Biomechanical Modeling to Inform Pulmonary Valve Replacement in Tetralogy of Fallot Patients After Complete Repair.

BACKGROUND: A biomechanical model of the heart can be used to incorporate multiple data sources (electrocardiography, imaging, invasive hemodynamics). The purpose of this study was to use this approach in a cohort of patients with tetralogy of Fallot after complete repair (rTOF) to assess comparative influences of residual right ventricular outflow tract obstruction (RVOTO) and pulmonary regurgitation on ventricular health. METHODS: Twenty patients with rTOF who underwent percutaneous pulmonary valve replacement (PVR) and cardiovascular magnetic resonance imaging were included in this retrospective study. Biomechanical models specific to individual patient and physiology (before and after PVR) were created and used to estimate the RV myocardial contractility. The ability of models to capture post-PVR changes of right ventricular (RV) end-diastolic volume (EDV) and effective flow in the pulmonary artery (Qeff) was also compared with expected values. RESULTS: RV contractility before PVR (mean 66 ± 16 kPa, mean ± standard deviation) was increased in patients with rTOF compared with normal RV (38-48 kPa) (P < 0.05). The contractility decreased significantly in all patients after PVR (P < 0.05). Patients with predominantly RVOTO demonstrated greater reduction in contractility (median decrease 35%) after PVR than those with predominant pulmonary regurgitation (median decrease 11%). The model simulated post-PVR decreased EDV for the majority and suggested an increase of Qeff-both in line with published data. CONCLUSIONS: This study used a biomechanical model to synthesize multiple clinical inputs and give an insight into RV health. Individualized modeling allows us to predict the RV response to PVR. Initial data suggest that residual RVOTO imposes greater ventricular work than isolated pulmonary regurgitation.

The Na+/Ca2+ exchange inhibitor SEA0400 limits intracellular Ca2+ accumulation and improves recovery of ventricular function when added to cardioplegia.

BACKGROUND: The Na+/Ca2+ exchange inhibitor SEA0400 prevents myocardial injury in models of global ischemia and reperfusion. We therefore evaluated its potential as a cardioplegia additive. METHODS: Isolated rat cardiomyocytes were exposed to hypoxia (45 min) followed by reperfusion. During hypoxia, cells were protected using cardioplegia with (n=25) or without (n=24) SEA0400 (1 µM), or were not protected with cardioplegia (hypoxic control, n=8). Intracellular Ca2+ levels were measured using Ca2+ sensitive dye (fura-2 AM). Isolated rat hearts were arrested using cardioplegia with (n=7) or without (n=6) SEA0400 (1 µM) then reperfused after 45 min of ischemia. Left ventricular (LV) function, troponin release, and mitochondrial morphology were evaluated. RESULTS: Cardiomyocytes exposed to hypoxia without cardioplegia had poor survival (13%). Survival was significantly improved when cells were protected with cardioplegia containing SEA0400 (68%, p=0.009); cardioplegia without SEA0400 was associated with intermediate survival (42%). Cardiomyocytes exposed to hypoxia alone had a rapid increase in intracellular Ca2+ (305 ± 123 nM after 20 minutes of ischemia). Increases in intracellular Ca2+ were reduced in cells arrested with cardioplegia without SEA0400; however cardioplegia containing SEA0400 was associated with the lowest intracellular Ca2+ levels (110 ± 17 vs. 156 ± 42 nM after 45 minutes of ischemia, p=0.004). Hearts arrested with cardioplegia containing SEA0400 had better recovery of LV work compared to cardioplegia without SEA0400 (23140 ± 2264 vs. 7750 ± 929 mmHg.µl, p=0.0001). Troponin release during reperfusion was lower (0.6 ± 0.2 vs. 2.4 ± 0.5 ng/mL, p=0.0026), and there were more intact (41 ± 3 vs. 22 ± 5%, p<0.005), and fewer disrupted mitochondria (24 ± 2 vs. 33 ± 3%, p<0.05) in the SEA0400 group. CONCLUSIONS: SEA0400 added to cardioplegia limits accumulation of intracellular Ca2+ during ischemic arrest in isolated cardiomyocytes and prevents myocardial injury and improves recovery of LV function in isolated hearts.

Protecting the aged heart during cardiac surgery: use of del Nido cardioplegia provides superior functional recovery in isolated hearts.

OBJECTIVES: Aged hearts are particularly vulnerable to ischemia-reperfusion injury. Our objective was to determine if del Nido cardioplegia, which contains lidocaine, less blood, and less calcium than our standard cardioplegia, provides superior protection for aged hearts. We also sought to determine if the lidocaine in del Nido cardioplegia is adequate to prevent Na(+) influx via the window current. METHODS: Sodium channel kinetics were measured in rat cardiomyocytes with and without lidocaine. Recovery after 60 minutes of cardioplegic arrest was assessed in isolated working senescent rat hearts. Del Nido cardioplegia was delivered as a single dose (n = 8) because it is used clinically, and standard cardioplegia was delivered as an induction dose with re-dosing every 20 minutes (n = 8). After 20 minutes of reperfusion, hearts were switched to working mode for 60 minutes. Flows were indexed to ventricular dry weight. Troponin release was assayed. RESULTS: Sodium channel kinetics indicated that the lidocaine concentration in del Nido cardioplegia minimizes the potential for Na+ influx via the window current. Spontaneous contractions occurred in fewer hearts arrested with del Nido cardioplegia (88% vs 13%; P = .01), and troponin release was reduced (0.24 vs 0.89 ng/mL; P = .017). Cardiac output was approximately 90% of baseline in the del Nido group compared with approximately 50% in the standard group (173 ± 14 vs 86 ± 22 mL · min(-1) · g(-1); P = .0008). Stroke work was higher in the del Nido group (93 ± 6 vs 41 ± 10 mL · mm Hg · g(-1); P = .0002). CONCLUSIONS: Del Nido cardioplegia prevents spontaneous contractions during arrest, reduces troponin release, and results in superior myocardial function in isolated aged hearts. Del Nido cardioplegia has the potential to provide superior myocardial protection for older patients undergoing cardiac surgery.

Protecting the aged heart during cardiac surgery: the potential benefits of del Nido cardioplegia.

OBJECTIVE: Aged hearts are more vulnerable than mature hearts to reperfusion injury during cardiac surgery because of altered cardiomyocyte Ca(2+) homeostasis. Inasmuch as immature cardiomyocytes have similar properties, a specialized cardioplegic solution (del Nido cardioplegia) designed to protect children's hearts may also be beneficial for elderly patients. Our objective was to evaluate the ability of del Nido cardioplegic solution, containing lidocaine and less Ca(2+) than our standard cardioplegic solution, to protect aged cardiomyocytes during cardioplegic arrest and reperfusion. METHODS: We used our novel isolated cell model of cardioplegic arrest and reperfusion to compare the effect of del Nido cardioplegic solution with that of our standard cardioplegic solution on intracellular Ca(2+) concentration, contractions, and membrane potential in cardiomyocytes from senescent rat hearts. RESULTS: The incidence of spontaneous contractions during cardioplegic arrest was lower with del Nido cardioplegia (3/11 vs 9/11 cells; P < .05) than with standard cardioplegia, and contractions could not be induced by field stimulation of cardiomyocytes arrested with del Nido cardioplegia (0/11 vs 9/11 cells; P < .05). Intracellular diastolic Ca(2+) levels were lower during arrest with del Nido cardioplegia (57.10 ± 3.06 vs 76.19 ± 3.45 nmol/L; P < .05). During early reperfusion, a potentially injurious rapid recovery of intracellular Ca(2+) associated with hypercontraction in cardiomyocytes arrested with standard cardioplegic solution was avoided in cells treated with del Nido cardioplegia (81.42 ± 2.99 vs 103.15 ± 4.25 nM; P < .05). CONCLUSIONS: Del Nido cardioplegic solution has the potential to provide superior myocardial protection in senescent hearts by preventing electromechanical activity during cardioplegic arrest and Ca(2+)-induced hypercontraction during early reperfusion.