Christoph Dommke

Defining the Transmurality of a Chronic Myocardial Infarction by Ultrasonic Strain-Rate Imaging Implications for Identifying Intramural Viability: An Experimental Study

Background—In a correlative functional/histopathologic study, we investigated the regional deformation characteristics of both chronic nontransmural and transmural infarctions before and after a dobutamine challenge. Methods and Results—After stenosing copper-coated stent implantation to produce circumflex artery endothelial proliferation, 18 pigs were followed up for 5 weeks. Posteuthanasia histology showed 10 to have a nontransmural and 8 a transmural infarction. Eight nonstented animals served as controls. Regional radial function was monitored by measuring ultrasound-derived peak systolic strain rates (SRSYS) and systolic strains (&egr;SYS) (1) before stent implantation and (2) at 5 weeks, at baseline (bs) and during an incremental dobutamine infusion. In controls, dobutamine induced a linear increase in SRSYS (dobutamine: bs, 4.8±0.4 s−1; 20 &mgr;g · kg−1 · min−1, 9.9±0.7 s−1;P <0.0001) and an initial increase of &egr;SYS at low dose (bs, 58±5%; at 5 &mgr;g · kg−1 · min−1, 78±6%;P <0.05) but a subsequent decrease during higher infusion rates. In the nontransmural group, bs SRSYS and &egr;SYS were significantly lower than prestent values (SRSYS, 2.9±0.5 s−1 and &egr;SYS, 32±6%, P <0.05 versus prestent). During dobutamine infusion, SRSYS increased slightly at 5 &mgr;g · kg−1 · min−1 (4.7±0.6 s−1, P <0.05) but fell during higher infusion rates, whereas &egr;SYS showed no change. For nontransmural infarctions, transmural scar extension correlated closely with &egr;SYS at bs (r =0.88). For transmural infarctions, SRSYS at bs was significantly reduced and &egr;SYS was almost not measurable (SRSYS, 1.8±0.3 s−1; &egr;SYS, 3±4%). Both deformation parameters showed no further change during the incremental dobutamine infusion. Conclusions—Ultrasonic deformation values could clearly differentiate chronic nontransmural from transmural myocardial infarction. The transmural extension of the scar could be defined by the regional deformation response.

Quantification of regional right and left ventricular function by ultrasonic strain rate and strain indexes after surgical repair of tetralogy of fallot

The quantification of regional myocardial function in tetralogy of Fallot (TOF) by conventional M-mode and 2-dimensional echocardiography is difficult because of the complex right ventricular (RV) and altered left ventricular (LV) geometry. In 30 asymptomatic postoperative TOF patients (aged 4 to 16 years) with a low pressure in the right ventricle and with varying degrees of pulmonary regurgitation and in 30 aged-matched healthy children, the ultrasonic-derived regional deformation parameters peak systolic strain rate (SR) and systolic strain (epsilon) were acquired from ventricles and compared. In TOF RV free walls, SR, and epsilon were reduced in the basal, mid-, and apical segments and averaged -1.5 +/- 0.6 second(-1) for SR and -22 +/- 8% for epsilon, respectively (p <0.001 vs normals). Peak systolic SR of the basal RV free wall correlated significantly with the QRS duration of the electrocardiogram (r = 0.81, p <0.0001). Abnormalities in RV deformation were more marked in patients with transannular patches versus infundibular patches. In the septum there was a homogeneous reduction in SR and epsilon in the basal, mid-, and apical segments. These averaged -1.4 +/- 0.3 second(-1) for SR and -19 +/- 4% for epsilon, respectively (p <0.01 vs normals). Longitudinal SR and epsilon values of the 3 LV lateral wall segments (averaged SR = -1.6 +/- 0.4 second(-1), averaged epsilon = -20 +/- 5%; p <0.05 vs normals), and radial SR and epsilon of the LV posterior wall (SR = 3.3 +/- 0.9 second(-1); epsilon = 51 +/- 14%; p <0.05 vs normals) were significantly reduced. Thus, abnormalities in regional RV and LV systolic myocardial function in asymptomatic postoperative TOF patients were quantified by the deformation parameters SR and epsilon. RV deformation abnormalities are associated with electrical depolarization abnormalities.

Reduced Force Generating Capacity in Myocytes From Chronically Ischemic, Hibernating Myocardium

The contractile dysfunction of the hibernating myocardium in situ results from local environmental factors, but also from intrinsic cellular remodelling that may determine reversibility. Previous studies have suggested defects in myofilament Ca2+ responsiveness. We prepared single myocytes from control (CTRL, npigs=7) and from hibernating myocardium (HIB, npigs=8), removed the membranes and measured isometric force development during direct activation of the myofilaments. One- and 2-dimensional polyacrylamide gel electrophoresis and specific phosphoprotein immunoblotting were performed on tissue homogenates from matched samples. Cellular ultrastructure was evaluated using electron microscopy. Normalized for cross-sectional area, passive force was not different but maximal isometric force was significantly reduced in myocytes from HIB (11.6±1.5 kN/m2 versus 18.7±1.6 kN/m2 in CTRL, P<0.05). Ca2+ sensitivity and steepness of the normalized force-pCa relationship were not different, and neither was the rate of force redevelopment (Ktr). No alterations were observed in isoform expression, phosphorylation or degradation of specific myofibrillar proteins. However, in HIB samples the total protein volume density was decreased by 23% (P<0.05). Histology showed glycogen accumulation and electron microscopy confirmed a reduction in myofilament density from 69.9±1.9% in CTRL to 57.1±0.9% of cell volume in HIB (P<0.05). In conclusion, decreased potential for force development in the hibernating myocardium is related to a reduction of myofibrillar protein per cell volume unit with replacement by glycogen and mitochondria. These changes may contribute to slow functional recovery on revascularization.

Post-Systolic Thickening in Ischaemic Myocardium: A Simple Mathematical Model for Simulating Regional Deformation

We present a one-dimensional mathematical model to explain changes in regional radial myocardial deformation during ischaemia. The model makes use of cellular contraction properties of normal and ischaemic myocytes extracted from an animal model of induced chronic, regional ischaemia of the posterior wall. Simulations of the model are compared to the deformation patterns observed in the experimental animal models of regional ischaemia.