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The Evaluation of Serum Digoxin Measurement Frequency In Patients Hospitalized In A University Hospital and Treated with Digoxin
Clinical Therapeutics antipsychotics) can be implicated in the occurrence of constipation in these patients. Methods: The main purpose of this study was to measure total laxative drug use in all four public psychiatric hospitals (meant for medium-long stays) in the Basque Country since January 2008 to October 2016. First, individual laxative (any drug from the A06 group in the ATC classification system) consumption data was obtained. Defined daily dose (DDD) values for individual laxatives were those assigned by the World Health Organization (WHO). Global laxative use was then calculated as the sum of individual DDD of all drugs divided by the annual hospital stay number. We also studied the use of rectal enemas separately. Total enema consumption was reported per 100 hospital stays. Results: During the study period of almost 9 years a total of 1.853.261 DDDs of laxatives were used in 1.964.250 hospital stays, yielding a mean consumption of almost 1 laxative DDD/ stay. Lactulose was by far the most frequently used individual drug accounting for 1.822.108 DDDs (98% of total). Macrogol use has recently increased, accounting for around 30% of all doses in October 2016. In the same period, a total of 18.776 rectal enemas were administered, resulting in almost 1 enema used per 100 hospital stays. Conclusions: The burden of constipation in psychiatric hospital is high, as shown by both laxative and rectal enema use.
Single Ingestion of Green Tea Substantially Decrease Plasma Concentrations of Nadolol In Healthy Volunteers S. Misaka; O. Abe; T. Ono; Y. Ono; H. Ogata; I. Miura; Y. Shikama; H. Yabe; and J. Kimura Fukushima Medical University School of Medicine, Fukushima, Japan Background: Our group has reported that repeated ingestion of a bottled green tea (700 ml/day) for two weeks reduced plasma concentrations of orally administered nadolol, a hydrophilic and nonmetabolized beta blocker, in healthy subjects. However, it is still unknown whether a single ingestion of green tea also affects nadolol pharmacokinetics. Methods: To evaluate the effects of a concomitant or 1 hour before ingestion of green tea infusion on nadolol pharmacokinetics, an open-label, three-period crossover study was conducted in 11 healthy Japanese volunteers. After overnight fasting, subjects received a single oral administration of nadolol (30 mg) with or 1 hour after green tea, or with water in a volume of 150 ml. Green tea infusion was made in every trial by putting commercial green tea leaves (3 g/100 mL) into hot water (90°C) for 4 min with stirring. Plasma and urinary concentrations of nadolol were determined over 48 hours. Results: Nadolol AUC and Cmax with green tea were 37% (P< 0.001) and 33% (P< 0.001) of those with water, respectively. In addition, ingestion of green tea 1 hour before nadolol administration also resulted in a significant reduction of nadolol AUC and Cmax by 55% (P< 0.01) and 52% (P< 0.01), respectively. The decrease in nadolol AUC by green tea correlated with nadolol AUC in water phase (r2= 0.93, P< 0.001). There were no differences in Tmax and the renal clearance of nadolol among three groups. Conclusions: Single concomitant ingestion of green tea substantially decreases plasma concentrations of nadolol without changing its renal clearance, presumably by inhibiting the intestinal absorption of nadolol. Moreover, the reduction in nadolol bioavailability could persist for at least 1 hour after drinking a cup of brewed green tea.
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High Dose Insulin For Treatment of Calcium Channel Blocker Overdose: A Case Series M.F. Tsoi; B.M.Y. Cheung; and T.T. Cheung The University of Hong Kong, Hong Kong Background: Calcium channel blocker (CCB) overdose may cause hypotension, shock and death. There has been limited evidence on the efficacy of high dose insulin (HDI) as supportive therapy for calcium channel blocker overdose patients. Therefore, we characterised and studied the survival of patients treated with HDI following a calcium channel blocker overdose. Methods: The Poison Information and Clinical Management System was used to identify patients with CCB overdose. For inclusion, patients must be documented to have CCB overdose and hypotension despite calcium salt infusion. Patients were stratified into two groups - with or without HDI treatment. The primary outcome was all-cause mortality. Results were analysed using SPSS version 23.0. Results: Seventeen patients were included in this study. Fifteen (88.0%) patients were diagnosed with hypertension. Four (23.5%) and five (29.4%) patients had diagnosis of a psychiatric disorder and diabetes mellitus, respectively. Six (35.3%) patients also took an overdose of anti-hypertensive medication. The mortality rates of patients were 38.5% and 0% in patients with or without HDI treatment, respectively (P= 0.152). There was no significant difference in the time-to-event relationship with respect to all-cause mortality (P= 0.594). Conclusions: CCB overdose can be fatal. HDI did not improve survival in patients with CCB overdose.
The Evaluation of Serum Digoxin Measurement Frequency In Patients Hospitalized In A University Hospital and Treated with Digoxin S. Oncu; A. Gelal; O. Aslan; and S.R. Ucku Dokuz Eylul University Medical Faculty, Izmir, Turkey Background: Therapeutic drug monitoring (TDM) for digoxin started nearly 50 years ago. However, inappropriate use of TDM for digoxin is still encountered despite so many years of practice. The aims of the study were to find out the frequency of serum digoxin concentration measurements, the rate of unnecessarily frequent measurements and the reasons for unnecessarily frequent measurements. Methods: This is a descriptive and a cross sectional study which evaluates the data of the patients who had been hospitalized between January 2011-December 2015, treated with oral digoxin. Patients who had more than one measurement of serum digoxin concentration were included in the study evaluation. When the time between consecutive measurements was less than 7 days, it was considered an “unnecessary measurement”. Descriptive statistical analysis was performed for serum digoxin measurement frequency, time between consecutive measurements, serum digoxin, potassium and creatinine levels, age, gender, diagnosis and the inpatient department. The chi-square, chi-square for trend and logistic regression analysis were used. Results: We evaluated 2065 hospital admissions for 1621 patients and 11407 serum digoxin measurements. The time between consecutive serum digoxin concentration measurements was 1.9±2.4 days and 96.7% of all measurements were classified as unnecessary. While no correlation between patient age, gender, serum creatinine level and measurement frequency was found, unnecessary measurement frequency was high when potassium levels were within the normal range. Unnecessary measurement frequency increased when serum digoxin level exceeded 2 ng/mL. Unnecessary measurements were often performed in all departments with the highest frequency in coronary care unit and cardiology department.
Volume 39 Number 8S
Posters Conclusions: In our study, unnecessary serum digoxin measurement frequency was found to be very high although only one of the appropriateness criteria was evaluated. The findings reveal the need for a continuous medical education on TDM in order to plan a proper treatment and reduce unnecessary costs.
Genetic Polymorphisms In Vasoactive Eicosanoids Modify The Risk of Cardiovascular Events and Mortality In Renal Transplant Recipients G. Gervasini1; E. Luna2; G. Garcia-Pino1; M. García-Cerrada3; L. Azevedo2; E. Vergara1; and J.J. Cubero2 1 Medical School, University of Extremadura, Badajoz, Spain; 2 Service of Nephrology, Infanta Cristina University Hospital, Badajoz, Spain; and 3Service of Clinical Analyses, Don BenitoVillanueva Hospital, Badajoz, Spain Background: Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases lead to eicosanoids, mainly epoxyeicosatrienoic (EETs) and 20-hydroxyeicosatetraenoic (20-HETE) acids, which are key for vascular homeostasis. We aim to determine whether genetic variability in these routes may contribute to CV risk in renal transplant recipients. Methods: In a cohort of 355 patients, we determined the presence of four polymorphisms known to affect eicosanoids levels, namely CYP2C8*3, CYP2J2*7, CYP4A1 F434S and CYP4F2 V433M. Associations with all-cause and CV mortality, CV event-free longterm survival and graft survival were retrospectively investigated. Results: CYP2J2*7 showed a statistical trend towards higher CV mortality (P= 0.06) and lower cardiac or cerebral event-free longterm survival (P= 0.05). These associations became significant when the analysis was restrained to 316 patients without a history of CV events prior to transplantation [hazard ratio (HR)= 11.52 (1.6879.10), p= 0.01 and 3.17 (1.01-9.95), p= 0.04 for CV mortality and event-free survival, respectively]. In this subgroup of patients, CYP2C8*3 showed an inverse association with event-free survival [HR= 0.36 (0.13-0.95), p= 0.04]. Conclusions: Our results show, for the first time to our knowledge, that variability in EET-synthesizing genes may modify CV outcomes in renal transplant recipients, a population that is already at a high risk of suffering these events.
Circadian Alteration of Plasma Calcitonin Gene-Related Peptide, Endothelin-1 and Hemodynamic Parameters In Normotensive and Hypertensive Rats N.V. Gongadze1; T.D. Kezeli2; Z.V. Chapichadze3; M.V. Okujava1; G.V. Sukoyan2; N.M. Dolidze2; M.K. Chipashvili2; and M.G. Mirzashvili1,2,3 1 Department of Medical Pharmacology, Tbilisi State Medical University, Tbilisi, Georgia; 2Department of Pharmacology, Iv. Javakhishvili Tbilisi, State University, Tbilisi, Georgia; and 3 Department of Pharmacology, LEPL State Regulation Agency for Medical Activities, Tbilisi, Georgia Background: Studies provide evidence that calcitonin gene-related peptide (CGRP) and endothelin-1 (E1) may be involved in the pathophysiology of hypertension. The purpose of this study was to evaluate the influence of the circadian profile of plasma CGRP and E1 on hemodynamic indices and baroreflex sensitivity (BRS) in 24 hours (h) period in normotensive Wistar-Kyoto (WKY) and hypertensive rats (HR). Methods: Experiments were performed in male unanesthetized WKY and HR (two-kidney, one clip) weighing 200-250g with preliminary
August 2017
implanted catheters into right jugular vein and carotid artery. Blood pressure (BP), heart period (HP) and BRS were assessed hourly during 24h. Blood samples for determination of CGRP and E1 plasma concentration (pg/ml) were drawn at 9:00, 15:00 and 21:00h. Results: In WKY animals the circadian acrophase for BP (125+6.4 mm Hg) was recorded at 11:44h, while the peak circadian values for HR (164+8.2 ms) and BRS (0.98+0.02 ms mm Hg-1) were occurred at 22:57h and 23:12h respectively. In HR in comparison to WKY rats the BP was significantly increased with its acrophase at 24:10h (184+8.6 mm Hg) which vs. WKY rats was associated with significant decreased in BRS (0.46+0.04 ms mm Hg-1, P< 0.001) and reduction in HP (135+5.6 ms, P< 0.05), by shifted their acrophase with respect to WKY rats to 14:12 h and 17:15 h respectively. The mean plasma content of CGPR in WKY rats significantly exceeded this value in HR with their corresponding acrophases at 21:00h (164.0+22.8 pg/ml) and at 15:00h (50.2+8.4 pg/ml), while E1 plasma peak concentration occurred at 9:00h in WKY rats (3.4+0.6 pg/ml), at 21:00 (8.6+0.2 pg/ml) in HR. Conclusions: It is suggested that CGRP and E1 plasma concentration undergo to circadian fluctuations in WKY and HR with corresponding alterations in hemodynamic indices and BRS, especially in HR, indicating their possible involvement in pathogenesis of hypertension.
Electrophysiological Properties of Calcium-Sensitiser Levosimendan During Rewarming From Severe Hypothermia In Vivo E.S. Dietrichs1,2,3,*; B. Håheim1,*; T. Kondratiev1; and T. Tveita1,2 UiT, The Arctic University of Norway; 2University Hospital of Northern Norway; and 3Norwegian Air Ambulance Foundation; *These authors contributed equally to this work Background: Previous research aimed at ameliorating hypothermia-induced cardiac dysfunction has shown that drugs working via phosphodiesterase 3-inhibition or sensitising the cardiac troponin C complex have promising inotropic effects during hypothermia. During rewarming of hypothermic patients, ventricular arrhythmias and cardiac arrest is however a lethal complication contributing to 30-40% mortality in this patient group. Earlier studies from our group indicate that such arrhythmias could be caused by an activation-repolarisation mismatch, where cardiac repolarisation is prolonged. We therefore tested the electrophysiological properties of levosimendan, a calcium sensitizer and dose-dependent phosphodiesterase 3-inhibitor during rewarming from experimental hypothermia. Methods: An in vivo rat model designed for cardiac studies during experimental hypothermia (3h at 15ºC) and rewarming was used, and two groups were included: 1) a hypothermic group receiving levosimendan the last hour of stable hypothermia and during rewarming, and 2) a hypothermic placebo (vehicle) control group. Electrocardiographic variables were monitored using a 3-channel Fe136 Animal Bio Amp device. Results: After rewarming to 37ºC, both cardiac activation time (QRS-interval) and repolarisation time (QT-interval), returned to within normothermic baseline values in the levosimendan-treated group. In control animals, both the QRS-interval and the QT-interval were prolonged compared to levosimendan-treated animals. Conclusions: The present data shows that levosimendan-treated animals have restored cardiac electrophysiology during rewarming from severe hypothermia. In untreated controls, conduction disturbances, with pro-arrhythmic potential occurred when compared to the treatment group. This study indicates that drugs with calcium sensitising and phosphodiesterase 3-inhibitory properties appear safe and may provide beneficial, electrophysiological effects during rewarming from severe hypothermia. 1
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Single Ingestion of Green Tea Substantially Decrease Plasma Concentrations of Nadolol In Healthy Volunteers S. Misaka; O. Abe; T. Ono; Y. Ono; H. Ogata; I. Miura; Y. Shikama; H. Yabe; and J. Kimura Fukushima Medical University School of Medicine, Fukushima, Japan Background: Our group has reported that repeated ingestion of a bottled green tea (700 ml/day) for two weeks reduced plasma concentrations of orally administered nadolol, a hydrophilic and nonmetabolized beta blocker, in healthy subjects. However, it is still unknown whether a single ingestion of green tea also affects nadolol pharmacokinetics. Methods: To evaluate the effects of a concomitant or 1 hour before ingestion of green tea infusion on nadolol pharmacokinetics, an open-label, three-period crossover study was conducted in 11 healthy Japanese volunteers. After overnight fasting, subjects received a single oral administration of nadolol (30 mg) with or 1 hour after green tea, or with water in a volume of 150 ml. Green tea infusion was made in every trial by putting commercial green tea leaves (3 g/100 mL) into hot water (90°C) for 4 min with stirring. Plasma and urinary concentrations of nadolol were determined over 48 hours. Results: Nadolol AUC and Cmax with green tea were 37% (P< 0.001) and 33% (P< 0.001) of those with water, respectively. In addition, ingestion of green tea 1 hour before nadolol administration also resulted in a significant reduction of nadolol AUC and Cmax by 55% (P< 0.01) and 52% (P< 0.01), respectively. The decrease in nadolol AUC by green tea correlated with nadolol AUC in water phase (r2= 0.93, P< 0.001). There were no differences in Tmax and the renal clearance of nadolol among three groups. Conclusions: Single concomitant ingestion of green tea substantially decreases plasma concentrations of nadolol without changing its renal clearance, presumably by inhibiting the intestinal absorption of nadolol. Moreover, the reduction in nadolol bioavailability could persist for at least 1 hour after drinking a cup of brewed green tea.
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High Dose Insulin For Treatment of Calcium Channel Blocker Overdose: A Case Series M.F. Tsoi; B.M.Y. Cheung; and T.T. Cheung The University of Hong Kong, Hong Kong Background: Calcium channel blocker (CCB) overdose may cause hypotension, shock and death. There has been limited evidence on the efficacy of high dose insulin (HDI) as supportive therapy for calcium channel blocker overdose patients. Therefore, we characterised and studied the survival of patients treated with HDI following a calcium channel blocker overdose. Methods: The Poison Information and Clinical Management System was used to identify patients with CCB overdose. For inclusion, patients must be documented to have CCB overdose and hypotension despite calcium salt infusion. Patients were stratified into two groups - with or without HDI treatment. The primary outcome was all-cause mortality. Results were analysed using SPSS version 23.0. Results: Seventeen patients were included in this study. Fifteen (88.0%) patients were diagnosed with hypertension. Four (23.5%) and five (29.4%) patients had diagnosis of a psychiatric disorder and diabetes mellitus, respectively. Six (35.3%) patients also took an overdose of anti-hypertensive medication. The mortality rates of patients were 38.5% and 0% in patients with or without HDI treatment, respectively (P= 0.152). There was no significant difference in the time-to-event relationship with respect to all-cause mortality (P= 0.594). Conclusions: CCB overdose can be fatal. HDI did not improve survival in patients with CCB overdose.
The Evaluation of Serum Digoxin Measurement Frequency In Patients Hospitalized In A University Hospital and Treated with Digoxin S. Oncu; A. Gelal; O. Aslan; and S.R. Ucku Dokuz Eylul University Medical Faculty, Izmir, Turkey Background: Therapeutic drug monitoring (TDM) for digoxin started nearly 50 years ago. However, inappropriate use of TDM for digoxin is still encountered despite so many years of practice. The aims of the study were to find out the frequency of serum digoxin concentration measurements, the rate of unnecessarily frequent measurements and the reasons for unnecessarily frequent measurements. Methods: This is a descriptive and a cross sectional study which evaluates the data of the patients who had been hospitalized between January 2011-December 2015, treated with oral digoxin. Patients who had more than one measurement of serum digoxin concentration were included in the study evaluation. When the time between consecutive measurements was less than 7 days, it was considered an “unnecessary measurement”. Descriptive statistical analysis was performed for serum digoxin measurement frequency, time between consecutive measurements, serum digoxin, potassium and creatinine levels, age, gender, diagnosis and the inpatient department. The chi-square, chi-square for trend and logistic regression analysis were used. Results: We evaluated 2065 hospital admissions for 1621 patients and 11407 serum digoxin measurements. The time between consecutive serum digoxin concentration measurements was 1.9±2.4 days and 96.7% of all measurements were classified as unnecessary. While no correlation between patient age, gender, serum creatinine level and measurement frequency was found, unnecessary measurement frequency was high when potassium levels were within the normal range. Unnecessary measurement frequency increased when serum digoxin level exceeded 2 ng/mL. Unnecessary measurements were often performed in all departments with the highest frequency in coronary care unit and cardiology department.
Volume 39 Number 8S
Posters Conclusions: In our study, unnecessary serum digoxin measurement frequency was found to be very high although only one of the appropriateness criteria was evaluated. The findings reveal the need for a continuous medical education on TDM in order to plan a proper treatment and reduce unnecessary costs.
Genetic Polymorphisms In Vasoactive Eicosanoids Modify The Risk of Cardiovascular Events and Mortality In Renal Transplant Recipients G. Gervasini1; E. Luna2; G. Garcia-Pino1; M. García-Cerrada3; L. Azevedo2; E. Vergara1; and J.J. Cubero2 1 Medical School, University of Extremadura, Badajoz, Spain; 2 Service of Nephrology, Infanta Cristina University Hospital, Badajoz, Spain; and 3Service of Clinical Analyses, Don BenitoVillanueva Hospital, Badajoz, Spain Background: Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases lead to eicosanoids, mainly epoxyeicosatrienoic (EETs) and 20-hydroxyeicosatetraenoic (20-HETE) acids, which are key for vascular homeostasis. We aim to determine whether genetic variability in these routes may contribute to CV risk in renal transplant recipients. Methods: In a cohort of 355 patients, we determined the presence of four polymorphisms known to affect eicosanoids levels, namely CYP2C8*3, CYP2J2*7, CYP4A1 F434S and CYP4F2 V433M. Associations with all-cause and CV mortality, CV event-free longterm survival and graft survival were retrospectively investigated. Results: CYP2J2*7 showed a statistical trend towards higher CV mortality (P= 0.06) and lower cardiac or cerebral event-free longterm survival (P= 0.05). These associations became significant when the analysis was restrained to 316 patients without a history of CV events prior to transplantation [hazard ratio (HR)= 11.52 (1.6879.10), p= 0.01 and 3.17 (1.01-9.95), p= 0.04 for CV mortality and event-free survival, respectively]. In this subgroup of patients, CYP2C8*3 showed an inverse association with event-free survival [HR= 0.36 (0.13-0.95), p= 0.04]. Conclusions: Our results show, for the first time to our knowledge, that variability in EET-synthesizing genes may modify CV outcomes in renal transplant recipients, a population that is already at a high risk of suffering these events.
Circadian Alteration of Plasma Calcitonin Gene-Related Peptide, Endothelin-1 and Hemodynamic Parameters In Normotensive and Hypertensive Rats N.V. Gongadze1; T.D. Kezeli2; Z.V. Chapichadze3; M.V. Okujava1; G.V. Sukoyan2; N.M. Dolidze2; M.K. Chipashvili2; and M.G. Mirzashvili1,2,3 1 Department of Medical Pharmacology, Tbilisi State Medical University, Tbilisi, Georgia; 2Department of Pharmacology, Iv. Javakhishvili Tbilisi, State University, Tbilisi, Georgia; and 3 Department of Pharmacology, LEPL State Regulation Agency for Medical Activities, Tbilisi, Georgia Background: Studies provide evidence that calcitonin gene-related peptide (CGRP) and endothelin-1 (E1) may be involved in the pathophysiology of hypertension. The purpose of this study was to evaluate the influence of the circadian profile of plasma CGRP and E1 on hemodynamic indices and baroreflex sensitivity (BRS) in 24 hours (h) period in normotensive Wistar-Kyoto (WKY) and hypertensive rats (HR). Methods: Experiments were performed in male unanesthetized WKY and HR (two-kidney, one clip) weighing 200-250g with preliminary
August 2017
implanted catheters into right jugular vein and carotid artery. Blood pressure (BP), heart period (HP) and BRS were assessed hourly during 24h. Blood samples for determination of CGRP and E1 plasma concentration (pg/ml) were drawn at 9:00, 15:00 and 21:00h. Results: In WKY animals the circadian acrophase for BP (125+6.4 mm Hg) was recorded at 11:44h, while the peak circadian values for HR (164+8.2 ms) and BRS (0.98+0.02 ms mm Hg-1) were occurred at 22:57h and 23:12h respectively. In HR in comparison to WKY rats the BP was significantly increased with its acrophase at 24:10h (184+8.6 mm Hg) which vs. WKY rats was associated with significant decreased in BRS (0.46+0.04 ms mm Hg-1, P< 0.001) and reduction in HP (135+5.6 ms, P< 0.05), by shifted their acrophase with respect to WKY rats to 14:12 h and 17:15 h respectively. The mean plasma content of CGPR in WKY rats significantly exceeded this value in HR with their corresponding acrophases at 21:00h (164.0+22.8 pg/ml) and at 15:00h (50.2+8.4 pg/ml), while E1 plasma peak concentration occurred at 9:00h in WKY rats (3.4+0.6 pg/ml), at 21:00 (8.6+0.2 pg/ml) in HR. Conclusions: It is suggested that CGRP and E1 plasma concentration undergo to circadian fluctuations in WKY and HR with corresponding alterations in hemodynamic indices and BRS, especially in HR, indicating their possible involvement in pathogenesis of hypertension.
Electrophysiological Properties of Calcium-Sensitiser Levosimendan During Rewarming From Severe Hypothermia In Vivo E.S. Dietrichs1,2,3,*; B. Håheim1,*; T. Kondratiev1; and T. Tveita1,2 UiT, The Arctic University of Norway; 2University Hospital of Northern Norway; and 3Norwegian Air Ambulance Foundation; *These authors contributed equally to this work Background: Previous research aimed at ameliorating hypothermia-induced cardiac dysfunction has shown that drugs working via phosphodiesterase 3-inhibition or sensitising the cardiac troponin C complex have promising inotropic effects during hypothermia. During rewarming of hypothermic patients, ventricular arrhythmias and cardiac arrest is however a lethal complication contributing to 30-40% mortality in this patient group. Earlier studies from our group indicate that such arrhythmias could be caused by an activation-repolarisation mismatch, where cardiac repolarisation is prolonged. We therefore tested the electrophysiological properties of levosimendan, a calcium sensitizer and dose-dependent phosphodiesterase 3-inhibitor during rewarming from experimental hypothermia. Methods: An in vivo rat model designed for cardiac studies during experimental hypothermia (3h at 15ºC) and rewarming was used, and two groups were included: 1) a hypothermic group receiving levosimendan the last hour of stable hypothermia and during rewarming, and 2) a hypothermic placebo (vehicle) control group. Electrocardiographic variables were monitored using a 3-channel Fe136 Animal Bio Amp device. Results: After rewarming to 37ºC, both cardiac activation time (QRS-interval) and repolarisation time (QT-interval), returned to within normothermic baseline values in the levosimendan-treated group. In control animals, both the QRS-interval and the QT-interval were prolonged compared to levosimendan-treated animals. Conclusions: The present data shows that levosimendan-treated animals have restored cardiac electrophysiology during rewarming from severe hypothermia. In untreated controls, conduction disturbances, with pro-arrhythmic potential occurred when compared to the treatment group. This study indicates that drugs with calcium sensitising and phosphodiesterase 3-inhibitory properties appear safe and may provide beneficial, electrophysiological effects during rewarming from severe hypothermia. 1
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