Negative inotropic effect of diazepam in isolated guinea pig heart

The inotropic effect of diazepam, a benzodiazepine derivative, and its mechanism of action were examined using guinea pig heart and single ventricular cell preparations. In Langendorff hearts and right ventricular free-wall preparations, diazepam (10 to 100 microM) produced a monophasic negative inotropic effect in a concentration dependent manner. Neither a central type (flumazenil 1 microM) nor a peripheral type (PK11195 10 microM) of benzodiazepine receptor antagonist antagonized the monophasic negative inotropic effects of diazepam. Diazepam (10 to 100 microM) shortened action potential duration of papillary muscle in a concentration dependent manner. In isolated single ventricular cells, diazepam (30 and 100 microM) inhibited the calcium current (I(Ca)) in a concentration dependent manner. Diazepam produced a significant decrease in I(Ca) elicited by first depolarizing pulses, however, the decrease of I(Ca) was not augmented during a train of depolarizing pulses. Thus, diazepam appears to produce a tonic block of cardiac calcium channels and the mode of inhibition is clearly different from the use-dependent block of verapamil. From these results, it was concluded that diazepam produces a monophasic negative inotropic effect that is independent of the benzodiazepine receptor, and is probably mediated through an inhibition of I(Ca) in guinea pig heart preparations.     

豚鼠维生素营养研究进展

维生素是豚鼠代谢所必需的营养物质 ,必须由饲粮提供。文章从豚鼠对各种维生素的需要量、维生素缺乏症状以及维生素中毒症等方面入手 ,对豚鼠维生素的营养进行了研究。     

Anaesthesia in the pregnant guinea pig

A method for anaesthetising pregnant guinea pigs is described which makes one hour available for abdominal surgery and subsequent recovery; it uses a combination of fentanyl, fluanisone and diazepam with atropine, prednisolone and glucose saline. Provided anaesthesia was performed no later than the 48th day of gestation, 85 per cent of pregnancies continued to term and 74 per cent of the pups survived the first 24 hours after birth.     

Techniques for the isolation of salmonellas from eggs.

1. When the contents of 4 or more naturally-contaminated intact eggs were combined, the isolation rate of Salmonella enteritidis was improved by extending incubation at 37 degrees C from 24 to 48 h before sub-culture. 2. The isolation rate of salmonellas from raw homogenised whole egg was significantly increased by the inclusion of Novobiocin and Cefsulodin in the primary culture media. 3. Rappaport Vassiliadis broth was found to be superior to Selenite as a selective enrichment medium.     

Anticholinergic effects of artemisinin, an antimalarial drug, in isolated guinea pig heart preparations

Concern has been growing about the cardiac toxicity of antimalarial drugs. Artemisinin, a unique type of antimalarial drug originating from a Chinese medicinal plant, has minimal adverse effects, but it has been reported to inhibit delayed rectifier potassium current, a voltage-gated potassium current. However, no studies have been published concerning the effect of artemisinin on ligand-gated potassium currents. Therefore, in the present study, we examined the influence of artemisinin on the acetylcholine receptor-operated potassium current (IK.ACh), a ligand-gated potassium current, in guinea pig atrial myocytes using a patch clamp technique. Artemisinin (1 to 300 microM) inhibited I(K.ACh) induced by extracellular application of both carbachol (1 microM) and adenosine (10 microM) and that induced by intracellular loading of GTPgammaS (100 microM) in a concentration-dependent manner. Artemisinin inhibited carbachol-induced, adenosine-induced, and GTPgammaS-activated IK.ACh within almost the same concentration range. In left atria, artemisinin (1 to 100 microM) partially reversed the shortening of action potential duration induced by carbachol in a concentration-dependent manner. Carbachol-induced negative inotropic action in left atria was also inhibited by artemisinin (10 to 300 microM). In conclusion, we suggest that the anticholinergic action of artemisinin is mediated through inhibition of IK.ACh via inhibition of the muscarinic potassium channel and/or associated GTP-binding proteins.     

Endotoxin-induced microvascular injury in isolated and perfused pig lungs

The lungs of 13 healthy Landrace piglets were isolated, perfused and maintained in an isogravimetric state under zone III conditions. By applying vascular occlusion methods, the total blood flow resistance (Rt) was partitioned into four components: arterial (Ra), pre- (Ra) and post-capillary (Rv), and venous (Rv). The capillary filtration coefficient (K _f,c) was evaluated using a gravimetric technique. A bolus of 55 µg ofEscherichia coli endotoxins (LPS) per 100 g of lung was injected into the arterial reservoir of eight lungs, followed by an infusion of LPS at a rate of 55 µg per 100 g of lung per hour for 180 min. A bolus of theophylline (85 mg per 100 g of lung weight) was injected into the arterial reservoir after the last determination of theK _f,c value. All the parameters were evaluated again when the lungs reached a new steady state. Endotoxin induced a significant increase inRt from 54.7 ± 7.0 at zero time to 184.7±44.2 cm H₂O min L^–1 (100 g)^–1 180 minutes later, which can be ascribed to the increase inRa andRv. These haemodynamic modifications were related to the increases in the arterial pressure and in the pressure at the distal end of the arterial segment and to the decreases in the pressure at the proximal end of the venous segment and in the blood flow. The capillary pressure and the lung weight remained unchanged. Endotoxin infusion infusion induced an increase in theK _f,c value from 0.208±0.011 (att=0) to 0.391±0.034 ml min^–1 (cmH₂O)^–1 (100 g)^–1 (att=180). Administration of theophylline significantly reducedRt,Ra,Ra andRv towards or under the baseline values and also induced a significant increase in the lung weight and in theK _f,c value. It was concluded that the endotoxin-induced increase in the total blood flow resistance can be ascribed to a vasospasm occurring at the level of the pre- and post-capillary small vessels and that changes in the permeability of the endothelium greatly contribute to the development of the pulmonary oedema observed in endotoxaemic pigs.     

Thermodilution cardiac output determination in the guinea pig

Thermodilution cardiac output was compared with simultaneously determined aortic flow in 5 guinea pigs during thoracotomy. Total cardiac output was affected by volume expansion, adrenergic stimulation, and the volume of hemorrhage. For the equation y = mx, where y is aortic flow, x is thermodilution cardiac output, and m is the slope of the regression line, m = 0.88 +/- 0.02 (95% confidence interval). The SE of the regression was 27.8 ml/min. Thermodilution may have been overestimated because the aortic flow measurement did not take into account the coronary arterial blood flow, which is approximately 4% of total cardiac output in the guinea pig. Indicator loss (ie, temperature) also may be an important factor in the calculation of cardiac output, as determinations of thermodilution cardiac output were affected by sampling site in the guinea pig. Thermodilution appears to be a useful and reliable means of determining cardiac output in the guinea pig.     

Furazolidone-induced injury in the isolated perfused chicken heart

The Langendorff isolated heart preparation was adapted to determine the effect of furazolidone (0.5 and 2 micrograms/ml of perfusate) on hearts of 3-week-old broiler chickens. Following 115 minutes of perfusion, both concentrations of furazolidone caused approximately a two-fold increase in myocardial vascular resistance and a six-fold increase in lactate dehydrogenase release into the effluent fluid, compared with a control perfused group of isolated hearts (P less than 0.01). Ultrastructural alteration differences were not found between the drug-treated and control groups. It was concluded that: (i) furazolidone, at concentrations only moderately above therapeutic plasma concentrations, caused detrimental changes in myocardial vascular resistance and lactate dehydrogenase release and (ii) the isolated chicken heart preparation is an example of a cost-effective, reliable laboratory tool for screening potential cardiotoxins.