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Background: Magnetic resonance imaging (MRI) is a versatile technique for examination of the cardiovascular system but only recently has assessment of myocardial ischaemia in coronary artery disease (CAD) become possible, for example by demonstrating abnormalities of regional ventricular contraction during stress. Global ventricular function during stress was assessed by MRI of aortic flow, which has not been previously attempted., Design: Variables measured by MRI reflecting the effect of ischaemia on global ventricular function during dobutamine stress were correlated with thallium-201 myocardial perfusion tomography., Patients: 10 normal controls and 25 patients with CAD., Setting: Tertiary cardiac referral centre., Methods: Novel MRI sequences and analysis systems were used to measure the following variables during staged dobutamine infusion to 20 micrograms/kg/min: stroke volume, cardiac output, cardiac power output, peak flow, peak flow acceleration, aortic back flow, and flow wave velocity. Heart rate, blood pressure, double product, and maximum tolerated dobutamine dose were also measured. Multiple regression analysis was used to compare changes during stress with 201TI tomography., Results: All parameters except for stroke volume and diastolic blood pressure increased in the controls. In the patients with CAD a significant relation was shown between the extent of reversible ischaemia and the change in peak flow acceleration (P < 0.00001), peak flow (P = 0.002), cardiac power output (P = 0.036), maximum dobutamine dose (P = 0.039), and systolic blood pressure (P = 0.04). Peak flow acceleration accounted for 58.4% of the variation in reversible ischaemia, and after allowing for this, only cardiac power output remained independently predictive adding a further 4.2% to the model (adjusted r2 = 0.626). A decrease in peak flow acceleration with an increase in dobutamine infusion indicated moderate or severe ischaemia (chi 2 = 10.2, P = 0.017)., Conclusion: MRI may be used to assess variables of aortic flow during stress, which includes acceleration with high temporal resolution. Peak flow acceleration was the most sensitive indicator of the effect of ischaemia on global ventricular function.

Studies in isolated superfused rabbit papillary muscles indicate that preconditioning (PC) is not confined to arterially perfused myocardium. In the present study PC of isolated human right atrial trabeculae was investigated avoiding the problems of invasive experimentation in patients. Atrial trabeculae were suspended in an organ bath, superfused with Tyrode's solution and field stimulated at 1 Hz. After stabilization, muscles were randomly allocated to five groups (n = 8 per group). Control (C) muscles had no additional treatment. PC was induced by 3 min rapid pacing at 3 Hz with hypoxic substrate-free buffer, followed by reoxygenation with substrate for 12 min. In two additional groups 8-p-sulfophenyltheophylline (SPT) was added to the superfusate either during stabilization in controls (C+SPT) or during preconditioning (PC+SPT). In the final group, R-phenyl-isopropyl adenosine (R-PIA) was added to the superfusate for 5 min to see whether or not this could substitute for preconditioning. All muscles were then exposed to 90 min hypoxia with no substrate and pacing at 3 Hz, followed by 120 min reoxygenation at 1 Hz. Recovery of developed tension was significantly improved by PC 46.5 +/- 2.4% v 24.6 +/- 2.3% in controls) and this protective effect was blocked by the addition of SPT without adversely affecting controls (recovery in PC+SPT, 25.8 +/- 4.1% and C+SPT, 22.7 +/- 2.9%). R-PIA protected the muscles to a similar extent as PC (43.8 +/- 1.9%). These data provide evidence for the involvement of adenosine in preconditioning in human myocardium.

Growth hormone excess is known to have adverse effects on the heart. The long term cardiac effects of growth hormone given to short normal children as part of a prospective randomised controlled trial of growth hormone treatment (Genotropin 30 IU/m2/week v no treatment) were therefore investigated. Echocardiographic findings are presented for 28 children who have been followed up for a minimum of four years. At the outset, the treated (n = 15) and untreated groups (n = 13) did not differ for any anthropometric or echocardiographic parameter. Their mean (SD) age at onset was 7.8 (0.5) years. After four years of treatment mean height SD score increased from -2.4 to -1.2 compared with no change (-2.5) in the untreated group. Left ventricular posterior wall and septal thickness and left ventricular shortening fraction did not differ between the groups, but a tendency towards increased left ventricular mass was seen in the treatment group (93 v 73 g). No such differential was observed after indexing left ventricular mass for body surface area (79 v 71 g/m2) or lean body mass (3.15 v 3.05 g/kg). It is concluded that prolonged growth hormone treatment does not cause important changes to the heart. A tendency towards increased left ventricular mass simply reflects the increase in lean body mass during treatment.

Dobutamine has favorable properties for the pharmacologic manipulation of myocardial oxygen demand in the provocation of ischemia during the investigation of coronary artery disease. The value of dobutamine infusion for thallium myocardial perfusion tomography was assessed in 50 patients with exertional chest pain undergoing coronary arteriography. Dobutamine was infused in 5-min stages at incremental rates from 5 to 20 micrograms/kg per min or until limited by symptoms. The myocardium was divided into nine segments for analysis of perfusion. Thirty-nine of 40 patients with coronary artery disease had a reversible perfusion defect demonstrated by dobutamine thallium tomography (sensitivity 97%) and 8 of 10 patients with normal coronary arteries had normal myocardial perfusion (specificity 80%). These values were significantly better than the sensitivity and specificity of exercise electrocardiography (78% and 44%, respectively; p less than 0.01). There was a significant relation between the mean number of segments with abnormal perfusion and the number of diseased coronary vessels (0.6, 2.6, 4.4 and 6 segments in zero-, one-, two- and three-vessel disease, respectively; p less than 0.001). There was also a significant relation between the maximal tolerated dose of dobutamine and the treadmill exercise time (r = 0.56, p less than 0.001), but a wide range of exercise times was achieved in the 15- and 20-micrograms/kg per min groups, principally because of exercise limitation by noncardiac symptoms. Dobutamine infusion was well tolerated in all patients, including six with asthma. There were no significant arrhythmias or limiting symptoms other than chest pain.(ABSTRACT TRUNCATED AT 250 WORDS)

An acute intravenous bolus of 10 mg ketanserin (a specific 5-HT antagonist) caused an abrupt fall in left ventricular systolic pressure of 17 +/- 9.2 mm Hg (P less than 0.025) in ten patients undergoing cardiac catheterisation for chest pains. A fall in pulmonary artery diastolic pressure of 2.1 +/- 0.74 mm Hg (P less than 0.02) was also observed. No changes in resting heart rate occurred and the response to pacing was largely unmodified by ketanserin, except for a reduction in pulmonary vascular resistance (3.70 +/- 1.27 units to 2.97 +/- 1.44 units, P less than 0.05), at the fastest rate (136 +/- 3 beats/min). At the highest pacing rate coronary sinus blood flow fell (83 +/- 12 ml 100 g-1 min-1 to 68 +/- 8 ml 100 g-1 min-1, P less than 0.05), as did myocardial oxygen consumption (18 +/- 2 ml-1 min to 14 +/- 1 ml min-1, P less than 0.05) after the drug. No changes in the parameters of left ventricular contractile function could be attributed to ketanserin, save for a modest increase in the ejection fraction (48 +/- 6% to 57 +/- 6%, P less than 0.05) in seven patients. There were no alterations in myocardial metabolism of lactate, pyruvate, hydroxybutyrate, glycerol nor free fatty acids after ketanserin. The findings are consistent with a peripheral site of action of this drug and its blood pressure lowering effect in the subjects suggest a non-specific hypotensive action rather than an anti-hypertensive effect.

When the heart-lung preparation is made from a dog treated with reserpine, catechol amines such as noradrenaline and isoprenaline have a greater effect on the rate of the heart than they have in a preparation from a normal dog. Other sympathomimetic amines such as tyramine and ephedrine, on the other hand, are found to have lost their action. Since treatment with reserpine has been shown to cause the store of noradrenaline in the heart to disappear, and the infusion of noradrenaline into the preparation made from a reserpine-treated animal restores the action of tyramine, it is concluded that substances like tyramine and ephedrine normally act by liberating noradrenaline from the store, and do not act directly. Cocaine, like reserpine, increases the effect of noradrenaline and decreases the effect of tyramine on the heart rate; it appears to block the release of noradrenaline from the store in the heart.

Isolated pairs of rabbit auricles have been observed in media containing 6, 24 or 75 mM-potassium, with corresponding reductions in sodium concentration. In 24 mM-potassium, adrenaline restored beating and excitability, as did calcium chloride, but ouabain had no effect. In 75 mM-potassium, adrenaline had no effect; calcium chloride caused a contracture; ouabain had no direct effect, but auricles which had been beating in the presence of ouabain contracted promptly on transfer to 75 mM-potassium. Left auricles, which do not beat spontaneously, were less sensitive to calcium and to ouabain. The results showed a membrane stabilizing action of calcium and an action on muscular contraction, and suggested that cardiac glycosides acted by causing accumulation of calcium at the activator site in the tissue.