Current Medical Research Programs

Hypothermic Reperfusion after Ischemia Improves Ventricular Myocyte Contractility and Intracellular Ca²⁺ Dynamics 

An energy-sparing effect of hypothermia has been described, such that lowering the temperature may lead to increases in cardiac work without increases in energy cost. We have recently reported improved myocardial function with hypothermia following resuscitation from cardiac arrest. In the present investigation, we hypothesized that reductions in reperfusion temperature from 37°C to 30°C after 10 minutes of ischemia would minimize the decreases in myocyte contractility and intracellular Ca²⁺ transients. Results: Hypothermic reperfusion following ischemia improved myocyte contractility. Increased myocyte intracellular Ca²⁺ dynamics during hypothermia accounted for the greater cell contractility.

Hypothermia Improves Ventricular Myocyte Sensitivity to Extracellular Ca²⁺

We have previously reported that hypothermia minimizes the impairment of myocyte contractility following ischemia. In the present study, we investigated the mechanisms accounting for these reduced impairments in contractility. We hypothesized that hypothermia would increase myocyte sensitivity to extracellular Ca²⁺ under conditions of normal perfusion and following reperfusion after ischemia. Results: Hypothermia increased myocyte sensitivity to extracellular Ca²⁺ content, and this accounted for greater contractility. Hypothermic reperfusion after ischemia maintained greater responsiveness of myocyte contractility to extracellular Ca²⁺ content, in comparison to normothermic reperfusion.

Current-Based Impedance Compensation Outperformed Duration-Based Technique in Defibrillation Efficacy in a High Impedance Pig Model

Transthoracic impedance (TI) for defibrillation varies widely in patients with a median value of approximately 95-100 ohms. High impedance patients are more difficult to defibrillate. The modern generation of external defibrillators therefore adjusts defibrillation output based on patient impedance measurement prior to shock delivery (impedance compensation). Commercial external defibrillators use different impedance compensation methods (ICM). Defibrillator A (DefA, rectilinear biphasic waveform) controls current with maximum E=200 Joules; Defibrillator B (DefB, truncated exponential waveform) increases shock duration with maximum E=360 Joules. The purpose of the study is to assess the effect of two ICM on defibrillation success for TI>100ohms. Results: For TI greater than average, the current-based compensation technique was much more efficient than the duration-based technique; higher defibrillation current, not higher energy from extending shock duration resulted in higher defibrillation success.

Nasopharyngeal Cooling Improves Coronary Perfusion Pressure and Amplitude Spectrum Area during CPR in Comparison to Systemic Cold Saline Infusion in a Porcine Model of Prolonged Cardiac Arrest

We have previously demonstrated that nasopharyngeal cooling (NPC) initiated during CPR improves the success of resuscitation. In the present study, we compared the effects of NPC with cold saline infusion (CSI) on hemodynamics, amplitude spectrum area (AMSA) during CPR and ultimate resuscitation outcome in a porcine model of prolonged cardiac arrest. We hypothesized that NPC would yield better resuscitation outcome when compared to CSI when both were initiated during CPR. Results: In this model, NPC improved hemodynamics and AMSA during CPR and this was associated with increases in the success of resuscitation.

Resuscitation Blanket during CPR for “Hands-on” Defibrillation

Uninterrupted chest compression has been recognized as a important factor for improving cardiopulmonary resuscitation (CPR) outcomes. We therefore introduced a resuscitation blanket made from insulating material which allows for uninterrupted chest compressions during shock delivery. We hypothesized that the resuscitation blanket used during CPR is safe, feasible and efficient to protect the rescuer from the risk of receiving current during defibrillation and therefore allowing performance of continuous chest compressions during CPR. Results: The resuscitation blanket allows for continuous precordial compression without interruption for delivering a defibrillation shock. It therefore minimizes the hands-off interruptions of chest compression and improves hemodynamics prior to delivering of an electrical shock and ultimately increases the defibrillation success.

Table.  Measurements from 15 Hand-on Shocks During External Defibrillation

 Values expressed as mean ± SD. † P<0.01 compared to “voltage delivered”; ‡ P<0.01 compared to “current delivered”;

Mild hypothermia minimized the adverse effects of epinephrine 

Epinephrine is administered during cardiac arrest to increase coronary perfusion and therefore favor return of spontaneous circulation (ROSC).  Experimentally, the a₁ and b adrenergic actions of epinephrine increase the severity of post resuscitation myocardial dysfunction and thereby reduce the duration of post resuscitation survival. We have previously demonstrated that therapeutic hypothermia after ROSC improves both post resuscitation myocardial and neurological function. In the present study, we investigated the combined effects of epinephrine and hypothermia. We hypothesized that hypothermia minimizes the detrimental effects of epinephrine on post resuscitation myocardial dysfunction and favors survival. Results: Except for one control animal, all were resuscitated. Post resuscitation (PR) ejection fraction (EF), neurological deficit scores (NDS) and survivals were significantly greater after both epinephrine and hypothermia. These findings provide evidence that mild hypothermia minimized the adverse effects of epinephrine on post-resuscitation neurological and myocardial functions and favored better survival.

Hypothermia initiated during cardiac arrest and CPR also reduced myocardial ischemic injury

Comparison between Invasive and Noninvasive Assessment of Myocardial Function in A Rat Model of Cardiac Arrest and CPR

Placement a pressure catheter into the left ventricle for monitoring myocardial function is a standard technique in animal models of cardiac arrest and CPR. However, this technique is invasive and time-limited. We therefore sought to compare this approach with the noninvasive echocardiographic assessment for monitoring myocardial function in rat model of cardiac arrest and CPR. We hypothesized that echocardiographically assessed myocardial function would be correlated to the invasive left ventricular function measurements. Results: All animals were successfully resuscitated. Both dP/dt40 and EF were significantly decreased after resuscitation (P < 0.05). The noninvasive assessed EF was highly correlated to dP/dt40 (R=0.75, P<0.01).  The echocardiographically assessed myocardial function is significantly correlated with the standard invasive monitoring measurements in a rat model of cardiac arrest and CPR.

AMSA is decreased during cardiac arrest and CPR, in rats with chronic ischemic heart

Ventricular fibrillation (VF) waveform features are altered in instance of acute myocardial ischemia and chronic coronary heart disease. Amplitude Spectrum Area (AMSA), in particular, have been investigated under conditions of electrical induced cardiac arrest or under condition of acute myocardial ischemia. However, no data on AMSA values during cardiac arrest in heart suffering of chronic ischemia have been previously investigated. In the present study we sought to investigate AMSA during VF induced in rats with chronic myocardial ischemia in comparison to that observed in rats with normal myocardium. Results: AMSA values are significantly decreased in rats with chronic ischemic heart in comparison to those assessed in rat with not ischemic heart. 

Apoptosis is not involved in the mechanisms of postresuscitation myocardial dysfunction in a rat model of cardiac arrest and CPR