1. Certain sugars were transported across the buccal mucosa by a carrier-mediated mechanism. 2. The metabolic loss of sugars from the mouth in a 5 min test period was negligible. 3. The buccal mucosal transport process was stereospecific for D-glucose and L-arabinose. 4. The absorption of D-glucose, galactose and 3-O-methyl-D-glucose was at least partly dependent on the presence of sodium ions in the luminal fluid. 5. The transport of D-glucose, was inhibited by galactose and 3-O-methyl-D-glucose, suggesting at least one common carrier system.

Adult↗

PubMedDate not supplied

Effect of chronic beta-blockade on the ischaemic myocardium: a comparative study with five drugs.

The long-term effects of chronic beta-blockade in the rat myocardium were investigated in terms of responses to ischaemic stress. Clinically relevant and equipotent doses of oxprenolol, propranolol, metoprolol, atenolol, and practolol were administered orally for 12 weeks. Twenty-four hours after the last dose, at a time when plasma drug levels were undetectable, hearts were excised and perfused as isolated preparations. During a 3-h period of low-flow, global ischaemia, the time to electromechanical failure following the onset of ischaemia was significantly increased in hearts from animals treated with drugs possessing intrinsic sympathomimetic activity (ISA). Similarly, with ischaemia-induced lactate and enzyme release, hearts from groups treated with drugs possessing ISA showed an increase in release above that of controls, or of hearts from rats treated with beta-blockers which did not possess ISA. These results suggest that in the isolated, globally ischaemic heart, when exogenous catecholamine drive is absent, long-term beta-blockade cannot exert a protective effect when circulating drug levels are undetectable, and compounds possessing ISA may increase tissue damage as measured by lactate and enzyme leakage.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Ischemia- and reperfusion-induced arrhythmias: beneficial actions of nifedipine.

The effects of nifedipine against ischemia- and reperfusion-induced arrhythmias were investigated using anesthetized rats with transient coronary artery occlusion. Nifedipine (5 micrograms/kg i.v.) administered 10 min prior to occlusion significantly decreased the incidence of arrhythmias occurring during 20-min coronary occlusion. The incidence and duration of reperfusion-induced ventricular fibrillation and subsequent mortality following 5-min coronary occlusion were also significantly reduced by this intervention. However, administration of nifedipine 1 min prior to reperfusion afforded no protection against reperfusion arrhythmias. To investigate whether nifedipine possesses a true antiarrhythmic action or merely extends the ischemic duration prior to reperfusion resulting in maximal rhythm disturbances, reperfusion was initiated after 3, 5, 7, 10, 20, and 30 min of ischemia. Nifedipine reduced the incidence of reperfusion-induced ventricular fibrillation after all ischemic intervals, with no change in the time of peak vulnerability to reperfusion arrhythmias. Measurements of coronary flow with 153Gadolinium microspheres indicated that flow within ischemic tissue relative to that in normal tissue was significantly increased by nifedipine. Thus, administration of nifedipine prior to occlusion affords a protective effect against ischemia- and reperfusion-induced arrhythmias, and this action is not due to extension of the ischemic duration prior to reperfusion resulting in maximal rhythm disturbances.

Animals↗

PubMedDate not supplied

Forskolin: effects on cyclic AMP and contractile function in the isolated rat and guinea pig heart.

The new inotropic agent, forskolin, is thought to act by stimulation of adenyl cyclase at a site remote from the beta-receptor. In this study we have characterized the action of forskolin in isolated, perfused rat and guinea-pig hearts. In both species, forskolin increased heart rate, left ventricular pressure and tissue cyclic AMP in a concentration-dependent manner. Significant responses were obtained with a minimum concentration of 2 X 10(-9)M forskolin in the rat and 2 X 10(-8)M in the guinea-pig. In both species maximal effects were observed with 2 X 10(-6)M forskolin. For any given forskolin concentration, the increases in cyclic AMP were greater in the rat heart than in the guinea-pig heart. In the rat heart, two beta-adrenoceptor blocking agents (1.6 X 10(-6)M propranolol or 2.6 X 10(-6)M timolol) were both able to reduce the increases in function and tissue cyclic AMP content caused by forskolin (2 X 10(-7) and 2 X 10(-8)M). However, no inhibition by beta-blockade was observed in hearts from catecholamine-depleted (reserpinized) animals or in hearts treated with high concentrations (2 X 10(-6)M) of forskolin. These results indicate that catecholamines may in some way be able to potentiate the actions of forskolin.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Forskolin and myocardial function in the normal, ischemic and reperfused rat heart.

Forskolin increases intracellular cyclic AMP content by direct stimulation of adenylate-cyclase independently of the beta receptor. Studies have been carried out in two different types of isolated rat heart preparation to compare the cardiovascular effects of forskolin and isoprenaline. The inotropic and chronotropic properties of these drugs, together with their ability to increase myocardial cyclic AMP content, have been studied under conditions of aerobic perfusion and also post-ischemic reperfusion. In studies with isolated rat hearts perfused in the Langendorff mode, the dose-response characteristics of forskolin have been characterized. At a concentration of 2 X 10(-7) moles/L, forskolin increased heart rate, coronary flow and left ventricular pressure by 24 +/- 4%, 33 +/- 6% and 33 +/- 3% respectively, and cyclic AMP content was increased seventeen fold (4.0 +/- 0.3 to 68.0 +/- 8.0 nanomoles/g dry wt). Investigation of the effects of three concentrations of forskolin in the isolated working heart revealed that some increases in contractile state could again be achieved. Thus, at a concentration of 5 X 10(-7) moles/L, forskolin increased heart rate by up to 27%, coronary flow by up to 18%, aortic flow by up to 10%, cardiac output by up to 8%, peak aortic pressure by up to 18%, pressure rate product by up to 45% and minute work by up to 25%. These increases, although relatively small, were greater and longer sustained than those seen with isoprenaline (10(-6) moles/L). In additional studies, forskolin (10(-7) moles/L) was included in the reperfusion solution of hearts recovering from a 30 minute period of ischemic cardioplegic arrest. In comparison with controls, which were reperfused without forskolin, small increases in contractile recovery (mostly relating to an increased chronotropic state) were observed. However, upon withdrawal of the drug the functional indices declined such that they were indistinguishable from control hearts which had not received the drug during reperfusion. It is speculated that the relatively poor response to forskolin in the working as opposed to the Langendorff perfused heart may be a reflection of the greater metabolic rate of the working heart and that it may be the rate of turnover of cyclic AMP and other metabolites rather than their steady state cellular level which might determine the responsiveness of tissue to forskolin.

Animals↗

PubMedDate not supplied

'Early' ischemia and reperfusion-induced arrhythmias: antiarrhythmic effects of diltiazem in the conscious rat.

The ability of diltiazem to prevent early ischemia and reperfusion-induced arrhythmias was investigated in conscious rats with coronary artery occlusion. During a 30-min period of occlusion of the left coronary artery, 100% of placebo-treated animals exhibited ventricular tachycardia, 65% exhibited ventricular fibrillation and the mean total number of premature ventricular complexes was 1076 +/- 254. Diltiazem (0.5 or 2.0 mg/kg body weight, given intravenously 10 mins prior to coronary occlusion), reduced the incidence of ventricular tachycardia to 62% (P less than 0.01) and 54% (P less than 0.001), respectively and the incidence of ventricular fibrillation to 31% (P = NS) and 15% (P less than 0.01), respectively. The total number of premature ventricular complexes was also reduced to 248 +/- 78 (P = NS) and 156 +/- 55 (P less than 0.02). The development of ST segment elevation, induced by coronary artery occlusion, was delayed in both drug-treated groups. Similarly, diltiazem, at the same doses, reduced the incidence of ventricular fibrillation induced by reperfusion after 5 mins of coronary artery occlusion from 100% to 50% (P less than 0.01) and 25% (P less than 0.001) and mortality from 87% to 42% (P less than 0.02) and 25% (P less than 0.01), respectively. The anti-arrhythmic effects of diltiazem were not related to changes in heart rate and all groups showed similar occluded zone sizes, as measured by a fluorescent microsphere technique. Thus, diltiazem affords substantial protection against both early ischemia-induced ventricular arrhythmias and reperfusion-induced arrhythmias and this action may be associated with the beneficial effects on ischemia-induced ST segment elevation.

Animals↗