Biomedical subjects

A F Rump

Publications and source records attributed to A F Rump.

At least 37 records · Page 2Linked to original sources

PubMed1995

Ocular concentrations of mitomycin C after extraocular application in rabbits.

To determine the intraocular concentrations of Mitomycin C (MMC) after extraocular application, we used pigmented rabbits and placed sponges soaked with MMC under the conjunctiva on top of the intact episclera. First, we soaked the sponges with volumes ranging from 0.025 ml to 0.3 ml of the solution containing MMC and sampled aqueous humour after 30 minutes. The concentrations, as determined by high performance liquid chromatography, did not correlate to the amount of MMC given. Then, we soaked the sponges with different concentrations of MMC with a volume of 0.1 ml and sampled aqueous humour, vitreous humour and sclera after 60 minutes. The concentrations of MMC were higher in the vitreous than in the aqueous, and, relative to these values, very high in the sclera. These results indicate that the amount of MMC reaching the interior of the eye after standard extraocular application may be highly variable, and that the concentrations of MMC in the sclera and formed vitreous can be considerably higher than in the aqueous humour.

Administration, Topical↗

PubMed1995

Changes in plasma cholinesterase activity and mivacurium neuromuscular block in response to normothermic cardiopulmonary bypass.

The effect of reduced plasma cholinesterase (ChE) activity in response to normothermic cardiopulmonary bypass (CPB) on mivacurium neuromuscular block was studied in nine patients anesthetized with propofol/fentanyl. Mivacurium was injected intravenously as an initial bolus of 150 micrograms/kg; repeat doses of 75 micrograms/kg were given when the evoked twitch tension attained 75% of control. With the institution of CPB, the previously normal ChE activity was reduced by 42% and remained low until the end of the procedure. The times of onset (time from the end of injection to maximum neuromuscular block) of the maintenance doses of mivacurium were 26% longer during than before or after CPB (P < 0.05). Their DUR25% (time from end of injection to recovery of neuromuscular transmission to 25% of control) were 13 +/- 3 min (means +/- SD) before, 14 +/- 4 min during, and 16 +/- 4 min (P < 0.05) after CPB. It is concluded, that, although markedly reducing the patient's previously normal ChE activity, normothermic CPB had little effect on the time characteristics of mivacurium neuromuscular block.

Aged↗

PubMed1995

Functional effects of adrenochrome in isolated rabbit heart.

The cardiotoxic effects of catecholamines have been explained in part by the generation of oxygen free radicals and aminochromes. The role of aminochromes remains however controversial. It has previously been demonstrated that adrenochrome, an oxidation product of adrenaline, shows cardiotoxic properties only at very high concentrations, and it has been suggested that the deleterious effects observed may be caused by a worsening in myocardial perfusion. The functional properties of adrenochrome were examined in isolated spontaneously-beating rabbit hearts with depleted catecholamine stores (reserpin 7.0 mg/kg 16-24 hr before preparation, Langendorff, constant pressure: 70 cm H2O, Tyrode solution, [Ca++]sol. 1.8 mmol/l, 37 degrees). Cumulative concentration-response curves show an adrenochrome-concentration-dependent increase of contractility (left ventricular pressure, EC50 = 3.6 x 10(-6) M; +dp/dtmax, EC50 = 1.6 x 10(-5) M), whereas myocardial relaxation was impaired (-dp/dtmax, EC50 = 2.6 x 10(-5) M; -dp/dtmax/+dp/dtmax = 0.68 at 10(-4) M). Heart-rate was only slightly enhanced (+10% at 10(-4) M), and the coronary flow was markedly influenced only by adrenochrome 10(-4) M (-17%). The relative coronary flow (= global coronary flow/pressure-rate product) was concentration-dependently reduced (EC50 = 10(-5) M; -49% at 10(-4) M). We conclude that in isolated rabbit hearts, adrenochrome has a positive inotropic action but impairs myocardial relaxation, and coronary constrictor activity prevents an increase of myocardial oxygen supply, thus worsening myocardial oxygen-demand/supply balance.

Adrenochrome↗

PubMed1995

Comparison of the cardioprotective efficacy of superoxide dismutase in a single and a repetitive coronary occlusion model in rabbit hearts.

The effects of exogenous superoxide dismutase (SOD) on acute myocardial ischemia (MI) was investigated in isolated electrically-driven rabbit hearts (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca++ 1.8 mmol/l, 37 degrees C). Acute regional ischemia (MI) was induced by occlusion of a coronary artery branch (CAO) and quantitated from epicardial NADH-fluorescence photography. SOD (48 U/ml) was applied either 30 min after CAO in a single coronary occlusion model (treatment) or 30 min before the 2nd CAO in a repetitive coronary occlusion model (pre-treatment). SOD had no significant influence on the left ventricular pressure or the global coronary flow (p > 0.05). MI was significantly diminished in hearts pre-treated with SOD before CAO (-25%)(p < 0.05), but remained unaffected when SOD was applied after CAO (p > 0.05). The results suggest that superoxide anion radicals contribute to ischemic tissue injury. SOD shows cardioprotective properties only if present in the ischemic zone, requiring the application of SOD before CAO in poorly collateralised rabbit hearts.

Animals↗

PubMed1995

Mitomycin-C concentration in human ocular aqueous humor after topical administration during trabeculectomy.

UNLABELLED: The concentration of the antitumor antibiotic mitomycin (CAS 50-07-7, mitomycin C, MMC), used in ophthalmic surgery for its antiproliferative effects, was measured in the aqueous humor of 7 glaucoma patients undergoing trabeculectomy. Sponges soaked with MMC-solution (100 microliters of MMC-solution 0.2 mg/ml: 20 micrograms) were applied intraoperatively on the scleral flap for 5 min. 100 to 200 microliters of aqueous humor were drawn with a needle 10 min following the end of topical MMC-treatment. Samples were assayed for MMC using a reverse-phase HPLC-system with ultraviolet detection (C18-column, elution: phosphate buffer (0.01 mol/l, pH: 6.5): methanol, v:v = 70:30, 365 nm). Swabs were extracted in phosphate-buffer (0.1 mol/l, pH: 7.0) before HPLC-analysis. External calibration was used for MMC quantitation. Quantitation limit was 10 ng/ml. In all aqueous humor samples MMC-concentration was below 10 ng/ml. MMC in the swabs amounted to 37% of the MMC amount applied. CONCLUSION: After intraoperative topical application, the MMC concentration in the aqueous humor of patients is very low. The substantial loss of MMC from the swabs used for the topical MMC-treatment suggests 1. rapid systemic absorption of MMC and/or 2. a loss through irrigation of the operative field following topical MMC-application.

Administration, Topical↗

PubMed1994

Evidence for norepinephrine cardiotoxicity mediated by superoxide anion radicals in isolated rabbit hearts.

UNLABELLED: Catecholamines have been demonstrated to be cardiotoxic. Besides hemodynamic alterations, oxygen free radicals generated by the auto-oxidation of catecholamines might contribute to their deleterious effects. We examined the influence of exogenous norepinephrine (NE), after inhibiting functional alterations by alpha and beta-adrenoceptor blockade, on acute regional ischemia (MI). METHOD: We used isolated electrically-driven rabbit hearts with depleted catecholamine stores (reserpine 7.0 mg/kg i.p. 16-24 h before preparation, Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l, 37 degrees C, 185-200 beats/min). Repetitive MI, separated by a reperfusion period of 50 min, was induced by coronary artery branch ligature and quantitated from epicardial NADH-fluorescence photography. Starting after a reperfusion period of 20 min, isolated hearts were treated with NE (10(-6) M), in the presence of propranolol (10(-6) M), phentolamine (10(-6) M) and vitamin C (3 x 10(-8) M) in the perfusion buffer to prevent the functional effects of NE. The influence of the free radical scavenger superoxide dismutase (SOD) (30 U/ml) or captopril (10(-6) M) on MI was also examined. RESULTS: Left ventricular pressure or coronary flow were not significantly affected by either treatment (p > 0.05). Epicardial NADH-fluorescence area and intensity were, however, significantly enhanced by NE (+22%) (P < 0.05), although propranolol, phentolamine and vitamin C had no significant influence on MI (P > 0.05). SOD had no significant effect on MI in control hearts (P > 0.05) but completely prevented MI enlargement by NE (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1994

Cardiotoxicity of adrenochrome in isolated rabbit hearts assessed by epicardial NADH fluorescence.

Noradrenaline in a micromolar concentration has recently been shown to contribute to ischemic tissue injury by direct cardiotoxic effects independent of functional alterations. Oxygen free radicals, generated during the auto-oxidation of catecholamines, are important mediators of catecholamine cardiotoxicity. However, the role of the oxidative products (aminochromes) is still unclear. We examined the effects of adrenochrome on functional parameters and on regional myocardial ischemia (MI) in isolated electrically-driven rabbit hearts with depleted catecholamine stores (reserpine 7.0 mg/kg i.p. 16-24 h before preparation, Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca++ 1.8 mmol/l, 37 degrees C). Repetitive MI, separated by a reperfusion period of 50 min, was induced by coronary artery branch ligature, and MI was quantitated from epicardial NADH fluorescence photography. Adrenochrome-treatment (10(-6) M or 10(-4) M) was started after a reperfusion period of 20 min. The left ventricular pressure (LVP) was significantly enhanced by adrenochrome (p < 0.05), but it fell thereafter to below its initial value in hearts treated with adrenochrome 10(-4) M. The global coronary flow (CF) was not affected by adrenochrome 10(-6) M (P > 0.05), but it was significantly decreased by adrenochrome 10(-4) M (P < 0.05). The relative CF (= CF/LVP x heart-rate) was numerically decreased by adrenochrome 10(-6) M (p > 0.05) and more markedly by adrenochrome 10(-4) M (p < 0.05). Whereas epicardial NADH fluorescence was similar after repetitive coronary artery occlusions in controls and in hearts treated with adrenochrome 10(-6) M (p > 0.05), it was significantly enhanced by adrenochrome 10(-4) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenochrome↗

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

A quantitative comparison of functional and anti-ischaemic effects of the phosphodiesterase-inhibitors, amrinone, milrinone and levosimendan in rabbit isolated hearts.

1. The functional and anti-ischaemic effects of the phosphodiesterase (PDE)-inhibitors, amrinone, milrinone and levosimendan, a new agent combining PDE-inhibitory with calcium-sensitizing properties, were investigated in rabbit isolated hearts (Langendorff, constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol l-1, 37 degrees C). Anti-ischaemic effects were studied in electrically-driven hearts (200 beats min-1). Acute regional ischaemia was induced by ligature of a branch of the circumflex coronary artery and quantified from epicardial NADH-fluorescence photography. 2. Cumulative concentration-response curves in spontaneously beating hearts in the presence of isoprenaline (10(-10) M), showed a higher inotropic and coronary vasodilator potency for levosimendan (EC50: 7 x 10(-7) M) compared to milrinone (EC50: 7.7 x 10(-6) M) or amrinone (EC50: 2 x 10(-5) M). Although the maximal coronary dilator activity was similar for the three agents, the maximal inotropic and chronotropic effects were lower for levosimendan than for amrinone or milrinone (P < 0.05). 3. In regionally ischaemic hearts, milrinone (10(-5) M) or levosimendan (5 x 10(-6) M) similarly enhanced the left ventricular pressure (+15-20%) (P < 0.05) and the global coronary flow (+40-50%) (P < 0.05). The epicardial NADH-fluorescence area was significantly diminished by milrinone or levosimendan (-20-30%) (P < 0.05) and there was no significant difference between the anti-ischaemic effects of either agent (P > 0.05). 4. It is concluded that amrinone and milrinone possess similar functional profiles in rabbit isolated hearts and a higher inotropic and chronotropic efficacy than levosimendan. At functionally equieffective concentrations, milrinone and levosimendan show similar anti-ischaemic effects, related to an improvement of myocardial perfusion. The calcium-sensitizing properties seem not to be relevant for cardioprotection by levosimendan at the concentration used.

Amrinone↗

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

Propranolol unmasks class III like electrophysiological properties of norepinephrine.

Isolated perfused spontaneously beating rabbit hearts were treated with increasing concentrations of norepinephrine (0.01, 0.1, 0.5 mumol/l) either alone or in presence of propranolol (0.1 mumol/l). For analysis of the epicardial activation and repolarization process and epicardial mapping (256 unipolar leads) was performed. For each electrode the activation and repolarization time was determined. From these data the "breakthrough-points" (BTP) of epicardial activation were determined. At each electrode an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similarity of various heart beats (under NE) compared to control was evaluated by determination of the percentage of identical BTP and of similar VEC (deviation < or = 5 degrees). Moreover at each electrode the local activation recovery interval (ARI) and its standard deviation (of 256 leads, dispersion, DISP) were determined. Norepinephrine alone (0.01, 0.1, 0.5 mumol/l) led to an increase in left ventricular pressure, heart rate and DISP with concomitant frequency dependent reduction in ARI, and to changes in the epicardial activation pattern (reduction in BTP, VEC). We found that in the presence of propranolol (0.1 mumol/l) norepinephrine prolonged ARI and reduced ARI-dispersion. This effect was not due to changes in heart rate. The disturbing effects on the activation pattern were diminished. These effects could be prevented by pretreatment with 1 mumol/l prazosin. From these results we conclude, that norepinephrine prolongs the relative action potential duration via stimulation of alpha 1-adrenoceptor and enhances cellular coupling.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

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

Influence of (-)-S-Bay K 8644, (+/-)-Bay W 5035 and (+/-)-Bay T 5006 on hemodynamics and FITC-dextran 3 elution kinetics in isolated rat hearts.

1. We investigated the effects of the new calcium-agonists (+/-)-Bay W 5035 and (+/-)-Bay T 5006 in comparison to (-)-S-Bay K 8644 on hemodynamics and epimyocardial perfusion in Langendorff rat hearts. 2. At equieffective inotropic concentration, vasoconstriction of coronary resistance vessels was significantly less after (+/-)-Bay W 5035 or (+/-)-Bay T 5006 than after (-)-S-Bay K 8644 application. 3. FITC-Dextran 3 elution kinetics indicated that the epimyocardial vascular volume was significantly reduced only by (-)-S-Bay K 8644. 4. Moreover, (-)-S-Bay K 8644 enhanced transcoronary exchange more markedly than (+/-)-Bay W 5035 or (+/-)-Bay T 5006, reflecting the differences in coronary constrictor activity. 5. We conclude that in comparison to (-)-S-Bay K 8644 the relation between inotropy and vasoconstriction is more favorable for (+/-)-Bay W 5035 or (+/-)-Bay T 5006.

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

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↗