Prussian blue nanozyme-mediated nanoscavenger ameliorates acute pancreatitis via inhibiting TLRs/NF-κB signaling pathway.

Rationale: Acute pancreatitis (AP) is a serious acute condition affecting the abdomen and shows high morbidity and mortality rates. Its global incidence has increased in recent years. Inflammation and oxidative stress are potential therapeutic targets for AP. This study was conducted to investigate the intrinsic anti-oxidative and anti-inflammatory effects of Prussian blue nanozyme (PBzyme) on AP, along with its underlying mechanism. Methods: Prussian blue nanozymes were prepared by polyvinylpyrrolidone modification method. The effect of PBzyme on inhibiting inflammation and scavenging reactive oxygen species was verified at the cellular level. The efficacy and mechanism of PBzyme for prophylactically treating AP were evaluated using the following methods: serum testing in vivo, histological scoring following hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescence staining, polymerase chain reaction array, Kyoto Encyclopedia of Genes and Genomes analysis and Western blotting analysis. Results: The synthetic PBzyme showed potent anti-oxidative and anti-inflammatory effects in reducing oxidative stress and alleviating inflammation both in vitro and in vivo in the prophylactic treatment of AP. The prophylactic therapeutic efficacy of PBzyme on AP may involve inhibition of the toll-like receptor/nuclear factor-κB signaling pathway and reactive oxygen species scavenging. Conclusion: The single-component, gram-level mass production, stable intrinsic biological activity, biosafety, and good therapeutic efficacy suggest the potential of PBzyme in the preventive treatment of AP. This study provides a foundation for the clinical application of PBzyme.

[Chronic thallium intoxication in five German pointers of one litter]. / Chronische Thalliumvergiftung bei fünf Deutsch Drahthaar Vorstehhunden aus einem Wurf.

The difficulty of diagnosis and therapy of chronic thallium intoxication is described in five German Pointers with the same skin disease. The detection of thallium in cases of skin lesions like the cutaneous erythema with oedema and crusts or in chronic cases with multifocal alopecia is difficult. The first diagnostic information was gathered in this case from the high thallium level in the urine. The thallium concentration in the hair is subject to great variations, even in physiologic conditions. The trichogramme showed in this case pathognomonic changes like adhesion of the hair follicles. Differential diagnosis for this symmetric alopezia without pruritus are hormonal disturbances or, in puppies, the generalized form of demodicosis. The five affected dogs were treated with Fe III-Hexacyanoferrat. The clinical appearance of the skin improved slowly during a period of 1-2 months.

Radial arterial pressure measurements may be a poor guide to the beneficial effects of nitroprusside on left ventricular systolic pressure in congestive heart failure.

The effect of nitroprusside on pressure wave transmission from ascending aorta to radial artery was studied in 10 patients with severe congestive heart failure. Nitroprusside resulted in a beneficial increase in cardiac index, reduction of pulmonary wedge pressure and reductions of aortic and radial arterial mean pressures. In 6 patients with an identifiable late systolic peak of aortic pressure (group I), nitroprusside reduced aortic systolic pressure more than radial systolic pressure, resulting in an increase in the difference between aortic and radial systolic arterial pressure (group I control 13 +/- 4, nitroprusside 20 +/- 6 mm Hg; p less than 0.025). Yet in 4 patients in whom no aortic late systolic pressure wave was apparent (group II), nitroprusside did not alter the difference between aortic and radial systolic pressures. Radial arterial pressure is often used to estimate the effect of nitroprusside on the arterial pressure load on the left ventricle. These results indicate that a reduction of radial systolic pressure induced by nitroprusside may underestimate the true reduction of aortic systolic pressure and thus the effect of the vasodilator on the arterial load on the left ventricle. The enhanced difference between aortic and radial arterial systolic pressures appears to be the consequence of nitroprusside on arterial pressure reflections.

Cardiovascular effects of forskolin (HL 362) in patients with idiopathic congestive cardiomyopathy--a comparative study with dobutamine and sodium nitroprusside.

Forskolin, a diterpene derivative of the Indian plant Coleus forskhohlii, proved to be a marked positive inotropic and vasodilatory compound in animal experiments with a mechanism of action distinct from catecholamines, cardiac glycosides, and phosphodiesterase-inhibiting compounds. The cardiovascular effects of forskolin seem to be mediated by a direct stimulatory action at the catalytic unit of sarcolemmal adenylate cyclase. The aim of the present study was to clarify the cardiovascular profile of this compound in 12 patients with stage III (NYHA) congestive cardiomyopathy. The effects of forskolin were investigated by invasive techniques using the thermodilution catheter method and compared to the beta 1-receptor agonist dobutamine and the vasodilator sodium nitroprusside in an intraindividual comparison. Forskolin dose-dependently reduced cardiac pre- and afterload values, and led to a reduction in systolic, diastolic, and mean pulmonary artery pressure as well as pulmonary wedge pressure by greater than 50% concomitant with an increase in cardiac output. There was a slight increase in heart rate. Cardiac stroke volume and stroke volume index was increased by approximately 70%. The cardiovascular effects of dobutamine and nitroprusside were less pronounced; however, it seemed that a similar hemodynamic profile could be achieved by the combination of both dobutamine and sodium nitroprusside. In view of the rapid development of tolerance toward beta 1-receptor stimulation, forskolin, with its receptor-independent mechanism of action, may be advantageous for the treatment of severe heart failure, especially in patients with catecholamine-insensitive heart failure.

Vasodilator therapy in microembolic porcine pulmonary hypertension.

The hemodynamic effects of prostaglandin E1, sodium nitroprusside (SNP), nitroglycerin, and hydralazine were studied in a porcine model of elevated pulmonary vascular resistance (PVR) due to glass bead microembolization (60-150-microns diameter). Each animal received all four drugs. Each drug was titrated to produce a 30% reduction in mean systemic arterial pressure. Although all four drugs decreased PVR, distinct differences in the hemodynamic profiles of the four drugs were evident. Prostaglandin E1 produced the largest reduction in mean pulmonary artery pressure (from 41 +/- 1 to 32 +/- 9 mm Hg, mean +/- SEM) and PVR (25 +/- 3 to 18 +/- 2 mm Hg.L-1.min-1), and did not affect the ratio of PVR to systemic vascular resistance (PVR/SVR). Sodium nitroprusside and nitroglycerin produced moderate decreases in PVR (nitroglycerin 21 +/- 2 to 18 +/- 2 mm Hg.L-1.min-1, SNP 22 +/- 2 to 19 +/- 2 mm Hg.L-1.min-1) and in mean pulmonary artery pressure (nitroglycerin 39 +/- 1 to 35 +/- 1; SNP 40 +/- 1 to 36 +/- 2 mm Hg). Both drugs significantly increased the PVR/SVR ratio. Hydralazine was the only drug that significantly increased cardiac output (1.6 +/- 0.2 to 1.9 +/- 0.3 L/min). Hydralazine had no significant effect on mean pulmonary artery pressure, reduced PVR to the smallest extent (11%), and resulted in the largest increase in the PVR/SVR ratio (from 0.52 +/- 0.04 to 0.80 +/- 0.08). In this model of increased pulmonary vasculature resistance prostaglandin E1 caused an equivalent amount of pulmonary and systemic vasodilation, as expressed by the PVR/SVR ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute reduction of atrial overload during vasodilator and diuretic therapy in advanced congestive heart failure.

Although acute afterload reduction is known to improve cardiac output in patients with congestive heart failure (CHF), the effect of therapy on the atrial overload directly causing congestive symptoms has not been systematically studied. Atrial volumes and mitral and tricuspid regurgitation, in addition to left ventricular ejection fraction and indexes of left ventricular contractility (mean acceleration, ejection time and peak systolic pressure/end-systolic volume index), were measured using 2-dimensional and Doppler echocardiography and color flow imaging in 30 patients with advanced CHF, before and after acute vasodilator and diuretic therapy tailored to hemodynamic goals. Therapy increased stroke volume by 64% (36 +/- 10 to 55 +/- 14 cc), decreased right atrial pressure by 45% (15 +/- 5 to 8 +/- 4 mm Hg), systemic vascular resistance by 36% (1,700 +/- 400 to 1,030 +/- 300 dynes s cm-5) and pulmonary capillary wedge pressure by 37% (31 +/- 6 to 19 +/- 6 mm Hg) (all p less than 0.001). Echocardiography showed simultaneous reductions in left and right atrial volumes: 24 +/- 19 and 18 +/- 12%, respectively (p less than 0.001). Mitral and tricuspid regurgitation measured by color flow fraction both decreased by a mean of 44% (p less than 0.001). While ejection fraction increased from 15 +/- 5 to 19 +/- 7% (p less than 0.001), there were no changes in relatively load-independent indexes of contractility. Therefore, acute therapy with vasodilators and diuretics in advanced CHF causes reductions in atrial volumes and atrioventricular valve regurgitation that are evident from serial noninvasive studies and may play a major role in the improvement of congestive symptoms.

A circulatory model for combined nitroprusside-dopamine therapy in acute heart failure.

A computer model was developed to approximate the hemodynamic responses of dopamine and nitroprusside in acute left ventricular pump failure. The model is intended to aid the design of a multiple drug infusion system. A non-linear electrical analog model with baroreflex feedback was used to simulate the circulatory system. Heart failure was represented by a reduction in left ventricular inotropy. Pharmacodynamic relationships between the drugs studied and several elements of the system were incorporated into the model to simulate the overall drug responses which include secondary interactions between vascular components. Despite several shortcomings, the model showed good agreement with experimental and clinical data.

Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension.

The renal and hemodynamic effects of intravenously administered fenoldopam mesylate, a novel dopamine-1 receptor agonist, were compared with those of sodium nitroprusside in 28 patients (18 male; 26 black, two white; average age, 49 +/- 3 years) with an average blood pressure of 219/137 mm Hg, most of whom presented with acute target organ damage. Fenoldopam and nitroprusside lowered blood pressure safely to an average pressure of 176/105 mm Hg; highly significant dose-response relations were found for the 13 patients receiving fenoldopam and the 15 receiving nitroprusside. Volume and sodium, potassium, and creatinine concentrations were measured in freely voided urine specimens both before and during intravenous therapy. In the fenoldopam-treated patients, there were significant increases in urinary flow (92 +/- 21 to 168 +/- 37 ml/hr, p less than 0.003), sodium excretion (227 +/- 73 to 335 +/- 90 mu eq/min, p less than 0.001), and creatinine clearance (70 +/- 11 to 93 +/- 13 ml/hr, p less than 0.003). In the nitroprusside-treated group, however, all these parameters decreased, but not significantly. For direct comparison of the two agents, the increments in urinary flow rate (+76 +/- 20 vs. -16 +/- 15 ml/hr, fenoldopam vs. nitroprusside), sodium excretion (+109 +/- 28 vs. -39 +/- 28 mu eq/min), and creatinine clearance (+23 +/- 6 vs. -11 +/- 7 ml/min) were significantly greater (p less than 0.001 for each) in the fenoldopam-treated group. Significant differences were also obtained when these parameters were calculated as percentage increase over baseline. Fenoldopam and nitroprusside are effective therapies for severe, accelerated, or malignant hypertension, but fenoldopam had additional salutary renal effects in these patients.

Intravenous fenoldopam versus sodium nitroprusside in patients with severe hypertension.

In an open-label study, we compared the efficacy and safety of intravenous infusion of fenoldopam mesylate with that of sodium nitroprusside in patients with severe hypertension or in hypertensive crisis. Both antihypertensive medications were infused at a maximal dose increment of 0.2 microgram/kg/min (fenoldopam) and 1 microgram/kg/min (nitroprusside), with a maximal infusion rate of 1.5 micrograms/kg/min fenoldopam mesylate or 8 micrograms/kg/min sodium nitroprusside. Once the desired reduction in diastolic blood pressure was achieved (less than 110 mm Hg if initial diastolic blood pressure was 120-149 mm Hg, or by at least 40 mm Hg if initial diastolic blood pressure was 150-190 mm Hg), the maximal infusion rate used was maintained for at least 1 hour, and then, the infusion was slowed gradually over 2 hours. After the infusion treatment, patients remained in the hospital for 2 days of follow-up. Both antihypertensive agents successfully controlled the blood pressure in all the patients by the end of the maintenance periods. Between the baseline and the end of the maintenance period, analysis of variance showed that the changes in the variables induced by fenoldopam mesylate did not differ significantly from those induced by sodium nitroprusside. The incidence of side effects listed were similar in both groups of patients. The detection of toxic levels of thiocyanate in two patients treated with nitroprusside, however, shows that fenoldopam might be preferable for the control of a hypertensive crisis or severe hypertension in patients with decreased renal function.

Cerebrospinal fluid drainage and steroids provide better spinal cord protection during aortic cross-clamping than does either treatment alone.

We investigated whether intravenous methylprednisolone (30 mg/kg) before 30 minutes of aortic cross-clamping and after 4 hours could enhance the effects of cerebrospinal fluid drainage on spinal cord perfusion pressure and postoperative paraplegia when proximal blood pressure was controlled with sodium nitroprusside and partial exsanguination. Dogs were randomized into three groups: group 1 (n = 6), control; group 2 (n = 7), steroids; and group 3 (n = 6), steroids with cerebrospinal fluid drainage. During aortic cross-clamping, blood pressure proximal to the clamp decreased significantly in each group compared with baseline (p less than 0.05), but did not differ among groups (group 1 = 82.2, group 2 = 82.1, group 3 = 86.6 mm Hg, p greater than 0.05). Mean distal pressure decreased from systemic values to 8.4, 8.5, and 3.7 mm Hg, respectively, after aortic cross-clamping (p less than 0.05); these values did not differ from one another (p greater than 0.05). During aortic cross-clamping, cerebrospinal fluid pressure in groups 1 and 2 did not differ significantly compared with baseline (12.2 versus 8.2, 14.2 versus 10.7 mm Hg, p greater than 0.05), whereas in group 3 the baseline cerebral spinal fluid pressure of 10.7 mm Hg decreased to 0.4 mm Hg (p less than 0.05). Spinal cord perfusion pressure in group 3 was significantly higher than in groups 1 and 2 (3.3 versus -3.9 and -5.7 mm Hg, p less than 0.05), but did not differ between groups 1 and 2 (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Afterload reduction with vasodilators and diuretics decreases mitral regurgitation during upright exercise in advanced heart failure.

In advanced heart failure, mitral regurgitation increases the burden of the failing ventricle and decreases effective stroke volume. Although tailored afterload reduction decreases mitral regurgitation at rest, it is not known if this benefit is maintained during upright exercise. Simultaneous radionuclide ventriculography and thermodilution stroke volumes were compared to measure the forward ejection fraction in 10 patients during upright bicycle exercise before and after therapy with vasodilators and diuretics tailored to decrease pulmonary capillary wedge pressure and systemic vascular resistance. Ventricular volumes, total ejection fraction and the forward ejection fraction did not change during exercise at baseline. At rest, tailored therapy decreased average pulmonary capillary wedge pressure from 36 to 19 mm Hg (p less than 0.01), systemic vascular resistance from 1,570 to 1,210 dynes.s.cm-5 (p less than 0.05), and left ventricular volume index from 251 to 177 ml/m2 (p less than 0.01), while increasing the forward ejection fraction from 0.53 to 0.85 (p less than 0.01) without change in total ejection fraction (0.18 from 0.17). During steady state exercise at low work load, tailored therapy decreased left ventricular volume index from 279 to 213 (p less than 0.05) and increased forward ejection fraction from 0.52 to 0.79 (p less than 0.01) without change in total ejection fraction (0.20 from 0.19). The total stroke volume during exercise was not increased after therapy; the increase in forward stroke volume after therapy appeared to result instead from the decrease in mitral regurgitant flow. The benefits of tailored afterload reduction are maintained throughout upright exercise.

Intravenous labetalol versus sodium nitroprusside for treatment of hypertension postcoronary bypass surgery.

Hypertension is common following coronary artery bypass surgery. The safety of labetalol, a recently released combined alpha-1 and beta-adrenergic blocking agent for treatment of hypertension in this clinical situation is controversial. The authors compared the hemodynamic effects of labetalol with those of sodium nitroprusside (SNP) in 91 patients with good left ventricular function and equally severe coronary artery disease and in whom coronary artery bypass surgery had been just completed. They were anesthetized using fentanyl, diazepam, and enflurane. If hypertension developed postoperatively, patients were randomized to receive labetalol, 2 mg/min to a maximum of 300 mg (20 patients) or sodium nitroprusside in 0.5 micrograms.kg-1.min-1 increments by infusion (20 patients) to return blood pressure to normal. Compared with control values, labetalol brought about significant (P less than 0.05) reductions in heart rate, and cardiac index. No change was noted in stroke volume or systemic vascular resistance, but slight increases were found in central venous pressure and pulmonary capillary wedge pressure. Sodium nitroprusside treatment caused significant increases in heart rate and cardiac index while reducing diastolic blood pressure, central venous pressure, and pulmonary capillary wedge pressure. Stroke volume remained unchanged. Following the study period, blood pressure was controlled in all patients with SNP. Total doses of SNP in the 16 h following the study period were significantly less in the labetalol group (46.6 +/- 11.7 mg) versus (116.1 +/- 10.3 mg) in the SNP group (P less than 0.05). In this clinical circumstance, labetalol can be safe and effective for controlling hypertension, but its mechanism of achieving this effect varies from that for sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ketanserin versus sodium nitroprusside in the treatment of hypertension following coronary surgery. Effect on intrapulmonary right and left shunt and arterial oxygenation]. / Ketanserin versus Natriumnitroprussid in der Behandlung der Hypertonie nach koronarchirurgischen Eingriffen. Einfluss auf den intrapulmonalen Rechts- und Links-Shunt und die arterielle Oxygenation.

Twenty patients requiring management of postoperative arterial hypertension following coronary artery bypass grafting (CABG) were randomly treated with either ketanserin (n = 10) or sodium nitroprusside (SNP) (n = 10). After surgery all patients were mechanically ventilated in the intensive care unit (F1O2:0.5; PEEP: +5 cm H2O). During the therapy with either drug F1O2 was adjusted to achieve normal blood oxygen tensions (F1O2 always greater than 0.3). Samples of arterial and mixed-venous blood were obtained simultaneously before administration of either drug and at each time point. Data acquisition followed over 12 h. Both drugs led to a significant decrease in arterial blood pressure, although 2 patients had to be withdrawn from the ketanserin group because there was no adequate decrease in systolic arterial pressure. A significant increase in heart rate was noted only in patients receiving SNP. In the SNP-treated patients F1O2 had to be increased because of a marked decrease in paO2, resulting in a significant increase in alveolar-arterial oxygen difference (A-aDO2). In 3 patients SNP had to be stopped because of an increase in intrapulmonary shunt (Qsp/Qt) more than 30%. No significant changes in Qsp/Qt, A-aDO2, or paO2 were seen in the ketanserin-treated patients.

Antihypertensive and anti-ischemic effects of nicardipine and nitroprusside in patients undergoing coronary artery bypass grafting.

The efficacy of nicardipine vs nitroprusside in controlling hypertension after sternotomy was compared in 120 patients undergoing coronary artery bypass grafting and anesthetized with fentanyl (100 micrograms/kg). All had good left ventricular function and had been receiving long term oral beta-blocking therapy. Patients were randomly allocated to 1 of 3 groups: group C, the control (n = 40), received no vasodilator; group N (n = 40) received intravenous nicardipine at an initial rate of 3 micrograms/kg/min; and group S (n = 40) received intravenous nitroprusside at an initial rate of 1 microgram/kg/min. Vasodilator infusion was begun before surgery and infusion rates were adjusted to maintain systolic blood pressure between 80 and 120% of postintubation (baseline) values. Additional measurements were obtained before incision and after sternotomy. In groups N and S, arterial blood pressure was effectively controlled in all patients. Before the incision, pulmonary artery pressure decreased in group S and systemic vascular resistance decreased in groups N and S. After sternotomy, mean arterial pressure, heart rate, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index and rate-pressure product increased in group C. At this time, pulmonary artery pressure returned to baseline values in group S. In groups N and S, heart rate, cardiac index and rate-pressure product increased, but, compared with baseline values, systemic vascular resistance remained low after sternotomy. Ischemic changes were seen in the electrocardiogram in 11 patients (28%) in group C, 10 patients (25%) in group S and 4 patients (10%) in group N. The concentration of creatine phosphokinase MB was not significantly different in the first 24 postoperative hours in any group.

Comparative effects of verapamil and nitroprusside on left ventricular function in patients with hypertension.

The effects of verapamil were compared with those of nitroprusside at matched mean arterial pressures and heart rates in 10 symptomatic hypertensive patients during cardiac catheterization. Simultaneous radionuclide angiography and micromanometer pressure measurements were obtained to assess left ventricular pressure-volume relations. Compared with control conditions, verapamil increased left ventricular end-diastolic volume index from 57 +/- 16 to 70 +/- 28 ml/m2 (p = 0.05) without a significant increase in left ventricular end-diastolic pressure (from 10 +/- 4 to 13 +/- 6 mm Hg). Despite a downward and rightward shift in the end-systolic pressure-volume relation indicating negative inotropic effects, ejection fraction did not decrease significantly (from 52 +/- 9% to 46 +/- 9%); cardiac index and stroke volume index remained unchanged. The change in stroke volume index with verapamil was directly related to the magnitude of change in end-diastolic volume index (r = 0.82, p less than 0.005), suggesting that the increase in end-diastolic volume did not arise purely from negative inotropic effects. Systemic vascular resistance index decreased from 42 +/- 8 to 34 +/- 7 mm Hg.min.m2/liter (p less than 0.05). In contrast, nitroprusside decreased left ventricular end-diastolic volume index from 57 +/- 16 to 41 +/- 10 ml/m2 (p less than 0.05), cardiac index from 3.2 +/- 0.7 to 2.8 +/- 0.6 liters/min per m2 (p less than 0.05) and stroke volume index from 28 +/- 6 to 24 +/- 5 ml/m2 (p less than 0.01), with no change in systemic vascular resistance index (40 +/- 10 mm Hg.min.m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Ketanserin in the treatment of pulmonary hypertension after valvular surgery: a comparison with sodium nitroprusside.

In a prospective randomized trial in patients with a history of preoperative pulmonary hypertension who were undergoing surgery for valvular replacement or annuloplasty, the effects of ketanserin (KET) (12 patients) and sodium nitroprusside (SNP) (14 patients) on the systemic and pulmonary circulation and pulmonary shunt fraction (Qsp/Qt) were studied in the immediate postoperative period. The agents were administered at the moment that pulmonary arterial pressure (PAP) tended to rise and cardiac output started to decrease. After administration, systemic arterial BP, PAP, systemic and pulmonary (PVR) vascular resistance, and right ventricular stroke work (RVSW) decreased significantly in both groups. The decrease in mean pulmonary arterial pressure (p less than .01), PVR (p less than .01), and RVSW (p less than .05) was significantly more pronounced in the KET than in the SNP group. Qsp/Qt significantly (p less than .001) increased in the SNP group, but significantly (p less than .05) decreased in the KET group; the response was significantly different between the two groups (p less than .001). In six patients, SNP converted pacemaker-dependent heart rate into a spontaneous rhythm, whereas this occurred in only one patient in the KET group. We concluded that KET, as opposed to SNP, reduces PVR without increasing Qsp/Qt in the lung, which is particularly advantageous in patients after valvular surgery.