Left Ventricular Function During Epinephrine Stimulation and Hypothermia: Effects at Spontaneous and Paced Heart Rates in a Porcine Model.

Postcardiac arrest patients treated with hypothermia, frequently require vasopressors and inotropic medication. The aim of this experimental study was to investigate the effect of epinephrine on left ventricular (LV) function during hypothermia. In an open-chest porcine model, seven animals were equipped with LV micromanometer and epicardial ultrasound transducers to provide LV pressure, Tau, and wall thickness and thickening velocities in systole (S') and early diastole (e'). Arterial, central venous, and pulmonal artery pressures were recorded. Cardiac output (CO) was measured by transit-time flow probe on the ascending aorta. Hypothermia was induced using a cooling catheter through the femoral vein. Pacemaker leads were attached to the right atrium for pacing. LV volumes were obtained by two-dimensional echocardiography. Measurements were made at normothermia (38°C) and hypothermia (33°C), without and with epinephrine infusion (0.03 µg/kg/min), at spontaneous and paced heart rates (HRs) 120 and 140 beats/min. Hypothermia reduced LV stroke volume (SV). Epinephrine during hypothermia increased the SV with reduced end-systolic volumes. LV dP/dtmax and wall-thickening velocity increased. During normothermia, epinephrine increased CO mainly due to accelerated HR, but during hypothermia, the increased CO resulted from augmented SV and, to a lesser degree, elevated HR. The incomplete relaxation and shortened diastolic filling time and the following reduction in SV seen in hypothermic animals, was repealed by epinephrine. The CO remained elevated also due to a shortened systolic duration, which gave time for complete relaxation during higher HRs. Epinephrine infusion improved systolic and diastolic function during hypothermia, and thereby reversed the effects induced by hypothermia considerably. Epinephrine augmented CO at hypothermia through increases in both SV and HR, in contrast to a mainly HR-dependent effect during normothermia. Systolic duration was shortened, which gave sufficient diastolic duration for complete relaxation. This allowed diastolic filling and maintained CO at elevated HRs.

Changes in left ventricular electromechanical relations during targeted hypothermia.

BACKGROUND: Targeted hypothermia, as used after cardiac arrest, increases electrical and mechanical systolic duration. Differences in duration of electrical and mechanical systole are correlated to ventricular arrhythmias. The electromechanical window (EMW) becomes negative when the electrical systole outlasts the mechanical systole. Prolonged electrical systole corresponds to prolonged QT interval, and is associated with increased dispersion of repolarization and mechanical dispersion. These three factors predispose for arrhythmias. The electromechanical relations during targeted hypothermia are unknown. We wanted to explore the electromechanical relations during hypothermia at 33 °C. We hypothesized that targeted hypothermia would increase electrical and mechanical systolic duration without more profound EMW negativity, nor an increase in dispersion of repolarization and mechanical dispersion. METHODS: In a porcine model (n = 14), we registered electrocardiogram (ECG) and echocardiographic recordings during 38 °C and 33 °C, at spontaneous and atrial paced heart rate 100 beats/min. EMW was calculated by subtracting electrical systole; QT interval, from the corresponding mechanical systole; QRS onset to aortic valve closure. Dispersion of repolarization was measured as time from peak to end of the ECG T wave. Mechanical dispersion was calculated by strain echocardiography as standard deviation of time to peak strain. RESULTS: Electrical systole increased during hypothermia at spontaneous heart rate (p < 0.001) and heart rate 100 beats/min (p = 0.005). Mechanical systolic duration was prolonged and outlasted electrical systole independently of heart rate (p < 0.001). EMW changed from negative to positive value (- 20 ± 19 to 27 ± 34 ms, p = 0.001). The positivity was even more pronounced at heart rate 100 beats/min (- 25 ± 26 to 41 ± 18 ms, p < 0.001). Dispersion of repolarization decreased (p = 0.027 and p = 0.003), while mechanical dispersion did not differ (p = 0.078 and p = 0.297). CONCLUSION: Targeted hypothermia increased electrical and mechanical systolic duration, the electromechanical window became positive, dispersion of repolarization was slightly reduced and mechanical dispersion was unchanged. These alterations may have clinical importance. Further clinical studies are required to clarify whether corresponding electromechanical alterations are accommodating in humans.

Left Ventricle Function During Therapeutic Hypothermia with Beta1-Adrenergic Receptor Blockade.

Therapeutic hypothermia is an established treatment in patients resuscitated from cardiac arrest. It is usually well-tolerated circulatory, but hypothermia negatively effects myocardial contraction and relaxation velocities and increases diastolic filling restrictions. A significant proportion of resuscitated patients are treated with long-acting beta-receptor blocking agents' prearrest, but the combined effects of hypothermia and beta-blockade on left ventricle (LV) function are not previously investigated. We hypothesized that beta1-adrenergic receptor blockade (esmolol infusion) exacerbates the negative effects of hypothermia on active myocardial motions, affecting both systolic and diastolic LV function. A pig (n = 10) study was performed to evaluate the myocardial effects of esmolol during hypothermia (33°C) and during normothermia, at spontaneous and pacing-increased heart rates (HRs). LV function was assessed by a LV pressure transducer, an epicardial ultrasonic transducer (wall thickness, wall thickening/thinning velocity) and an aortic ultrasonic flow-probe (stroke volume, cardiac output). The data were compared using a paired two-tailed Students t-test, and also analyzed using a linear mixed model to handle dependencies introduced by repeated measurements within each subject. The significance level was p ≤ 0.05. The effects of hypothermia and beta blockade were distinct and additive. Hypothermia reduced myocardial motion velocities and increased diastolic filling restrictions, but end-systolic wall thickness increased, and stroke volume and dP/dtmax (pumping function) were maintained. In contrast, esmolol predominantly affected systolic pumping function, by a negative inotropic effect. In combination, hypothermia and esmolol reduced myocardial velocities in systole and diastole by ∼40%, compared with normothermia without esmolol, inducing in combination both systolic and diastolic LV function impairment. The cardiac dysfunction deteriorated at increased HRs during hypothermia. Beta1-adrenergic receptor blockade (esmolol) exacerbates the negative effects of hypothermia on active myocardial contraction and relaxation. The combination of hypothermia with beta-blockade induces both systolic and diastolic LV function impairment.

Systolic left ventricular function is preserved during therapeutic hypothermia, also during increases in heart rate with impaired diastolic filling.

BACKGROUND: Systolic left ventricular function during therapeutic hypothermia is found both to improve and to decline. We hypothesized that this discrepancy would depend on the heart rate and the variables used to assess systolic function. METHODS: In 16 pigs, cardiac performance was assessed by measurements of invasive pressures and thermodilution cardiac output and with 2D strain echocardiography. Left ventricle (LV) volumes, ejection fraction (EF), transmitral flow, and circumferential and longitudinal systolic strain were measured. Miniaturized ultrasonic transducers were attached to the epicardium of the LV to obtain M-mode images, systolic thickening, and diastolic thinning velocities and to determine LV pressure-wall dimension relationships. Preload recruitable stroke work (PRSW) was calculated. Measurements were performed at 38 and 33°C at spontaneous and paced heart rates, successively increased in steps of 20 up to the toleration limit. Effects of temperature and heart rate were compared in a mixed model analysis. RESULTS: Hypothermia reduced heart rate from 87 ± 10 (SD) to 76 ± 11 beats/min without any changes in LV stroke volume, end-diastolic volume, EF, strain values, or PRSW. Systolic wall thickening velocity (S') and early diastolic wall thinning velocity decreased by approximately 30%, making systolic duration longer through a prolonged and slow contraction and changing the diastolic filling pattern from predominantly early towards late. Pacing reduced diastolic duration much more during hypo- than during normothermia, and combined with slow myocardial relaxation, incomplete relaxation occurred with all pacing rates. Pacing did not affect S' or PRSW at physiological heart rates, but stroke volume, end-diastolic volume, and strain were reduced as a consequence of reduced diastolic filling and much more accentuated during hypothermia. At the ultimate tolerable heart rate during hypothermia, S' decreased, probably as a consequence of myocardial hypoperfusion due to sustained ventricular contraction throughout a very short diastole. CONCLUSIONS: Systolic function was maintained at physiological heart rates during therapeutic hypothermia. Reduced tolerance to increases in heart rate was caused by lack of ventricular filling due to diastolic dysfunction and shorter diastolic duration.

Effects of therapeutic hypothermia on left ventricular function assessed by ultrasound imaging.

BACKGROUND: Therapeutic hypothermia is used after cardiac arrest. The aim of this study was to investigate the effects of therapeutic hypothermia on left ventricular (LV) function assessed by ultrasonic imaging. METHODS: In 10 pigs, LV volumes, ejection fractions, and longitudinal strain were measured using two-dimensional echocardiography. Midwall fractional shortening and end-systolic wall stress were calculated. Wall thickness was continuously measured using an epicardial ultrasonic transducer placed on the LV anterior wall. Wall thickening velocity (S') and pressure-wall thickness loops were used to assess systolic function. Diastolic function was assessed by echocardiographic transmitral flow and mitral annular velocity (e') measurements, calculation of the LV relaxation constant, and determination of LV stiffness and restoring forces using the end-diastolic pressure-wall thickness relation during volume unloading. Early wall thinning velocity (e'wt) and early diastolic wall thinning were calculated. Measurements were done at 38°C and 33°C, at spontaneous heart rate and at atrial pacing at 100 beats/min. RESULTS: End-diastolic volume, stroke volume, midwall fractional shortening, and longitudinal strain remained unchanged during hypothermia, but end-systolic wall stress, S', and pressure-wall thickness loop area decreased. A shift from early to late diastolic LV filling occurred during hypothermia, with concurrent decreases in e', e'wt, and early wall thinning fraction. Relaxation was prolonged, LV stiffness was increased, and restoring force was decreased during hypothermia. Hypothermia induced a decrease in relative diastolic duration at spontaneous heart rate, which was further reduced during pacing. During paced heart rate at 33°C, stroke volume, ejection fraction, and strain were reduced. CONCLUSIONS: Hypothermia induced systolic and diastolic dysfunction, with reduced tolerance to increased heart rate. These findings may have implications for patient management during hypothermia.