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Biomedical subjects

A Tosaki

Publications and source records attributed to A Tosaki.

71 records · Page 4Linked to original sources
PubMed1989

Effects of low extracellular sodium concentration on reperfusion induced arrhythmias: changes in the myocardial sodium, potassium and calcium contents in isolated guinea pig hearts.

Isolated guinea pig hearts subjected to global ischaemia were used to investigate whether low extracellular Na+ exerts an anti-arrhythmic action against reperfusion arrhythmias, and the effects of extracellular Na+ manipulation upon myocardial ion contents (Na+, K+ and Ca2+) during ischaemia and reperfusion were studied. Using an optimal concentration of 144 mmol.litre-1 of extracellular Na+, hearts were subjected to 10, 20, 25, 30 or 40 min of global ischaemia followed by 25 min reperfusion. A bell shaped curve was obtained such that with increasing durations of ischaemia from 20 to 30 min there was an increasing incidence of reperfusion arrhythmias. Beyond this optimum (at which 100% exhibited reperfusion induced ventricular fibrillation and tachycardia) there was a decline in the susceptibility of the hearts to arrhythmias. Low extracellular Na+ was given 5 min prior to the global ischaemia and maintained during reperfusion. With extracellular Na+ of 24, 54, 84 and 114 mmol.litre-1, reperfusion induced ventricular fibrillation and tachycardia were reduced from their control incidence of 91% and 100% to 8% (p less than 0.001) and 17% (p less than 0.001), 17% (p less than 0.01) and 17% (p less than 0.001), 41% (p less than 0.05) and 50% (p less than 0.05), and 91% and 91%, respectively. Both ischaemia induced Na+ gain and K+ loss were inhibited by low extracellular Na+ (24 mmol.litre-1). During reperfusion, myocardial Na+ was further increased in the control group and this value was lower in the low extracellular Na+ group. In control hearts, myocardial K+ was suddenly increased during the first 5 min of reperfusion, then continuously decreased until the end of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Possible involvement of platelet activating factor in anaphylaxis of passively sensitised, isolated guinea pig hearts.

There is evidence that cardiac tissue may be a target for antigen/antibody reactions. Platelet activating factor (PAF) is released during anaphylaxis and could mediate cardiac damage. To investigate this, guinea pigs were passively sensitised by anti-ovalbumin rabbit serum (6 mg.kg-1 intravenously) and 24 h later their hearts were excised and isolated according to a working heart preparation technique. After a 20 min equilibration period, anaphylactic challenge was induced by a bolus injection of ovalbumin (2 mg in 0.2 ml buffer) via the side arm of the aortic cannula. Heart rate, coronary flow, aortic flow, left ventricular developed pressure (LVDP), its first derivative (LVdp/dtmax) and left ventricular end diastolic pressure (LVEDP) were recorded. After ovalbumin challenge, heart rate and LVEDP were markedly increased, while coronary flow, aortic flow, LVDP, and LVdp/dtmax were profoundly decreased. All these alterations were over within 5 min, and the measured variables returned to approximately the pre-challenge values. BN 52021, a specific PAF receptor antagonist, was dissolved in the perfusion buffer and given in doses of 15, 30 and 60 mumol.litre-1 10 min prior to the induction of anaphylactic challenge until the end of the observation period. BN 52021 inhibited the increase in heart rate and LVEDP and the decrease in coronary and aortic flow, LVDP and LVdp/dtmax in a dose dependent manner. The changes produced by 30 and 60 mumol.litre-1 were statistically significant at the levels of p less than 0.01 and p less than 0.001 when compared to the control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗
PubMed1989

[Effect of cicletanine on arrhythmia and intracellular sodium accumulation in the isolated rat heart during ischemia and reperfusion].

The antiarrhythmic effects of cicletanine (CIC), a new antihypertensive drug, were studied on isolated hearts from SHR and WKY rats subjected to global normothermic ischaemia. The effects of CIC on variations in intracellular sodium concentration induced by ischaemia-reperfusion were measured. After a 14-day treatment with CIC in doses of 30 and 100 mg/kg/day, the results were as follows: in WKY rats the incidence of ventricular fibrillation (VF) was reduced from 91% in controls to 41% and 50% (p less than 0.05) and the incidence of ventricular tachycardia (VT) was reduced from 100% to 41% and 58% (p less than 0.05). In SHR rats the percentages of VF were 100% in controls and 17% (p less than 0.001) and 33% (p less than 0.01) respectively in treated animals. Similarly, the incidence of VT was reduced from 100% to 17% (p less than 0.001) and 25% (p less than 0.001) respectively. The effects of CIC were more pronounced on SHR rats than on WKY rats. CIC reduced the intracellular sodium accumulation induced by ischaemia and reperfusion. The antiarrhythmic activity of CIC seems to be correlated with its inhibitory activity on intracellular sodium accumulation.

Animals↗
PubMed1988

Free radicals and calcium: simultaneous interacting triggers as determinants of vulnerability to reperfusion-induced arrhythmias in the rat heart.

Using the isolated perfused rat heart with regional ischemia and reperfusion, we have two antiarrhythmic interventions (the spin trap agent PBN [N-tert-butyl-alpha-phenylnitrone] and perfusate calcium reduction), administered just before reperfusion, to investigate mechanisms determining the vulnerability of the heart to reperfusion-induced ventricular fibrillation. Hearts were subjected to regional ischemia (5, 10, 20, 30 or 40 min) followed by reperfusion. Four groups were studied for each ischemic time: (i) control hearts with no antiarrhythmic intervention; (ii) hearts perfused with PBN (30 mumol/l) during the final 1 min of ischemia and throughout reperfusion, (iii) hearts perfused with low-calcium buffer (0.4 mmol/l) during the final 1 min of ischemia and throughout reperfusion and (iv) hearts perfused with PBN (30 mumol/l) and low-calcium (0.4 mmol/l) during the final 1 min of ischemia and throughout reperfusion. In control hearts, a bell-shaped time-vulnerability curve was obtained with 0, 91, 67, 33 and 17% of the hearts exhibiting irreversible fibrillation during reperfusion after 5, 10, 20, 30 and 40 min of ischemia, respectively. In the PBN group, the values were 8, 41 (P less than 0.05), 41, 33 and 8%, respectively. In the calcium reduction group the values were 17, 50, 8 (P less than 0.05), 8 and 0, respectively. Thus, PBN caused a significant reduction in reperfusion-induced ventricular fibrillation after 10 min of ischemia but had no significant effect with reperfusion after 20 min of ischemia. In contrast, calcium reduction had no significant effect after 10 min of ischemia but caused a significant reduction after 20 min of ischemia. When PBN treatment with calcium reduction were combined we obtained significant anti-arrhythmic effects after both 10 min (P less than 0.05) and 20 min (P less than 0.05) of ischemia. The additive effects of these two interventions, and the different ischemic-times after which they are most effective, has led us to propose that multiple triggers, each with different underlying mechanisms may be capable of initiating events which lead to ventricular fibrillation.

Animals↗
PubMed1988

Pacing and reperfusion induced arrhythmias: protection by slow heart rate in the rat heart.

Using the isolated perfused rat heart with transient (10 min) regional ischaemia induced by coronary artery ligation, we have shown that slow heart rate can dramatically reduce the vulnerability of the myocardium to reperfusion induced ventricular fibrillation and ventricular tachycardia. In the heart rate range of 200-400 beats.min-1, slower heart rates exerted a frequency dependent protective effect against reperfusion induced arrhythmias. At the optimal rate of 200 beats.min-1, the incidence of total ventricular fibrillation (irreversible plus reversible) and ventricular tachycardia fell to 33% and 50% of their control values (100%). The anti-arrhythmic effect was achieved with only a minor (less than 20%) effect on coronary flow. To ascertain whether or not slow heart rate achieved an absolute reduction in vulnerability to arrhythmias irrespective of the duration of ischaemia, hearts were also subjected to 5, 10, 20, 30 or 40 min of ischaemia followed by 30 min of reperfusion with and without pacing at 200 beats.min-1. A bellshaped time-response profile was obtained in both groups. In unpaced controls (n = 12) this gave a maximal vulnerability to arrhythmias after 10 min of ischaemia. In the paced hearts (n = 12) the curve was shifted to the right, with a peak vulnerability at 20 min. These results show that the action of pacing is to exert a delaying effect which extends the duration of ischaemia that can be tolerated before the heart becomes vulnerable to reperfusion induced arrhythmias. Heart rate can have a substantial effect on reperfusion induced arrhythmias and should be considered when making therapeutic interventions and risk assessments in this setting.

Animals↗
PubMed1988

Protective effect of lidocaine against ischemia and reperfusion-induced arrhythmias and shifts of myocardial sodium, potassium, and calcium content.

Isolated guinea pig hearts subjected to global ischemia, were used to investigate whether lidocaine exerts an antiarrhythmic action against reperfusion-induced arrhythmias, and the effects of this drug upon myocardial ion contents during ischemia and reperfusion were studied. In the first series of experiments, the drug was administered 5 min prior to the induction of global ischemia and maintained during reperfusion. With 3.6 X 10(-6), 7.2 X 10(-6), 14.7 X 10(-6), and 29.5 X 10(-6) mol/L lidocaine, reperfusion-induced ventricular fibrillation and tachycardia were reduced from their control incidence of 83% and 100% to 41% and 58%, 33% (p less than 0.05) and 25% (p less than 0.001), 8% (p less than 0.01) and 8% (p less than 0.001), 0% (p less than 0.001) and 0% (p less than 0.001), respectively. The ion contents of myocardium were determined by atomic absorption spectrophotometer after washout of the ions from vasculature. Ischemia induced a marked accumulation of sodium and loss of potassium in the myocardial tissue. Both ischemia-induced sodium gain and potassium loss were significantly inhibited by lidocaine treatment. During reperfusion, sodium was further increased in the control group and this value was significantly lower in the lidocaine-treated group after 1 min of reperfusion. Sodium content remained at nearly constant level for the rest of reperfusion period. Potassium was suddenly increased during the first 5 min of reperfusion then continuously decreased until the end of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Diltiazem and the reduction of reperfusion-induced arrhythmias in the rat: protection is secondary to modification of ischemic injury and heart rate.

We have used the isolated rat heart with transient coronary artery occlusion to investigate whether diltiazem has an anti-arrhythmic action against reperfusion-induced ventricular arrhythmias. In the first series of studies (early administration group) the drug was administered 5 min prior to the induction of regional ischemia, this resulted in a dose-dependent reduction in reperfusion-induced ventricular fibrillation. With 5 X 10(-8), 10(-7), 5 X 10(-7), 10(-6) and 5 X 10(-6) mols of diltiazem/l, total ventricular fibrillation (reversible plus irreversible) was reduced from its control incidence of 100% (12/12) to 91%, 58% (P = less than 0.05), 17% (P = less than 0.001), 0% (P = less than 0.001) and 0% (P = less than 0.001) respectively. Heart rate was also reduced in a dose-dependent manner, falling from its control value of 268 +/- 6 beats/min to less than 50% with the highest concentration of diltiazem. Coronary flow was increased in a dose-dependent manner in the diltiazem treated groups. In additional studies with an anti-arrhythmic dose of diltiazem (5 X 10(-7) mols/l), hearts were paced to their drug free control value; under these conditions the anti-arrhythmic effect of diltiazem was lost. In further studies, diltiazem (10(-7) and 5 X 10(-7) mols/l) was administered just prior to reperfusion (late administration group), no anti-arrhythmic effects were observed. In additional studies we determined whether, with early administration, diltiazem (5 X 10(-7) mols/l) exerted its anti-arrhythmic effect by altering the relationship between the vulnerability to reperfusion-induced arrhythmias and the duration of preceding ischemia. In diltiazem-free control hearts a bell-shaped profile was observed with a maximum vulnerability after 10 min of ischemia (100% incidence of reperfusion-induced ventricular fibrillation). In diltiazem-treated hearts, a bell-shaped curve was also observed, however, its optimum was shifted to the right and downwards (20 min of ischemia gave maximum vulnerability [41%] to reperfusion-induced arrhythmias). We conclude that the ability of diltiazem to protect the isolated rat heart against reperfusion-induced arrhythmias is secondary to its anti-ischemic effect and in particular to its negative chronotropic properties.

Animals↗
PubMed1987

Reperfusion-induced arrhythmias and free radicals: studies in the rat heart with DMPO.

We have shown that the free radical spin trap DMPO (5,5-dimethyl-1-pyrroline-N-oxide) reduces reperfusion-induced arrhythmias in a dose-dependent manner in the isolated perfused rat heart subjected to 10 min regional ischemia and 3 min reperfusion. At its optimal concentration (1,000 mumol/L) DMPO, added to the perfusate 5 min prior to ischemia, reduced (p less than 0.05) the incidence of reperfusion-induced irreversible ventricular fibrillation from 83 (10 of 12) to 33% (4 of 12). When hearts were subjected to ischemia (10 min) and reperfusion, with DMPO (1,000 mumol/L) added to the perfusion fluid only 2 min before reperfusion, comparable protection was observed. To ascertain whether or not DMPO achieved an absolute reduction in vulnerability to arrhythmias irrespective of the duration of ischemia, hearts (12 for each group) were also subjected to 5, 10, 20, 30, or 40 min of ischemia; DMPO (1,000 mumol/L) was added to the perfusate either 5 min before ischemia or 2 min before reperfusion. In each instance a bell-shaped time-response profile was obtained. In the DMPO-free controls this gave a maximal vulnerability to arrhythmias after 10 min of ischemia. In the DMPO-treated hearts this curve was shifted to the right, with a peak vulnerability at 20 min. These results indicate that the primary action of DMPO is to exert a delaying effect which extends the duration of ischemia that can be tolerated before the heart becomes vulnerable to reperfusion-induced arrhythmias. However, this effect is achieved during the reperfusion period and not during the preceding period of ischemia. The precise mechanism by which this free radical spin trapping agent achieves this unusual effect remains to be resolved, but in studies with light-inactivated DMPO, this protective effect was lost, indicating that its ability to be oxidized, possibly by superoxide or hydroxyl radicals, may be critical to its mechanism of action.

Animals↗
PubMed1987

Metoprolol reduces reperfusion-induced fibrillation in the isolated rat heart: protection is secondary to bradycardia.

We studied the effect of metoprolol on the incidence of reperfusion-induced ventricular fibrillation in the isolated rat heart with transient coronary artery occlusion and reperfusion. When administered prior to ischemia, metoprolol produced a dose-dependent reduction in reperfusion-induced ventricular fibrillation. Thus, with 1, 10, 30, 50, 100, and 200 mumol/L metoprolol, total ventricular fibrillation (reversible plus irreversible) was reduced from its control incidence of 100% to 91%, 83%, 58% (p less than 0.05), 25% (p less than 0.001), 25% (p less than 0.001), and 0% (p less than 0.001), respectively. Heart rate was also reduced in a dose-dependent manner from its control value of 268 +/- 6 beats/min to less than 75% at the highest concentration of metoprolol. Coronary flow was unaffected by metoprolol. Doses of metoprolol (1 and 10 mumol/L) that had no significant effect on heart rate had no antiarrhythmic effect. In additional experiments with a higher dose of metoprolol (50 mumol/L), hearts were paced to the rate of the drug-free control group and the antiarrhythmic effect of metoprolol was lost. When drug-free control hearts had their heart rate reduced to that of the metoprolol-treated hearts, a similar antiarrhythmic effect was observed. When metoprolol was administered just prior to reperfusion, no antiarrhythmic effects were observed. In further studies, we investigated the effect of the early administration of metoprolol (50 mumol/L) on the relationship between the vulnerability to reperfusion-induced arrhythmias and the duration of preceding ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Protective effect of transient calcium reduction against reperfusion-induced arrhythmias in rat hearts.

By using the isolated rat heart with regional ischemia and a perfusate Ca2+ of 2.4 mM, we have observed a bell-shaped relationship between the incidence of reperfusion-induced ventricular fibrillation (VF) and the duration of preceding ischemia. With 5, 10, 20, 30, and 40 min of ischemia, 8, 83, 58, 25, and 8% of the hearts (n = 12 per group) exhibited irreversible VF. In additional studies (10 min ischemia) perfusate Ca2+ was reduced (to 0.1, 0.4, 0.8, 1.2, 1.6, and 2.0 mM) for 1 min before coronary occlusion (to trap low Ca2+ in the ischemic zone) and for 1 min before and throughout reperfusion. VF fell in a dose-dependent manner from its control incidence of 83% (2.4 mM Ca2+) to 17 (P less than 0.01), 25 (P less than 0.01), 41, 58, 91, and 83%, respectively. In further studies Ca2+ was reduced to 0.4 mM just before ischemia and also just before and during reperfusion, and the ischemic time was varied (5, 10, 20, 30, or 40 min), VF was reduced from its time-matched control (2.4 mM Ca2+) values of 8, 83, 58, 25, and 8% to 0, 25 (P less than 0.01), 8 (P less than 0.05), 0, and 0%, respectively. In a final series of experiments, Ca2+ reduction (to 0.4 mM) was carried out only during reperfusion (1 min before and throughout reperfusion). When time-vulnerability curves were constructed some protection was observed after 20 min of ischemia (VF fell from its control incidence of 58 to 8%). We conclude that extracellular Ca2+ concentration can influence vulnerability to reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Free radicals and reperfusion-induced arrhythmias: protection by spin trap agent PBN in the rat heart.

Using the isolated perfused rat heart with transient (10-minute) regional ischemia induced by coronary artery ligation, we have shown that PBN (N-tert-butyl-alpha-phenylnitrone), an organic spin trap agent designed specifically to form "stable" adducts with free radicals in electron spin resonance studies, can dramatically reduce the vulnerability of the myocardium to reperfusion-induced ventricular fibrillation. Studied in the concentration range of 5-1,000 microM/L, PBN added to the perfusate 5 minutes prior to ischemia exerted a dose-dependent protective effect. At the optimum concentration of 30 microM/L PBN reduced the incidence of ventricular fibrillation to 50% (6 of 12) from its control value of 100% (12 of 12). The antiarrhythmic effect was achieved without any substantial effect on coronary flow or heart rate. Investigating whether this was a direct antiarrhythmic effect, operating during reperfusion, or an indirect effect arising from the action of PBN on the heart during ischemia, PBN (30 microM/L) was added to the perfusion fluid 2 minutes before reperfusion. In the control group, 100% of the hearts fibrillated whereas only 50% fibrillated in the PBN group. Additional studies were designed to ascertain whether the drug caused an absolute reduction in vulnerability to reperfusion-induced arrhythmias (irrespective of the duration of ischemia) or whether it only shifted the ischemic time-reperfusion vulnerability curve to the right (i.e., delayed the onset of vulnerability). Thus, studies were undertaken to define the relation between the duration of ischemia and the incidence of reperfusion-induced arrhythmias in control hearts and hearts treated with PBN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Does the antiarrhythmic effect of DMPO originate from its oxygen radical trapping property or the structure of the molecule itself?

Using the isolated perfused rat heart with transient (30 min) normothermic global ischemia, it was shown that DMPO (5,5-dimethyl-pyrroline-N-oxide), an organic spin trap agent designed specifically to trap free radicals, dramatically reduced the vulnerability of the myocardium to reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT). DMPO (concentration range 30-500 mumol/l) infused in the heart at the moment and during the first 10 min of reperfusion exerted a dose-dependent antiarrhythmic effect. Thus, the doses of 30, 100, and 500 mumol/l of DMPO reduced the incidence of reperfusion-induced VF and VT from their control values of 100% and 100% to 83% and 91%, 50% (p < 0.05) and 67%, 25% (p < 0.01) and 50% (p < 0.05), respectively. Furthermore, the recovery of myocardial function was improved during postischemic reperfusion. A modification in the molecular structure of DMPO leading to HMIO (1,2,2,4,5,5-hexamethyl-3-imidazoline-oxide), so-called inactive DMPO which does not trap free radicals in the presence of a radical generating system or in the effluent of reperfused hearts, failed to reduce the incidence of reperfusion-induced arrhythmias or improve the recovery of postischemic reperfused myocardium. These findings suggest that the free radical trapping properties of DMPO or the effects of the formed DMPO-OH, a stable nitroxyl radical adduct, are responsible for the reduction of reperfusion-induced arrhythmias, and not the molecular structure of DMPO itself. Finally, it is of interest to note that the detection of free radicals was observed in fibrillating hearts, but not in nonfibrillating hearts. This consideration should be taken into account when making therapeutic interventions and risk assessments of a radical scavenger in this setting.

Animals↗
PubMedDate not supplied

Reperfusion-induced arrhythmias and myocardial ion shifts: a pharmacologic interaction between pinacidil and cicletanine in isolated rat hearts.

Pinacidil is a member of the new antihypertensive drug family possessing an action that involves an increased potassium efflux in vascular and cardiac muscle. We investigated the contribution of opening of ATP-sensitive potassium channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na+, K+, Ca2+, and Mg2+ in isolated rat hearts. After 30 min of normothermic global ischemia, pinacidil with 1 to 60 mumol/l failed to reduce the incidence of reperfusion-induced arrhythmias, even on the postischemic/reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (the duration of ischemia was reduced to 25 min), pinacidil treatment was associated with a greater incidence of reperfusion-induced arrhythmias (100%) as compared to the control value (50%). These proarrhythmic effects of pinacidil were also reflected in a maldistribution of myocardial ion contents both in nonischemic and ischemic/reperfused hearts. Cicletanine, a furopyridine antihypertensive agent that has no effect on coronary resistance, reduced the incidence of reperfusion arrhythmias, and its antiarrhythmic effect was antagonized by pinacidil. The same observation was made in relation to myocardial ion content, e.g., pinacidil-induced K+ loss and Ca2+ gain were antagonized by cicletanine, both in nonischemic and ischemic/reperfused hearts. It is hypothesized that the increased tendency to develop reperfusion-induced ventricular fibrillation is associated with the pinacidil-induced K+ efflux. The present study does not attempt to address the question of specific ionic currents; however, it has been suggested that proarrhythmic and antiarrhythmic effects of pinacidil and cicletanine, respectively, may relate to same receptor sites in which the latter may reflect a specific blockade of the outward K+ ion current via ATP-sensitive K+ channels. If this is so, the use of K+ channel openers as antihypertensive agents may be of particular concern in that population of postinfarction patients who are known to be at high risk of sudden coronary death.

Animals↗
PubMedDate not supplied

Fluoro-fatty acids and the impairment of cardiac function in the rat in vivo and in vitro.

Dichapetalum toxicarium seeds contain long chain fluoro-fatty acids, particularly fluoro-oleic acid, which in doses as low as 10 mg/kg can cause death. We have used the rat heart both in vivo and in vitro to assess the cardiovascular effects of various doses of the fluoro-oleic acid extract of the seeds of Dichapetalum toxicarium. Intraperitoneal administration of 0.25 ml of seed extract solution/kg body weight (estimated to be equivalent to 10 mg fluoro-oleic acid/kg body weight) or 0.5 ml/kg body weight (equivalent to 20 mg fluoro-oleic acid/kg body weight) resulted in death in all animals (n = 6 in each group). The mean time from administration to death was 36.4 +/- 4 h and 21.0 +/- 2 h, respectively. Death was attributable to severe bradycardia which developed progressively throughout the experiment. Thus, during the first 6 h, heart rate fell by 32.2% from 450 +/- 7 beats/min to 305 +/- 36 beats/min (p less than 0.01) in the 0.25 ml/kg group and by 66 +/- 10% to 150 +/- 20 beats/min (p less than 0.001) in the 0.5 ml/kg group. Administration of the extract solution alone or oleic acid alone (equivalent to 0.5 ml/kg seed extract) to control rats had no effect. Investigating the effects of the seed extract in vitro, hearts (n = 6 in each group) were perfused with buffer containing 0.5 ml/l seed extract (equivalent to 20 mg fluoro-oleic acid/l) or with buffer containing extract solution alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Role of nitric oxide and TPEN, a potent metal chelator, in ischaemic and reperfused rat isolated hearts.

1. The role of nitric oxide (NO) was studied in the control of ischaemic/reperfused cardiac function and the effect of N,N,N',N'-tetrakis-[2-pyridylmethyl]-ethylenediamine (TPEN), a potent metal chelator, on the regulation of cardiac NO formation. 2. Rat isolated working hearts were subjected to 30 min ischaemia and reperfusion. The incidence of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT) and the recovery of cardiac function were measured. Nitric oxide was detected by electron spin resonance (ESR) spectroscopy. 3. With 5.0, 7.5 and 10.0 mumol/L of TPEN administered prior to ischaemia, the drug produced a reduction in the incidence of VF from its control value of 100% to 25% (P < 0.05), 17% (P < 0.05) and 8% (P < 0.05), respectively. The incidence of VT followed the same pattern. 4. When TPEN was given at the moment of reperfusion, a reduction in the incidence of VF and VT was still observed. Reduction in the incidence of VF and VT was reflected in the improvement of cardiac function both in the pre- and post-ischaemic TPEN-treated groups. 5. TPEN reduced basal cardiac NO content and prevented the accumulation of NO during ischaemia/reperfusion. 6. The results show that TPEN exerts beneficial effects on postischaemic cardiac function and dysrhythmias in relation to inhibition of the accumulation of NO in ischaemic/reperfused myocardium.

Animals↗