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Background and aim This study aimed to assess right ventricular (RV) function during cardiogenic shock due to acute left ventricular (LV) failure, including during LV unloading with Impella CP and an added moderate dose of norepinephrine. Methods Cardiogenic shock was induced by injecting microspheres in the left main coronary artery in 18 adult Danish Landrace pigs. Conductance catheters were placed in both ventricles and pressure-volume loops were recorded simultaneously. Results Cardiogenic shock due to LV failure also impaired RV performance, which was partially restored during haemodynamic support with Impella CP, as demonstrated by changes in the ventriculo-arterial coupling (Ea/Ees ratio) (baseline (median [Q1;Q3]) 1.2 [1.1;1.6]), cardiogenic shock (3.0 [2.4;4.5]), Impella CP (2.1 [1.3;2.7]) (pBaseline vs CS < 0.0001, pCS vs Impella = 0.001)). Impella CP support also improved RV stroke work (SW) (cardiogenic shock 333 [263;530] vs Impella CP (830 [717;1121]) (p < 0.001). Moderate norepinephrine infusion concomitant with Impella CP further improved RV SW (Impella CP (818 [751;1065]) vs Impella CP+moderate norepinephrine (1231 [1142;1335]) (p = 0.01)) but at the expense of an increase in LV SW (Impella CP (858 [555;1392]) vs Impella CP+moderate norepinephrine (2101 [1024;2613]) (p = 0.04)). Conclusions The Impella CP provided efficient LV unloading, improved RV function, and end-organ perfusion. Moderate doses of norepinephrine during Impella support further improved RV function, but at the expense of an increase in SW of the failing LV.

AIMS: The aim of this study was to evaluate the Impella CP over veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and their impact on left ventricular unloading and end-organ perfusion.METHODS AND RESULTS: Cardiogenic shock (CS) was induced by injecting microspheres into the left coronary artery in fourteen adult female swine. Impella CP or VA-ECMO was initiated in the presence of CS and evaluated after 60 minutes. Left ventricular pressure-volume area (PVA, total mechanical work) was obtained from a conductance catheter. Results are presented as mean (95% confidence interval) and the rank-sum test was used to assess differences between devices. Compared to the CS state, PVA was unaffected by Impella CP and increased on VA-ECMO (from 2,548 [2,193; 2,904] mmHg x mL during CS to 5,775 [4,451; 7,099], between device p-value=0.02). Arterial lactate increased during CS and decreased on support with no difference between devices. Renal venous oxygen saturation decreased during CS and increased on support with no difference between devices. Cerebral venous oxygen saturation increased to 33% [25, 40] on Impella CP and to 69% [49, 89] on VA-ECMO, p=0.04.CONCLUSIONS: In this porcine model of profound CS, Impella CP unloaded the left ventricle compared to VA-ECMO. Both devices improved end-organ perfusion, with a tendency towards higher venous oxygen saturations on VA-ECMO.

Cardiac fibrosis contributes to the development of heart failure in pulmonary hypertension. We aimed to assess the development of fibrosis and the effects of treatment with the anti-fibrotic agent pirfenidone in pressure overload induced right ventricular (RV) failure. Wistar rat weanlings were randomized to pulmonary trunk banding (PTB) or sham surgery. One week after the procedure, PTB rats were randomized into two groups with either six weeks on standard chow or treatment with pirfenidone mixed in chow (700 mg/kg/day). RV hemodynamic effects were evaluated by echocardiography, cardiac magnetic resonance imaging (MRI), and pressure-volume measurements. Sections from the isolated RV, left ventricle, and septum were sampled systematically; stereological point grids and the nucleator were used to estimate volume of fibrosis and cardiac hypertrophy, respectively. PTB caused RV failure in all rats subjected to the procedure. The volume fraction of fibrosis in the RV increased threefold in PTB rats corresponding to a sixfold increase in total volume of RV fibrosis. Volume fraction of fibrosis and total volume of fibrosis also increased in the septum and in the left ventricle. Pirfenidone reduced body weight but did not improve RV hemodynamics or reduce cardiac fibrosis. RV cardiomyocyte profile area was increased twofold in PTB rats without any effect of pirfenidone. RV pressure overload after PTB induced not only RV but also septal and left ventricular fibrosis assessed by stereology. Treatment with pirfenidone reduced body weight but did not reduce the development of cardiac fibrosis or delay the progression of RV failure.

OBJECTIVES: Myocardial infarction and chronic heart failure induce specific metabolic changes in the neonatal myocardium that are closely correlated to outcome. The aim of this study was to examine the metabolic responses to noninfarct heart failure and inotropic treatments in the newborn heart, which so far are undetermined.DESIGN: A total of 28 newborn pigs were instrumented with a microdialysis catheter in the right ventricle, and intercellular citric acid cycle intermediates and adenosine metabolite concentrations were determined at 20-minute intervals. Stunning was induced by 10 cycles of 3 minutes of ischemia, which was performed by occluding the right coronary artery, followed by 3 minutes of reperfusion. Animals were randomized for treatment with epinephrine + milrinone, dopamine + milrinone, dobutamine, or saline.SETTING: University hospital animal laboratory.MAIN RESULTS: Ischemia-reperfusion induced right ventricular stunning and increased the concentrations of pyruvate lactate, succinate, malate, hypoxanthine, and xanthine (all, p < 0.01). During inotrope infusion, no differences in metabolite concentrations were detected between the treatment groups. In nonsurviving animals (n = 8), concentrations of succinate (p < 0.0001), malate (p = 0.009), and hypoxanthine (p = 0.04) increased compared with survivors, while contractility was significantly reduced (p = 0.03).CONCLUSIONS: Accumulation of citric acid cycle intermediates and adenosine metabolites reflects the presence of myocardial stunning and predicts mortality in acute noninfarct right ventricular heart failure in newborn pigs. This phenomenon occurs independently of the type of inotrope, suggesting that citric acid cycle intermediates represent potential markers of acute noninfarct heart failure.

Inodilators are used in the treatment of low cardiac output, mainly after cardiac surgery. At present, there is little knowledge of the effect of inodilators in the newborn heart. Immediately after birth and in the neonatal period, the metabolism and physiology of the heart undergo major changes. We hypothesised that effects of the inodilators milrinone and levosimendan on myocardial contractility and haemodynamics under normal physiological conditions were age dependent. Animal studies were conducted on 48 pigs using a closed-chest biventricular conductance catheter method. Pigs in two age groups, that is, 5-6 days and 5-6 weeks, were assigned to milrinone, levosimendan, or a control group. We observed that both milrinone - 19.2% with a p value of 0.05 - and levosimendan - 25.7% with a p value of 0.03 compared with the control group increased cardiac output, as well as myocardial contractility with a maximum pressure development over time: milrinone 28.2%, p = 0.01 and levosimendan 19.4%, p = 0.05. Milrinone improved diastolic performance (p < 0.05) in the left ventricle in the 5-6-week-old animals. In the newborn animals, neither of the inodilators increased ventricular contractility or cardiac output; however, we observed a significant decrease in the mean arterial pressure: milrinone 34.6%, p < 0.01 and levosimendan 30.1%, p = 0.02. Both inodilators demonstrated age-dependent haemodynamic effects, and it is noteworthy that neither milrinone nor levosimendan was able to increase cardiac output in the newborn heart.

The right ventricle (RV) tolerates acute pulmonary valvular regurgitation fairly well, however, in the long-term dilatation and failure often ensues. There is little known of the structural and functional myocardial alterations following this pathophysiology, and therefore animal models are sought. We aimed to develop an animal experimental model for RV dilatation emphasizing feasibility, reproducibility and human compatibility. Free pulmonary valve insufficiency and RV dilatation were created with a novel external suture plication technique in nine 5 kg piglets. Six matched animals served as controls. After 10 weeks cardiac dimensions and physiology were assessed with in vivo cardiovascular MRI and conductance technique. RV end-diastolic volume increased 31% in the intervention group (P=0.03). The regurgitation fraction was 37% in the intervention group compared to -2% in controls (P<0.001). Conductance measurements showed preserved RV contractile function, but significant left ventricular diastolic impairment. This study is the first to show that pulmonary valve regurgitation, RV dilatation and functional impairment can be achieved by external leaflet plication. Compared to known methods, the advantages of this model are: 1) no induction of stenosis over time, 2) no risk of stent migration, and 3) very simple and reproducible.