, two repetitions of alternated 0.4 and 0.1 FIO2 exposures did not restore hypoxic pulmonary vasoconstriction (HPV), defined as a hypoxia-induced increase in PAP at a given flow. Intravenous infusion of 2 M HCl (2 mmol.kg-1.h-1) decreased arterial pH from normal to around 7.20 in eight responders and eight nonresponders. This metabolic acidosis increased PAP at all levels of CI in hyperoxia and in hypoxia in all the dogs, enhanced HPV in the responders, and restored HPV in the nonresponders. In eight responders, 2 M HCl infusion (2 mmol.kg-1.h-1) together with a 7% sodium bicarbonate infusion (adjusted to maintain arterial pH unchanged) did not affect hyperoxic or hypoxic PAP/CI plots. Pretreatment with 1 g acetylsalicylic acid iv (6 dogs) did not affect the pulmonary vasoreactivity to HCl-induced (2 M HCl, 2 mmol.kg-1.h-1) metabolic acidosis. It was concluded that in intact dogs: 1) metabolic acidosis enhances HPV; 2) at the given dose, HCl does not produce pulmonary vascular effects unrelated to the circulating blood pH; and 3) it is unlikely that the pulmonary vasoreactivity to metabolic acidosis is mediated by products of the cyclooxygenase pathway.

Acidosis↗

PubMed1990

Effects of acidosis and alkalosis on hypoxic pulmonary vasoconstriction in dogs.

We studied the effects of metabolic and respiratory acidosis (pH 7.20) and alkalosis (pH 7.60) on pulmonary vascular tone in 32 pentobarbital-anesthetized dogs ventilated with hyperoxia (inspired oxygen fraction, FIO2 0.40) and with hypoxia (FIO2 0.10). Ventilation, pulmonary capillary wedge pressure (Ppw), and cardiac output (3 l.min-1.m-2) were maintained constant to prevent passive changes in pulmonary arterial pressure (Ppa). Metabolic acidosis and alkalosis were induced with HCl (2 mmol.kg-1.h-1) and NaHCO3-Na2CO3 (5 mmol.kg-1.h-1) infusions, respectively, and respiratory acidosis and alkalosis by modifying the inspiratory CO2 fraction. The hypoxia-induced rise in Ppa-Ppw gradient increased from 5 to 9 mmHg in metabolic acidosis (P less than 0.001), decreased from 6 to 1 mmHg in metabolic alkalosis (P less than 0.001), remained unchanged in respiratory acidosis, and decreased from 5 to 2 mmHg in respiratory alkalosis (P less than 0.001). Linear relationships were found between pH and Ppa-Ppw gradients. These data indicate that in intact anesthetized dogs, metabolic acidosis and alkalosis, respectively, enhance and reverse hypoxic pulmonary vasoconstriction (HPV). Respiratory acidosis did not affect HPV and respiratory alkalosis blunted HPV, which suggests an pH-independent vasodilating effect of CO2.

Acidosis↗

PubMed1990

Inhibition of hypoxic pulmonary vasoconstriction by increased left atrial pressure in dogs.

To further explore the mechanism of hypoxic pulmonary vasoconstriction, we studied the mean pulmonary arterial pressure (Ppa)/left atrial pressure (Pla) relationship at fixed cardiac index (Q) and the Ppa/Q relationship at several levels of fixed Pla in pentobarbital sodium-anesthetized dogs ventilated alternately in hyperoxia [fraction of inspired O2 (FIO2) 0.4 or 1.0] and in hypoxia (FIO2 0.1). In all experimental conditions, Ppa/Q plots were linear with extrapolated pressure intercepts (Pi) not significantly different from Pla. Hypoxia increased the slope of Ppa/Q plots and did not affect Pi. In hyperoxia, increasing Pla (3 to 26 mmHg) induced approximately equal increases in Ppa at fixed Q and shifted Ppa/Q plots toward higher pressures in a parallel manner. In hypoxia, increasing Pla (4 to 25 mmHg) did not affect Ppa at fixed Q until Pla exceeded 16 mmHg and shifted Ppa/Q plots toward higher pressures with a decrease in slope. Consequently, the hypoxia-induced increases in Ppa at constant Q and constant Pla were attenuated at higher Pla. Thus, in anesthetized dogs, hypoxia increases the slope of Ppa/Q plots without affecting Pi at fixed Pla, and an increase in Pla inhibits hypoxic pulmonary vasoconstriction. These results can be explained without invoking a hypoxia-induced Starling resistor mechanism in the pulmonary circulation.

Animals↗

PubMed1990

Nature of pulmonary hypertension in canine oleic acid pulmonary edema.

It has recently been suggested that pulmonary hypertension secondary to oleic acid lung injury mainly results from an increase in the critical closing pressure of the pulmonary vessels [Boiteau et al., Am. J. Physiol. 251 (Heart Circ. Physiol. 20): H1163-H1170, 1986]. To further test this hypothesis, we studied 1) the pulmonary arterial pressure- (Ppa) flow (Q) relationship with left atrial pressure (Pla) kept constant (n = 7) and 2) the Ppa-Pla relationship with Q kept constant (n = 9) in intact anesthetized and ventilated dogs before and after lung injury induced by oleic acid (0.09 ml/kg iv). Q was manipulated by use of a femoral arteriovenous bypass and a balloon catheter inserted in the inferior vena cava. Pla was manipulated with a balloon catheter placed by thoracotomy in the left atrium. Ppa-Q plots were rectilinear before as well as after oleic acid. Before oleic acid, the extrapolated pressure intercept of the Ppa-Q plots approximated Pla. Oleic acid administration resulted in a parallel shift of the Ppa-Q plots to higher pressure; i.e., the pressure intercept increased, whereas the slope was not modified. Increasing Pla at constant Q before oleic acid led to a proportional augmentation of Ppa. After oleic acid, however, changes in Pla over the same range affected Ppa only at the highest levels of Pla. These results suggest that oleic acid lung injury increases the critical closing pressure that exceeds Pla, becomes the effective outflow pressure of the pulmonary circulation, and is responsible for the pulmonary hypertension.

Animals↗

PubMed1990

Effects of PEEP on pulmonary hemodynamics in intact dogs with oleic acid pulmonary edema.

The effects of positive end-expiratory pressure (PEEP) on the pulmonary circulation were studied in 14 intact anesthetized dogs with oleic acid (OA) lung injury. Transmural (tm) mean pulmonary arterial pressure (Ppa)/cardiac index (Q) plots with transmural left atrial pressure (Pla) kept constant were constructed in seven dogs, and Ppa(tm)/PEEP plots with Q and Pla(tm) kept constant were constructed in seven other dogs. Q was manipulated by using a femoral arteriovenous bypass and a balloon catheter inserted in the inferior vena cava. Pla was manipulated using a balloon catheter placed by thoracotomy in the left atrium. Ppa(tm)/Q plots were essentially linear. Before OA, the linearly extrapolated pressure intercept of the Ppa(tm)/Q relationship approximated Pla(tm). OA (0.09 ml/kg into the right atrium) produced a parallel shift of the Ppa(tm)/Q relationship to higher pressures; i.e., the extrapolated pressure intercept increased while the slope was not modified. After OA, 4 Torr PEEP (5.4 cmH2O) had no effect on the Ppa(tm)/Q relationship and 10 Torr PEEP (13.6 cmH2O) produced a slight, not significant, upward shift of this relationship. Changing PEEP from 0 to 12 Torr (16.3 cmH2O) at constant Q before OA led to an almost linear increase of Ppa(tm) from 14 +/- 1 to 19 +/- 1 mmHg. After OA, Ppa(tm) increased at 0 Torr PEEP but changing PEEP from 0 to 12 Torr did not significantly affect Ppa(tm), which increased from 19 +/- 1 to 20 +/- 1 mmHg. These data suggest that moderate levels of PEEP minimally aggravate the pulmonary hypertension secondary to OA lung injury.

Animals↗