INTRODUCTIONThe effect of temperature on the action of drugs in animals and man has interested physiologists and pharmacologists for a long time. Several review articles have appeared in the last 25 years. In some, the effects of body temperature (22,38,92) were differentiated from those of environmental temperature (40, 90) on drug action. The effects of climate were considered by K. 1. Furman (41) and Weihe (111). F. A. Fuhrman (39) and K. 1. Furman (42) reported on the effects of heat, and Johnson (66) on the effects of cold. A different approach to the problem dealing exclusively with the sensitivity of laboratory animals is pre sented in the reviews by Laroche (75) and Ellis (34). All these reviews deal chiefly with experiments on animals which demonstrated striking effects of heat and cold on drug toxicity.Many proceedings of symposia and review articles have been published since 1960 on the mechanism of temperature regulation and the physiological effects of heat and cold (13,33,51,52,55,76,94) and on temperature regulation and drugs (77,83,108,109). In the same period, publications dealing with the specific problems of alteration of drug action by temperature or climate in man are rare (39,41).Most inVestigations on the modification of drug action were done with com mon homeothermic laboratory animals. They demonstrate either a variation of results in drug testing due to an improperly controlled thermal environment, or a change of sensitivity of the animal to drugs under controlled conditions of heat and cold. New problems have arisen from toxic effects of environment pollution in various climatic zones. Here, too, little has been published as yet. This paper will deal only with homeothermic species not subjected to induced hypo-or hyperthermia.THERMOREGULATION Normally, homeothermic species show a very small variation of core tempera ture within 24 hours. On exposure to extreme heat (> T. 33°C) and cold « T. 15°C) mice and rats maintain their body temperatures by means of powerful 1 Parts of this review were presented at the Symposium on the Pharmacology of Thermoregulation, San Francisco, 29-31 July 1972, and are published under the title .. The effect of temperature on the action of drugs" in .. The Pharmacology of thermoregulation" edited by P. Lomax and E. Schonbaum, Karger, Basel, 1973. 409 Annu. Rev. Pharmacol. 1973.13:409-425. Downloaded from www.annualreviews.org Access provided by Chinese University of Hong Kong on 02/05/15. For personal use only. Quick links to online content Further ANNUAL REVIEWS 410 WEIHE homeostatic mechanisms. In mice, Chen et al (17) measured at an ambient tem perature (T.) of 20°C a rectal temperature (T ro) of 34.7°C and at T a 4O°C a T ro of 38SC. Doss & Ohnesorge (30) found in mice after ISO min at T. 3SDC a T,. 38.4OC and at T. 30DC aT,. 36.8°C. At T. ISoC the T .. was 36.6°C. Usinger (106) working with 30DC adapted resting mice, recorded a decrease of Tre from 35.60 to 35.1 DC after a change to T. 20°C. In rats, Maickel (79) measured after a 4-hr exposure at ...
h i d l o w and J. S t r i t t m a t t e r * *
Eight mongrel dogs exercised for 8 weeks by treadmill running at 20 per cent incline 20 to 25 minutes twice daily, 4-5 days/week. Another eight dogs which were kept in the cages for a similar period served as controls. The exercise program was effective in inducing myocardial hypertrophy since the ratio left ventricular weight/body weight was significantly (P less than 0.001) higher in the trained dogs (5.04 g/kg) than in the sedentary animals (3.83 g/kg). In morphine-chloralose anesthesia the dogs were studied by left heart catherization and cineangiography at spontaneous heart rate (run I), at paced heart rate (run II), at paced heart rate following cardiac autonomic nervous blockade by bilateral vagotomy and the administration of propranolol (run III) and during acute pressure loading with methoxzmine at constant heart rate (run IV). Intergroup comparison yielded no significant difference in any hemodynamic or volumetric parameter throughout the entire study. However, with intragroup comparisons between run III and run IV a less significant increase in left ventricular end-diastolic pressure (from 5 to 15 mm Hg; P less than 0.05) was observed in the trained animals than in the control dogs (from 6 to 25 mm Hg; P less than 0.001). Left ventricular end-diastolic volume increased significantly only in the control dogs during acute pressure loading. Mean aortic pressure and left ventricular peak dP/dt increased to a similar extent in both groups. Since in the trained dogs the left ventricle encroaches less on the Frank-Starling mechanism than in normal animals for overcoming an acute pressure burden it is concluded that the development of hypertrophy concomitant with chronic exercise represents an adaptive mechanism with evidence of beneficial consequences for the intrinsic contractile function of the myocardium.
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