A proof-of-concept study evaluating cardiac compression techniques for cardiopulmonary resuscitation in laying hens (Gallus gallus).

OBJECTIVE: To determine in adult chickens which of 3 CPR techniques, sternal compressions (SC), SC with interposed caudal coelomic compressions (ICCC), or lateral compressions (LC), results in the highest mean systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) as measured directly from the carotid artery. DESIGN: Prospective, nonblinded, experimental crossover study. SETTING: University teaching hospital laboratory. ANIMALS: Ten retired laying hens. INTERVENTIONS: Birds were sedated, anesthetized, and placed in dorsal recumbency. A carotid artery catheter was placed to directly measure arterial pressure. Ventricular fibrillation was induced with direct cardiac stimulation using a 9-Volt battery. Each bird then received 2 minutes of the 3 different cardiac compression techniques in a random order by 3 different compressors, with the compressor order also randomized. Birds were subsequently administered IV epinephrine, and transthoracic defibrillation was attempted. At the end of experimentation, each bird was euthanized, and simple gross necropsies were performed. Linear mixed models followed by pairwise paired t-tests were performed to evaluate differences in pressures generated by each technique. MEASUREMENTS AND MAIN RESULTS: The primary study outcomes were SAP, DAP, and MAP over 2 minutes of compressions for each compression technique. Pressures from ICCC (SAP: 27.6 ± 5.3 mm Hg, DAP: 18.7 ± 5.2 mm Hg, MAP: 21.7 ± 5.2 mm Hg) were significantly higher than those from LC (SAP: 18.9 ± 5.4 mm Hg, DAP: 11.6 ± 4.1 mm Hg, MAP: 14.1 ± 4.5 mm Hg). Pressures from SC (SAP: 24.5 ± 6.4 mm Hg, DAP: 15.2 ± 4.3 mm Hg, MAP: 18.3 ± 5.0 mm Hg) were not significantly different from ICCC or LC. CONCLUSIONS: External compressions can generate detectable increases in arterial pressure in chickens with ventricular fibrillation. SC with ICCC generated significantly higher arterial pressures than LC. SC alone generated blood pressures that were not significantly different from those generated by SC with ICCC or LC.

MANAGEMENT OF ATRIAL FIBRILLATION, VENTRICULAR ARRHYTHMIA, LEFT VENTRICULAR DYSFUNCTION, AND SUBSEQUENT CARDIOPATHOLOGIC EVALUATION IN AN ORANGUTAN (PONGO PYGMAEUS × ABELII).

A 37-yr-old male vasectomized hybrid orangutan (Pongo pygmaeus × abelii) was diagnosed with left ventricular dysfunction during a preventative health care examination. Treatment was initiated with carvedilol. The following year, this orangutan was evaluated for intermittent lethargy. Following observation of an irregular cardiac rhythm during an echocardiogram, a lead II electrocardiogram revealed atrial fibrillation and ventricular arrhythmia. Additional treatment included amiodarone, furosemide, spironolactone, clopidogrel, and aspirin. An improved activity level was noted, and follow-up testing showed restoration of a sinus rhythm, reduced frequency of ventricular arrhythmia, and improved left ventricular function. The orangutan died 27 mon after initial diagnosis of heart disease, and a complete necropsy was performed. This article describes successful diagnosis and management of structural and arrhythmic heart disease in an orangutan, emphasizing the role of cardiac disease screening and behavioral training in apes, as well as the value of matching thorough antemortem and postmortem cardiac evaluation.

Magnitude of mitral valve closure plays a pivotal role in enhancing the forward blood flow during cardiac massage in dogs with ventricular fibrillation.

Motion of mitral valve during cardiac massage was examined using beagle dogs with ventricular fibrillation (n=4). Active compression-decompression cardiac massage (ACD-CM) exhibited greater peak aortic pressure than standard cardiac massage (S-CM), reverse of which was true for peak pulmonary capillary wedge pressure in each animal. Accordingly, peak aortic pressure was greater than peak pulmonary capillary wedge pressure with ACD-CM, whereas its reverse was true with S-CM. Transesophageal echocardiography revealed that mitral valve was incompletely closed with S-CM with showing regurgitation. The valve was more effectively closed during ACD-CM. These results indicate that effective closure of mitral valve during cardiac massage may increase forward blood flow, supporting "cardiac pump theory" rather than "thoracic pump theory" as a principle in dogs.

The development of ventricular fibrillation as a complication of pericardiectomy in 16 dogs.

OBJECTIVE: To describe the clinical characteristics, perioperative protocols, and outcomes in dogs diagnosed with ventricular fibrillation (VF) while undergoing pericardiectomy. STUDY DESIGN: Retrospective, multi-institutional study. ANIMALS: Sixteen client-owned dogs. METHODS: Cases were accrued through a listserve request posted to 3 subspecialty veterinary societies. Dogs were included if they developed VF during a pericardiectomy performed through an open or thoracoscopic approach. Data collected included signalment, history and physical examination, surgical approach, histopathology, treatment, and outcome. RESULTS: Indications for pericardiectomy included idiopathic chylothorax (n = 7), neoplasia (4), idiopathic pericardial effusion (4), and foreign body granuloma (1). Surgical approaches included thoracoscopy (12), intercostal thoracotomy (3) and median sternotomy (1). Electrosurgical devices were used to complete at least part of the pericardiectomy in 15 of 16 dogs. Ventricular fibrillation appeared to be initiated during electrosurgical use in 8/15 dogs. However, in 5/15 dogs it was not obviously associated with electrosurgical use. In 3/16 dogs the timing of initiation of VF was unclear. In 7/16 dogs, cardiac arrhythmias were noted prior to the development of VF. Fourteen of 16 dogs died from intraoperative VF. CONCLUSION: In most dogs ventricular fibrillation was a fatal complication of pericardiectomy. Ventricular fibrillation might be associated with the use of electrosurgical devices and cardiac manipulation during pericardiectomy although a causal link could not be established from the data in this study. CLINICAL SIGNIFICANCE: Surgeons must be aware of the risk of VF during pericardial surgery. Electrosurgery might need to be used judiciously during pericardiectomy, particularly in dogs exhibiting cardiac arrythmias.

Rhythm disturbances associated with lidocaine administration in four dogs with supraventricular tachyarrhythmias.

OBJECTIVE: To describe arrhythmias associated with administration of lidocaine in dogs treated for supraventricular tachyarrhythmias. CASE SUMMARIES: Four dogs with recent-onset supraventricular tachyarrhythmias: 3 dogs had atrial fibrillation (AF), and 1 had focal atrial tachycardia (FAT), which was thought to be AF at the time of assessment. The substrate of the supraventricular tachyarrhythmia was considered to be due to primary cardiomyopathy in 1 dog, high vagal tone in 2 dogs, and the change in hemodynamics from heavy sedation in 1 dog. Pharmacological cardioversion using lidocaine was only successful in the 2 dogs with vagally mediated AF. In these 2 cases, lidocaine administration resulted in a paroxysmal atrial flutter that was self-limiting and quickly led to sinus rhythm within 10 seconds in 1 dog but did not change over a 5-minute interval and required additional boluses in another dog. In the latter case, the dog showed severe bradycardia for 17.5 seconds prior to achieving sinus rhythm. The 2 unsuccessful cases both developed ventricular arrhythmias shortly after the lidocaine administration, with 1 case degenerating into ventricular fibrillation and cardiac arrest. NEW OR UNIQUE INFORMATION PROVIDED: Arrhythmias associated with lidocaine should be considered when treating dogs with supraventricular tachyarrhythmia.

Successful treatment of prolonged refractory ventricular fibrillation in an anesthetized dog.

OBJECTIVE: To describe a case of successful return of spontaneous circulation in an anesthetized dog that developed spontaneous ventricular fibrillation during CPR that was refractory to multiple defibrillation attempts by utilizing pharmacological antiarrhythmic therapy. CASE SUMMARY: Cardiopulmonary arrest occurred during surgical preparation in a 1-year-old German Shepherd Dog under general anesthesia for fluoroscopic implantation of an Amplatz canine duct occluder for treatment of a patent ductus arteriosus. Pulseless electrical activity was initially diagnosed, and resuscitative efforts were immediately initiated, including basic cardiac life support, discontinuation of anesthesia with administration of reversal agents, and low-dose epinephrine administration (0.01 mg/kg, IV). After 10 minutes of CPR, the patient developed ventricular fibrillation and single-dose monophasic defibrillation attempts of escalating energy were performed. Despite these efforts, return of spontaneous circulation was unable to be achieved. However, administration of magnesium sulfate (20 mg/kg, IV) along with an additional single monophasic defibrillation attempt was successful in achieving return of spontaneous circulation. NEW OR UNIQUE INFORMATION PROVIDED: Under current advanced cardiac life support guidelines, the best resuscitation strategy for refractory ventricular fibrillation, in which the arrhythmia persists despite multiple defibrillation attempts, remains unclear. This is especially true for veterinary patients, where refractory ventricular fibrillation is an uncommon cardiac arrest rhythm. Although guidelines for the use of antiarrhythmic therapy during cardiac arrest are well established in human medicine, evidence-based guidelines to support best practices in companion animals do not exist due to sparse data gathered through experimental studies. Only a few case reports describe successful return of spontaneous circulation following prolonged ventricular fibrillation in clinical veterinary patients. Although the use of magnesium sulfate as an antiarrhythmic agent during refractory ventricular fibrillation has been previously reported in people, this is the first case to our knowledge of refractory ventricular fibrillation in a dog that responded to magnesium sulfate.

Spontaneous torsade de pointes and ventricular fibrillation in a dog during pacemaker implantation.

Torsade de pointes is an unusual complication seen in dogs during pacemaker implantation, although ventricular fibrillation has been previously reported. This case report describes torsade de pointes in a dog during pacemaker implantation that degenerated into ventricular fibrillation and discusses the possible contributory factors. It also illustrates the relevance of a pre-emptive resuscitation plan and how this might have affected the outcome in the patient.

ST segment depression and ventricular fibrillation in a dog after contrast agent administration.

An 11-year-old Toy Poodle underwent a computed tomography examination with contrast (iohexol) enhancement under anesthesia. Heart rate and R-wave amplitude on electrocardiogram (ECG) increased 2.5 min after iohexol administration, and end-tidal carbon dioxide decreased to 12 mmHg. A progressive ST segment depression was observed on ECG. Subsequently, the ECG waveform changed to ventricular fibrillation. However, spontaneous circulation returned following cardiopulmonary resuscitation. Myocardial ischemia or anaphylactic shock was suspected in the dog, which explains the ST segment depression observed on ECG. When performing radiological examinations with a contrast agent, the ECG waveform changes, such as an increase in heart rate, R-wave amplitude, or ST segment depression, should be carefully monitored. This might enable early detection of cardiac dysfunction and the ensuing cardiac arrest in dogs.

Successful management of ventricular fibrillation and ventricular tachycardia using defibrillation and intravenous amiodarone therapy in a cat.

OBJECTIVE: To describe the successful management of ventricular fibrillation (VF) and ventricular tachycardia (VT) using cardiopulmonary resuscitation, including defibrillation, followed by continuous rate infusion of IV amiodarone, in a cat with cardiac arrest secondary to tachyarrhythmia. CASE SUMMARY: A 12-year-old previously healthy neutered male Scottish Fold cat presented following an acute episode of collapse. Initial physical examination revealed severe tachycardia and cardiovascular collapse. Within a few minutes after arrival, the cat experienced cardiopulmonary arrest. Electrocardiographic assessment was suggestive of VF, and CPR was initiated, including 2 rounds of defibrillation (2 joule/kg each), resulting in return of spontaneous circulation with sustained VT. After procainamide and lidocaine failed to result in conversion to normal sinus rhythm (NSR), continuous IV amiodarone therapy was initiated, and NSR was achieved. Echocardiography demonstrated severe systolic dysfunction, and tachycardia-induced cardiomyopathy (TICM) secondary to chronic VT was suspected; however, dilated cardiomyopathy (DCM) or end-stage hypertrophic cardiomyopathy could not be ruled out. The patient was discharged the following day with oral amiodarone and pimobendan. During a recheck examination performed 7 months later the cat was in NSR, with no direct evidence of long-term amiodarone adverse effects. The cat died acutely at home 8 months after discharge. NEW OR UNIQUE INFORMATION PROVIDED: This report is the first to describe the successful use of IV amiodarone in a cat to manage sustained VT following CPR.

Duty cycle of 33% increases cardiac output during cardiopulmonary resuscitation.

BACKGROUND: The aim of this study was to investigate whether 33% duty cycle increases end-tidal carbon dioxide (ETCO2) level, a surrogate measurement for cardiac output during cardiopulmonary resuscitation (CPR), compared with 50% duty cycle. METHODS: Six pigs were randomly assigned to the DC33 or DC50 group. After 3 min of induced ventricular fibrillation (VF), CPR was performed for 5 min with 33% duty cycle (DC33 group) or with 50% duty cycle (DC50 group) (phase I). Defibrillation was delivered until return of spontaneous circulation (ROSC) thereafter. After 30 min of stabilization, the animals were re-assigned to the opposite groups. VF was induced again, and CPR was performed (phase II). The primary outcome was ETCO2 during CPR, and the secondary outcomes were coronary perfusion pressure (CPP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and right atrial pressure (RAP). RESULTS: Mean ETCO2 was higher in the DC33 group compared with the DC50 group (22.5 mmHg vs 21.5 mmHg, P = 0.018). In a linear mixed model, 33% duty cycle increased ETCO2 by 1.0 mmHg compared with 50% duty cycle (P < 0.001). ETCO2 increased over time in the DC33 group [0.6 mmHg/min] while ETCO2 decreased in the DC50 group [-0.6 mmHg/min] (P < 0.001). Duty cycle of 33% increased SAP (6.0 mmHg, P < 0.001), DAP (8.9 mmHg, P < 0.001) RAP (2.6 mmHg, P < 0.001) and CPP (4.7 mmHg, P < 0.001) compared with the duty cycle of 50%. CONCLUSION: Duty cycle of 33% increased ETCO2, a surrogate measurement for cardiac output during CPR, compared with duty cycle of 50%. Moreover, ETCO2 increased over time during CPR with 33% duty cycle while ETCO2 decreased with 50% duty cycle.

Cardiovascular changes after administration of aerosolized salbutamol in horses: five cases.

Prevention and treatment of intraoperative hypoxemia in horses is difficult and both efficacy and safety of therapeutic maneuvers have to be taken into account. Inhaled salbutamol has been suggested as treatment of hypoxia in horses during general anesthesia, due to safety and ease of the technique. The present report describes the occurrence of clinically relevant unwanted cardiovascular effects (i.e. tachycardia and blood pressure modifications) in 5 horses undergoing general anesthesia in dorsal recumbency after salbutamol inhalation. Balanced anesthesia based on inhalation of isoflurane in oxygen or oxygen and air and continuous rate infusion (CRI) of lidocaine, romifidine, or combination of lidocaine and guaifenesine and ketamine was provided. Supportive measures were necessary to restore normal cardiovascular function in all horses but no long-term adverse effects were noticed in any of the cases.

La distensión de la región isquémica predice una mayor inducibilidad de fibrilación ventricular tras la oclusión coronaria en el modelo porcino / Distension of the ischemic region predicts increased ventricular fibrillation inducibility following coronary occlusion in swine

Introducción y objetivos. La distensión de la región isquémica se ha relacionado con una mayor incidencia de arritmias ventriculares espontáneas tras la oclusión coronaria. Analizamos si la distensión isquémica regional predice una mayor inducibilidad de fibrilación ventricular tras la oclusión coronaria en cerdos. Métodos. En 18 cerdos anestesiados con tórax abierto, se ocluyó la descendente anterior durante 60 min. Se monitorizó la longitud segmentaria en la región isquémica mediante cristales ultrasónicos. Se realizó estimulación programada basal, y después continuamente entre 10 y 60 min tras la oclusión. Resultados. La oclusión coronaria indujo un rápido aumento en la longitud telediastólica en la región isquémica, que alcanzó el 109,4±0,9% de los valores basales a los 10 min (p<0,001). Se completaron 6,6±0,5 protocolos de estimulación, que indujeron 5,4±0,6 episodios de fibrilación ventricular entre 10 y 60 min tras la oclusión. Ni los valores séricos de potasio ni el tamaño del área isquémica se asociaron significativamente con la inducibilidad de fibrilación ventricular. Por el contrario, el aumento en la longitud telediastólica 10 min tras la oclusión coronaria se asoció directamente (r=0,67; p=0,002) con el número de episodios inducidos de fibrilación ventricular e inversamente (r=–0,55; p=0,018) con el número de extraestímulos necesarios para inducir la arritmia. Conclusiones. La distensión regional isquémica predice una mayor inducibilidad de fibrilación ventricular tras la oclusión coronaria. Estos resultados subrayan la influencia potencial de los factores mecánicos, que actúan no sólo sobre los desencadenantes, sino también sobre el sustrato, en la génesis de las arritmias ventriculares malignas durante la isquemia aguda (AU)

Introduction and objectives. Distension of the ischemic region has been related to an increased incidence of spontaneous ventricular arrhythmias following coronary occlusion. This study analyzed whether regional ischemic distension predicts increased ventricular fibrillation inducibility after coronary occlusion in swine. Methods. In 18 anesthetized, open-chest pigs, the left anterior descending coronary artery was ligated for 60min. Myocardial segment length in the ischemic region was monitored by means of ultrasonic crystals. Programmed stimulation was applied at baseline and then continuously between 10 and 60min after coronary occlusion. Results. Coronary occlusion induced a rapid increase in end-diastolic length in the ischemic region, which reached 109.4% (0.9%) of baseline values 10min after occlusion (P<.001). On average, 6.6 (0.5) stimulation protocols were completed and 5.4 (0.6) ventricular fibrillation episodes induced between 10 and 60min of coronary occlusion. Neither baseline serum potassium levels nor the size of the ischemic region were significantly related to ventricular fibrillation inducibility. In contrast, the increase in end-diastolic length 10min after coronary occlusion was associated directly (r=0.67; P=.002) with the number of induced ventricular fibrillation episodes and inversely (r=–0.55; P=.018) with the number of extrastimuli needed for ventricular fibrillation induction. Conclusions. Regional ischemic expansion predicts increased ventricular fibrillation inducibility following coronary occlusion. These results highlight the potential influence of mechanical factors, acting not only on the triggers but also on the substrate, in the genesis of malignant ventricular arrhythmias during acute ischemia (AU)

Modificaciones de la fibrilación ventricular y de la capacidad de captura inducidas por una lesión lineal con radiofrecuencia / Modifications in ventricular fibrillation and capture capacity induced by a linear radiofrequency lesion

Introducción y objetivos. Analizar los efectos, en la fibrilación ventricular y en la capacidad de capturar al miocardio mediante estimulación a frecuencias rápidas, de una lesión lineal producida con radiofrecuencia. Métodos. En 22 corazones de conejo aislados y perfundidos, se utilizaron electrodos múltiples epicárdicos para registrar la fibrilación ventricular. Se analizaron los mapas de activación al aplicar trenes de estímulos a tres frecuencias distintas, cercanas a las de la arritmia, en tres situaciones: a) basalmente; b) tras producir con radiofrecuencia una lesión en la pared libre del ventrículo izquierdo (longitud, 10±1mm), y c) tras ampliar su extensión (longitud, 23±2mm). Resultados. Tras la lesión, se observó una disminución de la regularidad de las señales registradas y variaciones significativas en la dirección de los frentes de activación. Con la lesión ampliada, se incrementaron ligeramente los episodios con al menos tres capturas consecutivas al estimular con ciclos un 10% más largos que los de la arritmia (basal, 0,6±0,7; lesión inicial, 1±1, diferencias no significativas; lesión ampliada, 3±2,8; p<0,001), mientras que se redujeron los obtenidos al estimular con ciclos un 10% más cortos que los de la arritmia. Conclusiones. La lesión efectuada con radiofrecuencia aumenta la heterogeneidad de la activación miocárdica durante la fibrilación ventricular y modifica la llegada de los frentes de activación a las zonas adyacentes. La estimulación durante la fibrilación ventricular a frecuencias rápidas provoca capturas ocasionales durante al menos tres estímulos consecutivos. La lesión ampliada incrementa ligeramente la capacidad de captura al utilizar ciclos ligeramente más largos que los de la fibrilación ventricular (AU)

Introduction and objectives. An analysis was made of the effects of a radiofrequency-induced linear lesion during ventricular fibrillation and the capacity to capture myocardium through high-frequency pacing. Methods. Using multiple epicardial electrodes, ventricular fibrillation was recorded in 22 isolated perfused rabbit hearts, analyzing the activation maps upon applying trains of stimuli at 3 different frequencies close to that of the arrhythmia: a) at baseline; b) after radio-frequency ablation to induce a lesion of the left ventricular free wall (length=10 [1]mm), and c) after lengthening the lesion (length=23 [2]mm). Results. Following lesion induction, the regularity of the recorded signals decreased and significant variations in the direction of the activation fronts were observed. On lengthening the lesion, there was a slight increase in the episodes with at least 3 consecutive captures when pacing at cycles 10% longer than the arrhythmia (baseline: 0.6 [0.7]; initial lesion: 1 [1] no significant differences; lengthened lesion: 3 [2.8]; P<.001), while a decrease was observed in those obtained upon pacing at cycles 10% shorter than the arrhythmia. Conclusions. The radio-frequency -induced lesion increases the heterogeneity of myocardial activation during ventricular fibrillation and modifies arrival of the activation fronts in the adjacent zones. High-frequency pacing during ventricular fibrillation produces occasional captures during at least 3 consecutive stimuli. The lengthened lesion in turn slightly increases capture capacity when using cycles slightly longer than the arrhythmia (AU)

Successful biphasic transthoracic defibrillation of a dog with prolonged, refractory ventricular fibrillation.

OBJECTIVE: To describe a case of spontaneous ventricular fibrillation in a dog in which biphasic defibrillation was life saving. CASE SUMMARY: Ventricular fibrillation occurred in a 7-year-old female Australian Heeler during recovery from anesthesia following pacemaker implantation. Resuscitative efforts including immediate delivery of transthoracic monophasic defibrillation shocks of escalating energy and administration of vasopressors were unsuccessful. However, a single biphasic shock restored sinus rhythm despite prolonged duration of the arrhythmia. NEW OR UNIQUE INFORMATION PROVIDED: This case suggests greater efficacy of biphasic defibrillation compared with traditional monophasic defibrillation. In this dog the newer, biphasic technology was life saving after monophasic shocks failed repeatedly to terminate ventricular fibrillation.

Differences in ventricular vulnerability, serum enzyme activities, and electrolyte levels between male and female broilers.

Sudden death syndrome (SDS) is one of the most serious diseases of fast-growing broilers. The incidence of SDS may result from a decrease in ventricular function. The purpose of this study was to explore the mechanism of sexual difference in the sensitivity of broilers to SDS by measuring their ventricular vulnerability, serum enzyme activities, and serum electrolyte levels. Results were as follows. 1) Ventricular fibrillation thresholds induced by injection of KCl and by electrical stimulus of male broilers were both significantly lower than those of female broilers (P < 0.05), suggesting that the ventricular vulnerability of male broilers was higher than that of female broilers. 2) Serum lactate dehydrogenase and creatine kinase activities of male broilers were significantly higher than those of female broilers (P < 0.01), but there was not a significant difference in serum aspartate aminotransferase activity between male and female broilers. 3) No significant difference was observed in serum electrolyte levels of potassium, sodium, and chloride between males and females. From these results, we concluded that there is a significant difference between males and females in their ventricular vulnerability and serum enzyme activities, which may result in a higher sensitivity of male broilers to injury of the myocardium by stress and may further result in a sexual difference in sensitivity to SDS.

Nitric oxide involvement in the delayed antiarrhythmic effect of treadmill exercise in dogs.

We have shown previously that a single period of treadmill exercise in dogs protects the heart against the severe ventricular arrhythmias that arise when a major (anterior descending) branch of the left coronary artery is occluded following anaesthesia 24 h later. This protection is aminoguanidine sensitive, suggesting a role for nitric oxide (NO) in this exercise-induced delayed antiarrhythmic effect. The present study has further examined the possible role of NO as a mediator and/or as a trigger using the selective induced (iNOS) inhibitor S-(2-aminoethyl)-methyl-isothiourea (AEST) and the specific but not selective nitric oxide synthase inhibitor N(omega)-nitro-L-arginine-methyl-ester (L-NAME). Exercise markedly reduced the severity of ischaemia and reperfusion-induced ventricular arrhythmias 24 h later. Thus, only one of the dogs (8%) so exercised fibrillated on occlusion (contrast 46% in the control, non-exercised dogs; P<0.05) and the marked changes in the inhomogeneity of electrical activation that occur in the ischaemic region following occlusion were much reduced (P<0.05 compared to controls). This delayed exercise-induced cardioprotection was significantly attenuated by the nitric oxide synthase (NOS) inhibitors L-NAME, given prior to the exercise protocol and by AEST given prior to the coronary artery occlusion. For example, survival from the ischaemia-reperfusion insult was 54% in the exercise dogs, 0% in the controls and 14% in those dogs given a NOS inhibitor. We conclude that nitric oxide (NO) is both the trigger and the mediator of this delayed protection against ischaemia and reperfusion-induced arrhythmias.

Pentobarbital versus medetomidine-ketamine-fentanyl anaesthesia: effects on haemodynamics and the incidence of ischaemia-induced ventricular fibrillation in swine.

The present study was performed to compare haemodynamic variables at baseline and the incidence of ventricular fibrillation during the early phase of ischaemia in swine during pentobarbital or medetomidine-ketamine-fentanyl anaesthesia. Twenty-two swine (mean +/- SD: 29+/- 3 kg) were anaesthetized with sodium pentobarbital (induction with 36 mg/kg intraperitoneally, and maintenance with 5-20 mg/kg/h intravenously [i.v.]) and 6 swine (27+/- 3 kg) were anaesthetized with ketamine and fentanyl (premedicated with medetomidine 0.1 mg/kg and ketamine 10 mg/kg intramuscularly, induction with ketamine 20 mg/kg and fentanyl 0.025 mg/kg i.v., and maintenance with ketamine 20 mg/kg/h and fentanyl 0.025 mg/kg/h i.v.). After a stabilization period of 30 min, the left anterior descending coronary artery (LAD) was occluded for 10 min. Haemodynamic data and occurrence of ventricular fibrillation were recorded. The ischaemic area was measured by fluorescing microspheres. Swine anaesthetized with medetomidine-ketamine-fentanyl had significantly lower heart rate, myocardial contractility, peak left ventricular pressure, arterial blood pressure, aortic blood flow, myocardial blood flow and cardiac index at baseline, than swine anaesthetized with pentobarbital. Whereas none of the swine anaesthetized with pentobarbital fibrillated during the LAD occlusion, ventricular fibrillation occurred in 83% of the animals anaesthetized with medetomidine-ketamine-fentanyl (P< 0.001). No significant difference was found in size of ischaemic area between the two groups. Thus, we show a depression in haemodynamic variables at baseline and a higher incidence of ventricular fibrillation during the early phase of ischaemia in swine anaesthetized with medetomidine-ketamine-fentanyl compared to swine anaesthetized with pentobarbital.

Effects of biphasic vs monophasic defibrillation on the scaling exponent in a swine model of prolonged ventricular fibrillation.

OBJECTIVE: Mathematical analyses of ventricular fibrillation (VF) have resulted in the derivation of a measure termed the scaling exponent (ScE) that characterizes the duration of VF and probability of defibrillation success. The purpose of this study was to compare the effects of biphasic defibrillation waveform (BDW) and monophasic defibrillation waveform (MDW) rescue shocks on ScE in a swine model of prolonged VF. METHODS: Utstein guidelines for the laboratory study of cardiopulmonary resuscitation were followed. Twenty mixed-breed domestic swine (mass range 20.5-26.8 kg) were instrumented and randomized to receive either MDW or BDW rescue shocks. Ventricular fibrillation was induced and untreated for a nonintervention interval of 8 minutes. Rescue shocks were delivered at 8, 10, and 12 minutes of elapsed VF time. The energy sequence for the three MDW shocks was 70, 100, and 150 J (approximately 3, 4, and 6 J/kg). All BDW shocks were delivered at 50 J (approximately 2.5 J/kg). Only VF was shocked. Chest compressions and drugs were not provided. Rhythm analysis and ScE calculation were performed offline. Continuous and discontinuous linear regression models were fit to plots of ScE vs time. Defibrillation success and progression of ScE slope were analyzed using Fisher's exact test, paired t-tests, and repeated-measures analysis of variance (ANOVA). RESULTS: Baseline characteristics were similar for both groups. Successful termination of VF occurred on the first rescue shock in 1 of 10 (10%) in the MDW group and 3 of 10 (30%) in the BDW group; this difference was not statistically significant (p = 0.58). No other defibrillation successes were observed. No animals achieved return of spontaneous circulation. The ScE values during the protocol progressed from 1.330 (95% CI = 1.287 to 1.373) to 1.724 (95% CI = 1.603 to 1.845) for MDW and 1.338 (95% CI = 1.261 to 1.415) to 1.639 (95% CI = 1.530 to 1.745) for BDW. Both groups showed a trend toward increasing ScE values with successive rescue shocks. Repeated-measures ANOVA using both continuous and discontinuous models demonstrated no difference in overall ScE slope progression between study groups. CONCLUSIONS: Mode of defibrillation waveform (BDW vs MDW) does not appear to impact ScE trends. Additional studies must be performed to better evaluate the clinical implications of this finding.

Hemodynamic and electrophysiologic effects of ontazolast in dogs.

OBJECTIVE: To determine whether QT interval is prolonged or sudden death is caused by ventricular fibrillation resulting from torsades de pointes and to identify hemodynamic effects of ontazolast. ANIMALS: 28 Beagles. PROCEDURE: Physiologic variables were measured for 2 hours in conscious dogs given ontazolast (0, 1, or 3 mg/kg of body weight, IV) and for 1 hour in anesthetized dogs given cumulative doses of ontazolast (0, 1, 3, 6, or 8 mg/kg, IV). RESULTS: Ontazolast prolonged QT interval and QT interval corrected for heart rate (QTc) at doses of 6 mg/kg in anesthetized dogs. At 8 mg/kg, both variables remained prolonged but tended to decrease. In conscious dogs, ontazolast increased QT interval and QTc 15 minutes after administration, but both variables returned to reference ranges by 60 minutes. In conscious dogs, ontazolast increased maximum rate of increase of left ventricular pressure and maximal velocity of fiber shortening, indicators of inotropy, and increased tau, indicating a decreased rate of relaxation. One conscious dog receiving 3 mg/kg developed nonfatal torsades de pointes, but another conscious dog developed ventricular fibrillation. Two anesthetized dogs receiving 6 mg/kg developed early afterdepolarizations, and all dogs developed secondary components in theirT waves. CONCLUSION AND CLINICAL RELEVANCE: Ontazolast possesses potent class-III antiarrhythmic properties and induces prolongation of QTc in a dose-dependent fashion. Because there was a clear dose-dependent prolongation of QT interval in all instances, ontazolast may serve as a positive-control compound for studying other compounds that are believed to prolong the QT interval.