Respiratory toxicity of direct lytic factor in the venom of the southern Chinese cobra (N. naja atra) in dogs

1996 ◽  
Vol 15 (8) ◽  
pp. 629-632 ◽  
Author(s):  
Shou-Jian Huang ◽  
Fu Jian ◽  
Jia-Jun Sun

The effects of direct lytic factor (DLF) on respiratory ventilation, gas exchange as well as hemodynamics were studied in anesthetized dogs. After an intravenous DLF dose of 1 mg/kg, the initial manifestation of intoxication was observed as follows: (1) Increase in airway impedance characterized by slowed air flow rate and increased negative transpulmonary pressure. (2) Decrease in dy namic compliance. (3) Progressive increase in venoarter ial shunt (Qs/Qt) and decrease in PaO 2. (4) Elevation of pulmonary artery blood pressure and fall of mean systemic blood pressure and maximal left ventricular pressure. Above actions reached the peak values at 15 min and thereafter all respiratory functional parameters, except Qs/Qt and hypoxemia, returned gradually to approach the normal levels at 50 min. The tidal volume, PaCO2 and LVEDP remained unchanged until another DLF dose of 1.5 mg/kg was given. After a second dose of DLF (total 2.5 mg/kg), the respiratory functions and the cardiac performance deteriorated as follows: (1) Further increase in Qs/Qt and hypoxemia. (2) Appearance of hypercapnea and acidosis. (3) Fall of dP/dt max and elevation of LVEDP, widening of QRS complex of ECG. (4) Blood pressure run a downhill course. From above experimental evidence, we came to the conclusion that as well as the basic cardiotoxicity, respiratory toxicity of DLF must be considered as the primary, because of broad spectrum of action of DLF and early effect on respiratory function.

1976 ◽  
Vol 51 (s3) ◽  
pp. 353s-355s ◽  
Author(s):  
P. Kezdi

1. The renal sympathetic reflex responses to transient balloon occlusion of the descending aorta (systemic baroreceptor activation) and the ascending aorta (cardiac stretch-receptor activation) have been studied together with blood pressure increases after successive cutting of carotid sinus, aortic and vagus nerves in acute experiments in the dog. 2. Results from these experiments provide evidence for cardiac vagal afferent participation in the tonic regulation of systemic blood pressure. 3. In other experiments the reflex pressure-response curve of the isolated gracilis muscle at constant flow to transient ascending aorta occlusion was measured. This curve was moved to the right in renal hypertensive dogs as compared with normotensive dogs. The threshold response of left ventricular vagal afferent nerves was shifted to higher left ventricular pressure in the former. 3. These findings indicate resetting of ventricular receptors in hypertensive animals.


2012 ◽  
Vol 13 (3) ◽  
pp. 334-340 ◽  
Author(s):  
Kulwinder Singh ◽  
Kuldeepak Sharma ◽  
Manjeet Singh ◽  
PL Sharma

Hypothesis: This study was designed to investigate the cardio-renal protective effect of AVE-0991, a non-peptide Mas-receptor agonist, and A-779, a Mas-receptor antagonist, in diabetic rats. Materials and methods: Wistar rats treated with streptozotocin (50 mg/kg, i.p., once), developed diabetes mellitus after 1 week. After 8 weeks, myocardial functions were assessed by measuring left ventricular developed pressure (LVDP), rate of left ventricular pressure development (d p/d tmax), rate of left ventricular pressure decay (d p/d tmin) and left ventricular end diastolic pressure (LVEDP) on an isolated Langendorff’s heart preparation. Further, mean arterial blood pressure (MABP) was measured by using the tail-cuff method. Assessment of renal functions and lipid profile was carried out using a spectrophotometer. Results: The administration of streptozotocin to rats produced persistent hyperglycaemia, dyslipidaemia and hypertension which consequently produced cardiac and renal dysfunction in 8 weeks. AVE0991 treatment produced cardio-renal protective effects, as evidenced by a significant increase in LVDP, d p/d tmax, d p/d tmin and a significant decrease in LVEDP, BUN, and protein urea. Further, AVE-0991 treatment for the first time has been shown to reduce dyslipidaemia and produced antihyperglycaemic activity in streptozotocin-treated rats. However, MABP and creatinine clearance remained unaffected with AVE-0991 treatment. Conclusions: AVE-0991 produced cardio-renal protection possibly by improving glucose and lipid metabolism in diabetic rats, independent of its blood pressure lowering action.


Author(s):  
W.J. Du Plooy ◽  
P.J. Schutte ◽  
J. Still ◽  
L. Hay ◽  
C.P. Kahler

The stability of cardiodynamic and some blood parameters during a slow, continuous infusion of a combination of ketamine and diazepam is reported. Contractility (dP/dt), myocardial relaxation (Tln), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), arterial blood pressure and certain blood parameters were assessed in 3 male and 3 female juvenile baboons (Papio ursinus). Anaesthesia was induced with 15 mg/kg ketamine IM and maintained with a continuous IV infusion (40-60 mℓ/h) of ketamine and diazepam. The mixture consisted of 2 mℓ ketamine (100 mg/mℓ), 2 mℓ diazepam (5 mg/mℓ) and 50 mℓ saline. A period of 75 + 10 min was allowed for preparation of the animals, after which lead II of the ECG, femoral artery blood pressure and left ventricular pressure were recorded at 15-min intervals for a period of 2 h: the total duration of anaesthesia was 195 min. Arterial blood samples were analysed at 30-min intervals for blood gases, electrolytes, glucose and insulin. Left ventricular parameters were derived from the left ventricular pressure curve. Tln, LVSP and LVEDP showed small fluctuations. Contractility decreased (p < 0.037) at the 195-min interval. No arrhythmias or ECG changes were seen, while blood pressure decreased gradually. Serum calcium concentration decreased and blood glucose levels increased gradually over time. Anaesthesia and analgesia were sufficient and no other drugs were necessary. The animals appeared sedated and dazed 60-80 min after the procedure. A continuous infusion of a combination of ketamine and diazepam for a duration of 150 min can provide stable anaesthesia for cardiodynamic measurements.


Author(s):  
Nasibeh Yousefzadeh ◽  
Sajad Jeddi ◽  
Asghar Ghasemi

Background and Objective: All three isoforms of nitric oxide (NO) synthase (NOS) are targets for thyroid hormones in cardiovascular system. The aim of this study was to assess effects of hypoand hyperthyroidism on inducible (iNOS), endothelial (eNOS), and neural (nNOS) NOS levels in aorta and heart tissues of male rats. Methods: Rats were divided into control, hypothyroid, and hyperthyroid groups; hypo- and hyperthyroidism were induced by adding propylthiouracil (500 mg/L) and L-thyroxine (12 mg/L) to drinking water for a period of 21 days, respectively. At day 21, systolic blood pressure, heart rate, left ventricular developed pressure (LVDP), peak rate of positive and negative (±dp/dt) changes in left ventricular pressure as well as NO metabolites (NOx) and iNOS, eNOS, and nNOS protein levels in aorta and heart were measured. Results: Compared to controls, LVDP and ±dp/dt were lower in both hypo- and hyperthyroid rats. Compared to controls, heart rate and systolic blood pressure were lower in hypothyroid and higher in hyperthyroid rats. NOx levels in the heart of hypothyroid rats were lower (53%) whereas in the heart and aorta of hyperthyroid rats were higher (56% and 40%) than controls. Compared to controls, hypothyroid rats had lower levels of eNOS, iNOS, and nNOS in aorta (16%, 34%, and 15%, respectively) and lower iNOS and higher nNOS in heart tissue (27% and 46%). In hyperthyroid rats, eNOS levels were lower (54% and 30%) and iNOS were higher (63%, and 35%) in the aorta and heart while nNOS was lower in the aorta (18%). Conclusion: Hypothyroidism increased while hyperthyroidism decreased ratio of eNOS/iNOS in aorta and heart; these changes of NOS levels were associated with impaired cardiovascular function.


2002 ◽  
Vol 283 (5) ◽  
pp. H1846-H1855 ◽  
Author(s):  
Jamie W. Meyer ◽  
Michael Flagella ◽  
Roy L. Sutliff ◽  
John N. Lorenz ◽  
Michelle L. Nieman ◽  
...  

The basolateral Na+-K+-2Cl− cotransporter (NKCC1) functions in the maintenance of cellular electrolyte and volume homeostasis. NKCC1-deficient ( Nkcc1 −/−) mice were used to examine its role in cardiac function and in the maintenance of blood pressure and vascular tone. Tail-cuff measurements demonstrated that awake Nkcc1 −/− mice had significantly lower systolic blood pressure than wild-type ( Nkcc1 +/+) mice (114.5 ± 2.2 and 131.8 ± 2.5 mmHg, respectively). Serum aldosterone levels were normal, indicating that extracellular fluid-volume homeostasis was not impaired. Studies using pressure transducers in the femoral artery and left ventricle showed that anesthetized Nkcc1 −/− mice have decreased mean arterial pressure and left ventricular pressure, whereas myocardial contraction parameters were not significantly different from those of Nkcc1 +/+ mice. When stimulated with phenylephrine, aortic smooth muscle from Nkcc1 +/+ and Nkcc1 −/−mice exhibited no significant differences in maximum contractility and only moderate dose-response shifts. In phasic portal vein smooth muscle from Nkcc1 −/− mice, however, a sharp reduction in mechanical force was noted. These results indicate that NKCC1 can be important for the maintenance of normal blood pressure and vascular tone.


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