Low pressure radiofrequency balloon angioplasty: evaluation in porcine peripheral arteries.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of radiofrequency-powered thermal balloon angioplasty in an in vivo porcine model. BACKGROUND: Various modes of thermal energy used adjunctively during balloon angioplasty have demonstrated the potential to enhance the results of acute lumen dilation. METHODS: In normal pigs, 75 peripheral arteries were dilated with a newly designed, radiofrequency-powered, thermal angioplasty balloon. All inflations were performed at 2-atm pressure for 85 s. Dilations were performed either with (hot) or without (cold) the application of heat. Lumen dimensions and vessel morphology were assessed with intravascular ultrasonography. At the end of each study, dilated arterial segments were harvested for histologic examination. RESULTS: Single cold balloon inflations resulted in a 12.7% increase in arterial cross-sectional area whereas single hot inflations resulted in a 22.9% increase (p < 0.03). Similarly, when multiple cold inflations were compared with multiple hot inflations, two, three and four sequential hot inflations resulted in a significantly greater increase in cross-sectional area than an equivalent number of cold inflations (p < 0.03). Histologic examination demonstrated a temperature-dependent effect on the depth of medial necrosis and extent of arterial wall thinning (p < 0.001) as well as evidence for uniform alteration of elastic tissue fibers at temperatures of > or = 60 degrees C (p < 0.03). CONCLUSIONS: Low pressure radiofrequency thermal balloon angioplasty results in a greater increase in cross-sectional area in porcine peripheral arteries than does nonheated conventional balloon angioplasty. The pathologic basis for this enhanced dilation may be a temperature-dependent effect on medial necrosis, thinning of the arterial wall or alteration of vascular elastic fibers, alone or in combination.

Effects of different dosages and modes of sodium bicarbonate administration during cardiopulmonary resuscitation.

Systemic acidosis occurs during cardiac arrest and cardiopulmonary resuscitation (CPR). The present study investigated the effect of different modes of sodium bicarbonate administration on blood gas parameters during CPR. Arterial and venous blood gases were obtained during 10 minutes of CPR which was preceded by 3 minutes of unassisted ventricular fibrillation in 36 dogs. Following 1 minute of CPR, the animals received one of four treatments in a randomized and blinded manner: normal saline (NS), sodium bicarbonate bolus dose 1 mEq/kg (B), sodium bicarbonate continuous infusion 0.1 mEq/kg/min (I), and sodium bicarbonate bolus dose (0.5 mEq/kg) plus continuous infusion 0.1 mEq/kg/min (L+I). Eleven dogs completed NS, 8 B, 8 I, and 9 L+I protocol. Following NS infusion, both arterial and venous pH declined consistently over time. Significant differences compared with NS treatment in venous pH were observed at 12 minutes of ventricular fibrillation (L+I, 7.27 +/- 0.05; NS, 7.15 +/- 0.05; B, 7.20 +/- 0.05; I, 7.24 +/- 0.04, each bicarbonate treatment versus NS, and L+I versus B, (P < .05). The B group had an elevated venous PCO2 (mm Hg) concentration following 6 minutes of ventricular fibrillation compared with NS, L+I, and I groups (81 +/- 14 versus 69 +/- 10 versus 68 +/- 10 versus 71 +/- 8, respectively, (P = .07). Arterial pH and PCO2 values showed a similar trend as the venous data with the L+I group demonstrating arterial alkalosis (pH > 7.45) at 12 minutes of ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Diltiazem improves resuscitation from experimental ventricular fibrillation in dogs.

OBJECTIVE: To determine the effect of diltiazem on survival immediately after cardiac arrest and cardiopulmonary resuscitation (CPR) in dogs. DESIGN: Prospective, double-blind, randomized trial. SETTING: Laboratory at a large, university-affiliated medical center. SUBJECTS: Twenty-eight mongrel dogs, weighing 12 to 16 kg. INTERVENTIONS: After the administration of anesthesia, catheters were placed in the pulmonary artery, aortic arch, left ventricle, right ventricle, and great cardiac vein (12 dogs) for sample collection, pressure determinations, and induction of ventricular fibrillation. Dogs were randomized to receive either diltiazem, calcium chloride, or placebo (saline) either before or early during CPR. Dogs underwent 3 mins of unassisted fibrillatory arrest followed by 10 mins of standard CPR using a pneumatic device. After 13 mins of ventricular fibrillation, defibrillation was attempted repeatedly for less than or equal to 10 mins. Successful resuscitation was defined as an organized rhythm with an unassisted systolic BP of greater than 60 mm Hg for greater than or equal to 2 mins. MEASUREMENTS AND MAIN RESULTS: The resuscitation rate was significantly greater in diltiazem-treated animals (100%) than in those dogs receiving calcium (57%) or placebo (29%). Diltiazem-treated animals were resuscitated faster and required fewer defibrillation attempts than did dogs in the other groups. During CPR, coronary artery perfusion pressure and blood gases (arterial, venous, and myocardial) were similar among treatment groups. CONCLUSIONS: Diltiazem improves the resuscitation from experimentally induced ventricular fibrillation when administered before or early during CPR. This response may have important clinical implications in the treatment of patients undergoing cardiac arrest and CPR.

Evaluation and comparison of the adverse effects of streptokinase and alteplase.

The frequency and severity of adverse effects resulting from the administration of streptokinase and alteplase were determined in 126 consecutive patients who received standard dosages of these agents for the treatment of acute myocardial infarction. Evaluation was based on patient assessment by nursing staff, physicians, and the investigators before, during, and after thrombolytic administration. Overall, adverse effects occurred in 15 (41.7%) of 36 patients receiving streptokinase and 12 (13.3%) of 90 receiving alteplase (p = 0.001). No major bleeding or neurologic events were documented. Minor bleeding occurred in 13.9% and 7.8% of streptokinase and alteplase recipients, respectively (p = 0.47), and hypotension in 8 (22.2%) and 5 (5.6%), respectively (p = 0.01). The frequency of hypotension associated with streptokinase was significantly higher than that with alteplase. Thrombolytic-induced hypotension was easily managed and was not associated with sequelae.

The effect of CPR on plasma diltiazem concentrations in dogs.

STUDY OBJECTIVE: To determine the effect of cardiac arrest with CPR on diltiazem concentrations in dogs. DESIGN: Prospective, double-blind, randomized trial. SETTING: Laboratory at a large university-affiliated medical center. TYPE OF PARTICIPANTS: Twenty mongrel dogs. INTERVENTIONS: Following administration of anesthesia, catheters were placed in the pulmonary artery, aortic arch, left ventricle, and right ventricle. Dogs were randomized to receive diltiazem (0.5 mg/kg) either 60 minutes before or during cardiac arrest with CPR. After 13 minutes of cardiac arrest, defibrillation was attempted. MEASUREMENTS AND MAIN RESULTS: Frequent blood samples for diltiazem concentrations were obtained before, during, and after cardiac arrest. The mean diltiazem concentration rose 70% during CPR in the group that received diltiazem before cardiac arrest. The group that received diltiazem during CPR had concentrations five times greater than expected during sinus rhythm. CONCLUSION: Increased diltiazem concentrations are observed during CPR and are probably related to altered distribution encountered during CPR.

Epinephrine versus methoxamine in survival postventricular fibrillation and cardiopulmonary resuscitation in dogs.

Previous studies have indicated that methoxamine (an alpha adrenergic receptor agonist) may provide an advantage compared to epinephrine (a mixed alpha and beta adrenergic agonist) during cardiac arrest and CPR. To test this theory, we compared the effects of bolus injections of epinephrine vs. methoxamine on survival, hemodynamic variables, blood gases, and blood lactate concentrations during ventricular fibrillation and CPR in 12 dogs. Each dog underwent a 3-min fibrillatory arrest followed by 10 min of fibrillation and CPR, at which time the animals were defibrillated. Epinephrine (0.05 mg/kg, n = 6) or methoxamine (2 mg/kg, n = 6) was administered at the start of CPR. Both epinephrine and methoxamine produced identical survival rates (5/6) with no differences in coronary perfusion pressure gradients or blood gases (aortic, venous, or great cardiac venous pH, PaO2, or PaCO2) during CPR. Also, there were no differences between the two study groups in myocardial lactate or oxygen extraction ratios during CPR. We conclude that in the dosages tested in our experimental model, epinephrine and methoxamine produce similar results in the variables which we measured.

Differences in systemic and myocardial blood acid-base status during cardiopulmonary resuscitation.

Simultaneous arterial (aortic), mixed venous (pulmonary artery), and myocardial venous (great cardiac vein) blood gas and lactate concentrations were obtained in 12 dogs before and during cardiac arrest and CPR. We observed marked mixed venous and myocardial venous acidosis and increased PaCO2 but normal pHa and reduced PaCO2. Furthermore, the pH was significantly lower and the PCO2 significantly higher at the myocardial venous site compared to the mixed venous site, and marked myocardial lactate production occurred during CPR. Calculated bicarbonate and CO2 content (CCO2) did not increase during CPR from any site compared to control values and actually decreased significantly in arterial and myocardial venous samples. Changes in hydrogen ion concentration in both mixed venous and myocardial venous blood correlated with changes in lactate concentration but not total CCO2. Our results during CPR demonstrate a) a significant discrepancy between arterial and mixed venous blood gases but also a large and significant discrepancy between mixed venous and myocardial venous blood gases, b) significant anaerobic systemic and myocardial metabolism, and c) that mixed venous and myocardial venous acidosis is possibly a result of lactic acidosis.

Combination high dose amrinone and dopamine in the management of moribund cardiogenic shock after open heart surgery.

Two patients who suffered severe cardiogenic shock after open-heart surgery were successfully resuscitated with high doses of amrinone and dopamine. Both patients had required cardiopulmonary resuscitation and neither was responsive to more conventional mechanical and pharmacologic intervention. Neither patient suffered any serious side effects and both were eventually discharged from the hospital in good condition. These two case reports suggest the potential for using higher than previously reported doses of amrinone in combination with dopamine for the successful treatment of moribund cardiogenic shock in the post open-heart surgical patient. Further studies are needed to assess whether this high-dose drug combination will be successful in patients who present with severe cardiogenic shock unrelated to the post open-heart surgical setting.

Antifibrillatory effects of high dose bretylium and a lidocaine-bretylium combination during cardiopulmonary resuscitation.

Previous CPR studies from our laboratory have shown that a standard iv dose of lidocaine (2 mg/kg) has a rapid antifibrillatory effect, while a standard dose of bretylium (5 mg/kg) produces a delayed but more pronounced effect. In order to determine the optimal doses, we investigated the antifibrillatory effects of a) high dose bretylium (10 mg/kg) and b) a combination of lidocaine (2 mg/kg) and bretylium (5 mg/kg) during CPR in two groups of anesthetized dogs. Ventricular fibrillation threshold (VFT) was determined using a train method and CPR was performed by a pneumatic device. During both a control and drug phase, the VFT was determined in each dog before CPR, and after each of three consecutive 3-min CPR periods. The combination of lidocaine and bretylium (11 dogs) caused a significant increase in VFT compared to the control phase after each of the 3-min CPR periods and maintained this effect for greater than 2 h. Bretylium 10 mg/kg (eight dogs) significantly elevated the VFT only after the third 3-min CPR period. We conclude that the combination of standard doses of lidocaine and bretylium produces a rapid and prolonged antifibrillatory effect and may be the optimal regimen in the CPR setting. High dose bretylium has a delayed onset of effect and appears to produce no greater effect than standard doses of the drug.

Lorcainide for the treatment of refractory ventricular tachycardia: clinical and electrophysiologic results.

The electrophysiologic effects and antiarrhythmic efficacy of lorcainide were evaluated using programmed electrical stimulation (PES) in 14 patients with ventricular tachycardia (VT) refractory to conventional drug therapy. Lorcainide was administered orally (200-400 mg/d, eight patients), intravenously (150 mg/d, one patient), or by both routes (250-380 mg/d, five patients) prior to PES. In 13 patients undergoing both control and lorcainide PES, lorcainide increased the QRS duration (102 +/- 28 to 125 +/- 28 ms, P less than .001) and the QTc interval (430 +/- 39 to 471 +/- 32 ms, P less than .01) but had no effect on the RR interval (786 +/- 156 to 780 +/- 172 ms, P greater than .2). The right ventricular effective refractory period increased from 258 +/- 8 to 285 +/- 22 ms (P less than .001). Lorcainide prevented VT induction or resulted in induction of only well-tolerated, nonsustained VT in six of 14 patients (43%). The cycle length of induced VT increased from 264 +/- 32 to 306 +/- 34 ms (P less than .01). Of six patients started on chronic therapy, four still receive lorcainide after 18 +/- 7 months. Adverse effects have consisted mainly of sleep disturbances. Thus, it can be stated that lorcainide is effective in certain patients with VT refractory to conventional therapy.

Epoprostenol sodium (prostacyclin) infusion in acute myocardial infarction.

Epoprostenol (prostacyclin) is a potent inhibitor of platelet aggregation and causes relaxation of vascular smooth muscle. These effects may be beneficial in patients with acute myocardial infarction. The effect of epoprostenol infusion in patients with acute myocardial infarction was evaluated in a randomised double blind study of 45 patients with evidence of myocardial infarction of less than 16 hours' duration. The patients were given a 72 hour infusion of epoprostenol (23) or placebo (22). The maximum dose was 5 ng/kg/min. The mean time to treatment was 8.3 hours (range 3.8-15.9 hours). The mean dose was 4.9 ng/kg/min. The patients were followed until day 30. No significant differences were found between the groups in mortality, development of congestive heart failure, cardiogenic shock, arrhythmias, recurrent chest pain, reinfarction, peak creatine kinase concentration, or the time taken to attain peak creatine kinase concentration. No significant difference in baseline ejection fraction was noted between groups, and no significant change in ejection fraction occurred within each group or between groups. The only significant side effect was the development of facial flushing in the epoprostenol group. In this pilot study epoprostenol was well tolerated by patients with acute myocardial infarction. No benefit from epoprostenol could be demonstrated at the dose range used when the drug was administered within 16 hours of the onset of symptoms.

The effect of lidocaine and bretylium on the defibrillation threshold during cardiac arrest and cardiopulmonary resuscitation.

The effect of intravenous lidocaine, 2 mg/kg, and bretylium, 5 mg/kg, on defibrillation threshold (DFT) was investigated in alpha-chloralose anesthetized dogs undergoing conventional closed chest cardiopulmonary resuscitation (CPR) following induced ventricular fibrillation. Ventricular fibrillation was induced electrically and CPR was performed by a pneumatic device set to compress the chest 60 times and inflate the lung 12 times a minute. Defibrillation was achieved using underdamped sinusoidal current shocks from a special defibrillator which allowed determination of delivered energy. The DFT was defined as the peak current which defibrillated, but no more than 20% higher than a current which did not defibrillate. All DFTs were obtained within 5 min of CPR. The mean +/- SD current and energy thresholds required for defibrillation during lidocaine-CPR (seven dogs) were 17.0 +/- 8.9 A and 53.0 +/- 40.7 J as compared to 12.5 +/- 6.2 A and 34.3 +/- 30.7 J, respectively during control-CPR (P less than 0.05). The mean +/- SD current and energy thresholds during bretylium-CPR were 11.0 +/- 3.4 A and 24.1 +/- 1.3 J as compared to 11.8 +/- 1.7 A and 29.4 +/- 9.6 J, respectively, during control-CPR (NS). These results show that lidocaine acutely elevated defibrillation threshold whereas bretylium did not produce such an effect. The effect on DFT along with other pharmacologic properties should be considered when lidocaine or bretylium is used in the setting of cardiac arrest and CPR.

Antifibrillatory effects of lidocaine and bretylium immediately postcardiopulmonary resuscitation.

The antifibrillatory effects of lidocaine and bretylium in the postcardiopulmonary resuscitation (CPR) setting were examined using ventricular fibrillation threshold (VFT) determinations in anesthetized dogs. The dogs were fibrillated and CPR was carried out with a pneumatic device. Lidocaine and bretylium were administered intravenously at the onset of CPR, and VFT was serially determined after defibrillation following three consecutive 3-minute CPR periods. A dose of 2 mg/kg of lidocaine caused a significant increase in VFT determinations after the first but not subsequent 3-minute CPR periods; a dose of 1 mg/kg of lidocaine was ineffective at any time point. A dose of 5 mg/kg of bretylium elevated the VFT after the second and third but not the first 3-minute period. In dogs who received lidocaine, a significant elevation of VFT determinations were found to be associated with a high blood lidocaine concentration (mean 13.8 +/- 8.3 micrograms/ml). The present study demonstrates that a 2 mg/kg dose of lidocaine administered during CPR rapidly increases VFT determinations after CPR (within 5 minutes), whereas, a 5 mg/kg dose of bretylium significantly elevates VFT determinations but at a later time (within 10 minutes). The observed significant effect of lidocaine appears to be associated with high lidocaine blood concentrations (greater than 6 micrograms/ml).

Effect of external cardiopulmonary resuscitation on lidocaine pharmacokinetics in dogs.

Lidocaine pharmacokinetics were studied in five fibrillated dogs undergoing external cardiopulmonary resuscitation (CPR) and five comparable control dogs. All animals were anesthetized with sodium pentobarbital and their electrocardiogram, arterial blood pressure, left ventricular pressure and carotid blood flow were monitored continuously. All dogs received a 2 mg/kg i.v. bolus dose of lidocaine. Multiple blood samples from venous, arterial, left ventricular and right atrial sites were obtained for determination of blood lidocaine concentration. At 60 min, the dogs were sacrificed. Lung, liver, kidney, brain, skeletal muscle and heart tissue samples were collected. There were dramatic differences between the control and CPR groups in arterial pressure, left ventricular pressure and carotid blood flow. In the CPR dogs, lidocaine blood concentrations for the entire 60 min were significantly higher than the control dogs and lidocaine clearance was reduced at least by 8-fold. A comparison of extraction ratios across skeletal muscle demonstrated that the phase of tissue uptake was prolonged in the CPR group. In each of the tissue samples, significantly higher tissue concentrations were observed in the CPR group. The results of our study show that lidocaine disposition is greatly altered during CPR and this is most likely due to a tremendous reduction of cardiac output and blood flow during CPR.

Digoxin and propranolol in the prophylaxis of supraventricular tachydysrhythmias after coronary artery bypass surgery.

Supraventricular tachydysrhythmia is a bothersome and potentially harmful occurrence after coronary artery bypass graft operation (CABG). Use of digoxin prophylaxis preoperatively has yielded conflicting results in lowering the incidence of supraventricular tachydysrhythmia. In this study, three groups of patients were formed. Group 1 served as the control; no prophylactic medication was given. Group 2 was given digoxin prophylaxis beginning immediately after operation. Group 3 received digoxin postoperatively as did Group 2, plus orally administered propranolol beginning on postoperative day 2. No difference in the incidence of supraventricular tachydysrhythmia was found between Groups 1 and 2 (28.2% versus 28.9%). However, the incidence in Group 3 was 2.2%, and this represented a statistically significant difference (p less than 0.005) compared with either Group or 2. The combined use of digoxin and propranolol postoperatively significantly reduced the incidence of supraventricular tachydysrhythmia after CABG.

Disopyramide hemodialysis and kinetics in patients requiring long-term hemodialysis.

Disopyramide hemodialysis and kinetics after 200 mg orally in six patients receiving long-term hemodialysis were examined. Mean volume of distribution (area) was 66.5 +/- 13 l. Mean times of the peak serum concentration and mean peak serum concentration were 2.3 +/- 0.9 hr and 3.1 +/- 0.9 microgram/ml. Mean absorption half-life (t 1/2) was 21.6 +/- 12.5 min. Mean disopyramide elimination t 1/2 during dialysis was 16.8 +/- 11.9 hr, not significantly different from mean elimination t 1/2 without dialysis of 16.1 +/- 5.2 hr. End-dialysis bath concentrations of disopyramide showed that not more than 2.4% of the dose was dialyzed during a 2-hr dialysis period. Our data indicate that at therapeutic concentrations disopyramide was not appreciably dialyzed.