Adjustable model of chronic left ventricular dysfunction.

BACKGROUND: As an adjunct to the development of skeletal muscle-powered left ventricular assist devices, an adjustable model of chronic left ventricular failure was developed. METHODS: Implantation of a left ventricular balloon to induce heart failure was accomplished via left thoracotomy. Upon recovery, left ventricular failure was simulated by manipulation of left ventricular balloon volume to chronically raise left atrial pressure. RESULTS: Left atrial pressure increased from a baseline of 9.3 +/- 0.7 mm Hg to 18.5 +/- 1.2 mm Hg, 20.2 +/- 1.8 mm Hg, and 26.0 +/- 1.2 mm Hg by the 2nd, 6th, and 10th postoperative week, respectively. Cardiac index declined from a baseline of 4.4 +/- 0.3 L x min(-1) x m(-2), reaching stability by the 8th postoperative week at 3.0 +/- 0.4 L x min(-1) x m(-2). Stroke volume index declined from 1.12 +/- 0.1 mL x kg(-1) x beat(-1) to 0.60 +/- 0.1 mL x kg(-1) x beat(-1) by the 10th postoperative week. Mean survival was 75 +/- 7 days. Causes of death included left ventricular failure, thromboembolism, and euthanasia. CONCLUSIONS: This method of simulating chronic left ventricular dysfunction proved to be stable and adjustable and has been useful in the development of ventricular assist systems.

Perfluorocarbon supplementation and postischemic cardiac function.

BACKGROUND: During induced ischemia for cardiac surgery inefficient anaerobic energy mechanisms predominate. Sustaining aerobic metabolism with perfluorocarbon-supplemented blood cardioplegia theoretically could lead to improved postischemic recovery. Therefore we studied functional recovery after myocardial ischemia, comparing perflubron (C8F17Br) supplemented blood cardioplegia to standard blood cardioplegia. METHODS: Nineteen dogs underwent 15 minutes of 37 degrees C global ischemia on cardiopulmonary bypass, followed by 90 minutes of cardioplegic arrest by use of blood cardioplegia with or without perflubron and then 30 minutes of 37 degrees C reperfusion. During ischemia myocardial oxygen tension, temperature, and pH were measured. Postischemic left ventricular recovery was assessed by means of preload recruitable stroke work, exponential end-diastolic stress-strain regression, and preservation of adenosine triphosphate and energy charge. RESULTS: The addition of perflubron, a new shorter half-life, lecithin-emulsified perfluorocarbon, provided superior myocardial protection when compared with standard blood cardioplegia. This benefit was evidenced by significantly increased recovery of preload recruitable stroke work slope (71% +/- 8% versus 42% +/- 9%), decreased myocardial edema, and enhanced end ischemic myocardial oxygen and pH levels. CONCLUSIONS: The reliable oxygen delivery system and endothelial-preserving properties of the perfluorocarbons may prove to be an invaluable asset in addition to standard blood cardioplegia in the preservation of postischemic ventricular function. These data support the further investigation of perfluorocarbon-enriched blood cardioplegia.

Functional recovery after ischemia: warm versus cold cardioplegia.

Warm continuous retrograde cardioplegia has been introduced for myocardial protection during cardiac operations, particularly in the setting of acute myocardial ischemia because of its theoretical advantage of producing arrest without ischemia. To investigate the ability of warm continuous retrograde cardioplegia to provide myocardial protection after acute global ischemia, versus the more commonly used cold intermittent antegrade cardioplegia, 12 dogs were subjected to 15 minutes of normothermic global myocardial ischemia on cardiopulmonary bypass followed by 75 minutes of protected cardioplegic arrest using either warm continuous retrograde cardioplegia or cold intermittent antegrade cardioplegia. Standard blood cardioplegia at clinically used volumes and flow rates was used. Warm continuous retrograde cardioplegia animals received 30 mL/kg antegrade to induce arrest followed by 1.5 to 1.8 mL.kg-1.min-1 retrograde at 37 degrees C, whereas cold intermittent antegrade cardioplegia animals received 30 mL/kg antegrade to induce arrest followed by 15 mL/kg antegrade every 15 minutes at 10 degrees C. Load-insensitive left ventricular systolic function, diastolic function, high energy nucleotides, and edema formation were assessed before and after ischemia. Results showed that myocardial preservation using clinically reported flow rates and volumes of warm continuous retrograde cardioplegia was significantly inferior to that provided by clinically used cold intermittent antegrade cardioplegia, as demonstrated by decreased preload recruitable stroke work slope (28 +/- 11 versus 71 +/- 6), increased alpha constant of the end diastolic stress-strain relationship (14.2 +/- 3.0 versus 3.6 +/- 1.0), decreased total nondiffusable nucleotides (40.7 +/- 2.3 versus 57.4 +/- 2.3 microM/g wet weight) and increased water content (82.2% +/- 0.4% versus 80.4% +/- 0.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Early outcome of mitral valve reconstruction in patients with end-stage cardiomyopathy.

Uncontrollable severe mitral regurgitation is a frequent complication of end-stage cardiomyopathy, significantly contributing to heart failure in these patients, and predicts a poor survival. Although elimination of mitral valve regurgitation could be most beneficial in this group, corrective mitral valve surgery has not been routinely undertaken in these very ill patients because of the presumed prohibitive operative mortality. We studied the early outcome of mitral valve reconstruction in 16 consecutive patients with cardiomyopathy and severe, refractory mitral regurgitation operated on between June 1993 and April 1994. There were 11 men and five women, aged 44 to 78 years (64 +/- 8 years) with left ventricular ejection fractions of 9% to 25% (16% +/- 5%). Preoperatively all patients were in New York Heart Association class IV, had severe mitral regurgitation (graded 0 to 4+ according to color flow Doppler transesophageal echocardiography) and two were listed for transplantation. Operatively, a flexible annuloplasty ring was implanted in all patients. Four patients also had single coronary bypass grafting for incidental coronary disease. In four patients the operation was performed through a right thoracotomy because of prior coronary bypass grafting, and four patients also underwent tricuspid valve reconstruction for severe tricuspid regurgitation. No patient required support with an intraaortic balloon pump. There were no operative or hospital deaths and mean hospital stay was 10 days. There were three late deaths at 2, 6, and 7 months after mitral valve reconstruction, and the 1-year actuarial survival has been 75%. At a mean follow-up of 8 months, all remaining patients are in New York Heart Association class I or II, with a mean postoperative ejection fraction of 25% +/- 10%. There have been no hospitalizations for congestive heart failure, and a decrease in medications required has been noted. For patients with cardiomyopathy and severe mitral regurgitation, mitral valve reconstruction as opposed to replacement can be accomplished with low operative and early mortality. Although longer term follow-up is mandatory, mitral valve reconstruction may allow new strategies for patients with end-stage cardiomyopathy and severe mitral regurgitation, yielding improvement in symptomatic status and survival.

Stenosis of the central airways: evaluation by using helical CT with multiplanar reconstructions.

PURPOSE: To assess the accuracy of helical computed tomography (CT) with multiplanar reconstructions (MPRs) in the evaluation of stenoses of the central airways. MATERIALS AND METHODS: Thin-section axial CT and helical CT with MPRs were used to examine the central tracheobronchial tree for the presence of stenosis in 27 patients who underwent lung transplantation and 17 nontransplantation patients. The findings from these modalities were then compared with the findings obtained at conventional tomography and bronchoscopy, when available. RESULTS: Axial CT alone was 91% accurate in depicting stenosis, CT with MPRs was 94% accurate, and conventional tomography was 89% accurate in the evaluation of bronchial anastomosis in transplant recipients. CT and CT scans with MPRs were each 91% accurate in depicting stenosis in nontransplantation patients; the single false-negative finding showed focal tracheomalacia at bronchoscopy. CONCLUSION: CT with MPRs may be more accurate than thin-section axial CT in the demonstration of mild stenosis, the length of a stenosis, and horizontal webs.

Retrograde cerebral perfusion during hypothermic circulatory arrest reduces neurologic morbidity.

Hypothermic circulatory arrest has become an accepted technique for a variety of cardiac and complex aortic operations. However, prolonged periods (> 45 min) of hypothermic circulatory arrest in older patients is associated with marginal cerebral protection and an increased incidence of adverse neurologic events. In an effort to minimize such morbidity, we used a technique of retrograde cerebral perfusion with continuous monitoring of cerebral hemoglobin oxygen saturation during hypothermic circulatory arrest in 35 patients who underwent thoracic aortic operations or resection of intracardiac tumor. There were 27 men and 8 women (mean age 60 years, range 21 to 83 years). Sixteen patients had acute dissection, 6 had contained rupture of a thoracic aortic aneurysm, 10 had either a chronic dissection or aneurysm, and 3 had hypernephromas extending into the heart. Six patients underwent root replacement by means of an open technique for their distal anastomosis, 7 underwent root and partial arch replacement, 12 had root and total arch replacement, 7 had total arch replacement, and 3 had resection of tumor in the heart and retrohepatic vena cava. Seven patients had simultaneous coronary artery bypass grafting, 3 had replacement of one of the arch vessels, and 2 patients had a cesarean section. Sixteen cases were emergency, 6 urgent, and 13 elective. Nine (26%) were reoperations. Thirty-four patients underwent the procedure via a median sternotomy and one patient through a posterolateral thoracotomy. The mean retrograde cerebral perfusion time was 63 minutes (range 35 to 128 minutes), with 30 (86%) patients having more than 45 minutes, 12 (34%) having more than 65 minutes, and 4 (11%) having more than 90 minutes. There was 1 operative death caused by a preoperative myocardial infarction from an aortic dissection, and there were 2 late deaths (multiple organ failure and ruptured total aortic aneurysm). One patient had a stroke with a residual right hemiplegia and a pronounced aphasia. There were no other significant neurologic events or reoperations for bleeding. The average length of stay for patients having elective operations was 11 days and for those having emergency operations, 27 days. At a mean follow-up of 6 months all surviving patients (91%) are well. Hypothermic circulatory arrest is a relatively simple technique that provides a bloodless field and good visualization without the need for aortic crossclamps. Moreover, retrograde cerebral perfusion with continuous monitoring of cerebral oxygen saturation extends the "safe" time for hypothermic circulatory arrest, allowing ample opportunity to perform complicated cardiac and aortic operations with reduced risk of adverse neurologic events.

Recurrence of sarcoidosis following bilateral allogeneic lung transplantation.

We report the first case of recurrent sarcoidosis manifested by clinical symptoms, radiographic abnormalities, and pathologic changes in a patient following sequential double allogeneic lung transplantation. A 40-year-old male patient underwent bilateral allogeneic lung transplantation for end-stage pulmonary sarcoidosis. Thirteen months posttransplantation, he developed fatigue, shortness of breath, and bilateral upper lobe pulmonary infiltrates. Transbronchial biopsy specimens revealed noncaseating granulomata. The patient's symptoms and radiographic abnormalities resolved with an increased dose of oral prednisone.

Limitations of spirometry in detecting rejection after single-lung transplantation.

Pulmonary function testing has been extensively studied in the heart-lung transplant (HLT) population and has been advocated as a screening test for rejection or infection; however, few data are available in the single-lung transplant (SLT) population. The effect of acute episodes of infection, rejection, and bronchiolitis on the pulmonary function of 30 SLT patients with varying underlying disease states was prospectively evaluated. The native disease process was obstructive in 17 (SLT-OBS), restrictive in six (SLT-IPF), and pulmonary vascular in seven (SLT-PVD). Rejection was associated with a drop in FVC from 71 +/- 15 to 62 +/- 14% of predicted, with a significant drop seen in all three subgroups. Statistically significant drops in FEV1 were also seen in the SLT-OBS and SLT-PVD subgroups but not in the SLT-IPF subgroup. A drop in FEV25-75% was seen only in SLT-PVD. The greatest fall in FVC, FEV1, and FEF25-75% was seen with bronchiolitis, followed by acute rejection. The sensitivity and specificity of spirometry as a predictor of infection or rejection were significantly lower than those previously reported for HLT, with SLT-PVD having the most and SLT-OBS the least clinically useful values. We conclude that a fall in spirometry is seen in infection and rejection in SLT and that the underlying disease state has a significant influence on the diagnostic utility of specific spirometric indices.

Selective lung or heart-lung transplantation for pulmonary hypertension associated with congenital cardiac anomalies.

Fixed pulmonary hypertension has been a contraindication to correction of congenital heart defects. Beginning in February 1991, we pursued a policy of performing single-lung transplantation with intracardiac repair for selected patients with this physiology, reserving heart-lung transplantation for those with unreconstructable heart disease. Of 7 patients treated under this protocol, 5 underwent single-lung transplantation and intracardiac repair. The cardiac anomalies included complete atrioventricular canal (1), aortopulmonary window (1), atrial septal defect (1), and ventricular septal defect (2). One patient died perioperatively. All 4 patients surviving operation remained alive through the first postoperative year, but 3 died 13, 17, and 22 months after operation. Two other patients with pulmonary hypertension (1 with tricuspid atresia, 1 after failed Mustard procedure) received a heart-lung transplant and are well 15 and 18 months after operation. This experience demonstrates that selected patients with major intracardiac defects and pulmonary hypertension may have good early results after cardiac repair and single-lung transplantation, but that long-term results are considerably less favorable.

Pulmonary function in single lung transplantation for chronic obstructive pulmonary disease.

The primary determinants of pulmonary function after heart-lung or double lung transplantation are the volume and compliance of the recipient's thoracic cage. This study evaluated the influence of recipient chest wall factors on static and dynamic lung volumes after single lung transplantation for chronic obstructive pulmonary disease. Fourteen patients with chronic obstructive pulmonary disease received 15 single lung transplants (one retransplant). Posttransplantation follow-up data at 3 and 6 months, in the absence of infection or rejection, were available in nine patients. Overall pulmonary function at 6 months improved from preoperative levels to 55% to 65% of predicted values (forced vital capacity 38% to 55%, forced expiratory volume at 1 second 18% to 55%, maximum voluntary ventilation 21% to 65%), and allograft-specific pulmonary function improved to nearly normal predicted single-lung values (forced vital capacity 89%, forced expiratory volume at 1 second 90%, maximum voluntary ventilation 105%). Postoperative pulmonary function in these patients correlated significantly with preoperative thoracic volume measured by planimetry of chest radiographs. No correlation between postoperative pulmonary function was demonstrated with either the estimated volume of donated lung tissue or relative donor-to-recipient size matching. These findings support the concept that recipient chest wall factors determine postoperative pulmonary function in patients undergoing single lung transplantation for chronic obstructive pulmonary disease. Furthermore, the allograft lung functions at a normal level for the recipient and does not appear to be constrained by hyperinflation of the contralateral lung.

High-resolution CT detection of lacerations in the transplanted lung after transbronchial biopsy.

Relatively large tissue samples may be obtained from the lung with the "Alligator" biopsy forceps. We report the radiographic and high-resolution computed tomography (HRCT) appearances of six pulmonary lacerations in the transplanted lungs of three asymptomatic patients after transbronchial biopsy with this large caliber biopsy forceps. All patients had undergone transbronchial biopsy from 4 to 10 days before HRCT that was performed as part of routine surveillance after transplantation. The site and histopathologic findings of lung biopsies and negative microbiologic studies on bronchoalveolar washings correlated accurately with each pulmonary lesion seen. Laceration size varied from 9 to 20 mm (mean 14 mm) on HRCT. A thickened wall or surrounding alveolar reaction related to bronchoalveolar lavage or biopsy-induced hemorrhage was seen in five lesions. These simulated the appearance of lung abscess or invasive fungal disease. Only nonspecific alveolar opacities were noted on chest radiographs. The Alligator biopsy forceps may cause pulmonary lacerations in transplanted lungs that are detectable on HRCT but not on chest radiographs. Differentiation from opportunistic infection by CT criteria alone is difficult in these immunocompromised patients. CT studies in this population should be performed prior to transbronchial biopsy whenever possible.

Embryonic versus adult myocardium: adenine nucleotide degradation during ischemia.

Neonatal myocardium demonstrates better recovery from ischemia than does adult tissue. We tested the hypothesis that developmental differences in adenine nucleotide degradation might facilitate recovery by quantitating depletion of high-energy phosphates in nine-day-old embryonic (n = 9) and 15-month-old adult (n = 14) chicken hearts at 15-, 30-, 45-, and 60-minute intervals of normothermic ischemia in vitro. Nucleotides adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate and nucleosides adenosine, inosine, hypoxanthine, and xanthine were determined by high-performance liquid chromatography. Several observations in metabolite degradative response to ischemia were noted. The embryonic myocardium maintained higher adenosine triphosphate and adenosine monophosphate levels over the course of the investigation than did mature myocardium. Moreover, the adult group showed an increase in diffusible nucleoside pool metabolites. Relative immaturity of enzymes responsible for nucleotide degradation may facilitate postischemic recovery by preserving nondiffusible high-energy phosphate precursors to participate in salvage resynthesis of adenosine triphosphate.

Basal metabolic energy requirements of polarized and depolarized arrest in rat heart.

Basal energy requirements of polarized [tetrodotoxin (TTX), 25 microns] and depolarized [potassium (K), 20 mM] arrested hearts were studied by continuously measuring myocardial oxygen consumption (MVO2) during 60 min of normothermic arrest in isolated Langendorff-perfused rat hearts. TTX, a fast sodium channel blocker, was used to produce polarized arrest because of its specificity and reversibility. MVO2 was significantly lower in the polarized (TTX) group at all time points, a typical difference occurring 30 min after arrest (0.070 +/- 0.005 vs. 0.109 +/- 0.006 ml O2.min-1.g dry wt-1, P less than 0.001). Coronary flow was lower in the polarized group (14.3 +/- 1.4 vs. 28.4 +/- 2.2 ml.min-1.g dry wt-1, P less than 0.001, data at 30 min of arrest), but flow-restricted studies showed basal MVO2 to be independent of variation in coronary flow within this range. Recovery of function was similar in both groups. Ventricular pressure during cardiac arrest was lower in the polarized group (5.5 +/- 1.2 vs. 10.3 +/- 1.3 mmHg, P less than 0.01, data at 30 min of arrest), implying reduced myocardial wall tension and a lower intracellular calcium concentration. These results suggest that polarized arrest can decrease myocardial metabolic demands below that of depolarized arrest. A plausible mechanism is a reduction in myocardial wall tension caused by decreased calcium influx mediated by the Na-Ca exchanger.

Myocardial oxygen use during epinephrine administration to ischemically injured canine hearts.

The rationale for inotropic support by epinephrine during cardiac surgery and the early postoperative period was examined in 11 dogs after 20 minutes of normothermic ischemia and 1 hour of reperfusion. Ischemia reduced myocardial adenosine 5'-triphosphate (ATP) content by 37%. Left ventricular performance was assessed from pressure-dimension loops generated by minor-axis-diameter crystals for a range of controlled loading as high as end-diastolic pressures of 15 mm Hg. Myocardial oxygen consumption was determined at 6-9 steady-state steps throughout this range, including those at basal conditions of the empty beating ventricle. The hearts were artificially paced at 160 beats/min. Higher oxygen consumption with epinephrine (0.5 microgram/min/kg) administration was demonstrated at all levels of left ventricular performance and at all end-diastolic lengths. Several mechanisms for higher oxygen cost for similar external work performances have been suggested. From this study, it appears that increased uptake of free fatty acids, which increased threefold during epinephrine infusion, contributes to less efficient use of oxygen for mechanical work. We conclude that the use of inotropic support in ischemically injured hearts for reasons other than overt heart failure is not well based because myocardial oxygen consumption increases even when greater work is performed at lower end-diastolic dimensions.

Myocardial reperfusion injury. Role of myocardial hypoxanthine and xanthine in free radical-mediated reperfusion injury.

The aim of this study was to differentiate myocardial reperfusion injury from that of ischemia. We assessed the role of the myocardial adenosine 5'-triphosphate (ATP) catabolites, hypoxanthine and xanthine, generated during ischemia and the early phase of reperfusion, in reperfusion injury by modulating adenosine transport and metabolism with specific metabolic inhibitors. This was followed by intracoronary infusion of exogenous hypoxanthine and xanthine. Twenty-four dogs instrumented with minor-axis piezoelectric crystals and intraventricular pressure transducers were subjected to 30 minutes of normothermic global myocardial ischemia and 60 minutes of reperfusion. In Group 1 (n = 7), normal saline was infused into the cardiopulmonary bypass reservior before ischemia and before reperfusion. Saline solution containing 25 microM p-nitrobenzylthioinosine (NBMPR) and 100 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was infused in Group 2 (n = 10) dogs. Group 3 (n = 7) dogs were treated exactly like those in Group 2 except, at the end of the ischemic period and immediately before releasing the cross-clamp, a solution of EHNA-NBMPR containing 100 microM hypoxanthine and 100 microM xanthine was infused into the aortic root. Left ventricular performance and myocardial adenine nucleotide pool intermediates were determined before and after ischemia. ATP was depleted by about 50% (p less than 0.05 vs. preischemia) in all groups after 30 minutes of ischemia. Inosine was the major ATP catabolite (9.29 +/- 1.2 nmol/mg protein) in Group 1, while adenosine (9.91 +/- 0.7 nmol/mg protein) was the major metabolite in EHNA-NBMPR-treated dogs (Groups 2 and 3). Hypoxanthine levels were fivefold more in Group 1 compared with Groups 2 and 3 (p less than 0.05). Left ventricular performance in Group 1 decreased from 76.8 +/- 7.6 to 42.9 +/- 9.8 and 52.3 +/- 8.4 dynes/cm2 x 10(3) (p less than 0.05), while myocardial ATP decreased from 30.9 +/- 2.2 to 17.2 +/- 1.0 and 16.5 +/- 1.0 nmol/mg protein during 30 and 60 minutes of reperfusion, respectively (p less than 0.05 vs. preischemia). Ventricular function in Group 2 dogs completely recovered within 30 minutes of reperfusion, and myocardial ATP recovered to the preischemic level at 60 minutes of reperfusion. In Group 3, left ventricular performance was depressed by 39% and 30% during 30 and 60 minutes of reperfusion (p less than 0.05), respectively, and myocardial ATP did not recover during reperfusion despite a significant intramyocardial adenosine accumulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Direct measurement of nitroxide pharmacokinetics in isolated hearts situated in a low-frequency electron spin resonance spectrometer: implications for spin trapping and in vivo oxymetry.

The pharmacokinetics of two nitroxides were investigated in isolated rat hearts situated in a low-frequency electron spin resonance spectrometer. The spin labels 2,2,3,3,5,5-hexamethyl-1-pyrrolidinyloxy and 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy were chosen for their physiochemical analogy to the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and its corresponding spin-trapped adduct, 2-hydroxy-5,5-dimethyl-1-pyrrolidinyloxy (DMPO-OH). The bioreductive rates of the two nitroxides were measured during constant perfusion as well as during ischemia and are discussed in terms of a two-compartment pharmacokinetic model. These data provide information necessary to the design and application of spin traps to detect oxy radicals during reperfusion of ischemic tissue and suggest the feasibility of monitoring free-radical processes in intact, functioning mammalian tissues by using a low-frequency electron spin resonance spectrometer.

Traumatic fracture of the abdominal aorta. Rupture of a calcified abdominal aorta with minimal trauma.

We report the case of an elderly man whose infrarenal abdominal aorta ruptured when the patient fell getting out of bed. Unique features of this case are the lack of aneurysmal disease, the insignificant nature of the trauma, and the severe, rigid atherosclerotic plaque in the infrarenal aorta. Pathologic examination of the resected aorta demonstrated the point of rupture to be at the junction of atherosclerotic plaque and normal aorta, suggesting that atherosclerosis is a predisposing factor in traumatic rupture of the abdominal aorta.

The importance of load-independent analysis in assessment of the inotropic effect of prostaglandin E1 in vivo.

Load-independent pressure-dimension analysis was applied in 13 open-chest, anesthetized dogs during either left atrial (n = 7) or right atrial (n = 6) infusion of prostaglandin E1. Right atrial infusion of prostaglandin E1 in doses from 31 to 500 ng/kg/min resulted in no change in any parameters studied, including mean arterial pressure, cardiac output, and systemic and pulmonary vascular resistances. Left atrial infusion of prostaglandin E1 produced dose-dependent reductions in mean arterial pressure and systemic vascular resistance but no change in the slope of the relationship of left ventricular stroke work to end-diastolic length, a load-independent index of ventricular performance. In contrast to findings obtained with load-dependent parameters, these results suggest that prostaglandin E1 has no positive inotropic effect in vivo.

Myocardial protective effects of the class Ic antiarrhythmic agent flecainide.

The class Ic antiarrhythmic agent flecainide has recently become available in this country for management of ventricular arrhythmias. The pharmacologic and electrophysiologic features of this class of drug--marked sodium channel blockade producing inhibition of phase 0 of the myocardial action potential, moderate blockade of slow inward (calcium) channels, and general lack of systemic toxicity--suggest that these agents may exert significant myocardial protective effects. This hypothesis was tested in isolated, perfused rat hearts subjected to 30 minutes of global normothermic ischemia followed by 30 minutes of reperfusion after pretreatment with (1) Krebs-Henseleit buffer (n = 7); (2) Krebs-Henseleit buffer with potassium adjusted to 20.9 mmol/L with potassium chloride (n = 10); and (3) Krebs-Henseleit buffer plus flecainide acetate 50 mg/L (0.12 mmol/L) (n = 11). Severity of ischemic injury was assessed by time to ischemic contracture: 9.9 +/- 1.3 (Krebs-Henseleit buffer), 18.4 +/- 1.1 (potassium chloride), and 25.4 +/- 1.0 (flecainide) minutes (mean +/- standard error of the mean) (p less than 0.05 among all groups). Functional recovery after ischemia and reperfusion was measured by developed pressure (expressed as percent of preischemic control): 19.6 +/- 5.4 (Krebs-Henseleit buffer), 70.8 +/- 3.2 (potassium chloride), and 67.3 +/- 2.7 (flecainide). These results suggest that class Ic agents afford significant myocardial protection from global normothermic ischemia.