Efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease: A protocol of randomized controlled trial.

BACKGROUND: Coronary heart disease is a serious cardiovascular disease. There is coronary atherosclerosis, resulting in lumen stenosis, blockage, and then the symptoms of insufficient blood supply and hypoxia in the myocardium. Chronic heart failure is a kind of syndrome with abnormal ventricular filling and ejection function, which is the final stage of the development of coronary heart disease. At present, the treatment plan of Western medicine can significantly reduce the hospitalization rate, but it is still not satisfactory for the prognosis and mortality of patients. Shenfu injection has advantages in the treatment of heart failure in patients with coronary heart disease, but there is a lack of standard clinical studies to verify it, so the purpose of this randomized controlled study is to evaluate the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. The patients will be randomly divided into a treatment group and the control group according to 1:1, in which the treatment group is treated with Shenfu injection combined with sodium nitroprusside, and the control group is treated with sodium nitroprusside alone. Both groups will be treated with standard treatment for 7 days and followed up for 30 days to pay attention to their efficacy and safety indexes. The observation indexes include TCM syndrome score, N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction, brain natriuretic peptide, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, stroke volume, adverse reactions and so on. We will use SPSS 25.0 software for data analysis. DISCUSSION: This study will evaluate the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. The results of this experiment will provide a clinical basis for Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in coronary heart disease. TRIAL REGISTRATION: DOI 10.17605/OSF.IO/4KNG3.

Transcriptional analysis reveals sodium nitroprusside affects alfalfa in response to PEG-induced osmotic stress at germination stage.

Drought is one of the most common environmental factors that affect alfalfa germination and development. Nitric oxide (NO) could mediate stress tolerance in plants. The goal of this study was to determine exogenous NO donor-mediated drought adaption molecular mechanisms during the alfalfa germination stage. In this study, physiological and transcriptome analyses were performed on 7 days of the growth period seedlings by sodium nitroprusside (SNP) and polyethylene glycol (PEG) treatment. The results showed that SNP supplementation alleviated malondialdehyde accumulation, increased levels of proline and soluble sugars, and enhanced antioxidant enzyme activity under osmotic stress conditions. RNA-Seq experiments identified 5828 genes exhibiting differential expression in seedlings treated with PEG, SNP, or SNP+PEG relative to seedlings treated with distilled water. Of these DEGs, 3235 were upregulated, and 2593 were downregulated relative to the controls. Fifteen DEGs were amplified by qRT-PCR to verify the changes in expression determined by RNA-Seq, revealing that PIF3, glnA, PLCG1, and RP-S11e exhibited enhanced expression under the SNP+PEG treatment. SNP was found to modulate redox homeostasis-related genes such as GSTs, SOD2, GPX, and RBOH, and triggered calcium signaling transduction. It also induced some key genes relating to the abscisic acid, ethylene, and auxin signaling transduction in response to PEG stress. Conversely, genes associated with secondary metabolite biosynthesis and the metabolism of starch and sucrose during osmotic stress were downregulated by SNP. These results provide new insights into SNP-mediated drought adaption mechanisms at transcriptome-wide in alfalfa and reveal key drought tolerance pathways in this species.

A novel NIR-controlled NO release of sodium nitroprusside-doped Prussian blue nanoparticle for synergistic tumor treatment.

Nitric oxide (NO) has shown positive effects in tumor treatment. However, controlling NO release in specific targets is still a crucial challenge for antitumor therapy. Considering that sodium nitroprusside (SNP) and potassium ferricyanide have similar chemical structures, a near infrared (NIR) laser-controlled NO release nanoplatform has been fabricated by allowing SNP to participate in mesoporous Prussian blue (m-PB) nanoparticle formation. The resulting SNP-doped m-PB (m-PB-NO) exhibited a good NIR-controlled NO release behavior, and the amount of NO released can be controlled by adjusting the laser intensity and irradiation time. Given that m-PB-NO still has strong absorption in NIR region, it exhibited an excellent photothermal effect in vitro and in vivo. After carrying antitumor drug, docetaxel (DTX)-loaded m-PB-NO (DTX@m-PB-NO) can simultaneously achieve NIR-controlled NO release, good photothermotherapy, and chemotherapy. The combination therapy of DTX@m-PB-NO showed a significant synergistic effect compared with each monotherapy and can significantly improve the therapeutic effect. Combination therapy also significantly inhibited the lung metastasis of 4T1 breast cancer cells in tumor-bearing mice by ablating primary tumors.

Hypertensive emergencies of pregnancy.

Hypertension is commonly encountered in pregnancy and has both maternal and fetal effects. Acute hypertensive crisis most commonly occurs in severe preeclampsia and is associated with maternal stroke, cardiopulmonary decompensation, fetal decompensation due to decreased uterine perfusion, abruption, and stillbirth. Immediate stabilization of the mother including the use of intervenous antihypertensives is required and often delivery is indicated. With appropriate management, maternal and fetal outcomes can be excellent.

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure.

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.

Dutch guideline for the management of hypertensive crisis -- 2010 revision.

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.

Effect of nitric oxide inhibitor and donor substances on the infammatory process caused by endodontic irrigants

Nitric oxide (NO) has been considered a key molecule in infammation. OBJECTIVE: The aim of this study was to evaluate the effect of treatment with L-NAME and sodium nitroprussiate, substances that inhibit and release NO, respectively, on tissue tolerance to endodontic irrigants. MATERIAL AND METHODS: The vital dye exudation method was used in a rat subcutaneous tissue model. Injections of 2 percent Evans blue were administered intravenously into the dorsal penial vein of 14 male rats (200-300 g). The NO inhibitor and donor substances were injected into the subcutaneous tissue in the dorsal region, forming two groups of animals: G1 was inoculated with L-NAME and G2 with sodium nitroprussiate. Both groups received injections of the test endodontic irrigants: acetic acid, 15 percent citric acid, 17 percent EDTA-T and saline (control). After 30 min, analysis of the extravasated dye was performed by light absorption spectrophotometry (620 nm). RESULTS: There was statistically signifcant difference (p<0.05) between groups 1 and 2 for all irrigants. L-NAME produced a less intense infammatory reaction and nitroprussiate intensifed this process. CONCLUSIONS: Independently of the administration of NO inhibitors and donors, EDTA-T produced the highest irritating potential in vital tissue among the tested irrigating solutions.

Influence of dipyridamole and its combination with NO donor or NO synthase inhibitor on adjuvant arthritis.

The anti-arthritic and anti-inflammatory effects of dipyridamole and the possible involvement of NO in the dipyridamole action are not yet clear. The aim of this study was to evaluate the effects of dipyridamole alone and in combination with either the nitric oxide donor, sodium nitroprusside (SNP) or the non-selective nitric oxide synthase inhibitor, L-NG- monomethyl arginine (L-NMMA), on pathogenesis of adjuvant-induced arthritis model in rats. The results of the present work showed that prophylactic administration of dipyridamole alone and dipyridamole administration in combination with either low dose of SNP or L-NMMA significantly ameliorated pathogenesis of adjuvant arthritis in rats as evidenced by significant decrease in arthritis index, hind paws volume, loss of body weight, hyperalgesia compared with control vehicle (1% DMSO) treated adjuvant arthritic rats. Inflammatory cellular infiltrate in synovium of ankle joint and pannus formation were also markedly inhibited. Interleukin-10(IL-10) levels were significantly increased in these groups of animals. In contrast, a high dose of SNP counteracted the anti-inflammatory and anti-arthritic effects of dipyridamole. The inhibitory effect of therapeutic administration of dipyridamole alone on adjuvant arthritis syndrome was not significantly different from that of vehicle administration. In conclusion, dipyridamole has prophylactic but not therapeutic anti-arthritic and anti-inflammatory effects that appear to be dependent on inhibition of NO synthase. A synergistic combination between dipyridamole and NO synthase inhibitor or low dose of NO donor may have prophylactic and therapeutic values in autoimmune diseases like RA.

Pharmacotherapeutic options for the treatment of preeclampsia.

PURPOSE: Pharmacotherapeutic options for the treatment of preeclampsia are reviewed. SUMMARY: Risk factors for the development of preeclampsia include microvascular diseases, such as diabetes mellitus; vascular and connective tissue disorders; hypertension; antiphospholipid antibody syndrome; and nephropathy. Several pathophysiological factors contribute to the development of the preeclamptic state, including vasospasm onset, coagulation system activation, increased inflammatory response, and ischemia. The specific agents used for the treatment of preeclampsia are dependent on a number of factors including symptom severity, maternal or fetal compromise, the progression to eclampsia, gestational period, and cervical status. The diagnosis of preeclampsia beyond the gestation period of 38 weeks requires delivery. The presence of maternal compromise or eclampsia at gestation greater than 20 weeks also necessitates delivery. In cases of chronic or mild hypertension, oral methyldopa may be administered on an outpatient basis. Intravenous hydralazine is a commonly administered arteriolar vasodilator that is effective for hypertensive emergencies associated with pregnancies. The most common adverse effect of hydralazine administration is unpredictable hypotension. Labetalol decreases heart rate and may be preferred because of a lack of reflex tachycardia, hypotension, or increased intracranial pressure. However, the drug of choice for the prevention and control of maternal seizures in patients with severe preeclampsia or eclampsia during the peripartum period is i.v. magnesium sulfate. Therapeutic serum magnesium levels cause cerebral vasodilation, thereby reversing the ischemia produced by cerebral vasospasm during an eclamptic episode. The results of one study indicated that women receiving magnesium sulfate therapy had a 58% lower risk of eclampsia than placebo. CONCLUSION: Magnesium sulfate remains the drug of choice for the prevention and treatment of preeclampsia. Alternative antihypertensive agents may provide additional benefit in the management of hypertension for preeclamptic patients.

[Exogenous nitric oxide donor in the liver inflammatory and hemodynamic response after hemorrhagic shock]. / Donador exógeno de óxido nítrico en la respuesta inflamatoria hepática y hemodinámica después de choque hemorrágico.

BACKGROUND: Hemorrhagic shock (HS) results in oxidative stress to cells and in the induction of the inflammatory response, with an increased expression of a number of proinflammatory mediators and cytokines. We tested the ability of the nitric oxide (NO) donor sodium nitroprusside (NP) to reduce tissue injury in a rodent model of uncontrolled hemorrhagic shock. METHODS: Seventy two Sprague Dawley rats weighing 250-300 g were subjected to a model of uncontrolled hemorrhagic shock. Four groups of animals were included (n = 18 per group): sham/saline, sham/NP, shock/saline, shock/NP. Experimental design consisted of the development of hemorrhagic shock (3 ml/100 g) in a 15-min period, tail amputation (75%) and drug administration at 30 min, fluid resuscitation (FR) with Ringer's lactate (RL) solution to reach a mean arterial pressure (MAP) of 40 mmHg, a hospital phase of 60 min with hemostasis and FR with LR solution to reach a MAP of 70 mmHg, and a 3-day observation phase. Treatment at the beginning of resuscitation included either normal saline (groups 1, 3) or NP (0.5 mg/kg) (groups 2, 4). The following parameters were evaluated: fluid requirements for resuscitation, liver injury tests, liver tissue myeloperoxidase (MPO), liver histology, and 3-day survival. RESULTS: NP significantly reduced fluid requirements for resuscitation (p = 0.0001). We also observed an improved statistically significant difference in tests demonstrating hepatic injury (p = 0.0001), neutrophil infiltration as evidences by liver MPO (p <0.05), and histology studies (p = 0.001). Survival was also increased from 40% in controls to 60% with NP treatment. CONCLUSIONS: These data suggest that excess NO mediates hemorrhage-induced liver injury, and that the suppression of NO with NP may reduce the pathological consequences of severe hemorrhage, possibly by scavenging superoxide (O(2)(-)), thus limiting the production of more aggressive radicals.

Donador exógeno de óxido nítrico en la respuesta inflamatoria hepática y hemodinámica después de choque hemorrágico / Exogenous nitric oxide donor in the liver inflammatory and hemodynamic response after hemorrhagic shock

BACKGROUND: Hemorrhagic shock (HS) results in oxidative stress to cells and in the induction of the inflammatory response, with an increased expression of a number of proinflammatory mediators and cytokines. We tested the ability of the nitric oxide (NO) donor sodium nitroprusside (NP) to reduce tissue injury in a rodent model of uncontrolled hemorrhagic shock. METHODS: Seventy two Sprague Dawley rats weighing 250-300 g were subjected to a model of uncontrolled hemorrhagic shock. Four groups of animals were included (n = 18 per group): sham/saline, sham/NP, shock/saline, shock/NP. Experimental design consisted of the development of hemorrhagic shock (3 ml/100 g) in a 15-min period, tail amputation (75%) and drug administration at 30 min, fluid resuscitation (FR) with Ringer's lactate (RL) solution to reach a mean arterial pressure (MAP) of 40 mmHg, a hospital phase of 60 min with hemostasis and FR with LR solution to reach a MAP of 70 mmHg, and a 3-day observation phase. Treatment at the beginning of resuscitation included either normal saline (groups 1, 3) or NP (0.5 mg/kg) (groups 2, 4). The following parameters were evaluated: fluid requirements for resuscitation, liver injury tests, liver tissue myeloperoxidase (MPO), liver histology, and 3-day survival. RESULTS: NP significantly reduced fluid requirements for resuscitation (p = 0.0001). We also observed an improved statistically significant difference in tests demonstrating hepatic injury (p = 0.0001), neutrophil infiltration as evidences by liver MPO (p <0.05), and histology studies (p = 0.001). Survival was also increased from 40% in controls to 60% with NP treatment. CONCLUSIONS: These data suggest that excess NO mediates hemorrhage-induced liver injury, and that the suppression of NO with NP may reduce the pathological consequences of severe hemorrhage, possibly by scavenging superoxide (O(2)(-)), thus limiting the production of more aggressive radicals.

Synergistic antiglioma action of hyperthermia and nitric oxide.

To explore combined antiglioma effect of nitric oxide (NO) and hyperthermia, the rat C6 and human U251 glioma cells were exposed to NO-releasing agents sodium nitroprusside(SNP), S-nitrosoglutathione or PAPA-NONOate, followed by hyperthermia (1 h, 43 degrees C). While each treatment alone showed only moderate efficiency, a synergistic cytotoxicity of NO donors and hyperthermia was clearly demonstrated by crystal violet and MTT cytotoxicity assays. The flow cytometric analysis with the appropriate reporter fluorochromes confirmed that hyperthermia and SNP cooperated in inducing oxidative stress, mitochondrial depolarization, caspase activation and DNA fragmentation, leading to both necrotic and caspase-dependent apoptotic cell death. The acridine orange staining of intracellular acidic compartments revealed that SNP completely blocked hyperthermia-induced autophagy, while the inhibition of autophagy by 3-methyl adenine mimicked SNP-triggered oxidative stress, caspase activation and cell death in hyperthermia-exposed cells. Therefore, the synergistic cytotoxicity of SNP and hyperthermia could result from NO-mediated suppression of protective autophagic response in glioma cells.

[Endovascular treatment of vasospasm following subarachnoid aneurysmal haemorrhage]. / Traitements endovasculaires du vasospasme de l'hémorragie méningée anévrysmale.

An endovascular treatment of vasospasm following a subarachnoid aneurysmal haemorrhage is to be implemented if the patient presents clinical or biological symptoms arguing for brain ischemia in conjunction with increased Doppler velocities despite well controlled systemic haemodynamic. Treatment might be either pharmacological or haemodynamic. Calcium and phosphodiesterase inhibitors can be administered. The former could also provide a neuroprotective effect as compared to the latter. In Europe, nimodipine is widely used whereas nicardipine and verapamil are the major molecules administered in North America where iv nimodipine is not FDA approved. Papaverine is less used nowadays because of its short duration of action and of the risk of aggravation of raised intracranial pressure. Balloon angioplasty has a long lasting effect but can be applied only to proximal spasm. Complications of its use are rare but life threatening. In some cases, both the pharmacological approach and the mechanical approach are used in combination.

Can nitric oxide-generating compounds improve the oxidative stress response in experimentally diabetic rats?

1. The present study was designed to evaluate the protective effects of the nitric oxide (NO)-generating compounds L-arginine (L-Arg) and sodium nitroprusside (SNP) on oxidative stress markers in streptozotocin (STZ)-diabetic rats. 2. Diabetes was induced after a single intraperitoneal injection of STZ (60 mg/kg). Rats were divided into non-diabetic (control), diabetic and treated diabetic groups. The treated diabetic groups were supplemented with L-Arg (300 mg/kg), SNP (3 mg/kg per day) or glibenclamide (0.6 mg/kg per day) orally for 4 weeks. 3. At the end of the experiment, fasted rats were killed by cervical decapitation. Blood was collected for estimation of glucose, haemoglobin, glycosylated haemoglobin (HbA(1c)), total cholesterol, high-density lipoprotein-cholesterol and triglycerides. Thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation), superoxide dismutase, glutathione peroxidase, catalase, nitrate/nitrite (NO(x)) and reduced glutathione (GSH) were estimated in liver and kidney homogenates. 4. A significant increase was observed in plasma glucose levels and HbA(1c), with a concomitant decrease in haemoglobin levels, in diabetic rats. These alterations reverted back to near normal after treatment with the NO-generating compounds. A loss of bodyweight, polydipsia, polyphagia and elevated levels of serum cholesterol and triglycerides were observed in diabetic rats. Hyperglycaemia was accompanied by a significant increase in tissue TBARS and a decrease in NO(x), GSH and anti-oxidant enzymes, whereas, supplementation with L-Arg and SNP significantly reduced TBARS levels and increased GSH and anti-oxidant enzyme activities. Linear regression analysis indicated that blood glucose and TBARS had a significant positive correlation with HbA(1c), whereas a negative correlation was observed between GSH and NO(x). 5. It is concluded that NO-generating compounds improve most of the biochemical abnormalities and anti-oxidant levels in diabetic rats. The beneficial effects of NO-generating compounds can be attributed to the generation of NO and/or enhanced anti-oxidant enzyme activities.

Effect of NO donor sodium nitroprusside on lipopolysaccharide induced acute lung injury in rats.

Nitric oxide (NO) donor-sodium nitroprusside (SNP) mitigates acute lung injury (ALI), but the mechanism of this protection is incompletely known. We investigated the effect of SNP on lipopolysaccharide (LPS)-induced ALI in rats. Forty-eight male Wistar rats were randomly assigned into six groups: the sham-operation group (S group), the LPS instillation group (LPS group), the haemin, a haeme oxygenase-1 (HO-1) inducer, pretreatment group (HM group), the haemin pretreatment plus LPS instillation group (HM+LPS group), the SNP alone and SNP plus LPS treatment groups. Macroscopic and histopathological examinations and immunohistochemistry analysis were performed for the lung specimens 8h after LPS instillation. Intratracheal administration of LPS induced significant expressions of the inducible isoform of NO synthase (iNOS) and HO-1, while both haemin pretreatment and SNP treatment increased the expression of HO-1 and prevented the expression of iNOS. In the LPS group, the wet-dry weight ratio (W/D), bronchoalveolar lavage fluid (BALF) protein, and lung malondialdehyde (MDA) content were significantly higher than those in the sham-operation group, which were reversed by the pretreatment with haemin or administration of SNP. These results suggest that HO-1 plays a protective role against LPS-induced acute lung injury, which may be achieved at least in part, via inactivating the iNOS/NO system that is involved in the pathophysiological process of LPS-induced acute lung injury. The nitric oxide (NO) donor-SNP ameliorates LPS-induced ALI, which may be related to the induction of HO-1 and the subsequent inhibition of iNOS.

Hypertension in children with chronic renal failure.

Systemic hypertension (HTN) is one of the major problems associated with chronic renal failure (CRF). HTN is a symptom and complication of CRF. The prevalence of HTN varies with the cause of CRF. The incidence of HTN increased up to 90% with progressive deterioration of the glomerular filtration rate (GFR). HTN is the major risk factor for decline in renal function and progression of CRF. It is the most important risk factor for cardiovascular diseases and morbidity and mortality in patients with CRF and end-stage renal disease (ESRD) on dialysis. The target blood pressure for hypertensive children with CRF should be under the 95th percentile for sex and age. The therapeutic approach in CRF is directed at reducing volume expansion and sodium retention, and decreasing peripheral vascular resistance. Diuretics are first-line therapy for HTN in patients with CRF with sodium and water retention. ACE inhibitors are the first-class drugs because of their renoprotective effect in preventing deterioration of kidney function. Calcium channel blockers are excellent first-line antihypertensive drugs. Recently angiotensin II receptor blockers and ACE inhibitors have been efficiently used together for the treatment of HTN and to prevent further decline in renal function.

Effect of calcitonin gene related peptide vs sodium nitroprusside to increase temperature in spontaneous canine tumours during local hyperthermia.

The objectives of this study were to compare the effects of two vasodilators, sodium nitroprusside (SNP) and calcitonin gene-related peptide (CGRP) on mean arterial pressure (MAP), heart rate (HR) and temperatures in tumour and surrounding normal tissue during local hyperthermia treatment. Eleven tumour-bearing pet dogs with spontaneous soft tissue sarcomas were given SNP intravenously during local hyperthermia. The drug infusion rate was adjusted to maintain a 20% decrease in MAP. The median (95% CI) increase in the temperature distribution descriptors T(90) and T(50) was 0.2 degrees C (0.0-0.4 degrees C, p = 0.02) and 0.4 degrees C (0.1-0.7 degrees C, p = 0.02), respectively, in tumour. Normal subcutaneous tissue temperatures were mildly increased but remained below the threshold for thermal injury. The effects of CGRP were investigated in six tumour-bearing dogs following a protocol similar to that used for SNP. The median (interquartile (IQ) range) decrease in mean arterial pressure was 19% (15-26%) after CGRP administration and a significant increase was seen in tumour but not normal subcutaneous tissue temperatures. The median (95% CI) increase in the temperature distribution descriptors T(90) and T(50) was 0.5 degrees C (0.1-1.6 degrees C, p = 0.03) and 0.8 degrees C (0.1-1.6 degrees C, p = 0.13), respectively. Administration of SNP or CGRP did not result in local or systemic toxicity in tumour-bearing dogs. However, the magnitude of increase in tumour temperatures was not sufficient to improve the likelihood of increased response rates. Therefore, there is little justification for translation of this approach to human trials using conventional local hyperthermia.

[Study on protective effect of shenfu injection on cardiac function of patients undergoing valve replacement].

OBJECTIVE: To investigate the protective effect of Shenfu injection (SFI) on cardiac function of patients undergoing valve replacement operation under cardio-pulmonary bypass. METHODS: One hundred and twenty patients undergoing valve replacement operation under cardio-pulmonary bypass were randomly divided into the SFI group and the control group, 60 in each group. Intravenous infusion of 1 ml/kg SFI was given to the SFI group, 30 min before anesthesia, and to the control group, equal volume of normal saline was given instead. The following indices were observed: (1) the hemodynamic changes occurred in the operational period; (2) the dosage of vaso-active drugs used during and after operation; (3) the post-operational recovery time of patients. RESULTS: The mean arterial pressure and heart rate in the SFI group during operation were higher, while the central venous pressure was lower than those in the control group (P < 0.05). The dosage of vaso-active drugs, such as dopamine, dobutamine, sodium nitroprusside and lidocaine, used during and after operation was lower, and the extubation time and the intensive care unit (ICU) staying time were shorter in the SFI group when compared with those in the control group (P < 0.05). CONCLUSION: SFI has certain protective effects on the cardiac function of patients undergoing valve replacement operation under cardio-pulmonary bypass.

The diagnosis and management of hypertensive crises.

Severe hypertension is a common clinical problem in the United States, encountered in various clinical settings. Although various terms have been applied to severe hypertension, such as hypertensive crises, emergencies, or urgencies, they are all characterized by acute elevations in BP that may be associated with end-organ damage (hypertensive crisis). The immediate reduction of BP is only required in patients with acute end-organ damage. Hypertension associated with cerebral infarction or intracerebral hemorrhage only rarely requires treatment. While nitroprusside is commonly used to treat severe hypertension, it is an extremely toxic drug that should only be used in rare circumstances. Furthermore, the short-acting calcium channel blocker nifedipine is associated with significant morbidity and should be avoided. Today, a wide range of pharmacologic alternatives are available to the practitioner to control severe hypertension. This article reviews some of the current concepts and common misconceptions in the management of patients with acutely elevated BP.

The role of nitric oxide synthase/nitric oxide in vascular smooth muscle control.

Vascular compliance is dependent on endogenous and exogenous sources of nitric oxide (NO). In a discussion of therapeutics and NO derived via nitric oxide synthase (NOS) enzymes, it is necessary to examine the pathways of each drug to provide the clinical perfusionist with a greater understanding of the role of NOS/NO in vascular function. Endothelial-derived NO is a contributor in the vasoregulation of vascular smooth muscle. Therapeutics seek to mimic the vasodilatory effects of the endogenous NO. The therapeutics included in this review are nitroglycerin, nitroprusside, amyl nitrite, and inhalation of NO. L-Arginine supplementation provides additional substrate for the endogenous pathway that can augment NO production. NO is a small bioactive molecule involved in various biochemical pathways. Dysregulation of NO production can impair normal physiologic control of vascular compliance. Therefore, the purpose of this review is to provide the perfusionist with an understanding of the biochemical and pharmacological aspects of NOS/NO associated with vascular function.