Elamipretide mitigates ischemia-reperfusion injury in a swine model of hemorrhagic shock.

ischemia-reperfusion injury (IRI) after hemorrhage is potentiated by aortic occlusion or resuscitative endovascular balloon occlusion of the aorta (REBOA). Given the central role of mitochondrial injury in shock, we hypothesized that Elamipretide, a peptide that protects mitochondria, would mitigate IRI after hemorrhagic shock and REBOA. Twelve pigs were subjected to hemorrhagic shock and 45 min of REBOA. After 25 min of REBOA, animals received either saline or Elamipretide. Animals were transfused with autologous blood during balloon deflation, and pigs were resuscitated with isotonic crystalloids and norepinephrine for 4.25 h. Elamipretide-treated animals required less crystalloids than the controls (62.5 [50-90] and 25 [5-30] mL/kg, respectively), but similar amounts of norepinephrine (24.7 [8.6-39.3] and 9.7 [2.1-12.5] mcg/kg, respectively). Treatment animals had a significant reduction in serum creatinine (control: 2.7 [2.6-2.8]; Elamipretide: 2.4 [2.4-2.5] mg/dL; p = 0.04), troponin (control: 3.20 [2.14-5.47] ng/mL, Elamipretide: 0.22 [0.1-1.91] ng/mL; p = 0.03), and interleukin-6 concentrations at the end of the study. There were no differences in final plasma lactate concentration. Elamipretide reduced fluid requirements and protected the kidney and heart after profound IRI. Further understanding the subcellular consequences of REBOA and mitochondrial rescue will open new therapeutic avenues for patients suffering from IRI after hemorrhage.

Intramuscular adrenaline for out-of-hospital cardiac arrest is associated with faster drug delivery: A feasibility study.

BACKGROUND: Early adrenaline administration is associated with return of spontaneous circulation (ROSC) and survival in out-of-hospital cardiac arrest (OHCA). Animal data demonstrate a similar rate of ROSC when early intramuscular (IM) adrenaline is given compared to early intravenous (IV) adrenaline. AIM: To evaluate the feasibility of protocolized first-dose IM adrenaline in OHCA and it's effect on time from Public Safety Access Point (PSAP) call receipt to adrenaline administration when compared to IO and IV administration. METHODS: This is a before-and-after feasibility study of adult OHCAs in a single EMS service following adoption of a protocol for first-dose IM adrenaline. Time from PSAP call to administration and outcomes were compared to 674 historical controls (from January 1, 2013-February 8, 2021) who received at least one dose of adrenaline by IV or IO routes. RESULTS: During the study period, first-dose IM adrenaline was administered to 99 patients (December 1, 2019-February 8, 2021). IM adrenaline was given a median of 12.2 min (95% CI 11.4-13.1 min) after the PSAP call receipt compared to 15.3 min for the IV route (95% CI 14.6-16.0 min) and 15.3 min for the IO route (95% CI 14.9-15.7 min) with a time savings of 3 min (95% CI 2-4 min). Rates of survival to hospital discharge appeared similar between groups: 10% for IM, 8% for IV and 7% for IO. However, results related to survival were underpowered for statistical comparison. CONCLUSIONS: Within the limitations of a small sample size and before-and-after design, first-dose IM adrenaline was feasible and reduced the time to adrenaline administration.

Hypomagnesemia in brachycephalic dogs.

BACKGROUND: Brachycephalic dogs are at risk for arterial hypertension and obstructive sleep apnea, which are both associated with chronic magnesium (Mg) depletion. HYPOTHESIS/OBJECTIVES: To compare the period prevalence of hypomagnesemia between Boxers and Bulldogs presented to a referral teaching hospital. To screen a group of Bulldogs for evidence of hypomagnesemia, and to obtain pilot data regarding the utility of parenteral Mg tolerance testing (PMgTT) in the diagnosis of whole-body Mg deficiency. ANIMALS: Chemistry laboratory submissions were retrospectively analyzed for serum total Mg (tMg) in Boxers and Bulldogs. Prospectively, 16 healthy client-owned Bulldogs were enrolled. METHODS: Retrospective case study. tMg concentrations were compared between Boxers and Bulldogs. Dogs with low serum albumin or high serum creatinine concentrations were excluded. Prospectively, ionized Mg (iMg), tMg, and arterial blood pressure were measured and iMg-to-tMg ratio (iMg : tMg) was calculated. Parenteral Mg tolerance testing (PMgTT) was performed in 3/16 dogs. RESULTS: In the retrospective study, period prevalence of hypomagnesemia was 4.7% in Boxers and 15% in Bulldogs (P = .02). The risk ratio for hypomagnesemia in Bulldogs was 1.8 when compared to Boxers (CI: 1.3-2.7). In the prospective study, iMg was [median (interquartile)] 0.43 (0.42-0.46) mmol/L (reference range 0.4-0.52), tMg was 1.9 (1.8-1.9) mg/dL (reference range 1.9-2.5). iMg : tMg was [mean (±SD)] 0.59 ± 0.04. Percentage retention after PMgTT were 55%, 95%, and 67%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Mg deficiency is common in Bulldogs and could contribute to comorbidities often observed in this breed. iMg : tMg and PMgTT might prove helpful in detecting chronic subclinical Mg deficiency.

Evaluation of arterial blood gases and arterial blood pressures in brachycephalic dogs.

BACKGROUND: Brachycephalic dogs (BD) are prone to congenital upper airway obstruction (brachycephalic syndrome, BS). In humans suffering from sleep apnea, upper airway obstruction is known to cause hypertension. There is no information regarding the influence of BS in dogs on cardiorespiratory physiology. HYPOTHESIS: BD are prone to lower P(a) O(2), higher P(a) CO (2), and hypertension compared with meso- or dolicocephalic dogs (MDD). ANIMALS: Eleven BD and 11 MDD. METHODS: After a questionnaire was completed by the owner, a physical examination was performed. Height and thoracic circumferences were measured. Arterial blood gases, electrolyte concentrations, and packed cell volume (PCV) were measured. Systolic (SAP), mean (MAP), and diastolic (DAP) arterial blood pressure recordings were performed. RESULTS: A total of 7 French and 4 English bulldogs met the inclusion criteria. The control group consisted in 6 Beagles, 2 mixed breed dogs, 1 Staffordshire Bull Terrier, 1 Parson Russell Terrier, and 1 Australian Cattle Dog. Statistically, BD had lower P(a) O(2), higher P(a) CO2, and higher PCV when compared with controls (86.2 ± 15.9 versus 100.2 ± 12.6 mmHg, P = .017; 36.3 ± 4.6 versus 32.7 ± 2.6 mmHg, P = .019; 48.2 ± 3.5 versus 44.2 ± 5.4%, P = .026, respectively). Also, they had significantly higher SAP (177.6 ± 25.0 versus 153.5 ± 21.7 mmHg, P = .013), MAP (123.3 ± 17.1 versus 108.3 ± 12.2 mmHg, P = .014), and DAP (95.3 ± 19.2 versus 83.0 ± 11.5 mmHg, P = .042). BD with a P(a) CO (2) >35 mmHg were significantly older than those with a P(a) CO (2) ≤35 mmHg (58 ± 16 and 30 ± 11 months, P = .004). CONCLUSION: Results of this study suggest that some BD are prone to lower P(a) O(2), higher P(a) CO (2), and hypertension when compared with MDD. Age may be a contributing factor.