Post-hypothermic cardiac left ventricular systolic dysfunction after rewarming in an intact pig model

Abstract

Introduction: We developed a minimally invasive, closed chest pig model with the main aim to describe hemodynamic function during surface cooling, steady state severe hypothermia (one hour at 25°C) and surface rewarming.

Methods: Twelve anesthetized juvenile pigs were acutely catheterized for measurement of left ventricular (LV) pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were surface cooled to 25°C, while four animals were kept as normothermic time-matched controls.

Results: During progressive cooling and steady state severe hypothermia (25°C) cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), maximal deceleration of pressure in the cardiac cycle (dP/dt(min)), indexes of LV contractility (preload recruitable stroke work, PRSW, and maximal acceleration of pressure in the cardiac cycle, dP/dt(max)) and LV end diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen content in arterial and mixed venous blood increased significantly. LV end diastolic pressure (EDP) remained constant. After rewarming all the above mentioned hemodynamic variables that were depressed during 25°C remained reduced, except for CO that returned to pre-hypothermic values due to an increase in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming, while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac troponin T (TnT) and tumor necrosis factor-alpha (TNF-α) were significantly increased.

Conclusions: Progressive cooling to 25°C followed by rewarming resulted in a reduced systolic, but not diastolic left ventricular function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic increase in TnT indicates that hypothermia/rewarming may cause degradation of cardiac tissue. There were no signs of inadequate global oxygenation throughout the experiments.

Figure 1

Protocol layout.

Figure 2

Left ventricular contractility data. A. Preload recruitable stroke work (PRSW); B. end systolic elastance (E_es); C. arterial-ventricular coupling ratio (E_a/E_es); D. maximal acceleration of pressure in the cardiac cycle (dP/dt_max). *Significantly different from baseline (P ≤0.05). ‡ Significant difference between cooled animals and time matched normothermic controls (P ≤0.05).

Figure 3

Indexes of left ventricular diastolic function. A. Maximal deceleration of pressure in the cardiac cycle (dP/dt_min); B. end diastolic pressure (EDP); C. end diastolic pressure volume relationship (EDPVR); D. isovolumetric relaxation time (Tau). *Significantly different from baseline (P ≤0.05). ‡ Significant difference between cooled animals and time matched normothermic controls (P ≤0.05).

Figure 4

General hemodynamic recordings. A. Cardiac output (CO); B. heart rate (HR); C. stroke volume (SV); D. mean arterial pressure (MAP); E. systemic vascular resistance index (SVRI); F. end diastolic and systolic volumes (EDV and ESV). *Significantly different from baseline (P ≤0.05).

Figure 5

Oxygen variables. A. Blood hemoglobin concentration (Hb); B. global delivery of oxygen (DO₂); C. global consumption of oxygen (VO₂). *Significantly different from baseline (P ≤0.05). ‡ Significant difference between cooled animals and time matched normothermic controls (P ≤0.05) in Figure 5A.

Figure 6

Biochemical variables. A. Serum albumin concentration; B. serum troponin T concentration (TnT); C. serum tumor necrosis factor alpha concentration (TNF-α). *Significantly different from baseline (P ≤0.05). ‡ Significant difference between cooled animals and time matched normothermic controls (P ≤0.05).