PURPOSE: Atrial natriuretic peptide (ANP) has a variety of pharmacologic effects, including natriuresis, diuresis, vasodilatation, and suppression of the renin-angiotensin system. A recent study showed that ANP infusion improved hypoxemia and pulmonary hypertension in a lung injury model. On the other hand, the pulse contour cardiac output (PiCCO(TM)) system (Pulsion Medical Systems, Munich, Germany) allows monitoring of the intravascular volume status and may be used to guide volume therapy in severe sepsis and critically ill patients. MATERIALS AND METHODS: We treated 10 pulmonary edema patients without heart disease with human ANP (HANP). The patients were divided into two groups: a group with normal Intrathoracic Blood Volume (ITBV) (900-1100 mL/m2) (n = 6), and a group with abnormal ITBV (n = 4), as measured by the PiCCOtrade mark device; the extravascular lung water (EVLW) and pulmonary vascular permeability index (PVPI) in the two groups were compared. RESULTS: The average patient age was 63.9 +/- 14.4 years. The normal ITBV group showed significant improvement of the EVLW (before, 16.7 +/- 2.7 mL/kg; after, 10.5 +/- 3.6 mL/kg; p = 0.0020) and PVPI (before, 3.2 +/- 0.3; after, 2.1 +/- 0.7; p = 0.0214) after the treatment. The abnormal ITBV group showed no significant improvement of either the EVLW (before, 16.3 +/- 8.9 mL/kg; after, 18.8 +/- 9.6 mL/kg; p = 0.8387) or PVPI (before, 2.3 +/- 0.8; after, 2.7 +/- 1.3; p = 0.2782) after the treatment. In both groups, the EVLW and PVPI were strongly correlated with the chest X-ray findings. CONCLUSION: We conclude that HANP supplementation may improve the EVLW and PVPI in pulmonary edema patients without heart disease with a normal ITBV. The PiCCO(TM) system seems to be a useful device for the management of pulmonary edema.
Aged ; Atrial Natriuretic Factor/administration & dosage/*therapeutic use ; Cardiac Output/*drug effects/*physiology ; Female ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Monitoring, Physiologic/*instrumentation ; Pulmonary Edema/*drug therapy/*physiopathology

OBJECTIVESTo assess the changes of the levels of plasma endothelin (ET-1), nitric oxide (NO) and atrial natriuretic peptide (ANP) after cardiopulmonary bypass (CPB) and the influence of inhaled nitric oxide in patients with ventricular septal defect (VSD) and pulmonary hypertension (PH).

METHODSSixty patients with VSD were enrolled in this study. They were divided into 2 groups: group A [no-PH group, mean pulmonary artery pressure (mPAP) < 20 mm Hg (1 mm Hg = 0.133 kPa) n = 20] and group B (PH group, mPAP > 20 mm Hg, n = 40). Group B was subdivided into two groups by randomized block, group B(1) (inhaled NO group, n = 20) and group B(2) (contrast group, n = 20). The plasma ET-1, NO, ANP concentrations were assayed at 24 h pre-operation and 0 h, 1 h, 5 h, 12 h, 24 h, 48 h after CPB.

RESULTSThe preoperative plasma ET-1, NO and ANP concentrations in group B were significantly higher than those in group A. In three groups, the plasma ET-1 concentration at 0 h after CPB was significantly higher than that at 24 h pre-operation, and the plasma NO concentration at 0 h after CPB was significantly lower than that at 24 h pre-operation. In group B, the plasma ANP concentration at 0 h after CPB was significantly higher than that at 24 h pre-operation. After CPB, the plasma ET-1 concentration in group B(1) decreased faster than that in group B(2), and the plasma NO concentration in group B(1) increased faster than that in group B(2). In group B, the preoperative plasma ET-1 concentration negatively correlated with the preoperative plasma NO concentration and positively correlated with the preoperative ANP concentration.

CONCLUSIONSThe broken dynamic balance of ET-1/NO may take part in generation and development of pulmonary hypertension. ANP acts as a favorable physiological regulating factor in the pathogenesis of pulmonary hypertension. CPB can regulate the level of ET-1 up and NO and ANP down while inhaled NO can cause the level of ET-1 down and the level of NO up.

Administration, Inhalation ; Atrial Natriuretic Factor ; blood ; Cardiopulmonary Bypass ; Child, Preschool ; Endothelin-1 ; blood ; Female ; Heart Septal Defects ; blood ; surgery ; Humans ; Hypertension, Pulmonary ; blood ; surgery ; Male ; Nitric Oxide ; blood ; pharmacology

BACKGROUND AND OBJECTIVES: It has been suggested that nitric oxide (NO) and atrial natriuretic peptide (ANP) share a final common pathway for vascular smooth muscle relaxation. The aim of the present study was to determine the role of NO on the hypotensive and vasorelaxant effects of ANP. MATERIALS AND METHODS: Sprague-Dawley rats weighing 250-300 g each were anesthetized with thiopental (50 mg/kg IP). The femoral artery was cannulated and the arterial blood pressure and heart rate were continuously monitored in the anesthetized rats (n=19). ANP was administered into the jugular vein after L-NAME treatment. In vitro experiments were performed on intact and endothelium-denuded isolated thoracic aortic rings (n=51) in the presence of either L-NAME or methylene blue. RESULTS: Intravenous administration of ANP (5 ug/kg bolus and 0.2 ug/kg/min infusion) caused a decrease in the mean arterial pressure. L-NAME-pretreatment (1 mg/kg) suppressed the depressor response of ANP. In vitro, the ANP caused a dose-dependent relaxation, and the relaxation response to ANP was attenuated by L-NAME (10-4 M). Endothelium removal or methylene blue (10-5 M) also inhibited the ANP-induced vascular relaxation. CONCLUSION: These results suggest that the hypotensive and the vasorelaxant effect of ANP are, at least in part, NO-dependent.
Administration, Intravenous ; Animals ; Arterial Pressure ; Atrial Natriuretic Factor ; Endothelium ; Femoral Artery ; Heart Rate ; Jugular Veins ; Methylene Blue ; Muscle, Smooth, Vascular ; NG-Nitroarginine Methyl Ester ; Nitric Oxide* ; Rats* ; Rats, Sprague-Dawley ; Relaxation ; Thiopental

OBJECTIVE: To observe the changes of vasoactive substances in rabbits administered with mannitol at different dosages and to investigate the mechanism of acute renal failure (ARF) induced by massive mannitol administration. METHODS: Eighteen healthy male New Zealand rabbits were randomly divided into 3 groups: a minor mannitol group (n=6, mannitol 8 g/kg within 2 hours), a control group (n=6, saline of the same volume), and a massive mannitol group with free water taking (n=6, mannitol 40~60 g/kg within 3 days). The changes of renin, angiotensin-I (ang-I), angiotensin-II (ang-II), endothelin (ET), and atrial natriuretic factor(ANF) in the serum were observed. RESULTS: No significant changes in the renin, ang-I, ang-II, ET, and ANF in the serum were found between the minor mannitol group and the saline control group (P> 0.05). In the massive mannitol group with free water taking, renin, ang-I, and ang-II in the serum increased significantly compared with the other 2 groups; ET in the serum decreased significantly compared with the saline control group (P< 0.05); no significant changes in the ANF in the serum were found compared with the other 2 groups(P> 0.05). CONCLUSION ARF induced by massive mannitol administration is associated with a significant change of vasoactive substances.
Acute Kidney Injury ; blood ; chemically induced ; physiopathology ; Angiotensins ; blood ; Animals ; Atrial Natriuretic Factor ; blood ; Dose-Response Relationship, Drug ; Endothelins ; blood ; Male ; Mannitol ; administration & dosage ; toxicity ; Rabbits ; Random Allocation ; Renal Circulation ; drug effects ; Renin-Angiotensin System ; drug effects

BACKGROUNDThe clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls.

METHODSWe analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test.

RESULTSThe rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381).

CONCLUSIONSThe rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.

Administration, Inhalation ; Adult ; Aged ; Arterial Pressure ; drug effects ; Atrial Natriuretic Factor ; metabolism ; Calcium Channel Blockers ; administration & dosage ; therapeutic use ; Endarterectomy ; Familial Primary Pulmonary Hypertension ; drug therapy ; physiopathology ; Female ; Hemodynamics ; drug effects ; Humans ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Iloprost ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Protein Precursors ; metabolism ; Retrospective Studies ; Software ; Vasodilator Agents ; administration & dosage ; therapeutic use

OBJECTIVETo observe the effects of Shenqifuxin oral liquid(SQFXOL) on plasma kaliuretic peptide (KP), atrial natriuretic polypeptide(ANP), angiotension II (Ang II), endothelin(ET) and the left ventricular remodeling and the myocardial contractility and relaxation of left ventricle in experimental rats with heart failure(HF).

METHODThe SD rat model with HF was produced by constricting abdominal aorta. Hemodynamic parameters including maximum rate of intraventricular pressure rise (+dp/dtmax), left ventricular systolic pressure(LVSP), maximum velocity of contractile element shortening(Vmax), maximum rate of intraventricular pressure down(-dp/dtmax) and left ventricular end diastolic pressure(LVEDP) were measured by the method of the catheterization. Plasma concentrations of KP, ANP, Ang II and ET were determined by radioimmunoassays. The effects of treatment were evaluated by observing and comparing the changes of heart morphological structure, collagen element, heart weight/body weight ratio (HW/BW), left intraventricular area(LVA) and myocardial nuclei number (MNN) per square area.

RESULTIn high dose SQFXOL group, the LVSP, -dp/dtmax and Vmax were increased, while LVEDP was decreased, and plasma concentrations of KP, Ang II and ET were decreased. In comparision with those in model group, the difference was significant(P < 0.05 or P < 0.01). Though the +dp/dtmax and the level of ANP were decreased, the difference was insignificant(all P > 0.05). The collagen tissues around myocardial cells were reduced. HW/BW and LVA were lower, and MNN per square area was higher significantly (P < 0.05 or P < 0.01). The indices of +dp/dtmax in all of treatment groups and control group were not considerably different in comparison with those in model group. The levels of plasma ANP in middle dose group and low dose group were significantly lower than those in model group(all P < 0.01).

CONCLUSIONSQFXOL can reduce the plasma concentrations of KP, Ang II, ET, and ANP, improve the myocardial contractility and relaxation of left ventricular and inhibitate left ventricular remodeling in rats with HF.

Administration, Oral ; Angiotensin II ; blood ; Animals ; Astragalus membranaceus ; chemistry ; Atrial Natriuretic Factor ; blood ; Cardiotonic Agents ; administration & dosage ; pharmacology ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Endothelins ; blood ; Heart Failure ; blood ; physiopathology ; Male ; Myocardial Contraction ; drug effects ; Ophiopogon ; chemistry ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Protein Precursors ; blood ; Rats ; Rats, Sprague-Dawley ; Ventricular Function, Left ; Ventricular Remodeling ; drug effects