The potential carcinogenic effect of inhaled automobile exhaust emissions was examined in rodents. Both rats and hamsters were exposed to the emissions from (1) a gasoline engine, (2) a gasoline engine fitted with a three-way catalytic converter, (3) a diesel engine and (4) a diesel engine with particle filtration. Exposures were for 16 hours per day, 5 days per week, for 2 years. All hamsters were sacrificed at the end of the 2-year exposure period, whereas the rats surviving after 2 years of exposure were maintained for a further 6-month observation period without additional exposure to emissions. Some of the hamsters in each treatment group were pretreated with diethylnitrosamine to induce respiratory tract tumours. No statistically significant changes were seen in the incidence of respiratory tract tumours in emission-exposed hamsters compared to controls. This lack of a treatment-related effect was seen in both the nitrosamine pretreated and the non-pretreated hamsters. There was no increase in the incidence of lung tumours in rats exposed to filtered diesel exhaust or to the exhaust from the gasoline or gasoline-catalyst engines. There was a statistically significant increase in the incidence of lung tumours in rats exposed to diesel engine emissions compared to controls. A clear dose response was evident in both males and females, although the incidence of lung tumours was markedly higher in females (96% in rats surviving beyond 2 years) than in males (44% in rats surviving beyond 2 years). An increased incidence of lung tumours was observed only in rats exposed to mean concentrations of diesel soot particles of either 2200 or 6600 micrograms/m3.(ABSTRACT TRUNCATED AT 250 WORDS)

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Up to 8 variables in the respiratory patterns of rats and hamsters can be measured simultaneously. The technique uses modified restraint tubes and an animal pneumotachograph.

Tedisamil, a potassium channel blocker, is known to produce bradycardia. The hypothesis tested was that tcdisamil-induced bradycardia should improve the mechanical and metabolic properties of the ischemic myocardium.['sing isolated perfused rat heart with coronary-artery ligalion, tedisamil was compared with alinidine, verapamil, and propranolol. The end points were myocardial mechanical function and oxygen uptake. In coronary-ligated hearts, tedisamil (1.83 x 10 -~ M) decreased heart rate, increased left ventricular dl'/dt,,,,, and increased pressure power production. Efficiency of work rose with tedisamil. Alinidine (7 x l0 -~ ?,l) also decreased heart rate without altering left ventricular dP/dtm, ,, power production, or myocardial efficiency. Verapamil (1.5 x 10 -~ 31) did not alter heart rate but decreased left ventricular dl'/dtm, ~, while power production and myocardial efficiency also fell. I'roprano[ol (1 x 10 -3 )I) caused changes similar to verapamil, except that the heart rate also fell. Dobutamine (1.18 x 10-: M) increased cardiac output and oxygen uptake without altering mechanical efficieno'. Of the drugs tested and in the concentrations used in the coronary ligated rat heart, it was only tedisamil that had the capacity to cause less decrease in mechanical work and in myocardial efficiency than in controls.Tedisamil is an agent known to prolong the actionpotential duration of the rat heart and to induce bradycardia [1]. The mode of action is thought to be a combination of blockade of two time-dependent potassium channels, T O and the delayed rectifier. These properties should make tedisamil a useful drug in the management of acute myocardial isehemia, when both a reduction of myocardial oxygen uptake following a reduction of heart rate and inhibition of acute ischemic arrhythmias [2] are desired. These potentially antiischemic properties of tedisamil were assessed in the isolated working rat-heart preparation with coronary-artery ligation. This drug was compared with alinidine, another agent that causes a bradycardia independent of adrenergic or calcium blockade, and with established antiischemic agents, such as verapamil and propranolol. Because tedisamil appeared to have a positive inotropic effect in this preparation, comparisons were also made with the beta I agonist, dobutamine. Materials and MethodsHearts fl'om male Spraglm-Dawley rats (250-350 g) given 200 IU of hepavin were excised, arrested in icecold perfusate, and mounted by the aorta for a preperfusion period of 10 minutes. The left atrium was cannulated to allow atrial perfusion [3] with a filling pressure of 11 cm H,O and an aortic column height of 96 cm H.zO. The perfusate consisted of a KrebsHenseleit bicarbonate medium (pH 7.4 at 37°C) containing (mM) NaC1 118.5, KC1 4.75, CaCI., 2.5, KH.;P04 1.19, MgS04 1.19, and NaHCQ 25.0. Glucose 11 ram was the substrate. Experimental designHearts (n = 18 for tedisamil and control hearts with ligation; n = 6 for hearts perfused with alinidine, verapamil, propranolol, dobutamine, and control hea...