Verapamil Infusion Research Articles

Thermodilution-derived indices for assessment of left and right ventricular cardiac function in normal and impaired cardiac function*

The aim of this study was to assess whether thermodilution-derived parameters of right and left ventricular cardiac function (right ventricular ejection fraction, global ejection fraction, cardiac function index) are able to track changes of cardiac contractile function and whether they are influenced by substantial preload reduction. Prospective animal study. University-affiliated animal research laboratory. Domestic pigs. Sixteen domestic pigs were studied. Right ventricular ejection fraction, global ejection fraction, and cardiac function index were compared to direct measurement of left ventricular rate of maximum systolic pressure rise and the left ventricular rate of maximum systolic pressure rise corrected to preload. Measurements were done with normal cardiac function during normo- and hypovolemia. Thereafter, cardiac function was impaired by continuous infusion of verapamil and measurements were repeated during normo- and hypovolemia (withdrawal of blood 20 mL kg body weight). With normal cardiac function, hypovolemia led to a significant decrease of right ventricular ejection fraction from 36.7% ± 6.6% to 29.8% ± 5.8% (p < .001), global ejection fraction from 40.5% ± 6.2% to 33.6% ± 7.6% (p < .001), and the left ventricular rate of maximum systolic pressure rise from 2104 ± 390 mm Hg sec to 1297 ± 438 mm Hg sec (p < .001). Cardiac function index (8.92 ± 2.20 min to 7.93 ± 1.54 min) and the left ventricular rate of maximum systolic pressure rise corrected to preload (18.2 ± 4.7 mm Hg sec mL to 15.2 ± 4.3 mm Hg sec mL) did not change significantly. Infusion of verapamil led to a significant reduction of right ventricular ejection fraction, global ejection fraction, cardiac function index, the left ventricular rate of maximum systolic pressure rise, and the left ventricular rate of maximum systolic pressure rise corrected to preload (p < .001). Now, hypovolemia led to a significant decrease of right ventricular ejection fraction (29.1% ± 4.6% to 24.9% ± 5.9%; p < .001), global ejection fraction (37.1% ± 4.7% to 31.9% ± 3.9%; p < .05), cardiac function index (7.58 ± 1.02 to 6.27 ± 1.19 min; p < .05), and the left ventricular rate of maximum systolic pressure rise (733 ± 141 mm Hg sec to 426 ± 108 mm Hg sec; p < .05). Only the left ventricular rate of maximum systolic pressure rise corrected to preload did not change significantly (6.7 ± 1.3 mm Hg sec mL to 4.6 ± 1 mm Hg sec mL; p > .05). Right ventricular ejection fraction, global ejection fraction, and cardiac function index enable detection of changes in load-independent, intrinsic cardiac contractility. Importantly, they also reflect changes of contractile function caused by substantial decrease of preload, emphasizing the importance of assessing both cardiac contractile function in coherence with cardiac preload to differentiate between reduced intrinsic contractility and hypovolemia.

Effect of Cyclodextrin Infusion in a Rat Model of Verapamil Toxicity

Sulfobutylether-β-cyclodextrin (SBE-CD) is a pharmaceutical excipient known to bind verapamil. After intravenous administration, clearance of SBE-CD approximates glomerular filtration rate. We hypothesized that SBE-CD would complex with verapamil in vivo, enhance renal elimination, and increase time to death in a rat model of verapamil toxicity. Ten Wistar rats were allocated to control or intervention groups. All received isoflurane anesthesia followed by verapamil infusion (32 mg/kg) over 1 hour. The control group received saline bolus 7.5 mL/kg at 5 minutes. The intervention group received SBE-CD infusion 7.5 mL/kg (2.25 g/kg) at 5 minutes. Heart rate, respiratory rate, oxygen saturation, and temperature were monitored. The primary endpoint was time to death measured separately as time to asystole and time to apnea. There was no benefit derived from cyclodextrin infusion. Average time to death was significantly longer in the control group as measured by time to apnea (P < 0.05). Control group survival was significantly better as measured by time to asystole and time to apnea (Breslow P < 0.05). SBE-CD infusion resulted in a shorter time to death measured by time to apnea and asystole. Preliminary work demonstrated no effect in isoflurane anesthetized rats receiving only SBE-CD bolus. Verapamil poisoned rats treated with 2.25 g/kg of SBE-CD showed increased toxicity. We propose that this effect was related to the large hyperosmolar CD infusion combined with verapamil-induced cardiogenic shock. Additional studies are warranted to clarify the mechanism of increased toxicity in our study and to assess for potential beneficial effects at lower SBE-CD concentrations.

Basic and Clinical Research on the Therapeutic Effect of Intervention in Primary Liver Cancer by Targeted Intra-Arterial Verapamil Infusion

The aim of this study was assess the therapeutic effect of targeted intra-arterial verapamil infusion in liver cancer patients and its side-effects in a dog model. The blood verapamil levels in dogs were determined after one-off intra-arterial infusion (0.7 mg/kg). Blood pressure, breathing state, and II-lead electrocardiogram were measured. Primary liver cancer patients (100) were randomly assigned into two groups. Controls (50) were treated with targeted intra-arterial infusion, and every patient received once-a-month interventional therapy, twice. Treatment group (50) received chemotherapeutics plus verapamil. Therapeutic and toxic side effects were evaluated. Control (41) and treatment group (45) patients were further treated with a second round of targeted intra-arterial infusion of chemotherapeutics plus verapamil, in 30 days after the 2-time interventional therapy. Every patient accepted interventional therapy 4-5 times during the 6 months after the first confirmed diagnosis. Following verapamil infusion, verapamil in dog liver was tenfold higher than in blood and was 4- to 20-fold higher than that needed for reversing carcinoma drug resistance. After interventional therapy, there were no significant changes in iconographic evaluation indices between the groups. Average activities of aminotransferases were 332 and 178 U/l in the treatment and control groups (P < 0.05). The imaging parameters of the treatment group were significantly better than those of control group. No side effects were found among the 91 patients who accepted verapamil infusion. After verapamil infusion, verapamil levels in dog hepatic tissue exceeded the effective concentration that reverses carcinoma multidrug resistance without any visible changes in the vital signs. Targeted intra-arterial verapamil infusion could improve the chemotherapy for the primary liver cancer patients without any side effects.

Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation

AimExposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution.Methods and resultsTo determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 ± 4 vs. 133 ± 3 mmHg, P< 0.05) and attenuated vasodilatation to bradykinin (P= 0.005), acetylcholine (P= 0.008), and sodium nitroprusside (P< 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n= 6–9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P< 0.001) and sodium-nitroprusside (P= 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate.ConclusionCombustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions.

Clinical Efficacy of Chemotherapy Combined with Verapamil in Metastatic Colorectal Patients

In order to determine the clinical efficacy and adverse reactions of chemotherapy and verapamil infusion through a target artery to treat colorectal cancer patients with metastasis after failure with previous conventional treatments. Patients with metastatic colon cancer (n = 36) received an infusion of verapamil, interleukin-2, oxaliplatin (or hydroxy camptothecin or irinotecan hydrochloride), fluorouracil and calcium folinate through target artery using the Seldinger puncture technique. From the second day of infusion, the patients were treated with fluorouracil and calcium folinate via systematic intravenous injection for 2-3 days. Efficacy was evaluated after at least two treatment courses. The objective response including complete or partial response was 58.3% in the 36 patients; clinical benefit rate, evaluated by Karnofsky Performance Status score was 91.7%; by weight was 83.3%; by the amount of painkiller consumed was 80.6%. No patient experienced side effects associated with heart function. Post-treatment, the P-R period, Q-T period, QRS, and heart rate were not significantly different than before treatment. Liver function was significantly improved. Side effects of chemotherapy were minor in comparison to those observed with intravenous chemotherapy. Infusion of verapamil and chemotherapy directly into pelvic tumor tissue can increase treatment efficacy and has been shown to be a relatively safe technique.

Particle Traps Prevent Adverse Vascular and Prothrombotic Effects of Diesel Engine Exhaust Inhalation in Men

In controlled human exposure studies, diesel engine exhaust inhalation impairs vascular function and enhances thrombus formation. The aim of the present study was to establish whether an exhaust particle trap could prevent these adverse cardiovascular effects in men. Nineteen healthy volunteers (mean age, 25±3 years) were exposed to filtered air and diesel exhaust in the presence or absence of a particle trap for 1 hour in a randomized, double-blind, 3-way crossover trial. Bilateral forearm blood flow and plasma fibrinolytic factors were assessed with venous occlusion plethysmography and blood sampling during intra-arterial infusion of acetylcholine, bradykinin, sodium nitroprusside, and verapamil. Ex vivo thrombus formation was determined with the use of the Badimon chamber. Compared with filtered air, diesel exhaust inhalation was associated with reduced vasodilatation and increased ex vivo thrombus formation under both low- and high-shear conditions. The particle trap markedly reduced diesel exhaust particulate number (from 150 000 to 300 000/cm(3) to 30 to 300/cm(3); P<0.001) and mass (320±10 to 7.2±2.0 μg/m(3); P<0.001), and was associated with increased vasodilatation, reduced thrombus formation, and an increase in tissue-type plasminogen activator release. Exhaust particle traps are a highly efficient method of reducing particle emissions from diesel engines. With a range of surrogate measures, the use of a particle trap prevents several adverse cardiovascular effects of exhaust inhalation in men. Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefits and reduce the burden of cardiovascular disease.

Optimization of a fully implantable small animal infusion model involving multi‐pressure data collection

Collecting multiple, intra-subject pressures provides a broader physiological picture for many research applications, while potentially reducing animal use. Research decisions often hinge on cardiovascular (CV) data that previously could only be obtained from a large animal model due to the lack of appropriate, fully implantable solutions enabling simultaneous measurement of multiple pressures in small animals. DSI has optimized possibilities for multi-channel pressure evaluation by developing the dual pressure HD-S21 transmitter. Emulating a study pioneered by MPI Research with two independent pressure transmitters, DSI conducted a follow-up investigation to demonstrate the advantages obtained by using the HD-S21. Two male CD® IGS rats were implanted with the HD-S21 to monitor LVP, MAP, ECG and core temperature. iPRECIO® infusion pumps, also used in the MPI validation, delivered the same IV infusion program. While the initial (MPI) validation assessed verapamil and dobutamine infusion effects on temporally contiguous measures of LVP and MAP via independent devices, the HD-S21 enabled simultaneous and continuous monitoring of all parameters from a single device. Together, the HD-S21 and iPRECIO® provide pharmacology research the first fully implantable and easily validated small animal infusion model optimized to wirelessly record a comprehensive parameter battery with high sensitivity.

High-Dose Intra-arterial Verapamil for the Treatment of Cerebral Vasospasm After Subarachnoid Hemorrhage: Prolonged Effects on Hemodynamic Parameters and Brain Metabolism

Studies attempting to establish the safety and efficacy of standard and high-dose intra-arterial infusions of calcium channel blockers for treatment of cerebral vasospasm have focused on hemodynamic changes during the angiographic procedure. To evaluate longer-term drug effects over the hours following infusion and the effects on brain tissue oxygen tension or cerebral metabolism. We studied 11 patients with poor-grade aneurysmal subarachnoid hemorrhages who underwent multimodality brain monitoring and angiography with infusion of high-dose intra-arterial verapamil (≥15 mg total dose). Hourly intracerebral microdialysis measurements and continuously recorded mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Pbto₂ were analyzed for 6 hours before and 12 hours following treatment. A median dose of 23 mg (range, 15-55 mg) of intra-arterial verapamil was given. Compared with baseline values, reductions in CPP and MAP were maximal at 3 hours postangiography (from 105 ± 13 mm Hg to 95 ± 15 mm Hg and from 116 ± 12 mm Hg to 106 ± 16 mm Hg, P < .01) and persisted for up to 6 hours (P < .04); increases in vasopressor therapy were required in 8 procedures (53%). ICP significantly increased during the first 3 hours post angiography (P < .03). Brain glucose increased by 33% by hour 9 (P < .001). There were no significant changes in Pbto₂ or the lactate/pyruvate ratio. High-dose intra-arterial verapamil causes increases in ICP and reductions in CPP, followed by an increase in brain glucose levels, without altering brain oxygen tension or oxidative metabolism. Patients undergoing high-dose intra-arterial verapamil therapy warrant close hemodynamic and ICP monitoring for at least 12 hours following treatment.

Reversible Cerebral Vasoconstriction Syndrome: Treatment with Combined Intra-Arterial Verapamil Infusion and Intracranial Angioplasty

We report a case of severe RCVS treated with a combination of selective intra-arterial verapamil infusions and intracranial angioplasty, resulting in angiographic and clinical improvement. Endovascular techniques more commonly used in the treatment of SAH-induced vasospasm are potentially important adjuncts to systemic drug therapy in the management of severe RCVS.

Comparative Effects of Verapamil, Nicardipine, and Nitroglycerin on Myocardial Ischemia/Reperfusion Injury

The aim of this experiment was to establish whether verapamil, nicardipine, and nitroglycerin have (1) infarct size-limiting effects and (2) antiarrhythmic effects in in vivo rabbit hearts during ischemia/reperfusion. Rabbits received regional ischemia by 30 min of left anterior descending coronary artery occlusion followed by 3 hours of reperfusion under ketamine and xylazine anesthesia. The animals were randomly assigned to the following 4 treatment groups: a control group, a verapamil group, a nicardipine group, and a nitroglycerin group. A continuous infusion of verapamil, nicardipine, or nitroglycerin was initiated 5 min prior to ischemia. Infarct size/area at risk decreased in verapamil, and nitroglycerin. The incidence of ischemia-induced arrhythmia decreased in nicardipine, verapamil and nitroglycerin. The incidence of reperfusion-induced arrhythmias decreased in verapamil and nitroglycerin. From the present experimental results, verapamil and nitroglycerin rather than nicardipine did afford significant protection to the heart subjected to ischemia and reperfusion in a rabbit model.

Ultrahigh-dose intraarterial infusion of verapamil through an indwelling microcatheter for medically refractory severe vasospasm: initial experience

Vasospasm is one of the leading causes of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). Many patients suffer devastating strokes despite the best medical therapy. Endovascular treatment is the last line of defense for cases of medically refractory vasospasm. The authors present a series of patients who were treated with a prolonged intraarterial infusion of verapamil through an in-dwelling microcatheter. Over a 1-year period 12 patients with medically refractory vasospasm due to aneurysmal SAH were identified. Data were retrospectively collected, including age, sex, Hunt and Hess grade, Fisher grade, aneurysm location, aneurysm treatment, day of the onset of vasospasm, intracranial pressure, mean arterial pressures, intraarterial treatment of vasospasm, dosages and times of verapamil infusion, presence of a new ischemic area on CT scan, modified Rankin scale score at discharge and at the last clinical follow-up, and discharge status. Twenty-seven treatments were administered. Between 25 and 360 mg of verapamil was infused per vessel (average dose per vessel 164.6 mg, range of total dose per treatment 70-720 mg). Infusion times ranged from 1 to 20.5 hours (average 7.8 hours). The number of treated vessels ranged from 1 to 7 per patient. The number of treatments per patients ranged from 1 to 4. There was no treatment-related morbidity or death. Blood pressure and intracranial pressure changes were transient and rapidly reversible. Among the 36 treated vessels, prolonged verapamil infusion was completely effective in 32 cases and partially effective in 4. Only 4 vessels required angioplasty for refractory vasospasm after prolonged verapamil infusion. There was no CT scanning evidence of new ischemic events in 9 of the 12 patients treated. At last clinical follow-up 6-12 months after discharge, 8 of 11 patients had a modified Rankin Scale score ≤2. Prolonged intraarterial infusion of verapamil is a safe and effective treatment for medically refractory severe vasospasm and reduces the need for angioplasty in such cases.

E0419 The applying of aspiration catheter in revascularisation in patients with ST-elevation myocardial infarction

ObjectivesTo observe the immediate and recent treatment effects of applying the aspiration catheter in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).MethodsFrom March to June 2010,...

Endovascular Treatment of Medically Refractory Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

CV following aneurysmal SAH is a significant cause of morbidity and mortality. We review our experiences using PTA and IA verapamil infusion for treating medically refractory cases. We performed a retrospective review of patients with SAH admitted from July 2003 to January 2008. Of 546 patients admitted within 72 hours of symptom onset, 231 patients (42%) developed symptomatic CV and 189 patients (35%) required endovascular therapy. A total of 346 endovascular sessions were performed consisting of 1 single angioplasty, 286 IA verapamil infusions, and 59 combined treatments. PTA was performed on 151 vessel segments, and IA verapamil was infused in 720 vessel segments. IA verapamil doses ranged from 2.0 to 30.0 mg per vessel segment and from 3.0 to 55.0 mg per treatment session. Repeat treatments were necessary in 102 patients (54%) for persistent, recurrent, or worsening CV. There were 6 treatment-related complications, of which 2 resulted in clinical worsening. No deaths were attributable to endovascular therapy. At follow-up, 115 patients (61%) had a good outcome and 55 patients (29%) had a poor outcome. Sixteen patients died from causes related to SAH, while 3 died from other medical complications. Endovascular treatments are an integral part of managing patients with medically refractory CV. In our experience, PTA and IA verapamil are safe, with a low complication rate, but further studies are required to determine appropriate patient selection and treatment efficacy.

E-056 Endovascular treatment of medically refractory cerebral vasospasm following aneurysmal subarachnoid hemorrhage

Background and purposeCerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (SAH) is a significant cause of morbidity and mortality. We review our experiences using percutaneous transluminal angioplasty (PTA) and intra-arterial (IA)...

P-001 Quantification of parametric color coded digital subtraction angiography

PurposeColor coding of digital subtraction angiography (DSA) is a temporal and intensity post-processing color coded algorithm that generates a single composite image containing all information contained in a standard DSA...

Comparative Hemodynamic Effects of Levosimendan Alone and in Conjunction with 4-Aminopyridine or Calcium Chloride in a Rodent Model of Severe Verapamil Poisoning

Levosimendan (Levo) increases sensitivity of troponin-C to calcium, thus increasing myocardial contractility. It is also a vascular K+-ATP channel agonist producing peripheral vasodilation. Previous research with levosimendan revealed an increase in cardiac output (CO) but not blood pressure (BP) in experimental verapamil poisoning. Levosimendan's K+-channel agonist properties may augment verapamil's vasodilatory effects. 4-Aminopyridine (4-AP) is a K+-channel antagonist. It has successfully reversed hypotension in experimental verapamil poisoning. We hypothesized that coadministration of these agents may improve BP and CO in verapamil poisoning. Anesthetized, ventilated, and canulated male Wistar rats were poisoned with verapamil. Animals received one of six treatments, which are as follows: (1) n-saline infusion (control), (2) Levo 6.25 μg/kg loading dose and 36 μg/kg/h infusion, (3) 4-AP 2 mg/kg loading dose and infusion (4-AP), (4) Levo+4-AP, (5) CaCl₂ loading dose and infusion, and (6) Levo+CaCl(2). Hemodynamic parameters were recorded for 60 min. Outcome measures were changes in CO, BP, and heart rate (HR) compared to control. All groups had similar pretoxicity and peak toxicity CO (50% of pretoxicity value), BP (50% or pretoxicity value), and HR. Control group CO, BP, and HR progressively dropped during the verapamil infusion. Levosimendan produced a statistically significant improvement in CO (75% of pretoxicity level) but not BP in comparison to control. 4-AP produced a significant improvement in CO (110% of pretoxicity) and BP (78% of pretoxicity). Levo+4-AP and Levo+CaCl₂ groups improved CO (100% of pretoxicity) and BP (77% and 50% of pretoxicity, respectively), but there was no additive increase in CO or BP in animals compared to 4-AP or CaCl₂ alone. Levosimendan moderately improved CO but not BP in verapamil poisoning. The hypotensive effects of levosimendan were not overcome by coadministration of either 4-AP or CaCl₂. Levosimendan may not be an appropriate agent to use in the treatment of verapamil poisoning.

Optimization of a fully implantable small animal infusion model involving multi‐pressure data collection

Collecting multiple, intra‐subject pressures provides a broader physiological picture for many research applications, while potentially reducing animal use. Research decisions often hinge on cardiovascular (CV) data that previously could only be obtained from a large animal model due to the lack of appropriate, fully implantable solutions enabling simultaneous measurement of multiple pressures in small animals. DSI has optimized possibilities for multi‐channel pressure evaluation by developing the dual pressure HD‐S21 transmitter. Emulating a study pioneered by MPI Research with two independent pressure transmitters, DSI conducted a follow‐up investigation to demonstrate the advantages obtained by using the HD‐S21. Two male CD® IGS rats were implanted with the HD‐S21 to monitor LVP, MAP, ECG and core temperature. iPRECIO® infusion pumps, also used in the MPI validation, delivered the same IV infusion program. While the initial (MPI) validation assessed verapamil and dobutamine infusion effects on temporally contiguous measures of LVP and MAP via independent devices, the HD‐S21 enabled simultaneous and continuous monitoring of all parameters from a single device. Together, the HD‐S21 and iPRECIO® provide pharmacology research the first fully implantable and easily validated small animal infusion model optimized to wirelessly record a comprehensive parameter battery with high sensitivity.

Cerebrovasospasm Following Endoscopic Cerebrospinal Fluid Leak Repair

Endoscopic repair of spinal fluid leaks is a commonly performed procedure with low morbidity. However, this is the first report of cerebrovasospasm, following endoscopic repair of a cerebrospinal fluid (CSF) leak. A 51-year-old woman underwent endoscopic repair of a spontaneous CSF leak. She subsequently developed symptomatic cerebrovasospasm on postoperative day 3. This was successfully treated with intraarterial verapamil infusion.

Survival of Verapamil-Poisoned Rats Treated with Triiodothyronine

Life-threatening toxicity due to calcium channel blocker ingestion is commonly encountered by emergency medicine physicians and toxicologists. Despite a vast array of research on its treatment, results have proven inconsistent. The goal of this study is to evaluate potential vasopressor effects of triiodothyronine (T3) in rats poisoned with verapamil. Following anesthesia and intubation, ten Sprague-Dawley rats were given intravenous verapamil infusion of 10 mg/kg/h. This dose was titrated until a mean arterial pressure (MAP) of 50-55 mmHg was achieved and maintained for a period of at least 5 min. The verapamil infusion was then maintained at that rate. Five rats were randomized to receive a T3 bolus of 0.4 mcg/kg preceding an infusion of 1.5 mcg/kg/day which was doubled every 2 min until any of the following endpoints: systolic blood pressure of 100 mmHg, an elapsed time of 60 min, or death. The other five received an equal volume of normal saline solution. The primary outcome measure was survival with secondary outcomes of MAP and heart rate. The T3 group did have a slightly longer, yet not statistically significant, average time to cessation of electrical activity-30.0 +/- 14.4 min versus 23.8 +/- 9.5 min in the placebo group. Average MAP decreased nearly identically in the two groups. Heart rates were not reliable indicators of toxicity in this rat model as there was little decrease until immediately prior to death in most animals. Despite significant variability in toxicity among individual animals, no statistically significant difference in survival time, heart rate, or MAP was found between groups treated with T3 and those receiving saline.

Verapamil eliminates the hierarchical nature of activation frequencies from the pulmonary veins to the atria during paroxysmal atrial fibrillation

There is evidence that verapamil promotes the persistence of paroxysmal atrial fibrillation (AF). Little is known about the underlying mechanisms. The purpose of this study was to determine the effect of verapamil on dominant frequencies (DFs) in the pulmonary veins (PVs) and atria during paroxysmal AF with reference to its potential arrhythmogenicity. Forty-three patients with paroxysmal AF were studied. Bipolar electrograms were recorded simultaneously during AF from the right atrial free wall (RAFW), coronary sinus (CS) and three PVs, or two PVs and the left atrial appendage (LAA). The DFs were obtained by fast Fourier transform analysis before and after infusion of verapamil (0.1 mg/kg, intravenously). At baseline, the maximum DF among the PVs (6.9 +/- 0.9 Hz) was significantly higher than the DF in the RAFW (6.2 +/- 0.7 Hz), CS (5.7 +/- 0.5 Hz), or LAA (5.9 +/- 0.7 Hz) (P<.01); there was a substantial PV-to-atrial DF gradient (RAFW 0.7 +/- 0.9, CS 1.1 +/- 0.7, LAA 0.7 +/- 0.9 Hz). Verapamil increased the atrial DF to 6.9 +/- 0.8, 6.6 +/- 0.7, and 7.2 +/- 1.0 Hz in the RAFW, CS, and LAA, respectively (P<.0001) but did not affect the maximum PV DF (7.1 +/- 0.7 Hz). The PV-to-atrial DF gradient was eliminated after verapamil (RAFW 0.2 +/- 0.8, CS 0.5 +/- 0.6, LAA -0.4 +/- 0.8 Hz; P<.01 vs. baseline). Verapamil increases the activation frequency in the atria but not in the PVs, eliminating the PV-to-atrial DF gradient during paroxysmal AF.