Biomedical subjects

S Adnot

Publications and source records attributed to S Adnot.

At least 91 records · Page 5Linked to original sources

PubMed1993

Dilator effect of endothelins in pulmonary circulation: changes associated with chronic hypoxia.

To investigate dilator effects of endothelins (ETs) on the pulmonary circulation and possible changes induced by chronic hypoxia, we examined vascular responses to ET-1 and ET-3 as well as ET binding to receptor subtypes ETA and ETB in the lungs from rats exposed to either room air (controls), hypoxia (10% O2) for 3 wk (3 WH), or 3 WH followed by recovery to room air (3 WH+R). In controls, both ETA and ETB receptor binding was present in smooth muscle of airways and vessels. Infusion of ET-1 or ET-3 (3-100 pM) to isolated perfused lungs preconstricted by U-46619 produced dose-dependent vasodilation with a greater potency of ET-3 (P < 0.01). The vasodilator responses to ET-1 and ET-3 were potentiated by the cyclooxygenase blocker meclofenamate (3 x 10(-6) M) or by the thromboxane synthetase inhibitor R-68070. In meclofenamate-treated lungs, the vasodilator responses to ET-1 and ET-3 remained unaffected by the inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (5 x 10(-4) M) or by the guanylate cyclase inhibitor, methylene blue (10(-4) M). Conversely, the K+ channel blockers glibenclamide (10(-4) M) and tetraethylammonium (10(-4) M) attenuated the vasodilator responses to both ET-1 and ET-3. The selective ETA receptor antagonist BQ-123 did not alter ET-induced vasodilation, whereas it attenuated ET-induced vasoconstriction. Vasodilation to both ET-1 and ET-3 was abolished in lungs from 3 WH rats (P < 0.01) but was fully restored in lungs from 3 WH+R rats. Pulmonary vasodilation induced by the K+ channel opener pinacidil, which was suppressed by glibenclamide, did not differ between controls and 3 WH rat lungs. We found no change in ETA and ETB receptor binding from pulmonary vessels in H rat lungs compared with controls. In conclusion, endothelin-induced pulmonary vasodilation which may involve activation of K+ channels is abolished during chronic hypoxia. This abolition does not appear to be related to alterations in ET-receptor subtypes or to unresponsiveness of K+ channels in the pulmonary circulation.

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

PubMed1993

Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension.

To investigate endothelium-dependent and endothelium-independent nitric oxide (NO) mediated pulmonary vasodilation in patients with chronic obstructive lung disease (COLD), we examined the responses to incremental infusion rates of acetylcholine (ACh) or inhaled NO on hemodynamic and gas exchange. In 13 patients, ACh (15 mg/min) decreased pulmonary artery pressure (Ppa) from 31 +/- 1 to 28 +/- 1 mm Hg (p < 0.01) and systemic arterial pressure while increasing cardiac index from 3.7 +/- 0.4 to 4.7 +/- 0.4 L/min/m2 (p < 0.01). Inhaling 40 parts per million (ppm) NO decreased Ppa from 32 +/- 1 to 26 +/- 1 mm Hg (p < 0.001) with no associated hemodynamic change. ACh reduced PaO2 from 57 +/- 3 to 48 +/- 2 mm Hg (p < 0.01) and increased venous admixture (QVA/QT) from 35 +/- 3 to 45 +/- 3% (p < 0.01). Inhaling 40 ppm NO increased PaO2 from 57 +/- 3 to 60 +/- 3 mm Hg (p < 0.01) and decreased QVA/QT from 36 +/- 3 to 32 +/- 3% (p < 0.01). Pulmonary vascular resistance changes were similar in response to 40 ppm NO or 15 mg/min ACh. In COLD patients, ACh produces both pulmonary and systemic vasodilation but impairs arterial oxygenation whereas inhaled NO induces selective pulmonary vasodilation while improving gas exchange. The resistance to ACh in some patients could be related to pulmonary endothelial dysfunction.

Acetylcholine↗

PubMed1993

Role of atrial natriuretic factor in impaired sodium excretion of normocapnic and hypercapnic patients with chronic obstructive lung disease.

To investigate the mechanisms of sodium retention in patients with chronic obstructive lung disease (COLD), we examined the renal and hormonal responses to volume expansion with isotonic saline and to infusion of atrial natriuretic factor (ANF) in 10 hypercapnic (PaCO2 52 +/- 2 mm Hg) and 12 normocapnic patients (PaCO2 39 +/- 1 mm Hg). Sodium excreted within 4 h of loading (expressed as % sodium load) was 23.5 +/- 2.5% (p < 0.05) in normocapnic and 8.5 +/- 1.5% (p < 0.001) in hypercapnic patients, compared with 32.5 +/- 3.0% in 11 age-matched control subjects. Sodium excretion and renal blood flow correlated negatively with arterial PCO2 and positively with FEV1. Basal plasma ANF concentrations were 72 +/- 5 pg/ml in controls, 100 +/- 14 pg/ml in normocapnic patients, and 230 +/- 52 pg/ml in hypercapnic patients (p < 0.001). Plasma renin activity and aldosterone did not differ between groups. In response to volume expansion, plasma ANF increased in both normocapnic and controls (with a greater increase in normocapnic patients) but remained unchanged in hypercapnic patients. Exogenous ANF increased glomerular filtration rate, renal plasma flow, natriuresis, and diuresis in both groups of patients. Patients with COLD have depressed renal function that appears unrelated to activation of the renin-angiotensin-aldosterone system. An increased secretory response of ANF to volume expansion may help to maintain volume homeostasis in normocapnic patients, while a blunted secretory response of ANF may contribute to sodium retention in hypercapnic patients.

Aged↗

PubMed1993

Mechanisms of impaired arterial oxygenation in patients with liver cirrhosis and severe respiratory insufficiency. Effects of indomethacin.

The mechanisms of impaired arterial oxygenation that occur in certain patients with chronic liver cirrhosis are still debated. In the present study, we investigated nine cirrhotic patients with severe respiratory disability (mean PaO2, 64 +/- 5 mm Hg), using the inert gas elimination technique to assess the distribution of ventilation-perfusion (VA/Q) ratios. We also determined shunt fraction during pure oxygen breathing, both in supine and sitting positions. To test the hypothesis that vasodilating prostaglandins could contribute to alter gas exchange in such patients with cirrhosis, we examined the hemodynamic and gasometric responses to indomethacin, 50 mg IV, in six of them. During baseline conditions, patients had high cardiac index (CI, 4.9 +/- 0.2 L/min/m2), and low pulmonary (PVR, 1.78 +/- 0.37 mm Hg/L/min/m2) or systemic (SVR, 17.7 +/- 1.15 mm Hg/L/min/m2) vascular resistances. Large intrapulmonary shunt fraction was documented in each patient with a mean value of 19.6 +/- 2.7 percent. Small perfusion in low VA/Q areas was associated with shunt in only three patients (2.5 to 5.3 percent of blood flow). Arterial PO2 was negatively related to shunt (p < 0.01) and to the dispersion of blood flow distribution (p < 0.02). There was no difference between measured and predicted PaO2. Shunt estimates from the inert gas and the 100 percent O2 breathing techniques were, respectively, 19.6 +/- 2.7 percent and 21.7 +/- 3.0 percent. During 100 percent oxygen breathing, changing from supine to sitting position decreased PaO2 from 401 +/- 50 to 333 +/- 64 mm Hg (p < 0.02), while O2 shunt remained unchanged, arteriovenous difference widened, and mixed venous PO2 decreased, from 61 +/- 3 to 47 +/- 4 mm Hg (p < 0.001). Indomethacin did not improve gas exchange or VA/Q distribution and did not affect systemic or pulmonary hemodynamics. The results show that in cirrhotic patients with severe respiratory disability, intrapulmonary shunting is the main determinant of impaired gas exchange, with no evidence of a defect in oxygen diffusion or an extrapulmonary shunt. Vasodilating prostaglandins do not appear to contribute to these alterations.

Aged↗

PubMed1993

[Effects of intracoronary injection of SIN-1 on vasoconstriction of epicardial arteries induced by acetylcholine].

Linsidomine or SIN-1, a vasodilator of epicardial arteries, is the active metabolite of Molsidomine which is regularly used for intracoronary injection. Although its vasodilatory action has been demonstrated on the large coronary vessels, it is not known whether this molecule can vasodilate epicardial coronary arteries which have been vasoconstricted with acetylcholine. Twelve patients with left anterior descending artery (LAD) disease were studied. Intracoronary flow velocity was measured with a Doppler catheter (Millar) placed in the proximal segment of the LAD and the diameter of the artery was evaluated by quantitative angiography. After recording the basal haemodynamic parameters, 12 mg of papaverine were injected into the left main coronary artery. After regaining the basal state, three incremental doses of acetylcholine (5 x 10(-7), 1(-6) and 5 x 10(-6) M) were selectively injected into the LAD over a 3 minute period for each injection. Then, during continuous infusion of 5 x 10(-6) of acetylcholine, 1 mg of SIN-1 was injected in a bolus into the left coronary ostium. After the papaverine, the coronary flow velocity increased by 199 +/- 8% associated with a vasoconstrictive tendency in the proximal and distal segments of the LAD (NS). In response to acetylcholine a dose-dependent vasoconstriction vas observed attaining 50 +/- 21% at the last injection in the distal segment of the LAD (p < 0.001). After an initial increase in coronary flow velocity of 46 +/- 11% (p = 0.004) and of 26 +/- 11% (p < 0.05) after the first two doses of acetylcholine, it decreased after the final injection to close to basal values (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1992

Effects of infusion of L-arginine into the left anterior descending coronary artery on acetylcholine-induced vasoconstriction of human atheromatous coronary arteries.

Hypercholesterolemia and atherosclerosis are conditions associated with impaired endothelium-dependent relaxation. In hypercholesterolemic animals, intravenous administration of L-arginine, the precursor of nitric oxide, normalizes endothelium-dependent vasodilator activity. In the present study, we questioned whether intracoronary administration of L-arginine in patients with coronary artery disease could improve coronary vascular reactivity to acetylcholine. Thirteen hypercholesterolemic patients with diffuse coronary atherosclerosis but nonstenotic lesions of the left anterior descending (LAD) coronary artery were investigated. Quantitative coronary angiography and subselective intracoronary Doppler flow velocity measurements were performed to determine LAD diameters and coronary blood flow. Intracoronary infusion of acetylcholine was performed during 3 consecutive 3-minute periods at incremental rates adjusted to achieve estimated final concentrations of 5 x 10(-7), 10(-6) and 5 x 10(-6) M. After evaluation of the response to acetylcholine, L-arginine was infused into the LAD at the rate of 25 mg/min (10(-3) M) and the same stepwise 3-minute infusions of acetylcholine were repeated during infusion of L-arginine. Infusion of acetylcholine induced a dose-dependent reduction of distal epicardial LAD diameter reaching -48.5 +/- 17% at 5 x 10(-6) M (p < 0.01 vs control values). L-arginine alone had no effect on the distal LAD diameter but attenuated acetylcholine-induced vasoconstriction to -21 +/- 9% at 5 x 10(-6) M acetylcholine (p < 0.01). Coronary blood flow showed a biphasic response to acetylcholine, increasing by 41 +/- 12% at 5 x 10(-7) M (p < 0.01) and decreasing by 21 +/- 13% at 5 x 10(-6) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1992

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Beta-adrenergic contractile reserve as a predictor of clinical outcome in patients with idiopathic dilated cardiomyopathy.

To examine the ability of beta-adrenergic contractile reserve assessment to predict the outcome of patients with heart failure, a prospective study was undertaken in 35 patients with idiopathic dilated cardiomyopathy and radionuclide ejection fraction below 40%. During right- and left-sided catheterization, right atrial and left ventricular (LV) pressures, peak positive LV dp/dt, cardiac index, and plasma norepinephrine and epinephrine concentrations were measured at baseline. After a left main intracoronary infusion of dobutamine (25 to 200 micrograms.min-1), beta-adrenergic contractile responsiveness was assessed as the net increase in peak positive LV dp/dt (delta LV dp/dt). After the initial examination, patients were treated with diuretics, digitalis, and angiotensin converting enzyme inhibitors and then followed-up. After a mean follow-up period of 13 +/- 7 months, two groups of patients were distinguished: those who responded to medical therapy (group A, n = 26) and those with clinical deterioration (group B, n = 9) leading to death (n = 4) or heart transplantation (n = 5). Initial peak positive LV dp/dt, LV end-diastolic pressure, cardiac index, and LV ejection fraction were better in group A than in group B (p less than 0.001). Initial plasma norepinephrine and epinephrine concentrations were significantly higher and delta LV dp/dt was lower in group B than in group A (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Myocardial beta-adrenergic desensitization and neuronal norepinephrine uptake function in idiopathic dilated cardiomyopathy.

Desensitization of myocardial beta-adrenergic receptors may result both from an impairment of the norepinephrine (NE) neuronal uptake function and from an increase in circulating NE concentrations. The respective role of these two mechanisms of desensitization was examined in 18 patients with congestive heart failure related to an idiopathic dilated cardiomyopathy. The neuronal NE uptake system was evaluated by [123I]metaiodobenzylguanidine (MIBG) scintigraphy. The desensitization level of beta-adrenoceptors was assessed as the net increase in peak positive left ventricular (LV) dP/dt during intracoronary dobutamine infusion. Arterial NE concentrations were determined at baseline. To obtain control values, we performed MIBG scintigraphy and determined baseline NE concentration in 12 normal subjects. Cardiac MIBG uptake was significantly decreased in patients as compared with controls. This decrease was related to the severity of the disease based on hemodynamic indexes. The inotropic response to intracoronary dobutamine infusion of heart failure patients correlated with both increased baseline NE concentration and diminished cardiac MIBG uptake (r = -0.63, p less than 0.01 and r = 0.73, p less than 0.001, respectively). These findings indicate that the desensitization process is related both to impaired neuronal NE uptake function and increased circulating NE concentrations. Moreover, a subset of 11 patients with moderate heart failure was identified who had diminished cardiac MIBG uptake but normal circulating NE concentrations. This suggests that impairment of the NE uptake function is an early mechanism of desensitization in idiopathic cardiomyopathy. Cardiac MIBG imaging may be a noninvasive means to assess severity of heart failure patients and may also be used to evaluate therapy effects on myocardial alterations of the adrenergic pathway.

3-Iodobenzylguanidine↗

PubMed1992

Endothelin dilates bovine pulmonary circulation and reverses hypoxic pulmonary vasoconstriction.

To assess the effects of endothelin 1 (ET) on the pulmonary and systemic vascular beds simultaneously, we examined the hemodynamic responses to ET in awake calves implanted with a Jarvik total artificial heart (TAH), a device that maintains constant cardiac output (CO). During basal conditions, successive incremental intravenous (i.v.) injections of 1, 3, and 10 micrograms ET caused a dose-dependent decrease in pulmonary arterial pressure (PAP), (from 24 +/- 3 to 15 +/- 1 mm Hg, p less than 0.05) while having no effect on systemic arterial (SAP), left atrial (LAP), and right atrial (RAP) pressures. Administration of 30 micrograms ET i.v. also decreased PAP, had no effect on LAP and RAP, but increased SAP from 100 +/- 6 to 118 +/- 4 mm Hg (p less than 0.05). The decrease in PAP was rapid, occurring within seconds and lasting 10 min, whereas the increase in SAP occurred after 2-5 min and was prolonged for greater than or equal to 20 min. As compared with injection in the right atrium, administration of 30 micrograms ET into the left atrium reduced PAP to a similar extent, but induced a greater increase in SAP (+32.5 +/- 4 vs +17.5 +/- 2 mm Hg, p less than 0.05). ET also dose-dependently reversed the acute pulmonary vasoconstriction induced by inhalation of an hypoxic gas mixture. In all cases, pulmonary vasodilation occurred without evidence of short-term tolerance. The results demonstrate that ET is a potent in vivo pulmonary vasodilator. In calves, the predominant hemodynamic response to ET is pulmonary vasodilation, with systemic vasoconstriction apparent only at higher concentrations of the peptide.

Acute Disease↗

PubMed1992

L-arginine improves endothelium-dependent relaxation of conductance and resistance coronary arteries in coronary artery disease.

To assess the ability of L-arginine to improve endothelium-dependent vasodilation in atheromatous coronary arteries, we determined whether intracoronary infusion of L-arginine could improve coronary vascular reactivity to acetylcholine (ACh) examining both conductance and resistance vessels. Coronary blood flow velocity was assessed by positioning a 3 Fr Doppler catheter into the proximal coronary artery segment (six left anterior descending and one circumflex coronary artery). Computed quantitative angiography allowed the measurement of distal diameters. After baseline measurements, ACh was infused at incremental infusion rates through the Doppler lumen catheter (3 min period each) to obtain the estimated concentrations of 5 x 10(-7), 10(-6), and 5 x 10(-6) M. After returning to baseline, L-arginine was infused at the rate of 25 mg/min (10(-3) M) through the Doppler lumen catheter. Infusion of ACh was then repeated according to the same protocol than in the absence of L-arginine. The heart rate and mean arterial blood pressure did not change at any step of the protocol. Infusion of ACh induced dose-dependent vasoconstriction of coronary distal segments with a reduction in coronary distal segments by 39 +/- 15% at 5 x 10(-6) M (p < 0.01). During infusion of L-arginine, the coronary diameter was reduced by only 16 +/- 10% (p < 0.05) at the highest ACh dose. The coronary blood flow velocity increased by 100 +/- 15% at 5 x 10(-7) M ACh (p < 0.05) but only to 16 +/- 15% at 5 x 10(-6) M ACh (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1992

L-arginine restores endothelium-dependent relaxation in pulmonary circulation of chronically hypoxic rats.

We investigated whether loss of endothelial-derived relaxing factor (EDRF) activity in the pulmonary vessels of chronically hypoxic rats could be restored by pretreatment with L-arginine. We measured vasodilation to acetylcholine (ACh), calcium ionophore A23187, or linsidomine (Sin-1) under conditions of increased vascular tone induced by U-46619 (50 pmol/min), as well as vasoconstriction to endothelin-1 (ET) in isolated lungs pretreated with meclofenamate (3 microM). In lungs from normoxic (N) rats, in vitro L- or D-arginine (10(-3) M) did not alter vasodilation to the endothelium-dependent agents ACh (10(-9)-10(-6) M) and A23187 (10(-9)-10(-7) M), but NG-monomethyl-L-arginine (10(-3) M) completely abolished it. In lungs from rats exposed to 3 wk of hypoxia (H), vasodilation to ACh or A23187 was fully restored after in vitro L-arginine (10(-3) M) or N alpha-benzoyl-L-arginine (5 x 10(-5) M) but remained abolished after D-arginine, L-citrulline, L-ornithine, or L-argininosuccinic acid. In vivo pretreatment of H rats with L-arginine (300 mg/kg iv) 30 min before isolating the lung also restored vasodilation to A23187. Vasodilation to the endothelium-independent agent Sin-1 was similar in both groups of lungs and was not altered by in vitro L-arginine. L-arginine attenuated the increased pressor response to ET (300 pmol) of H rat lungs but had no effect in N rats. Our results demonstrate that loss of EDRF activity associated with hypoxic pulmonary hypertension may be reversed by supplying L-arginine.

Acetylcholine↗

PubMed1992

Pulmonary vasodilatory action of endogenous atrial natriuretic factor in rats with hypoxic pulmonary hypertension. Effects of monoclonal atrial natriuretic factor antibody.

We administered ascitic fluid containing atrial natriuretic factor (ANF) monoclonal antibody to rats after 3 weeks of exposure to hypoxia while the rats were still hypoxic. In additional chronically hypoxic rats, we infused synthetic rat ANF. In conscious chronically instrumented rats, after a bolus dose of 5 micrograms i.v. ANF, pulmonary arterial pressure fell significantly from 26.5 +/- 2 to 21 +/- 2 mm Hg (p less than 0.01), reaching its nadir at 5 minutes without change of systemic arterial pressure, cardiac output, or heart rate. Pulmonary arterial pressure increased gradually from 26 +/- 4 to 34 +/- 4 mm Hg within 30 minutes (p less than 0.05) after acute administration of ANF monoclonal antibody and decreased transiently to return to baseline within 15 minutes after infusion of control ascitic fluid containing monoclonal antibody against an apolipoprotein. Cardiac output and heart rate remained unchanged after both ANF monoclonal antibody and control ascitic fluid. In normoxic rats, acute administration of ANF monoclonal antibody did not cause significant changes in pulmonary arterial pressure, cardiac output, or heart rate. Rats receiving weekly intravenous injections of ANF monoclonal antibody that were started before initiation of exposure to hypoxia experienced significantly aggravated pulmonary hypertension and right ventricular hypertrophy compared with rats receiving repeated infusions of control ascitic fluid. However, there was no significant difference in small pulmonary arterial wall thickness or percentage of muscularized arteries at the alveolar duct level. These results suggest that endogenous ANF attenuates hypoxic pulmonary hypertension by decreasing pulmonary vascular tone.

Animals↗

PubMed1992

Severe hypoxemia-associated intrapulmonary shunt in a patient with chronic liver disease: improvement after medical treatment.

A 20-yr-old woman with chronic liver disease and angioimmunoblastic lymphadenopathy presented with marked hypoxemia caused by intrapulmonary shunt. Her respiratory tract showed her to be free of angioimmunoblastic lymphadenopathy manifestations. After 12 months of treatment with cyclophosphamide and corticosteroid, the immunologic disease disappeared. Unexpectedly, hypoxia-associated intrapulmonary shunt was no longer present either. To the best of our knowledge, this is the first case of dramatic improvement, with medical therapy, of severe hypoxemia related to noncirrhotic liver disease. However, the mechanism by which this treatment caused the regression of intrapulmonary shunt is unknown.

Adult↗

PubMed1991

Changes in the distribution of ventilation and perfusion associated with separation from mechanical ventilation in patients with obstructive pulmonary disease.

A trial of separation from mechanical ventilation may induce an abnormal respiratory pattern and a maldistribution of ventilation-to-perfusion ratios (VA/Q), especially in patients with chronic obstructive pulmonary disease. This study was designed to assess the effects of three different modes of ventilation on the distribution of global and also regional VA/Q in eight patients with chronic obstructive pulmonary disease recovering from acute respiratory failure who remained dependent on mechanical ventilation after more than 5 days of attempted separation from the ventilator. VA/Q distribution was assessed using the multiple inert gas and isotopic scanning methods after 30 min each of controlled mechanical ventilation (CMV), 10 cmH2O inspiratory pressure support, and spontaneous breathing (SB). Controlled ventilation was provided at a respiratory rate ranging from 12 to 18 breaths per min and a tidal volume of 8 ml.kg-1. In comparison to CMV, SB resulted in a decrease in tidal volume (from 512 +/- 144 to 301 +/- 102 ml, P less than 0.01), and an increase in respiratory rate (from 15.5 +/- 3.2 to 27.3 +/- 15.0 breaths per min, P less than 0.05), which increased dead space (+7.1% of minute ventilation), cardiac output (+36%), and the perfusion to areas of low VA/Q (+8.9% of cardiac output) (P less than 0.05, P less than 0.001, and P less than 0.05, respectively). Isotopic scans revealed a horizontal craniocaudal difference of VA/Q in all modes, with the lowest VA/Q zones at the basal part of the lungs (mean basal VA/Q 0.58 in SB and 1.05 in CMV).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Pulmonary vascular reactivity to endothelin-1 in normal and chronically pulmonary hypertensive rats.

The pulmonary vascular reactivity to endothelin-1 (ET-1) was assessed in rats previously exposed to 11% O2 (hypoxic) or room air (controls) for 3 weeks. In isolated control lung preparations studied during conditions of increased tone by U46619 (50 pmol/min) and treated with meclofenamate (3 microM), low doses of ET-1 (30 and 100 pM) reduced the pressor response to U46619 by 58 +/- 5% (p less than 0.01). Vasodilation induced by ET-1 was not abolished by the antagonist of endothelium-dependent relaxing factor (EDRF) NG-monomethyl-L-arginine (5 x 10(-4) M), which suppressed vasodilator response to ionophore A23187 (10(-8)-10(-7) M). Higher doses of ET-1 (300 and 1,000 pM) induced vasoconstriction during conditions of basal tone, and the pressor response to 300 pM ET-1 was enhanced by EDRF antagonists. Administration of ET-1 to lungs from hypoxic rats failed to cause pulmonary vasodilation and instead induced a greater pulmonary pressor response (300 pM) than in control rat lungs (7 +/- 1.5 vs. 1.6 +/- 0.5 mm Hg, p less than 0.01), which was not further potentiated by EDRF antagonists. Infusion of 300 pM ET to conscious catheterized animals induced a sustained increase in pulmonary resistance only in the hypoxic group (from 305 +/- 37 to 389 +/- 55 mm Hg/L/min, p less than 0.01) (n = 7). The results suggest that depending on the dose, ET-1 can cause pulmonary vasodilation (independent of EDRF release) or vasoconstriction (opposed by EDRF). During chronic hypoxic pulmonary hypertension, ET-1 behaves only as a pulmonary vasoconstrictor.

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

PubMed1991

Hemodynamic response to intracoronary infusion of atrial natriuretic factor in patients with normal or altered left ventricular function.

To assess the effects of atrial natriuretic factor (ANF) on cardiac function, synthetic human ANF was infused directly into the left main coronary artery of eight patients with congestive heart failure (CHF) and six subjects with normal left ventricular (LV) function (controls) who underwent cardiac catheterization. ANF infusion at the incremental rates of 60, 125, 400, and 800 ng/min induced a dose-related increase in plasma ANF concentrations in the coronary sinus, from 1,223 +/- 590 to 3,923 +/- 1,123 pg/ml in patients with CHF (p less than 0.01) and from 1,041 +/- 605 to 2,710 +/- 1,741 pg/ml in controls (p less than 0.01). Peripheral plasma ANF concentrations (femoral artery) increased from 538 +/- 278 to 752 +/- 262 pg/ml (p less than 0.01) in patients with CHF and from 193 +/- 63 to 401 +/- 147 pg/ml (p less than 0.01) in controls. The increase in peripheral or coronary sinus plasma ANF concentrations did not differ between patients with CHF and controls. At the three lowest ANF infusion rates, cardiac index (CI), systemic vascular resistance (SVR), and LV contractility assessed by peak positive dP/dt remained unchanged both in patients with CHF and in controls. At the highest ANF infusion rate, CI increased from 2.18 +/- 0.53 to 2.54 +/- 0.49 L/min/m2 (p less than 0.01) and SVR decreased from 14.6 +/- 3.6 to 12.8 +/- 4.5 mm Hg.min/L (p less than 0.01) in patients with CHF. There was no associated change in heart rate (HR), mean arterial blood pressure (MAP), cardiac filling pressures, or peak positive dP/dt.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Hormonal interactions and renal function during mechanical ventilation and ANF infusion in humans.

To investigate the influence of atrial natriuretic factor (ANF) on renal function during mechanical ventilation (MV), we examined the renal and hormonal responses to synthetic human ANF infusion in eight patients during MV with zero (ZEEP) or 10 cmH2O positive end-expiratory pressure (PEEP). Compared with ZEEP, MV with PEEP was associated with a reduction in diuresis (V) from 208 +/- 51 to 68 +/- 11 ml/h (P less than 0.02), in natriuresis (UNa) from 12.4 +/- 3.3 to 6.2 +/- 2.1 mmol/h (P less than 0.02), and in fractional excretion of sodium (FENa) from 1.07 +/- 0.02), 0.21 to 0.67 +/- 0.17% (P less than 0.02) and with an increase in plasma renin activity (PRA) from 4.83 +/- 1.53 to 7.85 +/- 3.02 ng.ml-1.h-1 (P less than 0.05). Plasma ANF levels markedly decreased during PEEP in four patients but showed only minor changes in the other four patients, and mean plasma ANF levels did not change (163 +/- 33 pg/ml during ZEEP and 126 +/- 30 pg/ml during PEEP). Glomerular filtration rate and renal plasma flow were unchanged. Infusion of ANF (5 ng.kg-1.min-1) during PEEP markedly increased V and UNa by 110 +/- 61 and 107 +/- 26%, respectively, whereas PRA decreased from 7.85 +/- 3.02 to 4.40 +/- 1.5 ng.ml-1.min-1 (P less than 0.05). In response to a 10 ng.kg-1.min-1 ANF infusion, V increased to 338 +/- 79 ml/h during ZEEP but only to 134 +/- 45 ml/h during PEEP (P less than 0.02), whereas UNa increased, respectively, to 23.8 +/- 5.3 and 11.3 +/- 3.3 mmol/h (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗