The role of prostaglandins in the antiarrhythmic effect of ischemic preconditioning

The role of prostaglandins in the antiarrhythmic effect of ischemic preconditioning (IP) was investigated in pentobarbital-anesthetized rats. In 5 unpreconditioned control rats, 30 min of occlusion of the left coronary artery elicited ventricular tachycardia (VT) and fibrillation (VF), with an average duration of VT and VF of 51 +/- 6 and 43 +/- 4 s, respectively. Frequent ventricular premature beats (VPBs; average 1,249 +/- 145) were also documented in these animals. Thirty minutes of reperfusion after the prolonged coronary occlusion in these animals caused more severe arrhythmias, including irreversible VF. In animals pretreated with IP (n = 5), which was achieved by 3 cycles of 3 min of occlusion followed by 5 min of reperfusion, 30 min of coronary artery occlusion caused neither VT nor VF, but occasional VPBs (average 2 +/- 1, p < 0.001 vs. control). Only occasional VPBs were observed during 30 min of reperfusion in this group. In animals pretreated with indomethacin (1 mg/kg i.v., n = 5) followed by IP, prolonged ischemia and reperfusion led to frequent VPBs but no VT or VF. The average number of VPBs during ischemia and reperfusion in this indomethacin-treated group was less than that of the controls but greater than the IP-only group (p < 0.01). In conclusion, prostaglandins appear to play a role in the protective effect of IP against VPBs during acute ischemia and reperfusion.     

Is Performance Time a Prerequisite for the Onset and Intensity of the Occlusion-Reperfusion Arrhythmias in Anaesthetised Rats?

The aim of the present study is to investigate the onset and the intensity of arrhythmias in anaesthetized rats as a function of time under a standardized experimental condition, which is composed of 30 min occlusion and 60 min reperfusion. Local bred rats (250-350 g) housed in a 12-h light-dark cycle (lights on at 09.00 h, lights off at 21.00 h) were anaesthetized by sodium thiopentone (60 mg kg^-1 i.p.) and left anterior descending coronary artery ligation method using 6/0 braided silk ligature was used to induce 30 min occlusion and 60-min reperfusion. Animals were randomly allocated into three groups to exposure to 30-min occlusion at 9.00 h and 60 min reperfusion at 9:30 h (Group I, n = 6); to 30 min occlusion at 15.00 h and 60 min reperfusion at 15:30 h (Group II, n = 6); and to 30 min occlusion at 21.00 h and 60 min reperfusion at 21.30 h (Group III, n = 6). ECG and haemodynamic parameters were recorded throughout the experiments. The onset of ventricular ectopic beats (VEBs), number of VEBs, incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) during the periods of occlusion-reperfusion were analysed. Total VF incidence during occlusion were lower than the VT incidence in all groups. Either VT or VF incidences during reperfusion showed same profiles in all groups but VT incidence was 2-fold higher than VF. Time-dependent application of occlusion-reperfusion induced by coronary artery ligation method in the anaesthetized rats did not result in a variation in the onset and the intensity of arrhythmias. The duration of the experimental ischaemia was the principal factor, which determines the time of onset and intensity of the occlusion-reperfusion arrhythmias.     

Beneficial effects of astringinin, a resveratrol analogue, on the ischemia and reperfusion damage in rat heart

Oxidative stress plays an important role in the pathogenesis of myocardial ischemia and infarction. Antioxidants might then be beneficial in the prevention of these diseases. Astringinin (3,3',4',5-tetrahydroxystilbene), a resveratrol (3,4',5-trihydroxystilbene) analogue with considerably higher antioxidative activity and free radical scavenging capacity, was introduced to examine its cardioprotective effects in ischemia or ischemia-reperfusion (I/R) rats. In the present study, the left main coronary artery was occluded by the following procedures: (i) 30 min occlusion, (ii) 5 min occlusion followed by 30 min reperfusion, and (iii) 4 h occlusion. Animals were infused with and without astringinin before coronary artery occlusion. Mortality, and the severity of ischemia- and I/R-induced arrhythmias were compared. Pretreatment of astringinin dramatically reduced the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during either ischemia or I/R period. Astringinin at 2.5 x 10(-5) and 2.5 x 10(-4) g/kg completely prevented the mortality of animals during ischemia or I/R. During the same period, astringinin pretreatment also increased nitric oxide (NO) and decreased lactate dehydrogenase (LDH) levels in the carotid blood. In animals subjected to 4 h coronary occlusion, the cardiac infarct size (expressed as a percentage of occluded zone) was reduced from 44.4 + or - 4.1% to 19.1 + or - 2.4% by astringinin (2.5 x 10(-4) g/kg). We conclude that, astringinin is a potent antiarrhythmic agent with cardioprotective activity in ischemic and ischemic-reperfused rat heart. The beneficial effects of astringinin in the ischemic and ischemic-reperfused hearts may be correlated with its antioxidant activity and upregulation of NO production.     

Protective role of protein kinase C epsilon activation in ischemia-reperfusion arrhythmia

PURPOSE: Ischemic heart disease carries an increased risk of malignant ventricular tachycardia (VT), fibrillation (VF), and sudden cardiac death. Protein kinase C (PKC) epsilon activation has been shown to improve the hemodynamics in hearts subjected to ischemia/reperfusion. However, very little is known about the role of epsilon PKC in reperfusion arrhythmias. Here we show that epsilon PKC activation is anti-arrhythmic and its inhibition is pro-arrhythmic. METHOD: Langendorff-perfused isolated hearts from epsilonPKC agonist (epsilonPKC activation), antagonist (epsilonPKC inhibition) transgenic (TG), and wild-type control mice were subjected to 30 min stabilization period, 10 min global ischemia, and 30 min reperfusion. Action potentials (APs) and calcium transients (CaiT) were recorded simultaneously at 37 degrees C using optical mapping techniques. The incidence of VT and VF was assessed during reperfusion. RESULTS: No VT/VF was seen in any group during the stabilization period in which hearts were perfused with Tyrode's solution. Upon reperfusion, 3 out of the 16 (19%) wild-type mice developed VT but no VF. In epsilonPKC antagonist group, in which epsilonPKC activity was downregulated, 10 out of 13 (76.9%) TG mice developed VT, of which six (46.2%) degenerated into sustained VF upon reperfusion. Interestingly, in epsilonPKC agonist mice, in which the activity of epsilonPKC was upregulated, no VF was observed and only 1 out of 12 mice showed only transient VT during reperfusion. During ischemia and reperfusion, CaiT decay was exceedingly slower in the antagonist mice compared to the other two groups. CONCLUSION: Moderate in vivo activation of epsilonPKC exerts beneficial antiarrhythmic effect vis-a-vis the lethal reperfusion arrhythmias. Abnormal CaiT decay may, in part, contribute to the high incidence of reperfusion arrhythmias in the antagonist mice. These findings have important implications for the development of PKC isozyme targeted therapeutics and subsequently for the treatment of ischemic heart diseases.     

Myocardial ischemia-reperfusion damage impacts occurrence of ventricular fibrillation in dogs

To define the relationship between ischemia-reperfusion-induced myocardial damage (IRD) and the occurrence of ventricular tachycardia (VT) and fibrillation (VF), we studied 23 dogs with a three-dimensional activation mapping system. Left anterior descending (LAD) coronary artery occlusion and reperfusion were performed while recording electrograms during VF and atrial pacing. Prior nonischemic sites showing IRD, defined as at least 10% loss of electrogram voltage after reperfusion, had the longest ventricular effective refractory periods (ERPs). IRD sites also occurred more frequently in dogs with reperfusion VF (44 +/- 2 sites, P < 0.01) compared with dogs with VT (18 +/- 5 sites) and no VT (16 +/- 3 sites). In dogs (n = 3) with 3 h of reperfusion, 95% of IRD sites still had lower voltage than those recorded during occlusion. Activation mapping of the first eight complexes of VF had Purkinje or endocardial focal origin in 57%, and complexes originated from IRD sites in 28%. In contrast, dogs with only reperfusion VT also had Purkinje or endocardial focal origin in 79%, but only 5% (P < 0.01 vs. VF dogs) of the sites of origin had IRD. Therefore, dogs with reperfusion VF had more IRD sites where the ERP was longest, and more focal ventricular complexes originated from IRD sites, indicating that IRD may be one important factor in the occurrence of VF during reperfusion.     

Cardioprotective actions of wild garlic (Allium ursinum) in ischemia and reperfusion

The susceptibility to ventricular arrhythmias under the conditions of cardiac ischemia and reperfusion was investigated in the Langendorff heart preparation of rats fed for eight weeks a standard chow enriched with 2% of pulverized wild garlic leaves. The isolated hearts were perfused with a modified Krebs-Henseleit solution. The incidence of ventricular fibrillation (VF) during 20 min occlusion of thedescending branch of the left coronary artery (LAD) was significantly reduced in the wild garlic group as compared to untreated controls (20% vs 88%). The same holds for the size of the ischemic zone (33.6% vs 40.9% of heart weight). In the reperfusion experiments (5 min after 10 min ischemia), ventricular tachycardia (VT) occurred in 70% of the wild garlic group vs 100% in untreated controls and VF in 50% vs 90%. The time until occurrence of extrasytoles, VT or VR was prolonged. No significant alterations in cardiac fatty acid composition could be observed. Although the prostacyclin production was slightly increased in hearts of the wild garlic group, inhibition of cyclooxygenase by acetylsalicylic acid (ASA; aspirin) could not completely prevent the cardioprotective effects suggesting that the prostaglandin system, does not play, a decisive role in the cardioprotective action of wild garlic. Furthermore, a moderate angiotensin converting enzyme (ACE) inhibiting action of wild garlic was foundin vitro as well asin vivo that could contribute to the cardioprotective and blood pressure lowering action of wild garlic. Whether a free radiacal scavenging activity of wild garlic is involved in its cardioprotective effects remains to be established.     

Catecholamine release and ventricular arrhythmias during coronary occlusion and reperfusion in the dog

In anesthetized dogs, 60-min occlusions of either the proximal (n = 14), distal (n = 8) left circumflex (LCX), or left anterior descending (LAD, n = 10) arteries were followed by reperfusion. Coronary sinus and aortic norepinephrine and epinephrine plasma concentrations were measured. The ventricular arrhythmias were ventricular premature depolarizations (VPDs), unsustained ventricular tachycardia (VT) (greater than or equal to 3 and less than 20 VPDs), sustained VT (greater than or equal to 20 VPDs), and ventricular fibrillation (VF). A gradual twofold increase (p less than 0.05) in myocardial norepinephrine overflow followed occlusion in all three groups. The increases in the amounts of norepinephrine released in the coronary sinus blood during reperfusion were significant and proportional to the size of the occluded area: proximal LCX, from 0.236 +/- 0.038 to 1.528 +/- 0.490 ng/mL of plasma (p less than 0.001); LAD, from 0.180 +/- 0.027 to 0.795 +/- 0.286 ng/mL (p less than 0.05); distal LCX, from 0.215 +/- 0.039 to 0.404 +/- 0.110 ng/mL (p less than 0.05). Aortic epinephrine concentrations were significantly increased only by LAD occlusion; at 15 min, the value had increased to 0.187 +/- 0.053 ng/mL from an initial value of 0.069 +/- 0.029 ng/mL (p less than 0.001). Two phases of ventricular arrhythmias followed both occlusion and reperfusion. Phase 1 postocclusion was characterized by VPDs and phase 2 by VPDs and unsustained VT. Sustained VT was seen only in phase 1 postreperfusion, whereas unsustained VT was seen in phase 2. VF was seen in 50, 35, and 25% of the dogs with proximal LCX, LAD, and distal LCX occlusion and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antiarrhythmic effect of magnesium sulfate against occlusion-induced arrhythmias

The antiarrhythmic effect of magnesium sulfate (Mg) as well as the hemodynamics were studied using the coronary ligation and reperfusion models in rats.In the study on coronary ligation arrhythmia, i.v. administration of Mg (0.6, 2, 6, 20 and 60 \sgmaelig;mol) was conducted at 5 min after coronary ligation. Mg had an action to decrease the total number of premature ventricular contraction (PVC), the duration of ventricular tachycardia (VT), the frequency of VT and ventricular fibrillation (Vf) and the mortality ratio for 30 min after coronary ligation. In the 6-60 \sgmaelig;mol groups, significant antiarrhythmic action (p < 0.01 vs. control) was attained.In the study on reperfusion arrhythmia, i.v. administration of Mg (20, 60 and 200 \sgmaelig;mol) was conducted at 4 min after coronary ligation, and at 1 min after ligation, the coronary artery was reperfused. Mg had an action to decrease the frequency of Vf, the mortality ratio and the duration of VT and Vf and to extend the interval between the initiation of reperfusion and the occurrence of VT and Vf for 10 min after reperfusion. In the 200 \sgmaelig;mol group, significant antiarrhythmic action (p < 0.05 vs. control) was attained. Administration of Mg decreased the heart rate and blood pressure.We concluded that Mg can control myocardial ischemia-induced and reperfusion-induced arrhythmia and that sudden cardiac death which occurs as a result of arrhythmia can be prevented.     

Comparison of the effects of prostaglandins E1 and A1 on coronary occlusion induced arrhythmia.

The present study compares the effects of PGE1 and PGA1 on ventricular arrhythmias following coronary artery occlusion. The left anterior descending coronary artery (LAD) was occluded abruptly in 55 cats anesthetized with alpha-chloralose. Lead II of the ECG along with arterial blood pressure were monitored for one hour after occlusion. Either vehicle or prostaglandin was infused into the left atrium (LA) or femoral vein (IV) 15 min prior to and for 1 hour after LAD occlusion at a rate of 0.15 ml/min. Prostaglandin was infused at either a high dose (1.0 microgram/kg/min) or a low dose (0.1 microgram/kg/min). Infusion of either PGE1 or PGA1 produced a marked fall in blood pressure and heart rate which returned toward control before occlusion. Abrupt occlusion of the LAD produced ventricular arrhythmia in all cats ranging from ventricular premature beats to ventricular fibrillation (VF). The control animals had a 38% incidence of VF. VF occurred in 75% of the animals in which PGE1 was administered into the LA at either the high or low dose while the occurrence in those administered PGA1 was 67% and 50%, respectively. Intravenous administration of the high dose of PGE1 or PGA1 resulted in VF in 13% and 67% of the animals after LAD occlusion, respectively. These data indicate that the IV administration of PGE1 may protect the heart from VF while the infusion of PGE1 or PGA1 into the LA may enhance VF after LAD occlusion.     

Susceptibility to ischemia-induced arrhythmias and the effect of preconditioning in the diabetic rat heart

Diabetic heart is suggested to exhibit either increased or decreased resistance to ischemic injury. Ischemic preconditioning suppresses arrhythmias in the normal heart, whereas relatively little is known about its effects in the diseased myocardium. Our objective was to investigate whether development of diabetes mellitus modifies the susceptibility to ischemia-induced arrhythmias and affects preconditioning in the rat heart. Following 1 and 9 weeks of streptozotocin-induced (45 mg/kg, i.v.) diabetes, the hearts were Langendorff-perfused at constant pressure of 70 mm Hg and subjected to test ischemia induced by 30 min occlusion of the left anterior descending (LAD) coronary artery. Preconditioning consisted of one cycle of 5 min ischemia and 10 min reperfusion, prior to test ischemia. Susceptibility to ischemia-induced arrhythmias was lower in 1-week diabetics: only 42 % of diabetic hearts exhibited ventricular tachycardia (VT) and 16 % had short episodes of ventricular fibrillation (VF) as compared to VT 100 % and VF 70 % (including sustained VF 36 %) in the non-diabetics (P<0.05). Development of the disease was associated with an increased incidence of VT (VT 92 %, not significantly different from non-diabetics) and longer total duration of VT and VF at 9-weeks, as compared to 1-week diabetics. Preconditioning effectively suppressed arrhythmias in the normal hearts (VT 33 %, VF 0 %). However, it did not provide any additional antiarrhythmic protection in the acute diabetes. On the other hand, in the preconditioned 9-weeks diabetic hearts, the incidence of arrhythmias tended to decrease (VT 50 %, transient VF 10 %) and their severity was reduced. Diabetic rat hearts are thus less susceptible to ischemia-induced arrhythmias in the acute phase of the disease. Development of diabetes attenuates increased ischemic tolerance, however, diabetic hearts in the chronic phase can benefit more from ischemic preconditioning, due to its persisting influence.     

Protective Effect of ACE Inhibitors on Ischemia-Reperfusion-induced Arrhythmias in Rats: Is this Effect Related to the Free Radical Scavenging Action of these Drugs?

The antiarrhythmic effects of captopril, a sulphydrylcontaining angiotensin converting enzyme (ACE) inhibitor, were compared with those of the non-sulphydryl-containing ACE inhibitor lisinopril and the sulphydryl-containing agent glutathione in an in vivo rat model of coronary artery ligation. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. Captopril (3 mg kg^-1) and lisinopril (0.1, 0.3 or 1 mg kg^-1) caused marked decreases in mean arterial blood pressure (BP) and heart rate, whereas glutathione (5 mg kg^-) had no effect on them. The incidence of ventricular tachycardia (VT) on ischemia and reperfusion was significantly reduced by captopril and lisinopril. Captopril and 1 mg kg^-1 lisinopril also significantly decreased the number of VEB during occlusion and the duration of VT on reperfusion, respectively. These drugs also attenuated the incidence of reversible ventricular fibrillation (VF) and the number of ventricular ectopic beats (VEB) during reperfusion. However, glutathione only reduced the incidence of VT on reperfusion, significantly. These results suggest that, in this experimental model, ACE inhibitors limit the arrhythmias following ischemia-reperfusion and free radical scavenging action of these drugs does not have a major contributory role in their protective effect.     

Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat

Despite decades of research, there are few effective ways to treat ventricular fibrillation (VF), ventricular tachycardia (VT), or cardiac ischemia that show a significant survival benefit. Our aim was to investigate the combined therapeutic effect of two common antiarrhythmic compounds, adenosine and lidocaine (AL), on mortality, arrhythmia frequency and duration, and infarct size in the rat model of regional ischemia. Sprague-Dawley rats (n = 49) were anesthetized with pentobarbital sodium (60 mg.ml(-1).kg(-1) i.p.) and instrumented for regional coronary occlusion (30 min) and reperfusion (120 min). Heart rate, blood pressure, and a lead II electrocardiogram were recorded. Intravenous pretreatment began 5 min before ischemia and extended throughout ischemia, terminating at the start of reperfusion. After 120 min, hearts were removed for infarct size measurement. Mortality occurred in 58% of saline controls (n = 12), 50% of adenosine only (305 microg.kg(-1).min(-1), n = 8), 0% in lidocaine only (608 microg.kg(-1).min(-1), n = 8), and 0% in AL at any dose (152, 305, or 407 microg.kg(-1).min(-1) adenosine plus 608 microg.kg(-1).min(-1) lidocaine, n = 7, 8, and 6). VT occurred in 100% of saline controls (18 +/- 9 episodes), 50% of adenosine-only (11 +/- 7 episodes), 83% of lidocaine-only (23 +/- 11 episodes), 60% of low-dose AL (2 +/- 1 episodes, P < 0.05), 57% of mid-dose AL (2 +/- 1 episodes, P < 0.05), and 67% of high-dose AL rats (6 +/- 3 episodes). VF occurred in 75% of saline controls (4 +/- 3 episodes), 100% of adenosine-only-treated rats (3 +/- 2 episodes), and 33% lidocaine-only-treated rats (2 +/- 1 episodes) of the rats tested. There was no deaths and no VF in the low- and mid-dose AL-treated rats during ischemia, and only one high-dose AL-treated rat experienced VF (25.5 sec). Infarct size was lower in all AL-treated rats but only reached significance with the mid-dose treatment (saline controls 61 +/- 5% vs. 38 +/- 6%, P < 0.05). We conclude that a constant infusion of a solution containing AL virtually abolished severe arrhythmias and prevented cardiac death in an in vivo rat model of acute myocardial ischemia and reperfusion. AL combinational therapy may provide a primary prevention therapeutic window in ischemic and nonischemic regions of the heart.     

Donors of nitric oxide mimic effects of ischaemic preconditioning on reperfusion induced arrhythmias in isolated rat heart

NO has been implicated in the mechanism of ischaemic preconditioning. To verify this hypothesis further we have attempted to reproduce effects of ischaemic preconditioning by nitric oxide donors administration prior to the ischaemia. The effect of glyceryl trinitrate (GTN) and 3-morpholino-sydnonimine-hydrochloride (SIN- 1), NO donors, on reperfusion induced ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff perfused rat hearts subjected to 10 min regional ischaemia followed by 10 min reperfusion were examined. Results: GTN, 500 M and SIN-1, 10 M, administered for 5 min and washed for another 5 min prior to ischaemia (to mimic ischaemic preconditioning), almost completely abolished reperfusion induced VF. GTN and SIN-1, administered at the time of reperfusion, increased the incidence of sustained VF and the duration of VT and VF. When given 5 min before the ischaemia and throughout the ischaemia and the reperfusion, SIN-1 abolished VF. Adenosine, 10 M, applied according to the above three protocols, did not affect reperfusion arrhythmias, although adenosine induced changes in coronary flow and post-ischaemic reflow were similar to those produced by the NO donors. In conclusions: (1) NO is able to mimic the effect of ischaemic preconditioning on reperfusion arrhythmias in rat heart, supporting the view that NO may be one of the endogenous substances triggering ischaemic preconditioning; (2) In crystalloid-perfused heart, NO may be deleterious when its administration is restricted to the reperfusion period.     

Alpha 2-Adrenergic stimulation is protective against ischemia-reperfusion-induced ventricular arrhythmias in vivo

We previously reported that alpha(2)-adrenergic receptor (alpha(2)-AR) stimulation in Purkinje fibers in vitro prolongs action potential duration and suppresses beta-adrenergic-induced delayed afterdepolarizations and sustained triggered activities. We examined the effects of alpha(2)-AR stimulation on reperfusion-induced ventricular arrhythmias [ventricular tachycardia/ventricular fibrillation (VT/VF)] in vivo. Arterial blood pressure, heart rate, surface electrocardiogram, and renal sympathetic nerve activities were recorded simultaneously in Sprague-Dawley rats. The incidence of VT/VF was 87.5% for controls, 50% for the beta-blocker group, 72% for the alpha(1)-blocker group, and 12.5% for the alpha(1) + beta-blockers group (unopposed alpha(2)-adrenergic activation). Direct alpha(2)-AR stimulation with UK-14304 also prevented VT/VF. These effects were reversed by the alpha(2)-adrenergic antagonist yohimbine. Increases in renal sympathetic nerve activity were associated with left anterior descending coronary artery ligation and reperfusion (33 +/- 1.5 and 62 +/- 1.7% over baseline, respectively) in controls. Similar patterns were observed among all experimental groups irrespective of the incidence of VT/VF on reperfusion. We conclude that alpha(2)-AR stimulation has a potent antiarrhythmic effect on ischemia-reperfusion-induced VT/VF in vivo and that this effect is not centrally mediated.     

Ischaemic preconditioning in the rat heart: The role of G-proteins and adrenergic stimulation

Since recent findings indicate the involvement of G-proteins in the mechanisms of ischaemic preconditioning (PC), the present study was aimed to investigate the role of adrenergic mechanisms, such as G-proteins and stimulation of adrenergic receptors, in this phenomenon. For this purpose, isolated Langendorff-perfused rat hearts were subjected to regional ischaemia (30 min occlusion of LAD) followed by reperfusion. The effect of PC (a single 5 min occlusion/reperfusion before a long occlusion) on ischaemia- and reperfusion-induced arrhythmias was studied in conjunction with an assessment of G-proteins in the myocardial tissue by means of Western blotting and ADP-ribosylation with bacterial toxins. To follow the link between G-proteins and adrenergic receptors, their stimulation by exogenous norepinephrine (NE) was applied to test whether it can mimic the effect of PC on arrhythmias. Thirty min ischaemia and subsequent reperfusion induced high incidence of ventricular tachycardia (VT) and fibrillation (VF). PC significantly reduced a total number of extrasystoles, incidence of VT and abolished VF. It was, however, insufficient to suppress reperfusion-induced sustained VF. Measurement of G-proteins revealed that PC led to a reduction of stimulatory Gs proteins, whereas inhibitory Gi proteins were increased. NE (50 nmol) introduced in a manner similar to PC (5 min infusion, 10 min normal perfusion) reduced ischaemic arrhythmias in the same way, as PC. In addition, in NE-pretreated hearts reperfusion induced mostly transient VF, which was spontaneously reverted to a normal sinus rhythm. A transient increase in heart rate and perfusion pressure during NE infusion completely waned before the onset of ischaemia, indicating that antiarrhythmic effect was not related to haemodynamic changes and to conditions of myocardial perfusion. Conclusion: Antiarrhythmic effect of PC may be mediated by a stimulation of adrenergic receptors coupled to appropriate G-proteins. Consequently, the inhibition of adenylate cyclase activity and reduction in cAMP level, as well as the activation of protein kinase C may be considered as two possible pathways leading to a final response.     

Comparison of the effects of prostaglandins E1 and A1 on coronary occlusion induced arrhythmia

The present study compares the effects of PGE₁ and PGA₁ on ventricular arrhythmias following coronary artery occlusion. The left anterior descending coronary artery (LAD) was occluded abruptly in 55 cats anesthetized with α-chloralose. Lead II of the ECG along with arterial blood pressure were monitored for one hour after occlusion. Either vehicle or prostaglandin was infused into the left atrium (LA) or femoral vein (IV) 15 min prior to and for 1 hour after LAD occlusion at a rate of 0.15 ml/min. Prostaglandin was infused at either a high dose (1.0 μg/kg/min) or a low dose (0.1 μg/kg/min). Infusion of either PGE₁ or PGA₁ produced a marked fall in blood pressure and heart rate which returned toward control before occlusion. Abrupt occlusion of the LAD produced ventricular arrhythmia in all cats ranging from ventricular premature beats to ventricular fibrillation (VF). The control animals had a 38% incidence of VF. VF occurred in 75% of the animals in which PGE₁ was administered into the LA at either the high or low dose while the occurrence in those administered PGA₁ was 67% and 50%, respectively. Intravenous administration of the high dose of PGE₁ or PGA₁ resulted in VF in 13% and 67% of the animals after LAD occlusion, respectively. These data indicate that the IV administration of PGE₁ may protect the heart from VF while the infusion of PGE₁ or PGA₁ into the LA may enhance VF after LAD occlusion.     

Chemical preconditioning effect of 3-nitropropionic acid in anesthetized rat heart

Short ischemic episodes increase tolerance against subsequent severe ischemia in the heart. Nitropropionate (3-NP), an irreversible inhibitor of succinic dehydrogenase of the mitochondrial complex II, was shown to induce protective effect against ischemic brain injury. The aim of this study was to investigate the possible protective effect of 3-NP on regional ischemia in preconditioned rat heart in vivo. Hearts were assigned into three groups: first, in order to induce ischemic preconditioning (IP) 5 min ischemia separated by 10 min reperfusion protocol was used; second, non-preconditioned group was used as control; and third, 3-NP (20 mg/kg, i.p.) was injected 3 h before the surgical procedure in order to induce chemical preconditioning. In all these groups, 30 min regional ischemia was followed by 60 min reperfusion. Infarct size, bax expression, number of ventricular ectopic beats (VEB), duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) were significantly decreased in ischemic preconditioning and 3-NP pretreatment groups, whereas bcl-2 values were not markedly changed in these groups during occlusion period. These results showed that in the anesthetized rat heart 3-NP induced chemical preconditioning by decreasing infarct size, number of VEB, duration of VT and VF. Protective effect is associated with via decreased production of bax protein expression.     

Purkinje involvement in arrhythmias after coronary artery reperfusion

Previous studies have indicated that the endocardium may be responsible for a large portion of ventricular tachycardia (VT) seen with reperfusion of ischemic myocardium. To evaluate the role of the Purkinje system in nonreentrant VT arising from the endocardium after reperfusion, the anterior descending coronary artery was occluded for 20 min and then reperfused in 23 dogs after instrumentation of the risk zone with 21 multipolar plunge needles. VT with focal Purkinje origin was defined as a focal endocardial VT with Purkinje potentials recorded before the earliest endocardial myopotential. A total of 19 VTs (mean cycle length 214 +/- 2 ms) were observed with 11 (58%) having focal Purkinje origin. Fifty-eight percent of the VTs degenerated to ventricular fibrillation, with occurrences of two or more independent foci per complex (seen in 7 of 11 compared with 1 of 8 nonsustained VTs). In conclusion, these data show that Purkinje tissue may be important in the genesis of reperfusion VT.     

Cardioprotective mechanisms of Prunus cerasus (sour cherry) seed extract against ischemia-reperfusion-induced damage in isolated rat hearts

The effects of kernel extract obtained from sour cherry (Prunus cerasus) seed on the postischemic cardiac recovery were studied in isolated working rat hearts. Rats were treated with various daily doses of the extract for 14 days, and hearts were then isolated and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The incidence of ventricular fibrillation (VF) and tachycardia (VT) fell from their control values of 92% and 100% to 50% (not significant) and 58% (not significant), 17% (P<0.05), and 25% (P<0.05) with the doses of 10 mg/kg and 30 mg/kg of the extract, respectively. Lower concentrations of the extract (1 and 5 mg/kg) failed to significantly reduce the incidence of VF and VT during reperfusion. Sour cherry seed kernel extract (10 and 30 mg/kg) significantly improved the postischemic recovery of cardiac function (coronary flow, aortic flow, and left ventricular developed pressure) during reperfusion. We have also demonstrated that the extract-induced protection in cardiac function significantly reflected in a reduction of infarct size. Immunohistochemistry indicates that a reduction in caspase-3 activity and apoptotic cells by the extract, beside other potential action mechanisms of proanthocyanidin, trans-resveratrol, and flavonoid components of the extract, could be responsible for the cardioprotection in ischemic-reperfused myocardium.     

Drug effects on myocardial ischemia- and reperfusion-induced arrhythmias in anesthetized rats

The effects of drugs on ischemia and reperfusion-induced arrhythmias were studied in vivo in anesthetized rats. The chest was opened under artificial respiration and the heart was exposed. The left anterior descending coronary artery was occluded, followed by reperfusion for 10 min each. The drugs (mannitol 10-50 mg/kg, aspirin 0.25-5 mg/kg, verapamil 5-50 micrograms/kg and propranolol 1 mg/kg iv) were tested in the vagotomized animals. The test agent was dissolved in saline and 0.5 ml infused 15 min before the coronary occlusion. The results indicated that mannitol and aspirin reduced the incidence and duration of arrhythmias (ventricular premature contraction, ventricular tachycardia and ventricular fibrillation) during ischemia and reperfusion, while verapamil and propranolol reduced the incidence of arrhythmias during ischemia.