pituitrin and Asphyxia

To study the effects of the combination of adrenaline (epinephrine) and vasopressin compared to adrenaline alone on initial resuscitation success, 24h survival, and neurological outcome in a swine model of asphyxial cardiac arrest (CA).. This prospective randomized experimental study was conducted at a laboratory research department. Twenty female Landrace/Large-White pigs, 12-15 weeks of age, were investigated. Asphyxial CA was induced by clamping of the endotracheal tube. After 4min of untreated CA, resuscitation was initiated by unclamping the endotracheal tube, mechanical ventilation, chest compressions and adrenaline (Group A) or a combination of adrenaline with vasopressin (Group A+V) administered intravenously. In case of restoration of spontaneous circulation (ROSC), the animals were monitored for 30min and then observed for 24h.. Hemodynamic variables were measured at baseline during CPR and in the post-resuscitation period. Statistically significant difference was observed in groups A and A+V regarding coronary perfusion pressure (CPP) during the first minute of CPR. In both groups, ROSC and survival rates were comparable (p=NS). Neurological deficit score (NDS) was significantly higher in the combination group 24h following CA (p<0.001). Brain histological damage score (HDS) was also better in the combination group (p<0.001). Total HDS and NDS showed a statistical significant correlation (p<0.001).. In this porcine model of asphyxial CA, adrenaline alone as well as the combined administration of adrenaline and vasopressin resulted in similar ROSC and survival rates, but the combination of adrenaline and vasopressin resulted in improved neurological and cerebral histopathological outcomes.

Topics: Analysis of Variance; Animals; Asphyxia; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Combined Modality Therapy; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epinephrine; Female; Heart Arrest; Hemodynamics; Infusions, Intravenous; Nervous System Diseases; Random Allocation; Recovery of Function; Reference Values; Risk Assessment; Survival Rate; Sus scrofa; Swine; Time Factors; Vasopressins

Hypoxia and reoxygenation (H-R) contributes to multi-organ failure in neonates, including cardiac and systemic complications. Use of vasopressin, an endogenous vasoconstrictive hormone commonly used to treat refractory hypotension in adults, in neonates with shock remains limited and not yet fully studied. We hypothesize that vasopressin will improve mean arterial pressure (MAP), without compromising cardiac, mesenteric, or carotid hemodynamics using a swine model of neonatal asphyxia.. Anesthetized piglets (1-4 days old, 1.4-2.5 kg, n = 33) were instrumented for continuous monitoring of cardiac index (CI), MAP, and regional arterial [common carotid (CA), superior mesenteric (SMA)] flow. The animals underwent hypoxia at 10-15% oxygen (2 h) followed by reoxygenation at 100% (0.5 h) and 21% (3.5 h) oxygen. Vasopressin infusion was initiated after 2 h reoxygenation at 0.005, 0.01, or 0.02 units/kg/h i.v. for 2 h (n = 7/group). H-R control (saline infusion) and sham-operated (non-asphyxiated) groups were also included. Intermittent blood gases and plasma lactate were determined as well as tissue lactate levels. Statistical significance was determined using ANOVA.. All H-R piglets had hypotension (36-49% decrease in MAP) and decreased regional blood flows (CA -28 to -34%, SMA -12 to +32% of baseline) at 2 h reoxygenation. Vasopressin infusion dose-dependently increased MAP (14% at 0.02 units/kg/h, P < 0.05) without significant detrimental effects in CI, regional blood flows, and intestinal or cerebral tissue lactate levels.. Vasopressin treatment causes a dose-dependent baro-specific effect, while preserving cardiac function and cerebral and mesenteric hemodynamics in newborn piglets following H-R.

Topics: Analysis of Variance; Animals; Animals, Newborn; Asphyxia; Disease Models, Animal; Dose-Response Relationship, Drug; Hemodynamics; Mesentery; Oxygen; Perfusion; Random Allocation; Resuscitation; Vasopressins

The aim of the present study was to assess whether the combination of epinephrine, vasopressin, and nitroglycerin would improve initial resuscitation success, 24-hour survival, and neurologic outcome compared with epinephrine alone in a swine model of asphyxial cardiac arrest (CA).. This prospective randomized experimental study was conducted at a laboratory research department. Twenty male Landrace/Large-White pigs 12 to 15 weeks of age were investigated. Asphyxial CA was induced by occlusion of the endotracheal tube. Pigs remained untreated for 4 minutes before attempting resuscitation by unclamping the endotracheal tube, mechanical ventilation, chest compressions, and epinephrine (group E) or a combination of epinephrine with vasopressin and nitroglycerin (group EVN) administered intravenously. In case of restoration of spontaneous circulation, the animals were supported for 30 minutes and then observed for 24 hours.. Coronary perfusion pressure and mean arterial pressure were significantly increased during cardiopulmonary resuscitation in group EVN. In both groups, restoration of spontaneous circulation and survival rates were comparable (P value, nonsignificant). At 24 hours after CA, neurologic deficit score was significantly better in animals treated with the combination pharmacotherapy (P < .001). Brain histologic damage score was also higher in group EVN compared with group E (P < .001). Total histologic damage score and neurologic deficit score showed a statistical significant correlation (P < .001).. In this porcine model of asphyxial CA, the addition of nitroglycerin to vasopressin and epinephrine maintained elevated coronary perfusion pressure during asphyxia CA and resulted in significantly better neurologic and histopathologic outcome in comparison with epinephrine alone.

Topics: Animals; Asphyxia; Blood Pressure; Brain; Cardiopulmonary Resuscitation; Drug Therapy, Combination; Epinephrine; Heart Arrest; Heart Rate; Hypoxia, Brain; Male; Nitroglycerin; Swine; Vasopressins

The advantage of vasopressin over epinephrine in the treatment of cardiac arrest (CA) is still being debated, and it is not clear whether a high dose of vasopressin is beneficial or detrimental during or after cardiopulmonary resuscitation (CPR) in a rat model of CA. In this study, asphyxial CA was induced in 40 male Sprague-Dawley rats. After 10 minutes of asphyxia, CPR was initiated; and the effects of different doses of vasopressin (low dose, 0.4 U/kg; medium dose, 0.8 U/kg; and high dose, 2.4 U/kg; intravenous; n = 10 in each group) and a saline control (isotonic sodium chloride solution, 1 mL, intravenous) were compared. Outcome measures included the rate of restoration of spontaneous circulation (ROSC) and changes of hemodynamic and respiratory variables after ROSC. The rates of ROSC were 1 of 10 in the saline group and 8 of 10 in each of the 3 vasopressin groups. There were no differences in mean aortic pressure or changes of respiratory function after CPR among the vasopressin groups. However, the heart rate was lower in the high-dose vasopressin group than in the low- and medium-dose groups. These findings indicate that different doses of vasopressin result in a similar outcome of CPR, with no additional benefits afforded by a high dose of vasopressin during or after CPR, in a rat model of asphyxial CA. The mechanism and physiologic significance of the relative bradycardia that occurred in the high-dose vasopressin group are currently unknown and require further investigation.

Topics: Animals; Asphyxia; Cardiopulmonary Resuscitation; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Arrest; Male; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents; Vasopressins

Topics: Animals; Asphyxia; Cardiopulmonary Resuscitation; Disease Models, Animal; Electrocardiography; Epinephrine; Heart Arrest; Rabbits; Vasopressins

In a porcine model, we compared the effect of the combination of vasopressin/epinephrine with that of a lipid emulsion on survival after bupivacaine-induced cardiac arrest.. After administration of 5 mg/kg of a 0.5% bupivacaine solution i.v., ventilation was interrupted for 2 +/- 0.5 (mean +/- SD) min until asystole occurred. Cardiopulmonary resuscitation (CPR) was initiated after 1 min of untreated cardiac arrest. After 2 min of CPR, 10 animals received, every 5 min, either vasopressin combined with epinephrine or 4 mL/kg of a 20% lipid emulsion. Three minutes after each drug administration, up to three countershocks (4, 4, and 6 J/kg) were administered; all subsequent shocks with 6 J/kg. Blood for determination of the plasma bupivacaine concentration was drawn throughout the experiment.. In the vasopressor group, all five pigs survived, whereas none of five pigs in the lipid group had restoration of spontaneous circulation (P < 0.01). There was no significant difference between groups in the plasma concentration of total bupivacaine.. In this model of a bupivacaine-induced cardiac arrest, the vasopressor combination of vasopressin and epinephrine compared with lipid emulsion resulted in higher coronary perfusion pressure during CPR and survival rates.

Topics: Anesthetics, Local; Animals; Asphyxia; Bupivacaine; Cardiopulmonary Resuscitation; Coronary Circulation; Disease Models, Animal; Electric Countershock; Epinephrine; Fat Emulsions, Intravenous; Female; Heart Arrest; Hemodynamics; Injections, Intravenous; Male; Swine; Time Factors; Vasoconstrictor Agents; Vasopressins

Although vasopressin has been reported to be more effective than epinephrine for cardiopulmonary resuscitation in ventricular fibrillation animal models, its efficacy in asphyxia model remains controversy. The purpose of this study was to investigate the effectiveness of vasopressin vs epinephrine on restoration of spontaneous circulation (ROSC) in a rabbit model of asphyxia cardiac arrest. Cardiac arrest was induced by clamping endotracheal tube. After 5 minutes of basic life-support cardiopulmonary resuscitation, animals who had no ROSC were randomly assigned to receive either epinephrine alone (epinephrine group; 200 microg/kg) or vasopressin alone (vasopressin group; 0.8 U/kg). The coronary perfusion pressure (CPP) was calculated as the difference between the minimal diastolic aortic and simultaneously recorded right atrial pressure. Restoration of spontaneous circulation was defined as an unassisted pulse with a systolic arterial pressure of 60 mm Hg or higher for 5 minutes or longer. We induced arrest in 62 rabbits, 15 of whom had ROSC before drug administration and were excluded from analysis. The remaining 47 rabbits were randomized to epinephrine group (n = 24) and vasopressin group (n = 23). Before and after drug administration, CPP in epinephrine group increased significantly (from -4 +/- 4 to 36 +/- 9 mm Hg at peak value, P = .000), whereas CPP in vasopressin group increased only slightly (from 9 +/- 5 to 18 +/- 6 mm Hg at peak value, P = .20). After drug administration, 13 of 24 epinephrine rabbit had ROSC, and only 2 of 23 vasopressin rabbit had ROSC (P < .01). Consequently, we conclude that epinephrine, but not vasopressin, increases survival rates in this adult rabbit asphyxia model.

Topics: Analysis of Variance; Animals; Asphyxia; Cardiopulmonary Resuscitation; Disease Models, Animal; Electrocardiography; Epinephrine; Heart Arrest; Rabbits; Vasopressins

Recently, vasopressin has been reported as a more effective drug than epinephrine (adrenaline) for cardiopulmonary resuscitation (CPR). However, vasopressin decreases myocardial blood flow (MBF) because of its strong vasoconstriction, to maintain better coronary perfusion pressure (CPP) compared with epinephrine. Nitroglycerin is well known to be able to maintain MBF and increase survival rate. In a VF model, vasopressin combined with nitroglycerin maintained CPP; however, low survival rates were observed compared with vasopressin alone. We investigated the effectiveness of the delayed use of nitroglycerin combined with vasopressin in a severe asphyxia model. Fourteen Sprague-Dawley male rats were divided into two groups: vasopressin 0.8 U/kg alone (V-Gr.), and nitroglycerin 0.3 microg/kg 45 s after the administration of 0.8 U/kg vasopressin (VN-Gr.). Six min after asphyxia induced by obstructing the tracheal tube, CPR was performed in two ways. Three animals resuscitated in the V-Gr. (42%) and six/seven (84%) in the VN-Gr. (P<0.05). In the 6 min of asphyxia rat model, vasopressin combined with delayed nitroglycerin is more effective than vasopressin alone.

Topics: Animals; Asphyxia; Cardiopulmonary Resuscitation; Coronary Circulation; Disease Models, Animal; Drug Therapy, Combination; Epinephrine; Nitroglycerin; Rats; Rats, Sprague-Dawley; Vasopressins

Epinephrine has been administered as a drug essential for cardiopulmonary resuscitation (CPR). Recently, vasopressin has been reported to be more effective than epinephrine for CPR in a ventricular fibrillation (VF) model. As a different myocardial pathology is speculated to exist between the VF model and the asphyxia model, we investigated whether vasopressin is also effective in a rat asphyxia model. Twenty-one Sprague-Dawley male rats were divided into three groups: vasopressin 0.8 U/kg (Vaso-Gr), epinephrine 0.05 mg/kg (Epi-Gr), and saline same volume as the other two drugs (Sal-Gr). Five minutes after suffocation induced by obstruction of the tracheal tube, CPR was performed using each drug. Although only one animal survived (17%) in the Sal-Gr, 6/7 (85%) survived in both Vaso-Gr and Epi-Gr (P<0.01). Vasopressin is as effective as epinephrine for CPR in asphyxia-induced rats.

Topics: Animals; Asphyxia; Cardiopulmonary Resuscitation; Epinephrine; Male; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents; Vasopressins

The purpose of this study was to investigate the effects of vasopressin versus epinephrine, and both drugs combined, in a porcine model of simulated adult asphyxial cardiac arrest.. At approximately 7 minutes after the endotracheal tube had been clamped, cardiac arrest was present in 24 pigs and remained untreated for another 8 minutes. After 4 minutes of basic life support cardiopulmonary resuscitation, pigs were randomly assigned to receive, every 5 minutes, either epinephrine (45, 200, or 200 microgram/kg; n=6); vasopressin (0.4, 0.8, or 0.8 U/kg; n=6); or epinephrine combined with vasopressin (high-dose epinephrine/vasopressin combination, microgram/kg and U/kg: 45/0.4, 200/0.8, or 200/0.8; n=6; optimal-dose epinephrine/vasopressin combination, 45/0.4, 45/0.8, or 45/0.8; n=6). Mean+/-SEM coronary perfusion pressure was significantly (P<0.05) higher 90 seconds after high- or optimal-dose epinephrine/vasopressin combinations versus vasopressin alone and versus epinephrine alone (37+/-10 versus 25+/-7 versus 19+/-8 versus 6+/-3 mm Hg; 42+/-6 versus 40+/-5 versus 21+/-5 versus 14+/-6 mm Hg; and 39+/-6 versus 37+/-4 versus 9+/-3 versus 12+/-4 mm Hg, respectively). Six of 6 high-dose, 6 of 6 optimal-dose vasopressin/epinephrine combination, 0 of 6 vasopressin, and 1 of 6 epinephrine pigs had return of spontaneous circulation (P<0.05).. Epinephrine combined with vasopressin, but not epinephrine or vasopressin alone, maintained elevated coronary perfusion pressure during cardiopulmonary resuscitation and resulted in significantly higher survival rates in this adult porcine asphyxial model.

Topics: Animals; Asphyxia; Blood Pressure; Cardiopulmonary Resuscitation; Drug Combinations; Epinephrine; Heart; Heart Arrest; Hemodynamics; Kinetics; Myocardial Reperfusion; Survival Rate; Swine; Vasopressins

Topics: Animals; Asphyxia; Epinephrine; Heart Arrest; Hospitalization; Humans; Swine; Vasoconstrictor Agents; Vasopressins

This study was designed to compare the effects of vasopressin vs. epinephrine vs. the combination of epinephrine with vasopressin on vital organ blood flow and return of spontaneous circulation in a pediatric porcine model of asphyxial arrest.. Prospective, randomized laboratory investigation using an established porcine model for measurement of hemodynamic variables, organ blood flow, blood gases, and return of spontaneous circulation.. University hospital laboratory.. Eighteen piglets weighing 8-11 kg.. Asphyxial cardiac arrest was induced by clamping the endotracheal tube. After 8 mins of cardiac arrest and 8 mins of cardiopulmonary resuscitation, a bolus dose of either 0.8 units/kg vasopressin (n = 6), 200 microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered in a randomized manner. Defibrillation was attempted 6 mins after drug administration.. Mean +/- SEM coronary perfusion pressure, before and 2 mins after drug administration, was 13 +/- 2 and 23 +/- 6 mm Hg in the vasopressin group; 14 +/- 2 and 31 +/- 4 mm Hg in the epinephrine group; and 13 +/- 1 and 33 +/- 6 mm Hg in the epinephrine-vasopressin group, respectively (p = NS). At the same time points, mean +/- SEM left ventricular myocardial blood flow was 44 +/- 31 and 44 +/- 25 mL x min-(1) x 100 g(-1) in the vasopressin group; 30 +/- 18 and 233 +/- 61 mL x min(-1) x 100 g(-1) in the epinephrine group; and 36 +/- 10 and 142 +/- 57 mL x min(-1) x 100 g(-1) in the epinephrine-vasopressin group (p < .01 epinephrine vs. vasopressin; p < .02 epinephrine-vasopressin vs. vasopressin). Total cerebral blood flow trended toward higher values after epinephrine-vasopressin (60 +/- 19 mL x min(-1) x 100 g(-1)) than after vasopressin (36 +/- 17 mL x min(-1) x 100 g(-1)) or epinephrine alone (31 +/- 7 mL x min(-1) x 100 g(-1); p = .07, respectively). One of six vasopressin, six of six epinephrine, and four of six epinephrine-vasopressin-treated animals had return of spontaneous circulation (p < .01, vasopressin vs. epinephrine).. Administration of epinephrine, either alone or in combination with vasopressin, significantly improved left ventricular myocardial blood flow during cardiopulmonary resuscitation. Return of spontaneous circulation was significantly more likely in epinephrine-treated pigs than in animals resuscitated with vasopressin alone.

Topics: Adrenergic Agonists; Age Factors; Animals; Asphyxia; Blood Circulation; Blood Gas Analysis; Cerebrovascular Circulation; Coronary Circulation; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Electric Countershock; Epinephrine; Female; Heart Arrest; Heart Ventricles; Hemodynamics; Random Allocation; Resuscitation; Swine; Time Factors; Vasoconstrictor Agents; Vasopressins

Acute foetal asphyxia, caused by arrest of uterine blood flow, increases both sympathetic activity and peripheral vascular resistance and decreases blood flow to peripheral organs (Jensen et al., J. Dev. Physiol., 9, 543-559). The rapidity and uniformity of this peripheral vasoconstriction suggest that the sympatho-neuronal system may reflexly cause these initial blood flow changes during acute asphyxia. To test this hypothesis, we studied 5 intact and 6 chemically sympathectomized (6-hydroxy-dopamine, 46.1 +/- 6 mg/kg foetal weight) chronically prepared normoxaemic foetal sheep in utero at 0.9 of gestation. Organ blood flows (microsphere method), plasma concentrations of catecholamines, vasopressin, and angiotensin II, acid-base balance and blood gases were measured before, during and after arrest of uterine blood flow for 2 min, i.e., at 0, 1, 2, 3, 4 & 30 min. In intact foetuses there was a progressive increase in arterial blood pressure and a rapid circulatory centralization in favour of the brain stem and heart and at the expense of most of the peripheral organs. The changes in peripheral blood flow during and after asphyxia were well reflected by those in the skin and scalp. In chemically sympathectomized foetuses, arterial blood pressure fell transiently at 1 min of asphyxia and cardiac output was redistributed towards the carcass and intestinal organs at the expense of the heart, spinal medulla, and placenta. We conclude that in foetal sheep at 0.9 of gestation, the short-term adaptation to arrest of uterine blood flow is a rapid and profound peripheral vasoconstriction to effect an increase in arterial blood pressure. This initial response during circulatory centralization, which is necessary to increase or maintain blood flow to the heart, brain stem, and placenta, is blunted by sympathectomy. Thus, the foetal sympatho-neuronal system is important for short-term adaptation to and intact survival of asphyxia.

Topics: Adaptation, Physiological; Angiotensin II; Animals; Asphyxia; Blood Pressure; Catecholamines; Female; Fetus; Homeostasis; Oxidopamine; Pregnancy; Regional Blood Flow; Sheep; Sympathectomy, Chemical; Sympathetic Nervous System; Uterus; Vasoconstriction; Vasopressins

Marked elevations in the vasopressin concentrations in human umbilical cord blood have been reported previously (4, 8). This could either be a part of generalized increase in the activity of fetal endocrine system at the time of birth, a phenomenon that has led to the concept of fetal participation in the onset of labor, or simply due to the stress of delivery. The present study is an attempt to examine the later possibility. Plasma vasopressin was determined by radioimmunoassay [9] in separately collected arterial and venous blood from the umbilical cords of 24 babies spontaneously delivered and 14 babies born after Caesarian Section in the absence of labor. Arterial acid-base determinations were done in each case. The Apgar Score was evaluated by one individual. In order to obtain a general idea of circulating concentration of this hormone in the neonatal period, vasopressin concentrations were determined in the systemic venous blood of 12 normal and 10 stressed babies. Vasopressin concentrations in the umbilical arterial blood of babies born after spontaneous delivery were remarkably high, as compared to all the other groups. Despite a wide range, between 5-2200 pg/ml, there was no correlation between the magnitude of vasopressin elevation and the severity of fetal asphyxia (Fig. 1). The present finding in part, confirms and expands previously observed increased vasopressin levels in the cord blood after spontaneous vaginal delivery. In addition, a lack of correlation between fetal asphyxia and the vasopressin levels suggests that these high levels may not be related to this form of stress.

Topics: Acid-Base Equilibrium; Asphyxia; Cesarean Section; Female; Fetal Blood; Humans; Infant, Newborn; Labor, Obstetric; Pregnancy; Stress, Physiological; Vasopressins

Topics: Aconitum; Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Asphyxia; Barium; Calcium Chloride; Cats; Chlorides; Chloroform; Disease Models, Animal; Electrocardiography; Epinephrine; Guinea Pigs; Magnesium; Male; Potassium; Quinidine; Rats; Sodium Chloride; Strophanthins; Sympatholytics; Vasopressins

Topics: Acute Disease; Adenosine Triphosphate; Alkaloids; Animals; Arrhythmias, Cardiac; Asphyxia; Drug Synergism; Electrocardiography; Epinephrine; Fluorides; Glycogen; Hypercapnia; Male; Norepinephrine; Quinidine; Rats; Vasopressins

Topics: Aconitum; Amides; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Asphyxia; Barium; Calcium Chloride; Cardiac Complexes, Premature; Chlorides; Depression, Chemical; Electrocardiography; Guinea Pigs; Heart Rate; Magnesium; Male; Potassium Chloride; Quinidine; Rats; Strophanthins; Tachycardia; Vasopressins; Ventricular Fibrillation