scholarly journals Cardiovascular Effects of Epinephrine During Experimental Hypothermia (32°C) With Spontaneous Circulation in an Intact Porcine Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Rizwan Mohyuddin ◽  
Erik Sveberg Dietrichs ◽  
Predip Sundaram ◽  
Timofey Kondratiev ◽  
Marie Fjellanger Figenschou ◽  
...  

Aims: Rewarming from accidental hypothermia and therapeutic temperature management could be complicated by cardiac dysfunction. Although pharmacologic support is often applied when rewarming these patients, updated treatment recommendations are lacking. There is an underlying deficiency of clinical and experimental data to support such interventions and this prevents the development of clinical guidelines. Accordingly, we explored the clinical effects of epinephrine during hypothermic conditions.Materials and methods: Anesthetized pigs were immersion cooled to 32°C. Predetermined variables were compared at temperature/time-point baseline, after receiving 30 ng/kg/min and 90 ng/kg/min epinephrine infusions: (1) before and during hypothermia at 32°C, and after rewarming to 38°C (n = 7) and (2) a time-matched (5 h) normothermic control group (n = 5).Results: At 32°C, both stroke volume and cardiac output were elevated after 30 ng/kg/min administration, while systemic vascular resistance was reduced after 90 ng/kg/min. Epinephrine infusion did not alter blood flow in observed organs, except small intestine flow, and global O2 extraction rate was significantly reduced in response to 90 ng/kg/min infusion. Electrocardiographic measurements were unaffected by epinephrine infusion.Conclusion: Administration of both 30 ng/kg/min and 90 ng/kg/min at 32°C had a positive inotropic effect and reduced afterload. We found no evidence of increased pro-arrhythmic activity after epinephrine infusion in hypothermic pigs. Our experiment therefore suggests that β₁-receptor stimulation with epinephrine could be a favorable strategy for providing cardiovascular support in hypothermic patients, at core temperatures >32°C.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
James J Menegazzi ◽  
Jon C Rittenberger ◽  
Brian P Suffoletto ◽  
Eric S Logue ◽  
David D Salcido ◽  
...  

Introduction: Induced hypothermia has been shown to improve survival and neurologic outcomes for ventricular fibrillation (VF) cardiac arrest. Clinical studies have not begun inducing hypothermia until after return of spontaneous circulation (ROSC). The effects of cooling during the resuscitation are not well-studied. Hypothesis: We hypothesized that inducing hypothermia at the start of resuscitation would increase the rates of ROSC and short-term survival (20 minutes) in an established porcine model of prolonged VF. We compared intra-resuscitation hypothermia (IRH) with a normothermic control group (CTL). Methods: We anesthetized and instrumented 28 domestic swine (mean mass 26.5 ±2.4 kgs) with ECG, esophageal temperature, and micromanometer-tipped aortic and right atrial catheters. We then randomly assigned them to IRH and CTL groups (n= 14 each). VF was electrically induced and untreated for 8 minutes. Then resuscitation was begun with mechanical chest compression and ventilation. Hypothermia was induced by rapid IV infusion of ice-cold normal saline (30 mL/kg) at the beginning of resuscitation in the IRH group. The CTL group got 30 mL/kg of body-temperature saline at the start of resuscitation. After 8 minutes of VF, two minutes of CPR was followed by delivery of drugs (epinephrine 0.1 mg/kg, vasopressin 40 U, and propranolol 1.0 mg) and 3 more minutes of CPR (first rescue shock at 13 minutes of VF). ROSC (systolic BP above 80 mmHg for one minute continuously) and survival were recorded, as was total fluid given and hematocrits. Temperatures are reported in degrees C. Rates were compared with 2-tailed Fisher’s exact test, with alpha=0.05. Results: Baseline temperatures at 8 minutes VF did not differ (IRH=37.9° and CTL=37.7°). Post-infusion temperatures at 13 minutes of VF were IRH=34.9° and CTL=37.9°. ROSC occurred in 12/14 (86%) IRH animals and in 6/14 (43%) CTL, with p=0.046. Survival occurred in 8/14 (57%) IRH animals and 4/14 (36%) CTL, with p=0.15. Total fluid volumes given and hematocrits did not differ between groups. Conclusions: IRH doubled the rate of ROSC compared to CTL. There was a non-significant 58% relative improvement in short-term survival. In this porcine model, rapid infusion of ice-cold saline quickly cooled during resuscitation.


2009 ◽  
Vol 19 (4) ◽  
pp. 630-637 ◽  
Author(s):  
Erdinc Aydin ◽  
Helin Deniz Demir ◽  
Huseyin Yardim ◽  
Unal Erkorkmaz

Purpose To investigate the clinical effects and outcomes of intravitreal injection of 4 mg of triamcinolone acetonide (IVTA) after or concomitant with macular laser photocoagulation (MP) for clinically significant macular edema (CSME). Methods Forty-nine eyes of 49 patients with nonproliferative diabetic retinopathy and CSME were randomized into three groups. The eyes in the laser group (n=17), group 1, were subjected to MP 3 weeks after IVTA; the eyes in the IVTA group (n=13), group 2, were subjected to MP, concomitant with IVTA; the eyes in the control group (n=19), group 3, underwent only IVTA application. Visual acuity (VA), fundus fluorescein angiography, and photography were performed in each group. Results In the first group, the mean VA improved from 0.17±0.09 at baseline to 0.28±0.15 (p=0.114) and in the second group, deteriorated from 0.19±0.08 at baseline to 0.14±0.08 at the sixth month (p=0.141), respectively. In Group 3, the mean VA improved from 0.16±0.08 at baseline to 0.28±0.18 (p=0.118) at the end of the follow-up. When VA was compared between the control and study groups, significant difference was detected at the sixth month (p=0.038). Conclusions MP after IVTA improved VA, rather than MP concomitant with IVTA, and only IVTA application for CSME. MP after IVTA may reduce the recurrence of CSME and needs further investigations in a longer period.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jiefeng Xu ◽  
Sen Ye ◽  
Zilong Li ◽  
Moli Wang ◽  
Zhengquan Wang ◽  
...  

Introduction: Systemic ischemia-reperfusion injury produced by CA and resuscitation can result in severe post-cardiac arrest syndrome; which includes systemic inflammatory response and multiple organ dysfunction syndrome such as acute pulmonary edema. We previously demonstrated that remote ischemic post-conditioning (RIpostC) improved post-resuscitation myocardial and cerebral function in a rat model of CA. In this study, we investigated the effects of RIpostC on inflammatory response and pulmonary edema after CPR in a porcine model. Hypothesis: RIpostC would alleviate post-resuscitation inflammatory response and pulmonary edema in a porcine model of CA. Methods: Fourteen male domestic pigs weighing 37 ± 2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. The animals were then randomized to receive RIpostC or control. Coincident with the start of CPR, RIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results: Six of the seven animals in each group were successfully resuscitated. After resuscitation, significantly lower levels of tumor necrosis factor-α and interleukin-6 were measured in the animals that received RIpostC when compared with the control group. Post-resuscitation extra-vascular lung water index was lower in the RIpostC group than in the control group; in which the differences were significant at 2,3 and 4 hrs (Table). Conclusion: In a porcine model of CA, RIpostC significantly alleviates post-resuscitation inflammatory response and pulmonary edema.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomohiko Shindo ◽  
Kenta Ito ◽  
Kenichiro Hanawa ◽  
Kentaro Aizawa ◽  
Takashi Shiroto ◽  
...  

Purpose: Despite recent progress in the management of ischemic heart disease (IHD), the number of patients with severe IHD is increasing. In this study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD and to elucidate the underlying molecular mechanisms for the LIPUS-induced angiogenesis. Methods and Results: We first confirmed that the LIPUS up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle in cultured human vascular endothelial cells (HUVECs). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n=28). The heart was treated with either sham or LIPUS (32-cycle, 20 min) at 3 different short axis levels (n=14 each). Four weeks after the therapy, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05), whereas it remained unchanged in the control group. Capillary density and regional myocardial blood flow in the ischemic region were also increased in the LIPUS group but not in the control group. The protein expressions of VEGF, eNOS and bFGF in the ischemic area were enhanced in the LIPUS group compared with the control group. To further examine the signaling pathways responsible for the LIPUS-induced angiogenesis, HUVECs were transfected with siRNA or scrambled siRNA of either β1 integrin or caveolin-1. Knockdown of either β1 integrin or caveolin-1 with siRNA suppressed the LIPUS-induced up-regulation of VEGF. siRNA-mediated suppression of either focal adhesion kinase (FAK) or Fyn also inhibited the LIPUS-induced up-regulation of VEGF. Knockdown of these molecules with siRNA was confirmed with real-time PCR. Conclusions: These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD and that β1 integrin and caveolin-1 may be involved in underlying molecular mechanisms for the beneficial effects of the LIPUS.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ian R Drennan ◽  
Steve Lin ◽  
Kevin E Thorpe ◽  
Jason E Buick ◽  
Sheldon Cheskes ◽  
...  

Introduction: Targeted temperature management (TTM) reduces neurologic injury from out-of-hospital cardiac arrest (OHCA). As the risk of neurologic injury increases with prolonged cardiac arrests, the benefit of TTM may depend upon cardiac arrest duration. We hypothesized that there is a time-dependent effect of TTM on neurologic outcomes from OHCA. Methods: Retrospective, observational study of the Toronto RescuNET Epistry-Cardiac Arrest database from 2007 to 2014. We included adult (>18) OHCA of presumed cardiac etiology that remained comatose (GCS<10) after a return of spontaneous circulation. We used multivariable logistic regression to determine the effect of TTM and the duration of cardiac arrest on good neurologic outcome (Modified Rankin Scale (mRS) 0-3) and survival to hospital discharge while controlling for other known predictors. Results: There were 1496 patients who met our inclusion criteria, of whom 981 (66%) received TTM. Of the patients who received TTM, 59% had a good neurologic outcome compared to 39% of patients who did not receive TTM (p< 0.001). After adjusting for the Utstein variables, use of TTM was associated with improved neurologic outcome (OR 1.60, 95% CI 1.10-2.32; p = 0.01) but not with survival to discharge (OR 1.23, 95% CI 0.90-1.67; p = 0.19). The impact of TTM on neurologic outcome was dependent on the duration of cardiac arrest (p<0.05) (Fig 1). Other significant predictors of good neurologic outcome were younger age, public location, initial shockable rhythm, and shorter duration of cardiac arrest (all p values < 0.05). A subgroup analysis found the use of TTM to be associated with neurologic outcome in both shockable (p = 0.01) and non-shockable rhythms (p = 0.04) but was not associated with survival to discharge in either group (p = 0.12 and p = 0.14 respectively). Conclusion: The use of TTM was associated with improved neurologic outcome at hospital discharge. Patients with prolonged durations of cardiac arrest benefited more from TTM.


2021 ◽  
pp. 1-7
Author(s):  
Marta Altieri ◽  
◽  
Mariangela Fratino ◽  
Flavia Pauri ◽  
Antonella Conte ◽  
...  

Background: Italy was one of the first affected countries by coronavirus disease 2019 (COVID-19) pandemic. Public health measures like quarantine or national lockdown were adopted, with negative psychological and clinical effects on patients with chronic diseases. To investigate the impact of lockdown on patients with multiple sclerosis (MS), we developed a 36 items self-report questionnaire. Methods: Questionnaires were emailed to 120 patients with MS and 100 with chronic migraine (CM) as a control group, matched for age, sex, and education. The questionnaire was divided into five domains, evaluating concerns about 1) MS and therapy during COVID-19 pandemic, 2) personal and family caregiving, 3) working activities, 4) general and disease-related emotions during the lockdown, 5) future expectations concerning health status, social life, and working activity. Results: patients with MS had higher scores than those with CM in domains 4 and 5, investigating respectively general and disease-related emotions and future expectations (p= 0.05 and 0.02 respectively). About half of the patients with MS expressed some concern about the need to continue their therapy during the pandemic compared to people with CM (p= 0.0002). Conclusions: Covid-19 pandemic had a more negative impact on psychological status of patients with MS compared with those with CM


2019 ◽  
Author(s):  
Claudio Peixoto Crispi ◽  
Claudio Peixoto Crispi ◽  
Fernando Luis Fernandes Mendes ◽  
Claudio Moura de Andrade ◽  
Leon Cardeman ◽  
...  

ABSTRACTInfertility has been a common postoperative problem caused by peritoneal adhesions. Since several prophylactic agents have recently shown promising preliminary results, more complete studies comparing their real efficacy and safety are needed urgently. The aim of this study was to investigate and describe practical considerations of a porcine model that can be used to assess such prophylactic agents. First, 10 healthy 5½ months old female pigs (24.3 – 31.3 Kg) underwent a standardized laparoscopy to provoke peritubal adhesion formation without prophylactic agents. After 30 days, a second-look laparoscopy was performed to evaluate adhesions and perform adnexectomy for histopathological evaluation. Adhesions at different sites were classified by grade, for which the scores range from 0 (no adhesion) to 3 (very strong vascularized adhesions), and also by area, with scores ranging from 0 (no adhesion) to 4 (>75% of the injured area). The histopathological evaluation of the distal uterine horns, oviducts and ovaries were compared withthose from a control group of six healthy pigs with no previous surgery. Biological samples were collected to assess vitality, inflammation and renal, hepatic and hematopoietic systems. There were small (but significant) changes in serum albumin (P=0.07), globulin (P=0.07), C-reactive protein (P=0.011), fibrinogen (P=0.023) and bilirubin (P<0.01) after 30 days, but all values were within the normal range. No inflammation or abscess formation was observed, but different degrees of adhesion were identified. The estimated occurrence of adhesion (scores >0) and of strong / very strong adhesion (scores >1) was 75% (95% CI: 55 – 94.9) and 65% (95% CI: 45 – 85), respectively. The porcine model represents a useful animal platform that can be used to test the efficacy and safety of candidate prophylactic agents intended to prevent postoperative peritubal adhesions formation. We present several practical considerations and measures that can help to minimize animal suffering and avoid problems during such experiments.


Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Felipe Teran ◽  
Claire Centeno ◽  
Alex L Lindqwister ◽  
William J Hunckler ◽  
William Landis ◽  
...  

Background: Lifeless shock (LS) (previously called EMD and pseudo-PEA) is a global hypotensive ischemic state with retained coordinated myocardial contractile activity and an organized ECG. We have previously described our hypoxic LS model. The role of standard external chest compressions remains unclear in the setting of LS and its associated intrinsic hemodynamics. Although it is known the patients with LS have better prognosis compared to PEA, it is unclear what is the best treatment strategy. Prior work has shown that chest compressions (CC) when synchronized with native systole results in significant hemodynamic improvement, most notably coronary perfusion pressure (CPP), and hence it is plausible that standard dyssynchronous CC may be detrimental to hemodynamics. Furthermore, retrospective clinical data has shown that LS patients treated with vasopressors and no CC, may have better outcomes. We compared epinephrine only versus epinephrine and chest compression, in a porcine model of LS. Methods: Our porcine model of hypoxic LS has previously been described. We randomized pigs to episodes of LS treated with epinephrine only (control) (0.0015 mg/kg) versus epinephrine plus standard external chest compressions (intervention). Animals were endotracheally intubated and mechanically ventilated, and the fraction of inspired oxygen (FiO 2 ) was gradually lowered from room air (20-30% O 2 ) to a target FiO 2 of 3-7% O 2 . This target FiO 2 was maintained until the systolic blood pressure (SBP) dropped to 30 mmHg for 30 seconds, or the animal became bradycardic (HR less than 40), which was defined as the start of LS. FiO 2 was then raised to 100%, and then animal would receive control or intervention. Return of spontaneous circulation (ROSC) was defined as SBP 60 mmHg, stable after 2 minutes. Results: Twenty-six episodes of LS in 11 animals received epinephrine only control and 21 episodes the epinephrine plus chest compression intervention. The rates of ROSC in two minutes or less were 5/26 (19%) in the control arm vs 14/21 (67%) in the intervention arm (P=0.001;95% CI 19.7 %-67.2%). Conclusions: In a swine model of hypoxia induced LS, epinephrine plus CPR may be superior to epinephrine alone.


2021 ◽  
Author(s):  
Yanan Yu ◽  
Ziren Tang ◽  
Jiabao Li ◽  
Miaorong Xie ◽  
Chenchen Hang ◽  
...  

Abstract Background: Rapid changes in glucocorticoid (GC) levels and adrenal insufficiency are related to the development of post-cardiac arrest syndrome. However, changes in glucocorticoid receptors (GR) have not been studied. Hence, this study aimed to investigate the association of early changes in GR and prognosis and immune response in patients who experienced cardiac arrest (CA). Methods: In this observational single-center case-control study, we enrolled patients who were in the early period of return of spontaneous circulation after CA and were admitted to the emergency department of the Beijing Chaoyang Hospital between October 2018 and October 2019. Age- and sex-matched healthy individuals were recruited for the control group after a physical examination.GR expression and cell counts of circulatory T and B lymphocytes, natural killer, and regulatory T (Treg) cells were assessed. Plasma total cortisol and adrenocorticotrophic hormone (ACTH) levels were tested. Since the data for total cortisol and ACTH levels had a skewed distribution, we compared our results with the natural logarithmic conversion values after adding 1 (ln [total cortisol+ 1], ln [ACTH+ 1]). Measurement data with a skewed distribution are expressed as medians (25th and 75th percentiles). The Mann–Whitney U test was used to compare variables between groups. The qualitative parameters in the 2 × 2 contingency table were used for analysis.Results: Overall, 85 patients who experienced CA and 40 healthy individuals were enrolled. All cell counts were lower and plasma total cortisol levels were higher (P<0.001) in patients who experienced CA than those in the healthy control group. GR expression in Treg cells and CD3+CD4+ T lymphocytes was not significantly different, but the mean fluorescence intensity and GR expression in other cells were lower in patients who experienced CA (P<0.05) than those in the healthy control group. ACTH levels did not show any difference. There were no significant differences between survivors and non-survivors. Conclusion: Our findings provide insights into GC sensitivity and immunosuppressive status in these patients, and a new perspective for GC targeted treatment.


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