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Biomedical subjects

R Rösen

Publications and source records attributed to R Rösen.

At least 19 recordsLinked to original sources
PubMed2001

Endothelial dysfunction and oxidative stress during estrogen deficiency in spontaneously hypertensive rats.

BACKGROUND: Postmenopausal estrogen deficiency is associated with an increased cardiovascular risk, hypertension, and oxidative stress. Angiotensin type 1 (AT(1)) receptor regulation is involved in the pathogenesis of atherosclerosis. To characterize vascular function, oxidative stress, and AT(1) receptor regulation during estrogen deficiency, ovariectomized spontaneously hypertensive rats (SHR) were investigated in comparison with sham-operated animals and with ovariectomized rats receiving estrogen replacement therapy with 17beta-estradiol. METHODS AND RESULTS: Arterial blood pressure was similar in all 3 groups investigated. Five weeks after ovariectomy, endothelial dysfunction in aortic rings was observed, which was reversed by estrogen replacement therapy. Estrogen deficiency led to an enhanced vasoconstriction by angiotensin II. Vascular superoxide production was significantly increased compared with that in sham-operated rats, as measured by lucigenin chemiluminescence assays. Estrogen substitution normalized the production of free radicals in the vessel wall. Vascular AT(1) receptor expression was significantly upregulated by estrogen deficiency, as shown by quantitative reverse transcription-polymerase chain reaction, whereas endothelial NO synthase mRNA expression and NO release were unchanged. Five-week treatment of the animals with the AT(1) receptor antagonist irbesartan prevented endothelial dysfunction in ovariectomized rats and normalized the vascular production of free radicals. CONCLUSIONS: In SHR, estrogen deficiency leads to increased vascular free radical production and enhanced angiotensin II-induced vasoconstriction via increased vascular AT(1) receptor expression, resulting in endothelial dysfunction. Estrogen replacement therapy and AT(1) receptor antagonism prevent these pathological changes. Therefore, estrogen deficiency-induced AT(1) receptor overexpression and oxidative stress may play an important role in cardiovascular diseases associated with menopause.

Angiotensin II↗
PubMed2001

HMG-CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) significantly reduce cardiovascular mortality associated with hypercholesterolemia. There is evidence that statins exert beneficial effects in part through direct effects on vascular cells independent of lowering plasma cholesterol. We characterized the effect of a 30-day treatment with atorvastatin in normocholesterolemic, spontaneously hypertensive rats (SHR). Systolic blood pressure was significantly decreased in atorvastatin-treated rats (184+/-5 versus 204+/-6 mm Hg for control). Statin therapy improved endothelial dysfunction, as assessed by carbachol-induced vasorelaxation in aortic segments, and profoundly reduced angiotensin II-induced vasoconstriction. Angiotensin type 1 (AT(1)) receptor, endothelial cell NO synthase (ecNOS), and p22phox mRNA expression were determined with quantitative reverse transcription-polymerase chain reaction. Atorvastatin treatment downregulated aortic AT(1) receptor mRNA expression to 44+/-12% of control and reduced mRNA expression of the essential NAD(P)H oxidase subunit p22phox to 63+/-7% of control. Aortic AT(1) receptor protein expression was consistently decreased. Vascular production of reactive oxygen species was reduced to 62+/-12% of control in statin-treated SHR, as measured with lucigenin chemiluminescence assays. Accordingly, treatment of SHR with the AT(1) receptor antagonist fonsartan improved endothelial dysfunction and reduced vascular free-radical release. Moreover, atorvastatin caused an upregulation of ecNOS mRNA expression (138+/-7% of control) and an enhanced ecNOS activity in the vessel wall (209+/-46% of control). Treatment of SHR with atorvastatin causes a significant reduction of systolic blood pressure and a profound improvement of endothelial dysfunction mediated by a reduction of free radical release in the vasculature. The underlying mechanism could in part be based on the statin-induced downregulation of AT(1) receptor expression and decreased expression of the NAD(P)H oxidase subunit p22phox, because AT(1) receptor activation plays a pivotal role for the induction of this redox system in the vessel wall.

Angiotensin Receptor Antagonists↗
PubMed2001

Studies on the role of superoxide anion radicals for the cardiotoxicity of adrenochrome.

Adrenochrome is an oxidative product of adrenaline and possesses cardiotoxic properties. As oxygen free radicals play a role in the cytotoxic effects of catecholamines, the role of superoxide anion radicals, as mediators of adrenochrome toxicity, was investigated using electrically-driven Langendorff rabbit hearts with depleted catecholamine stores. Repetitive regional myocardial ischemia (MI) was induced by coronary artery branch ligature, and MI was quantitated from epicardial NADH-fluorescence photography. Adrenochrome (10(-6) mol/l) was added to the perfusion solution after a reperfusion period of 20 min, 30 min before the 2nd coronary occlusion, with or without the additional application of SOD (30 U/ml). Left ventricular pressure was significantly enhanced by adrenochrome (p < 0.05), but it fell rapidly down below its initial value (p < 0.05). Coronary flow was significantly decreased by adrenochrome (p < 0.05). Whereas epicardial NADH-fluorescence was similar after repetitive coronary occlusions in untreated controls, it was significantly enhanced by adrenochrome (p < 0.05). The deleterious effects of adrenochrome on MI were not inhibited by SOD. Thus, there is no evidence for superoxide anion radicals as mediators of the deleterious effects of adrenochrome on MI in isolated rabbit hearts. The deleterious effects of adrenochrome on MI in isolated rabbit hearts might be caused by functional effects, impairing the oxygen consumption/oxygen supply balance.

Adrenochrome↗
PubMed1997

Evidence for a NO synthase in porcine platelets which is stimulated during activation/aggregation.

We tried to characterize the porcine platelet nitric oxide (NO) synthase and its L-arginine (L-arg)/NO metabolism. Using RT-PCR we could show a constitutive endothelial NOS (ecNOS) and an inducible NOS (iNOS) similar mRNA in platelets. The NOS protein could be evidenced by an ecNOS specific antibody which also bound in platelets. This finding could be confirmed by Western blot showing an ecNOS in the membrane but not the cytosolic fraction; iNOS protein could not be detected. Using NADPH-diaphorase staining we could show NO synthase in preactivated platelets but not in resting platelets, indicating that the platelet NOS may be activated during platelet activation/aggregation. Porcine L-arg plasma levels (9.31 x 10(-5) mol/l +/- 10%) could be shown to be in the same range as human plasma levels. Moreover, we could show that the NO precursor L-arg and hydroxy-L-arginine (OHarg) concentration dependently inhibited collagen induced platelet aggregation. Summarizing these results confirm the existence of and further characterize porcine platelet NO synthases.

Animals↗
PubMed1996

Influence of angiotensin-converting enzyme inhibition by fosinopril on myocardial perfusion in streptozotocin-diabetic rats.

We examined the influence of the new angiotensin-converting enzyme inhibitor (ACEI) fosinopril on function and perfusion of the diabetic rat heart. Streptozotocin-diabetic rats (60 mg/kg body weight) were treated with fosinopril (10 mg/kg body weight/day) for 4 months. Cardiac performance was analyzed in the isolated heart perfused at constant volume. Epicardial perfusion was determined by measuring epicardial fluorescence changes after injection of FITC-dextrane (3 kDa) as described previously. As compared with controls, fosinopril prevented or diminished the increase in end-diastolic pressure (EDP), coronary perfusion pressure (CPP), and vascular resistance in diabetes. The intravascular volume strongly reduced in diabetes was increased, and the epicardial perfusion rate was accelerated in hearts of diabetic rats treated with fosinopril. The vascular exchange diminished in hearts of untreated diabetic rats was enhanced, and the transcapillary permeability was slightly accelerated at low flow rates. These data indicate that treatment of streptozotocin-diabetic rats with fosinopril prevents severe disturbances of coronary autoregulation and at least partly the impairment of cardiac perfusion generally observed in diabetic rats. Together with previously published morphological data demonstrating an inhibition of interstitial and perivascular fibrosis in hearts of diabetic rats with fosinopril, our observations suggest that ACE inhibition by fosinopril is cardioprotective in diabetes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

The ACE-inhibitor captopril improves myocardial perfusion in spontaneously diabetic (BB) rats.

The aim of this study was to examine the influence of inhibition on angiotensin converting enzyme (ACE) of myocardial function and perfusion of the rat impaired by diabetes. Spontaneously diabetic rats were treated with the ACE-inhibitor captopril for 4 months. Cardiac performance was analysed in the isolated heart perfused at constant volume. Epicardial perfusion was determined by measuring changes in epicardial fluorescence after injection of a bolus of fluoresceinisothiocyanate-dextrane (3 kDa) as described previously. As compared to untreated diabetic controls, captopril prevented the increase of end diastolic pressure, coronary perfusion pressure and vascular resistance. The intravascular volume was enlarged and the epicardial perfusion rate increased in hearts of diabetic rats treated with captopril as compared to diabetic controls. Treatment of diabetic rats with the ACE-inhibitor captopril (1) increases the number of perfused capillaries, and (2) can partly prevent the development of cardiac dysfunction in diabetes. Together with morphological data demonstrating an inhibition of interstitial and perivascular fibrosis in hearts of diabetic rats treated with captopril, our data suggest that ACE-inhibition is cardioprotective in diabetes. These observations are also compatible with the assumption that an accelerated generation of angiotensin II may be involved in the pathophysiological chain of events leading to diabetic cardiopathy.

Analysis of Variance↗
PubMed1995

Effects of different inotropes with antioxidant properties on acute regional myocardial ischemia in isolated rabbit hearts.

1. The antiischemic properties of the flavonoids acetylvitexin-rhamnoside (AVR) and luteolin-7-glucoside-(LUT), combining phosphodiesterase (PDE)-inhibitory and antioxidant properties, were studied in comparison to amrinone (AMR) or superoxide dismutase (SOD). The effects of the new dihydropyridine-type calcium-agonist Bay T 5006 were studied in comparison to Bay K 8644. 2. In isolated Langendorff-rabbit hearts perfused at constant pressure, acute regional ischemia (MI) was induced by coronary artery occlusion (CAO) and quantitated from epicardial NADH-fluorescence photography. Drugs were applied either before or after CAO (pre-treatment or treatment) to permit distinguishing the influence of functional and direct cytoprotective actions in the poorly collateralized rabbit hearts. 3. SOD did not affect left ventricular pressure (LVP) or coronary flow (CF) and reduced MI only if applied before CAO. LVP and CF were enhanced by LUT or AMR but not by AVR. MI was reduced to a similar extent in hearts treated with either drug. Cardioprotection by LUT was not improved by starting drug application before CAO. 4. Bay K 8644 reduced LVP and particularly CF, whereas Bay T 5006 did not affect functional parameters. MI was enlarged by Bay K 8644 and remained unaffected by treatment or pretreatment with Bay T 5006. 5. AMR, LUT and AVR possess antiischemic properties related to an improvement of myocardial perfusion. Although oxygen free radicals contribute to ischemic tissue injury, as shown by the cardioprotective effectiveness of SOD, antioxidant properties of the flavonoids LUT and AVR do not seem to be relevant for the antiischemic effects. Our findings also give no evidence for antioxidant properties of dihydropyridines relevant for cardioprotection.

Animals↗
PubMed1994

Functional and antiischemic effects of luteolin-7-glucoside in isolated rabbit hearts.

1. The functional effects of the flavonoid luteolin-7-glucoside (LUT) were investigated in Langendorff-rabbit hearts perfused at constant pressure. Repetitive myocardial ischemia was induced by coronary artery ligature and quantified from NADH-fluorescence photography. 2. LUT significantly enhanced left ventricular pressure and the global and relative coronary flow (= global coronary flow/pressure-rate product). 3. LUT significantly diminished epicardial NADH-fluorescence area and intensity. 4. LUT is an inodilator possessing cardioprotective properties. These might be related to an improvement of myocardial perfusion and/or to free radical scavenging properties.

Animals↗
PubMed1994

Comparative effects of the dihydropyridine-type calcium-agonists (-)-S-Bay K 8644, (+/-)-Bay-W 5035 and (+/-)-Bay-T 5006 on human platelet aggregability.

1. Human platelet aggregation induced by collagen is concentration-dependently inhibited by dihydropyridine (DHP)-type calcium(Ca)-agonists. 2. There was no significant difference between the maximal anti-aggregatory effects or the anti-aggregatory potencies of (-)-S-Bay-K 8644 (EC50: 5.3 +/- 1.5 x 10(-5) M), (+/-)-Bay-W 5035 (EC50: 14.9 +/- 8.8 x 10(-5) M) or (+/-)-Bay-T 5006 (EC50: 2.7 +/- 1.9 x 10(-5) M) (P > 0.05). 3. Antiaggregatory effects of DHP-type Ca-agonists seem to be independent of Ca-channel activation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

The calcium modulator nifedipine exerts its antiaggregatory property via a nitric oxide mediated process.

The in vitro effect of nifedipine, a calcium channel blocker of the dihydropyridine (DHP) type, on platelet aggregation was reinvestigated considering especially the capability of platelets to form endogenous nitric oxide (NO). We studied the dose-dependent antiaggregatory property of nifedipine in porcine platelet rich plasma. Aggregation was stimulated by collagen (7.5 micrograms/ml). Nifedipine inhibited collagen-induced platelet aggregation with an IC50 of 380 nmol/l. The antiaggregatory effect of nifedipine could be significantly diminished by N-nitro-L-arginine (NNA) in a concentration dependent manner, whereas oxy haemoglobin (4 microM), a NO scavenger, totally abolished the effect of nifedipine. L-Arginine, the precursor of NO, dose-dependently inhibited the collagen-induced platelet aggregation but did not potentiate the effects of nifedipine. Therefore, we propose that in platelet rich plasma the nifedipine induced inhibition of platelet aggregation is mediated by NO, a potent endogenous inhibitor of aggregation. We could confirm this hypothesis by measuring NO directly with a specific electrode.

Animals↗
PubMed1993

Cardioprotection by ramiprilat in isolated rabbit hearts.

The anti-ischemic properties of the ACE inhibitor ramiprilat (ram) were investigated in electrically driven Langendorff hearts from rabbits whose endogenous angiotensin-I content has been previously shown to be very low (constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). Cumulative concentration-response curves showed that the reduction in global coronary flow (CF) by exogenous angiotensin-I was concentration dependently inhibited by ram (P < 0.05). Myocardial ischemia (MI) was induced by occlusion of a left coronary artery branch and MI was quantified by NADH surface fluorescence photography. MI was significantly enlarged (+23%) (P < 0.05) by exogenous angiotensin-I (6 x 10(-9) mol/l). Addition of ram (10(-8) mol/l) to the perfusion buffer simultaneously with angiotensin-I, completely prevented the reduction of CF by angiotensin-I (P > 0.05) and significantly diminished MI even below control values (-25%) (P < 0.05). In the absence of exogenous angiotensin-I, ram alone (10(-8) mol/l) did not significantly enhance CF (P > 0.05), supporting findings demonstrating a very low endogenous angiotensin-I content in isolated rabbit hearts. However, ram alone (10(-8) mol/l) significantly diminished MI (-24%) (P < 0.05). We conclude that ram does possess direct cardioprotective properties that are independent of the inhibition of angiotensin-II generation but that may be related to potentiation of the effects of bradykinin.

Angiotensin I↗
PubMed1993

Free radical scavenging properties of beta-adrenoceptor blockers are not relevant for cardioprotection in isolated rabbit hearts.

UNLABELLED: Several beta-adrenoceptor-blocking agents have been shown to possess free radical scavenging properties. Therefore, the direct cardioprotective properties of propranolol or pindolol were investigated in comparison to superoxide dismutase (SOD). We used isolated rabbit hearts paced at a constant rate (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). Acute regional myocardial ischemia (MI) was induced by left coronary artery branch occlusion and quantitated from epicardial NADH-fluorescence photography. Propranolol (10(-8) mol/l), pindolol (10(-6) mol/l) or SOD (48 I.U./ml) had no significant influence on left ventricular pressure, pressure-rate product or global coronary flow (p > 0.05). Whereas epicardial NADH-fluorescence area after repetitive coronary occlusions was significantly diminished by SOD-treatment (-25%) (p < 0.05), MI size was not significantly affected by either propranolol or pindolol (p > 0.05). CONCLUSION: Oxygen-derived free radicals contribute to tissue injury during myocardial ischemia, and propranolol or pindolol do not possess free radical scavenging properties relevant for cardioprotection in a repetitive coronary occlusion model in isolated rabbit hearts.

Adrenergic beta-Antagonists↗
PubMed1993

Beneficial effect of amrinone on the size of acute regional ischemia in isolated rabbit hearts.

The effect of inotropes on myocardial ischemia is difficult to predict because they may influence the determinants of myocardial O2 demand and O2 supply differently. Several PDE-inhibitors have been reported to possess antiischemic properties related to their hemodynamic and O2-sparing effects. To assess whether PDE-inhibitors also possess direct cardioprotective properties, the effects of amrinone (2.5 x 10(-5) mol/L) in comparison to isoproterenol (5 x 10(-9) mol/L) and ouabain (1.5 x 10(-7) mol/L) were studied in isolated rabbit hearts perfused according to Langendorff at a constant pressure (70 cmH2O) and electrically driven at a constant pacing rate. Regional ischemia was induced by coronary artery ligation and quantified by epicardial NADH fluorescence. All substances significantly increased the actively developed left ventricular pressure to a similar extent (+20%) (P < 0.05). Coronary flow was significantly decreased by ouabain (-15%) and significantly increased by isoproterenol (+25%) and particularly by amrinone (+50%) (P < 0.05). Neither ouabain nor isoproterenol significantly changed the intensity or the distribution pattern of NADH fluorescence, whereas the size of the ischemic zone was significantly reduced by amrinone (-25%) (P < 0.05). The PDE-inhibitor amrinone was shown to possess a direct cardioprotective effect by improving myocardial perfusion and O2 supply in isolated rabbit hearts.

Amrinone↗
PubMed1993

Deleterious effect of exogenous angiotensin-I on the extent of regional ischaemia and its inhibition by captopril.

The endogenous activity of the local renin-angiotensin system (RAS) and the anti-ischaemic properties of captopril were investigated in electrically driven rabbit Langendorff hearts (constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol.l-1). Cumulative concentration-response curves showed no significant difference (P > 0.05) between the reduction of the global coronary flow (CF) by exogenous angiotensin-I or angiotensin-II (EC50 = 10(-10) mol.l-1). It is concluded that the local RAS in isolated rabbit hearts is highly sensitive, whereas its endogenous activity is very low due to very low endogenous angiotensin-I content. Myocardial ischaemia (MI) was induced by the occlusion of a left coronary artery branch and MI was quantified from NADH surface fluorescence photography. MI was significantly enlarged (+35%) (P < 0.05) by exogenous angiotensin-I (6 x 10(-9) mol.l-1). The reduction in CF and the increment in MI by angiotensin-I could be completely prevented by adding captopril at a low concentration (10(-6) mol.l-1) to the perfusion buffer. In the absence of exogenous angiotensin-I, captopril alone (10(-6) mol.l-1) neither significantly enhanced CF (P > 0.05), nor diminished MI (P > 0.05), supporting the finding of very low endogenous activity of the local RAS in this model. We, moreover, conclude that at a low concentration (10(-6) mol.l-1) captopril does not possess direct cardioprotective properties independent of its ACE inhibiting action.

Angiotensin I↗
PubMed1993

Cardioprotection by superoxide dismutase: a catecholamine-dependent process?

Oxygen-derived free radicals may contribute to tissue injury in myocardial ischemia although the mechanism is unclear. Catecholamines possibly could be involved in the genesis of free radicals because it has been demonstrated that oxygen free radicals may be generated by autooxidation of noradrenaline. Superoxide dismutase (SOD) protects the myocardium against injury by superoxide anion radicals. We, therefore, examined whether the cardioprotective effect of superoxide dismutase still could be demonstrated after depletion of catecholamine stores by reserpine (7 mg/kg intraperitoneally 24 h premortem). We used electrically paced isolated hearts perfused according to Langendorff (Tyrode's solution, Ca2+ 1.8 mmol/L, constant perfusion pressure: 70 cm H2O, 3 Hz). Myocardial ischemia was induced by occlusion of a left coronary artery branch. Epicardial NADH-fluorescence was used for quantitation of the myocardial ischemia. SOD (48 U/mL) did not influence global coronary flow or left ventricular pressure significantly (P > 0.05). In control hearts, SOD significantly diminished both size and intensity of epicardial NADH-fluorescence after repetitive coronary ligatures (-45%) (P < 0.05). In hearts with depleted catecholamine stores, this cardioprotection by SOD was no longer observed (P > 0.05). Stimulation of noradrenaline overflow by increasing the pacing rate of control hearts from 180/min up to 300/min after coronary occlusion also significantly enlarged myocardial ischemia (P < 0.05). This pacing rate-dependent growth of myocardial ischemia could be prevented completely by either prior depletion of catecholamine stores with reserpine or SOD. Therefore, noradrenaline seems to be the most important source for the generation of oxygen free radicals during myocardial ischemia in isolated saline-perfused rabbit hearts.

Animals↗
PubMed1993

Influence of dihydropyridine-type calcium agonists on hemodynamics and myocardial ischemia in isolated rabbit hearts.

Calcium (Ca) agonists like Bay k 8644 ((-)-S-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate (CAS 93468-89-4), may represent a new principle in the treatment of heart failure. Because of marked vasoconstrictive properties, these agents may have a deleterious effect on myocardial ischemia (MI). It was however demonstrated that contractility enhancement and coronary flow (CF) reduction do not automatically enlarge MI. Therefore, we investigated the influence of Bay k 8644 (10(-8) mol/l) in comparison to ouabain (1.5 x 10(-7) mol/l) in non-arrhythmogenic concentrations on MI in electrically paced isolated rabbit hearts (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l, 180 beats/min). MI was induced by coronary artery ligation and quantified by epicardial NADH-fluorescence. Left ventricular pressure (LVP) was significantly increased by ouabain (+10-20%) but slightly diminished by Bay k 8644 (-10%) (p < 0.05). CF reduction after Bay k 8644 (-30%) was more pronounced than after ouabain (-10%) (p < 0.05), but both substances did reduce relative CF (CF/LVP x heart rate) to the same extent (-20-30%) (p > 0.05). Nevertheless, ouabain did not significantly influence epicardial NADH-fluorescence area or intensity (p > 0.05), whereas MI was significantly enlarged by Bay k 8644 (+30%) (p < 0.05). It is concluded that in isolated rabbit hearts ouabain and Bay k 8644 might influence CF-distribution differently with a more pronounced diminuation of the nutritive CF induced by Bay k 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Effects of propranolol, pindolol and carteolol on acute regional myocardial ischemia in isolated rabbit hearts.

Catecholamines play a major role during initiation and propagation of myocardial ischemia (MI). Therefore their influence on the size of an acute regional MI was investigated in isolated, coronary ligated rabbit hearts during electrical pacing at different rates (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). MI was quantified from NADH-surface-fluorescence-photography. After coronary occlusion the stimulation-rate was increased stepwise from 180 beats/min to 300/min. Experiments were performed in hearts of control and reserpinized rabbits (reserpine 7.0 mg/kg i.p. 24 h before preparation). Hearts of control animals were submitted to beta-blockade by propranolol (10(-8) mol/l) or the partial agonists pindolol (10(-6) mol/l) or carteolol (10(-6) mol/l). In untreated control hearts MI was significantly enlarged with increasing heart-rate (p < 0.05). At 300/min MI was doubled as compared to that observed at 180/min. In hearts of reserpinized animals this effect was absent (p > 0.05). Moreover, in control hearts the growth of MI could be prevented by beta-blockade with propranolol, pindolol or carteolol (p > 0.05), however, these hearts became insufficient as indicated by an increase in left ventricular enddiastolic pressure. Therefore we conclude that the pacing-rate dependent growth of MI seems not to be primarily related to myocardial left ventricular pressure nor to the heart rate. Nevertheless the growth of MI is strictly related to the release of catecholamines and might be caused by oxygen free radicals generated from noradrenaline by autoxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗