Effect of sarcomere length and filament lattice spacing on force development in skinned cardiac and skeletal muscle preparations from the rabbit

Summary Skinned cardiac and skeletal muscle freeze-dried preparations were activated in solutions strongly buffered for Ca²⁺. The response of single skeletal muscle fibres or thin strips of papillary muscle was investigated in relation to changes in Ca content of the perfusate. Sarcomere length was set and controlled during the experiments. The relation between the negative logarithm of the Ca concentration, the pCa, and the normalized developed force proved to be sigmoidal. The exact position of these curves proved to be dependent upon both sarcomere length and the distance between the filaments. The latter was shown by means of osmotic compression of the fibres using dextran. As a consequence of these observations. it was concluded that the length-tension relation is dependent upon the actual Ca concentration. The results are discussed in terms of cross-bridge interaction.     

Voltage-dependent calcium release in guinea-pig cardiac ventricular muscle as antagonized by magnesium and calcium

Summary An increase in extracellular potassium concentration from 4 to 16 mmol/l caused a decrease in membrane potential from –92 to –59 mV and selectively diminished the earlier of two contraction components of guinea-pig papillary muscles at 0.2 Hz stimulation frequency in the presence of noradrenaline. The influence on the early contraction component had a threshold of 8 mmol/l K⁺, corresponding to a membrane potential of –77 mV. However, test contractions elicited 800 ms after the 5 s stimulation interval exhibited an unimpaired early component. Since the activator calcium responsible for the early contraction component is derived, in mammalian ventricular muscle, from the junctional sarcoplasmic reticulum (20), it is assumed that the release site of the reticulum was filled with calcium shortly (800 ms) after a regular contraction, and lost its calcium at 16 mmol/l extracellular K⁺ during the 5 s stimulation interval. The potassium-induced depolarization determined the rate of calcium leakage during rest from the intracellular store. The depolarization-induced decline of the early contraction component was equally well antagonized by Mg²⁺ or Ca²⁺ without influencing the measured transmembrane potential. Both divalent cations shifted the relation between potassium concentration or membrane potential and the strength of the early contraction component to less negative membrane potentials. In order to reduce the early contraction component by 25% in the presence of 9.6 instead of 1.2 mmol/l Mg²⁺, the potassium concentration had to be increased from 9.6 to 22.0 mmol/l, with a respective decrease in resting membrane potential from –72.6 to –51.1 mV. The antagonistic effect of both divalent cations is thought to result from the neutralization of negative charges outside the sarcolemma with a respective decrease in the outside surface potential.     

Improvement of relaxation velocity parameters by calcium channel blockers in the aging rabbit myocardium

Summary Normal aging in man is known to be associated with a reduction in left-ventricular diastolic function, including the rates of relaxation and filling. Calcium channel blockers have been reported to improve left-ventricular diastolic function in patients with various forms of heart disease. Clinically, the action of calcium channel blockers may be related to either a direct myocardial effect or may be secondary to the peripheral or coronary vasodilation effects. The purpose of this study is to investigate a possible direct effect of calcium channel blockers on modulation of the reported age-related reduction in myocardial relaxation.The direct effects on myocardial relaxation of the dihydropyridine calcium channel blocker, nifedipine, were studied in isolated, perfused interventricular septa and left-ventricular wall from eight young (ages 9 to 18 months) and 14 old (ages 3 to 5 years) rabbits. Septa were perfused with oxygenated Ringer's solution and paced at 48 beats/min. Maximum relaxation velocity per unit of developed tension [–dT/dt]/T, and relaxation time per unit of developed tension t_r/T were continuously measured before and after infusion of calcium channel blockers. In absence of drugs, the older rabbits demonstrated a mean [–dT/dt]/T which was 32% lower (p<0.003) and a mean t_r/T which was 45% higher (p<0.005) than the younger rabbits. When nifedipine was introduced at concentrations>10^–8 M equivalent to doses above the therapeutic free-plasma concentration in humans, all contraction and relaxation parameters were depressed. However, at lower doses, equivalent to doses in the clinical therapeutic range, [–dT/dt]/T was increased in the older rabbit septa by 18% in the presence of nifedipine. t_r/T was shortened in the older rabbit septa by 17% in the presence of nifedipine. Myocardial relaxation in older rabbits after drug infusion approximated these parameters in the younger rabbits prior to drug infusion (P=NS). Calcium channel blockers had similar beneficial effects on the relaxation properties of the myocardium in younger rabbits. All beneficial effects were observed at concentrations of calcium channel blockers which were within and below the clinically therapeutic range of plasma free drug concentration, i.e., 5×10^–9 to 4×10^–8 M.Potential differences in relaxation effects related to different segments of the myocardium and different mechanical recording vectors were evaluated. Isolated left ventricle preparations from aging rabbits demonstrated improvements in t_r/T and [–dT/dt]/T similar to those observed in the septum. Furthermore, improvement in mechanical function along the y-axis and x-axis vectors of the septum was similar. The data suggest that, in this rabbit model, calcium channel blockers may improve or reverse the age-related reduction in myocardial relaxation.     

Heterogeneity of the response of venous smooth muscle to arterial endothelium-derived relaxing factor (EDRF) in respect of the role of nitric oxide

Summary In bioassay and organ bath experiments, the responses of different canine venous preparations to arterial and their own EDRF were studied. Vena jugularis, vena femoralis and vena mesenterica relaxed on both EDRFs released by acetylcholine. Vena saphena, venae cordis and vena portae did not showendothelium-dependent dilation, either under bioassay or in organ bath experiments. All the veins tested relaxed completely after sodium nitroprusside administration. The identity of EDRF and nitric oxide is not confirmed by this study.     

Selective percutaneous “biopsy” of atheromatous plaque tissue for cell culture

Summary The combination of percutaneous atherectomy and angioscopy enabled a selective biopsy of protruding atheromatous plaque material from 11 patients with arterial occlusive disease. The removed specimens were cultivated as adhering explants or single cells were obtained by enzymatic disintegration. The vast majority of the cultivated cells resembled fibroblasts, but could be identified as smooth muscle cells by their smooth muscle -actin content. Proliferation rate was slow with 0.1 doublings per day. Endothelial cells were not observed by immunologic criteria. The described biopsy technique and in vitro evaluation of cultured human atheromatous plaque material may be useful for a better understanding of atherogenesis.     

Age-dependent changes of relaxation and its load sensitivity in rat cardiac muscle

Summary The relaxation phase and its load dependence were studied in papillary muscles isolated from the left ventricle of rats of the following ages: 20 days, 2, 8, 18, and 24 months. The myofibrillar ATPase activity and the force-velocity relation were determined in each age group in order to characterize the kinetic properties of the contractile material. Both shortening velocity and myofibrillar ATPase activity showed a progressive reduction with maturation and aging. This observation suggested an age-dependent decrease in cross bridge formation rate. The relaxation phase was characterized by its duration and the maximum rate of tension decline in isometric conditions, and by the speed of relenthenning in isotonic conditions. Relaxation became faster and of shorter duration with maturation from 20 days to 2 months and then became slower and of longer duration with further maturation and aging. The sensitivity of relaxation to changes in length or load was evaluted by measuring how much earlier tension declined in the presence of a given length change. An increase in load sensitivity of relaxation was observed during maturation from 20 days to 8 months. This increase was followed by a reduction during aging from 8 to 24 months. Such a biphasic trend of the age-related changes in load sensitivity of relaxation could result from the interplay between the progressive decrease in cross bridge formation rate and a reduction in activation decay rate. The latter was suggested by the prolongation of the relaxation phase and by the maintenance of developed tension during aging.     

Regional differences of substrate oxidation capacity in rat hearts: Effects of extra load and endurance training

Summary Male rats, aged 17 weeks at the end of experiments, were divided into four groups. Two groups lived in normal cage conditions with or without extra load (20% of the body weight) and two groups were trained by running with or without extra load for 8 weeks. Oxidation rates of succinate, glutamate + malate, palmitoylcarnitine, and pyruvate, and the activities of lactate dehydrogenase, citrate synthase, isocitrate dehydrogenase and cytochrome oxidase were measured in homogenates of the right ventricle and in those of the subendocardial and subepicardial layers of the left ventricle. Oxidation rates of succinate and palmitoylcarnitine tended to be higher in the subendocardium than in the subepicardium of sedentary control animals (p<0.1 and p<0.05, respectively). Transmural differences of succinate and palmitoylcarnitine oxidation rates were even more clear after running training (p<0.01 and p<0.05, respectively), after carrying extra load (p<0.001 and p<0.001, respectively) and after training carrying extra load (p<0.001 and p<0.05, respectively). Training also enhanced pyruvate oxidation rate in the subendocardium. Oxidation rates of all substrates were lower in the right ventricle than in the left ventricle. In control animals there were no regional differences in the myocardial enzyme activities and the training- or extra-load-induced changes were modest compared with the changes in the oxidation rates. The most significant change was the training-induced enhancement in the lactate dehydrogenase activity of the subendocardium (p<0.001 vs subepicardium). These results show greater subendocardial than subepicardial oxidation rates of certain substrates in the normal heart. These results also suggest that the myocardium adapts to increased work by increasing the subendocardial oxidation rate of some but not all substrates, indicating further that there may be qualitative mitochondrial differences in the different regions of the heart.Supported by a grant from the Research Council for Physical Education and Sport, Ministry of Education, Finland     

Regional myocadial blood flow and cardiac mechanics in dog hearts with CO2 laser-induced intramyocardial revascularization

Summary Laser-induced intramyocardial revascularization (LIR) has been used to promote direct communications between blood within the ventricular cavity and that of the existing myocardial vasculature in an attempt to increase perfusion in patients with ischemic heart discase. This study was conducted to measure the effects of LIR channels on regional myocardial flood flow (microspheres), cardiac mechanics (sonomicrometers), and myocardial tissue pressures in 18 dogs. Under baseline hemodynamic conditions (mean HR=165.2±11.4 bpm, LVP=123.6±22.9/4.0±1.8 mmHg, AoP=112.8±27.1/77.0±22.5 mmHg), myocardial blood flow in laser-treated tissue (mean =1.11±.10 cc/min/gm before laser; .71±.19 cc/min/gm after laser) was reduced as compared to blood flow in control tissue (mean=1.12±.15 cc/min/gm before laser; 1.25±.22 cc/min/gm after laser). Regional myocardial systolic shortening (11.32%±3.82% before laser; 7.49%±2.86% after laser) was decreased by 33%. During simultaneous reversible ligation of the LAD and LCCA for 2 min, when intramyocardial channels represented the only tissue access for the injected microspheres, blood flow in laser-treated tissue was not increased above that of the control non-lasered tissue. However, regional blood flow was greater in laser-treated ischemic tissue (mean=.61±.12 cc/min/gm) than in untreated ischemic areas (mean=.04±.03 cc/min/gm) when left ventricular pressure (LVP) was acutely elevated (mean SLVP=207.0±16.1 mmHg). Using these measurements, a model is proposed to predict regional systolic pressure gradients between the left ventricular cavity and coronary intramyocardial vasculature required to permit restoration of blood flow to ischemic myocardium. We conclude that improved perfusion via laser-induced intramyocardial channels does not occur in otherwise normal myocardium exposed to acute coronary ligation and only small improvements in perfusion are noted when LVP is significantly elevated. Consideration of further clinical application of this approach is seriously cautioned awaiting additional experimental studies.This study was supported by U.S. Public Health Service Grant R01 HL32897-01 from the National Heart, Lung, and Blood Institute, by grants in aid from the American Heart Association, and by the Fulbright-Hays Scholarship Grant.     

2-mercaptopropionylglycine improves aortic flow after reoxygenation in working rat hearts

Summary The cardioprotective concentration range of the thiol drug 2-mercaptopropionylglycine (MPG) was investigated during reoxygenation after 30 min of hypoxia. It was found that aortic flow and frequency were increased by 1 mM MPG. Coronary flow, systolic and diastolic pressure were not significantly influenced by the drug. Mitochondria, isolated from hearts after termination of the perfusion phases, revealed increased values of RCI, when MPG had been present in the previous reoxygenation phase at 1 mM concentration. 5 mM MPG no longer showed a protective influence on the above cardiac and mitochondrial parameters. ATPase activities were decreased at 1 mM MPG by 14% and at 5 mM MPG by 40% of the controls. The latter concentration of MPG also doubled the inhibitory action of carboxyatractyloside on ATPase activity, indicating a structural change of the adenine nucleotide carrier. 1 mM MPG is considered an optimal therapeutic range in this model. The mechanism of action most probably includes an SH/-S-S-interchange reaction as well as a free radical scavenging mechanism. For many thiols, the latter is known to occur in the presence of metal ions.This work was supported by the Deutsche Forschungsgemeinschaft (DFG) Zi 80/19-2     

Exposure of rats to low concentration of cigarette smoke increases myocardial sensitivity to ischaemia/reperfusion

Summary It is suggested that passive smoking or smoke-exposure increase the risk of coronary heart disease. The same mechanisms as active smoking might play a role. The aim of this study was to determine whether exposure to smoke aggravated ischaemia/reperfusion injury. As a parameter of cellular function and integrity mitochondrial oxidative function was measured. Low molecular weight iron (LMWI) and -tocopherol levels were determined to assess the possibility of toxic hydroxyl radical involvement in myocardial ischaemia/reperfusion injury of smoke-exposed rats. Rats were exposed to a small concentration of cigarette smoke for 2 months (the carboxyhemoglobin concentration did not increase), whereafter hearts were isolated and subjected to ischaemia and ischaemia followed by reperfusion. Mitochondrial oxidative function, low molecular weight iron and -tocopherol were determined. The impairment in mitochondrial oxidative function, LMWI content elevation and the decrease in -tocopherol concentration during ischaemia/reperfusion were significantly more severe in hearts of smoke-exposed rats than non-smokers. These results suggest that exposure to smoke increased the sensitivity of hearts to ischaemia/reperfusion injury, and that a free radical mechanism might participate.     

The role of lipid peroxidation in pathogenesis of arrhythmias and prevention of cardiac fibrillation with antioxidants

Summary The present paper shows the arrhythmogenic effect of a direct induction of lipid peroxidation (LP) on isolated auricles; it is demonstrated that preendured stress potentiates this effect, while antioxidants prevent it. Subsequently, in studying the mechanism of the LP arrhythmogenic effect it was established that stress, like the LP induction, disorders the activity of Na, K-ATPase and accelerates thermodenaturation of this enzyme which plays a key role in maintaining the transmembrane potential and the electrical stability of the heart. Antioxidants prevent the enumerated shifts. Based on these data, the antioxidant BHT was successfully applied for prevention of the fall in cardiac fibrillation threshold in stress and experimental myocardial infarction, and also for prevention of cardiac fibrillation itself under acute ischemia and reoxygenation of the heart.     

Different responses of left ventricular systolic function to changes in right ventricular volume and shortening —comparison between aorto-femoral vein and aorto-left atrium shunts in dog hearts

Summary It has been reported that left ventricular end-systolic volume decreases during arteriovenous shunt and increases during subclavian artery-left atrium shunt at a constant end-systolic pressure. The mechanism of the opposing changes in end-systolic volume during the two types of shunt is not clear. One possible cause is that left ventricular pump function with enhanced right ventricular ejection differs from that without enhancement. To investigate this hypothesis, we studied the two types of shunt (Aorto-femoral vein shunt, AoFV; aorto-left atrium shunt, AoLA) with matched reduction of systemic vascular resistance in open-chest dogs with -blockade. Both right and left ventricular volumes and shortenings were assessed from short-axis views by two-dimensional (2D)-echocardiogram. Left ventricular end-systolic short-axis area decreased from 76 ± 3 to 62 ± 3% in AoFV shunt (p < 0.05), but tended to increase in AoLA shunt (76 ± 4 in control state vs 81 ± 5% in AoLA, NS) in spite of a similar reduction in left ventricular end-systolic pressure. There was no difference in left ventricular shortening, but significant differences were observed in right ventricular shortening (50 ± 8 in AoFV vs 24 ± 7% in AoLA, p < 0.05) and right ventricular short-axis area at end-diastole (142 ± 6 in AoFV vs 96 ± 3% in AoLA, p < 0.01), and at end-systole (92 ± 8 in AoFV vs 73 ± 7% in AoLA, p < 0.05) between the two types of shunt. We conclude that the different changes in left ventricular end-systolic short-axis area found in the two shunts are not caused by the different left ventricular shortenings, but by the different right ventricular mechanical actions. These findings suggest that left ventricular pumping action in the high output state changes, depending on whether it is accompanied by augmented ejection of the right ventricle or not.     

High-frequency and low-frequency heart-rate fluctuation analysis in newborns—A review of possibilities and limitations

Summary Respiratory sinus arrhythmia (RSA) has been traditionally defined as the high-frequency component of heart-rate fluctuations (HRF) synchronous with the respiratory movements (RM), i.e., the frequency of RSA corresponds to the respiration rate. It can be shown that at defined relations of mean heart and respiration rate some essential effects must be taken into consideration in studies using RSA parameters The relevance of these effects is shown and a new strategy of RSA quantification demanded, at least in neonates.The diagnostic importance, physiological background and future application of the low-frequency components of the neonatal HRF are reviewed on the basis of our own results. Nonrespiratory cardiovascular HRF cannot always be detected in the neonate by power spectral analysis.Movement-related HRF have a potential diagnostic importance per se, but may also artefactually disturb the quantification of other HRF components. Long-term trends can be used to describe sleep-state related trends and their disturbances.     

Functional significance of ventricular dilatation

Summary On the basis of theoretical considerations and experimental data this study deals with the functional consequences of structural dilatation, particularly in view of Linzbach's concept of chronic heart failure (34–38). After a short review of the literature, a theoretical analysis of the relationship between stroke volume and ventricular inner radius is presented assuming a thick-walled sphere. Presupposing constant contractility, end-diastolic sarcomere length, end-diastolic wall thickness and end-systolic pressure, only a considerable increase of ventricular radius could be the direct cause of ventricular pumping failure — despite increasing wall stress and reduced ejection fraction. Impaired contractility, as well as insufficient hypertrophy and increased systemic pressure, would intensify the adverse consequences of ventricular enlargement to a predictable extent. Thus, hemodynamic and energetic consequences of dilatation, although mutually interacting, should in principle be distinguished. Despite considerable simplifications involved in model calculations, the relative significance of contractility, ventricular size, wall thickness, and extracardiac factors (mechanical overload; neuroendocrine reactions) can be estimated in various animal models with congestive failure. Hence, this theoretical and experimental approach permits the modification and deepening of previous concepts of structural dilatation and also has implications for interpreting the effects of therapeutical interventions.Supported by the Deutsche Forschungsgemeinschaft (Ja 172/14-1)Dedicated to Dr. Erwin Riesch, Honorary Senator of the University of Tübingen, on the occasion of his 80th birthday     

The oxygen consumption paradox of “stunned myocardium” in dogs

Summary The contractile state of the heart is a major determinant of myocardial oxygen consumption. Since regional myocardial contractility can be severely impaired following a transient coronary occlusion, post-ischemic myocardium is frequently assumed to consume less oxygen. To test this assumption, regional myocardial function and oxygen consumption were studied in ancsthetized dogs during 2 h of myocardial reperfusion following either a 15-min (Group I) or 4-h (Group II) left anterior descending coronary artery occlusion. Both groups developed similar post-ischemic regional dysfunction characterized by paradoxical motion (negative shortening). Measured as a percent of baseline segment shortening, anterior wall function in Group I (n=8) and Group II (n=5) at 30 min of reperfusion was –33±11% and –34±16% (p=NS) and at 120 min was –23±9% and –40±16% (p=NS). However, the two groups showed a marked difference in regional myocardial oxygen consumption during reperfusion. Despite the abnormal wall motion, regional oxygen consumption in Group I at 30 and 120 min of reperfusion was unchanged from pre-ischemic levels as measured as a percent of bascline: 104±20% (p=NS) and 111±21% (p=NS). In contrast, regional oxygen consumption in Group II was markedly depressed from bascline at 30 and 120 min of reperfusion: 42±7% (p<.01) and 40±8% (p<.01). To determine whether the dissociation between regional myocardial oxygen consumption and function in Group I was related to mitochondrial uncoupling, six additional dogs were studied. Tissue samples were obtained from post-ischemic myocardium after 120 min of reperfusion following a 15-min coronary artery occlusion, and compared to non-ischemic myocardium. There were no differences in the in vitro mitochondrial respiratory rates or oxidative phosphorylation capacity between the post-ischemic and non-ischemic myocardium. Therefore, in the post-ischemic myocardium, significant depressions in regional contractility may not be associated with falls in oxygen consumption. Following a 15-min coronary artery occlusion, the injured myocardium maintains a paradoxically high oxygen consumption with normal mitochondrial function despite decreased contractility and abnormal wall motion.Grant Support: Dr. Dean was a Fellow of the American Heart Association. Dr. Nicklas is supported by the NIH Clinical Investigator Award, HL 011170.     

Arrhythmias and infarction in the ischemic pig heart are not mediated by xanthine oxidase-derived free oxygen radicals

Summary Xanthine oxidase activities of pig myocardium and blood during and following myocardial ischemia were measured using HPLC, and electrochemical detection of hypoxanthine, xanthine and uric acid. Myocardial ischemia was produced by occluding the anterior descending coronary artery two-thirds of the way from its origin. There was no accumulation of either xanthine orurate in the ischemic pig myocardium during occlusion periods of 90 min, but there was a substantial accumulation of hypoxanthine. Similarly, there was no increase in myocardial xanthine or urate during the 30 min reperfusion following coronary artery occlusion periods of 15, 30, 60 or 90 min. Following in vitro incubation at pH 8 of myocardial homogenates or blood with either hypoxanthine or xanthine and NAD, no urate production was detectable. In contrast, significant amounts of xanthine and/or urate were produced, following addition of xanthine oxidase to the reaction mixtures. Additional in vitro experiments showed that the following pig tissues were lacking xanthine oxidase activity: left and right atrial appendage, left and right ventricle, interventricular septum, anterior descending and circumflex coronary arteries, ascending aorta, lung, and blood. Large amounts of xanthine oxidase (9.3±1.8 SEM mU/g wet weight, n=7) were found in pig liver. In the ischemic pig heart, transmural infarction developed within 60 min of ischemia. Ventricular arrhythmias and fibrillation occured most frequently within 45 min of ischemia and within seconds after reperfusion. These results showed that the pig heart and blood were xanthine oxidase deficient, suggesting that xanthine oxidase-derived free oxygen radicals were not involved in the cytotoxic and arrhythmogenic effects brought about by myocardial ischemia and/or reperfusion in the pig.This work was supported by grant Po 252/1-1 from the Deutsche Forschungsgemeinschaft.     

Relationship of myocardial morphometry in aortic valve regurgitation to myocardial function and post-operative results

Summary In 24 patients with aortic insufficiency undergoing aortic valve replacement, a clinical and hemodynamic study was performed pre-operatively. Left ventricular biopsies were obtained perioperatively for morphometric study.No significant relations were found when morphometric data were compared to functional class, cardiothoracic radio and ECG findings.The percentage of interstitial fibrosis was not correlated with any of the measured hemodynamic parameters. Myocardial cell diameter was weakly correlated with left ventricular systolic function parameters. A decrease in the percentage of contractile material was strongly correlated with an impaired left ventricular function, assessed pre-operatively. During clinical follow-up, patients were divided into two groups: Group A (17 patients) included patients who were in class I or II of NYHA after surgery. Group B (seven patients) included patients who died or were in functional class III or IV. As compared with Group A, Group B patients had a significantly lower ejection fraction; their myocardial cell diameter was larger and the percentage of myofibrils, and the content of contractile material were significantly lower. This suggests that, in aortic regurgitation left ventricular dysfunction is correlated with contractile material loss and not with interstitial fibrosis, and that morphometric changes are good predictors of follow-up after surgery.     

The protective effect of desferal on rat myocardial mitochondria is not prolonged after withdrawal of desferal

Summary Reperfusion of ischaemic myocardium is necessary to sustain tissue viability (without it the tissue becomes necrotic), but reperfusion, on the other hand, can damage cells which have survived ischaemia. There is now considerable evidence that oxygen radicals, especially hydroxyl radicals produced via the Haber-Weiss and Fenton reactions, are responsible for reperfusion damage. Various investigators have reported that desferal, an iron chelator, has a beneficial effect on the myocardium during ischaemia and reperfusion. The aim of this study was two-fold: i) whether superoxide anions in the absence of LMWI can impair mitochondrial function, and ii) whether the protective effect of desferal on the mitochondrial function persists after withdrawal of desferal. Experiments were done on isolated rat hearts subjected to normothermic ischaemic cardiac arrest (NICA), with or without desferal, followed by 15-min reperfusion with desferal, followed by 15-min perfusion without desferal, or a hypoxanthine/xanthine oxidase medium that generates superoxide anions (with or without desferrioxamine (desferal) in the perfusate). Mitochondrial function (QO₂ (state 3), ADP/O and OPR) as well as LMWI were measured. Our results indicated that i) superoxide anions and/or hydrogen peroxide can, independently of LMWI, damage the mitochondria, and ii) withdrawal of desferal after the respiratory burst resulted in the same or more severe mitochondrial damage than without any desferal.Abbreviation list LMWI Low molecular weight iron - NICA normothermic ischaemic cardiac arrest - QO₂ (state 3) nmol oxygen consumed in the presence of ADP/mg mitochondrial protein/min - ADP/O nmol ADP consumed/nmol oxygen consumed - OPR oxidative phosphorylation rate, nmol ADP consumed/mg mitochondrial protein/min     

Rapid changes in myofibrillar proteins after reperfusion of ischemic myocardium in dogs

Summary The effect of reperfusion on cardiac myofibrillar proteins in the irreversibly injured ischemic myocardium was studied in dogs. Ischemia of the myocardium was produced by complete occlusion of the left anterior descending coronary artery for 90 min (the group of 901). Occlusion of the coronary artery was then released (reperfusion) for 0.5 min (the group of 90I+0.5R), 5 min (the group of 90I+5R), or 20 min (the group of 90I+20R). In control dogs, the coronary artery was not occluded (the group of no ischemia). Myofibrils (Mfp) were prepared from the myocardium (with centrifugation) in each of the groups, and subjected to electrophoretic analysis in terms of myofibrillar proteins. The yield of Mfs in the groups of 90I, 90I+0.5R, 90I+5R, and 90I+20R was lower than that in the group of no ischemia. There were no marked differences, however, in the electrophoretic pattern of Mfp among the five groups. These results suggest that myofibrils are broken down during reperfusion after ischemia. Therefore, supernatant solution after first stage of homogenization during the course of preparation of myofibrils (mfs) was also examined. There were many unidentified bands in Mfs, being assumed to be originated from myofibrillar proteins, in the groups of both 90I+0.5R and 90I+5R, although these bands were not observed in the group of 90I. These results indicate that degradation of myofibrillar proteins occurs rapidly after reperfusion of the irreversibly injured myocardium. It is uncertain, however, whether reperfusion has a detrimental effect on the reversibly injured myocardium, too.Maiden name: H. Sashida     

Open chest and open pericardium affect the distribution of myocardial blood flow in the right ventricle

Summary We have investigated the effects of open chest and open pericardium on the distribution of myocardial blood flow assessed with the radioactive microsphere technique (15 m). Five dogs with intact thorax served as controls (group I) and six dogs were studied after a right-sided thoracotomy and pericardiotomy (group II). Global myocardial blood flow (mean±S.D.) was 0.73±0.17 ml·min^–1·g^–1 in group I and 1.22±0.09 ml·min^–1·g^–1 in group II (p<0.05). Analysis of transmural blood flow distribution revealed that flow was 44% higher in the right and 60% higher in the left ventricular endocardial layers in the open-chest animals, whereas epicardial flow increased by 105% and 90%, respectively. As a result of the preferential blood flow to the epicardial layers of the right ventricle, the endo/epi ratio was reduced from 1.30±0.26 in group I to 0.86±0.11 in the open-chest group (p<0.05). Left ventricular endo/epi ratio was 1.27±0.16 and 1.06±0.11 (n.s.), respectively. External work and diastolic filling pressure of the right ventricle did not differ between the two groups and therefore cannot account for the redistribution of myocardial blood flow. It is concluded that the distribution of myocardial blood flow, particularly in the RV, is severely disturbed by thoracotomy and pericardiotomy. This is an important aspect for the planning and evaluation of studies under open-chest/open-pericardium conditions.Supported by Deutsche Forschungsgemeinschaft grant SFB 320