摘要:

SUMMARY1. The effect of nifedipine infusion on myocardial O2supply and consumption in flow‐restricted and normal regions of the left ventricle was tested in anaesthetized open‐chest rabbits after ligation of the left anterior descending coronary artery for one hour.2. Ten min after occlusion, nifedipine‐treated animals were given either a low or high dose of the drug: a 5 μg/kg bolus followed by 1 μg/kg per min infusion or a 10 μg/kg bolus and 10 μg/kg per min infusion, respectively. Regional blood flow was measured before and after occlusion using radioactive microspheres and O2saturation was measured microspectrophotometrically; the Fick Principle was then employed to determine regional O2consumption.3. After a 60 min occlusion, blood flow was reduced overall to 51% of pre‐ligation flows in the occluded region, and treatment with nifedipine or vehicle did not significantly alter this flow reduction.4. Blood flow in nonoccluded regions increased 1.6‐fold only with the high dose of nifedipine and was unchanged in all other groups.5. Microspectrophotometric analysis of low dose nifedipine and control hearts showed that O2extraction was greater in occluded than in normal myocardium (9.0, s.d. = 0.9, ml O2/100 ml bloodvs7.2, s.d. = 0.7, respectively) and that subendocardial extraction exceeded subepicardial.6. These data suggest that nifedipine administration at this dose had no apparent beneficial effect on O2supply or O2consumption in normal or flow‐restricted regions of the left ventricle during 1 h of coronary a

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00880.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. The renal effects of dopamine, the dopamine antagonist spiperone and the combination of dopamine and spiperone were examined in the isolated perfused rat kidney preparation. Studies were carried out at constant perfusion pressure and the following were measured at 10 min intervals for 1 h: perfusate flow; GFR (3H‐inulin); urine flow rate; sodium, potassium and kallikrein excretion; perfusate renin concentration; perfusate and urinary‐dopamine levels.2. Low‐dose dopamine infusion (6 × 10‐10mol/min) resulted in significant diuresis, natriuresis and kaluresis but little change in GFR. These effects were blocked by spiperone (10‐10mol/min) which had no significant effects when infused alone.3. At a higher dose (10‐8mol/min) dopamine significantly increased urine flow alone; this too was reversed by spiperone.4. Dopamine had no significant effects on perfusate flow, renin release or kallikrein excretion.5. Perfused control kidneys excreted amounts of dopamine (328 pmol/h, s.e.m. = 57,n= 6) far in excess of kidney dopamine content (49 pmol/g, s.e.m. = 6,n= 32). Renal handling of infused dopamine was dose‐related; the fraction of the administered dose taken up and/or metabolized by the kidney on the higher dose infusion was considerably less than on the lower dose (40%, s.e.m. = 3vs.82%, s.e.m. = 6) while more was excreted (13%, s.e.m. = 3vs.2%, s.e.m. = 1).6. These studies indicate that dopamine at low doses can produce diuresis, natriuresis and kaluresis independently of extrarenal or haemodynamic influences and not mediated by renal renin or kallikrein systems. The kidney also exhibits a saturable capacity for dopamine uptake and

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00881.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. Responses of the toad isolated rectus abdominis muscle to cumulative doses of acetylcholine were recorded in the absence or presence of varying concentrations of cimetidine, ranitidine or oxmetidine. The corresponding cumulative log concentration‐response curves for acetylcholine were then plotted for each antagonist studied.2. Cimetidine (5 mmol/1), ranitidine (1 mmol/1) and oxmetidine (0.02 mmol/1) potentiated the effect of acetylcholine by 4‐fold, 2.6‐fold and 1.3‐fold, respectively.3. At higher concentrations all three histamine H2‐receptor antagonists produced a concentration‐dependent and non‐parallel shift of the acetylcholine curve to the right of the corresponding control curve accompanied by a depression of the maximal response.4. The results provide further evidence that the H2‐antagonists studied possess anticholinesterase activity and also suggest that the H2‐antagonists may produce neuromuscular blockade by ion‐channel block. The clinical implications of the results obtained

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00882.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. The effects of intravenously administered ethanol and morphine on pain threshold, reaction time, motor skills and short‐term memory were investigated, and the ability of naloxone to reverse any changes was studied.2. Morphine (loading dose 0.2 mg/kg with an infusion of 0.004 mg/kg per min) and ethanol (loading dose 0.75 ml/kg with an infusion of 0.0025 ml/kg per min) produced a similar increase in pain threshold of 6.3 (s.e.m. = 1.5,n= 8) pain units and 7.7 (s.e.m. = 1.9,n= 8) pain units, respectively. Naloxone 0.015 mg/kg produced a significant reduction in pain threshold in the morphine group, but not in the ethanol group, and there was a significant difference between the groups following naloxone (P<0.05,t‐test, 7 d.f.).3. Ethanol produced a significantly greater deterioration in motor skills than did morphine (P<0.05,t‐test, 7 d.f.) and performance in both groups was improved following naloxone (P<0.05,t‐test, 7 d.f.).4. There was no significant change in the other modalities studied.5. It is concluded that the reversal of ethanol effects by naloxone is probably due to a non‐specific analeptic action rather than blockade of opioid

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00883.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. A measuring system is described for the long‐term continuous beat‐to‐beat measurement of mean aortic pressure and heart period (interval between beats) in the conscious unrestrained rabbit. Pressures and heart periods were collected in hourly histograms. The histograms were summed into day (0800–2000 h), night (2000–0800 h) and 24‐hour histograms. Separate histograms were formed for resting and active periods. From each histogram the mean value, standard deviation, fifth percentile, 50th percentile and 95th percentile were calculated and stored on a floppy disc together with the histograms. Off‐line, histograms and their descriptive parameters were plotted and sent to a HP 1000 computer for bulk storage and further analysis.2. The measuring system is capable of handling up to eight animals simultaneously for an indefinite period.3. The design functioned properly in the long‐term measurement (more than 4 weeks) of mean level and variability of arterial pressure and heart period. The measuring system is useful in the study of arterial blood pressure behaviour after sino‐aortic denervation and in the evaluation of drug effects in

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00884.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. The effects of naloxone on contractility and cardiac rhythm were studied in the rat isolated perfused heart during myocardial ischaemia and reperfusion.2. Pretreatment of the rat isolated perfused heart with naloxone abolished the reduction in left ventricular pressures and attenuated greatly the arrhythmias due to myocardial ischaemia and reperfusion.3. Administration of naloxone into the fibrillating rat isolated heart induced by myocardial ischaemia and reperfusion also attenuated the arrhythmias in a dose‐dependent manner.4. The results indicate a possible involvement of the endogenous opioid peptides in the cardiac effects due to myocardial ischaemia and reperfusion. The anti‐arrhythmic effect of naloxone has great clinical implicati

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00885.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. The effects of naloxone and propranolol on cardiac arrhythmias and durations from respiratory arrest to ventricular asystole and cardiac standstill were studied in unanaesthetized young rats induced to suffer respiratory arrest and exhibit ventricular fibrillation (VF) by a modified chloroform hypoxia technique.2. Both naloxone and propranolol reduced the incidence of VF dose dependently, indicating that they have antiarrhythmic effects. Addition of naloxone to propranolol shifted the dose‐response curve of propranolol to the left significantly, indicating an additive effect of the two drugs in their antiarrhythmic activity.3. Both naloxone and propranolol prolonged the duration from respiratory arrest to ventricular asystole. However, joint administration of both did not further prolong this duration indicating an absence of additive effects.4. Naloxone prolonged the duration from respiratory arrest to cardiac standstill, indicating that naloxone prolonged the survival time. In contrast, propranolol did not produce the same effect.5. That naloxone both produced antiarrhythmic effect and prolonged the survival time whereas propranolol only corrected cardiac arrhythmias suggests that the antiarrhythmic effect of naloxone may not result in prolongation of survival time and that different mechanisms may be involved in the antiarrhythmic effec

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00886.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. The determination of ratios of capillary permeabilities to multiple indicators is secured by constructing upper bounds on effects of early back‐diffusion following a single arterial injection. The analysis does not exclude highly extracted indicators, and it allows for effects of asymmetric blood‐tissue exchange and of tissue concentration gradients.2. The concept of flow limitation of uptake is delimited operationally.3. It is shown how to identify effects of heterogeneity of uptake for data sets extended over large ranges of rate of blood flow.4. These new methods are used to show, for several sets of previously published data from muscle, that back‐diffusion cannot change appreciably the permeability ratios determined previously without any quantification of back‐diffusion.5. The main application is to data published by Perry and Granger (1981) on the permeability of cat intestinal capillaries to raffinose and inulin. The permeability ratios deduced from these data imply paradoxically restricted diffusion; it is shown that this cannot be attributed to effects of back‐diffusion, heterogeneity of extraction, or of solvent drag. It is shown that the paradox is removed if tissue‐to‐blood permeability to raffinose is at least double the blood‐to‐tissue permeability, possibly as part of the active transport of sugars from the intestinal lumen.6. It is shown that corresponding results on permeability ratios in dog gastric capillaries are not paradoxical (against the standard of unrestricted diffusion) under symmetric permeabi

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00887.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. Nifedipine has been reported to aggravate symptoms of ischaemic heart disease in some patients. To investigate the possible reasons for this, vascular resistance changes in the systemic and coronary beds of sheep were compared with and without coronary artery stenoses.2. In six anaesthetized sheep, the dose‐response curve comparing vascular resistance to nifedipine dose showed greater sensitivity than that reported for either dogs or humans. The coronary vascular bed was more reactive than the systemic vascular bed but this difference did not reach a level of statistical significance.3. With fixed non‐elastic proximal coronary artery stenoses, the relationship of both coronary flow and coronary resistance to a standard dose of nifedipine (5 μg/kg) was indirectly related to the degree of stenosis. With stenosis reducing flow at rest by 50% or more, nifedipine usually produced a reduction in coronary flow in the stenosed artery and associated ST elevation, consistent with severe ischaemia in the distribution of the coronary. This effect is related to the reduction in perfusion pres

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00888.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. The radioactive microsphere technique was used to study the systemic and regional haemodynamic effects of the converting enzyme inhibitor captopril (0.1, 0.3 and 1.0 mg/kg) 10 min after intravenous administration in conscious rabbits with bilateral cellophane perinephritis hypertension, an experimental model of hypertension associated with normal plasma renin levels.2. Captopril lowered arterial blood pressure as a result of a dose‐dependent decrease in total peripheral resistance. The fall in blood pressure was accompanied by an increase in cardiac output after the second and third dose of captopril; heart rate was not significantly altered.3. Captopril produced a generalized peripheral vasodilatation; the changes in vascular conductance being most pronounced in the kidneys, intestines and skin which resulted in a significant increase in blood flow to these vascular beds.4. The effective antihypertensive properties of captopril in this ‘low plasma renin’ model of hypertension and the uniform increase in vascular conductances produced by captopril, which antagonizes the generalized increase in vascular resistances that characterizes cellophane perinephritis hypertension, may indicate the involvement of an increased activity of the renin‐angiotensin system, possibly in tissues, such as the vascular wall and brain, in the maintenance of the elevated blood pressure in this hypertensi

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00889.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY