Duration Of Ventricular Arrhythmias Research Articles

PO-455617-5 ANTI-ARRHYTHMIC EFFECTS OF BIOINSPIRED MODIFIED Y RNA IN RATS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION

Exosomes secreted from cardiosphere-derived cells (CDCs) attenuate ventricular arrhythmias and prolong survival of rats with heart failure and preserved ejection fraction (HFpEF). Y RNA fragments were abundant in exosomes secreted from CDCs, and they mediate the anti-inflammatory and anti-fibrotic effects of CDCs. We tested the hypothesis that bioinspired modified Y RNA decrease ventricular arrhythmias in rats with HFpEF by reversing electrical remodeling. Dahl salt-sensitive (DSS) rats (n=19) were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF. Echocardiogram was performed at 14 weeks of age to confirm the development of diastolic dysfunction (increased E/E’ ratio). Symptomatic rats with diastolic dysfunction were diagnosed with HFpEF. TY1 (Therapeutic Y RNA1, a modified Y RNA in transfection reagent) was injected via the tail vein (twice weekly for 4 weeks) to rats with HFpEF (n=7). Vehicle (phosphate-buffered saline in transfection reagent) and scramble (in transfection reagent) were also injected via the tail vein as placebo (n=8 and 4, respectively). Echocardiogram and programmed electrical stimulation (PES) were performed after 4 weeks of TY1 vs. vehicle or scramble injections. Electrocardiogram was performed to measure QTc intervals as a marker for adverse electrical remodeling. Ventricular arrhythmias were induced in 80% of vehicle-injected and 100% of scramble-injected HFpEF rats by PES, as compared to only 33% of TY1-injected HFpEF rats (p=0.036). The duration of ventricular arrhythmias was significantly lower in TY1-injected HFpEF rats as compared to vehicle-injected and scramble-injected HFpEF rats (4 [IQR 0-5] beats in TY1 vs. 30 [IQR 8-54] beats in vehicle, p=0.034; vs. 21 [16-48] beats in scramble; p=0.031). QTc interval was reduced in TY1-injected HFpEF rats as compared to vehicle or scramble-injected HFpEF rats (QTc interval 238±16 ms in TY1 vs. 271±24 ms in vehicle, p=0.034; vs. 280±7 ms in scramble, p=0.017). Survival was prolonged in TY1-injected HFpEF rats as compared to vehicle or scramble-injected HFpEF rats, although statistically insignificant due to a low number of rats (86% in TY1 vs. 63% in vehicle or 75% in scramble). TY1, a modified Y RNA, reduced ventricular arrhythmias in rats with HFpEF by reversing adverse electrical remodeling of HFpEF (as manifested by a shortened QTc interval). Given these encouraging data, TY1 merits further investigation as a novel therapeutic candidate for ventricular arrhythmias.

PO-02-209 ANTI-ARRHYTHMIC EFFECTS OF BIOINSPIRED MODIFIED Y RNA IN RATS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION

Exosomes secreted from cardiosphere-derived cells (CDCs) attenuate ventricular arrhythmias and prolong survival of rats with heart failure and preserved ejection fraction (HFpEF). Y RNA fragments were abundant in exosomes secreted from CDCs, and they mediate the anti-inflammatory and anti-fibrotic effects of CDCs. We tested the hypothesis that bioinspired modified Y RNA decrease ventricular arrhythmias in rats with HFpEF by reversing electrical remodeling. Dahl salt-sensitive (DSS) rats (n=19) were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF. Echocardiogram was performed at 14 weeks of age to confirm the development of diastolic dysfunction (increased E/E’ ratio). Symptomatic rats with diastolic dysfunction were diagnosed with HFpEF. TY1 (Therapeutic Y RNA1, a modified Y RNA in transfection reagent) was injected via the tail vein (twice weekly for 4 weeks) to rats with HFpEF (n=7). Vehicle (phosphate-buffered saline in transfection reagent) and scramble (in transfection reagent) were also injected via the tail vein as placebo (n=8 and 4, respectively). Echocardiogram and programmed electrical stimulation (PES) were performed after 4 weeks of TY1 vs. vehicle or scramble injections. Electrocardiogram was performed to measure QTc intervals as a marker for adverse electrical remodeling. Ventricular arrhythmias were induced in 80% of vehicle-injected and 100% of scramble-injected HFpEF rats by PES, as compared to only 33% of TY1-injected HFpEF rats (p=0.036). The duration of ventricular arrhythmias was significantly lower in TY1-injected HFpEF rats as compared to vehicle-injected and scramble-injected HFpEF rats (4 [IQR 0-5] beats in TY1 vs. 30 [IQR 8-54] beats in vehicle, p=0.034; vs. 21 [16-48] beats in scramble; p=0.031). QTc interval was reduced in TY1-injected HFpEF rats as compared to vehicle or scramble-injected HFpEF rats (QTc interval 238±16 ms in TY1 vs. 271±24 ms in vehicle, p=0.034; vs. 280±7 ms in scramble, p=0.017). Survival was prolonged in TY1-injected HFpEF rats as compared to vehicle or scramble-injected HFpEF rats, although statistically insignificant due to a low number of rats (86% in TY1 vs. 63% in vehicle or 75% in scramble). TY1, a modified Y RNA, reduced ventricular arrhythmias in rats with HFpEF by reversing adverse electrical remodeling of HFpEF (as manifested by a shortened QTc interval). Given these encouraging data, TY1 merits further investigation as a novel therapeutic candidate for ventricular arrhythmias.

Ventricular arrhythmias following balloon-expandable transcatheter pulmonary valve replacement in the native right ventricular outflow tract.

Ventricular arrhythmia incidence in children and adolescents undergoing transcatheter pulmonary valve replacement (TPVR) within the native right ventricular outflow tract (nRVOT) is unknown. We sought to describe the incidence, severity, and duration of ventricular arrhythmias and identify associated risk factors in this population. This was a retrospective cohort study of 78 patients <21 years of age who underwent TPVR within the nRVOT. Patients were excluded for pre-existing ventricular arrhythmia or antiarrhythmic use. Study variables includedsurgical history, valve replacement indication, valve type/size, and ventricular arrhythmia. Univariable logistic regression models were used to evaluate factors associated with ventricular arrhythmias, followed by subset analyses. Nonsustained ventricular arrhythmia occurred in 26/78 patients (33.3%). The median age at the procedure was 10.3 years (interquartle range [IQR]: 6.5, 12.8). Compared with other nRVOT types, surgical repair with transannular patch was protective against ventricular arrhythmia incidence: odds ratio (OR): 0.35 (95% confidence interval [CI], 0.13-0.95). Patient weight, valve type/size, number of prestents, and degree of stent extension into the RVOT were not associated with ventricular arrhythmia occurrence. Beta blocker was started in 16/26 (61.5%) patients with ventricular arrhythmia. One additional patient was lost to follow-up. The median beta blocker duration was 46 days (IQR 42, 102). Beta blocker was discontinued in 10 patients by 8-week follow-up and in the remaining four by 9 months. Though common after balloon-expandable TPVR within the nRVOT, ventricular arrhythmias were benign and transient. Antiarrhythmic medications were successfully discontinued in the majority at 6- to 8-week follow-up, and in all patients by 20 months.

Integrated Pharmacogenetics Analysis of the Three Fangjis Decoctions for Treating Arrhythmias Based on Molecular Network Patterns.

Aim: To explore the diverse target distribution and variable mechanisms of different fangjis prescriptions when treating arrhythmias based on the systems pharmacology.Methods: The active ingredients and their corresponding targets were acquired from the three fangjis [Zhigancao Tang (ZT), Guizhigancao Longgumuli Tang (GLT), and Huanglian E'jiao Tang (HET)] and the arrhythmia-related genes were identified based on comprehensive database screening. Networks were constructed between the fangjis and arrhythmia and used to define arrhythmia modules. Common and differential gene targets were identified within the arrhythmia network modules and the cover rate (CR) matrix was applied to compare the contributions of the fangjis to the network and modules. Comparative pharmacogenetics analyses were then conducted to define the arrhythmia-related signaling pathways regulated by the fangjis prescriptions. Finally, the divergence and convergence points of the arrhythmia pathways were deciphered based on databases and the published literature.Results: A total of 187, 105, and 68 active ingredients and 1,139, 1,195, and 811 corresponding gene targets of the three fangjis were obtained and 102 arrhythmia-related genes were acquired. An arrhythmia network was constructed and subdivided into 4 modules. For the target distribution analysis, 65.4% of genes were regulated by the three fangjis within the arrhythmia network. ZT and GLT were more similar to each other, mainly regulated by module two, whereas HET was divided among all the modules. From the perspective of signal transduction, calcium-related pathways [calcium, cyclic guanosine 3′,5′-monophosphate (cGMP)-PKG, and cyclic adenosine 3′,5′-monophosphate (cAMP)] and endocrine system-related pathways (oxytocin signaling pathway and renin secretion pathways) were associated with all the three fangjis prescriptions. Nevertheless, heterogeneity existed between the biological processes and pathway distribution among the three prescriptions. GLT and HET were particularly inclined toward the conditions involving abnormal hormone secretion, whereas ZT tended toward renin-angiotensin-aldosterone system (RAAS) disorders. However, calcium signaling-related pathways prominently feature in the pharmacological activities of the decoctions. Experimental validation indicated that ZT, GLT, and HET significantly shortened the duration of ventricular arrhythmia (VA) and downregulated the expression of CALM2 and interleukin-6 (IL-6) messenger RNAs (mRNAs); GLT and HET downregulated the expression of CALM1 and NOS3 mRNAs; HET downregulated the expression of CRP mRNA.Conclusion: Comparing the various distributions of the three fangjis, pathways provide evidence with respect to precise applications toward individualized arrhythmia treatments.

A Clinical Study on the Influence of Shenmai Injection on the Cardiac Function and Arrhythmias in Patients with Chronic Heart Failure

To investigate the clinical effect of Shenmai injection on cardiac function and arrhythmias in patients with chronic heart failure. A total of 120 patients with chronic heart failure who were hospitalized in our hospital from December 2017 to June 2019 were selected and randomly divided into Shenmai group and control group after signing the informed consent form. The patients in the control group were given conventional treatment and the Shenmai group was treated with Shenmai injection on the basis of the control group. The course of the treatment in both groups was 14 d. Holter was performed in both groups before and after treatment, and the differences in the frequency and duration of atrial or ventricular arrhythmias were compared between the two groups. The main adverse cardiovascular events were recorded during 6-12 mo follow-up. The clinical total effective rate of Shenmai group was 87.66 % and that of control group was 85.96 % (p<0.05). After treatment, the frequency and duration of atrial or ventricular arrhythmias in Shenmai group were significantly improved (p<0.05); the frequency of atrial arrhythmias in the control group were increased and the difference was statistically significant (p<0.05), but there was no significant difference in the duration of atrial arrhythmias and the frequency or duration of ventricular arrhythmias before and after treatment. There was no significant difference in main adverse cardiovascular events between the two groups after 6-12 mo of follow-up (χ2=1.115, p>0.05). Shenmai injection has a definite effect in the treatment of chronic heart failure, which can effectively improve the heart function, arrhythmias and life quality of the patients with good safety.

Anti-ischemic and antiarrhythmic activity of dibornol in conditions of multiple transitory myocardial ischemia in rats

Aim. To investigate anti-ischemic and antiarrhythmic activity of Dibornol in conditions of multiple transitory ischemia of myocardium from in vivo experiments with rats. Material and Methods. The experiment was performed on male Wistar rats with a model of myocardial ischemia caused by 5-time 3-minute occlusions of the left coronary artery, followed by 15-minute reperfusion periods. Rats of the experimental group received Dibornol 10 mg/kg intragastrically once for 4 days; control animals received an equivalent volume of 1% starch mucus. On the ECG, the magnitudes of the ST segment elevation were determined for minutes 1, 2, and 3 of each episode of ischemia and for minutes 5, 10, and 15 of reperfusion; the nature and duration of ventricular arrhythmias were determined as well. Results. In the control group, the ST segment was elevated during all five episodes of ischemia. During reperfusion periods, a decrease in the elevation of the ST segment was detected, but no normalization occurred. Ischemic and reperfusionrelated ventricular arrhythmias were observed in the rats of the control group. Mortality in the control group reached 67% (6 animals out of 9). In the experimental group, in animals receiving Dibornol at a dose of 10 mg/kg, the occlusion of the left coronary artery was associated only with a slight elevation of the ST segment and its rapid recovery during reperfusion. Magnitudes of the ST segment elevation were significantly lower than the corresponding control values during all the episodes of ischemia. During reperfusion periods, the differences with the control group were more significant during the first to fourth periods and at minute 15 of the fifth reperfusion period. The death rate in the experimental group (1 animal out of 9) was significantly lower relative to the corresponding value in the control group. Conclusion. The course preventive use of Dibornol in multiple myocardial ischemia/reperfusion had significant anti-ischemic and antiarrhythmic effects during reperfusion periods and significantly increased the survival rate in animal models.

0228 : Beneficial effects of zinc on incidence and severity of ventricular reperfusion arrhythmias

Intermittent hypoxia (IH), a major component of obstructive sleep apnea syndrome (OSA), causes several cardiovascular alterations such as hypertension, increased infarct size and ventricular arrhythmias. Indeed, IH exposure enhances the incidence of severe ventricular arrhythmias during both ischemia and reperfusion. Oxidative stress is a common feature behind the deleterious effects of both IH and ischemia-reperfusion on the myocardium. Zinc is an essential metal associated with numerous proteins and playing a vital role in various cellular functions. Its homeostasis is closely linked to the cell redox state since zinc release by oxidation can induce protein conformation changes. The resulting modification in protein activity could thus be restored by zinc administration. Thereby, the effects of zinc supplementation were investigated in isolated perfused rat hearts presenting severe ventricular reperfusion arrhythmias following a 15-min regional ischemia. Incidence, severity and duration of ventricular arrhythmias were assessed during the first 10min of reperfusion. Three groups were compared in which zinc (pyrithione form, Zn-Pyr, 2.10-5M in DMSO), DMSO (vehicle) or pyrithione sodium (Na-Pyr) was added to the Krebs upon reperfusion. Reperfusion with Zn-Pyr significantly enhanced survival (40%) compared to DMSO or Na-Pyr (6%) (n=17 per group, p<0.05). Moreover, the time spent in sinus rhythm was significantly increased in the Zn-Pyr group compared to other groups (p<0.01). Accordingly, the duration of ventricular tachycardia/fibrillation was significantly decreased in the Zn-Pyr group (p<0.05). Therefore, zinc administration during reperfusion improves survival in response to a severe ischemic insult. Zinc supplementation upon myocardial reperfusion procedures could thus represent a valuable approach to prevent the occurrence of arrhythmias and could be of interest in the prevention of IHand OSA-related ventricular arrhythmias.

Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors

BackgroundClinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion.Methods & Results6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury.ConclusionsPulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.

Suppression of Ischemic and Reperfusion Ventricular Arrhythmias by Inhalational Anesthetic-Induced Preconditioning in the Rat Heart

Inhalational anesthetic-induced preconditioning (APC) has been shown to reduce infarct size and attenuate contractile dysfunction caused by myocardial ischemia. Only a few studies have reported the effects of APC on arrhythmias during myocardial ischemia-reperfusion injury, focusing exclusively on reperfusion. Accordingly, the aim of the present study was to examine the influence of APC on ventricular arrhythmias evoked by regional no-flow ischemia. APC was induced in adult male Wistar rats by 12-min exposures to two different concentrations (0.5 and 1.0 MAC) of isoflurane followed by 30-min wash-out periods. Ventricular arrhythmias were assessed in the isolated perfused hearts during a 45-min regional ischemia and a subsequent 15-min reperfusion. Myocardial infarct size was determined after an additional 45 min of reperfusion. The incidence, severity and duration of ventricular arrhythmias during ischemia were markedly reduced by APC. The higher concentration of isoflurane had a larger effect on the incidence of ventricular fibrillation than the lower concentration. The incidence of ventricular tachycardia and reversible ventricular fibrillation during reperfusion was also significantly reduced by APC; the same was true for myocardial infarct size. In conclusion, we have shown that preconditioning with isoflurane confers profound protection against myocardial ischemia- and reperfusion-induced arrhythmias and lethal myocardial injury.

Both Mitochondrial KATP Channel Opening and Sarcolemmal KATP Channel Blockage Confer Protection Against Ischemia/Reperfusion-Induced Arrhythmia in Anesthetized Male Rats

this study was performed to assess the effect of selective sarcolemmal adenosine triphosphate (ATP)-sensitive K(+) channel (K(ATP)) inhibition and the mitochondrial K(ATP) channel activation on ischemia and reperfusion (I/R)-induced arrhythmias in different gender of rats. We compared the effect of a selective sarcolemmal K(ATP) channel blocker HMR 1098, a selective mitochondrial K(ATP) channel opener diazoxide, a nonselective K(ATP) channel opener pinacidil, and the combination of pinacidil with HMR 1098 on the incidence and duration of ventricular arrhythmias in 2 groups: anesthetized males (n = 31) and females (n = 31). ischemia and reperfusion was produced by occluding the left main coronary artery of Sprague-Dowley rats for 6 minutes followed by re-opening of the artery for 6 minutes. the arrhythmia score and the duration of arrhythmias were significantly reduced by HMR 1098, diazoxide, and pinacidil in male rats. The combination of the pinacidil with HMR 1098 did not change the antiarrhythmic effect of pinacidil. The duration of arrhythmas was shorter in females than that in the corresponding males. Drug treatments were not effective in decreasing arrhythmias in female groups to the same extent as in the male group. However, the mitochondrial K( ATP) channel activation that is provided by the combination of pinacidil with HMR 1098 significantly decreased the total length of arrhythmias in females. results of the current study indicate that both mitochondrial K(ATP) channel activation and sarcolemmal K(ATP) channel inhibition exert antiarrhythmic action in male rats. The antiarrhythmic effect of pinacidil is not depend on the sarcolemmal K(ATP) channel opening. These results also indicate that K(ATP) channel modulators show no discernable effect in female rats due to the already low incidence of arrhythmias in females.

Noninvasive Limb Ischemic Preconditioning Protects Against Myocardial I/R Injury in Rats

Transient limb ischemia induces remote early preconditioning that protects the myocardium from ischemia/reperfusion (I/R). However, it is unknown whether limb ischemia induces remote late preconditioning and whether it induces the same magnitude of cardioprotection compared with cardial ischemic preconditioning (CIP). We tested the hypothesis that late remote preconditioning of noninvasive limb ischemia (NLIP) offers the same magnitude of cardioprotection against myocardium I/R injury. Thirty Wistar rats weighing 240-260 g each were randomly divided into three groups: I/R, CIP, and NLIP. The mean arterial pressure (MAP), heart rate (HR), ST-segment, ventricular arrhythmia, and CK-MB, cTnI, and superoxide dismutase (SOD) activity were measured after 0 and 30 min of ischemia and after 120 min of reperfusion. Myocardial infarct size, histologic examination, MMP-2, MMP-9, and TIMP-1 protein expression were determined at the end of the experiment. Compared with I/R groups, CIP and NLIP reduced ST-segment elevation (P<0.01), decreased incidence and duration of ventricular arrhythmia (P<0.01) during ischemia, decreased CK-MB (P<0.05), and cTnI (P<0.01) activity, and increased SOD (P<0.05) activity after reperfusion. The myocardial infarct size (P<0.01) was significantly reduced, and cell injury was attenuated in the CIP and NLIP groups compared with the I/R group. MMP-2 and MMP-9 protein expression was significantly decreased in the CIP and NLIP groups (P<0.01), while TIMP-1 expression was significantly increased in the CIP and NLIP groups compared with the I/R group (P<0.01). Remote preconditioning via NLIP has late cardioprotection against myocardium I/R injury and has a similar magnitude of cardioprotection compared with CIP in rats.

Granulocyte Colony-stimulating Factor Reduces Mortality by Suppressing Ventricular Arrhythmias in Acute Phase of Myocardial Infarction in Rats

Our aim was to evaluate the effects of granulocyte colony-stimulating factor (G-CSF) on early cardiac arrhythmias after myocardial infarction (MI) and the impact on survival. Male Wistar rats received repeated doses of 50 mug/kg G-CSF (MI-GCSF group) or vehicle (MI group) at 7, 3, and 1 days before surgery. MI was induced by permanent occlusion of left coronary artery. The electrocardiogram was obtained before occlusion and then for 30 minutes after surgery. Events and duration of ventricular arrhythmias were analyzed. The levels of connexin43 (Cx43) were measured by Western blot immediately before MI production. Survival was significantly increased in MI-GCSF pretreated group (74% versus 52.9% MI, P < 0.05). G-CSF pretreatment also significantly reduced the ventricular premature beats when compared with the untreated-MI group (201 +/- 47 versus 679 +/- 117, P < 0.05). The number and the duration of ventricular tachycardia were smaller in the MI-G-CSF group, as well as the number of ventricular fibrillation episodes (10% versus 69% in MI, P < 0.05). Cx43 levels were significantly increased by G-CSF treatment (1.27 +/- 0.13 versus 0.86 +/- 0.11; P < 0.05). The MI size 24 hours after occlusion was reduced by G-CSF pretreatment (36 +/- 3% versus 44 +/- 2% of left ventricle in MI group; P < 0.05). The increase of Cx43 expression in the heart may explain the reduced incidence in ventricular arrhythmias in the early phases after coronary artery occlusion in rats, thus increasing survival after MI.

Effect of desflurane-induced preconditioning following ischemia-reperfusion on nitric oxide release in rabbits

Nitric oxide (NO) is the mediator of ischemic preconditioning against myocardial infarction. Desflurane produces anesthetic preconditioning to protect the myocardium against infarction. In the model of myocardial ischemia-reperfusion injury in rabbits, we evaluated desflurane-induced ischemic preconditioning and studied its mechanism of NO synthesis. Thirty-two male adult New Zealand white rabbits were anesthetized with intravenous (IV) 30 mg/kg pentobarbital followed by 5 mg/kg/hr infusion. All rabbits were subjected to 30 minutes (min) long lasting left anterior descending coronary artery (LAD) occlusion and three hours (hr) of subsequent reperfusion. Before LAD occlusion, the rabbits were randomly allocated into four groups for preconditioning treatment (eight for each group). The control group did not receive any preconditioning treatment. The desflurane group received inhaled desflurane 1.0 MAC (minimal end-tidal alveolar concentration) for 30 min that was followed by a 15 min washout period. The L-NAME-desflurane group received L-NAME (N G-nitro-L-arginine methyl ester; non-selective Nitric Oxide Synthetase (NOS) inhibitor) 1 mg/kg IV 15 min before 1.0 MAC inhaled desflurane for 30 min. The L-NAME group received L-NAME 1 mg/kg IV. Infarct volume, ventricular arrhythmia, plasma lactate dehydrogenase (LDH), creatine kinase (CK) activity and myocardial perfusion were recorded simultaneously. We have found that hemodynamic values of the coronary blood flow before, during, and after LAD occlusion were not significantly different among these four groups. For the myocardial ischemia-reperfusion injury animals, the infarction size (mean ± SEM) in the desflurane group was significantly reduced to 18 ± 3% in the area at risk as compared with 42 ± 7% in the control group, 35 ± 6 in the L-NAME group, and 34 ± 4% in the L-NAME-desflurane group. The plasma LDH, CK levels, and duration of ventricular arrhythmia were also significantly decreased in the desflurane group during ischemia-reperfusion injury. Our results indicate that desflurane is an anesthetic preconditioning agent, which could protect the myocardium against the ischemia-reperfusion injury. This beneficial effect of desflurane on the ischemic preconditioning is probably through NO release since L-NAME abrogates the desflurane preconditioning effect.

Antiarrhythmic Effect of Magnolol and Honokiol during Acute Phase of Coronary Occlusion in Anesthetized Rats: Influence of L-NAME and Aspirin

This study was designed to evaluate the in vivo effect of magnolol and honokiol on the acute phase of coronary ligation in the presence of nitric oxide inhibitor (L-NAME) or cyclooxygenase inhibitor (aspirin). After Sprague-Dawley rats were anesthetized with urethane, the changes of ventricular arrhythmia induced by coronary ligation for 30 min were determined with or without pretreatment with study medications. The incidence and duration of ventricular arrhythmia were significantly reduced after intravenous pretreatment (15 min before coronary ligation) with 10^–7 g/kg magnolol or 10^–7 g/kg honokiol. However, the antiarrhythmic effect of magnolol or honokiol could be abolished with the pretreatment of 1 mg/kg L-NAME, but not with pretreatment of 100 mg/kg aspirin. The abolishment of the myocardial beneficial effect of magnolol and honokiol by L-NAME, instead of aspirin, suggests an involvement of an increased nitric oxide synthesis in the protection offered by magnolol and honokiol against arrhythmia during myocardial ischemia.

Suppression of reperfusion induced arrhythmias in the isolated rat heart: pretreatment with 7-oxo prostacyclin in vivo

The aim was to investigate the late effect of pretreatment with 7-oxo prostacyclin on reperfusion induced arrhythmias in the isolated rat heart. Forty eight hours after intramuscular administration of drug in vivo (50 micrograms.kg-1 body weight), isolated Langendorff perfused rat hearts were subjected to 30 minutes of regional ischaemia and 5 minutes of reperfusion. Incidence and duration of ventricular arrhythmias in both pretreated and control groups were evaluated on reperfusion. Morphological examination was also performed. In the untreated group reperfusion induced 75% of sustained ventricular fibrillation. Incidence of ventricular fibrillation, its duration, and arrhythmia score were significantly lower in the pretreated group. Pretreatment with 7-oxo prostacyclin had no effect on heart rate and coronary flow throughout the whole course of perfusion. Neither was the occluded zone size affected. Ultrastructure of ischaemic and reperfused myocardium was better preserved in the pretreated group. Antiarrhythmic action of 7-oxo prostacyclin was unrelated to changes in haemodynamics, thus suggesting the direct influence of the myocardium. The possible mechanism of action may involve maintenance of intracellular cation homeostasis (particularly of Na+ and Ca2+) due to a stimulation of sarcolemmal Na+ pump activity.

Influence of halothane and catecholamines on heart rate and rhythm in the horse.

1. Ventricular ectopic beats were recorded in eight of thirteen conscious horses following the intravenous administration of adrenaline in doses of 3 mug/kg. Following pre-treatment with either atropine sulphate (0.1 mg/kg) or propranolol hydrochloride (0.1 mg/kg), the same dose level of adrenaline failed to produce ventricular ectopic beats.2. Halothane anaesthesia sensitized the equine heart to the arrhythmogenic actions of adrenaline; the incidence and duration of ventricular arrhythmias being greater than in conscious animals. In comparison with the findings in conscious horses, ether anaesthesia appeared to protect the heart against adrenaline-induced arrhythmias.3. From a comparison of the arrhythmogenic, chronotropic and pressor actions of adrenaline, noradrenaline and isoprenaline during halothane anaesthesia, it was concluded that sensitization to the arrhythmogenic actions of catecholamines resulted primarily from the action of halothane on the ventricle. The results also indicated that the pressor responses to catecholamines during halothane anaesthesia probably played some part in the genesis of arrhythmias.4. No "spontaneous" ventricular arrhythmias were recorded in twenty-four horses anaesthetized with halothane or in sixteen animals under ether anaesthesia.5. The available evidence indicates that a moderate to fairly severe degree of hypercapnia produced little increase in sympathetic control of the myocardium during halothane anaesthesia; the absence of irregularities in ventricular rhythm during halothane anaesthesia were attributed to this factor.

Digitalis toxicity: II. The effect of metabolic alkalosis

The influence of metabolic alkalosis on the amount of acetylstrophanthidin necessary to produce ventricular tachycardia was studied in anesthetized dogs. Although an infusion of sodium hydroxide to produce an average pH of 7.57 resulted in hypokalemia, no significant difference in the amount of acetylstrophanthidin necessary to cause digitalis toxicity during control and metabolic alkalosis was noted. Acute digitalization produced an elevation of serum potassium, a slower heart rate, and an increase in arterial blood pressure. The duration of ventricular arrhythmias caused by acetylstrophanthidin, however, was greatly prolonged in the alkalotic animals. Possible mechanisms to explain this observation were discussed.