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Various methods of heart preservation for 24 hr were compared and the viability of organs was tested by means of heterotopic cervical homotransplantation. The hearts were preserved under hypothermic (2–3 C) and hyperbaric (7 atmospheres (atm) of air) conditions. There were three groups of hyperbaric hearts: (1) hearts stored in Krebs-Ringer bicarbonate solution; (2) hearts stored in cardioplegic solution according to Bretschneider; and (3) hearts stored in cardioplegic solution with additional application of succinate, 3-hy-droxybutyrate, and adenosine triphosphate. In another group the hearts were stored in 15 solution of dimethylsulphoxide at a temperature of —20 C. The hearts were perfused before and after, but not during, hyperbaric preservation. The determination of viability of hearts before reimplantation was performed by investigation of various metabolic characteristics of the tissue and by electron microscopic investigations. After reimplantation, the metabolic state and ultrastructural alterations were investigated. Only hearts from the second and third hyperbaric groups were resuscitated. In all experiments it was possible to achieve a spontaneous coordinated heart action; at the same time metabolic and ultrastructural recovery could be observed. The best results were obtained with the hyperbaric hearts of group 3.

Objectives-Hearts of rats with diabetes mellitus (DM) are characterized by energy demands exceeding their energy production, but they might also exhibit decreased vulnerability to ischemia and calcium overload. This indicates adaptation in cardiac energetics (CE), where energy transport is not rate-limiting. Aim-This study was designed to elucidate the functional significance of the DM-induced adaptation in CE by investigating the formation of mitochondrial contact sites (MiCS), facilitating the Ca-dependenthigh-capacity energy transfer from mitochondria, in conjunction with testing the ischemic tolerance (IT) of hearts. Methods-After 1 week of streptozotocin-induced DM (45 mgkg iv), the hearts of male diabetic and age-matched control rats (C) were isolated and Langendorff-perfused with either 1.6 or 2.2 mmolL of CaCl2. MiCS formation was assessed by cytochemical detection of mCPK octamers and was quantified stereologically as MiCS to mitochondrial surface ratio (SS). IT was evaluated in anesthetized open-chest animals subjected to 30-min occlusion of the LAD coronary artery followed by 4-h reperfusion, by monitoring ischemic arrhythmias and by measuring the size of infarction (tetrazolium double staining). Results-In C hearts, increasing Ca2induced both positive inotropic response (dPdtincrease from 2270 ± 220 to 2955 ± 229, p< 0.01 ) and elevated MiCS formation (SSincrease from 0.070 ± 0.011 to 0.123 ± 0.012, p< 0.01 ). In DM hearts, basic MiCS formation was already comparable with that induced by elevated Ca2in C hearts and could not be further stimulated by Ca2. In C, ventricular tachycardia represented 55.4 of the total arrhythmias and occurred in 90 of the animals. In DM rats, the arrhythmia profile was similar to that in C, and the incidence of tachyarrhythmias and their severity were not enhanced (arrhythmia score: 3.18 ± 0.4 vs. 3.30 ± 0.3 in C). The infarct size normalized to the size of area at risk was smaller in the DM than in C hearts (52.3 ± 5.8 vs. 69.2 ± 2.2, respectively; p< 0.05 ). Conclusions-Ca-signaling represents the link between energy delivery from mitochondria (via MiCS) and energy requirements of the heart. In DM hearts, energy transport via MiCS is elevated to the maximum value. This contributes to increased resistance of DM hearts to irreversible cell damage.

The in vitroeffect of tedisamil on the specific activity and kinetic parameters of the sarcolemmal (Na,K)-ATPase as well as its ex vivoeffect on the (Na,K)-ATPase in the isolated, perfused rat hearts was determined. Five μmol/l of tedisamil was added 5 min before the onset of 30 min global normothermic ischemia followed by 10 min reperfusion. At the conditions of its maximal cardioprotective effect (heart rate reduction, improved postischemic recovery of left ventricular developed pressure), the hearts were immediately used for isolation of sarcolemmal vesicles. In vitro, 1–100 μmol/l of tedisamil produced a concentration-dependent stimulatory effect on (Na,K)-ATPase activity, with a peak seen at 20 μmol/l (p < 0.01), while Mg-dependent ATPase was almost unchanged. Kinetic analysis revealed a significant increase in the affinity of the Na-binding sites on ATPase molecule at 20 μmol/l of tedisamil. These biochemical findings were confirmed by cytochemistry. Moreover, ex vivoexperiments revealed that tedisamil rendered the sarcolemmal (Na,K)-ATPase activity to be a more resistant to detrimental effects of ischemia. In conclusion, the cardioprotective action of tedisamil was accompanied with a better preservation of the specific activity of (Na,K)-ATPase.

The absorption rate of the β-adrenoceptor blocking drug, exaprolol, from the gastrointestinal tract was studied using in-situ methods in the rat and dog. Exaprolol was rapidly absorbed from the small and large intestine of rats and from the ileum of dogs. The cardiac output and regional blood flow decreased in rats to approximately one half of the original values within 30 min of the in-situ experiment. The logarithm of the amount vs time plots from dogs were linear, whereas with rats a curvilinearity appeared apparently because of the blood flow-limited absorption kinetics of this highly lipophilic drug. The data obtained suggest that exaprolol is suitable for administration in sustained release form.

Summary The effect of 7-oxo PGI2 on function and metabolism of postischemic reperfused (30-min ischemia and 30-min reperfusion) rat hearts was studied with special regard to calcium overload as one of the main factors of the postischemic reperfusion damage to the heart. The drug (50 μg/kg i.p.) was applied 48 h prior to starting the experiments on isolated rat hearts (Langendorff preparation at 37 °C and constant perfusion pressure of 65 mm Hg). A late protective effect of 7-oxo PGI2 was manifested by an improved recovery of heart function during reperfusion and calcium overload, better preservation of myocardial ATP contents during ischemia and also after calcium overload, as well as by a normalization of the lactate content, otherwise extremely increased during ischemia. Electron microscopic data also supported the above results. The beneficial effect of pretreatment with PGI2 may be explained not only by its vasodilating action, but more by its membrane stabilizing effect with a consequently decreased sodium accumulation, potassium loss, as well as intracellular calcium overload.

Ohne Zusammenfassung:

<$O_ST_ABS>AUTHORS SYNOPSIS<$C_ST_ABS>Intra-aortic balloon counterpulsation (IABCP) is generally known to have a profound effect on several physiological parameters of the heart with coronary occlusion, but only few data concerning its metabolic and ultrastructural effects are thus far available. In this paper evidence is presented that IABCP acts on the metabolism and structure of the myocardium besides improving circulatory and functional parameters. IABCP thus prevents the full development of changes characteristic of the ischaemic and/or failing heart in noninfarcted and also partially in infarcted areas of the myocardium.