fixed-volume-intercept-approach-for-serial-contractility-assessment

Fixed Volume-Intercept Approach for Serial Contractility Assessment with Closed-Chest Pressure-Volume Loops in a Porcine Model

The end-systolic pressure&#8211;volume relationship (ESPVR) is widely regarded as the gold standard, load-independent descriptor of left-ventricular (LV) ...

Aarhus University

Odense University Hospital

Aarhus University Hospital

Invasive mechanical ventilation (IMV) is widely used in patients with cardiogenic shock following acute myocardial infarction (AMICS), but evidence to guide practice remains sparse. We sought to evaluate trends in the rate of IMV utilization, applied settings, and short term-outcome of a contemporary cohort of AMICS patients treated with IMV according to out-of-hospital cardiac arrest (OHCA) at admission.

Invasive mechanical ventilation in cardiogenic shock complicating acute myocardial infarction: A contemporary Danish cohort analysis.

The Thrombolysis in Myocardial Infarction (TIMI) risk score estimates mortality for patients with ST-elevation myocardial infarction (STEMI). This study aimed to investigate whether biomarkers reflecting the neurohormonal response (pro-atrial natriuretic peptide (proANP), mid-regional pro-adrenomedullin (MR-proADM), and copeptin), inflammation (suppression of tumorigenicity 2 (ST2), C-reactive protein (CRP), and leukocytes), and troponin add prognostic value to the TIMI risk score.

The prognostic value of neurohormonal and inflammatory biomarkers in addition to the TIMI risk score in patients with ST-elevation myocardial infarction.

Cardiogenic shock (CS) is associated with high mortality and medical therapies have failed to improve survival. Treatment with lactate is associated with improved cardiac function which may benefit this condition. Comprehensive hemodynamic assessment of lactate administration in CS is lacking, and the mechanisms underlying the cardiovascular effects of lactate in CS have not yet been elucidated. In this study we aimed to study the cardiovascular and cardiometabolic effects of treatment with lactate in experimental ischemic CS.

Lactate infusion improves cardiac function in a porcine model of ischemic cardiogenic shock.

Cardiogenic shock (CS) is characterized by reduced cardiac output (CO), reduced end-organ perfusion, and high mortality. Medical therapies have failed to improve survival. The ketone body 3-hydroxybutyrate (3-OHB) enhances cardiac function in heart failure and CS. We aimed to elucidate the cardiovascular and cardiometabolic effects of 3-OHB treatment during CS. In a randomized, assessor-blinded crossover design, we studied 16 female pigs (60 kg, 5 months of age). CS was induced by left main coronary artery microsphere injections. Predefined criteria for CS were a 30% reduction in CO or mixed venous saturation (SvO). Intravenous 3-OHB infusion and a matching control solution were administered for 120 min in random order. Hemodynamic measurements were obtained by pulmonary artery catheterization and a left ventricular (LV) pressure-volume catheter. Myocardial mitochondrial function was assessed using high resolution respirometry. During CS, infusion with 3-OHB increased CO by 0.9 L/min (95%CI 0.4-1.3 L/min) compared with control infusion. SvO (P = 0.026) and heart rate (P < 0.001) increased. Stroke volume (P = 0.6) was not altered. LV contractile function as determined by LV end-systolic elastance improved during 3-OHB infusion compared with control infusion (P = 0.004). Systemic and pulmonary vascular resistance decreased, and diuresis increased. LV mitochondrial function was higher after 3-OHB infusion compared with control. We conclude that 3-OHB infusion enhances cardiac function by increasing contractility and reducing vascular resistance, while also preserving myocardial mitochondrial respiratory function in a large animal model of ischemic CS. These novel findings support the therapeutic potential of exogenous ketone supplementation in CS management.

The ketone body 3-hydroxybutyrate increases cardiac output and cardiac contractility in a porcine model of cardiogenic shock: a randomized, blinded, crossover trial.

The acute pathophysiological changes after myocardial ischemia complicated by cardiogenic shock (CS) remain poorly defined, especially regarding compensatory mechanisms and myocardial mitochondrial function. We investigated immediate cardiovascular and mitochondrial effects in a porcine model of ischemic CS. CS was induced in 32 Danish Landrace pigs (60 kg) via repeated microembolization of the left coronary artery until a 30% reduction in cardiac output (CO) or mixed venous saturation. Monitoring included pulmonary artery and left ventricular pressure-volume catheters, with analysis of endomyocardial biopsies and arterial, mixed venous, and coronary sinus blood samples. CO deteriorated promptly due to decreased stroke volume. Contractility declined, and afterload increased, causing rapid ventriculo-arterial decoupling. Forward flow parameters were compromised prior to pressure-parameters. Diastolic function was impaired and mitochondrial damage was observed. CS rapidly impairs LV hemodynamic and mitochondrial function, highlighting the importance of monitoring forward flow and targeting mitochondrial function in treatment.

Article	Year
Invasive mechanical ventilation in cardiogenic shock complicating acute myocardial infarction: A contemporary Danish cohort analysis. International journal of cardiology\| PubMed ID: 38423479	2024
The prognostic value of neurohormonal and inflammatory biomarkers in addition to the TIMI risk score in patients with ST-elevation myocardial infarction. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals\| PubMed ID: 39773138	2025
Lactate infusion improves cardiac function in a porcine model of ischemic cardiogenic shock. Critical care (London, England)\| PubMed ID: 40083003	2025
The ketone body 3-hydroxybutyrate increases cardiac output and cardiac contractility in a porcine model of cardiogenic shock: a randomized, blinded, crossover trial. Basic research in cardiology\| PubMed ID: 40220139	2025
The Immediate Cardiovascular and Mitochondrial Response in Ischemic Cardiogenic Shock. Journal of cardiovascular translational research\| PubMed ID: 40555857	2025

Ole Kristian Lerche Helgestad

Biography

JoVE Journal Publications

Other Publications