A novel ultrasound-guided mouse model of sudden cardiac arrest

Abstract

Aim Mouse models of sudden cardiac arrest are limited by challenges with surgical technique and obtaining reliable venous access. To overcome this limitation, we sought to develop a simplified method in the mouse that uses ultrasound-guided injection of potassium chloride directly into the heart. Methods Potassium chloride was delivered directly into the left ventricular cavity under ultrasound guidance in intubated mice, resulting in immediate asystole. Mice were resuscitated with injection of epinephrine and manual chest compressions and evaluated for survival, body temperature, cardiac function, kidney damage, and diffuse tissue injury. Results The direct injection sudden cardiac arrest model causes rapid asystole with high surgical survival rates and short surgical duration. Sudden cardiac arrest mice with 8-min of asystole have significant cardiac dysfunction at 24 hours and high lethality within the first seven days, where after cardiac function begins to improve. Sudden cardiac arrest mice have secondary organ damage, including significant kidney injury but no significant change to neurologic function. Conclusions Ultrasound-guided direct injection of potassium chloride allows for rapid and reliable cardiac arrest in the mouse that mirrors human pathology without the need for intravenous access. This technique will improve investigators’ ability to study the mechanisms underlying post-arrest changes in a mouse model.

Metformin preconditioning protects against myocardial stunning and preserves mitochondrial dynamics and protein translation in a mouse model of cardiac arrest

“…Importantly, there were no differences among groups for body weight in these non-diabetic mice. Twenty-four hours after surgery, untreated arrest mice had significantly lower EF than untreated sham mice (sham: 59.5±1.7%; untreated arrest: 41.1±2.7%, p<0.0001, Figure 2A), as expected based on our previous description of this model (32). Importantly, metformin pretreatment significantly improved EF 24 hours post-SCA (arrest metformin: 51.6±2.6%, p<0.01 vs. untreated arrest) to a level not significantly different from sham mice (Figure 2A).…”

“…The long ischemic duration in these models involves substantial cardiomyocyte necrosis, and much of metformin’s beneficial effect has been attributed to reduction of mPTP-mediated cell death in the infarct border zone (49). In contrast, our data demonstrates metformin’s protection of in vivo EF in a SCA model that features 8 minute ischemia period without evidence of cardiac cell death (31). Therefore, with a shorter ischemic duration and no evidence of apoptosis, we have identified a unique pathway of metformin’s cardiac protection.…”

“…Previous studies have also shown that metformin protects cardiac function acutely through a vasodilatory effect in a rat heart model of cardiac stunning from ex vivo ischemia (39). In contrast, our data demonstrate metformin’s protection of in vivo EF in a SCA model (Figure 2) that features an 8-minute ischemia period without evidence of cardiac cell death (32) (Figure 1). Therefore, using metformin pretreatment and short ischemia, we were able to identify intracellular processes that adapt the cardiomyocyte to maintain function rather than alter cell survival.…”

“…In ligation-mediated ischemia/reperfusion experiments in vivo , 125 µg/kg metformin injection into the LV lumen at the time of reperfusion resulted in a decreased infarct area and improved EF in non-diabetic mice (40). In contrast to coronary artery ligation experiments, which generally rely on >30 minute ischemic times and generate significant cardiomyocyte death, our SCA model is 8 minutes of ischemia and lacks overt cell death (32). In our SCA model, when metformin was given directly into the LV at resuscitation as a rescue therapy (1,250 µg/kg), there was no change to EF at one day after SCA (arrest rescue metformin: 42.1±2.4%) compared to untreated arrest mice (Figure 3B).…”

Circulating Biomarkers Reflecting Destabilization Mechanisms of Coronary Artery Plaques: Are We Looking for the Impossible?

“…Hence, a search for different methods is warranted to appropriately recognize a vulnerable plaque in a timely manner. So far, most of the knowledge gathered regarding the plaque vulnerability and consequent rupture has been based on either animal models or patients with sudden cardiac deaths following the myocardial infarction [7,17,18]. Yet, pathological studies are very limited by their cross-sectional design and teleological nature, therefore, development of imaging tools which are capable of assessment of morphological characteristics in vivo were needed.…”