Advances in the differentiation of constrictive pericarditis and restrictive cardiomyopathy.

The diagnosis of constrictive pericarditis should be considered in any patient with unexplained right heart failure. The differentiation between constrictive pericarditis and restrictive cardiomyopathy is based on a combination of clinical presentation, history and imaging, and on occasion, on the basis of invasive hemodynamic studies or biopsy. Pertinent anatomic and physiologic findings on cardiac imaging modalities including echocardiography, computed tomography and cardiac magnetic resonance imaging are reviewed, and in many cases the diagnosis can be determined on the basis of imaging. Hemodynamic studies may clarify the diagnosis, and biopsy may find treatable causes of disease.

Heart regeneration in adult MRL mice.

The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary capacity to heal surgical wounds, a complex trait that maps to at least seven genetic loci. Here, we extend these studies to cardiac wounds and demonstrate that a severe transmural, cryogenically induced infarction of the right ventricle heals extensively within 60 days, with the restoration of normal myocardium and function. Scarring is markedly reduced in MRL mice compared with C57BL/6 mice, consistent with both the reduced hydroxyproline levels seen after injury and an elevated cardiomyocyte mitotic index of 10-20% for the MRL compared with 1-3% for the C57BL/6. The myocardial response to injury observed in these mice resembles the regenerative process seen in amphibians.

Radio frequency transmyocardial revascularization enhances angiogenesis and causes myocardial denervation in canine model.

BACKGROUND AND OBJECTIVE: Transmyocardial revascularization (TMR) relieves angina and improves exercise tolerance in patients. Angiogenesis and myocardial denervation have been proposed as factors contributing to these benefits. To test whether radio frequency transmyocardial revascularization (RF-TMR) enhances angiogenesis and causes myocardial denervation. STUDY DESIGN/MATERIALS AND METHODS: RF-TMR channels were created in 12 dogs which survived up to 4 weeks. Bromodeoxyuridine was administered subcutaneously to mark proliferating cells as an assay of angiogenesis. Western blot analysis of tyrosine hydroxylase and blood pressure response to topical bradykinin were used as indices of myocardial denervation. RESULTS: RF-TMR increased local vascularity by an average of 50%, whereas the rate of vascular cell proliferation was tripled over that of the untreated region. Changes in mean arterial pressure with bradykinin and tyrosine hydroxylase content were significantly decreased in RF-TMR regions as compared with normal myocardium in the same hearts. CONCLUSION: RF-TMR enhances angiogenesis and causes myocardial denervation in canine myocardium as with laser TMR.

Chronic exercise training preserves prostaglandin-induced dilation of epicardial coronary artery during development of heart failure in awake dogs.

Although it has been shown that long-term exercise training preserves endothelium-mediated nitric oxide vasodilator function in chronic heart failure (CHF), whether exercise training exerts similar beneficial effects on endothelial/prostaglandin-mediated vasodilator capacity in coronary circulation during the development of CHF has not been determined. Fifteen mongrel dogs were surgically instrumented for measurement of left ventricular pressure, aortic pressure, coronary blood flow and left circumflex coronary artery diameter. Dogs (n = 5) who underwent 4 weeks of cardiac pacing (210 b/min for 3 weeks and 240 b/min for the 4th week) developed CHF as characterized by significant reduction in left ventricular systolic pressure, mean arterial pressure and left ventricular dP/dt, increases in left ventricular end-diastolic pressure and heart rate, as well as clinical signs of CHF. Endothelial prostaglandin-mediated vasodilation of the epicardial coronary artery was impaired, as manifested by an attenuated arachidonic acid (AA)-induced dilation of the artery (epicardial artery diameter increased by: 0.78 +/- 0. 84% in CHF versus 4.6 +/- 0.89% in normal, P < 0.05); however, prostacyclin (PGI(2))-induced and nitroglycerin-induced vasodilation of the coronary circulation were not altered. In contrast, dogs (n = 6) with cardiac pacing plus daily exercise training (4.4 +/- 0.3 km/h, 2 h/day) only developed mild cardiac dysfunction, and the response of the epicardial coronary artery diameter to AA was preserved (epicardial artery diameter increased by 4.2 +/- 0.98% from baseline, P 0.05 compared to its respective control). Thus, long-term exercise training preserves endothelial/prostaglandin-mediated dilation of epicardial coronary artery during development of CHF.

Feasibility of real-time 3-dimensional treadmill stress echocardiography.

Rapid acquisition of echocardiographic images is critical for the predictive accuracy of stress echocardiography. Real-time 3-dimensional echocardiography (RT3D) allows review of several standard 2-dimensional images from a single volumetric data set. To assess the feasibility of RT3D for treadmill stress echocardiography, we performed treadmill stress RT3D on 20 volunteers (10 men and 10 women; mean age 32 +/- 6 years) with a device that uses a matrix phased-array transducer in a 60-degree pyramidal volume. Images are displayed as 2 steerable, intersecting B-scan sectors with adjustable C-scan planes parallel to the transducer face. At pre-exercise and immediate postexercise assessment, the volumetric data were obtained from apical and parasternal windows, respectively. Left ventricular segments were divided into 16 standard segments according to criteria defined by the American Society of Echocardiography. The use of both volume sets resulted in visualization of 98% of the segments at peak exercise. Even with only an apical volume set, 89% of the segments were adequately visualized. Image optimization and acquisition time at peak exercise was 35 +/- 18 seconds from the apical window and 50 +/- 28 seconds from the parasternal window. This preliminary study indicates that RT3D treadmill stress echocardiography is feasible and may be an important application of this new 3-dimensional device.

Real-time, 3-dimensional echocardiography acquires all standard 2-dimensional images from 2 volume sets: a clinical demonstration in 45 patients.

To test the hypothesis that real-time, 3-dimensional (3-D) echocardiography can obtain all standard 2-dimensional (2-D) views from acquisition of 2 volume sets, we scanned 45 patients (24 men, 21 women; mean age 49 +/- 17 years). This real-time 3-D device (VOLUMETRICS Medical Imaging, Durham, NC) uses a matrix phased array transducer in a 60 degree pyramidal volume. Images are displayed as 2 steerable, intersecting, conventional 2-D image sectors that can be oriented throughout 3-D space. By using this equipment, we were able to obtain 93.3% of standard views from a parasternal volume set and 85.2% of standard views from an apical volume set. The mean scanning time was 91 +/- 19 seconds for the parasternal volume set and 86 +/- 22 seconds for the apical volume set. We conclude that standard 2-D views can be obtained in the majority of patients by using this method. This equipment has the potential to substantially decrease the imaging time compared with the standard 2-D echocardiography.

Hemodynamic effects of a calcium channel promoter, BAY y 5959, are preserved after chronic administration in ischemic heart failure in conscious dogs.

BAY y 5959 is a dihydropyridine derivative that binds to L-type calcium channels in a voltage-dependent manner and promotes calcium entry into the cell during the plateau of the action potential by influencing mean open time. Because myofilament responsiveness to calcium is preserved in congestive heart failure (CHF), the inotropic responsiveness to this compound should be preserved in CHF, and tolerance should not develop despite long-term treatment. To test these hypotheses, CHF was induced in 14 chronically instrumented dogs by daily (30 +/- 5 days) intracoronary microsphere injections. The effects of BAY y 5959 (2-h i.v. infusions of 3 microg/kg/min and 10 microg/kg/min) were determined before heart failure, after heart failure was established and then 2 h after the end of a 5-day continuous BAY y 5959 intra-atrial infusion. Before CHF, the positive inotropic effect of BAY y 5959 at a dose of 10 microg/kg/min [left ventricular dP/dt (LVdP/dt) increased from 2955 +/- 132 mmHg to 4897 +/- 426 mmHg, P < .05] was associated with bradycardia (HR decreased from 92 +/- 4 to 78 +/- 6 b/min, P <.05), slight increases in mean arterial pressure (it increased from 100 +/- 2 mmHg to 113 +/- 5 mmHg, P <.05) and did not alter left ventricular end-diastolic pressure. In CHF, BAY y 5959 continued to induce dose-dependent increases in left ventricular systolic pressure, LVdP/dt and mean arterial pressure, as well as causing bradycardia and a significant decrease in left ventricular end-diastolic pressure. After a 5-day infusion of BAY y 5959, base-line LVdP/dt and left ventricular end-diastolic pressure improved. The responses of LVdP/dt and mean arterial pressure to BAY y 5959 were similar to those of the control state. The sustained responses in CHF and after long-term infusion suggest that BAY y 5959 may be an effective and potent inotropic agent for treatment of CHF that does not lead to tolerance to its positive inotropic effects.

Interrelating of ventricular pressure and intracellular calcium in intact hearts.

Although the mechanistic link between variations in intracellular calcium and its effects on myofilament regulatory proteins and subsequent impact on cardiac muscle force production have been known for some time, characterization of cardiac contractile properties are predominantly confined to phenomenological descriptions of the relationship between either muscle length and force or ventricular pressure and volume. However, as recognition of the limitations of these theories grow, investigators have begun to look toward more fundamental theories of cardiac contraction to explain whole heart function. The goal of the present study was first to explore, on a theoretical level, the degree of complexity required in a biochemical model necessary to adequately explain both equilibrium and twitch contraction behavior of cardiac muscle. Central to this analysis was a critical examination of the evidence for and against the importance of a calcium-free, force-generating state. Next, we determined whether such theories can actually account for the interrelationships between the experimentally measured time courses of pressure generation and the calcium transient measured from intact ventricles during both normal twitches as well as during complex contraction sequences. The results of this analysis provide strong support for a four-state model, including the calcium-free, force-generating state. These results will help guide the continuing quest for a mechanistic theory of ventricular function.