No abstract

1. The effect of a-and /1-adrenoceptor stimulation on isotonic contraction was investigated on right ventricular papillary muscles of the rat, stimulated at a rate of 0 5 Hz. 2. Adrenaline (0 5 /M) induced a slight but significant negative inotropic effect: shortening decreased from 0-137 + 0-058 to 0-122 + 0 059 muscle lengths (mean + S.D.; -11%, P< 0-0001) and maximum shortening velocity from 2-9 + 12 to 2-7 + 1-3 muscle lengths s-5 (-7 %, P < 0 025). 3. The negative inotropic effect of adrenaline was enhanced after blocking the fl-adrenoceptors with 50 uM atenolol. On the other hand, exposure to adrenaline after blocking the a-adrenoceptors with 50,uM phentolamine resulted in an increase in shortening as well as in maximum shortening velocity. 4. Stimulation of the f-adrenoceptors with 0-5 /M isoprenaline caused marked positive inotropic effects, whereas stimulation of the az-adrenoceptors with 0-5 FM phenylephrine regularly resulted in a long-lasting decrease in shortening and maximum shortening velocity. 5. 1,2-Dioctanoyl-sn-glycerol (1,2-DOG) and adrenaline induced an activation of protein kinase C (PKC) with translocation of this enzyme from the cytosol to the sarcolemma.6. Activation of PKC with 10,uM 1,2-DOG and 0-5 #M adrenaline was accompanied by a decrease in shortening and maximum shortening velocity. Inhibition of PKC with 0-1 M staurosporine abolished the negative inotropic effect of adrenaline.7. From these results we conclude that a low dose of adrenaline stimulates not only fa-but also a-adrenoceptors and that the observed negative inotropic effect of adrenaline is mediated by a1-adrenoceptors, linked to the diacylglycerol-PKC signal transduction pathway.The sympathetic nervous system modulates cardiac contraction via a-and l6-adrenoceptors. The activation of the ,-adrenoceptors results principally in an increase in cAMP, whereas the a-adrenoceptors are linked to two signal transducing pathways, i.e. inositol trisphosphate and diacylglycerol (Berridge, 1984).The modulation of cardiac contractility by az-adrenoceptors has been reviewed recently in detail (Fedida, 1993;Terzic, Puceat, Vassort & Vogel, 1993). Positive inotropic effects of az-adrenoceptor stimulation have been well established, although significant differences exist from species to species.

The effect of long-term application of Crataegus oxyacantha on ischemia and reperfusion induced arrhythmias was investigated in Wistar rats on the heart in situ and on Langendorff preparations. Seventeen rats were fed for 8 weeks with 0.5 g/kg b.w. Crataegus extract per day, standardised to 2.2% flavonoids. Twenty age-matched untreated rats served as controls. In the hearts in situ as well as in the Langendorff preparations the left anterior descending coronary artery (LAD) was ligated for 20 min and subsequently reperfused for 30 min. ECG was continuously recorded and the time spent between start of ischemia and onset of arrhythmias was measured. In addition, during ischemia and reperfusion the number of ventricular premature beats and bigemini and the duration of salvos and ventricular flutter and fibrillation were determined. The ischemic area was evaluated in all experiments and coronary flow was measured in Langendorff preparations. In the present experiments, no cardioprotective effects of Crataegus oxyacantha could be detected, neither in the heart in situ nor in the Langendorff preparations. Although the ischemic areas were identical, arrhythmias occurred even earlier in the Crataegus collectives than in the controls. Also the number and duration of ischemia and reperfusion induced arrhythmias tended to occur longer and more frequently in the Crataegus collectives, whilst coronary flow remained unchanged. The phenomenon that Crataegus rather aggravates than prevents arrhythmias may be reduced to a Crataegus induced increase in intracellular Ca(2+)-concentration proven true for the positive inotropic effects of Crataegus.

A modified heart-lung preparation of the rat, which permits measuring systolic and diastolic coronary flow separately and enables coronary compliance to be evaluated, is described. The systemic circulation was substituted by a shunt circuit, and the elastic properties of the arterial tree were mimicked by a rubber balloon. Systolic and diastolic coronary flow was evaluated from the pulmonary and aortic flow signal. Integrated phasic pulmonary flow represented right ventricular stroke volume. Integrated phasic systolic aortic flow represented left ventricular stroke volume minus that volume flowing into the coronary arteries during systole, because the aortic flow probe had to be inserted distal to the origin of the coronary vessels. Because right and left ventricular stroke volume was identical under steady-state conditions, the difference between systolic pulmonary and systolic aortic flow resulted in systolic coronary flow. Diastolic coronary flow was measured by means of the retrograde flow through the aortic flow probe. Coronary compliance was calculated according to Frank's windkessel model from coronary resistance and from central diastolic aortic pressure, which decayed exponentially after switching out the rubber balloon and the shunt circuit. It could be shown that the proportion of systolic to diastolic coronary flow depends on coronary compliance.